Molecules

21 pages, 2370 KB

Open AccessPerspective

History Matters in Solid-State Hydrogen Storage: Hidden State Variables and Pathway-Dependent Reactivity in Mg-Based Hydrides

by Chen Chen, Quanhui Hou, Liangjuan Gao and Zhao Ding

Molecules 2026, 31(11), 1982; https://doi.org/10.3390/molecules31111982 (registering DOI) - 5 Jun 2026

Abstract

Magnesium-based hydrides remain among the most intensively studied solid-state hydrogen storage materials because they combine high theoretical hydrogen capacity, elemental abundance, and relatively low cost. Yet their practical behavior often varies far more strongly than nominal composition alone would suggest. Materials described under [...] Read more.

Magnesium-based hydrides remain among the most intensively studied solid-state hydrogen storage materials because they combine high theoretical hydrogen capacity, elemental abundance, and relatively low cost. Yet their practical behavior often varies far more strongly than nominal composition alone would suggest. Materials described under similar chemical labels may show markedly different activation profiles, sorption kinetics, reversible capacities, and cycling responses, even when they appear compositionally comparable. This Perspective argues that such discrepancies are best understood by recognizing that Mg-based hydrogen storage materials are not fully defined by composition, catalyst identity, and equilibrium thermodynamics alone. Instead, they react from historically written states produced by synthesis, activation, and cycling. These histories generate hidden state variables, including defects, residual strain, metastable structural motifs, interfacial topology, and catalyst transformation states, that reshape the operative hydrogen sorption pathway. The discussion therefore moves from a conventional composition-centered view toward a pathway-centered interpretation of reactivity. First, it examines how hidden state variables are written into Mg-based materials through processing, activation, and repeated use. It then shows how metastability serves as the structural bridge that allows these variables to persist into the reaction window. On that basis, the article argues that hydrogen sorption in Mg-based hydrides is fundamentally pathway-dependent, with history influencing hydrogen entry, transport-network selection, interfacial route construction, and pathway evolution during cycling. This perspective also provides a more coherent explanation for the long-standing reproducibility problem in the field, which is reinterpreted here as a pathway-mismatch problem arising from comparisons among historically different reactive states. Finally, a metadata-aware, pathway-aware, and boundary-aware design framework is proposed as a more realistic basis for cumulative materials development. From this viewpoint, the future of Mg-based solid-state hydrogen storage depends not only on better compositions, but on better-defined, better-constructed, and better-preserved reactive pathways under clearly specified internal and external constraints. Full article

(This article belongs to the Special Issue Recent Advances in Energy Storage Systems: From Materials Innovation to Practical Applications)

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26 pages, 18248 KB

Open AccessArticle

Structure and Wound-Healing Activity of a Branched Levan-Type Fructan from Cyathula officinalis Roots

by Yujie Qiu, Chengcheng Cai, Lijuan Wu, Xinyi Zhao, Tianle Liu, Qingmiao Li, Sizhe Shui, Rui Li, Mengliang Tian and Hai Lan

Molecules 2026, 31(11), 1981; https://doi.org/10.3390/molecules31111981 (registering DOI) - 5 Jun 2026

Abstract

Cyathula officinalis Kuan, a medicinal plant used in traditional medicine, remains underexplored as a source of structurally defined wound-repair polysaccharides. In this study, a water-soluble polysaccharide fraction, CoPS, was isolated from C. officinalis roots and structurally characterized using methylation analysis and 1D/2D NMR [...] Read more.

Cyathula officinalis Kuan, a medicinal plant used in traditional medicine, remains underexplored as a source of structurally defined wound-repair polysaccharides. In this study, a water-soluble polysaccharide fraction, CoPS, was isolated from C. officinalis roots and structurally characterized using methylation analysis and 1D/2D NMR spectroscopy. Purified CoPS had a total carbohydrate content of 94.8%, a weight-average molecular weight (M_w) of 7.491 kDa, and a narrow dispersity (M_w/M_n = 1.04). Monosaccharide composition analysis showed that CoPS was mainly composed of fructose and glucose at a molar ratio of 95.60:4.40. Structural analyses identified CoPS as a branched levan-type fructan with a β-(2→6)-linked fructofuranosyl backbone and β-(2→1)-linked branching motifs. CoPS was incorporated into a Carbomer/alginate topical formulation, termed CoPS-CPG, and evaluated in vitro and in vivo. CoPS-CPG showed good cytocompatibility and promoted HaCaT keratinocyte migration, reducing the residual scratch area to 48.10% at 12 h compared with 70.13% in the control group and 65.18% in the vehicle (Blank-CPG) group. In a murine full-thickness excisional wound model, CoPS-CPG reduced the residual wound area to 8.70 ± 1.20% on day 14, compared with 24.83 ± 1.51% in the control group and 14.20 ± 0.72% in the vehicle group. Histological and immunological analyses further indicated improved tissue reconstruction, a reduced inflammatory burden, enhanced CD206-associated macrophage signals, increased CD31-associated vascular structures, improved α-SMA-associated perivascular coverage, and lower late-stage HIF-1α expression. These findings identify CoPS as a structurally defined plant-derived levan-type fructan that supports cutaneous wound repair. Full article

(This article belongs to the Special Issue Chemical Composition, Pharmacological and Therapeutic Activity of Plant Extracts)

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27 pages, 6298 KB

Open AccessReview

Pesticide Residues in Fruits: From Surveillance Data to Risk-Based Interpretation and Mitigation

by Jarosław Chmielewski, Barbara Gworek, Ewa Beata Górska, Maciej Masłyk, Łukasz Szarpak and Grażyna Nowak-Starz

Molecules 2026, 31(11), 1980; https://doi.org/10.3390/molecules31111980 (registering DOI) - 5 Jun 2026

Abstract

Background: Interpretation of pesticide residues in fruits requires tight integration of surveillance evidence, analytical capability, regulatory context, and mitigation data. Methods: This critical integrative review synthesises analytical chemistry, cumulative risk assessment (CRA), regulatory divergence, and mitigation evidence, strengthened by quantitative monitoring summaries and [...] Read more.

Background: Interpretation of pesticide residues in fruits requires tight integration of surveillance evidence, analytical capability, regulatory context, and mitigation data. Methods: This critical integrative review synthesises analytical chemistry, cumulative risk assessment (CRA), regulatory divergence, and mitigation evidence, strengthened by quantitative monitoring summaries and auditable regulatory examples. Routine enforcement continues to rely on validated QuEChERS extraction coupled with targeted LC-MS/MS and GC-MS/MS. High-resolution mass spectrometry (HRMS) adds unique value for metabolites, transformation products (TPs), and incident response, but its routine enforcement role remains constrained by confirmation logic and harmonised validation. Results: Monitoring shows that exposure is typically multi-residue rather than single-compound; the key interpretive challenge therefore shifts toward CRA prioritisation, sensitive-subpopulation assumptions, and transparent distinction between compliance signals and toxicological inference. We provide (i) headline compliance metrics from EU and US programmes, (ii) surveillance-derived high-frequency residue patterns and co-occurrence motifs to guide CRA prioritisation, (iii) an illustrative, traceable comparison of EU/US/Codex MRL divergence for emblematic citrus residues with EU evidence extracts and US/Codex traceability records, and (iv) mitigation evidence statements standardised by study type and transformation-product reporting. Conclusions: Pesticide residues in fruits should be interpreted through a risk-based framework that distinguishes compliance findings from toxicological concern, prioritises relevant multi-residue drivers, and evaluates mitigation according to both residue reduction and transformation-product uncertainty. Full article

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31 pages, 6266 KB

Open AccessArticle

Ester-Bond-Cleavable Self-Degradable Gel Particles for Temporary Plugging and Controlled Deplugging in Multi-Fracture Reservoir Systems

by Zhe Li, Yaguang Qu, Li Han and Gang Wang

Molecules 2026, 31(11), 1979; https://doi.org/10.3390/molecules31111979 (registering DOI) - 5 Jun 2026

Abstract

Temporary plugging and flow diversion in multi-fracture reservoirs require gel particles that can provide stable plugging in dominant fractures while enabling low-residue deplugging after treatment. In this study, ester-bond-cleavable self-degradable gel particles were prepared by aqueous free-radical crosslinking using acrylamide, 2-acrylamido-2-methylpropanesulfonic acid, N-vinyl-2-pyrrolidone, [...] Read more.

Temporary plugging and flow diversion in multi-fracture reservoirs require gel particles that can provide stable plugging in dominant fractures while enabling low-residue deplugging after treatment. In this study, ester-bond-cleavable self-degradable gel particles were prepared by aqueous free-radical crosslinking using acrylamide, 2-acrylamido-2-methylpropanesulfonic acid, N-vinyl-2-pyrrolidone, and polyethylene glycol diacrylate as a hydrolysable crosslinker. An MBAA-crosslinked particle was used as a nondegradable control. FTIR and SEM results confirmed the formation of ester-containing crosslinked networks with tunable morphology. Among the prepared samples, EGP-2 showed a balanced hydration and mechanical response, with an equilibrium swelling ratio of 7.12 g/g at 80 °C and 100,000 mg/L salinity, a storage modulus of 205 Pa at 1 Hz, a compressive stress of 54.2 kPa at 30% strain, and a height recovery ratio of 91.8%. In single-fracture tests, EGP-2 achieved plugging efficiencies of 98.6% and 97.4% in 0.5 and 1.0 mm fractures, respectively, with corresponding erosion retention ratios of 94.1% and 92.6%. In a three-parallel-fracture model, EGP-2 reduced the dominant-fracture flow split ratio from 78.4% to 32.8%, while increasing the combined flow split ratio of the medium and narrow fractures from 21.6% to 67.2%, corresponding to a flow diversion efficiency of 58.2%. After aging at 120 °C for 96 h, EGP-2 exhibited a mass loss ratio of 78.4% and a G′ retention ratio of 25.4%. Subsequent flowback tests showed a flowback ratio of 82.6%, a permeability recovery ratio of 88.7%, and a residue ratio of 10.9%. These results demonstrate that ester-bond-cleavable gel particles can integrate temporary plugging, flow diversion, and controlled deplugging, offering a low-residue strategy for multi-fracture reservoir conformance control. Full article

14 pages, 7604 KB

Open AccessArticle

Monitoring Ethylene Oxide Residues in Food: A Simplified QuEChERS-Based GC-MS/MS Method for Routine Analysis

by Tabita Mauti, Daniela Delfino, Valentina Nicolini, Barbara Droghei, Daniele Colangelo, Daniela Triolone, Fulvia Fiorucci, Paolo Di Giustino, Marta Mancuso, Marianna Leo, Francesca D’Onofrio, Alessandro Ubaldi and Katia Russo

Molecules 2026, 31(11), 1978; https://doi.org/10.3390/molecules31111978 (registering DOI) - 5 Jun 2026

Abstract

Ethylene oxide (EtO) has been banned in the European Union since 1991 as a fumigant for food commodities. Nevertheless, recurrent contamination incidents, especially since 2020, involving imports from India, have raised significant food safety concerns. Despite regulatory measures, EtO and its metabolite, 2-chloroethanol [...] Read more.

Ethylene oxide (EtO) has been banned in the European Union since 1991 as a fumigant for food commodities. Nevertheless, recurrent contamination incidents, especially since 2020, involving imports from India, have raised significant food safety concerns. Despite regulatory measures, EtO and its metabolite, 2-chloroethanol (2-CE), continue to be detected in a variety of food products, including dried foods, dietary supplements, and food additives. This study presents a QuEChERS-based method involving the conversion of EtO into 2-CE, which is subsequently quantified by isotope dilution gas chromatography–tandem mass spectrometry (GC-MS/MS). In contrast to previously published methods, this protocol utilises an Agilent HP-5ms Ultra Inert column (30 m × 250 μm × 0.25 mm), routinely employed in our laboratory for multi-residue pesticide analysis. The proposed approach is therefore readily adaptable to laboratories already performing multi-residue analyses, as it does not require modifications to existing instrumental configurations. The method was validated in accordance with SANTE/11312/2021 guidelines. A total of 84 samples, primarily imported from India, as well as from Brazil, Argentina, and the United Kingdom, were analysed. 2-CE was detected in four samples, and in two cases, the sum of EtO and 2-CE, expressed as EtO, exceeded the European Union (EU) maximum residue limit (MRL). Full article

(This article belongs to the Special Issue Emerging Analytical Methods for Contaminants in Food and Environment)

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27 pages, 4020 KB

Open AccessArticle

Chemo-Diversity Landscape Using Physico-Biochemical, Elemental, and Metabolic Profiling in Different Stages and Accessions of Madhuca longifolia Flowers for Unveiling Their Processing Value and Utilization

by Shalini Purwar, Ankit Verma, Ravi Prakash Jaiswal, Vigya Mishra, Vishal Chugh, Chandra Mohan Singh, Akbare Azam, Nitin Kumar, Priti Upadhyay, Tribhuvan Chaubey and Ashutosh Rai

Molecules 2026, 31(11), 1977; https://doi.org/10.3390/molecules31111977 (registering DOI) - 5 Jun 2026

Abstract

Variations in sweetness and bitterness among Madhuca longifolia flowers strongly influence their processing value and market acceptance, yet the chemo-diversity underlying these traits remains poorly characterized. This study aimed to unravel accession- and stage-specific differences by integrating physico-biochemical, elemental, and metabolic profiling across [...] Read more.

Variations in sweetness and bitterness among Madhuca longifolia flowers strongly influence their processing value and market acceptance, yet the chemo-diversity underlying these traits remains poorly characterized. This study aimed to unravel accession- and stage-specific differences by integrating physico-biochemical, elemental, and metabolic profiling across thirteen accessions (BM−1 to BM−13) from BUAT, Banda. Sensory and textural evaluations revealed wide diversity, with BM−5 displaying superior sweetness and aroma, whereas BM−6, BM−7, and BM−10 were differentiated by firmness, elasticity, and gumminess. Biochemical analyses across flower development showed that BM−5 consistently maintained higher sugars and β-carotene, while BM−1 exhibited marked reductions in sugars and total phenolics content; meanwhile, antioxidant activity increased with maturity, with BM−5 remaining the most stable. ICP-MS elemental analysis confirmed BM−5 as mineral-rich compared with lower-performing accessions. GC-MS metabolomic profiling of contrasting accessions (BM−1 and BM−5) across stages identified 303 volatile and semi-volatile metabolites, and multivariate analyses (PCA, VIP, volcano plots, pathway enrichment) revealed distinct stage- and accession-dependent patterns. Mature BM−5 was enriched in fermentation- and aroma-related metabolites such as melibiose, furfural, 5-HMF, and furaneol, whereas BM−1 accumulated defense-linked compounds including catechol, benzyl nitrile, and maltol. Overall, the integrated chemo-diversity landscape identifies BM−5 as a superior accession with high processing potential and value-addition prospects. Full article

(This article belongs to the Special Issue Fruits and Vegetables as Prospective Reserves of Bioactive Compounds—Second Edition)

16 pages, 3355 KB

Open AccessArticle

Parametric Optimization and Performance Analysis of an Internally Cooled Structured Reactor for CO₂ Direct Air Capture via Temperature–Vacuum Swing Adsorption

by Jiale Zheng, Wenqi Fan, Chuanruo Yang, Ming Xue, Zhexuan An, Xinglei Zhao, Xingchun Li, Aiguo Zhou and Liang Huang

Molecules 2026, 31(11), 1976; https://doi.org/10.3390/molecules31111976 (registering DOI) - 5 Jun 2026

Abstract

Direct air capture (DAC) based on adsorption is a promising negative-emission technology owing to its operational flexibility, modular deployment potential, and comparatively low regeneration temperature. In this study, a dynamic three-dimensional mathematical model was developed to investigate a structured adsorption-based DAC reactor operating [...] Read more.

Direct air capture (DAC) based on adsorption is a promising negative-emission technology owing to its operational flexibility, modular deployment potential, and comparatively low regeneration temperature. In this study, a dynamic three-dimensional mathematical model was developed to investigate a structured adsorption-based DAC reactor operating under a temperature–vacuum swing adsorption cycle. The model couples heat and mass transfer among the gas, adsorbent, metal structure, and heat-transfer fluid and was used to evaluate the temporal and spatial evolution of temperature and CO₂ adsorption capacity during adsorption and regeneration. The effects of internal cooling, heat-source temperature, and vacuum pressure on cyclic performance were systematically analyzed. The results show that introducing an internal cooling source significantly accelerates adsorbent-bed cooling and increases the cyclic working capacity by approximately 10%. Parametric simulations indicate that higher regeneration temperature and lower vacuum pressure enhance CO₂ desorption, with optimal performance achieved at a heat-source temperature of 90 °C and a vacuum pressure of 1 kPa. Under these conditions, the DAC system reaches an annual CO₂ productivity of 125 tCO₂·year⁻¹, with mechanical and thermal energy consumptions of 4.72 and 11.91 GJ·tCO₂⁻¹, respectively. This work provides a useful modeling framework for reactor design and operating-parameter optimization in adsorption-based DAC systems. Full article

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31 pages, 1072 KB

Open AccessArticle

Effects of Chemical Composition on Anaerobic Digestion Kinetics of Sugar Beet Pulp: Gompertz and Two-Fraction Kinetic Modelling

by Krzysztof Pilarski, Agnieszka A. Pilarska, Piotr Boniecki, Karol Durczak and Piotr Sołowiej

Molecules 2026, 31(11), 1975; https://doi.org/10.3390/molecules31111975 (registering DOI) - 5 Jun 2026

Abstract

Anaerobic digestion (AD) of agro-industrial residues supports the green energy transition by converting organic matter into renewable biogas. Sugar beet pulp is a highly fermentable feedstock, although its process response may vary with chemical composition. This study examined how chemical composition affects mesophilic [...] Read more.

Anaerobic digestion (AD) of agro-industrial residues supports the green energy transition by converting organic matter into renewable biogas. Sugar beet pulp is a highly fermentable feedstock, although its process response may vary with chemical composition. This study examined how chemical composition affects mesophilic biogas-production kinetics of sugar beet pulp prepared under laboratory conditions from surplus sugar beet roots. The roots represented ten sugar beet varieties (A–J), and the prepared pulp was characterised for pH, dry matter, organic dry matter, mineral composition, and the relative shares of simple sugars, polysaccharides, protein, and fibre. Batch digestion tests were performed at 39 °C for 30 days. Production curves were analysed using complementary kinetic models (modified Gompertz and a two-fraction first-order model) to capture the lag phase and the contributions of rapidly and slowly degradable substrate pools. Biogas yields ranged from 126 to 141 m³ Mg⁻¹ fresh matter with 50–55% CH₄, corresponding to 64.3–76.1 m³ CH₄ Mg⁻¹ organic dry matter, while organic matter conversion reached 71.2–82.4%. Varieties enriched in simple sugars exhibited a higher share of the fast-degradable fraction and shorter lag phases, indicating faster onset and stronger methane formation. In contrast, higher fibre contents reduced the slow-fraction rate constant and lowered overall conversion, consistent with hydrolysis-limited degradation of the structural carbohydrate matrix. The mineral ion background, particularly K and Na, indicated moderate ionic buffering and stable operation without inhibition. The novelty of this work lies in integrating detailed compositional profiling with dual kinetic modelling to translate chemical fingerprints into tentative process-relevant implications. These implications include feeding strategy, organic loading control and hydraulic retention time selection, and they require further validation in continuous or semi-continuous AD systems. Full article

21 pages, 17712 KB

Open AccessArticle

Mechanism Through Which Antioxidant Polysaccharide from Tetrastigma hemsleyanum Protects Against DSS-Induced Ulcerative Colitis: Insights from Multi-Omics

by Ling Zhang, Wei Xu, Xinyu Liao, Guoqi Yuan, Chen Jin, Huan Xiao, Huabin Liu, Zhitong Jin, Yaqiong Deng and Yang Liu

Molecules 2026, 31(11), 1974; https://doi.org/10.3390/molecules31111974 (registering DOI) - 5 Jun 2026

Abstract

Tetrastigma hemsleyanum polysaccharide (TH-P) exhibited anti-inflammatory and intestinal protective activities, but its mechanism against ulcerative colitis (UC) remained unclear. This study used a multi-omics approach to elucidate the effects of TH-P in protecting against dextran sulfate sodium (DSS)-induced UC mice and the underlying [...] Read more.

Tetrastigma hemsleyanum polysaccharide (TH-P) exhibited anti-inflammatory and intestinal protective activities, but its mechanism against ulcerative colitis (UC) remained unclear. This study used a multi-omics approach to elucidate the effects of TH-P in protecting against dextran sulfate sodium (DSS)-induced UC mice and the underlying mechanisms. In vitro, TH-P dose-dependently suppressed LPS-induced ROS production and pro-inflammatory cytokine release in RAW264.7 cells. In vivo, TH-P alleviated DSS-induced weight loss, disease activity index, colon shortening, edema, and mucosal damage. Transcriptomic analysis and Western blotting revealed that TH-P significantly reversed DSS-induced gene expression alterations, with particular enrichment of the PI3K/AKT signaling pathway. Serum metabolomics showed that TH-P restored metabolic disturbances in glycerophospholipid and arachidonic acid metabolism. The results of 16S rRNA sequencing indicated that TH-P increased microbial diversity, enriched beneficial Bacteroidota, and reduced opportunistic Actinomycetota and Pseudomonadota. Untargeted metabolomics further demonstrated elevated acetate, propionate, and butyrate levels. Collectively, TH-P alleviated UC through a multi-target mechanism involving antioxidant and anti-inflammatory activities, gut microbiota modulation, enhanced SCFA production, and activation of the PI3K/AKT signaling pathway. Full article

(This article belongs to the Special Issue Bioactive Compounds as Modulators of Antioxidant Activity and Inflammatory Processes in Related Diseases)

16 pages, 2072 KB

Open AccessArticle

On the Question of the Full Selective Synthesis of Potentially Bioactive of 2-(tert-Butyl)-3-hydroxy-7-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-1-ones and Their Derivatives: Experimental and DFT Computational Study

by Magdalena Ciechańska, Ewelina Wielgus, Rafał Dolot, Andrzej Jóźwiak and Radomir Jasiński

Molecules 2026, 31(11), 1973; https://doi.org/10.3390/molecules31111973 (registering DOI) - 5 Jun 2026

Abstract

The practical aspects of the full regioselective preparation of 2-(tert-butyl)-3-hydroxy-7-2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-1-ones and their derivatives were described. Created in our laboratory, the reaction protocol is simple and occurs under mild conditions. It is important that all obtained products are stable, pure, [...] Read more.

The practical aspects of the full regioselective preparation of 2-(tert-butyl)-3-hydroxy-7-2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-1-ones and their derivatives were described. Created in our laboratory, the reaction protocol is simple and occurs under mild conditions. It is important that all obtained products are stable, pure, crystalline and can be easily identified based on spectral data and X-ray analysis results. Key aspects of the reaction course were explained based on the DFT quantum chemical calculations. Full article

(This article belongs to the Special Issue Small Molecules Derived from and Inspired by Natural Sources: Structure–Activity Relationships and Pharmaceutical Potential)

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19 pages, 1924 KB

Open AccessArticle

A Bond-Level Sequence Framework for Molecular Representation Learning with Structural Constraints

by Haoran Fan, Haoqiang Qi, Xin Huang, Dongyang Zhu, Na Wang, Ting Wang and Hongxun Hao

Molecules 2026, 31(11), 1972; https://doi.org/10.3390/molecules31111972 (registering DOI) - 5 Jun 2026

Abstract

Molecular property prediction is a fundamental task in drug discovery and materials design. While graph neural networks (GNNs) and SMILES-based Transformers have made significant strides, the former are often limited by local message-passing bottlenecks such as over-squashing, while the latter frequently lack explicit [...] Read more.

Molecular property prediction is a fundamental task in drug discovery and materials design. While graph neural networks (GNNs) and SMILES-based Transformers have made significant strides, the former are often limited by local message-passing bottlenecks such as over-squashing, while the latter frequently lack explicit topological constraints and suffer from severe vocabulary imbalance. In this work, we revisit the granularity of molecular modeling and propose a representation learning framework built upon bond-level sequences. Our framework models molecules as sequences of directed bond tokens and introduces a structure-aware hybrid attention mechanism. By imposing hard topological constraints on a subset of attention heads to reinforce local connectivity while preserving global receptive fields in the remaining heads, the design is intended to separate short-range chemical bonding from long-range contextual dependencies. For pre-training, we implemented a multi-scale consistency learning paradigm, which utilizes an atom-centric group masking strategy to induce a hierarchical loss of local structural information and employs contrastive and triplet losses to ensure identity consistency across varying scales of structural degradation. Furthermore, by incorporating macro-scale physicochemical descriptors (e.g., LogP, TPSA) as global anchors, we examined how the inclusion of global attribute bias can provide weak physicochemical priors during pre-training, while its effect during downstream fine-tuning remains task-dependent. Experimental results demonstrate that our lightweight model, with approximately 3.5 million parameters, exhibits a dataset-dependent performance profile across MoleculeNet benchmarks and shows promising behavior on selected topology-sensitive tasks, particularly MUV. Ablation studies further analyze the contribution of bond-level connectivity, the stage-dependent dynamics of global attribute bias, structured masking, and pre-training configurations. Ultimately, this work provides an alternative representation design for molecular modeling, offering a parameter-efficient option for future molecular learning systems alongside traditional SMILES-based and graph-based formulations. Full article

(This article belongs to the Section Computational and Theoretical Chemistry)

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17 pages, 1275 KB

Open AccessFeature PaperArticle

Imidazole-Based AT₁ Receptor Ligands: Design, Synthesis and Pharmacological Evaluation

by Florian Descamps, Marouane Rami, Jean-François Goossens, Patricia Melnyk, Maxime Liberelle and Saïd Yous

Molecules 2026, 31(11), 1971; https://doi.org/10.3390/molecules31111971 (registering DOI) - 5 Jun 2026

Abstract

The angiotensin II type 1 (AT₁) receptor is a key component of the renin–angiotensin system (RAS) and a validated target for cardiovascular and renal disorders. Developing small molecules with defined AT₁ versus AT₂ binding profiles remains important for both [...] Read more.

The angiotensin II type 1 (AT₁) receptor is a key component of the renin–angiotensin system (RAS) and a validated target for cardiovascular and renal disorders. Developing small molecules with defined AT₁ versus AT₂ binding profiles remains important for both therapeutic and mechanistic studies. Here, a series of novel imidazole-based compounds was synthesized and evaluated for their binding affinities toward angiotensin II type 1 (AT₁) and type 2 (AT₂) receptors. Binding studies were conducted by measuring the displacement of radiolabeled [³H]-angiotensin II ([³H]-AII) in PLC-PRF-5 human hepatoma cells for AT₁ receptors and calf cerebellum membranes for AT₂ receptors. Structure–activity relationship (SAR) analysis revealed that sulfonamide substitution significantly enhanced AT₁ receptor affinity, whereas sterically hindered derivatives and ester-containing compounds were less active. Molecular docking studies using the AT₁ receptor crystal structure (PDB: 8TH4) rationalized the observed activity trends. The most active compound showed high AT₁ affinity (Ki = 5 nM), comparable to losartan, and all compounds displayed preferential binding for AT₁ over AT₂ receptors. Full article

(This article belongs to the Special Issue Advances in the Synthesis of Heterocyclic Compounds and Their Applications, 2nd Edition)

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19 pages, 2805 KB

Open AccessArticle

Classification of Traditional Handmade Papers from China, Japan, and Korea Using NIR Hyperspectral Imaging

by Yong Ju Lee, Seong Bin Park, Seo Young Won, Soon Wan Kweon, Tai-Ju Lee and Hyoung Jin Kim

Molecules 2026, 31(11), 1970; https://doi.org/10.3390/molecules31111970 (registering DOI) - 5 Jun 2026

Abstract

Traditional handmade papers from China, Japan, and Korea, including Xuan paper, Washi, and Hanji, are difficult to distinguish visually because they share cellulose-rich compositions and similar appearances. This study applied near-infrared hyperspectral imaging (NIR-HSI) and machine-learning classifiers to identify selected traditional handmade papers [...] Read more.

Traditional handmade papers from China, Japan, and Korea, including Xuan paper, Washi, and Hanji, are difficult to distinguish visually because they share cellulose-rich compositions and similar appearances. This study applied near-infrared hyperspectral imaging (NIR-HSI) and machine-learning classifiers to identify selected traditional handmade papers by country and product type. Spectra in the 1250–1700 nm region were analyzed using k-nearest neighbors, support vector machines, and artificial neural networks. The models achieved high classification performance, with F1-scores of up to 1.000, and Y-scrambling confirmed that the results were not attributable to random class assignment. SHAP analysis identified important wavelength regions near 1256, 1360, 1404, 1449, 1537, 1576, 1635, and 1685 nm, which were associated with C–H, O–H, phenolic, hydrogen-bonded polysaccharide, and lignin-related vibrations. These bands varied among paper groups and provided chemically meaningful information for classification, while SAM visualization revealed pixel-level spectral similarity. These results show that NIR-HSI provides a compact, nondestructive, and interpretable approach for classifying selected East Asian handmade papers. Full article

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15 pages, 1595 KB

Open AccessArticle

Integrating Single-Cell Profiling with Generative AI for De Novo Design of MMP9 Protein Binders in Diffuse Large B-Cell Lymphoma

by Ziyang Miao, Siyi Zhu, Liwei Qin, Dawei Ma, Mingyang Lai, Pingping Xu, Yaping Jin, Huimin Cai, Shuai Zhao and Yang Wang

Molecules 2026, 31(11), 1969; https://doi.org/10.3390/molecules31111969 (registering DOI) - 5 Jun 2026

Abstract

To clarify the cellular origin of matrix metalloproteinase-9 (MMP9) and explore targeted research, we utilized single-cell RNA sequencing analysis, which revealed that MMP9 is predominantly enriched in specific macrophages within the activated B-cell-like (ABC) subtype. Guided by this target information, we applied a [...] Read more.

To clarify the cellular origin of matrix metalloproteinase-9 (MMP9) and explore targeted research, we utilized single-cell RNA sequencing analysis, which revealed that MMP9 is predominantly enriched in specific macrophages within the activated B-cell-like (ABC) subtype. Guided by this target information, we applied a generative AI pipeline incorporating RFdiffusion, ProteinMPNN, and AlphaFold to de novo design protein binders targeting the hemopexin (PEX) domain of MMP9. ELISA experiments confirmed the in vitro binding capability of these designs; among them, MMP9-30 displayed the strongest binding, with an apparent EC50 of approximately 1.1 μM, followed by MMP9-34, while MMP9-97 showed the weakest interaction. This study successfully integrates single-cell sequencing with AI-assisted protein design, providing a preliminary exploratory framework for subsequent MMP9-targeted research and protein binder development. Full article

(This article belongs to the Special Issue Harnessing Peptides and Peptidomimetics in Modern Drug Discovery)

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35 pages, 2735 KB

Open AccessReview

Research Progress of Composite Films in Postharvest Preservation of Fruits and Vegetables

by Yiru Zhu, Danni Li, Junzhe Qu, Hongliang Zhu and Liqun Ma

Molecules 2026, 31(11), 1968; https://doi.org/10.3390/molecules31111968 (registering DOI) - 5 Jun 2026

Abstract

Fruits and vegetables are vulnerable to enhanced respiratory metabolism, water loss, enzymatic browning, and microbial invasion during postharvest storage and transportation, leading to spoilage and reduced shelf life. Traditional preservation methods, such as physical, chemical, and single-component film technologies, offer limited benefits due [...] Read more.

Fruits and vegetables are vulnerable to enhanced respiratory metabolism, water loss, enzymatic browning, and microbial invasion during postharvest storage and transportation, leading to spoilage and reduced shelf life. Traditional preservation methods, such as physical, chemical, and single-component film technologies, offer limited benefits due to their single function and instability. Composite films, however, show great promise in postharvest preservation by integrating the strengths of different substrates and active components. This review discusses the research progress of composite films in preserving fruits and vegetables, covering their definition, classification, and key performance characteristics. It also examines the functional roles of substrates like polysaccharides, proteins, and lipids, and explores the mechanisms of composite films, including gas regulation, metabolic inhibition, water retention, antimicrobial effects, antioxidant activity, and browning delay. Additionally, it compares the applications of composite films in whole and fresh-cut fruits and vegetables. Current research highlights the shift from general applications to targeted designs based on the unique deterioration mechanisms of different produce. Future studies should focus on optimizing the matching between product characteristics and film design, advancing composite films towards safer, more stable, and practical applications. Full article

(This article belongs to the Special Issue Molecular Design and Functional Materials for Food Packaging Applications)

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13 pages, 2527 KB

Open AccessArticle

Thermal Curing-Enhanced Circularly Polarized Phosphorescence

by Shouchang Jiao, Rui Du, Jingcheng Wang and Hanlin Ou

Molecules 2026, 31(11), 1967; https://doi.org/10.3390/molecules31111967 (registering DOI) - 5 Jun 2026

Abstract

Developing circularly polarized phosphorescence (CPP) materials integrating long-afterglow room-temperature phosphorescence (RTP) and chiral optical properties is highly attractive but challenging. Herein, we report a facile and efficient strategy to achieve enhanced CPP by doping chiral naphthyl phosphoric acid derivatives (BNP-CZ, BNP-DPA, BNP-TPA) into [...] Read more.

Developing circularly polarized phosphorescence (CPP) materials integrating long-afterglow room-temperature phosphorescence (RTP) and chiral optical properties is highly attractive but challenging. Herein, we report a facile and efficient strategy to achieve enhanced CPP by doping chiral naphthyl phosphoric acid derivatives (BNP-CZ, BNP-DPA, BNP-TPA) into a thermally cured Bisphenol A Epoxy Resin (DGEBA) matrix crosslinked with 1,8-diaminooctane (DAO). The rigid crosslinked network effectively suppresses nonradiative transitions and stabilizes triplet excitons, affording a long phosphorescence lifetime of up to 973 ms and a high photoluminescence quantum yield of 26.55%. Significantly, the BNP-CZ@DAO exhibits remarkably boosted CPP signals and realizes the switch from circularly polarized fluorescence (CPF) in solution to CPP in the thermally cured resin film. Benefiting from the long afterglow and chiral optical properties, these polymers are successfully applied in multi-dimensional anticounterfeiting with high security. This work provides a universal and scalable approach for developing high-performance CPP materials. Full article

(This article belongs to the Special Issue 30th Anniversary of Molecules: Recent Advances in Photochemistry)

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10 pages, 4185 KB

Open AccessArticle

Eco-Friendly Low-Cost Design of Superhydrophobic Cu Mesh for Efficient Oil–Water Separation

by Meizi Tian, Hong Zhao, Yanyan Liu, Ge Liu and Xiaogang Guo

Molecules 2026, 31(11), 1966; https://doi.org/10.3390/molecules31111966 (registering DOI) - 5 Jun 2026

Abstract

Promising network materials with controllable porosity and tunable structures have demonstrated numerous advantages in oil–water separation applications. However, existing preparation methods generally have problems such as complex processes and adverse environmental impacts. Therefore, inspired by lotus leaves and rose petals, we have successfully [...] Read more.

Promising network materials with controllable porosity and tunable structures have demonstrated numerous advantages in oil–water separation applications. However, existing preparation methods generally have problems such as complex processes and adverse environmental impacts. Therefore, inspired by lotus leaves and rose petals, we have successfully designed an efficient oil–water separator based on copper meshes using in situ chemical etching, environmentally friendly fatty acid modification, and mild microwave curing treatment. Characterization results from FESEM, EDX, and XRD demonstrate that the product has high purity and a relatively uniform structure. In addition, this efficient oil–water separator has low surface energy, high hydrophobicity, and excellent oil–water separation efficiency (>98%). Moreover, after aging tests, the product has excellent structural stability and repeatable recyclability. Therefore, this research provides a convenient, cost-effective, and environmentally friendly approach for designing feasible superhydrophobic metal mesh-based devices, highlighting their wide application potential in treating industrial oily wastewater. Full article

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19 pages, 2876 KB

Open AccessArticle

Lipid Composition Drives Mutant Huntingtin Dimerization and Membrane Association: Insights from Computational Simulations

by Catalin Nicoara, Emanuele Criscuolo, Angela De Cristofaro, Filomena Fezza and Mauro Maccarrone

Molecules 2026, 31(11), 1965; https://doi.org/10.3390/molecules31111965 (registering DOI) - 5 Jun 2026

Abstract

Huntington’s disease (HD) is a neurodegenerative disorder caused by the expansion of the CAG trinucleotide in the exon 1 of the huntingtin gmodellerene. This abnormal expansion produces a mutant huntingtin (mHTT) protein with extended polyglutamine (polyQ) tracts. Although the molecular mechanisms underlying HD [...] Read more.

Huntington’s disease (HD) is a neurodegenerative disorder caused by the expansion of the CAG trinucleotide in the exon 1 of the huntingtin gmodellerene. This abnormal expansion produces a mutant huntingtin (mHTT) protein with extended polyglutamine (polyQ) tracts. Although the molecular mechanisms underlying HD onset and progression remain poorly understood, aberrant folding, aggregation, and membrane interactions of mHTT are considered central to disease pathogenesis. In this study, we used molecular dynamics (MD) simulations to investigate the structural properties, dimerization propensity, and membrane lipid interaction of mHTT carrying 70 polyQ repeats (mHTT-Q70). Our analyses revealed that mHTT-Q70 retains partially structured α-helical conformations with increased flexibility within the polyQ domain, thus being predisposed to misfolding. Coarse-grained MD simulations further revealed a strong tendency of mHTT-Q70 to dimerize, indicating that early oligomerization may represent a critical step in protein aggregation. Interestingly, we show that membrane cholesterol content dose-dependently promotes dimeric mHTT-Q70—but not monomeric mHTT-Q70—association with neuronal membrane models, which was observed for 70% of simulation time at 40% cholesterol content. Such a cholesterol-dependent membrane binding of dimeric mHTT-Q70 suggests that membrane lipid composition may represent a critical checkpoint in the early stages of mHTT-Q70 aggregation, and of cytotoxicity thereof. Moreover, distinct neuronal membrane lipids like phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine differently contributed to mHTT-Q70 binding, highlighting the complexity of such a lipid-dependent modulation. Taken together, these findings underscore the dynamic interplay between polyQ-driven misfolding, dimerization, and membrane lipids in HD pathogenesis, suggesting that modulation of membrane composition, and in particular of cholesterol levels, may be a novel action point to design therapeutic drugs for HD. Full article

(This article belongs to the Special Issue Molecular Conformational Diversity)

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13 pages, 730 KB

Open AccessArticle

On the Calculations of Electron Impact Ionization Cross-Sections for Selected Nucleosides and Deoxyribose Molecules

by Paweł Możejko

Molecules 2026, 31(11), 1964; https://doi.org/10.3390/molecules31111964 (registering DOI) - 5 Jun 2026

Abstract

Total cross-sections for the single electron impact ionization of deoxyribose (C₅H₁₀O₄), Uridine (C₉H₁₂N₂O₆), Thymidine (C₁₀H₁₄N₂O₅), Cytidine (C₉H₁₃N [...] Read more.

Total cross-sections for the single electron impact ionization of deoxyribose (C₅H₁₀O₄), Uridine (C₉H₁₂N₂O₆), Thymidine (C₁₀H₁₄N₂O₅), Cytidine (C₉H₁₃N₃O₅), Adenosine (C₁₀H₁₃N₄O₄), and Guanosine (C₁₀H₁₃N₅O₅) have been calculated using the binary-encounter-Bethe model from the first ionization threshold up to 4 keV. Electronic structure calculations of the studied targets have been performed at the Hartree–Fock (H-F) level using quantum chemical methods, including the outer valence Green function (OVGF) method, in order to obtain all the necessary physical input parameters for the BEB method. The possibility and feasibility of estimating the ionization cross-sections of larger DNA building blocks, such as nucleosides, based on the sum of the ionization cross-sections of DNA bases and simple sugar analogs, such as

α

-tetrahydrofurfuryl alcohol or deoxyribose, are also discussed. Full article

(This article belongs to the Section Computational and Theoretical Chemistry)

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