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The chemical constituents and neuroprotective potential of Schizophyllum commune remain insufficiently characterized. Therefore, we isolated and identified five secondary metabolites (A–E) from S. commune, and investigated their neuroprotective activities and underlying mechanisms. Compound C showed the most significant protective effect against H₂O₂-induced cytotoxicity in C17.2 neural stem cells. Spectroscopy was used to structurally characterize the isolated compounds. Using RNA sequencing (RNA-seq), compound C was found to significantly modulate genes associated with G protein-coupled receptor (GPCR)-related signaling pathways and neuroactive ligand–receptor interactions. Differentially expressed genes, including Adora2a, S1pr1, Adm, Tbxa2r, and Grin3b, were validated using quantitative real-time PCR. They are associated with GPCR-related signaling and neurotransmission pathways, consistent with the RNA-seq data. As indicated by the functional enrichment analysis, compound C may regulate neuronal stress responses through GPCR-associated signaling networks. In the Western blot, compound C markedly attenuated H₂O₂-induced protein kinase A (PKA) C phosphorylation without altering total PKA C expression, suggesting that modulation of the cAMP/PKA signaling pathway may contribute to the neuroprotective effects of compound C. Collectively, compound C may exert neuroprotective effects against oxidative stress-induced neuronal injury, potentially through the modulation of GPCR-mediated PKA signaling. S. commune is a promising natural bioactive compound source for further development in neuroprotective research. Full article

Encapsulation for wireless dairy-cattle implants must resist acidic, moisture-rich gastrointestinal conditions while remaining transparent to radio-frequency (RF) signals. This study evaluated vulcanized natural rubber (NR) latex as an intraruminal encapsulant, examining how total solid content (TSC; 30, 40, 50 wt%), stirring duration (24–72 h), and TiO₂ loading affect tensile and tear strength, acidic swelling, dip-coating thickness, and received signal strength indicator (RSSI) at 433 MHz. Multilayer dip-coating produced films 0.25–0.38 mm thick. Tensile strength rose with TSC and stirring (26.6 → 32.2 MPa), whereas tear strength peaked at 40 wt% (31.97 N mm⁻¹). Adding 5 phr (parts per hundred rubber) TiO₂ cut pH-4 swelling ~four-fold (21.1 → 5.25%) with a negligible RSSI penalty, and 3–5 coating layers kept the link well above the −120 dBm sensitivity floor over 5–55 m. The optimum—40 wt% TSC, 72 h stirring, 5 phr TiO₂—best balanced mechanical integrity, swelling resistance, thickness, and wireless performance. Vulcanized NR is therefore a promising bio-based encapsulant under simulated conditions; dielectric characterization, long-term aging, and in vivo validation remain future work. Full article

In this study, nine barium sulfate (BaSO₄)-supported heterogeneous catalysts (C1–C9) were synthesized via three modification strategies: stearic acid coating (C1–C3), physical doping (C4, C6, and C8), and sol-gel processing with calcination (C5, C7, and C9). Their comprehensive characterization revealed that sol-gel-synthesized C7 exhibited the most favorable surface properties, including well-dispersed Al–O–Si species, tetrahedrally coordinated Al³⁺, and abundant Brønsted acid sites. Their catalytic performance was evaluated in the chlorination of toluene, fluorobenzene, bromobenzene, and iodobenzene, using hydrochloric acid (HCl) as the chlorine source and either hydrogen peroxide (H₂O₂) or ammonium persulfate ((NH₄)₂S₂O₈) as the oxidant. C7 achieved complete toluene conversion (100%) at 60 °C under optimized conditions and exhibited high conversions of fluorobenzene (55%), bromobenzene (76%), and iodobenzene (46%). Notably, ammonium persulfate enabled a unique in situ halogen exchange pathway, yielding chlorobenzene as the exclusive product from bromobenzene and iodobenzene. XRD and XPS analysis of crystalline by-products confirmed the formation of NH₄HSO₄, BaSO₄, and NH₄Cl, providing evidence for the persulfate-driven radical mechanism. Iodine detection in upper-layer crystals confirmed iodobenzene products, while the absence of chlorine signals in the upper layer confirmed separation of organic and inorganic species. The detection of barium sulfate peaks confirms that the catalyst support retains its structural integrity under harsh reaction conditions, demonstrating chemical stability and reusability potential. Collectively, these findings establish a clear structure–activity relationship and demonstrate that the synergy between modified BaSO₄ surfaces and persulfate-generated radicals provides an efficient, sustainable platform for aromatic chlorination, offering significant potential for pharmaceutical, agrochemical, and fine chemical manufacturing applications. Full article

Photocatalytic CO₂ reduction to CH₄ with H₂O is hindered by rapid charge recombination and sluggish multielectron/proton-coupled hydrogenation kinetics. Herein, we show that Mn doping induces charge-carrier redistribution within Co₃O₄, thereby enhancing CO₂ photoreduction to CH₄ under sacrificial-agent-free conditions. The optimized Mn5–Co₃O₄ achieves CH₄ and CO production rates of 16.9 and 9.8 μmol g⁻¹ h⁻¹, respectively, with its CH₄ production rate reaching 10.6 times that of pristine Co₃O₄. Mechanistic investigations indicate that Mn doping modulates carrier dynamics and surface-intermediate hydrogenation. Photoelectrochemical and photoluminescence measurements demonstrate that Mn incorporation promotes charge-carrier separation, with Mn5–Co₃O₄ exhibiting the most favorable separation efficiency, as reflected in an extended average photoluminescence lifetime of 23.17 ns compared with 9.95 ns for pristine Co₃O₄. In situ irradiated X-ray photoelectron spectroscopy shows shifts of the Mn and Co signals toward lower and higher binding energies, respectively, indicating electron enrichment at Mn sites and hole accumulation at Co sites. In situ Fourier-transform infrared spectroscopy further reveals enhanced bands tentatively assigned to *COOH, *CHO, and *CH₃O intermediates, supporting their progressive hydrogenation toward CH₄. These findings provide a mechanistic framework for coordinating charge redistribution with surface hydrogenation during multielectron/proton-coupled CO₂ conversion with H₂O. Full article

Glioblastoma (GBM) frequently recurs after temozolomide (TMZ) therapy and exhibits substantial redox plasticity. Our previous work showed that the effects of hydrogen peroxide (H₂O₂) vary with its level and between parental and TMZ-resistant GBM cells. Succinate dehydrogenase subunit D (SDHD), a membrane-anchoring component of mitochondrial complex II, is positioned at the interface of electron transport and redox homeostasis, but its regulation in GBM remains unclear. We therefore examined whether SDHD expression changes across distinct H₂O₂-responsive contexts involving aquaporins (AQPs) and AKT. TCGA transcriptomic analysis showed higher SDHD mRNA expression in WHO grade IV than in grade II/III gliomas, whereas paired primary/recurrent high-grade glioma samples showed heterogeneous SDHD changes at recurrence. TMZ reduced SDHD, and SDHD knockdown decreased intracellular reactive oxygen species. Combined redox perturbation reduced SDHD, whereas AKT inhibition restored SDHD expression. Under receptor-associated signaling conditions, EGFRvIII expression or CXCL12 stimulation increased measured H₂O₂ together with AQP3, AKT Ser473 phosphorylation, and SDHD. In TMZ-resistant cells, pharmacological perturbation of aquaporin-associated signaling decreased AQP9 together with AKT Ser473 phosphorylation and SDHD. An AQP3-targeting compound further reduced cell density when combined with TMZ. Together, these findings suggest that changes in SDHD expression are consistent with a compensatory redox response in GBM cells and that its regulation varies with the nature of H₂O₂-associated signaling during TMZ-related stress. Full article

Background: Plant flavonoids are candidate alternatives to ionophores for modulating rumen fermentation, yet the intact glycoside rutin (quercetin-3-O-rutinoside) has received little attention. The objective of this study was to determine whether rutin changes the in vitro ruminal fermentation of total mixed rations (TMR) differing in forage-to-concentrate ratio; monensin was included at a single dose as a reference additive rather than a direct comparator. Methods: In a 2 × 4 factorial batch-culture experiment, a roughage-based (60:40) and a concentrate-based (40:60) TMR were incubated for 24 h without additive (control) or with rutin at 2.5% or 5% of substrate dry matter or monensin at 30 ppm. Results: Rutin did not change the gas production kinetics, ruminal pH, the volatile fatty acid (VFA) profile, or the stoichiometrically estimated methane and carbon dioxide at either dose (p > 0.05), and no dose response was found. Substrate type likewise left the VFA profile and the estimated gases unchanged (p > 0.05). Ammonia nitrogen (NH₃-N) responded to the additive group (p = 0.027) and to the substrate × additive interaction (p = 0.022), but Tukey comparisons separated no individual means, so this response is preliminary. Conclusions: Neither rutin nor monensin markedly altered fermentation of these silage-, alfalfa- and cereal-based rations in the 24 h batch system; the substrate-dependent NH₃-N signal warrants confirmation, and direct methane measurement is required before any anti-methanogenic potential can be claimed. Full article

Traditional wound therapies continue to be predominantly exogenous and address extracellular causes of the pathology without addressing the impaired function of cellular pathways that are trapped in the state of constant inflammation. The present review explores a novel putative nutriepigenetic framework, discussing how the honey matrix could act as a proposed modulator of the altered epigenetic landscape in non-healing ulcers. Honey contains a complex mixture of bioactive agents (polyphenols, flavonoids, and plant-derived xenomiRs) that are hypothesized to interact with multiple chromatin control points simultaneously. We discuss models wherein honey-induced aquaporin-mediated H₂O₂ influx and intracellular calcium transients may correlate with SIRT1/SIRT6 modulation and CRM1-mediated nuclear export of Class IIa HDACs. This review evaluates whether such multi-target signaling could foster chromatin relaxation to support gene expression required for cell migration and tissue remodeling. Full article

Banana Fusarium wilt, caused by the soil-borne fungus Fusarium oxysporum f. sp. cubense (Foc), is a devastating disease and a major threat to global banana production. Here, we identified 24 genes predicted to encode heme-dependent peroxidase- or catalase–peroxidase-related proteins in Foc race 4 (Foc4), whereas nine genes encoding thiol-dependent peroxide-reducing proteins were catalogued separately. Phylogenetic, synteny, and Ka/Ks analyses indicated a conserved peroxidase repertoire under strong purifying selection, without substantial lineage-specific expansion. Motif, domain, gene-structure, and promoter analyses revealed subgroup-specific features and abundant putative stress- and hormone-responsive cis-regulatory motifs. Expression profiling during banana infection and H₂O₂ treatment showed distinct temporal and oxidative-stress responses. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses linked subsets of these genes to antioxidant activity, peroxide metabolism, peroxisomal functions, and stress signaling. A F. oxysporum f. sp. lycopersici ortholog-based interaction network combined with co-expression analysis prioritized five peroxidases potentially associated with pathogenicity-related expression programs. FoCP, selected separately based on its rapid H₂O₂ response and catalase–peroxidase annotation, enhanced oxidative-stress tolerance when heterologously expressed in yeast. Overall, Foc4 appears to adapt to oxidative stress through condition-specific regulation of a conserved peroxidase repertoire rather than gene-family expansion. The network-prioritized peroxidases provide candidates for further functional and pathogenicity studies. Full article

Although exposure to heavy metals such as cadmium and inorganic arsenic has declined in recent decades, they remain prevalent environmental contaminants in food, drinking water, and tobacco smoke. This study aimed to identify and compare molecular endpoints of arsenite and cadmium toxicity at the gene and protein expression levels, with a focus on metal homeostasis, the oxidative stress response and redox-regulated processes. Human bronchial epithelial cells (BEAS-2B) were used as an in vitro model. First, the appropriate exposure conditions were defined by assessing cytotoxicity and intracellular metal accumulation. The cells were then incubated with 1–10 µM NaAsO₂ or 1–5 µM CdCl₂ for 24 h, after which gene and protein expression were analyzed. When compared to arsenite, cadmium was a markedly stronger inducer of metallothionein (MT) expression, indicating distinct effects on metal homeostasis. Both metals induced a concentration-dependent upregulation of oxidative stress-related genes. Cadmium led to a stronger activation of NF-κB signaling, while arsenite decreased selenoprotein-associated gene expression and affected genes involved ferroptosis regulation. Differences in gene and protein expression patterns were also observed, suggesting that transcriptional responses do not necessarily translate into corresponding changes at the protein level after 24 h. These findings highlight shared and compound-specific mechanisms, as well as the importance of multi-level analyses. Full article

The simultaneous and accurate detection of multiple pesticide residues remains a critical challenge in electrochemical sensing. Herein, a strategy is proposed for the in situ growth of interconnected Zn₃(OH)₂V₂O₇·2H₂O (ZVO) nanosheets on carbon cloth (CC), forming ZVO/CC electrodes for the simultaneous detection of thiophanate-methyl and diuron. A negative-potential pre-reduction treatment is employed to regulate the interfacial electronic structure and activate sensing sites of ZVO/CC electrodes. During pre-reduction, partial V⁵⁺ is reduced to V⁴⁺, accompanied by the formation of oxygen vacancies, which reconstruct local electronic states and decrease charge-transfer resistance. Meanwhile, the chemically integrated Zn–O–V framework exhibits a performance synergy, resulting in significantly enhanced and well-distinguished electrochemical responses toward the target pesticides. The ZVO/CC electrode achieves linear detection ranges of 0.1–25 μM for thiophanate-methyl and 0.1–40 μM for diuron, with low detection limits of 12.4 nM and 28.5 nM, respectively. Furthermore, machine learning algorithms are introduced to resolve partial overlapping signals, enabling simultaneous pesticide classification and concentration prediction. The integration of interfacial engineering with machine learning provides an effective strategy for achieving simultaneous multi-pesticide detection at the nanomolar level. Full article

In this work, amino-functionalized Al-based MOF Al-GM was fabricated via a mild room-temperature aqueous route, which was applied as a ratiometric fluorescent probe for the specific detection of Cr₂O₇²⁻ in water. Characterizations including XRD, FT-IR, SEM, and BET verify that Al-GM synthesized in pure water exhibits high crystallinity and abundant mesoporous channels, with fully exposed amino recognition sites on the framework, delivering dual fluorescence emission signals. Sensing performance experiments demonstrate outstanding selectivity toward Cr₂O₇²⁻ with negligible interference from coexisting metal ions. Fluorescence titration reveals a wide linear detection range and an ultralow limit of detection, which is far lower than the discharge standard of Cr(VI) for industrial wastewater. pH-dependent tests confirm the stable sensing performance of the probe in water at a pH range of 5–9. XRD and FTIR spectra before and after Cr₂O₇²⁻ adsorption confirm intact crystal and organic coordination frameworks during ion recognition. Cr₂O₇²⁻ anions are selectively captured by the synergy of electrostatic attraction and intermolecular hydrogen bonds with amino sites. This study proposes a mild, organic-solvent-free synthetic strategy for MOFs, and the prepared Al-GM displays promising application potential for trace Cr(VI) monitoring in aquatic environments. Full article

Rising atmospheric CO₂ is altering carbon–nitrogen interactions in C₃ crops, with tomato (Solanum lycopersicum L.) showing enhanced carbon assimilation but frequently reduced nitrogen acquisition and assimilation. Nitrate reductase (NR), the rate-limiting enzyme in nitrate reduction, plays a central role by integrating nitrate assimilation with carbon metabolism and nitric oxide (NO) signaling. This review summarizes current knowledge of NR regulation in tomato under elevated CO₂ (eCO₂), focusing on post-translational mechanisms and their contribution to photosynthetic acclimation. Elevated CO₂ modulates NR activity through interconnected changes in photorespiration, carbohydrate-mediated feedback, redox regulation, source–sink dynamics, and nitrogen availability. While eCO₂ generally suppresses leaf nitrate assimilation by reducing photorespiratory support, root-zone CO₂ enrichment can transiently stimulate root NR activity, highlighting tissue-specific regulation. Multi-omics studies further demonstrate extensive metabolic and molecular reprogramming affecting carbon skeleton supply, amino acid biosynthesis, and nitrogen assimilation. In addition, NR-dependent NO production links nitrogen metabolism with stomatal regulation through ABA-independent H₂O₂–NO signaling. Despite these advances, the roles of NR phosphorylation, 14-3-3 protein interactions, and redox-mediated regulation under eCO₂ remain poorly understood. Overall, NR functions as a key metabolic and signaling hub coordinating carbon and nitrogen metabolism under future climate conditions. Understanding these regulatory mechanisms will facilitate strategies to improve nitrogen-use efficiency, sustain photosynthesis, and enhance tomato productivity under elevated atmospheric CO₂ while identifying priorities for future physiological, molecular, and multi-omics research. Full article

Neurodegenerative diseases remain a major therapeutic challenge, with oxidative stress playing a central role in central and peripheral immune system dysfunction that leads to neuronal loss. Natural products from extreme environments represent an underexplored source of neuroprotective agents. In this study, viridicatin, a quinoline-derived alkaloid, was isolated from the Antarctic fungus Penicillium sp. collected from sediments taken from Deception Island, and its structure was unambiguously confirmed by 1D/2D-NMR spectroscopy and single-crystal X-ray diffraction. Viridicatin (100 µM) significantly attenuated H₂O₂-induced cytotoxicity in HMC-3 human microglial cells, preserving cell viability and mitochondrial membrane potential. Viridicatin modulated the Nrf2 antioxidant signaling pathway, accompanied by increased expression of the downstream antioxidant enzymes HO-1 and NQO1. Moreover, molecular docking revealed preferential binding to the KEAP1 Kelch domain (−8.0 kcal/mol), suggesting indirect Nrf2 pathway modulation. A 100 ns molecular dynamics simulation with MM-GBSA analysis supported the stability of the viridicatin–KEAP1 complex. Notably, viridicatin rescued peripheral immune cells, i.e., peripheral blood mononuclear cells (PBMCs) obtained from older adults with mild cognitive impairment from H₂O₂-induced cell death, bridging the gap between in vitro mechanistic evidence and clinically relevant human cellular models. This is the first report of neuroprotective activity for viridicatin, positioning this Antarctic-derived alkaloid as a compelling candidate for further preclinical development against age-related neurodegeneration. Full article

Objectives: This study focuses on exploring the mechanism by which Schisandrin B (Sch B) regulates metabolic dysfunction-associated steatotic liver disease (MASLD) mice induced by a high-fat methionine–choline-deficient (MCD) diet through the activation of peroxisome proliferator-activated receptor γ (PPARγ). Methods: Male C57BL/6 mice were fed a high-fat MCD diet for 8 weeks to establish a mouse MASLD model, and the effects of Sch B on MASLD and the mechanisms were investigated. PPARγ overexpression (OE) was induced by adeno-associated virus (AAV) administration via intrahepatic portal vein injection in mice, and a negative control (NC-OE) was also established. Body weight; wet liver weight; hepatic index; serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β); and hepatic triglyceride (TG) levels were measured in the mice. The histopathology and lipid deposition were observed by hematoxylin and eosin (H&E) staining and Oil Red O staining, while the fibrosis was assessed using Masson staining. Western blot was employed to detect the expression levels of PPARγ, sterol regulatory element-binding protein 1c (SREBP-1c), carnitine palmitoyltransferase 1A (CPT1A), transforming growth factor β1 (TGF-β1), α-smooth muscle actin (α-SMA), collagen type I (collagen I), Smad family members 2/3 (Smad2/3), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38), and extracellular signal-regulated kinase 1/2 (ERK1/2), along with the phosphorylation activation status of these kinases. Results: It was confirmed that Sch B caused effects similar to those induced by PPARγ overexpression, reducing the hepatic index, AST, and ALT levels while alleviating lipid accumulation and fibrosis; and upregulating PPARγ and CPT1A while inhibiting SREBP-1c; and the phosphorylation of the TGF-β/Smad and MAPK pathways were involved in the mechanisms. Conclusions: Sch B can alleviate high-fat MCD-induced MASLD by activating PPARγ in mice. Full article

Nitrogen-containing fused tetracyclic systems, exemplified by the synthetic 11H-indeno[1,2-b]quinoxalin-11-one core and the natural alkaloid tryptanthrin (indolo[2,1-b]quinazolin-6,12-dione), constitute structural scaffolds whose rigid, planar architecture enables high-affinity interaction with nucleic acids and kinase active sites. Converting the exocyclic carbonyls at C-11 and C-6, respectively, into oximes has become a productive strategy in medicinal chemistry. This transformation modulates frontier orbital energies, installs N,O- and N,N-chelating pharmacophores, and enables nitric oxide (NO) release. Here, we summarize current knowledge of the synthesis, stereochemical characterization, and diverse biological activities of these tetracyclic ketoximes and related derivatives. Microwave, sonochemical, visible-light photocatalytic, and multicomponent methods now afford efficient, economical routes to the parent ketones and their oximes. X-ray crystallography, spectroscopy, and density functional theory have firmly established the thermodynamic preference for the E-oxime configuration and clarified how this geometry, along with potential target-induced isomerization, shapes binding. The oximes bind c-Jun N-terminal kinases (JNK1–3) with high affinity, a property that accounts for their neuroprotective effects in models of cerebral ischemia and Alzheimer-like pathology, their dual JNK inhibition and NO-mediated cardioprotection in hypertension and myocardial infarction, and their anti-inflammatory activity via suppression of NF-κB/AP-1 signaling. Broader studies also document anticancer, antimicrobial, antiviral, and antidiabetic activities arising from DNA intercalation, topoisomerase inhibition, metal-ion coordination, and kinase blockade. Compelling preclinical profiles notwithstanding, low oral bioavailability and rapid hepatic clearance remain major pharmacokinetic obstacles. Ongoing work on new formulations, prodrug strategies, and structure–activity optimization seeks to slow systemic elimination. Precise stereochemical definition combined with pleiotropic pharmacology positions tetracyclic ketoximes as attractive candidates for next-generation agents against complex multifactorial diseases. Full article