Molecules doi: 10.3390/molecules31162847

Authors: Agnieszka Szymaszek-Wawryca Michał Szymaszek Robert Kosydar Dorota Duraczyńska Monika Motak

CO2 methanation is a promising power-to-gas technology that enables the conversion of carbon dioxide into methane. However, the development of efficient catalysts based on naturally abundant and inexpensive support remains an important challenge. In this work, metakaolin from natural kaolin was investigated as a novel support for high-loading (30 wt.%) Ni catalysts prepared using a melt infiltration method. The influence of CeO2 and alkaline earth metal oxides (MgO, CaO) on the physicochemical properties and catalytic performance was systematically evaluated. It was evidenced that CeO2 improved NiO reducibility, whereas MgO and CaO promoted Ni0 dispersion and modified textural and surface properties. In particular, Mg addition increased the SBET from 23 to 39 m2/g and the total pore volume from 0.06 to 0.17 cm3/g compared with the Ni-MK sample. The promoted catalysts exhibited enhanced low-temperature activity and reached approximately 80% CO2 conversion at 400 °C, close to thermodynamic equilibrium, maintaining CH4 selectivity above 97%. Stable catalytic performance was preserved during 24 h time-on-stream tests. The results demonstrate that metakaolin is a promising sustainable support for Ni CO2 methanation catalysts and that melt infiltration provides a simple and effective preparation route for obtaining high nickel loading.

Molecules doi: 10.3390/molecules31162846

Authors: Yrysgul Bakytkarim Zhazira Mukatayeva Dinara Zhetpisbay Nurgul Shadin Ainur Yerezhepova Yerzhan Imanbayev Ainura Rakhimova Yernar Kanzharkhan

In this study, a novel SiC/rGO nanocomposite-modified glassy carbon electrode (SiC/rGO/GCE) was developed as a simple, cost-effective, and efficient electrochemical platform for metronidazole (MTZ) detection. The combination of silicon carbide (SiC) and reduced graphene oxide (rGO) provides a favorable interface with a high electroactive surface area, efficient electron transfer, and enhanced electrocatalytic activity. The mor-phology and surface characteristics of the modified electrode were investigated by scan-ning electron microscopy (SEM), while its electrochemical properties were evaluated by cyclic voltammetry and electrochemical impedance spectroscopy. The results confirmed successful electrode modification and improved electron-transfer kinetics compared with the bare GCE. The main experimental parameters were systematically optimized, with the optimum conditions established at pH 10, an accumulation time of 300 s, and an accu-mulation potential of 0.5 V. Under these conditions, the SiC/rGO/GCE exhibited a broad linear response to MTZ over the concentration range of 5–5000 µmol/dm3, with a detection limit of 0.5 µmol/dm3 (S/N ≥ 3). The enhanced analytical performance is attributed to the synergistic contribution of rGO and SiC, where rGO promotes rapid electron transport and provides a large electroactive surface, while SiC contributes additional active sites and structural stability. The sensor was successfully applied to pharmaceutical samples, providing recoveries of 99.85–102.29% with RSD values below 2%. These results demon-strate the practical potential of the proposed sensor for reliable MTZ determination. Fur-ther validation in food and biological matrices and comparison with reference chromato-graphic methods will be necessary to establish its broader analytical applicability.

Molecules doi: 10.3390/molecules31162845

Authors: Lucia Maddaloni Giuliana Vinci Paola Russo Giuseppina Adiletta Nicholas Torchia Sabrina Antonia Prencipe

Background: Fresh-cut apples are highly susceptible to quality deterioration due to enzymatic browning and oxidative degradation of bioactive compounds. This study investigated the effects of conventional polyethylene packaging (PE, Pack 1) and two innovative biodegradable packaging materials (Pack 2 and Pack 3) on the stability of bioactive compounds in fresh-cut Golden Delicious apples during refrigerated storage. Individual phenolic compounds ((+)-catechin, caffeic acid, (−)-epicatechin, p-coumaric acid, rutin, and quercetin) were quantified by HPLC-PDA, while spectrophotometric assays were used to determine total phenolic content (TPC), total flavonoid content (TFC), and antioxidant capacity (ABTS and DPPH). The environmental performance of the packaging materials was assessed through Life Cycle Assessment (LCA) using SimaPro v.9.5.5. Results: Polyphenol stability was significantly influenced by packaging and storage time (p < 0.001). Compared with fresh-cut apples at t0, Pack 2 promoted a 17.4% increase in total phenolic content after 21 days, whereas Pack 1 and Pack 3 showed reductions of 31.0% and 37.6%, respectively. HPLC analysis revealed compound-specific responses, with rutin and quercetin being markedly better preserved in Pack 3 after 21 days (17.65 and 1.93 mg/100 g, respectively) than in Pack 1 (0.67 and 0.19 mg/100 g, respectively). Two-way ANOVA confirmed significant effects of storage time, packaging, and their interaction on TPC, TFC, ABTS activity, and all individual phenolic compounds (p < 0.001), whereas DPPH activity was not significantly affected (p > 0.05). Pearson correlation (TPC–ABTS, r = 0.6885, p < 0.001) and principal component analysis indicated that antioxidant capacity was more closely associated with the qualitative phenolic profile than with total phenolic concentration alone. LCA highlighted environmental trade-offs among the packaging systems: Pack 1 showed lower impacts in several categories, Pack 2 displayed an intermediate environmental profile, whereas Pack 3 reduced dependence on fossil resources but exhibited higher land- and water-use impacts together with limitations related to end-of-life management. Conclusion: Packaging materials significantly affected the preservation of phenolic compounds and antioxidant activity in fresh-cut apples while exhibiting distinct environmental profiles. The results demonstrate that no packaging system simultaneously maximized product quality and environmental sustainability, highlighting the importance of integrating analytical performance with life-cycle assessment when developing innovative food packaging solutions.

Molecules doi: 10.3390/molecules31162844

Authors: Juan Jia Wen Zhang Sitong Nan Haiyun Liu Qian Xue Congying Liu Keming Yun Jiangwei Yan

Nitrous oxide (N2O), commonly known as laughing gas, is widely used for its anesthetic and analgesic properties in medical settings. However, its recreational abuse has escalated, leading to severe neurological complications including cognitive impairment, yet the underlying mechanisms remain poorly understood. In this study, male C57BL/6 J mice were exposed to either normal air inhalation or nitrous oxide inhalation for 28 days to evaluate the effects of repeated nitrous oxide exposure on cognitive function. We employed hippocampal transcriptome sequencing, real-time PCR, Western blotting, and non-targeted plasma metabolomics to explore potential regulatory mechanisms. Repeated nitrous oxide exposure impaired motor skills, learning, and cognitive abilities in mice. Integrative multi-omics analysis revealed that differentially expressed metabolites and genes synergistically disrupted energy metabolism through co-regulation of the TCA cycle, MAPK signaling pathway, and pyrimidine metabolism, ultimately leading to impaired cellular signaling, nucleic acid synthesis, and cognitive dysfunction. Our study provides novel multi-omics insights into the MAPK/ERK/CREB-mediated neurotoxicity and energy metabolism collapse induced by nitrous oxide as a recreational drug of abuse, offering new directions for clinical intervention.

Molecules doi: 10.3390/molecules31162843

Authors: Ligang Ma Tingting Chen Jingxuan Zhou Jiulei Zhao Xinlan Li Huilin Jiang Liping Li Xiaoqian Ai

Organic pollutants in industrial wastewater present a severe threat to both the environment and human health. Photocatalytic technology, recognized for its eco-friendliness and high efficiency, has become a leading approach for degrading such pollutants. In this work, BiOCl nanosheets were first synthesized using a hydrothermal method. Subsequently, an anion exchange reaction with TAA in an oil bath generated a Bi2S3 intermediate layer on the BiOCl surface, followed by the in situ growth of ZIS nanostructures, successfully constructing a BiOCl@Bi2S3@ZIS double Z-scheme heterojunction. By adjusting the amount of BiOCl, the interface contact and dispersion of the heterojunction were optimized. Characterization results demonstrate that the BiOCl@ZIS-25 heterojunction possesses the highest specific surface area (103.5 m2·g−1) and the most efficient charge separation. Under visible light irradiation, it achieved 97.88% degradation of methylene blue within 20 min, with a reaction rate constant 8 and 4 times higher than those of pure BiOCl and ZIS, respectively. Mechanistic investigations indicate that Bi2S3 interlayer acts as an electron-transfer bridge between BiOCl and ZIS, establishing a double Z-scheme charge transfer pathway that significantly enhanced the separation and utilization efficiency of photogenerated charge carriers. This study offers valuable insights for designing highly efficient and stable photocatalytic composite materials.

Molecules doi: 10.3390/molecules31162842

Authors: Aida S. Rakhimzhanova Irina A. Pustolaikina Alfiya F. Kurmanova Ruslan A. Muzaparov Tatyana V. Rybalova Zarina T. Shulgau Alena L. Stalinskaya Ivan V. Kulakov

Herein, we report an unexpected pseudo-multicomponent transformation discovered during attempts to selectively nitrate the pyridine core of 3-acetyl-2,4,6-trimethylpyridine (3). Despite employing standard nitration conditions, including KNO3–H2SO4 and HNO3–H2SO4 mixtures, electrophilic substitution of the aromatic ring did not occur. Instead, the reaction sequence promoted an in situ nitrozation, dehydration to nitrile oxide intermediates, and subsequent [3+2]-cycloaddition involving two substrate molecules. This process yielded a novel, highly functionalized furoxan derivative, precisely identified as 3,4-bis(2,4,6-trimethylnicotinoyl)-1,2,5-oxadiazole 2-oxide (5). The molecular architecture of compound 5 was established by 1H and 13C NMR spectroscopy, mass spectrometry, elemental analysis, and single-crystal X-ray diffraction (XRD) analysis. To elucidate the stereochemical and electronic features governing compound 5, DFT calculations were performed at the ωB97X-D/6-311++G(d,p) level of theory. The experimental crystallographic disorder of the N-oxide oxygen atom was computationally rationalized by the thermodynamic near-degeneracy (ΔG < 0.63 kcal/mol) of two orientational isomers (5a and 5b). Furthermore, frontier molecular orbital analysis within the framework of perturbation theory accounted for the head-to-tail regioselectivity during cyclization, while wide energy gaps (ΔE = 8.13–8.27 eV) and high chemical hardness (η = 4.07–4.14 eV) underscored the kinetic stability of the heterocycle. Phenotypic and target-specific in silico profiling using PASS Online identified Matrix Metalloproteinase-9 (MMP-9) as a relevant target for potential hemorheological and cardioprotective applications. Validated molecular docking simulations across three human MMP-9 crystallographic domains (PDB: 8K5Y, 6ESM, 4XCT) demonstrated competitive binding affinities and balanced Ligand Efficiency metrics (LE = 0.26–0.29 kcal/mol/heavy atom), anchoring compound 5 within the catalytic pocket via conventional hydrogen bonds and π-mediated interactions. Finally, in vitro evaluations using a blood hyperviscosity model confirmed significant hemorheological efficacy, as compound 5 effectively prevented the rise in blood viscosity, outperforming the reference drug pentoxifylline. The convergence of computational insights and experimental functional activity establishes this novel bis(nicotinoyl)furoxan framework as a promising candidate for further hemorheological and cardioprotective applications.

Molecules doi: 10.3390/molecules31162841

Authors: Fangying Chen Wan Yin Tew Ming Thong Ong Mun Fei Yam

Background: The specific mechanisms underlying the antihypertensive actions of corosolic acid (CA) have not been systematically elucidated. Methods: Evidence was categorized according to major signaling and physiological pathways, including the renin–angiotensin system (RAS), oxidative and inflammatory responses, endothelial and smooth muscle regulation (NO/cGMP and H2S/KATP), and kinase-mediated signaling (AMPK, NF-κB, JAK/STAT, PKC). Results: Consistent with in vitro and animal studies, CA has been reported to attenuate pro-hypertensive signaling through multiple pathways: (i) downregulating renin–angiotensin system-related cascades; (ii) reduction in reactive oxygen species and inflammatory mediators through activation of AMPK and inhibition of NF-κB and JAK/STAT pathways; (iii) improved vascular tone by enhancing NO/cGMP signaling, partly involving the H2S/KATP pathway, and inhibiting PKC. CA may indirectly contribute to blood pressure reduction by improving glucose and lipid metabolism and adipose tissue inflammation, thereby affecting metabolic risk factors. The existing evidence gaps include: lack of direct studies on voltage-gated, receptor-gated and store-regulated calcium channels; the specific effects on the isoforms of nitric oxide synthase (eNOS/iNOS/nNOS) and PKC are not known; limited human data on the antihypertensive efficacy, dose effect and safety of CA in humans are available. Conclusions: CA may have multi-targeted blood-pressure-lowering potential. Its clinical efficacy and safety require further confirmation.

Molecules doi: 10.3390/molecules31162840

Authors: Lulu Liu Jiacheng Qi Chi Ding Dinghui Wang Shoutao Zhang

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Molecules doi: 10.3390/molecules31162836

Authors: Abderrahman Atifi

Spectroelectrochemistry (SEC) provides unique information-rich datasets by coupling molecular spectroscopic fingerprints with electrochemical activity. Despite its richness, direct machine-learning (ML) analysis of SEC data under realistic experimental constraints and scarcity remains unexplored. This work examines how much spectroscopically encoded electrochemical information can be learned from minimal SEC training data in a chemically reversible two-electron redox system, and how model choice interacts with limited experimental diversity across scan rate. Using purely experimental SEC datasets collected at four scan rates (2, 3, 5, and 7 mV/s), partial least squares (PLS) and convolutional neural networks (CNNs) regressors are evaluated under several SEC-level training, validation, and test configurations. Model performance is assessed across three targets of increasing physical complexity, including species concentrations, derivative cyclic voltabsorptometry (DCVA) current, and experimental cyclic voltammetry (CV) current. Under single-SEC training, both models achieve the expected near-quantitative concentration prediction (R2 ~0.99), while performance decreases for DCVA (R2 ~0.93) and most substantially for CV current (R2 ~0.78), reflecting the progressively weaker and more indirect encoding of these targets within the absorbance data. Introducing minimal experimental diversity with only two distinct training SEC datasets enables both PLS and CNN models to generalize strongly to an unseen third SEC dataset, achieving maximum CV R2 values approaching ~0.98 in the most favorable configurations. CNN models extend the apparent linear performance ceiling observed for PLS by capturing localized, scan-rate-conditioned nonlinear correlations between spectral evolution and the experimentally measured CV response, yielding improved waveform reconstruction and greater robustness to training SEC dataset selection. These results demonstrate that, within the present chemically reversible and spectroscopically well-resolved SEC system, high-fidelity prediction of electrochemical targets can be achieved without large datasets when limited but strategically selected electrochemical diversity is introduced. SEC dataset linearity is further shown to be target-dependent and becomes operationally meaningful only when scan-rate space is sufficiently sampled. More broadly, this work establishes a controlled framework for investigating ML-enabled SEC dataset analysis under experimentally scarce conditions and provides guidance for experimental design and calibration in low-data spectroelectrochemical settings.

Molecules doi: 10.3390/molecules31162839

Authors: Valeria Gigli Elisabetta Tomaino Davide Piccinino Lorenzo Botta Eliana Capecchi Raffaele Saladino

The electrochemical sensing of similar catecholamines remains challenging due to their overlapping redox behavior and similar reactivity, which often results in poorly selective reaction pathways. Herein, we report a bioinspired tyrosinase electro-catalytic system that enables the modulation of the catecholamine reactivity through the integration of enzymatic oxidation with electrochemical transformation. The biocatalytic platform consisted of electroactive lignin nanoparticles (LNPs) supporting tyrosinase drop cast on the graphene-based screen-printed electrode. The overall reaction included the oxidation of catecholamines to ortho-quinones, followed by nucleophile addition of cysteine under control of the redox environment. Overall, coupling enzymatic catalysis with electrochemical regulation enabled selectivity in the oxidative functionalization of catecholamines, providing a sustainable strategy for tuning reactivity in advanced bioinspired catalytic systems.

Molecules doi: 10.3390/molecules31162838

Authors: Łukasz Sikorski Agnieszka Bęś Wojciech Truszkowski Amit Kumar Andrzej Brandyk Maja Radziemska

This study evaluated the phytotoxicity of diesel oil (DO) using the green alga Pseudokirchneriella subcapitata and the aquatic plant Lemna minor. Toxic effects were assessed in 7-day Algaltoxkit and Lemna bioassays by measuring growth, chlorophyll fluorescence, and biogenic amine (BA) content. L. minor was less sensitive to DO in terms of growth than the alga. Toxicity thresholds (LOEC, 7 days) showed that DO concentrations above 0.11–0.12% significantly inhibited the growth and productivity of both model organisms. Chlorophyll fluorescence proved to be an early and sensitive indicator of DO toxicity. This study also provides the first characterization of BAs in P. subcapitata, identifying histamine, tyramine, putrescine, cadaverine, agmatine, spermidine, and spermine. Agmatine emerged as a common indicator of DO contamination in both species. Its content decreased in P. subcapitata (EC50 = 0.85%) but increased in L. minor (EC50 = 0.38%) under diesel exposure. The findings herein suggest that BA profiling, especially agmatine, can support early detection of hydrocarbon stress in aquatic organisms.

Molecules doi: 10.3390/molecules31162837

Authors: Taiqi Qu Yujuan Chen Yijia Zhang Yuan Wang Yixuan Li Yanan Sun

Age-related skeletal muscle atrophy (sarcopenia) poses a major public health challenge, emphasizing the need for safe and effective interventions. Our previous studies demonstrated that C-C chemokine receptor type 5 (CCR5) is a key therapeutic target for skeletal muscle atrophy, as its activation by C-C motif chemokine ligand 11 (CCL11) promotes the dissociation and degradation of the structural protein α-actin, ultimately contributing to muscle loss. To identify potential CCR5 inhibitors, a database of 7860 natural alkaloids was constructed for pharmacophore-based virtual screening using the CCR5–Maraviroc crystal structure. Screening yielded 789 candidates, and subsequent batch molecular docking analysis identified Isoliensinine (ISO), a lotus seed alkaloid, as a potential CCR5 inhibitor with low binding energy (−10 kcal/mol) and stable hydrogen bonding interactions with Glu283 and Tyr251. Molecular dynamics simulations further confirmed the structural stability of the ISO–CCR5 complex. Molecular dynamics simulations further confirmed the structural stability of the ISO-CCR5 complex. In vitro, ISO dose-dependently inhibited CCL11-induced CCR5 activity (IC50 = 1.314 μM) with low cytotoxicity in C2C12 myotubes, and markedly alleviated CCL11-induced myotube atrophy by suppressing CCR5 activation and the upregulation of the muscle atrophy–related markers MAFbx and MuRF1. These findings provide preliminary evidence for ISO as a potential CCR5-targeting candidate for further investigation in sarcopenia.

Molecules doi: 10.3390/molecules31162834

Authors: Oleg S. Butorlin Anna S. Petrova Aleksei E. Mikhaltsov Mikhail N. Ryazantsev Nikita A. Bogachev Mikhail Yu. Skripkin Andrey S. Mereshchenko

A series of novel heterometallic rare-earth chloroterephthalate metal–organic frameworks with the general formula (TbxGd1−x)2(Cl-1,4-bdc)3·5H2O (x = 0–1) were synthesized via direct precipitation from aqueous solutions. The structural and photophysical properties of these compounds were studied in detail. All compounds exhibit bright luminescence upon UV excitation into the ligand absorption band due to an efficient antenna effect. The photoluminescence quantum yield shows a non-monotonic dependence on the concentration of the terbium ion with a maximum value of 71% achieved for the compound containing equal molar fractions of the lanthanide ions. The (Tb0.5Gd0.5)2(Cl-1,4-bdc)3·5H2O sample was evaluatedfor its utility in both qualitative and quantitative analysis of selected metal ions and in latent fingerprint development. It was shown to enable the detection of Cr(III), Fe(III), and Cu(II) ions through luminescence quenching, with the emission intensity being concentration-dependent. This behaviour highlights the compound’s potential as a basis for analytical protocols and materials aimed at the quantitative determination of these metal ions.

Molecules doi: 10.3390/molecules31162835

Authors: Thanh Sang Vo Vo Thi Ngoc My Phan Van Hoai Luan Dai-Hung Ngo

Phyllanthus amarus has long been used in traditional medicine and contains diverse bioactive compounds with potential pharmacological properties. This study aimed to purify the compounds from P. amarus and investigate their inhibitory effects on mast cell degranulation in vitro. It was found that the ethyl acetate fraction from P. amarus possesses potential inhibitory effects on mast cell degranulation. Subsequently, three compounds, including 3,3′,4-tri-O-methylellagic acid (P1), ethyl brevifolincarboxylate (P2), and 4′,4′′′-di-O-methyl cupressuflavone (P3), were purified and identified. These compounds significantly inhibited mast cell degranulation via decreasing histamine release and IL-4 and TNF-α production from the activated mast cells without any cytotoxicity. Furthermore, Western blot analysis confirmed that these compounds suppressed phosphorylation of Syk and PLCγ, suggesting inhibition of the degranulation-related signaling cascade. These findings provide preliminary in vitro evidence that purified constituents from P. amarus may inhibit mast cell degranulation, potentially in association with modulation of Syk/PLCγ signaling, and support further mechanistic and in vivo investigations.

Molecules doi: 10.3390/molecules31162833

Authors: Massimiliano Runfola Beatrice Polini Anna Mazzierli Lorenzo Raffellini Fabio Di Ricco Italo Cirone Simona Sagona Sheraz Gul Marco Lessi Angela Rosa Cuzzola Rosarita D’Orsi Fabio Bellina Clementina Manera Grazia Chiellini Simona Rapposelli

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder involving metabolic impairment, neuroinflammation, synaptic failure, and comorbidities. Hence, therapeutic development for AD is rapidly shifting from a single-target approach, centred on amyloid-beta (Aβ) reduction, to multi-target strategies. In this study, we investigated the neuroprotective profile of two acetanilide derivatives, SG-22 and SG-23, originated from the halogen-free thyronamine-like lead compound SG-2. Their efficacy was evaluated through an integrated approach combining in vitro cellular models, in vivo phenotypic screening in a Caenorhabditis elegans AD model, and comprehensive ADME-Tox profiling. In U87MG cells, both SG-22 and SG-23 effectively prevented Aβ25–35-induced cytotoxicity and restored autophagy-related gene expression, including LC3, SIRT1, and SIRT6, while reducing mTOR and SIRT5 levels. Furthermore, all compounds exhibited anti-inflammatory effects in activated HMC3 microglial cells, reducing IL-6 and increasing IL-10 levels, with evidence suggesting partial involvement of TAAR1 signalling. ADME-Tox analyses revealed improved safety and metabolic profiles for the tested compounds, particularly SG-22, which showed reduced hERG liability and enhanced cytochrome P450 stability. However, in vivo studies demonstrated that only SG-2 and SG-23 improved motility and fitness in the C. elegans AD model, consistent with their ability to activate autophagy, whereas SG-22 was ineffective due to limited organismal uptake. Ultimately, the monoacetylated analogue SG-23 emerges as a promising candidate, balancing neuroprotective efficacy and drug-like properties, and supporting thyronamine-like analogues as multi-target agents for AD.

Molecules doi: 10.3390/molecules31162832

Authors: Xiaohe Zhang Pengrui Du Lingxia Chen Minlong Wang Xiangyu Liu Ruoyan Yang Jie An

Sulfur(VI) fluoride exchange (SuFEx) chemistry is a powerful click reaction for modular synthesis, distinguished by high chemoselectivity, broad functional-group tolerance and the formation of robust sulfur(VI)-based linkages. These attributes are particularly valuable for polymer functionalization, as S(VI)–F handles on either the polymer or the modifier enable covalent coupling under controlled conditions. This review spans SuFEx-mediated post-polymerization modification and architectural control of synthetic polymers, surface, interfacial and porous-material functionalization, and SuFEx-based conjugation and covalent capture in natural and sequence-defined biopolymers. Across these contexts, we compare the advantages, supporting mechanistic and analytical evidence, current limitations and future opportunities of SuFEx-enabled polymer functionalization.

Molecules doi: 10.3390/molecules31162831

Authors: Leila Bellebcir Imene Derardja Redouane Rebai Luc Jasmin Abdennacer Boudah

Astragalus species have long been recognized for their pharmacological relevance, yet the antidiabetic properties of Astragalus cruciatus Link (Ac) remain poorly explored. This study aimed to investigate the antidiabetic potential of A. cruciatus Link and to elucidate possible underlying mechanisms. The ethanolic extract of Ac (AcEE) was prepared and analyzed for phenolic and flavonoid content. Antioxidant activity was assessed through a series of in vitro assays. The in vitro inhibition of α-amylase and α-glucosidase was assessed, followed by molecular docking to probe ligand-enzyme interactions. LC-ESI-MS analysis revealed a polyphenol-rich profile, with rutin (953.54 µg/g extract) and quinic acid (797.18 µg/g of extract) identified as main compounds. The AcEE showed significant inhibitory activity against both α-amylase and α-glucosidase (IC50 = 239.30 ± 7.40 and 192.60 ± 15.51 μg/mL, respectively). Moreover, low cytotoxic effects were observed in hepatic cell lines. Computational analysis revealed stable interactions between rutin and both enzymes (−12.935 and −8.073 Kcal/mol, respectively). Network pharmacology revealed that AcEE may modulate key targets, including IL-6, TNF-α, IL-1β, Akt-1, STAT3, EGFR, and INSR as well as pathways related to insulin resistance, AGE-RAGE, and inflammation. These findings suggest that AcEE exerts significant antidiabetic effects through multitarget modulation, highlighting its potential as a natural therapeutic agent for T2DM.

Molecules doi: 10.3390/molecules31162830

Authors: Maria A. Trestsova Daria A. Andreeva Mikhail A. Kiskin Maria V. Komelkova Pavel M. Vassiliev Alena. S. Taran Ludmila A. Yolshina Alexander G. Kvashnichev Veronika A. Isaeva Irina A. Utepova Oleg N. Chupakhin Alexey P. Sarapultsev

A light-promoted C–H/C–H coupling of imidazo[1,2-a]pyridines with 5-(hetero)aryl-1,2,5-oxadiazolo[3,4-b]pyrazines was developed using a heterogeneous oxidative photocatalytic system based on molecular oxygen, nanosized TiO2, and light irradiation. The method provides direct access to C3-heteroarylated imidazo[1,2-a]pyridines under metal-free conditions and expands the synthetic utility of electron-deficient oxadiazolopyrazine partners in the construction of biheteroaryl scaffolds. The synthesized compounds were evaluated computationally using a fully connected convolutional correlation neural network based on multiple-docking energy spectra, which prioritized the series as potential COX-1 and COX-2 ligands. To test this prioritization experimentally, all 18 compounds were screened in fluorometric COX-1 and COX-2 inhibitor assays at 1 µM. Compound 3f emerged as a strong preliminary COX-1 hit at 1 µM (86.64 ± 5.18% inhibition), whereas 3h and 3l showed weaker COX-1 inhibition. No compound showed high or moderate COX-2 inhibition at the screening concentration; only weak COX-2 inhibitory signals were observed for several derivatives. Thus, the combined synthetic, computational, and enzymatic data identify compound 3f as the main COX-1-skewed hit in this series and provide a basis for further dose–response, selectivity, and cell-based anti-inflammatory studies. It should also be noted that the COX-1 inhibition assay used ovine COX-1, whereas the computational models were built on human COX-1 and COX-2 structures; this species difference is an additional reason to treat the in silico–experimental comparison as approximate.

Molecules doi: 10.3390/molecules31162829

Authors: Camila Ramalho Bonturi Bruno Ramos Salu Kathleen Chwen Ming Lie Márcia Bonini Rita de Cassia Sinigaglia Miryam Paola Alvarez-Flores Ana Marisa Chudzinski-Tavassi Heloisa Sobreiro Selistre-de-Araujo Maria Luiza Vilela Oliva Oliva

Melanoma dissemination depends on tumor cell plasticity, extracellular matrix remodeling, and adaptive signaling pathways that promote survival, migration, invasion, and therapeutic resistance. In this study, we investigated the antitumor effects of the plant-derived Kunitz-type protease inhibitor EcTI using both in vitro B16F10-Nex2 melanoma cells and an in vivo murine melanoma model, focusing on adhesion-dependent signaling, autophagy, mitochondrial dysfunction, and regulated cell death. EcTI was efficiently internalized by melanoma cells and showed partial colocalization with lysosomal and mitochondrial compartments, suggesting intracellular trafficking toward these organelles. Treatment reduced cell adhesion to extracellular matrix proteins, particularly fibronectin and laminin, and inhibited migration, invasion, and angiogenic signaling. These effects were associated with modulation of the adhesion-dependent FAK/Src/ERK signaling axis and decreased MMP-9 activity. EcTI also disrupted autophagy, as indicated by accumulation of acidic vesicular organelles, increased LC3-II levels, and modulation of ULK1, Ambra1, and Beclin-1 signaling. In parallel, EcTI induced mitochondrial dysfunction, characterized by loss of mitochondrial membrane potential, intracellular Ca²⁺ dysregulation, and increased reactive oxygen species production. These alterations triggered regulated cell death involving apoptotic and necroptosis-like mechanisms. Importantly, EcTI significantly suppressed tumor growth in vivo without detectable systemic toxicity and modulated inflammatory mediators associated with tumor progression. Overall, these findings demonstrate that EcTI exerts broad antitumor activity by modulating multiple signaling pathways associated with melanoma progression and represents a promising therapeutic candidate for melanoma treatment.

Molecules doi: 10.3390/molecules31162828

Authors: Matthieu Jorandon Nadia Patino Elisabet Duñach Mohamed Mehiri

Lewis acid-catalyzed epoxide openings efficiently promote intramolecular cyclizations forming complex oxygenated frameworks. Herein, we investigated the reactivity of epoxyolefins under catalytic conditions using various metal triflates. The study focuses on the competition between epoxide isomerization and intramolecular cyclization involving a pendant olefin. Screening of several metal triflates revealed that Lewis superacids, particularly Bi(OTf)3, promote efficient transformations at room temperature with low catalyst loadings (1 mol%). Structural variation in the substrates significantly influenced product distribution likely through coordination effects, impacting cyclization efficiency with higher yields observed for non-chelating epoxyolefins. Substrates derived from geraniol underwent selective cyclization to cis-cyclic alcohols and bicyclic ethers in good yields, with stereochemical outcomes consistent with the Eschenmoser model. Reaction conditions such as temperature and catalyst loading further modulated selectivity, allowing control over product distribution. These results highlight the potential of metal triflates as versatile and efficient catalysts for the stereoselective intramolecular cyclization of epoxyolefins, offering access to cyclic frameworks under mild conditions.

Molecules doi: 10.3390/molecules31162827

Authors: Alberto Medina-Ortíz José Luis Olivares-Romero Alfonso Reyes-Luna David Cruz Cruz Clarisa Villegas Gómez

3,4-dihydrocoumarins and spiro compounds constitute an important class of privileged frameworks present in a wide variety of natural and synthetic molecules with diverse applications. In this study, we developed an organocatalytic methodology for the construction of complex and diverse chiral spiro-bridged 3,4-dihydrocoumarins through a Diels–Alder/Nucleophilic ring-closing cascade via trienamine activation. The reaction proceeds efficiently with different trienamine precursors and a range of coumarin-3-carboxamides, which act as both dienophile and intramolecular nucleophile species. This process affords the desired products in good yields and with a high degree of stereocontrol. Furthermore, several transformations on the newly formed spiro-piperidone ring demonstrate the synthetic utility of the obtained compounds.

Molecules doi: 10.3390/molecules31162826

Authors: Carolina Rojas Neida Santacruz Frank Mendoza Sebastián A. Michea Gerardo Morell Brad R. Weiner

A novel low-temperature method to synthesize a hybrid carbon material (HCM) is reported. The synthesis relies on a chemical vapor deposition (CVD) approach, using zeolite NaY as a scaffold structure and acetone as the carbon source. The deposition temperature was 500 °C at a pressure of 46 ± 1 kPa. Following the growth of the HCM, the material was treated with HF to remove the scaffold, and the resultant materials were characterized by high-resolution scanning electron microscopy (HR-SEM), energy-dispersive X-ray spectroscopy (EDS) mapping, transmission electron microscopy (TEM), X-ray diffraction (XRD), Raman microscopy, and Brunauer–Emmett–Teller (BET) surface area analysis, showing heterogeneous morphology. The results demonstrate that synthesis at low temperatures produces a robust hybrid material that can adopt different configurations and/or morphologies by modifying the scaffold structure.

Molecules doi: 10.3390/molecules31162825

Authors: Ange Murielle Djidjou Tagne Kotoe Ishii Yasukiyo Yoshioka Kouichi Sugaya Jun-ichi Onose Shunsuke Yajima Naoki Abe

The bioregulatory function of food-derived bioactive factors in complementary therapies for lifestyle-related diseases is attracting worldwide attention. Vialinin A, a p-terphenyl compound isolated from the edible Chinese mushroom Thelephora vialis, inhibits the production and release of tumor necrosis factor α and Syk kinase activity, a key protein involved in the development of allergic rhinitis. However, its effect on other calcium-independent signaling molecules remains unclear. This study investigated the effects of vialinin A on microtubule formation signaling pathways in RBL-2H3 cells. The results showed that vialinin A inhibited Fyn kinase activity and reduced PI3K (class IA) phosphorylation in a dose-dependent manner. Notably, vialinin A inhibited PI3Kδ kinase activity and reduces Akt phosphorylation even at low concentrations. These findings suggest that vialinin A suppresses microtubule formation and granule translocation required for mast cell degranulation through inhibition of the Fyn–PI3K–Akt signaling pathway. Collectively, vialinin A may represent a promising lead compound for the development of anti-allergic therapeutics.

Molecules doi: 10.3390/molecules31162824

Authors: Huan Yue Shigang Li Yixian Lv Xueqing Wang Jinlong Pan Hao Wu Heng Zhang Hexin Zhang

The development of lightweight multifunctional materials integrating electromagnetic interference (EMI) shielding, Joule heating and flame retardancy is highly demanded for advanced electronics and aerospace systems. Herein, we fabricate graphene/Fe3O4@hollow glass microsphere (G/Fe3O4@HGM) composite foam with an ultralow density of 0.36 g/cm−3. The porous structure synergizes graphene’s conductivity, Fe3O4’s magnetism and HGM’s low thermal conductivity to optimize impedance matching. The foam delivers absorption-dominated EMI shielding with a maximum X-band shielding effectiveness (SE) of 60.1 dB and an average absorption coefficient of 0.56, which effectively suppresses secondary electromagnetic reflection pollution. The composite exhibits stable voltage-controllable Joule heating: the 25 wt% Fe3O4@HGM sample reaches 91.3 °C at 16 V, enabling rapid de-icing within 200 s and stable thermal maintenance at −20 °C. Flame tests confirm no combustion or structural collapse under open flame. This work provides a simple fabrication strategy for lightweight multifunctional materials applicable to aerospace stealth, electronic thermal management and anti-icing systems.

Molecules doi: 10.3390/molecules31162818

Authors: Ning Sun Xinyu Guo Enxi Li Yan Zhou Shuli Yin Peizhe Cui

In this study, five levulinic acid-based deep eutectic solvents (DESs) were evaluated for the ultrasound-assisted extraction of curcuminoids from Curcuma longa. The relationship between DES composition, intermolecular interactions, and extraction performance was investigated by combining extraction experiments with spectroscopic characterization and quantum chemical calculations. The levulinic acid–ethylene glycol system at a 1:2 molar ratio exhibited the best performance, achieving an extraction yield of 99.9 mg·g−1. FTIR and 1H NMR analyses characterized the interactions within the DES, while SEM observations indicated structural disruption of the turmeric matrix after ultrasound treatment. Molecular analyses suggested that hydrogen bonding and van der Waals interactions contributed to the association between the DES and curcuminoids. These results provide molecular insights into the extraction process and a basis for designing greener solvent systems for curcuminoid extraction.

Molecules doi: 10.3390/molecules31162823

Authors: Coleen E. Grobler Blessing Mabate Justin B. Safari Brett I. Pletschke

Fucoidans are sulphated polysaccharides from brown macroalgae that have attracted considerable interest due to their diverse biological activities and potential applications in metabolic health. In this study, fucoidan-rich extracts were obtained from three South African brown macroalgal species, Ecklonia maxima, Ecklonia radiata, and Sargassum incisifolium, and comparatively characterised using biochemical and physicochemical analyses. The extracts were evaluated for carbohydrate, sulphate, L-fucose, protein, polyphenol, and uronic acid contents, while molecular weight distribution, Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and proton Nuclear Magnetic Resonance (1H NMR) spectroscopy were used to investigate structural characteristics. All extracts displayed features characteristic of fucoidans, including sulphated fucose-containing polysaccharides. Notable species-dependent differences were observed, with S. incisifolium exhibiting the highest sulphate (~24%) and polyphenol (~6.76%) contents, stronger sulphate-associated FTIR signals, greater molecular weight heterogeneity, and enhanced thermal stability. The fucoidan-rich extracts exhibited concentration-dependent pancreatic lipase and α-glucosidase inhibitory activities, together with DPPH radical-scavenging activity. At 1.0 mg/mL, S. incisifolium demonstrated approximately 66% DPPH radical scavenging and 49% pancreatic lipase inhibition. S. incisifolium and E. radiata exhibited strong α-glucosidase inhibition, with IC50 values of ~29 and ~46 µg/mL, respectively, compared to ~354 µg/mL for acarbose. The findings highlight South African brown macroalgae as promising sources of fucoidans and contribute to understanding the relationships among fucoidan composition, structure, and bioactivity.

Molecules doi: 10.3390/molecules31162822

Authors: Fangying Chen Wan Yin Tew Ming Thong Ong Mun Fei Yam

The effect of Corosolic acid (CA) on vascular tone and the possible mecha-nisms involved remain unclear. The SPF-grade male Sprague-Dawley rats (Animal Ethics Approval ID: USM/IACUC/2025/(155)(1406)) were used. The vasorelaxant effects of CA were evaluated in endothelium-intact and endothelium-denuded rings precontracted with phenylephrine (PE), and in endothelium-intact rings precontracted with KCl. Possible mechanisms were examined using L-NAME, ODQ, methylene blue, indomethacin, atropine, propranolol, and potassium channel blockers (glibenclamide, TEA, BaCl2, and 4-AP). The effects of CA on voltage-operated calcium channels (VOCCs) and IP3 receptor (IP3R)-mediated sarcoplasmic reticulum calcium release were also assessed. CA concentration-dependently relaxed endothelium-intact aortic rings precontracted with PE (RMAX = 90.08 ± 7.33%; pD2 = 4.21 ± 0.08). The relaxation response was markedly reduced after endothelial removal and in KCl-precontracted rings. EDRF pathway inhibitors (L-NAME, ODQ, methylene blue, and indomethacin) and GPCR-related antagonists (atropine and propranolol) attenuated CA-induced relaxation. Among potassium channel blockers, glibenclamide and TEA showed stronger inhibitory effects. CA did not significantly inhibit VOCC-mediated CaCl2-induced contraction but partially reduced PE-induced contraction under calcium-free conditions. The mechanisms for CA treating hypertension may involve NO/cGMP signalling, COX-related prostanoid pathways, GPCR-related mechanisms, potassium channel modulation, and partial inhibition of IP3R-mediated calcium release.

Molecules doi: 10.3390/molecules31162821

Authors: Maurice K. H. Essers Hans Leemhuis Johannes H. Bitter Lambertus A. M. van den Broek

Starch-modifying glycoside hydrolases (GHs) typically operate via a retaining double-displacement mechanism, involving formation of a covalent glycosyl–enzyme intermediate. This intermediate can be resolved either by water, resulting in hydrolysis, or by a glucan acceptor, leading to transglucosylation. Many GHs exhibit both catalytic activities, although they are classified according to their predominant reaction. For example, branching enzymes (BEs) catalyse α-(1→4) bond cleavage and α-(1→6) branch formation via transglucosylation, while also exhibiting minor hydrolytic and disproportionation activities that broaden their catalytic repertoire. More recent research indicates that the different catalytic activities of BEs can be interconnected, thereby collectively determining the final α-glucan architecture. This challenges the classical view that the predominant branching activity of BEs is catalysed independently. Moreover, the balance between these coupled activities influences substrate specificity and can broaden the substrate scope to include chemically modified starches. Furthermore, the co-application of BEs with other GHs reveals synergistic interactions between catalytic activities, enabling the generation of α-glucan structures that cannot be produced by any of the enzymes individually. In this perspective paper, and based on recent developments, we argue that the catalytic framework of BEs provides multiple strategies for tailoring diverse α-glucan architectures. This enables modulation of structural features across hierarchical levels, from supramolecular to macromolecular organisation. As a result, BEs represent versatile tools for engineering starch functionality beyond digestibility, extending their potential toward pharmaceutical and non-food applications. Looking ahead, we discuss how enzyme-designed and chemically functionalised α-glucan polymers may emerge as a new class of sustainable materials. These materials could provide biodegradable, water-soluble, and renewable alternatives to petrochemical-derived polymers used in personal and home care products.

Molecules doi: 10.3390/molecules31162820

Authors: Siyuan He Yongqiu Yan Feifei Xiong Wenwen Diao Fuhuai Jia Xiaodong Yan Jing Wang

Excessive ultraviolet A (UVA) irradiation disrupts extracellular matrix (ECM) homeostasis in skin photoaging by impairing the balance between synthesis and degradation, yet whether silk fibroin peptide (SF), a small bioactive peptide from Bombyx mori, can restore this balance through mechanotransduction pathways remains unknown. Herein, we demonstrate that SF dose-dependently rescues human dermal fibroblasts (HDFs) from UVA-induced oxidative stress, senescence, and ECM disintegration. Notably, SF not only suppresses reactive oxygen species (ROS) and restores activities of antioxidant enzymes, but is also associated with the recovery of the ITGB1-FAK mechanotransduction axis, as evidenced by restored fibronectin levels and increased focal adhesion kinase (FAK) phosphorylation, whereas integrin β1 (ITGB1) expression itself was not significantly altered. This mechanosensory recovery is accompanied by restoration of downstream transforming growth factor-β (TGF-β)/Smad signaling, upregulation of COL1A1, COL3A1 and ELN transcription, and simultaneous suppression of MMP1, MMP3 and MMP9. Unlike conventional antioxidants or exogenous collagen supplements that merely counteract oxidative damage or provide structural substitutes, SF may facilitate recovery of the disrupted cell–matrix interface potentially through modulation of integrin-mediated mechanochemical signal conversion, which may contribute to ECM homeostasis restoration. Collectively, SF promotes mechanotransduction, offering a potential paradigm for anti-aging strategies that target ECM homeostasis through integrin signaling.

Molecules doi: 10.3390/molecules31162819

Authors: Rosa Zullo Rosaria Lauceri Alberto Zullo Luigi Sorrentino Angela Boggero Lyudmila Kamburska Andrea Lami Silvia Zaupa Maria Oliviero

Freshwater crayfish impact ecosystems and the food industry. The aim of the study was to valorize shells from the invasive crayfish, Faxonius limosus, to extract novel bioactive biopolymers and prepare biodegradable films, thereby contributing to economic and environmental sustainability. Chitin from crayfish shells was isolated and converted into chitosan through a new protocol to retain astaxanthin, with a shorter procedure, reduced use of organic solvent and energy consumption. The resulting biopolymers were used to prepare chitosan-based films. Thermal, spectroscopic, barrier properties, and surface microstructure of the biomaterials were identified. Spectrophotometric and chromatographic techniques were used on crayfish shells and biopolymers to track astaxanthin throughout the extraction and formulation processes. Crayfish chitosan film exhibited higher stiffness, enhanced thermal stability and water vapor barrier properties with respect to commercial chitosan films. 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and 2,2-diphenyl-1-picrylhydrazyl antioxidant assays showed that all crayfish biomaterials exhibited antioxidant activity. Astaxanthin greatly enhanced the antioxidant properties of crayfish chitosan, but chemical degradation during film processing limited this effect in the film matrices. Therefore, crayfish-derived biopolymers and films are promising for incorporation into functional foods and active packaging and support shell waste reduction, offering a viable strategy for managing and valorizing invasive species.

Molecules doi: 10.3390/molecules31162817

Authors: Junjie Wang Xueyan Liu Dian Zhuang Zixuan Ren Weihong Chen Mingqiong Guo Zenglai Xu Qiong Wang

Abelmoschus manihot (L.) flowers are widely used in traditional Chinese medicine, whereas the roots are often discarded as agricultural waste. The compact cellular and tissue architecture of the roots hinders the release of intracellular metabolites, thus impeding their reutilization. Here, enzyme-assisted ultrasonic extraction was developed to obtain a polysaccharide-rich crude extract from A. manihot roots. Orthogonal optimization identified pH 4.5, a temperature of 60 °C and a cellulase dosage of 6% (w/w) as the optimal extraction conditions, giving an extraction yield of 21.59%. The phenol–sulfuric acid assay indicated a total carbohydrate content of 75.09% (glucose equivalents). Structural analysis by Fourier transform infrared (FT−IR) confirmed the presence of characteristic polysaccharide functional groups, while monosaccharide composition analysis via high-performance liquid chromatography (HPLC) revealed the major components of glucose, glucuronic acid, rhamnose, galacturonic acid, etc. Inspired by the traditional use of A. manihot extract in papermaking, its preliminary hair care-related properties were further evaluated. At a concentration of 30 mg/mL, the extract solution inhibited Malassezia furfur growth by 84%, reduced wet and dry combing work by 16.93% and 30.86%, and increased tensile strength and tensile fracture energy by 13.04% and 14.84%, respectively. Scanning electron microscope (SEM) images suggested smoother hair fiber surfaces after treatment. These results highlight the extract’s great potential for hair care cosmetic products.

Molecules doi: 10.3390/molecules31162816

Authors: Roozbeh Kalateh Danmei Sun Aimaro Sanna

The valorisation of textile wool waste through sustainable conversion technologies such as pyrolysis has gained increasing attention as an effective strategy to reduce textile waste, recover valuable resources, and support the transition toward a circular economy. Herein, we investigated the pyrolysis of processed wool textile waste in CO2 and N2 atmospheres to recover valuable products and reduce the environmental impact. Key factors such as the temperature, carrier gas type, feed size, condensation set-up, and reactor configuration were evaluated for their influence on product distribution and quality. Pyrolysis at 900 °C in the presence of CO2 led to greater gas formation (79 wt%), enhanced the stability and BET surface area of the char (10–12 wt%), and increased byproducts including phenol and indole in the bio-oil (13 wt%) product. CO made up over 65% of the gas at 900 °C due to the prevalence of the reverse (endothermic) Boudouard reaction, with the remnant gas made of CO2 (21%) and small amounts of NH3 (2%), HCN (0.8%) and SO2 (0.3%). This CO-rich gas could have industrial applications such as Fischer–Tropsch after conditioning and N/S removal. Moreover, the higher carbon content (82.5% at 900 °C) increased the stability of char produced with CO2 (compared to N2), making it suitable for soil enhancement (~10% N at 900 °C) or pollutant removal and allowing it to be categorised and marketed as biochar. Despite low-temperature pyrolysis (350 °C) not being efficient in decomposing the whole wool waste, a staged pyrolysis with an initial low-temperature stage was shown to be effective in separately removing bromine-rich compounds. In summary, this study provides insights into the thermal decomposition behaviour of wool and the influence of the reaction conditions and reactor type on product distribution.

Molecules doi: 10.3390/molecules31162815

Authors: Sérgio Fallone de Andrade Eduardo Breviglieri Ivan Limachi Luisa Mota da Silva Thaise Boeing Lincon Bordignon Somensi Olov Sterner Alberto Gimenez Valdir Cechinel Filho

The treatment of gastric ulcers based on antisecretory drugs is often associated with side effects and high recurrence rates, reinforcing the need for new therapeutic alternatives. Medicinal chemistry guided by natural prototypes represents a productive strategy in this context. The antiulcer potential of 2-phenylquinoline (2-PQ), an alkaloid from Conchocarpus longifolius (A.St.-Hil.) Kallunki & Pirani (syn. Galipea longiflora Krause), has been previously reported by our research group. In the present work, four 2-PQ derivatives were synthesized—2,4-diphenylquinoline (1), 2-(4-methoxyphenyl) quinoline (2), 2-phenylquinolin-4-ol (3), and 4-methoxy-2-phenylquinoline (4)—and evaluated for gastroprotective activity in the HCl/ethanol-induced gastric ulcer model in mice. The quinoline derivatives were prepared mainly by trifluoroacetic acid-catalyzed condensations of aminated benzaldehyde or benzophenone precursors with the corresponding ketones under reflux at 100 °C, affording yields of 68–94%. Compound 3 was synthesized via a two-step sequence involving the acylation of 2-aminobenzophenone followed by base-induced cyclization, providing an 85% yield. Compound 4 was obtained by O-methylation of compound 3 using iodomethane (MeI) and potassium carbonate (K2CO3) in dimethylformamide (DMF), affording a 95% yield. So, this study provides the first comparative analysis linking structural modifications to gastroprotective activity in synthetic quinoline derivatives inspired by 2-phenylquinoline, a natural alkaloid previously shown to exert gastroprotective effects. Carbenoxolone (200 mg/kg, p.o., positive control) inhibited gastric lesion formation by 94.1%. The synthetic quinoline derivatives also showed significant gastroprotective activity after oral administration (30 mg/kg), reducing ulcer area by 72.4% (compound 1), 76.1% (compound 2), 49.1% (compound 3), and 66.1% (compound 4). Compounds 2, 3, and 4 further retained efficacy following intraperitoneal administration (3 mg/kg), whereas compound 1 was inactivated by this route. Overall, compound 4 exhibited the greatest efficacy, significantly reducing the gastric lesion area, decreasing lipid hydroperoxide (LOOH) and tumor necrosis factor-alpha (TNF-α) levels, and increasing glutathione (GSH) content in ulcerated gastric tissue. These findings suggest that its gastroprotective effects are mediated by antioxidant and anti-inflammatory mechanisms, identifying compound 4 as the most promising candidate for the prevention and treatment of peptic ulcers. Its promising pharmacological profile warrants further investigation to elucidate its molecular mechanisms of action, assess its safety and efficacy in additional preclinical studies, and explore its potential for future therapeutic development.

Molecules doi: 10.3390/molecules31162814

Authors: Qi He Pengju Wang Xudong He Jincang Zhang Yi Liu

Accurate energy prediction in organic molecular crystals, such as cyclotrimethylenetrinitramine (RDX) and cyclotetramethylenetetranitramine (HMX), is hindered by the scarcity of descriptors capable of encoding their hierarchical architecture. Furthermore, while reactive force field (ReaxFF) offers a pathway to simulating chemical reactions, its accuracy for polymorph stability remains suboptimal, and machine learning (ML) driven refinement of ReaxFF for molecular systems remains unexplored. Herein, we report the first construction of a Hierarchical “Center-Environment” (HCE) feature framework specifically tailored for molecular crystals. The HCE framework hierarchically decomposes structural complexity into intramolecular (ring vs. nitro groups) and intermolecular (central molecule vs. coordination shell) attributes, integrating physics-based priors with distance-weighted attention. Using this compact descriptor set, we present the first attempt to rectify ReaxFF predictions via ML, benchmarking against 5930 RDX and 3335 HMX DFT-calculated energies. Our models achieve a significant reduction in mean absolute error: from ~116.7 to 42.2 meV/atom for RDX (kernel ridge regression, KRR) and from 112.3 to 53.7 meV/atom for HMX (support vector regression, SVR). Crucially, HCE features enable robust cross-molecule transferability; a neural network pre-trained on RDX yields a validation error of 52.9 meV/atom on HMX, surpassing models trained exclusively on HMX data. This work not only establishes a pioneering paradigm for interpretable ML-driven force field refinement but also provides the first feature engineering solution incorporating chemical, physical, and structural information specifically designed for the machine learning of energetic molecular crystals.

Molecules doi: 10.3390/molecules31162813

Authors: Carlos Iván Méndez-Barrientos Zuriel Natanael Cisneros-García José Guadalupe Facio-Muñoz Alessandro Romo-Gutiérrez Jaime Gustavo Rodríguez-Zavala

Nitrites and nitrates are admitted into the body through the consumption of various foods, primarily cured meat products. These nitrites and nitrates are precursors of reactive nitrogen species NO and NO2, which, in excess, promote nitrosative stress. Attempts have been made to combat oxidative and nitrosative stress through C60 fullerenols in animal models. Furthermore, experimental and theoretical studies have shown that the use of carbon nanomaterials such as defective or doped graphene and C60 metallofullerenes facilitates the capture of NOx pollutants contained in the air. This leads us to propose that the inclusion of metals in C60 fullerenols may have the potential to capture these reactive nitrogen species and be considered in nitrosative stress tests in animal models. Alternatively, viewed from another perspective, a certain grade of hydroxylation of metallofullerenes could enhance the capture of atmospheric nitrogen pollutants. Therefore, Li, Ca and Y metals were included in C60 fullerenols at different coating grades. Using density functional theory (DFT), we analyzed the antiradical character of these metallofullerenols, and the adsorption energies of the free radicals (NOx) were calculated to evaluate the ability of these metallofullerenols to adsorb these nitrogen species. Although both fullerenols and endohedral metallofullerenes have individually shown promise as radical scavengers, a systematic understanding of how the encapsulated metal and the grade of hydroxylation jointly govern the capture of nitrogen species is still lacking. In particular, it remains unclear whether increasing the number of hydroxyl groups monotonically enhances the capture capacity or whether optimal combinations of metal identity and surface functionalization exist. Addressing this gap is crucial, since excessive hydroxylation may alter the electronic structure, stability, and mechanism of interaction with NOx radicals, potentially compromising capture capacity. Therefore, a rational evaluation that simultaneously considers electronic donor–acceptor properties, local reactivity, and adsorption thermodynamics is required to identify metallofullerenols with possible potential to sense or scavenge NOx.

Molecules doi: 10.3390/molecules31162812

Authors: Marta Kinga Lemieszek Michał Chojnacki Iwona Paśnik Ilona Leśniowska Jakub Anisiewicz Wiktoria Gawryś Alicja Wilczyńska Michał Kiełbus

Our earlier studies have revealed the beneficial impact of vitamin D3 (VD3) metabolites on the development of pulmonary fibrosis in a murine model of hypersensitivity pneumonitis (HP). Despite the discovery of the great antifibrotic potential of both the bioactive form of VD3, 1,25(OH)2-VD3 and its direct precursor, 25(OH)-VD3, study designs based on the co-administration of VD3-metabolites and fibrosis-inducers do not reflect the clinical situation. Thus, the presented study aims to examine the effectiveness of therapeutic interventions based on the mentioned inhalations, initiated during the acute phase of HP at the first signs of pulmonary fibrosis. The research was performed using VD3-deficient mice with HP, while VD3-sufficient mice were used as the main control. The data were collected after 28 days of daily exposure of the mice to a fibrosis-inducer (an antigen of Pantoea agglomerans, a well-known etiological factor in HP), with 25(OH)-VD3 or 1,25(OH)2-VD3 administered daily during the last 14 days of the experiment. The effect of the intervention was monitored by whole-body plethysmography, histological assessment, flow cytometry, RealTime-PCR, and ELISA. Treatment with VD3 metabolites initiated during the acute phase of HP alleviated the disease courses and restored respiratory function, thanks to inhibition of pathological extracellular matrix deposition, immune-cell infiltration of lung parenchyma, profibrotic cytokine production, and EMT progression. Despite the discovery of the beneficial features of the investigated VD3-based therapies, none of them caused full recovery in mice with HP. Nevertheless, after verification in additional animal models and a deeper understanding of the underlying molecular mechanisms, the identified beneficial features of the investigated metabolites have the potential to serve as a foundation for future therapies for HP fibrosis.

Molecules doi: 10.3390/molecules31162811

Authors: Yiran Li Wenhong Fan Shuting Hou Yue Ding Xiuqing Jia Xi Zhu Yuemeng Yuan Yufei Zhang Yanrong Cao Xi Qin Chenggang Liang Lan Wang

Bietti crystalline dystrophy like retinal degeneration (BCD) is an inherited retinal degenerative disease caused by defects in the CYP4V2 gene. Recombinant AAV-based gene replacement therapy holds promise for this disease, yet reliable enzymatic activity assays for product potency evaluation remain urgently needed. This study established and validated a method for determining the enzymatic activity of CYP4V2 based on the bioluminescent substrate Luciferin-MultiCYP.HEK293-AAVR cells were seeded at 1 × 104 cells/well and transduced with rAAV-hCYP4V2 across an MOI gradient (1.17 × 103–2.4 × 106). After incubating at 37 °C for 72 h, medium was replaced with Opti-MEM containing 20 µM Luciferin-MultiCYP and incubated for 90 min ± 30 min. Next, cell supernatants were mixed with luciferase reagent, and bioluminescence was measured. Methodological validation results revealed that the method has good specificity, with an accuracy recovery rate of 100.94% ± 2.84% (RSD = 2.81%). Repeatability (GCV%) was 4.21%, and intermediate precision (RSD) was 6.16%. Linearity was good within the MOI range of 1.17 × 103 to 2.4 × 106 (R2 = 0.9902 ± 0.0061, n = 9). Lastly, the method was successfully applied to activity testing the products of three AAV serotypes (AAV8, AAV2/8, and AAV2). This bioluminescent method meets regulatory potency assay requirements and serves as an effective QC tool for process development, batch release, and stability evaluation of rAAV-hCYP4V2 products.

Molecules doi: 10.3390/molecules31162808

Authors: Ziyue You Yitong Qin Yubing Gao Zhengzhi Mu Fu Liu Shuzhi Sam Ge

Small experimental datasets make synthesis-condition modelling particularly sensitive to overfitting and data leakage. Here, a graph convolutional neural network (GCNN) was coupled with approximate attribution enhancement (AAE) and evaluated on 54 gold-nanocluster synthesis records using a strict fold-local pipeline. All preprocessing, supervised representation learning, augmentation, model selection, and calibration were confined to each training fold, and metrics were calculated only on untouched original records. The strongest no-augmentation model achieved a Matthews correlation coefficient (MCC) of 0.729. With 20,000 fold-local AAE samples, Logistic Regression reached an accuracy of 0.864, an F1 score of 0.862, and an MCC of 0.758. The corresponding MCC values decreased to 0.579, 0.526, and 0.652 under leave-one-ligand-out, leave-one-publication-out, and leave-region-out evaluation, respectively, indicating that extrapolation beyond represented chemistry remained more difficult than random-fold interpolation. Feature, label-weight, augmentation-baseline, covariance, calibration, and stability analyses consistently identified ligand aromaticity, temperature, and HAuCl4 concentration as the most influential factors. An interpretable analysis of a 34-record aqueous Au25 subset further produced condition rules and a pH–temperature map, while nine literature formulations provided an external audit within the represented domain. The results position AAE as a local regularisation strategy for data-limited synthesis modelling rather than as a source of new chemical information.

Molecules doi: 10.3390/molecules31162809

Authors: Peng Xiang Jian Zheng Zhaokai Yu Yan Wang

Biogas slurry can enhance soil fertility, but the heavy metals it contains may pose potential ecological risks to soil-crop systems. To mitigate heavy metal pollution resulting from the application of biogas slurry to soil, this study investigated potential remediation strategies through the use of blended biochar application. In this study, soil incubation experiments were conducted to evaluate the immobilization performance of cow dung biochar (CB), corn straw biochar (SB), and blended biochar (cow dung + corn straw) (C3S7, C5S5, and C7S3) toward Pb, Zn, Ni, Cr, Cu, As, and Cd under different biogas slurry ratios (Z0, Z1:8, and Z1:4). The results concluded that immobilization efficiency consistently followed the order C7S3 ≥ C5S5 > C3S7 > CB ≈ SB, indicating that the blended biochar generally outperformed the two single biochar in the biogas slurry-irrigated soil system. Batch adsorption experiments showed that adsorption of all metals was better described by the pseudo-second-order model (R2 > 0.94). Isotherm fitting further indicated that Zn, Ni, Cr, Cu, and Cd were better fitted by the Langmuir model, whereas Pb and As were better fitted by the Freundlich model. Physicochemical characterization, scanning electron microscopy–energy-dispersive X-ray spectroscopy (SEM–EDS), and Fourier transform infrared spectroscopy (FTIR) analyses collectively suggested that the superior performance of blended biochar was associated with the integration of mineral-related characteristics from CB and surface chemical properties from SB, which together enhanced the synergistic fixation of coexisting metals. Consistently, biochar application reduced the potential ecological risk index (RI) of bioavailable heavy metals in soil, with blended biochar showing lower RI values than CB and SB. C7S3 exhibited the best performance in all treatments, highlighting the potential of blended biochar as an effective amendment for mitigating multi-metal pollution risks with biogas slurry utilization.

Molecules doi: 10.3390/molecules31162810

Authors: Daniel A. Jacobo-Velázquez

Quercetin is a plant-derived flavonol positioned at the interface of metabolic health and food preservation. This review integrates quercetin chemistry, plant biosynthesis and metabolism, production-relevant extraction and microbial synthesis, bioavailability, mechanisms of action, preclinical and clinical evidence in metabolic syndrome (MetS), and applications in clean-label food preservation. Experimental studies indicate that quercetin modulates obesity-associated inflammation, dyslipidemia, hepatic steatosis, insulin resistance, hypertension, endothelial dysfunction, and gut-barrier impairment through interconnected Nrf2/HO-1, NF-κB/NLRP3, AMPK/SIRT1, PI3K/Akt, eNOS/NO, lipid metabolism, and microbiota-related pathways. Human evidence is narrower and heterogeneous: modest reductions in systolic blood pressure constitute the most consistent signal, whereas effects on fasting glucose, lipids, inflammatory markers, endothelial function, liver fat, and body weight vary by population, formulation, dose, and duration. In food systems, quercetin has been investigated as an antioxidant, antimicrobial, antibiofilm agent, and photodynamic photosensitizer. It is incorporated into edible films, coatings, freshness indicators, and controlled-release packaging, although most evidence remains laboratory-scale. Key translational challenges include limited aqueous solubility, variable bioavailability, incomplete long-term safety evidence, matrix-dependent efficacy, sensory constraints, manufacturing scale-up, migration, and regulation. Overall, quercetin is promising, but clinical use and industrial deployment require formulation-specific, adequately powered human studies and validation in clinically relevant populations and under commercially realistic processing conditions.

Molecules doi: 10.3390/molecules31162807

Authors: Lúcia Raquel Ramos Berger Thayza Christina Montenegro Stamford Marcos Antonio B. de Lima Danielle Silva Araújo Mateus Henrique Freire Farias Krause Gonçalves Silveira Albuquerque Leonie Asfora Sarubbo Mayri Alejandra Diaz De Rienzo André Luiz Cabral Monteiro de Azevedo Santiago Gerla Castello Branco Chinelate

The sustainable reuse of industrial by-products in fermentation processes supports the transition toward a circular bioeconomy. This study evaluated the production yield of fungal chitosan (FuCho) by nine Mucorales strains, including novel species isolated from Brazilian biomes, cultivated in alternative culture media composed of corn steep liquor (CSL) and biodiesel-derived glycerol (GLY). Furthermore, the physicochemical properties, potential of irritation, and broad-spectrum antimicrobial activity of the extracted FuCho were investigated. Among the strains tested in CSL-GLY medium, FuCho yields ranged from 17.88 mg/g (Absidia aguabelensis) to 126.56 mg/g (Absidia caatinguensis). Optimization using a 22 central composite rotatable design (CCRD) yielded maximum FuCho productions of 128.26 mg/g for A. caatinguensis (center point condition) and 164.92 mg/g for Cunninghamella elegans (lower CSL concentration). Physicochemical characterization revealed degrees of deacetylation of 85% (A. caatinguensis) and 75% (C. elegans), crystallinity indices of 36.74% and 37.93%, and viscometric molecular weights (Mv) of 1.6×103 g/mol and 2.0×103 g/mol, respectively. In the HET-CAM assay, both FuCho samples were classified as non-irritating, exhibiting no inflammatory, vascular, or vasoconstrictive effects. FuCho demonstrated minimum inhibitory concentrations (MIC) against all tested pathogenic bacterial strains and Candida species, with A. caatinguensis FuCho displaying lower MIC values for the majority of microorganisms compared to C. elegans FuCho. Confocal laser scanning microscopy confirmed a significant reduction in microbial cell viability, driven by membrane disruption in Escherichia coli and Staphylococcus aureus. These findings validate the CSL-GLY mixture as a cost-effective, eco-friendly culture medium for producing high-value biopolymers with pharmaceutical potential, underscoring the biotechnological relevance of Brazilian Mucorales strains.

Molecules doi: 10.3390/molecules31162806

Authors: Neli Ghukasyan Naira Shaboyan Elena Arutinian Arshaluys Ghazaryan Vahe Hovhannisyan Gayane Poghosyan Marine Hovhannisyan Kostandin Manukyan Greta Ulikhanyan Sona Feschyan Maya Hovsepyan Lusine Danielyan Hrachya Hovhannisyan Naira Chichoyan Serkos Haroutounian

This study is the first report on the chemical composition and antimicrobial activity of Chaerophyllum bulbosum L. sampled from the Armenian flora. Essential oil (EO) and hydrosol were obtained from the aerial parts by hydrodistillation, and their chemical compositions were determined by GC–MS, identifying a total of 48 volatiles. The EO was composed of 60.42% monoterpenes and their oxygenated derivatives and 18.75% sesquiterpenes and their oxygenated derivatives, while the hydrosol was composed of 75% oxygenated monoterpenes, with the remaining 20% and 5% being monoterpenes and sesquiterpenoids respectively. Pulegone (21.55%) was identified as the major constituent. With regard to the non-volatile fraction, the methanolic extract displayed a total phenolic content of 1.17 ± 0.03 mg GAE/g dry weight and a total flavonoid content of 0.62 ± 0.02 mg QE/g, as well as significant antioxidant capacity, with IC50 values of 2.87 ± 0.06 μg Trolox/g dried plant sample for the DPPH• assay and 46.87 ± 1.2 μmol Fe2+/g dried plant sample for the FRAP assay. The evaluation of EO and hydrosol antimicrobial properties revealed notable antibacterial activity against Gram-positive bacteria, with inhibition zones ranging from 13.5 to 20 mm. The respective minimum inhibitory concentration (MIC) values ranged from 0.4 to 6.0 mg/mL for the EO and from 62.5 to 400 μL/mL for hydrosol, while the minimum bactericidal concentration (MBC) values ranged from 0.8 to 10.0 mg/mL and from 125 to 800 μL/mL, respectively. Streptococcus mutans was the most susceptible microorganism (MIC = 0.4 mg/mL), whereas Pseudomonas aeruginosa was the most resistant (MIC = 6.0 mg/mL). Both the EO and hydrosol exhibited antifungal activity against Candida albicans, with inhibition zones of 13.0 ± 1.2 mm and 11.0 ± 0.8 mm, respectively. The MIC and MBC values were 1.0 and 2.0 mg/mL for the EO, while the respective values for the hydrosol were 400 and 800 μL/mL. These findings highlight the C. bulbosum plant as a promising source of bioactive compounds with significant activity against Gram-positive bacteria and moderate antifungal effects that may be associated with the high content of pulegone, a monoterpene known for its membrane-disruptive properties.

Molecules doi: 10.3390/molecules31162803

Authors: Kazuki Koike Takeharu Murakami Kentaro Inoue Takayo Ogawa Katsushi Fujii Satoshi Wada Atsushi Ogura

Electrochemical CO2 reduction reaction (eCO2RR) is a promising technology for carbon utilization, yet achieving high product selectivity and long-term stability remains a critical challenge. In this study, we investigated the performance and surface stability of Cu electrodes modified with Ag nanoparticles using a spray-coating method. While a bare Cu reference electrode exhibited an initial starting period dominated by hydrogen evolution before shifting toward hydrocarbon production after two hours, the Ag-spray-coated Cu electrode demonstrated immediate and stable catalytic activity. Electrode potential remained stable throughout the 12 h evaluation, in contrast to the negative shifts observed with the bare Cu electrode. Ambient pressure hard X-ray photoelectron spectroscopy (AP-HAXPES) revealed that while the bare Cu surface remained metallic, the Ag-spray-coated Cu surface existed as Cu2O during the reaction. The enhanced selectivity and stability are attributed to a spillover mechanism, where CO generated on the Ag nanoparticles migrates to adjacent Cu2O sites, inhibiting hydrogen evolution and facilitating efficient reduction to methane and ethylene from the onset of electrolysis. These findings demonstrate that surface modification via nanoparticle spray coating is a highly effective strategy for achieving selective and stable CO2 conversion on bimetallic catalysts.

Molecules doi: 10.3390/molecules31162805

Authors: Kamel A. Saleh Tahani H. Albinhassan Serage Eldin I. Elbehairi Mohammed A. Alshehry Mohammad Y. Alfaifi Adel M. Al-Ghazzawi Mohamed A. Al-Kahtani Abdullah D. A. Alasmari

The journal retracts the article “Cell Cycle Arrest in Different Cancer Cell Lines (Liver, Breast, and Colon) Induces Apoptosis under the Influence of the Chemical Content of Aeluropus lagopoides Leaf Extracts” [...]

Molecules doi: 10.3390/molecules31162804

Authors: Antonella Maria Aresta Giada Stefania Signorile Antonietta Clemente Nicoletta De Vietro Carlo Zambonin

The oral cavity represents an extremely complex and dynamic microbial ecosystem capable of rapidly adapting to antimicrobial stress. These characteristics make it a promising environment for the identification of novel bioactive molecules with therapeutic potential. At the same time, the increasing prevalence of resistant pathogens in dental and oral-maxillofacial infections highlights the limitations of current therapeutic strategies and the urgent need for new effective antibacterial agents. This review examines the central role of advanced analytical techniques, with particular emphasis on mass spectrometry, in the discovery and characterization of bioactive metabolites and biomarkers relevant to future antibacterial discovery and to the understanding of biological responses to pathogens or therapeutic interventions. It discusses how the integration of metabolomics approaches, imaging mass spectrometry, and bioinformatics platforms is transforming the antibacterial discovery process by accelerating the identification of active compounds and improving the understanding of microbial interactions within the oral cavity. Overall, this work provides an up-to-date overview of current knowledge regarding the oral microbiome as a source of bioactive molecules and biomarkers. It highlights how emerging analytical technologies are opening new perspectives for the development of innovative therapeutic strategies against resistant oral infections.

Molecules doi: 10.3390/molecules31162802

Authors: Molecules Editorial Office Molecules Editorial Office

With this notice, the Molecules Editorial Office wishes to alert readers to concerns related to this article [...]

Molecules doi: 10.3390/molecules31162801

Authors: Xiang Li Tingting Wang Linfeng Mo Huixin Cao Zhongting Lv Jia Yu Shuang Liu Yantong Sun Tianli Chen

Disruption of neuronal excitation–inhibition balance and mitochondrial quality control may contribute importantly to lead (Pb)-induced neurotoxicity, but nutritional modulators targeting these processes remain poorly characterized. This study investigated the protective effects and underlying mechanisms of ginsenoside Rh1, a ginseng-derived bioactive compound, in Pb-exposed mice and Pb-treated HT22 hippocampal cells. Chronic Pb exposure caused spatial recognition deficits, reduced exploratory activity, anxiety-like behaviors, and marked neuronal injury, accompanied by Pb accumulation in blood and brain tissues, elevated IL-1β, TNF-α, and IL-6 levels, oxidative stress, reduced Gama-aminobutyric acid (GABA) content, and dysregulated NKCC1/KCC2 expression. In HT22 cells, Pb increased intracellular ROS generation and disrupted mitophagy-related signaling, as indicated by alterations in PINK1, Parkin, LC3, P62, and GABARAP. Rh1 treatment alleviated Pb-induced behavioral abnormalities and neuronal pathology, reduced Pb burden, suppressed neuroinflammatory responses, enhanced antioxidant defenses, improved Pb-associated alterations in GABAergic regulation, and modulated mitochondrial quality-control signaling in vivo and in vitro. These findings suggest that Rh1 may represent a promising nutritional intervention strategy for mitigating Pb-associated neurotoxicity.

Molecules doi: 10.3390/molecules31162800

Authors: Peng Zhao Jianming Zhang Li Li Long Zhao

In this work, to meet the requirements of high-performance electronic devices for high-frequency/speed telecommunication and semiconductor packaging, we developed a norbornene (NB)-backboned epoxy/cyanate ester compound system to modify the commercial bisphenol-A (BPA) diglycidyl ether (DGEBA) epoxy resin. A norbornene-based epoxy monomer (ENBDE) and cyanate ester (ENBCY) were synthesized using 5-ethylidene-2-norbornene (ENB) as the key starting material. The ENBDE was blended with DGEBA as the epoxy resin compound, which was cured using ENBCY as the curing agent to form a cross-linked thermoset. The effect of ENBDE content on thermal stability, mechanical properties, dielectric performance, and bonding strength of the thermosets was investigated. The optimized formula showed a significantly improved thermal stability of the cured resin with a glass-transition temperature of 249.2 °C and a 5% weight-loss temperature (T5%) of 351.5 °C; the dielectric constant and dissipation factor at a high frequency of 10 GHz were measured to be as small as 2.57 and 0.0068, respectively, showcasing great potential as a high-performance dielectric epoxy material for high-frequency/speed electronic applications.

Molecules doi: 10.3390/molecules31162798

Authors: Alexandre C. P. M. Alves Luís M. N. B. F. Santos José C. S. Costa

The formation and stabilization of silver nanoparticles (AgNPs) in thin films of ionic liquids (ILs) based on long-chain alkylimidazolium cations are demonstrated in this work. IL films were prepared by vacuum thermal evaporation using the Knudsen effusion method onto ITO/glass substrates, leading to the formation of micro- and nanosized structures distributed across the surface. The investigated ILs were symmetrical dialkylimidazolium-based systems: [C7C7im][NTf2], [C8C8im][NTf2], and [C10C10im][NTf2]. Increasing the alkyl side-chain length of the imidazolium cation resulted in larger droplet domains. AgNPs were subsequently deposited onto the IL films by sputtering. The formation of AgNPs was confirmed by scanning electron microscopy (SEM), ultraviolet (UV)–visible spectroscopy, and X-ray photoelectron spectroscopy (XPS). The results show that increasing the alkyl side-chain length promotes more effective confinement and stabilization of AgNPs, leading to improved nanoparticle formation and a narrower size distribution. The temporal stability of the Ag-containing IL films was evaluated under both air exposure and inert argon storage, revealing a strong influence of the surrounding atmosphere on nanoparticle evolution. Among the ILs studied, [C10C10im][NTf2] exhibited the most favorable behavior for AgNP formation and stabilization, providing a more stable and homogeneous nanoparticle distribution over time.

Molecules doi: 10.3390/molecules31162799

Authors: Gulnaz Adilbayeva Sestager Aknazarov Olga Golovchenko Aigul Abisheva Zhanibek Amir Makhmud Biisenbayev Ainur Muratova Assem Zh. Askarova Aitugan Sabitov

This study presents a comparative analysis of the effect of the structural–mineralogical type of clay matrices on the phase and structure formation in composite aluminosilicate materials within the multi-component Fe-Al-C-Si system. Highly plastic Saryozek montmorillonite clay and moderately plastic Alekseevskaya kaolinite–illite clay were investigated as binding matrices to consolidate iron–aluminosilicate fly ash from the Almaty CHPP-2. The raw materials and binary batches containing 10 to 50 wt.% fly ash were evaluated using XRD, XRF, TG/DTA, and SEM techniques. The results demonstrate that the superior plastic and binding properties of the Saryozek clay ensure enhanced consolidation of the non-plastic, fragmented ash particles. Simultaneous thermal analysis reveals that increasing the compaction pressure from 20 to 30 MPa induces a kinetic shift in the montmorillonite dehydroxylation interval toward higher temperatures (580–720 °C) due to increased partial water vapor pressure within the dense green body. This thermal shift scientifically necessitates introducing an isothermal dwell at 600 °C to mitigate firing defects. The optimal composite properties are achieved at a molding pressure of 30 MPa, a firing temperature of 1050 °C, and a fly ash concentration of 10–20 wt.%, yielding a peak compressive strength of 38.4 MPa. SEM confirmed that under these conditions, the locally formed silicate melt uniformly encapsulates the crystalline mullite and quartz microparticles, whereas increasing the ash content to 50 wt.% results in a loose, highly porous structure that degrades strength down to 17.9 MPa. These findings lay a scientifically substantiated foundation for optimizing composite ceramic synthesis and reducing structural defects.

Molecules doi: 10.3390/molecules31162797

Authors: Dujun Chen Mailin Gan Yuhang Lei Xinyi Wang Jincheng Zan Qing Ye Xiaofeng Zhou Lei Chen Yan Wang Ye Zhao Li Zhu Linyuan Shen

Skeletal muscle is a core component of the motor system, responsible for movement, posture maintenance, and energy metabolism. It plays a vital role in physiological stress, injury repair, and metabolic homeostasis. In recent years, with the advancement of epigenetic research, RNA modification has become a hot topic in skeletal muscle biology. This article systematically reviews the progress in the study of RNA modification in regulating the fate of skeletal muscle, focusing on the dynamic regulatory mechanisms and pathophysiological significance of N6-methyladenosine (m6A) modification in muscle differentiation, regeneration, and atrophy. It also briefly introduces the existing evidence for 5-methylcytidine (m5C), adenosine-to-inosine (A-to-I) editing, and pseudouridine (Ψ) in skeletal muscle. A comprehensive understanding of these mechanisms is crucial for elucidating the physiological regulation of skeletal muscle and the pathogenesis of related diseases and also provides a new direction for the development of intervention strategies.

Molecules doi: 10.3390/molecules31162796

Authors: Viive Sarv Hedi Kaldmäe Alar Aluvee

This study evaluated the compositional and processing characteristics of 17 rowanberry (Sorbus spp.) genotypes, including sweet cultivars, interspecific hybrids, and a wild rowanberry. Fruit weight, colour parameters, soluble solids content (SSC), and titratable acidity (TA) were determined to assess fruit quality, and the distribution of soluble sugars and organic acids among whole fruit, juice, and pomace fractions was investigated. Significant (p < 0.05) variation was observed among genotypes, with fruit weight ranging from 0.40 g in wild rowanberry to 1.55 g in ‘Alaja Krupnaja’. Hierarchical cluster analysis grouped the genotypes into two major clusters according to colour characteristics. Based on the SSC/TA ratio, ‘Burka’ and ‘Oranzevaja’ exhibited the most favourable balance between sweetness and acidity. Sorbitol was the predominant soluble carbohydrate and showed pronounced cultivar-dependent variation, ranging from 46.2 mg/g DW in ‘Likernaja’ to 189.0 mg/g DW in ‘Krasnaja’. Malic acid was the dominant organic acid in all fractions, reaching 70.9 mg/g DW in the pomace of ‘Krasnaja’. This study provides the first comprehensive comparison of sugar and organic acid partitioning among fruit, juice, and pomace fractions in a diverse set of rowanberry genotypes, revealing cultivar-specific patterns of carbon allocation relevant to fruit quality, processing, and by-product valorisation.

Molecules doi: 10.3390/molecules31162795

Authors: Zirui Zhang Lina Zhu Yue Gao Caoqing Ji Yong Ling

Insomnia is a common sleep disorder that significantly impairs quality of life and increases the risk of various chronic diseases. Although conventional sedative–hypnotic agents are effective, their clinical use is limited by tolerance, dependence, and residual next-day effects. The orexin system plays a critical role in sleep–wake regulation through orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R), with OX2R serving as the primary mediator of wakefulness. Based on this mechanism, orexin receptor antagonists (ORAs) have been developed to promote sleep by suppressing wake-promoting signaling pathways. This review systematically summarizes the structural and functional characteristics of the orexin system, with particular emphasis on the functional divergence of OX1R and OX2R and their therapeutic relevance. Recent advances in dual orexin receptor antagonists (DORAs) and selective orexin receptor antagonists are discussed, and the pharmacological properties and clinical performance of approved and investigational agents are compared. In addition, the safety profiles, adverse effects, and clinical limitations of ORAs are reviewed. Future perspectives are highlighted, including receptor selectivity, pharmacokinetic optimization, and personalized treatment strategies. Collectively, ORAs offer a mechanism-based therapeutic approach that may improve both the efficacy and safety of insomnia treatment.

Molecules doi: 10.3390/molecules31162793

Authors: Makhach Gadzhiev Elena Vorobyova Valeriya Krasnova Nadezhda Aluker Arsen Muslimov Sergey Antipov Maksim Il’ichev Yury Kulikov Andrey Chistolinov Damir Yusupov Ivan Volchkov Alexander Tyuftyaev Vladimir Kanevsky

In this work, a comprehensive analysis of the relationship between photoluminescent, thermo-oxidative, and photocatalytic (upon simulated sunlight exposure) properties of ZnO powders is performed. The correlation between the X-ray diffraction and microscopic data is studied. ZnO powders of various sizes and morphologies were used: pseudo-spherical nanoparticles (30–50 nm), submicron faceted crystallites (100–500 nm), and plate- and rod-like microstructures (up to 20 μm). The mean specific surface area values were 32 m2/g, 3.8 m2/g, and 2.6 m2/g for pseudo-spherical nanoparticles, submicron faceted crystallites, and plate- and rod-like microstructures, respectively. According to the XRD data, microstresses and carbon-based impurities were present in ZnO nanoparticles, which is characteristic of nanomaterials synthesized at low temperatures. According to the photoluminescence spectroscopy data, the emission in ZnO was reduced due to high defectiveness, and characteristic emission bands indicated the presence of organic impurities. Upon long signal registration times, an intensive luminescence band with an effective maximum at 579 nm occurred, which indicated the presence of long-term components exhibiting decay times τ ~300 μs. According to the XRD data, the crystal structure parameters of ZnO submicro- and microparticles were close, with no impurities present. In their photoluminescence spectra, pronounced UV and defect-related bands were present with intensity ratios of 11.6 and 6.88, respectively. The decrease in the UV and defect-related luminescence band intensity ratios indicates deviation from the stoichiometry toward an increased Zn over oxygen content. At long signal registration times, in submicron ZnO particles, a luminescence band with maxima at 425 and 490 nm is present, which decays rapidly. An emission band in the 530 nm region is also present, which decays for ≤80 μs, and a weak long-wavelength emission decaying for ~100 μs. At long delay and strobe times (up to milliseconds), only an emission in the 460 nm region is observed, which we connect to the triplet–singlet transition of a defect center (F*, F+*). At lower intensities, an emission connected to the surface contamination by organic impurities is observed. In photoluminescence spectra of ZnO microparticles, no long-wavelength emission components are observed. However, upon immersing into methylene blue solution, a modification of the surface and UV region of the spectra is observed with signs of charge carrier recombination rate acceleration. It is shown that the catalytic action of ZnO powders in polyethylene thermo-oxidation processes is determined by a combination of factors. In addition to dispersity and concentration, which are the key parameters, the morphology of ZnO particles, the presence of impurities, the surface state, and the distribution of active sites have a significant influence on catalysis. It has been experimentally demonstrated that these secondary factors can markedly affect the rate of radical formation in polyethylene films and alter their resistance to oxidation. ZnO nanoparticles exhibited low catalytic activity in both photocatalysis (rate constant 0.146 min−1) and thermocatalysis due to the high defect density of the crystallites and the presence of carbon-containing impurities. Submicron ZnO particles, owing to a high carrier generation rate and suppressed recombination (via trapping), demonstrated the highest photoactivity (rate constant 0.729 min−1). Submicron ZnO particles exhibit a catalytic effect on the thermo-oxidation of polyethylene (PE films); however, at concentrations above 8 wt.% a transition to an inhibiting effect is observed. ZnO microparticles catalyzed the oxidation of PE films over a broader concentration range (1–12 wt.%), with oxidation inhibition observed only at 18 wt.%. At the same time, they demonstrated moderate photocatalytic activity (rate constant 0.256 min−1). These characteristics of the samples correlate with data obtained by microscopy, photoluminescence spectroscopy, and X-ray diffraction analysis.

Molecules doi: 10.3390/molecules31162794

Authors: Qian Tong Li-Ting Xiao Ming-Yang Gu Xue-Qiang Chu Danhua Ge

A metal-free, efficient, iodine(III)-promoted oxidative transformation of allylic sulfones/allylic triflones with water participation for accessing sulfonyl ketones and triflyl allylic alcohols is reported. This strategy enables the selective construction of two SO2-containing compounds with chemical and biological significance, and its success mainly relies on the substitution effect of the starting materials. Water serves as an eco-friendly oxygen atom source. This transformation has excellent selectivity, broad substrate scope, mild reaction conditions, and ease of scale-up.

Molecules doi: 10.3390/molecules31162792

Authors: Jie Gao Liheng Li Yan Li

Lonicera japonica Thunb. (honeysuckle), a traditional herb with “food-medicine homology” status in Chinese medicine, is valued for its antipyretic and detoxifying properties. This review systematically summarizes its chemical composition—over 507 identified compounds, including phenylpropanoids, flavonoids, triterpenoids, saponins, and the plant-specific miR2911—as well as its multi-target pharmacological mechanisms and emerging translational applications, with particular emphasis on the gut–brain axis-mediated neuroprotective effects. Despite low oral bioavailability, honeysuckle polysaccharides and chlorogenic acid have been shown to exert significant neuroprotection in Alzheimer’s disease models by modulating gut microbiota composition, increasing short-chain fatty acid production, and restoring intestinal barrier integrity—a mechanism that challenges conventional direct-action paradigms. We also outline the applications of honeysuckle in functional foods, pharmaceuticals, animal husbandry, and cosmetics, and propose future directions including precision fermentation and mechanism-driven clinical trials. By integrating phytochemistry, pharmacology, and biotechnology, this review provides a roadmap for the evidence-based development of honeysuckle as a precise medicinal and edible resource.

Molecules doi: 10.3390/molecules31162791

Authors: Tom Kalathil Raju Pablo Garrido Josune García-Sanmartín Alfredo Martínez

Growth factors are molecules that interact with specific membrane receptors and induce cellular proliferation. In malignancy, this growth factor–receptor interaction constitutes one of the “hallmarks of cancer” and may result in uncontrolled cell growth. Proadrenomedullin N-terminal 20 peptide (PAMP) derives from proadrenomedullin and acts as an angiogenic peptide, and recent studies suggest it may be a tumor growth factor. In addition, it has been suggested that CXCR7 may be PAMP’s membrane receptor in particular cell types. Here, we combined advanced docking and molecular dynamic simulation studies to evaluate PAMP’s binding to CXCR7. Then, we used two melanoma cell lines and checked whether PAMP influences their shape, proliferation, migration, and invasion capacities. The signal transduction activated by PAMP was tested by Western blotting, and receptor involvement was investigated with specific inhibitors. This study shows that PAMP binds to active site 1 of CXCR7. It also increases melanoma cell proliferation through an autocrine growth loop. In contrast, PAMP reduced migration and invasion of these cells in a dose-dependent manner. PAMP was also responsible for modifying the actin cytoskeleton of both cell lines, producing a more elongated morphology. In addition, the presence of PAMP elevated ERK and AKT phosphorylation and increased CXCR7 and β-arrestin expression. Furthermore, specific inhibitors confirmed that these effects are mediated by the CXCR7/CXCR4/β-arrestin axis. In summary, we have shown that PAMP acts as a growth factor for melanoma cells while reducing their migration and invasion potential. These effects seem to be mediated by the CXCR7/CXCR4/β-arrestin axis. Altogether, these results suggest that PAMP inhibitors may be used as antitumor agents in melanoma.

Molecules doi: 10.3390/molecules31162790

Authors: Ludmila Ferreira de Almeida Fiuza Denise da Gama Jaen Batista Carolinna Silva Bressan Marcos Meuser Batista Raquel Silva de Azevedo Ketlym da Conceição Vagner Pereira da Silva Ana Luíza Rangel Bérenger Flávia da Cunha Camillo André Mesquita Marques Maria Raquel Figueiredo Maria de Nazaré Correia Soeiro

Chagas disease, caused by Trypanosoma cruzi (T. cruzi), affects more than 6 million people worldwide, predominantly in Latin America. Current chemotherapy relies on Benznidazole (Bz) and Nifurtimox, which are associated with adverse effects and limited efficacy during chronic infection, underscoring the need for new therapeutic options. Natural products remain an important source of bioactive molecules for antiparasitic drug discovery. In this study, 34 extracts obtained from 18 Brazilian plant species were evaluated for anti-T. cruzi activity. After cytotoxicity assessment, extracts were screened against intracellular amastigotes (Tulahuen strain, DTU VI) and bloodstream trypomastigotes (Y strain, DTU II). Most samples exhibited low toxicity toward mammalian cells (LC50 > 120 μg/mL). Among them, the inflorescence extract of Piper claussenianum (Miq.) C. DC. (PCFLD) showed the highest activity. At 20 μg/mL, PCFLD reduced intracellular parasite burden by 94%, with an EC50 of 3.6 ± 0.36 μg/mL and a selectivity index of 20. Against trypomastigotes, the extract displayed an EC50 of 11.56 ± 5.88 μg/mL and a selectivity index of 11. In an acute murine model, PCFLD (10 mg/kg/day) reduced peak parasitemia by 40%, outperforming Bz at the same dose. These findings identify P. claussenianum as a promising source of anti-T. cruzi compounds.

Molecules doi: 10.3390/molecules31162789

Authors: Dominika Kusyk Beata Mruk Ilona Górna Magdalena Kowalówka Izabela Bolesławska Hanna Markowska Sławomira Drzymała-Czyż

Microplastics have emerged as one of the most widespread and significant environmental pollutants, occurring in aquatic and terrestrial ecosystems, the atmosphere, food, and living organisms. Given the rapid expansion of research in this field, a comprehensive synthesis of the current state of knowledge is warranted. The aim of this study was to map the available literature on microplastics, with particular emphasis on advanced identification and characterisation techniques, environmental transport and transformation processes, life cycle assessment, and remediation strategies. This scoping review was conducted in accordance with the PRISMA-ScR guidelines using publications retrieved from the PubMed, Scopus, Web of Science, and Google Scholar databases. The analysis demonstrated substantial advances in analytical methodologies, particularly spectroscopic and microscopic techniques, enabling the accurate characterisation of micro- and nanoplastic particles. It also highlighted the complex mechanisms governing the transport and transformation of microplastics across environmental compartments, as well as their important role as vectors of chemical contaminants. From a systems perspective, life cycle assessment of plastics was identified as an essential tool for evaluating their environmental impacts. Current mitigation approaches, including filtration technologies, wastewater treatment processes, and biological remediation strategies, were also reviewed, along with their limitations and potential for future development. This review identifies the lack of standardised analytical methodologies and the limited capability for nanoplastics detection as two major challenges hindering the global harmonisation of microplastics research. The findings emphasise the need for further interdisciplinary studies and the implementation of integrated strategies encompassing the entire life cycle of plastics to effectively reduce microplastics emissions and mitigate their environmental impacts.

Molecules doi: 10.3390/molecules31162788

Authors: Patrycja Skwarek-Jóźwiak Małgorzata Karwowska

In recent years, increasing attention has been paid to limiting the use of nitrates and nitrites in meat products due to concerns regarding their potential health implications. Despite their important technological role in ensuring microbiological safety, oxidative stability, and the development of sensory characteristics of meat products, their use raises health concerns among consumers. These concerns are primarily associated with the potential formation of N-nitrosamines, some of which have been classified possible human carcinogens. In this context, there is growing interest in natural functional additives consistent with the clean-label concept and the zero-waste approach, including raw materials derived from fruit-processing by-products. Fruit-processing by-products, especially berry pomace, are a rich source of phenolic compounds with antioxidant and antimicrobial properties. Current evidence indicates that the bioactive compounds present in berry pomaces effectively reduce lipid oxidation and exhibit antimicrobial potential, which may contribute to inhibiting the growth of undesirable microorganisms in meat products. However, the effectiveness of this activity depends on several factors, including the type of berry pomace, its phenolic profile, the form of application (e.g., powder, extract, or freeze-dried material), the concentration applied, the type of meat product and the storage conditions. Consequently, berry pomaces should be regarded as natural ingredients supporting nitrite reduction strategies in meat products rather than as complete substitutes for nitrites. Furthermore, although berry pomaces exhibit considerable functional potential, their effectiveness in reducing nitrite levels depends on the type of meat product, its formulation, and the applied processing conditions. Among berry pomaces, red currant pomace (Ribes rubrum) has recently attracted increasing scientific interest because of its rich phenolic profile and promising functional properties. However, compared with chokeberry, blueberry, blackberry, and blackcurrant pomaces, relatively few studies have investigated its application in meat products. Therefore, further research is needed to confirm its technological functionality, antimicrobial efficacy, and potential contribution to nitrite-reduction strategies under different meat-processing conditions.

Molecules doi: 10.3390/molecules31162787

Authors: Anna Kurek-Górecka Małgorzata Kłósek Dagmara Jaworska Anna Mertas Radosław Balwierz Sebastian Granica Mirosław Szczepański Katarzyna Piszczatowska Sevgi Kolayli Zenon P. Czuba

Bee venom (BV) is valued therapeutically mainly for its peptides, melittin and apamin. This study determined the dose-dependent biological activity of bee venom standardized to its melittin and apamin content by UHPLC-ESI-MS, as well as that of its principal peptides, melittin and apamin, tested at matched concentrations. Antibacterial activity was assessed as showing the minimum inhibitory and minimum bactericidal concentrations (MIC, MBC) against Staphylococcus aureus (MSSA and MRSA) and Staphylococcus epidermidis (MRSE). Cytotoxicity toward primary human keratinocytes (HEKa) was determined by MTT and LDH assays and the mode of cell death by Annexin V-FITC/propidium iodide staining. The standardized bee venom contained 608.21 µg/mg of melittin and 22.17 µg/mg of apamin. Melittin was the only active constituent (MIC 2.5 to 5 µg/mL, MBC/MIC ≤ 2), whereas apamin was inactive (>10 µg/mL). Bee venom was active only against Staphylococcus epidermidis (MRSE), with both MIC and MBC values equal to 10 µg/mL. At concentrations of 5 and 10 µg/mL, both bee venom and melittin were markedly cytotoxic to keratinocytes. The selectivity index (CC50/MIC) did not exceed 1.6 for melittin and reached 0.2 for bee venom. On a melittin-equivalent basis, whole venom was more cytotoxic than pure melittin (CC50 1.33 versus 3.91 µg/mL), indicating that constituents other than melittin contribute to keratinocyte damage. Melittin is therefore the principal antibacterial constituent, but its narrow selectivity does not support direct topical use. Combination experiments evaluating bee venom or its isolated peptides in combination with antibiotics were not performed here and remain a defined direction for future work. Standardization to melittin content predicts potency but not safety, which has to be assessed on the whole standardized venom.

Molecules doi: 10.3390/molecules31162786

Authors: Congying Li Wenyi Wu Qing Huang Yishun Huang

The precise detection and profiling of biotoxins are of paramount importance in analytical and forensic toxicology. Investigating these toxicants within highly chaotic background matrices—ranging from postmortem biological fluids to suspected poisoning vehicles such as complex dietary and environmental samples—requires robust recognition molecules capable of overcoming severe interference. This comprehensive review summarizes recent analytical developments in biotoxin detection, categorizing molecular recognition platforms into three primary types: immunological recognition (antibodies and recombinant derivatives), aptamer-based recognition, and entirely synthetic recognition (molecularly imprinted polymer, MIP). To meet the rigorous ultra-trace demands of medicolegal analysis, we further discuss the strategic integration of these recognition elements with powerful catalytic amplification cascades, highlighting the transition from natural biological enzymes to highly durable nanozymes and DNAzymes. By detailing recent structural optimizations and preparation strategies, this review critically evaluates the respective advantages, matrix tolerances, and limitations of each recognition mode when applied to diverse and challenging analytical samples. Finally, we provide a forward-looking perspective on the translational potential of these specific binding agents, emphasizing how computational rational design and portable integration will overcome practical bottlenecks in modern toxicological investigations.

Molecules doi: 10.3390/molecules31162785

Authors: Milica Petrović Slobodan Najdanović Nena Velinov Georgiev Jelena Mitrović Miljana Radović Vučić Miloš Kostić Aleksandar Bojić

Electrochemical oxidation is an effective method for degrading environmentally harmful textile dyes that are difficult to remove by conventional treatments. The novel graphite–Co3O4 anode, prepared by electrochemically modifying recycled graphite tubes for AAS samples and characterized by SEM, EDX, FTIR, XRD, and BET, was used for electrochemical degradation of RB 4 dye in model solutions and textile dyeing effluent. Modification did not disrupt the graphite crystal structure but altered its surface properties, improving its dye degradation performance. It increased the decolorization rate constant of a model solution from 0.0148 min−1 to 0.0753 min−1 and maximum COD decay from 59% to 91%, reducing decolorization energy consumption from 3.26 kWh m−3 to 0.89 kWh m−3. Degradation at the graphite–Co3O4 anode proceeded via ·OH radicals and most likely the Co3+/Co2+ redox couple. It followed the pseudo-first-order kinetics. Pastel- and dark-shade dyeing textile effluents (containing 53 mg dm−3 and 159 mg dm−3 RB 4, respectively) were decolorized in about 70 and 110 min; COD decay reached about 87% and 80% after 180 min of electrolysis, respectively. The corresponding energy consumption was 1.75 kWh m−3, 2.39 kWh m−3, 2.97 kWh m−3, and 2.91 kWh m−3, respectively. The anode was efficient and stable in the given working conditions.

Molecules doi: 10.3390/molecules31162784

Authors: Lidija Jakobek Petra Matić Lidija Šoher Daniela Kenjerić

The effects of phenolic compounds in the gastrointestinal tract are linked to their intake in the diet and their interactions with the food matrix. The aim was to estimate the intake of phenolic compounds from two olive oils and to assess their behavior in the gastrointestinal tract after simulated static in vitro digestion without or with added cellulose, as a preliminary result on the influence of cellulose on their behavior. Individual phenolic compounds were quantified by RP-HPLC. The two olive oils were characterized by phenyl alcohols (1.8% and 5.3%), flavones (1.1% and 2.4%), lignans (0.8% and 1.7%), and unidentified secoiridoid derivatives (96.3% and 90.7%). The estimated population daily intake of phenolic compounds based on EFSA consumption data for the analyzed olive oil samples had means 0.75 to 1.27 and 0.30 to 0.51 mg per day, with the 95 percentile up to 5.91 and 2.38 mg per day for olive oil 1 and 2, respectively. The total amounts after gastric and intestinal digestion significantly decreased. Phenolic subgroups showed different behavior. In the stomach, phenyl alcohols increased, while all other subgroups decreased. After the intestinal phase, some subgroups additionally increased (phenyl alcohols, flavones, lignans), while others decreased (secoiridoids). Cellulose increased recovery in the stomach. As a preliminary result, the influence of cellulose needs to be studied further.

Molecules doi: 10.3390/molecules31162783

Authors: Zainab M. Almalki Ashwaq H. Batawi Asma Almuhammadi Safaa A. Alowaidi Suad H. Almasoudi Jehan Alamri Mona A. AL-Thepyani

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by impaired social communication and repetitive behaviors. Oxidative stress is increasingly recognized as a key contributor to the neuro-degeneration and behavioral abnormalities associated with ASD. Bacopa monnieri (BM), a medicinal herb with potent antioxidant and neuro-protective properties, has shown promise in mitigating oxidative damage. This study evaluated the preventive effects of BM extract on behavioral and neuro-histological alterations in a valproic acid (VPA)-induced mouse model of ASD. Pregnant mice received BM extract (400 mg/kg, orally) throughout gestation, while VPA (600 mg/kg) was administered intraperitoneally on embryonic day 12 (E12). Behavioral assessments included the open field test, righting reflex, three-chamber social interaction, marble burying, and hot plate tests. Oxidative stress markers, malondialdehyde (MDA) and glutathione (GSH), were quantified in hippocampal and cerebellar tissues. BM-treated offspring showed significant behavioral improvements, including reduced hyperactivity in the open field test (p < 0.0001), along with restored brain tissue architecture. Moreover, BM extract decreased MDA levels and elevated GSH concentrations, indicating attenuation of oxidative stress. In conclusion, Bacopa monnieri extract exerts protective effects against autism-like symptoms by enhancing antioxidant defenses and preserving neural integrity, suggesting its potential as a natural preventive strategy for ASD.

Molecules doi: 10.3390/molecules31162782

Authors: Milan Jovanović Teodora Djikic-Stojsic Branislav Stanković Marija Popovic-Nikolic Katarina Nikolic

Background: Phosphatidylinositol 3-kinase (PI3K) is a promising anticancer drug target, and selective PI3Kα inhibition may provide both efficacy and an improved safety profile. This study aimed to design new potentially selective PI3Kα inhibitors using computer-aided drug design (CADD). Methods: Benzoxazepine and thiazole derivatives were investigated using molecular dynamics, ensemble docking, and Three-Dimensional Quantitative Structure–Activity Relationship (3D-QSAR) analyses. Scaffold hopping, substituent replacement, structure-based virtual screening, and density functional theory (DFT) calculations were then applied to guide the design and characterization of new derivatives. Results: The study identified new chemotypes capable of interacting with PI3Kα Val851 (αVal851) in the hinge region, including chromeno[3,4-d]imidazole, 2H-benzo[b]oxazine, and quinoline derivatives. Additional substructures directed toward hydrophobic region II and the αGln859 interaction environment supported predicted selectivity over PI3Kβ, PI3Kγ, and PI3Kδ. Conclusions: The results establish a comprehensive CADD framework for the rational design of selective PI3Kα inhibitors and provide new compounds with improved predicted selectivity profiles for further development.

Molecules doi: 10.3390/molecules31162780

Authors: Hong-Jia Lin Shih-Horng Su Wen-Chung Wu

Glaucoma is an ocular disease caused by the improper management of elevated intraocular pressure (IOP). IOP-lowering via topical administration is the first choice to prevent further progression. However, patients may forget to administer their medication, compromising IOP control. To address this problem, a prolonged active pharmaceutical ingredient (API) release system is proposed. A new prodrug (latanoprost acid–brimonidine conjugate, LBJ) was designed and expected to achieve potential long-lasting release of APIs. LBJ was synthesized by two methods. First, Steglich esterification without protecting the hydroxyl group led to a yield of 34.24%. However, the integral ratio between LPA and BM obtained from NMR was 1.25:1, indicating a potential side product resulting from further coupling through the unprotected hydroxyl group in LBJ. As an alternative route, Steglich esterification with a protecting agent, tert-butyldimethylchlorosilane (TBDMSCl), resulted in a yield of 39.35%, and the integral ratio between LPA and BM obtained from NMR was 1:1. The hydrolysis time of LBJ was investigated and compared with that of latanoprost (LP). In the presence of esterase (0.4 U/mL), the hydrolysis times of LP and LBJ were 4 h and 28 days, respectively. The prolonged hydrolysis time results in sustained APIs release, which is beneficial for the development of a sustained drug release system.

Molecules doi: 10.3390/molecules31162781

Authors: Ye Yang Lei Huang Yaru Du Qingyue Zhu Li Dai Bingjun Qian

PARP1/2 inhibitors have received FDA approval for pancreatic cancer harboring BRCA1/2 mutations and homologous recombination (HR) deficiency; however, their limited indications restrict their broader clinical application. Previous studies have demonstrated that PARP7, a member of the PARP family, enhances tumor sensitivity to PARP1/2 inhibition. However, the mechanisms underlying their synergistic effects in pancreatic cancer remain unclear. Herein, we found that combined inhibition of PARP1/2 and PARP7 using Olaparib and XYL-1 significantly inhibited the proliferation of SW1990 and CFPAC cells compared with either single agent. Furthermore, XYL-1 and Olaparib cooperatively caused DNA damage and induced cell apoptosis in SW1990 cells. Consistently, combined treatment with XYL-1 and Olaparib significantly suppressed SW1990 tumor growth compared with single-agent treatment in mouse xenograft models, accompanied by elevated levels of phosphorylated H2AX in tumor tissues. Notably, bioinformatic analyses and mechanistic studies identified SCD1 and BRCA1 as key mediators of the synergistic antitumor effects of XYL-1 and Olaparib. More importantly, the combination of XYL-1 and Olaparib synergistically downregulated the expression of SCD1 and BRCA1, thereby impairing the HR-mediated DNA repair pathway. Collectively, these findings suggest that dual targeting of PARP7 and PARP1/2 may represent a promising therapeutic strategy for BRCA-proficient pancreatic cancer.

Molecules doi: 10.3390/molecules31162779

Authors: María Conde-Rioll Aiora Cenigaonandia-Campillo Silvia Sanz José Antonio Esteban Oscar Aguilera

Pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC) are aggressive malignancies frequently driven by oncogenic Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations associated with metabolic reprogramming and resistance to apoptosis. In this study, we evaluated the antitumor and anti-inflammatory activity of a Lepidium latifolium L.-derived formulation (CTP) enriched in glucosinolate hydrolysis products in KRAS-mutant colorectal and pancreatic cancer models. The formulation was designed to promote the generation of the epithionitrile 1-cyano-2,3-epithiopropane (CETP) through iron-dependent myrosinase-mediated sinigrin hydrolysis. CTP induced dose-dependent cytotoxicity and morphological alterations consistent with apoptosis in KRAS-mutant cancer cell lines. Treatment significantly reduced mitochondrial membrane potential, ATP production, oxygen consumption rate (OCR), and extracellular acidification rate (ECAR), indicating severe bioenergetic impairment. In parallel, CTP downregulated the metabolic and proliferative regulators C-myc, PKM2, GLUT1, and Cyclin E1. RNA-seq analysis revealed extensive transcriptional reprogramming associated with oxidative stress, metabolic adaptation, and cell-cycle regulation. In addition, CTP significantly suppressed nitric oxide, IL-6, and IL-8 production in LPS-stimulated RAW 264.7 macrophages. These findings demonstrate that glucosinolate-derived metabolites from L. latifolium interfere with metabolic and inflammatory pathways critical for KRAS-driven tumor survival and support the therapeutic potential of Brassicaceae-derived epithionitriles as multitarget anticancer agents.

Molecules doi: 10.3390/molecules31162778

Authors: Laura Kazhygeldiyeva Lazzyat Orazzhanova Binur Mussabayeva Alfira Sabitova Batiyash Silybayeva Akmaral Issayeva

This study presents the phytochemical profile and antioxidant activity of the aboveground organs of Salicornia europaea L. collected from a natural population in East Kazakhstan. The chemical composition of the plant sample was studied using a complex of modern analytical methods, including HPLC, GC-MS, IR-Fourier spectroscopy, and elemental analysis. Metabolites were putatively annotated based on mass spectrometry data, corresponding to MSI level 2. It was found that the content of flavonoids was 2.40 ± 0.02 mg QE/g of dry raw materials, and the content of polyphenols was 6.73 ± 0.03 mg GAE/g. The antioxidant activity (ABTS test) reached 7.85 ± 0.04 mg TE/g. The concentration of fat-soluble and water-soluble vitamins was C—1.27 ± 0.12 mg/100 g, A—1.16 ± 0.11 mg/100 g and E—3.89 ± 0.38 mg/100 g. The IR characterization of plant raw materials and ash was carried out, the indicators of the elemental composition (TC, TOC, TIC, TN, TS) were determined. The totality of the obtained data indicates the phytochemical potential of Salicornia europaea L. growing in the territory of East Kazakhstan and may serve as a basis for further applied research.

Molecules doi: 10.3390/molecules31162775

Authors: Binyu Wang Cong Feng Huan Liu

To clarify the role of metal dopants in low-temperature NH3-SCR of NO, FeMnTiOx catalysts were synthesized by coprecipitation and separately modified with Ce, Co, or W. The catalysts were evaluated for NO conversion, separate O2/H2O switching response and dry-feed time-on-stream stability and characterized by XRD, SEM, N2 adsorption–desorption, XPS, H2-TPR and NH3-TPD. Ce doping at Ce/Mn = 0.3 suppressed TiO2 crystallization, increased the BET surface area from 136 to 231 m2 g−1 and the pore volume from 0.19 to 0.58 cm3 g−1, raised the Mn4+/Mn3+ ratio from 0.70 to 1.25, and increased the medium-strong-acid relative peak area from 555.4 to 1293.2 a.u. FeMnCe0.3TiOx maintained at least 90% NO conversion from 140 to 360 °C, gave 75% conversion at 400 °C, and averaged 97.4% during a 40 h dry-feed test at 350 °C. The results show that the superior Ce-modified catalyst arises from the combined regulation of texture, surface redox balance and acidity.

Molecules doi: 10.3390/molecules31162777

Authors: Nimo Hussein Yussuf Eylem Odabas Fatma Oznur Afacan Bulent Kabak

Acrylamide is a thermally induced process contaminant formed predominantly through Maillard-type reactions in carbohydrate-rich foods and is considered a major food safety concern due to its potential genotoxic and carcinogenic properties. In the present study, a modified QuEChERS (quick, easy, cheap, effective, rugged, and safe)-based extraction and clean-up procedure followed by high-performance liquid chromatography coupled with photodiode array detection (HPLC-PDA) analysis was developed and optimised for the determination of acrylamide in French fries. Different clean-up strategies involving primary secondary amine (PSA), C18, and salt-assisted extraction systems were comparatively evaluated to improve analytical selectivity and chromatographic performance in complex potato matrices. The optimised procedure demonstrated satisfactory analytical performance and chromatographic selectivity for acrylamide analysis in thermally processed potato matrices, with an LOQ value of 32.3 µg kg−1, recoveries ranging from 79.4 to 86.6%, and relative standard deviation (RSD) values below 8%. The validated method was subsequently applied to investigate the influence of thermal processing conditions on acrylamide formation in frozen French fries processed using sunflower oil, riviera olive oil, and palm oil. Deep-fat frying formed substantially higher acrylamide concentrations (526.7–829.6 µg kg−1) than oven baking (285.5–480.6 µg kg−1) and air frying (272.1–673.6 µg kg−1), whereas repeated frying cycles markedly enhanced acrylamide formation, particularly in sunflower oil systems. The proposed analytical strategy offers a reliable and analytically robust approach for acrylamide determination while providing mechanistic insights into processing-dependent chemical transformations associated with acrylamide formation in potato-based foods.

Molecules doi: 10.3390/molecules31162776

Authors: Noemi Bertoli Giorgio Gargari Margherita Paracini Elisa Clagnan Emanuela Gobbi Stefano Dall’Acqua Gregorio Peron

The increasing generation of agro-industrial residues requires the development of sustainable valorization strategies for converting low-value biomasses into high-added-value products within a circular bioeconomy framework. In this study, tomato peels (TP) derived from the tomato-processing industry and green waste (GW) from urban pruning activities were investigated as substrates for solid-state fermentation (SSF) mediated by Trichoderma harzianum, with the aim of evaluating fungal growth, metabolomic remodeling, and the production of antioxidant bioactive compounds. Different substrate formulations containing TP and GW were subjected to SSF for 7 days, and fungal colonization was monitored. The highest fungal colonization was observed in substrates containing high proportions of GW, whereas pure tomato peels showed negligible colonization, indicating a strong substrate-dependent effect on fungal development. UPLC-QToF-MS metabolomic profiling was subsequently performed on the fermented substrate formulations using three independent biological replicates per treatment, whereas the 100% TP formulation, which showed negligible fungal colonization, was excluded from metabolomic analysis. Results revealed marked differences among fermented substrates, and 22 discriminant metabolites significantly enriched in those containing higher proportions of TP were identified. These metabolites mainly included hydroxycinnamic acid derivatives, flavonoids, lignans, phenolic glycosides, and organic acids, such as coumaric acid, hydroxycaffeic acid, cinnamoylglucose, citric acid, and cyanidin glycosides, suggesting fermentation-associated transformation and release of phenolic compounds. Fermented extracts obtained from mixed substrates enriched in TP exhibited the highest antioxidant activity, with DPPH and ABTS radical scavenging capacities reaching up to 63.48 µmol TE/g dw and 119.67 µmol TE/g dry weight, respectively, together with increased total phenolic content. The integration of microbiological, metabolomic, and antioxidant analyses demonstrated that co-fermentation of tomato-processing byproducts with green waste can modulate fermentation outcomes and enhance antioxidant potential. Overall, this study provides new insights into substrate-driven metabolic transformations during Trichoderma-mediated SSF and highlights the potential of mixed agro-industrial residues as sustainable feedstocks for the production of antioxidant-rich extracts with possible nutraceutical and biotechnological applications.

Molecules doi: 10.3390/molecules31162774

Authors: Edwin Rojo-Gutiérrez Leticia Xochitl López-Martínez Mónica Alejandra Villegas-Ochoa Ezequiel Muñoz-Márquez Ramiro Baeza-Jiménez

Modern food systems face the challenge of improving nutritional quality while reducing environmental impact and conserving agrobiodiversity. This study evaluated the effects of thermal processing and fortification with ayocote (Phaseolus coccineus) and quintonil (Amaranthus hybridus) flours on the physicochemical, nutritional, and functional properties of blue maize tortillas, baked tortilla chips (BTCs), and fried tortilla chips (FTCs). Two nominal fortification levels (F1: 6% and F2: 9%) were incorporated into nixtamalized blue maize flour. The resulting products were characterized for proximate composition, mineral profile, color, texture, phenolic and flavonoid contents, antioxidant activity, and in vitro phenolic bioaccessibility. Fortification significantly increased protein, ash, mineral, phenolic, and flavonoid contents, particularly in F2 formulations, while maintaining adequate technological quality. Thermal processing influenced phytochemical content and antioxidant activity, although these effects depended on the parameter evaluated. BTCs generally exhibited higher flavonoid content and antioxidant capacity, whereas total phenolic content remained comparable between BTCs and FTCs. Fortification improved tortilla flexibility but increased tortilla chip hardness. During simulated gastrointestinal digestion, fortified products released more phenolics than the controls. BTC-F2 maintained the highest phenolic content after digestion, whereas tortilla formulations exhibited the greatest relative phenolic bioaccessibility. These findings demonstrate the potential of the underutilized native species ayocote and quintonil to enhance the nutritional and functional value of maize-based products.

Molecules doi: 10.3390/molecules31162773

Authors: Jun Tong Yulin Shen Minhua Huang Huiwen Pang Qian Yan Lihong Yao

Bamboo is a renewable and mechanically robust bio-based material with potential for sand-barrier construction; however, its long-term outdoor use is limited by ultraviolet-induced photoaging, moisture uptake, wind-sand abrasion, and biological colonization. In this study, a fluorine-free EP/TiO2/ODTMS superhydrophobic coating was deposited on moso bamboo using a simple spraying process. Rutile TiO2 was incorporated as a roughness-building and ultraviolet-shielding filler, waterborne epoxy resin served as a film-forming binder to improve particle anchoring and coating cohesion, and octadecyltrimethoxysilane was used to reduce the surface energy. The formulation containing 50–100 nm rutile TiO2 and 2 wt.% epoxy resin provided the best overall balance between surface wettability and mechanical durability, with a water contact angle of 156.4° and a sliding angle of 6.9°. SEM observations revealed a hierarchical surface composed of TiO2 particles and microscale agglomerates immobilized within the epoxy matrix. EDS and FTIR results supported the incorporation of TiO2- and ODTMS-derived components, while UV–Vis–NIR diffuse-reflectance measurements showed an improved optical response in the ultraviolet region. The coating retained superhydrophobicity after sandpaper abrasion, gravel impact, and tape-peeling tests. After 672 h of xenon-lamp aging, the coated bamboo maintained a water contact angle above 150°, exhibited a total color difference of approximately 7.65, and retained 91.1% of its initial flexural strength. In addition, qualitatively reduced visible mildew colonization was observed during 45 days of high-humidity exposure. These results demonstrate that the spray-deposited coating provides a fluorine-free and potentially scalable approach for improving the water repellency, mechanical durability, and accelerated-weathering resistance of bamboo sand-barrier materials.

Molecules doi: 10.3390/molecules31162772

Authors: Phan Thi Minh Huyen Nguyen Xuan Dung

Antibiotic contamination of water, particularly by tetracycline (TC), requires effective and sustainable treatment strategies. In this study, CoFe2O4 nanoparticles were synthesized using lime juice as a natural stabilizing agent and combined with ZnO to obtain a ZnO/CoFe2O4 nanocomposite for visible-light-driven TC degradation. Complementary characterization confirmed the coexistence of ZnO and CoFe2O4 without detectable secondary phases, with predominantly spherical and irregular particles. The composite exhibited ferromagnetic behavior, suggesting potential magnetic recovery, and showed broader visible-light absorption and a reduced band gap of 3.05 eV compared with 3.23 eV for ZnO. Although its specific surface area and pore volume were lower than those of CoFe2O4, the nanocomposite displayed the highest photocatalytic performance. Under the optimized conditions of pH 6, 20 mg L−1 TC, and 1 g L−1 catalyst, 96.8% degradation was achieved after 120 min, with a pseudo-first-order rate constant of 0.029 min−1. The degradation efficiency remained 88.3% after five cycles. Scavenger experiments identified photogenerated holes (h+) and hydroxyl radicals (·OH) as the dominant reactive species. The improved photocatalytic activity may be associated with interfacial interactions between ZnO and CoFe2O4, suggesting that the green-synthesized nanocomposite has potential as a visible-light photocatalyst for TC degradation under the investigated conditions.

Molecules doi: 10.3390/molecules31162771

Authors: Florina Brânzoi Denisa-Ioana Răuță (Gheorghe) Roxana-Doina Truşcă Sorin-Marius Avramescu

This study investigates the efficiency of green corrosion inhibitors derived from spent coffee grounds (SCGs) for OL 37 carbon steel in 0.5 M H2SO4 and 1 M HCl environments. The aqueous extracts, labeled K1 and K2, were obtained through specialized extraction techniques and characterized by HPLC. Their protective performance was investigated using potentiodynamic polarization and electrochemical impedance spectroscopy (EIS). FT-IR spectroscopy and SEM-EDX analysis confirmed the presence of a protective inhibitor film on the OL 37 surface, attributed to the adsorption of organic molecules from the SCGs extract (K1 and K2). The adsorption behavior followed the Langmuir isotherm, with high adsorption constants and standard free energy values (ΔG°ads), indicating a mixed-mode adsorption mechanism. Furthermore, the negative Gibbs free energy values of adsorption confirm the spontaneity of the adsorption process. Thermodynamic studies conducted between 293 K and 333 K demonstrated the temperature dependence of the inhibition process. Results showed that at a concentration of 800 ppm and 1000 ppm, both inhibitors exhibited high efficiency, reaching 96% for K1 and 95% for K2.

Molecules doi: 10.3390/molecules31162770

Authors: Essa M. Sabi Ahmed H. Mujamammi Khalil I. Zarea Ziyad M. Althafar Khalid M. Sumaily

Lung cancer remains a leading cause of cancer-related mortality worldwide, underscoring the need for safer and more effective therapeutic strategies. In this study, zinc oxide nanoparticles (ZnO NPs) were synthesized via a green, biogenic approach using Lantana camara L. flower aqueous extract and evaluated for their anticancer potential against human non-small cell lung cancer (NSCLC) NCI-H460 cells. The biosynthesized ZnO NPs were characterized using UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), Transmission electron microscopy (TEM), energy-dispersive X-ray analysis (EDX), X-ray diffraction (XRD) and particle size analysis, confirming the formation of nanocrystalline ZnO. LC-MS profiling of the Lantana camara flower extract revealed the presence of several bioactive phytochemicals, including phenolic compounds, terpenoids, fatty acids, and alkaloids, which may contribute to the reduction and stabilization of ZnO NPs during green synthesis. Cytotoxicity assessment of ZnO NPs using MTT and trypan blue exclusion assays revealed a dose-dependent reduction in cell viability, with an IC50 value of 50 µg/mL. Mechanistic investigations demonstrated that ZnO NP exposure induced significant oxidative stress, evidenced by increased nitric oxide, lipid peroxidation, and reactive oxygen species levels, along with depletion of intracellular glutathione. Apoptotic cell death was further confirmed by nuclear DNA fragmentation, mitochondrial membrane depolarization, and G0/G1 phase cell cycle arrest. Quantitative real-time PCR analysis revealed upregulation of the pro-apoptotic genes Bax and p53, accompanied by downregulation of the anti-apoptotic gene Bcl-2, indicating activation of a mitochondrial-dependent intrinsic apoptotic pathway. Collectively, these findings suggest that Lantana camara L. flower-mediated ZnO nanoparticles induced apoptotic responses associated with oxidative stress in NSCLC cells, highlighting their ability as an eco-friendly nanoplatform for further anticancer investigations.

Molecules doi: 10.3390/molecules31162769

Authors: Yuping Zhong Xinran Xiong Yunxuan Lv Yongchang Chen Zhiwei Liu Xiaonan Zhang Zuoliang Zheng

This study systematically optimized the extraction processes of two bioactive constituents, total flavonoids and crude polysaccharides, from the dried underground tubers of Nephrolepis cordifolia (L.) C. Presl, and further comprehensively characterized their in vitro antioxidant activities. For total flavonoid extraction, an ethanol–ammonium sulfate aqueous two-phase system (ATPS) was integrated with ultrasonic-assisted aqueous two-phase extraction (UATPE), and the process parameters were optimized via Box–Behnken design-based response surface methodology (RSM) using total flavonoid content (TFC) as the primary response indicator. The validated optimal conditions were determined as follows: extraction time of 40.67 min, solid-to-liquid ratio of 1:30.71 (g/mL), ammonium sulfate mass fraction of 24.03%, and ethanol concentration of 35% (v/v). Under these optimized conditions, the TFC reached (54.83 ± 1.58) mg rutin equivalents per gram dry weight (mg RE/g DW), which was significantly higher than the values obtained from conventional ATPS [(49.05 ± 0.41) (mg RE/g DW)] and traditional ethanol extraction [(28.68 ± 1.54) (mg RE/g DW)] (p < 0.05). For crude polysaccharide production, an ultrasonic-assisted water extraction followed by ethanol precipitation protocol was adopted, and parameters were screened through an L9 (33) orthogonal experimental design. The obtained optimal extraction parameters were an extraction time of 10 min, three extraction cycles, and solid-to-liquid ratio of 1:15 (g/mL). A maximum crude polysaccharide yield of (14.89 ± 0.18) % was achieved under these conditions, with a relative standard deviation of 1.21% (n = 3) across parallel validation tests. Subsequent antioxidant assays demonstrated that the total flavonoid fraction from Nephrolepis cordifolia exhibited potent scavenging capacities against both 1,1-Diphenyl-2-picrylhydrazyl radical (DPPH•) and 2,2′-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) radical cation (ABTS•+) radicals. Within the tested concentration range of 0.1–0.5 m g/mL, the crude polysaccharide presented a significant positive concentration-dependent enhancement of activity in four classical in vitro antioxidant systems, including DPPH radical scavenging, ABTS cation radical scavenging, hydroxyl radical scavenging, and total reducing power. Collectively, these findings confirm that the introduced ultrasonic-assisted extraction strategy remarkably improves the recovery efficiency of target bioactive components from Nephrolepis cordifolia. Both total flavonoids and crude polysaccharides display excellent in vitro free radical scavenging potential. This work provides a solid methodological basis for the efficient preparation of the two bioactive compounds, and highlights that Nephrolepis cordifolia is a promising candidate for further exploration as a natural antioxidant source.

Molecules doi: 10.3390/molecules31162768

Authors: Chenliang Li Lijin Xiao Wei Wu Lingyang Kong Shuyuan Yue Zhijie Zhan Jiao Xu Wei Ma

Apigenin (API) is a flavonoid compound widely distributed in nature. The global prevalence of asthma is increasing year by year, influenced by various factors and difficult to cure completely, and new drugs and therapies are constantly emerging. Although API is a low-toxicity flavonoid compound, its poor water solubility and low bioavailability present limitations in the treatment of asthma. In this study, the structure of API was chemically modified by introducing acyl and alkyl groups while preserving its original structure. The structures were identified using FT-IR, 1H-NMR and 13C-NMR spectroscopy, yielding derivatives (A–J). To further investigate the effects of structural modifications on API’s biological activity, an ovalbumin (OVA)-induced asthma model was established in mice to evaluate the antioxidants’ activity. Hematoxylin-eosin staining was used to observe pathological changes in lung tissue, and oxidative stress-related parameters, including ROS, SOD, and MDA, were measured to assess the derivatives’ protective effects against oxidative damage. The results showed that the 10 synthetic derivatives exhibited varying degrees of oxidative stress during treatment. Compared with the model group, the API derivative treatment group significantly reduced ROS and MDA levels and increased SOD activity. Moreover, treatment with the compounds reduced the levels of pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, and decreased serum IgE levels. Histopathological examination further demonstrated that the compounds alleviated inflammatory cell infiltration and tissue damage in the lungs. Structure-activity analysis indicated that, among the 10 derivatives, the tri-substituted API derivatives exhibited superior antioxidant activity compared to the di-substituted API derivatives. By modifying the chemical structure of API, its antioxidant activity in OVA-induced bronchial asthma was significantly enhanced. 5,7,4′-O-triethyl API and 5,7,4′-O-triacetyl API demonstrated therapeutic effects comparable to those of dexamethasone and show promise as lead compounds for the development of novel asthma treatments.

Molecules doi: 10.3390/molecules31162767

Authors: Junyu Li Zhican Lu Qihui Zeng Fang Wang Bo Yuan Zeyu Zheng Xiaolin Tang Yifu Zhang Chi Huang

Due to its abundant active sites, the bimetallic zeolite imidazole framework ZnCo-ZIF-67 exhibits excellent catalytic performance on the key oxidant ammonium perchlorate in composite solid propellants. In addition, carbon fiber has been proven to promote the combustion of propellants due to its high thermal conductivity efficiency. In order to integrate the advantages of both, this study designed and prepared a novel composite catalyst, ZnCo-ZIF-67/CF, by a co-precipitation method. The thermal decomposition test demonstrated that the ZnCo-ZIF-67/CF composite exhibited significant catalytic activity. When the addition amount was 5 wt%, the high-temperature decomposition peak temperature of AP decreased significantly from 424.3 °C to 337.2 °C, and the combustion process was also significantly accelerated. Furthermore, analysis of the products of thermal decomposition gases revealed a significant increase in the proportion of N2O in the catalyzed products to 55.7%, whilst the proportion of high oxidation state nitrogen-containing oxides such as NO2 and NOCl decreased. This finding suggests that the highly dispersed metal active sites in ZnCo-ZIF-67/CF synergistically promote the decomposition reaction pathway of AP, leading to enhanced N2O generation. This study proposes a novel approach for the development of efficient and stable AP decomposition catalysts, which has positive significance for the regulation of the combustion performance of propellants.

Molecules doi: 10.3390/molecules31162766

Authors: Ke Yue Yanzhi Zhang Xing Zhang Kunmiao He Chong Yuan Jiusi Chen Hongtao Ren Na Wang Gaiping Zhang

Traditional injectable vaccine adjuvants are limited by local granulomatous reactions, chronic inflammation, and reduced compliance, creating an urgent need for safe, host-directed strategies to enhance vaccine immunogenicity. Proanthocyanidins (PACs)—natural polyphenols abundant in grapes, cocoa, and tea—are food-derived bioactive compounds with antioxidant, anti-inflammatory, and immunomodulatory activities, positioning them as attractive candidates for oral immunostimulants. Using classical swine fever virus (CSFV), a Pestivirus within the Flaviviridae that shares conserved genomic and immunological features with human pathogens such as hepatitis C and dengue virus, we systematically evaluated oral PACs (15, 30, and 60 mg/kg/d) combined with attenuated live or subunit CSFV vaccines in mice. PACs were well tolerated across the full dose range, with no impact on body weight or major organs, while selectively increasing the splenic index—suggesting spleen-targeted immune activation without systemic inflammation. Compared with vaccine alone, the moderate dose (30 mg/kg/d) produced the strongest immunostimulation, particularly with the subunit vaccine: peak antigen-specific IgG titer reached 1:409,600, a 4-fold increase versus 1:102,400 for subunit alone and exceeding the 3.4-fold gain observed with the attenuated vaccine. IgG2a and IgG2b rose by 199.4% and 269.1%, respectively, alongside coordinated elevations of Th1 (IL-2 +160.6%, IFN-γ +91.9%) and Th2 (IL-4, IL-10) cytokines, enhanced B- and T-lymphocyte proliferation, and expansion of CD4+ and CD8+ subsets, establishing a balanced and durable Th1/Th2 response. These findings provide preclinical evidence that food-derived PACs can serve as safe oral immunostimulants for low-immunogenicity subunit vaccines, supporting their further development in human and veterinary vaccinology.

Molecules doi: 10.3390/molecules31162765

Authors: Hongqiang Yuan Zheyuan Zhan Ying Zhang Shuo Wang Kang Chen Xiangyang Huang

A major limitation hindering the practical application of heterogeneous Fenton-like systems is their inherently slow reaction kinetics, particularly near neutral pH. To address this issue, a hydroxylamine (HA)-enhanced NiFe2O4/H2O2 system was developed for phenol degradation. At an initial pH of 7, with 5 mmol/L HA and 10 mmol/L H2O2, the system achieved 97.8% phenol degradation within 60 min, compared with 17.4% in the HA-free system. XPS analysis showed that the Fe2+ proportion increased from 49.1% to 53.6% and the Ni2+ proportion increased from 52.1% to 63.4% after reaction. These changes are consistent with HA facilitating the formation or regeneration of reduced metal species, suggesting that HA may be related to accelerated Fe3+/Fe2+ or Ni3+/Ni2+ cycling. Radical scavenging experiments and electron paramagnetic resonance (EPR) results indicated that identified hydroxyl (•OH) and superoxide (O2•−) radicals were the predominant reactive species. Metal-leaching and catalyst-removal experiments indicated that both heterogeneous and homogeneous processes contributed to phenol degradation. The results provide mechanistic insights into HA-enhanced H2O2 activation while also highlighting the need to consider metal leaching, HA-derived nitrogen products, and catalyst reusability.

Molecules doi: 10.3390/molecules31162764

Authors: Beatriz Adriana Rodríguez-Romero David Paniagua-Vega Orlando Esau Flores-Maldonado Aurora de Jesús Garza-Juárez Ariana Arlene Huerta-Heredia Perla Giovanna Silva-Flores

Functional foods enriched with plant-derived bioactive compounds have emerged as promising complementary dietary strategies to improve glycemic regulation. The aim of this study was to evaluate the physicochemical properties, sensory acceptance, and microbiological characteristics of a functional yogurt enriched with Moringa oleifera leaf extract, as well as its effect on blood glucose levels in an alloxan-induced diabetic rat model. Phytochemical characterization of the hydroethanolic leaf extract by HPLC and direct-infusion ESI-IT-MS2 revealed phenolic compounds, including chlorogenic acid, rutin, quercetin, and kaempferol, together with additional glycosylated flavonoids. M. oleifera extract increased the yogurt’s protein content. Sensory evaluation indicated moderate acceptance compared to natural yogurt, with color being the least-accepted attribute. Microbiological analysis showed no inhibitory effect against representative bacterial genera of the gastrointestinal microbiota under the experimental conditions evaluated. In vivo evaluation in alloxan-induced diabetic female Wistar rats demonstrated a significant reduction in blood glucose levels, from 396.50 ± 17.85 mg/dL to 254.50 ± 32.79 mg/dL after 15 days of treatment. These findings support further investigation of M. oleifera functional yogurt as a potential functional food in the context of glycemic control.

Molecules doi: 10.3390/molecules31162762

Authors: Katarzyna Kirchof Anna Marzec Bolesław Szadkowski

Inorganic pigments are widely used in elastomer technology primarily as coloring agents; however, the broader effects of these additives on the structure–property relationships of rubber composites remain insufficiently understood, particularly across different elastomer matrices. This study addresses this gap by systematically evaluating and comparing the effects of zirconium cerulean blue (Pigment Blue 71, PB71) and earth pigment iron ocher (IO) in natural rubber (NR), acrylonitrile–butadiene rubber (NBR), and styrene–butadiene rubber (SBR) composites. The influence of pigment loading (2–10 phr, parts per hundred parts of rubber) on rheometric behavior, crosslink density, mechanical performance, thermo-oxidative aging resistance, and combustion behavior was investigated to determine whether inorganic pigments provide benefits beyond coloration. The incorporation of pigments did not adversely affect vulcanization behavior, with the crosslink density of NR increasing from approximately 1.5 × 10−5 mol cm−3 for the unfilled vulcanizate to 1.5–2.3 × 10−5 mol cm−3 for pigment-containing composites, while SBR exhibited an increase from approximately 1.0 × 10−5 to 1.5–2.0 × 10−5 mol cm−3. Selected formulations also exhibited improved tensile strength and enhanced resistance to thermo-oxidative aging. Pyrolysis combustion flow calorimetry (PFCF) demonstrated that the incorporation of 10 phr IO reduced the peak heat release rate (pHRR) by approximately 11% (NR), 10% (NBR), and 3% (SBR), whereas 10 phr PB71 decreased this parameter by approximately 13%, 8%, and 38%, respectively. These findings demonstrate that inorganic pigments can serve as multifunctional colorants, simultaneously improving mechanical performance, thermo-oxidative stability, and fire resistance while maintaining effective coloration.

Molecules doi: 10.3390/molecules31162763

Authors: Hümeyra İspirli Akif Emre Kavak Enes Dertli

Lactic Acid Bacteria (LAB) from traditional fermented foods serve as a promising source of novel exopolysaccharides (EPSs) with desirable techno-functional properties. In this study, the EPS production ability of LAB strains from traditional pickles was tested and a strong slimy isolate grown in a sucrose-rich environment was further selected. The isolate was identified as Leuconostoc mesenteroides VB113 and its EPS production characteristics were determined. HPLC analysis revealed that glucose was the only monomer in the EPS repeating structure, whereas 1H and 13C NMR spectroscopy analysis demonstrated a branched dextran structure with 20% (1 → 3)-linked α-D-glucose units. Dextran VB113 showed a molecular weight of 2.4 × 106 Da tested by GPC analysis. The functional groups within dextran VB113 were determined by FTIR analysis, and XRD analysis demonstrated its amorphous physical status. TGA and DSC analysis were applied for thermal characterization and a degradation temperature of 272.25 °C was observed for dextran VB113, suggesting its high thermal resistance. The micro-structural features of dextran VB113 were tested by SEM and AFM analysis that revealed spherical and fibrillary properties, respectively. These findings revealed the importance of testing different niches to obtain novel EPS-producing LAB strains that can be further evaluated to enhance the techno-functional properties of food systems. The branched nature of dextran VB113, together with its molecular weight and thermal characteristics, offers practical advantages for its potential usage as a thermal-stable thickening agent, emulsion stabilizer, and fat replacer in high-temperature food processing applications, such as bakery products, processed dairy, and plant-based meat analogs.

Molecules doi: 10.3390/molecules31162761

Authors: Fanjiang Yang Chunfang Tang Yutong Zhang Xinyu Xu Meifang Li Chengyun Zhou Lei Qin Jiaqin Deng Xinjiang Hu Xiaoxi Cai Shaoheng Liu

Lead (Pb) accumulation in paddy soils promotes its transfer to rice grains, posing persistent risks to food safety and human health. Here, we developed a GSNO-encapsulated chitosan–biochar-supported sulfidized nanoscale zero-valent iron composite (GSNO-CS@S-nZVI/BC) to integrate sustained nitric oxide (NO) delivery with Pb immobilization in rice–soil systems. The novelty of this strategy lies in coupling a biocompatible NO donor with a Pb-reactive CS@S-nZVI/BC matrix to simultaneously alleviate Pb-induced physiological stress in rice and suppress Pb migration from soil to edible grains. In hydroponic experiments, Pb exposure reduced rice fresh weight, dry weight, and chlorophyll levels by 71.2%, 55.6%, and 75.1%, respectively. Compared with Pb treatment alone, GSNO-CS@S-nZVI/BC increased rice dry weight and chlorophyll levels by 68.5% and 260%, respectively, while decreasing Pb concentrations in roots and shoots by 78.2% and 85.8%. In soil pot experiments, GSNO-CS@S-nZVI/BC reduced Pb concentrations in roots, shoots, panicles, and grains by 57.6%, 57.0%, 40.3%, and 64.3%, respectively. It also decreased the grain Pb bioconcentration factor by 80.7%, reduced the soil-to-root Pb translocation factor by 84.41%, and lowered the grain Pb bioconcentration factor to 0.043 ± 0.007. Mechanistically, GSNO-CS@S-nZVI/BC promoted root iron plaque formation by 176.1% and increased Pb adsorption by root iron plaque by 156.9%, while decreasing the oxidizable Pb fraction in soil by 11% and increasing the reducible Pb fraction by 10%. These results indicate that GSNO-CS@S-nZVI/BC mitigates Pb toxicity through sustained NO release, enhanced root iron plaque-mediated Pb sequestration, and soil Pb stabilization. Overall, this nano-enabled amendment provides a promising strategy for reducing Pb transfer from contaminated paddy soils to rice grains and improving the safe utilization of Pb-contaminated farmland.

Molecules doi: 10.3390/molecules31162760

Authors: Xinyu Zhang Lidong Dai Haiying Hu Ziqiang Xu Juxiang Shao Hongchun Luo Jiajun Zhu Zhongying Mi Tao Wang Miao Ren Yu Gao Meiling Hong

Cadmium phosphorous trisulfide (CdPS3), a prototypical member of metal thio- and selenophosphates (MTPs), has garnered tremendous research interest due to its fundamental properties and potential for novel applications. In this paper, we conducted a comprehensive investigation on the structural evolution and electrical transport behaviors of CdPS3 up to 59.1 GPa under different hydrostatic environments by means of Raman spectroscopy and electrical conductivity measurements. Under non-hydrostatic compression, CdPS3 experienced a succession of structural modifications from C2/m to R3¯ phases at 1.4(5) GPa, then to the isostructural R3¯ phase at 7.8(5) GPa and sequentially to the P3¯1m phase at 29.8(11) GPa, followed by a semiconductor-to-metal transition at 51.3(8) GPa. Under hydrostatic pressurization, ~2.0 GPa pressure hysteresis for the R3¯-to-P3¯1m structural modification and metallization was identified, which can be reasonably interpreted by the impact of deviatoric stress. Upon decompression, the structural transitions of CdPS3 were demonstrated to be reversible with the existence of considerable pressure hysteresis under different hydrostatic environments. Our findings on CdPS3 not only lay a solid foundation for exploring the physicochemical properties of other MTPs under extreme conditions but also push forward its applications in high-performance multifunctional devices.

Molecules doi: 10.3390/molecules31162759

Authors: Panpan Liu Peijun He Yixin Wu Xiufang Li Xianmang Xu Jianing Duan Peng Bai

In this study, we prepared a magnetic University of Oslo-66 (UiO-66) composite material, Fe3O4@SiO2@UiO-66, and applied it as an adsorbent for the effective removal of benzoic acid from wastewater. The resulting magnetic MOF composite retained the structural and property characteristics of MOFs, along with magnetic separation capabilities, allowing for swift recovery from water through external magnetic fields. A potential synergistic effect between magnetic particles and UiO-66 was observed, leading to enhanced benzoic acid adsorption. The adsorption capacity per Zr6 cluster unit in Fe3O4@SiO2@UiO-66 measured 569.5 g/mol, surpassing that of UiO-66 by more than 26%. We conducted investigations into adsorption properties as a function of initial concentration, contact time, and pH values. The adsorption of magnetic UiO-66 composites was well described by pseudo-second-order and Langmuir models, indicating predominant chemisorption on the homogeneous surface. Thermodynamic studies of adsorption revealed a spontaneous exothermic process. Furthermore, we analyzed possible mechanisms of benzoic acid adsorption, highlighting the contributions of electrostatic interactions, coordination interactions, and π–π stacking interactions. Magnetic UiO-66 exhibited remarkable adsorption capacity, along with reliable regeneration performance and convenient magnetic separation capabilities, making it an exceptional adsorbent for industrial applications in the removal of benzoic acid.

Molecules doi: 10.3390/molecules31162757

Authors: Elisa Visentin Nicola De Zordi Angelo Cortesi Ramona Iseppi Eva Pericolini Cristina Forzato

Cornus mas L. fruits are a valuable source of bioactive natural products with potential applications in functional foods and food preservation. In the present study, supercritical carbon dioxide (Sc-CO2) extraction was applied for the recovery of lipophilic fractions from Cornus mas fruits under different operating conditions of pressure, temperature, and extraction time. The influence of extraction parameters on the extraction yield was investigated using a design of experiments (DoE) approach. The chemical composition of the obtained extracts was characterized via high-resolution gas chromatography (HRGC), revealing a fatty acid profile dominated by linoleic acid (58–63%) and oleic acid (22–24%), followed by palmitic acid (8–9%), stearic acid (2–4%), arachidic acid (about 2%), and behenic acid (about 1%). The extracts were further evaluated for antimicrobial activity against selected Gram-positive and Gram-negative bacteria, including Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, as well as against the yeast Candida albicans. The results demonstrated that supercritical CO2 extraction represents an effective green technology for the selective recovery of lipophilic bioactive compounds from Cornus mas fruits. The extracts exhibited measurable antimicrobial activity in broth microdilution assays against selected Gram-positive and Gram-negative bacteria, as well as Candida albicans, supporting their potential as natural antimicrobial agents. The combination of green extraction technology, analytical characterization, and bioactivity evaluation contributes to the valorization of Cornus mas fruits as a source of food-derived natural products.

Molecules doi: 10.3390/molecules31162758

Authors: Yanping Zhang Haichao Zuo Chenxi Zhang Di Gao Yibo Wen Xinxin Jiang

In this study, total flavonoids from Polygonum perfoliatum L. (PPTF) were extracted using ionic liquid-assisted ultrasound and purified by macroporous resin. After optimization, the total flavonoid content increased from 33.9% to 71.2%. HPLC identified hyperoside, kaempferol-3-O-rutinoside, and quercetin. In vitro experiments showed that PPTF exhibited good free radical scavenging activity and inhibitory effects on α-glucosidase and α-amylase. Within the concentration range of 3.13–12.50 μg/mL, PPTF was non-toxic to HepG2 cells and improved glucose uptake, promoted glycogen synthesis, and reduced lipid accumulation in insulin-resistant cells in a dose-dependent manner. In a type 2 diabetic mouse model induced by high-fat diet combined with streptozotocin, intragastric administration of PPTF for four weeks significantly lowered fasting blood glucose in the high-dose group, improved oral glucose tolerance and insulin sensitivity, increased hepatic and muscle glycogen, normalized serum lipid profiles, and alleviated pathological damage in the liver and pancreas. PPTF exhibits favorable hypoglycemic and lipid-regulating effects in both cellular and animal models, demonstrating its potential for development as an adjunctive functional product for glycemic management.

Molecules doi: 10.3390/molecules31162756

Authors: Ren He Wei Liu Bingyi Tao Shaoxiong Liang Xuchong Tang

D-tagatose, a low-calorie sugar substitute, widely used in the food and pharmaceutical industries, can be produced from the substrate D-galactose using L-arabinose isomerase (L-AI). L-AI genes derived from Lactobacillus fermentum (LFAI), Lactobacillus brevis (LBAI), Lactobacillus plantarum (LPAI), and Lactobacillus sakei (LSAI) for the bioconversion of D-galactose into D-tagatose using whole Escherichia coli (E. coli) cells were investigated. The temperature, time, pH, whole-cell concentration, and metal ion concentration were optimized to enhance catalytic production. The results revealed that at the low substrate concentration of 10 g/L, LFAI, LBAI, LPAI, and LSAI exhibited considerable catalytic activity, with conversion rates of 55.31%, 68.17%, 61.45%, and 58.22%, respectively. In contrast, at the high substrate concentration of 250 g/L, their conversion rates were 19.78%, 18.47%, 20.26%, and 36.24%, respectively, with LSAI demonstrating superior catalytic performance. In order to facilitate the industrial production of D-tagatose, site-directed mutagenesis was performed on LSAI. Among the engineered LSAI variants, the P99H, K142R, and L465R mutants all showed increased catalytic rates for D-tagatose. Specifically, at the high substrate concentration of 250 g/L, the P99H mutant achieved a conversion rate of 45.73%, representing a 32.7% improvement compared to the optimized LSAI. These results indicate that the designed site-directed mutagenesis strategy effectively enhanced whole-cell bioconversion performance of LSAI toward D-galactose.

Molecules doi: 10.3390/molecules31162755

Authors: Hongqiang Yuan Zheyuan Zhan Ying Zhang Yue Ran Chaofan Tan Jialian Xie

In this study, oil sludge was utilized as a carbon source to prepare a carbon-based catalyst. By leveraging the oil sludge’s inherent iron content and subsequently introducing exogenous copper, a CuO/Fe2O3/carbon composite material (OSC-0.75Cu) was synthesized for the activation of peroxymonosulfate (PMS) to degrade p-nitrophenol. The OSC-0.75Cu/PMS system achieved a degradation efficiency of 92.19%, which was 2.91 times that of the OSC/PMS system (31.71%), and its reaction rate constant (kobs) was 8.9 times greater. Furthermore, in simulated water matrices (containing anions and fulvic acid) and three real water matrices (rainwater, moat water, and Yangtze River water), the OSC-0.75Cu/PMS systemachieved PNP degradation efficiencies ranging from 71.63% to 76.36%. The degradation of p-nitrophenol in this system involves three primary reactive species: hydroxyl radicals (•OH), sulfate radicals (•SO4−), and singlet oxygen (1O2), among which 1O2 plays the dominant role. The coexistence of Cu and Fe species may facilitate surface redox reactions during PMS activation, while defect-related oxygen sites may contribute to PMS adsorption and activation and the generation of 1O2. This study provides a novel strategy that enables the resource utilization of oil sludge while simultaneously addressing environmental remediation challenges.

Molecules doi: 10.3390/molecules31162754

Authors: Hazem S. Elshafie Amira A. Mohamed Ippolito Camele

Chitosan, a chitin-derived biopolymer, is widely used in agriculture and food preservation. Fungal-derived chitosan offers a sustainable alternative to crustacean sources, and Ganoderma lucidum represents a promising source of this functional material. This study characterized fungal chitosan (F.Cs) extracted from G. lucidum cell-wall chitin by FT-IR, molecular weight, viscosity, and degree of deacetylation. Its antimicrobial activity was evaluated in vitro, and its preservative and disease control efficacy against Monilinia fructicola on postharvest apples was compared to commercial chitosan (C.Cs). DNA/protein leakage of the studied FGs and C.Cs were investigated to reveal the antimicrobial mechanisms. In particular, F.Cs exhibited promising in vitro antimicrobial activity, with MIC/MFC values of 0.75/0.75 mg/mL against M. fructicola and 0.75/1.5 mg/mL against Botrytis cinerea, compared to C.Cs. In addition, F.Cs induced greater membrane damage in M. fructicola than C.Cs, as evidenced by higher DNA leakage (24% vs. 13%) and more pronounced protein leakage (102% vs. 98%). In vivo assay demonstrated that F.Cs formed an effective protective coating layer, reducing fruit moisture loss, preserving firmness s, and significantly limiting M. fructicola-induced decay compared to C.Cs. Particularly, F.Cs (1.5%) were most effective, reducing disease incidence to 12.5% (preventive) and 20.8% (curative), with decay rates of 18 and 31%, respectively. C.Cs (1.5%) provided moderate protection, with disease incidences of 37.5 and 43.7% in preventive and curative treatments, respectively. These results demonstrate the superior efficacy of F.Cs over C.Cs in preserving apple quality and enhancing resistance to M. fructicola, highlighting the potential of G. lucidum-derived chitosan as a sustainable, multifunctional biopolymer for postharvest disease control and fruit quality preservation.

Molecules doi: 10.3390/molecules31162753

Authors: Weiwei Zhu Yi Ren Yaxin Xiao Shaoyu Du Xiaoli Xie Kao Chen

Due to the fact that municipal sludge incineration generates a large amount of toxic sewage sludge ash (SSA), cement solidification is becoming an efficient harmless treatment method. However, the large amount of phosphorus in sludge ash can delay the setting time of cement pastes and lead to a decrease in its later strength. Moreover, as an important non-renewable resource, the recycling and utilization of phosphorus is also a current research hotspot. To this end, this paper proposes to remove phosphorus from incinerated sewage sludge ash (ISSA) by the acid washing process, and, in response to the problem of reduced volcanic ash activity in acid-washed sewage sludge ash (ASSA), calcium chloride (CaCl2) is added as an activator to explore the optimal process and hydration mechanism for enhancing ASSA activity. This study removed phosphorus from calcined SSA (800 °C, 2 h) via acid washing (0.3 mol/L H2SO4, L/S = 10:1, 2 h) to obtain ASSA, and used CaCl2 as an activator to improve its pozzolanic activity. Different CaCl2 dosages (1–3%) were tested for paste setting time, 3/7/28 d compressive strength, and characterized by hydration heat, XRD, SEM, etc. Experimental results indicated that the synergistic addition of 2 wt.% CaCl2 and 20 wt.% ASSA shortened the initial and final setting times by 38% and 23% to 142 min and 289 min, respectively. Meanwhile, the compressive strength at 28 days was improved by 24%, with a final strength value of 42 MPa. Microanalysis revealed abundant Friedel’s salt formation and a denser structure (fine mesopores 60%, coarse mesopores 26%), confirming CaCl2 effectively activates ASSA for cement admixture use.

Molecules doi: 10.3390/molecules31162752

Authors: Kenna L. Whitnell Jackson J. Villemaire-McCutcheon Ulli K. C. Bodnar M. Sameer Al-Abdul-Wahid Tariq A. Akhtar

A key factor that regulates melanogenesis is the activity of tyrosinase, and inhibitors of this enzyme are used as skin-whitening and lightening agents in the skincare and cosmetics industries. The methanolic extract from male inflorescences of Artocarpus altilis (Parkinson) Fosberg (breadfruit) was investigated for its bioactivities which are important for the skincare industry, including anti-tyrosinase activity. Bioassay-guided fractionation led to the isolation of a geranylated dihydrochalcone, 2-Geranyl-2’,3,4,4’-tetrahydroxydihydrochalcone (hereinafter referred to as Artochalcone), present at 1.64% of the inflorescence dry weight. Its structure was determined by a combination of 1D and 2D-NMR and HR-ESI-MS analysis. Artochalcone was found to inhibit tyrosinase with an IC50 value of 28.4 μM, making it sixteen times more effective than the leading commercial skin-whitening agent, arbutin. In addition, Artochalcone displayed significant antioxidant activity determined by 2,2-diphenyl-1-picrylhydrazyl (IC50 = 20.4 μM) and nitric oxide scavenging assays (IC50 = 20.7 μM).

Molecules doi: 10.3390/molecules31162750

Authors: Ang Yu Yingjie Ji Guangrun Hu Qi Zhang Zhaodi Wang Yi Zhang

Lithium–sulfur (Li-S) batteries, featuring a superior theoretical energy density of 2600 Wh/kg and a high specific capacity of 1675 mAh/g for sulfur cathodes, have emerged as a promising candidate for next-generation, high-energy-density energy storage technologies. Nevertheless, their commercialization has been hindered by some bottlenecks, including the polysulfide (LiPSs) shuttle effect, severe volume expansion, and sluggish reaction kinetics. Density Functional Theory (DFT), serving as an atomic-scale computational tool, offers essential theoretical assistance for clarifying the mechanisms and guiding the precision design of S cathode of Li-S batteries. This review focuses on the role of DFT in the mechanism of polysulfide conversion and the shuttle effect. By simulating the adsorption energy, charge density distribution, and reaction pathways of LiPSs using DFT calculations, the key reaction steps of polysulfide conversion can be clearly identified. In addition, DFT calculations also play a vital role in the inhibition of lithium dendrites and the regulation of the solid-electrolyte interphase (SEI) film. This review suggests that DFT calculations could provide more applications in the development of Li-S batteries.

Molecules doi: 10.3390/molecules31162751

Authors: Aleksandra Such Ewelina Węsierska Magdalena Surma Anna Winiarz Aneta Koronowicz

Synthetic plastics remain widely used in food packaging despite environmental concerns. This laboratory-scale study evaluated biodegradable chitosan-alginate films enriched with oregano or turmeric two-phase equilibrium condensates as active packaging films for highbush blueberries (Vaccinium corymbosum L.). Film hydration properties were assessed, and blueberries were stored at 4 °C or 22 °C for 7 or 14 days. Dry matter, proximate composition, total phenolic content (TPC), antioxidant activity, vitamin C, and total viable bacterial count (TVC) were measured. Simulated gastrointestinal film digestates were evaluated in Nthy-ori 3-1 thyroid epithelial and CCD 841 CoN colonic epithelial cells. Oregano-enriched films (OS3) showed greater water uptake and swelling than control and turmeric-enriched films. Blueberry responses depended on formulation and storage conditions. After 14 days at 4 °C, OS2- and OS3-packaged blueberries showed higher vitamin C contents than plastic controls, corresponding to approximately 20% lower vitamin C loss. TVC was primarily influenced by temperature, with no significant main effect of packaging type. Digestates did not significantly alter evaluated DNA-damage markers under short-term exposure conditions. Concentration-dependent cell-cycle changes occurred in Nthy-ori 3-1 cells after OS2 and OS3 exposure, whereas no significant changes were observed in CCD-841CoN cells.

Molecules doi: 10.3390/molecules31162749

Authors: Mohammad Maaz Agilan Balupillai Saravanabhavan Periyakali Jasmin Padhan Kumar Kalavathy Murugan Joen-Rong Sheu Jayakumar Thanasekaran

Natural products represent an important source of bioactive compounds with therapeutic potential in the fields of thrombotic and oxidative stress-related disorders. This study focuses on identifying active compounds from the ethanolic extract of Ocimum sanctum L. leaves (EEOSL) and validating its antiplatelet and hepatoprotective activities. GC-MS and LC-MS (both positive and negative ionization modes) analyses identified 155 and 113 compounds, respectively, constituting several bioactive compounds. Collagen-induced human platelet activation (CIHPA) and carbon tetrachloride (CCl4)-induced hepatotoxicity were used as rat models to assess the activity of EEOSL. EEOSL (1–10 mg/mL) was shown to significantly and dose-dependently inhibit collagen-induced platelet aggregation. The extract also inhibited P-selectin expression, ATP release and intracellular Ca2+ mobilization, suggesting inhibition of major pathways involved in platelet activation. To understand the mechanisms, molecular docking was carried out with key platelet signaling molecules such as GPVI, SYK, PLCγ2, P2RY12, and PI3Kβ. Some phytoconstituents showed good binding affinities, with apigenin having the highest binding affinity for PI3Kβ (−8.01 kcal/mol). This binding was further validated by molecular dynamics simulations showing the formation of stable complexes. Intraperitoneal injection of CCl4 significantly increased the serum hepatic markers (SGOT, SGPT, LDH and SALP); EEOSL treatment significantly reduced these increases in vivo. The extract normalized antioxidant enzyme activities (catalase, SOD and glutathione peroxidase) and antioxidant isozyme patterns. Histopathological results revealed a significant level of protection against liver damage. Overall, the results showed that EEOSL has phytoconstituents that could provide strong antiplatelet and hepatoprotective properties, likely due to their ability to modulate platelet signaling pathways and enhance antioxidant defense mechanisms.

Molecules doi: 10.3390/molecules31162746

Authors: Iva Rezić Meštrović Darinka Cvetković Antonio Zandona Maja Katalinić Ernest Meštrović Maja Somogyi Škoc

Functional coatings based on natural bioactive compounds have attracted increasing interest in topical and biomedical applications. In this study, textile substrates were coated with formulations containing propolis and selected biopolymers to create biocompatible surfaces with enhanced physicochemical and biological properties. The coating preparation process was optimized to achieve uniform deposition and stable incorporation of bioactive constituents. The chemical composition and interactions between propolis, biopolymers, and textile fibers were investigated using Fourier-transform infrared spectroscopy (FTIR), while surface morphology and coating distribution were characterized by scanning electron microscopy (SEM). The presence and stability of key phenolic compounds in propolis were analyzed by high-performance liquid chromatography (HPLC). Optical properties and UV-shielding performance of the coated textiles were evaluated using UV–Vis spectroscopy. The coffee-ring effect was investigated during coating formulation, as this phenomenon significantly reveals coating homogeneity, surface microstructure, and the spatial distribution of active compounds. The influence of formulation parameters on deposit morphology and coating quality was systematically assessed. The biocompatibility of the developed coatings was evaluated through in vitro cytotoxicity testing, demonstrating their suitability for direct skin contact. The combined analytical results confirmed successful incorporation of propolis into the biopolymer matrix, indicating that propolis–biopolymer coatings represent a promising approach for the fabrication of functional textiles intended for topical applications, including wound care, skin protection, and antimicrobial textile products.