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35 pages, 1367 KB  
Review
Plant-Derived Bioactive Compounds in Agricultural Waste Anaerobic Digestion: Mechanisms of Inhibition, Process Stability and Methane Production
by Anna Rygało-Galewska and Kinga Borek
Agriculture 2026, 16(15), 1676; https://doi.org/10.3390/agriculture16151676 - 3 Aug 2026
Abstract
Anaerobic digestion (AD) plays a key role in the circular bioeconomy by converting organic waste into renewable energy and facilitating the sustainable utilisation of waste materials. Agricultural and agro-industrial by-products are increasingly recognised as valuable AD feedstocks due to their widespread availability and [...] Read more.
Anaerobic digestion (AD) plays a key role in the circular bioeconomy by converting organic waste into renewable energy and facilitating the sustainable utilisation of waste materials. Agricultural and agro-industrial by-products are increasingly recognised as valuable AD feedstocks due to their widespread availability and significant bioenergy potential. However, many of these substrates contain plant-derived bioactive compounds, such as polyphenols, tannins, flavonoids and terpenes, which can influence microbial communities and process performance. Depending on their concentration and chemical characteristics, these compounds may inhibit microbial activity, impair process stability, and ultimately decrease methane production. This review critically synthesises current knowledge on the occurrence, bioavailability and biological activity of plant-derived bioactive compounds in agricultural feedstocks used for anaerobic digestion, with particular emphasis on their implications for process performance and reactor stability. The principal mechanisms through which phytochemicals influence anaerobic digestion include enzyme inhibition, membrane disruption, interference with syntrophic interactions and trace metal chelation. The available evidence demonstrates a pronounced dose-dependent response, whereby low concentrations may exert neutral or selective modulatory effects. In contrast, elevated concentrations disrupt microbial activity, leading to volatile fatty acid accumulation, prolonged lag phases and reduced methane production. Current mitigation strategies include substrate pretreatment, co-digestion, microbial adaptation, adsorbent-assisted detoxification and the use of DIET-promoting materials. An integrated evidence matrix is proposed to link phytochemical composition with reactor configuration, operational parameters and mitigation strategies, thereby providing a practical framework for feedstock-specific process optimisation. Overall, the available evidence demonstrates that reliable evaluation of agricultural feedstocks should extend beyond conventional biochemical methane potential assessment to incorporate phytochemical composition, microbial functional responses and key operational parameters. Such an integrated approach can improve the prediction of methane recovery and support evidence-based optimisation of anaerobic digestion within circular bioeconomy systems. Full article
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24 pages, 2069 KB  
Article
Biological Evaluation, Molecular Docking, and in Ovo Hatchability Assessment of Selected Mannich-Type 1,2,4-Triazol-5-one Derivatives
by Songül Ulufer Bulut, Özlem Durna, Songül Boy, Fevzi Aytemiz, Gül Özdemir Toraman, Önder Albayrak, Murat Beytur, Ahmet Harmankaya, Haydar Yüksek and Gültekin Yildiz
Int. J. Mol. Sci. 2026, 27(15), 6948; https://doi.org/10.3390/ijms27156948 - 2 Aug 2026
Abstract
1,2,4-Triazole derivatives are widely investigated as bioactive heterocyclic compounds with diverse biological properties; however, their potential effects on avian embryonic development remain insufficiently characterized. This study aimed to synthesize selected Mannich-type 1,2,4-triazol-5-one derivatives and evaluate their in vitro biological activities, predicted enzyme interactions, [...] Read more.
1,2,4-Triazole derivatives are widely investigated as bioactive heterocyclic compounds with diverse biological properties; however, their potential effects on avian embryonic development remain insufficiently characterized. This study aimed to synthesize selected Mannich-type 1,2,4-triazol-5-one derivatives and evaluate their in vitro biological activities, predicted enzyme interactions, and in ovo hatchability outcomes in broiler embryos. Three derivatives (3a3c) were synthesized and structurally characterized using Fourier-transform infrared (FT-IR), proton nuclear magnetic resonance (1H-NMR), and carbon-13 nuclear magnetic resonance (13C-NMR) spectroscopy. Their reducing capacity, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity, metal-chelating capacity, and antimicrobial activity were evaluated. Molecular docking analyses were performed against carbonic anhydrase II and catalase, using acetazolamide and 3-amino-1,2,4-triazole as reference inhibitors, respectively. For the in ovo assessment, fertilized Ross 308 eggs were allocated to non-injected control, vehicle control, and compound-treated groups. Compounds 3a, 3b, and 3c were administered on incubation day 17 at 20, 10, and 5 mg/egg, respectively, as literature-supported, compound-specific exploratory exposure levels. The compounds exhibited weak reducing capacity, negligible DPPH radical-scavenging activity, pronounced metal-chelating capacity, and selective antimicrobial activity against several bacterial strains, whereas no inhibition was observed against Escherichia coli. Docking analysis predicted favorable interactions with both enzyme targets, with compound 3c showing the most favorable binding energies. Baseline egg weights were comparable among groups, indicating that initial egg weight was unlikely to influence hatchability outcomes. Complete hatch failure occurred in all compound-treated groups, whereas hatchability was observed in the control groups. These findings suggest that the tested derivatives may adversely affect embryonic development under the applied in ovo conditions. Their pronounced metal-chelating capacity, together with the predicted interactions with carbonic anhydrase II and catalase, provides a plausible mechanistic framework for interpreting the observed embryonic outcomes. The molecular docking results complement the experimental findings and provide supportive in silico evidence for these potential interactions. These findings contribute to the limited literature on the in ovo evaluation of synthetic Mannich-type 1,2,4-triazol-5-one derivatives and provide preliminary evidence regarding their embryotoxic potential. Further dose-dependent, mechanistic, histopathological, and enzyme-based studies are required to clarify the biological basis of the observed effects and to guide future evaluation of these compounds in in ovo, biomedical, and veterinary applications. Full article
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14 pages, 2709 KB  
Communication
Time-Dependent Modulation of Metabolite Profile and Antioxidant Capacity of Hamamelidis Cortex Extract During Kombucha Fermentation
by Wiktoria Pacuła, Jan Sawicki, Magdalena Wójciak and Ireneusz Sowa
Appl. Sci. 2026, 16(15), 7657; https://doi.org/10.3390/app16157657 - 2 Aug 2026
Abstract
Fermentation is increasingly used to improve the functional properties of plant-derived cosmetic ingredients. This study evaluated the effect of kombucha fermentation on the phytochemical composition and antioxidant activity of Hamamelidis cortex extract obtained by accelerated solvent extraction (ASE). Changes occurring during 15 days [...] Read more.
Fermentation is increasingly used to improve the functional properties of plant-derived cosmetic ingredients. This study evaluated the effect of kombucha fermentation on the phytochemical composition and antioxidant activity of Hamamelidis cortex extract obtained by accelerated solvent extraction (ASE). Changes occurring during 15 days of fermentation with a symbiotic culture of bacteria and yeasts (SCOBY) were monitored by UHPLC–DAD–ESI–MS, while antioxidant activity was assessed using ABTS, DPPH, and metal-chelating assays. The extract was rich in galloylated phenolics, with hamamelitannin as the dominant constituent. Fermentation increased the levels of hamamelitannin (456.4–675.7 µg/mL), gallic acid, galloyl-hexoses, catechin, and protocatechuic acid, whereas high-molecular-weight gallotannins declined. These compositional changes were accompanied by a decrease in pH from 4.4 to approximately 3.0 and by enhanced antioxidant properties. ABTS and DPPH radical scavenging capacity increased, while Fe2+ and Cu2+ chelating activities reached 69.5% and 85.9%, respectively. Correlation analysis indicated that galloylated phenolics were closely associated with metal-chelating activity. Overall, kombucha fermentation enhanced the antioxidant potential of Hamamelidis cortex extract and improved its functional properties, supporting its application as a multifunctional cosmetic ingredient for protecting the skin against oxidative stress. Full article
(This article belongs to the Special Issue Development of Innovative Cosmetics—2nd Edition)
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24 pages, 6751 KB  
Article
Ionomic and Transcriptomic Reprogramming Reveal Contrasting Iron Deficiency and Excess Responses in Potato (Solanum tuberosum L.)
by Xiangying Ma, Yongzhen Ma, Shenglong Yang, Wang Su, Miaomiao He, Guonian Pu, Guangji Ye and Jian Wang
Horticulturae 2026, 12(8), 945; https://doi.org/10.3390/horticulturae12080945 - 1 Aug 2026
Viewed by 50
Abstract
Iron (Fe) is an essential micronutrient for plant growth, serving as a cofactor in chlorophyll synthesis, photosynthetic electron transport, and redox reactions. Both Fe deficiency and excess disrupt mineral nutrient homeostasis, but the ionomic and transcriptomic mechanisms underlying genotype-specific responses in potato remain [...] Read more.
Iron (Fe) is an essential micronutrient for plant growth, serving as a cofactor in chlorophyll synthesis, photosynthetic electron transport, and redox reactions. Both Fe deficiency and excess disrupt mineral nutrient homeostasis, but the ionomic and transcriptomic mechanisms underlying genotype-specific responses in potato remain elusive. We profiled the ionome and transcriptome of two potato genotypes, 05P and CI5, grown under Fe-deficient, Fe-sufficient and Fe-excess conditions represented by 1, 40.4 and 120 mg L−1 FeNaEDTA, respectively. Ionomic analysis detected significant alterations in Fe, Mn, Zn, Ca, Mg, and Cu concentrations across roots, stems, and leaves, with the direction and magnitude of change varying by organ and genotype. Under Fe deficiency, CI5 showed steeper declines in root and stem Fe than 05P, while 05P retained higher leaf Fe, reflecting genotype-dependent patterns of shoot Fe distribution. Fe excess caused Fe accumulation in both genotypes, but coincided with Mn depletion in shoots, raising Fe/Mn ratios, consistent with potential antagonistic Fe–Mn interactions at the transport level. This pattern is consistent with potential antagonistic Fe–Mn interactions, although alternative mechanisms such as Mn uptake inhibition or dilution effects cannot be ruled out without direct experimental evidence. Transcriptome analysis showed organ-biased responses: Fe deficiency upregulated more genes in stems, whereas Fe excess triggered stronger transcriptional shifts in roots. No KEGG pathways remained significant after false discovery rate (FDR) correction, suggesting that genotype-dependent Fe-responsive divergence was not concentrated in a limited number of canonical KEGG pathways under the present analytical framework. Joint analysis of ionomic and transcriptomic data highlighted ferric-chelate reductase oxidase (FRO) and zinc-regulated transporter/iron-regulated transporter-like protein (IRT/ZIP) family members as genes associated with Fe reduction, divalent metal uptake, and Fe–Mn balance based on differential expression and orthology with functionally characterized Arabidopsis homologs. Comparative genomics showed that FRO and ZIP families have expanded in potato, with conserved domain architectures but divergent gene structures and promoter architectures, consistent with potential functional diversification related to metal transport. In conclusion, under Fe deficiency, genotype-dependent transcriptional divergence was most pronounced in stems, whereas under Fe excess it was more evident in roots, jointly maintaining systemic Fe–Mn homeostasis in potato. Full article
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20 pages, 9707 KB  
Article
Integrated Proteomic and Characterization Analyses Revealed the Different Colors of Edible Bird’s Nest
by Si Yang, Bu-Tao Yu, Nan Qian, Guan-Dong Fang, Jing Yao, Dong-Liang Wang and Xiang-Rong Cheng
Foods 2026, 15(15), 2712; https://doi.org/10.3390/foods15152712 - 1 Aug 2026
Viewed by 62
Abstract
Edible bird’s nest (EBN) is considered to moisten the lung and nourish yin in China. EBN from different geographical sources vary in morphology, material composition and commercial value. In this study, EBN samples with four different colors were collected, and their protein compositions [...] Read more.
Edible bird’s nest (EBN) is considered to moisten the lung and nourish yin in China. EBN from different geographical sources vary in morphology, material composition and commercial value. In this study, EBN samples with four different colors were collected, and their protein compositions were analyzed by proteomics technology. Combined with characterization analysis, the physicochemical properties and material composition were analyzed, including physical morphology, protein composition, and metal element composition. Proteomic analysis initially identified 73 differential peptide sequences, of which 59 showed significant abundance differences (p < 0.05). After removing redundant peptide assignments, these sequences corresponded to 51 non-redundant proteins exhibiting significant abundance changes among the four EBN color groups. Among them, the beige edible bird’s nest (BEBN) contained a large number of amino acids with iron-chelating ability, which was consistent with its high Fe content. Gene Ontology (GO) analysis revealed that the functions of the differential proteins in EBN were mainly related to glycoprotein hydrolysis. In conclusion, this study elucidated different expressed proteins and their potential functions in EBN with various colors, which provided a basis for production standardization and processing advances in EBN industry. Full article
(This article belongs to the Section Foodomics)
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29 pages, 18097 KB  
Article
Ferroptosis Inducers Combined with Copper Ionophores Aggravate Lung Cancer-Related Fatigue via GSH Depletion and FKBP5-Associated Impairment of Nrf2/HO-1 Signaling
by Ming Chen, Ying Pang, Yi He, Yunan Ma and Lili Tang
Cells 2026, 15(15), 1394; https://doi.org/10.3390/cells15151394 - 31 Jul 2026
Viewed by 72
Abstract
Cancer-related fatigue (CRF) remains difficult to manage, and the impact of metal ion-regulated cell death on peripheral fatigue during anticancer therapy is unclear. Here, we investigated whether ferroptosis inducers (FINs) potentiate copper ionophore (CIN)-triggered cuproptosis in skeletal muscle and aggravate lung cancer-related fatigue [...] Read more.
Cancer-related fatigue (CRF) remains difficult to manage, and the impact of metal ion-regulated cell death on peripheral fatigue during anticancer therapy is unclear. Here, we investigated whether ferroptosis inducers (FINs) potentiate copper ionophore (CIN)-triggered cuproptosis in skeletal muscle and aggravate lung cancer-related fatigue (LCaRF), and evaluated redox-based interventions. LCaRF cellular models were established using C2C12 exposed to LLC/M109 tumor-conditioned supernatants and treated with FINs (sorafenib/erastin) plus CIN + CuCl2 (CIN–Cu + FINs). Cell viability, lipid peroxidation, DLAT aggregation (cuproptosis hallmark), copper/glutathione (GSH), mitochondrial function, and FKBP5/Nrf2–HO-1 signaling were assessed with pharmacologic and genetic modulation. An orthotopic lung cancer mouse model underwent wheel-running, tail suspension, and open-field testing with tetrathiomolybdate (TTM) or hydrogen as interventions. FINs sensitized C2C12 cells to CIN–Cu cytotoxicity and increased DLAT aggregation; copper chelation with TTM attenuated these effects. FINs depleted GSH and amplified mitochondrial dysfunction/ROS; exogenous GSH or hydrogen reduced DLAT aggregation and restored mitochondrial indices. FKBP5 was markedly upregulated by CIN–Cu + FINs and linked to suppressed antioxidant defense (Nrf2/HO-1). In vivo, CIN–Cu + FIN treatment exacerbated fatigue-like behaviors, while TTM or hydrogen partially improved performance. FIN–CIN combinations may aggravate skeletal muscle injury and fatigue-like phenotypes in LCaRF models by promoting cuproptosis via GSH depletion and FKBP5/Nrf2-HO-1 dysregulation. Full article
20 pages, 18842 KB  
Article
Fibrinogen Adsorption and Sponge-like Aggregate Formation on Titanium Modified by Electrochemically Deposited CaCO3
by Zubair Ahmed and Huiliang Cao
J. Funct. Biomater. 2026, 17(8), 366; https://doi.org/10.3390/jfb17080366 - 30 Jul 2026
Viewed by 162
Abstract
Fibrinogen adsorption governs biological responses to implantable medical devices; however, surface properties influence the overall functionality of the biomaterial, and guided fibrinogen adsorption remains limited. In the present work, CaCO3 was electrochemically deposited on commercial Ti at −1.6 V for 1 h, [...] Read more.
Fibrinogen adsorption governs biological responses to implantable medical devices; however, surface properties influence the overall functionality of the biomaterial, and guided fibrinogen adsorption remains limited. In the present work, CaCO3 was electrochemically deposited on commercial Ti at −1.6 V for 1 h, 2 h, and 3 h. Furthermore, the effects on fibrinogen adsorption were detailed by using dye-assisted scanning electron microscopy (d-SEM), X-ray photoelectron spectroscopy (XPS), and Fourier Transform Infrared Spectroscopy (ATR-FTIR). Longer deposition times produced thicker calcite layers with maximum surface coverage of 99.80 ± 0.40%, accompanied by progressively greater calcium-ion release, ranging from 3.5 mg·L−1·cm−2 (1 h) to 12.2 mg·L−1·cm−2 (3 h) over 240 min. The results show that electrochemically deposited calcite crystals for 3 h lead to the formation of sponge-like fibrinogen aggregates via calcium ion-mediated conformational activation, particularly by chelating with the histidine and carboxylate residues of the Bβ chain segment Gly-His-Arg-Pro (β15–β18). This structural reorganization was supported by XPS N 1s binding energy at 398.80 eV and a red shift in Amide I and Amide II bands in FTIR spectra. Overall, this study reveals that careful modification of surface chemistry can guide fibrinogen adsorption, which can be beneficial for advanced biomaterials to orchestrate tissue integration at the protein and cellular levels. Full article
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22 pages, 5261 KB  
Article
Synergic Effect of Fluconazole and Quinoline Derivatives Combination Against Cryptococcus spp., Mechanisms of Action and Toxicity
by Luana Candice Genz Bazana, Ânderson Ramos Carvalho, Rodrigo Foss da Silva, Solange Cristina Garcia, Marcelo Dutra Arbo, Mario Lettieri Teixeira and Alexandre Meneghello Fuentefria
Microorganisms 2026, 14(8), 1654; https://doi.org/10.3390/microorganisms14081654 - 29 Jul 2026
Viewed by 215
Abstract
Cryptococcosis is a severe fungal infection affecting immunocompromised individuals, with treatment limited to FLZ, AMB, and FC. This study investigated the antifungal potential of fluconazole (FLZ)-, amphotericin B (AMB)-, 8-hydroxyquinoline (8HQ)-, and clioquinol (CQ)-based combinations against Cryptococcus neoformans and C. gattii. Drug [...] Read more.
Cryptococcosis is a severe fungal infection affecting immunocompromised individuals, with treatment limited to FLZ, AMB, and FC. This study investigated the antifungal potential of fluconazole (FLZ)-, amphotericin B (AMB)-, 8-hydroxyquinoline (8HQ)-, and clioquinol (CQ)-based combinations against Cryptococcus neoformans and C. gattii. Drug interactions were assessed by checkerboard assay, followed by time–kill curves, irritability, toxicity, and virulence factors inhibition tests. The FLZ + AMB combination showed weak synergism, whereas FLZ combined with CQ or 8HQ exhibited strong synergistic effects (p < 0.001) at low concentrations (0.125–0.25 µg/mL), up to three times greater than those of FLZ + AMB. This effect persisted across other strains, including less FLZ-susceptible isolates. Moreover, FLZ + CQ inhibited melanin production in both species without causing significant irritability or toxicity in the tested models. These results indicate that combining drugs with distinct mechanisms of action can enhance antifungal efficacy while potentially reducing treatment doses. The FLZ + CQ/8HQ combinations represent promising candidates for future in vivo models for therapeutic evaluation. Full article
(This article belongs to the Special Issue Advances in Antimicrobial Treatment)
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27 pages, 3622 KB  
Article
Preparation of Deer Brain Peptide Chelated with Zinc and Its Effect on Improving Memory Impairment in Insomnia Mice Induced by Para-Chlorophenylalanine
by Jiapeng Song, Ran Ning, Yike Du, Junkoo Yi, Zhongmei He, Jia Zhou, Xuezhen Li and Weijia Chen
Nutrients 2026, 18(15), 2462; https://doi.org/10.3390/nu18152462 - 28 Jul 2026
Viewed by 275
Abstract
Background/Objectives: Chronic insomnia commonly induces progressive memory decline, severely compromising human daily life and work capability. At present, there are no safe long-term available agents that can concurrently relieve insomnia symptoms and rescue accompanying memory dysfunction. This study aimed to optimize the [...] Read more.
Background/Objectives: Chronic insomnia commonly induces progressive memory decline, severely compromising human daily life and work capability. At present, there are no safe long-term available agents that can concurrently relieve insomnia symptoms and rescue accompanying memory dysfunction. This study aimed to optimize the preparation of deer brain peptides (DBPP) and zinc-chelated DBPP (Zn-DBPP), and explore their protective effects and molecular mechanism against insomnia-caused memory impairment, hoping to develop novel functional candidates for related neurological disorders. Methods: Single-factor experiments combined with response surface methodology were used to optimize the synthesis process of DBPP and Zn-DBPP. A para-chlorophenylalanine-induced insomnia mouse model was established. The structural characteristics, amino acid composition, and antioxidant activity of the products were verified via multiple spectroscopic and biochemical assays. Pentobarbital sodium sleep test and Morris water maze test assessed behavioral changes. Hippocampal neuronal morphology and BDNF-TrkB pathway expression were detected by histological staining, immunofluorescence and Western blotting. Results: The optimized DBPP achieved a hydrolysis rate of 43.89%, and Zn-DBPP possessed a zinc content of 143.37 mg/g. Successful zinc chelation, rich amino acid components, and strong antioxidant capacity were confirmed in Zn-DBPP. In vivo results showed that Zn-DBPP elevated brain zinc levels, improved learning and memory deficits, and restored hippocampal neuronal damage in insomniac mice. Mechanically, Zn-DBPP alleviated memory impairment by upregulating the BDNF-TrkB signaling pathway. Conclusions: The optimized Zn-DBPP exhibits excellent neuroprotective effects against insomnia-induced memory dysfunction. This work provides a reliable theoretical basis for the application of Zn-DBPP as a promising functional food or drug candidate for intervening in insomnia and cognitive decline. Full article
(This article belongs to the Section Proteins and Amino Acids)
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18 pages, 16514 KB  
Article
Influence of Chelator Type on the Efficiency and Mechanisms of Electrokinetic Remediation of Copper- and Lead-Contaminated Loess
by Yunxiao Jin, Longping Luo, Shixu Zhang and Zheng Yuan
Toxics 2026, 14(8), 658; https://doi.org/10.3390/toxics14080658 - 26 Jul 2026
Viewed by 169
Abstract
With the continued advancement of industrialization and urbanization in northwestern China, heavy metal contamination of loess sites has become an increasingly serious environmental issue. Heavy metals such as copper (Cu) and lead (Pb) are toxic, persistent, and readily retained by the mineral-pore framework [...] Read more.
With the continued advancement of industrialization and urbanization in northwestern China, heavy metal contamination of loess sites has become an increasingly serious environmental issue. Heavy metals such as copper (Cu) and lead (Pb) are toxic, persistent, and readily retained by the mineral-pore framework of loess, which makes remediation difficult and threatens regional ecological security and human health. This study investigated electrokinetic (EK) remediation of artificially prepared loess co-contaminated with Cu and Pb using tartaric acid (TA), citric acid (CA), and disodium ethylenediaminetetraacetate (EDTA) as catholytes. Cu was generally removed more effectively than Pb because Pb was less adsorbed and immobilized more strongly. All three chelators enhanced metal desorption and migration through complexation, particularly in the cathode-side section. EDTA produced the greatest enhancement because it formed stable, negatively charged complexes with Cu and Pb over a broad pH range. Relative to the deionized-water control, EDTA increased the overall removal efficiencies of Cu and Pb to 55.4% and 27.2%, respectively, and promoted their transfer from the soil to the anolyte. These findings demonstrate that chelator-assisted EK treatment, particularly with EDTA, can effectively improve Cu and Pb removal from loess, while field application requires control of energy use, residual chelator, and post-treatment metal mobility. Full article
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32 pages, 1616 KB  
Review
From the Cosmos to the Cell: The Central Role of Iron in the Chemistry and Evolution of Life
by Paolo Arosio and Fadi Bou-Abdallah
Int. J. Mol. Sci. 2026, 27(15), 6651; https://doi.org/10.3390/ijms27156651 - 25 Jul 2026
Viewed by 271
Abstract
Iron, with the unique stability of its nucleus, occupies an unusual position among the elements: its abundance on Earth is not simply a geological accident but a direct consequence of nuclear reactions that happened inside stars billions of years ago. Formed at the [...] Read more.
Iron, with the unique stability of its nucleus, occupies an unusual position among the elements: its abundance on Earth is not simply a geological accident but a direct consequence of nuclear reactions that happened inside stars billions of years ago. Formed at the final stages of fusion in stars, iron spread through space by supernova explosions and became part of the material that formed Earth, eventually becoming the dominant component of the planet’s core. At the surface, iron’s redox chemistry shaped the early atmosphere and oceans, and its availability as a soluble ferrous ion in the anaerobic Archean ocean made it a natural cofactor for the first enzymatic reactions. That same redox flexibility and the ability of iron to shuttle between Fe2+ and Fe3+ across a wide range of electrochemical potentials explain why virtually every major metabolic pathway in biology depends on iron in one form or another. Yet iron is also dangerous: free and chelated iron can catalyze the production of toxic hydroxyl radicals through Fenton chemistry, the reactivity of which depends strongly on the nature of the chelating ligand, and every living system must balance its need for iron against the oxidative damage that uncontrolled iron causes. This tension between catalytic necessity and chemical toxicity has driven much of the regulatory complexity we observe in modern iron metabolism. In this review, we first outline iron’s journey from its formation in stars to its role in shaping Earth’s structure and the emergence of early iron-dependent biology. We then discuss in detail how fundamental physical and chemical factors continue to influence living systems. Full article
(This article belongs to the Collection Latest Review Papers in Endocrinology and Metabolism)
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29 pages, 9032 KB  
Article
Ni(II) Complexes with Mixed Ligands, Reduced N2O2 Schiff Bases and β-Diketones: Redox Modulation, ROS Generation and Antiproliferative Activity in Cancer Cells Associated with Caspase-3
by Erika Lorena Cedillo-Gutiérrez, Adrián Espinoza-Guillén, Luis Felipe Hernández-Ayala, Esther Reveles-Ayala, Marcos Flores-Álamo, Luis Antonio Ortiz-Frade, Carmen Mejía and Lena Ruiz-Azuara
Int. J. Mol. Sci. 2026, 27(15), 6601; https://doi.org/10.3390/ijms27156601 - 24 Jul 2026
Viewed by 280
Abstract
This study addresses the development of nickel(II) complexes with potential antiproliferative activity. Two novel hydrogenated Schiff base ligands (N2O2-type), L1 and L2, were synthesized using environmentally friendly routes within a green chemistry framework and fully characterized. These ligands [...] Read more.
This study addresses the development of nickel(II) complexes with potential antiproliferative activity. Two novel hydrogenated Schiff base ligands (N2O2-type), L1 and L2, were synthesized using environmentally friendly routes within a green chemistry framework and fully characterized. These ligands were coordinated to Ni(II) to obtain mixed octahedral complexes of general formulae [Ni(N2O2)(NO3)2] and [Ni(N2O2)(O–O)]NO3, where O–O denotes β-diketones (acetylacetonate and fluorinated analogs). Structural, spectroscopic, and electrochemical characterization, including cyclic voltammetry, was performed to evaluate the effect of ligand substitution on redox properties. Antiproliferative activity was assessed in HeLa cells. The results show that all complexes exhibit octahedral geometry, while [Ni(N2O2)(O–O)]NO3 complexes behave as 1:1 electrolytes, with redox potentials influenced by electron-withdrawing fluorinated substituents on the secondary ligand. Complexes containing fluorinated diketones and the methoxy-substituted L1 ligand displayed enhanced antiproliferative effects compared to non-fluorinated and unsubstituted analogues. Mechanistic studies suggest apoptosis induction associated with early caspase-3 activation, likely mediated by reactive oxygen species. Overall, ligand electronic effects play a key role in modulating redox behavior and biological activity in these nickel(II) complexes. Full article
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19 pages, 2147 KB  
Article
Palladium-103 as a Theranostic Auger Electron Emitter: From Cyclotron Production to Preclinical SPECT Evaluation in Murine and Canine Models
by Aicha Nour Laouameria, Domokos Máthé, Anikó Kubovje, Péter Vajdovich, Gyula Balka, Mátyás Hunyadi, Ralf K. Bergmann, Christer Halldin, László Forgách, Ildikó Horváth, Krisztián Szigeti, Roland Psáder, Jan Rijn Zeevaart, Lóránt Csige and Zoltán Szűcs
Pharmaceuticals 2026, 19(8), 1140; https://doi.org/10.3390/ph19081140 - 23 Jul 2026
Viewed by 226
Abstract
Background/Objectives: Palladium-103 (103Pd) is an Auger electron-emitting radionuclide with nanometer-scale penetration ranges that result in highly localized energy deposition, making it well suited for molecularly targeted radionuclide therapy. However, efficient production, separation, and in vivo evaluation workflows remain limited. This study [...] Read more.
Background/Objectives: Palladium-103 (103Pd) is an Auger electron-emitting radionuclide with nanometer-scale penetration ranges that result in highly localized energy deposition, making it well suited for molecularly targeted radionuclide therapy. However, efficient production, separation, and in vivo evaluation workflows remain limited. This study aimed to establish a scalable workflow for the production, separation, purification, radiolabeling, and preclinical assessment of 103Pd for theranostic applications. Methods: 103Pd was produced via the 103Rh(p,n)103Pd reaction. An upgraded dry-distillation radionuclide separation equipment (RSE) enabled high-efficiency separation from irradiated rhodium foils, while a cotton-assisted acid recovery process yielded purified 103Pd suitable for radiolabeling. Chelation with NOTA and DOTA-TATE was performed, and radiochemical purity was assessed using iTLC, SPE, and a C18 column. In vivo SPECT/CT imaging was conducted in NMRI Nu/Nu mice and in a canine model with spontaneous liver metastatic spread of insulinoma, injected with [103Pd]Pd-labeled compounds. Results: The upgraded RSE achieved separation efficiencies of 64–86% and overall recovery yields of 81–94%, outperforming conventional wet-chemistry methods. Radiolabeling produced stable complexes with >95% radiochemical purity. SPECT/CT imaging confirmed in vivo stability in mice. In the canine model, a slight reduction in tumor size and increased glucose levels were observed during 24 days post-systemic application of 520 MBq of 103Pd-DOTA-TATE radioactivity. Conclusions: This study establishes a complete and efficient radiochemical and preclinical pipeline for 103Pd, demonstrating its feasibility as a theranostic radionuclide. The combination of high-yield production, robust separation chemistry, and localized Auger-mediated energy deposition highlights 103Pd as a promising candidate for future targeted radionuclide therapy applications. Full article
(This article belongs to the Section Radiopharmaceutical Sciences)
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26 pages, 18163 KB  
Review
Food-Derived Zinc-Chelating Peptides: Coordination Chemistry, Intestinal Transport, and Nutritional Functionality
by Lanshi Tian, Shan Yang, Peng Li, Jinzi Yin, Jia Zhou and Zhongmei He
Nutrients 2026, 18(15), 2409; https://doi.org/10.3390/nu18152409 - 23 Jul 2026
Viewed by 257
Abstract
Food-derived zinc-chelating peptides (ZCPs) have emerged as promising nutritional carriers that enhance zinc bioavailability and exert diverse biological activities. Compared with conventional zinc supplements, peptide-mediated zinc delivery systems exhibit superior gastrointestinal stability, reduced mineral precipitation, and improved intestinal transport efficiency. The present study [...] Read more.
Food-derived zinc-chelating peptides (ZCPs) have emerged as promising nutritional carriers that enhance zinc bioavailability and exert diverse biological activities. Compared with conventional zinc supplements, peptide-mediated zinc delivery systems exhibit superior gastrointestinal stability, reduced mineral precipitation, and improved intestinal transport efficiency. The present study demonstrates that ZCPs regulate zinc homeostasis through multiple mechanisms, including coordination chemistry, transporter-mediated absorption, regulation of the epithelial barrier, and interactions with the intestinal microenvironment. Beyond facilitating zinc absorption, peptide–zinc complexes exhibit antioxidant, anti-inflammatory, immunomodulatory, metabolic regulatory, and gut-protective activities through the synergistic effects of coordinated zinc ions and peptide bioactivity. Advances in spectroscopic characterization, computational modeling, and systems nutrition approaches have further expanded current understanding of peptide–zinc coordination behavior and physiological functionality. Nevertheless, current studies remain limited by insufficient clinical validation and an incomplete understanding of intestinal transport kinetics and controlled zinc release mechanisms. Overall, food-derived ZCPs demonstrate considerable potential for precision nutrition interventions and the development of next-generation functional zinc delivery systems. Full article
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Article
Schiff-Base-Engineered Fibrous Mesoporous Silica (KCC-1) as an Efficient Sorbent for Dispersive Solid-Phase Extraction of Trace Ni(II) and Cd(II) from Water
by Yassin T. H. Mehdar, Awadh O. Alsuhaimi, Sultan K. Alharbi, Manal A. Almalki, Khaled M. AlMohaimadi, Bandar R. Alsehli, Khalid Althumayri, Bader M. Altayeb and Belal H. M. Hussein
Nanomaterials 2026, 16(15), 903; https://doi.org/10.3390/nano16150903 - 23 Jul 2026
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Abstract
The development of reusable nanomaterials for the extraction of trace-metals from complex matrices remains challenging because strong metal-chelating functionalities often hinder desorption and regeneration, whereas weaker binding sites compromise selectivity and enrichment efficiency. This limitation has been addressed by designing a ligand-engineered fibrous [...] Read more.
The development of reusable nanomaterials for the extraction of trace-metals from complex matrices remains challenging because strong metal-chelating functionalities often hinder desorption and regeneration, whereas weaker binding sites compromise selectivity and enrichment efficiency. This limitation has been addressed by designing a ligand-engineered fibrous mesoporous silica nanomaterial (Van-KCC-1) via the integration of the unique structural features of KCC-1 with an o-vanillin-derived Schiff-base chelator. The material was synthesized throughout the chemical grafting of 3-aminopropyltriethoxysilane (APTES) onto fibrous mesoporous silica KCC-1, followed by condensation with 3-methoxy-2-hydroxybenzaldehyde (o-vanillin). The successfulness of functionalization and Schiff-base formation were confirmed by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), Thermogravimetric analysis (TGA), and X-ray photoelectron spectroscopy (XPS). The radially oriented fibrous channels of KCC-1 provide a highly accessible surface that remains available for interaction with the targeted ions even after chemical modification. This architecture facilitates rapid mass transfer and efficient utilization of binding sites, while the incorporated Schiff-base ligand introduces imine, phenolic, and methoxy donor groups capable of selectively and reversibly coordinating Ni(II) and Cd(II). The resulting balance between adsorption strength and desorption efficiency enables both effective metal capture and sorbent reusability. More importantly, the study demonstrates how KCC-1 can serve as a versatile nanosilica scaffold for the incorporation of tailored chelating ligands without sacrificing structural accessibility. The functionalized nanomaterial was evaluated as a dispersive solid-phase extraction (DSPE) sorbent coupled with inductively coupled plasma optical emission spectrometry (ICP-OES). Under optimized conditions, linear ranges of 0.035–50 μg L−1 for Ni(II) and 0.058–50 μg L−1 for Cd(II) were obtained, with limits of detection of 0.011 and 0.019 μg L−1, respectively. The method exhibited excellent precision (relative standard deviation ≤ 3.6%) and recoveries of 92.00–98.83% in certified reference materaisl (NIST CRM 1643d), mineral water, tap water and synthetic wastewater. In addition, the nanochelator has retained more than 87% of its initial sorption efficiency after six adsorption–desorption cycles and showed minimal interference from common coexisting ions. These findings establish Van-KCC-1 as an efficient, selective, and reusable DSPE sorbent in the determination of trace-metals while highlighting the broader potential of fibrous mesoporous silica KCC-1 as a platform for the rational design of next-generation chelated nanomaterials. Full article
(This article belongs to the Special Issue Advanced Nanomaterials for Water Remediation (3rd Edition))
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