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Formation of environmental persistent free radicals in soil of ammunition demolition site: Roles of 2,4,6-trinitrotoluene and heavy metals.

Environmental Persistent Free Radicals (EPFRs) are a particular type of contaminant present in soil. This study investigated the formation process, environmental behavior, and main influencing variables of EPFRs in soils contaminated with heavy metals and 2,4,6-trinitrotoluene (TNT) from an ammunition demolition site. The results showed that the concentration of total organic carbon (TOC) in the soil was negatively correlated with EPFRs (r = -0.29). In contrast, the content of TNT and copper was significantly positively correlated with EPFRs (r = 0.90 and 0.78, respectively), indicating that TNT acts as a precursor macromolecule in the formation of EPFRs in this type of contaminated soil. Transition metal Cu may be an essential carrier in EPFR production. In order to explore the possible formation mechanism of EPFRs, a simulation experiment was carried out under different temperature and light conditions. The results showed that the photolysis process of TNT was impacted by external energy sources such as heat and light. TNT was firstly adsorbed onto the surface of a transition metal (Cu), and then EPFRs were formed through further electron transfer. This is the first study to detect significant levels of EPFRs in the soil at ammunition demolition sites.

Trinitrotoluene

Discovery and characterisation of catedehas A-C, a new class of antioxidant α,β-dehydroamino acid derivatives.

Dehydroamino acids are a class of noncanonical unsaturated amino acids commonly found in various naturally occurring peptides and proteins. In this study, we successfully cloned and heterologously expressed the cda biosynthetic gene cluster from Streptomyces nitrosporeus ATCC 12769 in Streptomyces lividans TK24, leading to the identification of three α,β-dehydroamino acid derivatives, designated as catedehas A-C (1-3). Among these, compound 2, although previously reported, lacked any detailed characterisation data. Their structures were elucidated by high-resolution electrospray ionisation mass spectrometry, 1D and 2D nuclear magnetic resonance spectroscopy, along with other spectroscopic techniques. Compounds 1-3 exhibited remarkable antioxidant activity in DPPH· free radical scavenging assay, with IC50 values of 27.52, 12.51, and 8.32 μM, respectively.

Antioxidants

Obeticholic Acid and Edaravone Protect Against Cisplatin-Induced Hepatotoxicity Through Modulation of Keap1/Nrf2/ARE, TNF-α/NF-κB, and AKT/GSK-3β Pathways.

Hepatotoxicity is one of the most crucial side effects of chemotherapy administration. Obeticholic acid (OCA) is a semisynthetic bile acid and farnesoid X receptor (FXR) agonist derived from chenodeoxycholic acid, with reported antioxidant and anti-inflammatory effects in liver disorders. This study investigated the hepatoprotective effect of OCA against commonly used chemotherapy cisplatin (CP)-induced hepatotoxicity in rats, as well as the modulatory effects of edaravone (EDA), a potent free radical scavenger, on its effects. Rats were divided into five groups: control (received vehicle), CP (7.5 mg/kg), EDA (30 mg/kg) + CP, OCA (30 mg/kg) + CP, and EDA + OCA + CP. The results of the present study demonstrated that both OCA and EDA significantly mitigated liver damage caused by CP, as evidenced by restoring liver enzymes and histological structure, reestablishment of oxidant/antioxidant status, suppression of inflammation, and attenuation of pro-death signaling. The study highlights the role of key molecular pathways, including Keap1/Nrf2/HO-1,HO-1, TNF-α/NF-κB, and AKT/GSK-3β, in the hepatoprotective mechanisms of OCA. Collectively, these findings suggest that OCA and EDA, particularly in combination, attenuate CP-induced hepatotoxicity and are associated with coordinated modulation of oxidative stress, inflammatory signaling, and AKT/GSK-3β-associated pro-survival/pro-death pathways.

Animals

Integrated Multiomics Analyses of the Molecular Landscape of Sarcopenia in Alcohol-Related Liver Disease.

BACKGROUND: Skeletal muscle is a major target for ethanol-induced perturbations, leading to sarcopenia in alcohol-related liver disease (ALD). The complex interactions and pathways involved in adaptive and maladaptive responses to ethanol in skeletal muscle are not well understood. Unlike hypothesis-driven experiments, an integrated multiomics-experimental validation approach provides a comprehensive view of these interactions. METHODS: We performed multiomics analyses with experimental validation to identify novel regulatory mechanisms of sarcopenia in ALD. Studies were done in a comprehensive array of models including ethanol-treated (ET) murine and human-induced pluripotent stem cell-derived myotubes (hiPSCm), skeletal muscle from a mouse model of ALD (mALD) and human patients with alcohol-related cirrhosis and controls. We generated 13 untargeted datasets, including chromatin accessibility (assay for transposase accessible chromatin), RNA sequencing, proteomics, phosphoproteomics, acetylomics and metabolomics, and conducted integrated multiomics analyses using UpSet plots and feature extraction. Key findings were validated using immunoblots, redox measurements (NAD+/NADH ratio), imaging and senescence-associated molecular phenotype (SAMP) assays. Mechanistic studies included mitochondrial-targeted Lactobacillus brevis NADH oxidase (MitoLbNOX) to increase redox ratio and MitoTempo as a mitochondrial free radical scavenger. RESULTS: Multiomics analyses revealed enrichment in mitochondrial oxidative function, protein synthesis and senescence pathways consistent with the known effects of hypoxia-inducible factor 1&#x3b1; (HIF1&#x3b1;) during normoxia. Across preclinical and clinical models, HIF1&#x3b1; targets (n&#x2009;=&#x2009;32 genes) and signalling genes (n&#x2009;>&#x2009;100 genes) (n&#x2009;=&#x2009;3 ATACseq, n&#x2009;=&#x2009;65 phosphoproteomics, n&#x2009;=&#x2009;10 acetylomics, n&#x2009;=&#x2009;6 C2C12 proteomics, n&#x2009;=&#x2009;106 C2C12 RNAseq, n&#x2009;=&#x2009;64 hiPSC RNAseq, n&#x2009;=&#x2009;30 hiPSC proteomics, n&#x2009;=&#x2009;3 mouse proteomics, n&#x2009;=&#x2009;25 mouse RNAseq, n&#x2009;=&#x2009;8 human RNAseq, n&#x2009;=&#x2009;3 human proteomics) were increased. Stabilization of HIF1&#x3b1; (C2C12, 6hEtOH 0.24&#x2009;&#xb1;&#x2009;0.09; p&#x2009;=&#x2009;0.043; mALD 0.32&#x2009;&#xb1;&#x2009;0.074; p&#x2009;=&#x2009;0.005; data shown as mean difference&#x2009;&#xb1;&#x2009;standard error mean) was accompanied by enrichment in the early transient and late change clusters, -log(p-value)&#x2009;=&#x2009;1.5-3.8, of the HIF1&#x3b1; signalling pathway. Redox ratio was reduced in ET myotubes (C2C12: 15512&#x2009;&#xb1;&#x2009;872.1, p&#x2009;<&#x2009;0.001) and mALD muscle, with decreased expression of electron transport chain components (CI-V, p&#x2009;<&#x2009;0.05) and Sirt3 (C2C12: 0.067&#x2009;&#xb1;&#x2009;0.023, p&#x2009;=&#x2009;0.025; mALD: 0.41&#x2009;&#xb1;&#x2009;0.12, p&#x2009;=&#x2009;0.013). Acetylation of mitochondrial proteins was increased in both models (C2C12: 107364&#x2009;&#xb1;&#x2009;4558, p&#x2009;=&#x2009;0.03; mALD: 40036&#x2009;&#xb1;&#x2009;18&#x2009;987, p&#x2009;=&#x2009;0.049). Ethanol-induced SAMP was observed across models (P16: C2C12: 0.2845&#x2009;&#xb1;&#x2009;0.1145, p&#x2009;<&#x2009;0.05; hiPSCm: 0.2591, p&#x2009;=&#x2009;0.041). MitoLbNOX treatment reversed redox imbalance, HIF1&#x3b1; stabilization, global acetylation and myostatin expression (p&#x2009;<&#x2009;0.05). CONCLUSIONS: An integrated multiomics approach, combined with experimental validation, identifies HIF1&#x3b1; stabilization and accelerated post-mitotic senescence as novel mechanisms of sarcopenia in ALD. These findings show the complex molecular interactions leading to mitochondrial dysfunction and progressive sarcopenia in ALD.

Sarcopenia

Micro- and nanoplastics-induced neurotoxicity: a CNS-centered, evidence-graded adverse outcome pathway framework based on systematic weight-of-evidence assessment.

Micro- and nanoplastics (MPs/NPs) are ubiquitous anthropogenic particulate pollutants posing emerging threats to human neurological health. Severe heterogeneity in particle physicochemical properties, environmental aging status, exposure paradigms and experimental platforms has created persistent mechanistic uncertainties in MP/NP neurotoxicology, hindering reliable hazard characterization and risk translation. Here, we systematically consolidate empirical toxicological evidence and construct a dedicated central nervous system (CNS)-targeted adverse outcome pathway (AOP) network integrated with rigorous weight-of-evidence (WoE) grading to elucidate the hierarchical, particle-specific toxic cascades underlying MP/NP-induced neural injury. Our synthesis overturns the conventional linear toxicity paradigm, demonstrating that MPs/NPs trigger neurotoxicity via a complex multi-input mechanistic network. We definitively establish oxidative stress as a robust early convergent key event-rather than a universal molecular initiating event-orchestrating ROS overproduction, lipid peroxidation, mitochondrial dysfunction, and neuroinflammation to propagate neuronal damage. This core module is driven by five distinct particulate upstream triggers: particle-biomolecule interfacial perturbation, corona-facilitated cellular internalization, plastic-associated chemical leaching, aging-derived free radical reactivity, and gut-borne systemic neurotoxic signaling. Downstream pathogenic outcomes encompass glial overactivation, neurotransmitter dyshomeostasis, autophagy-lysosome dysfunction, metabolic reprogramming, regulated neuronal cell death, and behavioral impairments. Tiered WoE analysis confirms strong validation for early oxidative/inflammatory cascades, moderate support for gut-brain axis crosstalk and intracellular trafficking disruption, and nascent evidence for synaptic dysfunction and neurodegeneration-linked proteostatic defects. Extrapolation to human health risk remains constrained by the frequent use of high-dose exposure paradigms, limited validated data on internal dosimetry in the human brain, discrepancies between effective concentrations in experimental models and environmentally relevant human tissue burdens, and insufficient causal validation of distal adverse outcomes. We highlight key research priorities including aged mixed-particle exposure systems, leachate-controlled assays, quantitative internal dose evaluation, and mechanistic intervention verification. This evidence-stratified AOP framework resolves longstanding mechanistic ambiguities in particulate neurotoxicity, providing a standardized, causality-based foundation for future mechanistic exploration and health risk assessment of global plastic pollution.

Adverse outcome pathway

Mapping the Molecular Evolution and Role of Wild Rice GLYIII Protein-Encoding Genes in Abiotic Stress Response.

To address the need for sustainable food production amid rapid global climate change, developing rice varieties that grow optimally even under harsh conditions is essential. An effective approach in this direction would be to harness the stress resilience traits of the crop wild relatives (CWRs) of rice. Among the various crucial stress-responsive genes, the Glyoxalase III (GLYIII) gene family is of utmost importance for its ability to detoxify the toxic glycolytic byproduct, methylglyoxal (MG), in a less energy-intensive, single-step process, as well as for its multifaceted cytoprotective role. In our study, a comprehensive genome-wide search across the Oryza genus revealed that GLYIII genes are conserved across wild rice genotypes. Their number has expanded during domestication, driven by gene duplications. Interestingly, only a few orthologous pairs showed positive selection, suggesting that the functions of most others need to be constrained and or conserved.We found that higher GLYIII activity, Total Antioxidant Capacity, endogenous glutathione (GSH) levels, and free radical scavenging activity contributes to the stress resilience of wild rices O. punctata, O. meridionalis, and O. nivara, in addition to other factors. , , . , . Our qRT-PCR analysis revealed differential expression of the OpGLYIII, OmGLYIII, and OnGLYIII genes across different developmental stages and in response to various abiotic stresses. Furthermore, we report that wild rice GLYIII proteins, specifically OpGLYIII-3, OmGLYIII-3, and OnGLYIII-5, exhibit high catalytic efficiency over a broad pH range and at higher temperatures under in vitro assay conditions. Overexpression of these proteins was found to impart substantial stress resilience to the transformed E. coli cells. These findings collectively suggest that GLYIII proteins constitute a key component of the abiotic stress response machinery in wild rice.

Oryza

Multi-omics insights into aroma formation in congou black tea during fermentation.

This study used multi-omics technologies to analyze aroma formation during Congou black tea fermentation. Volatile compounds were analyzed by headspace solid phase microextraction coupled with gas chromatography mass spectrometry using two columns of different polarity. Fermentation increased total volatile normalized peak area fivefold, with alcohols, aldehydes, and acids increasing over sevenfold. 29 differential metabolites were screened, including amino acid derived phenylacetaldehyde, phenylethanol, and 2-methylbutanal; fatty acid derived (E,E)-2,4-heptadienal, hexanal, and 1-hexanol; and isoprenoid derived linalool, geraniol, and beta ionone. Transcriptomic, proteomic, and enzyme analyses revealed that biosynthesis contributed to early accumulation of amino acid and isoprenoid derived aromas, whereas ortho quinone mediated Strecker degradation and free radical induced fatty acid auto oxidation dominated generation of amino and fatty acid derived aromas during middle and late fermentation. In conclusion, aroma formation during fermentation results from biosynthesis and non-enzymatic oxidation, with the latter possibly dominating amino and fatty acid derived aromas.

Fermentation

Chronic nitric oxide mediates dual-layer gene regulation through mRNA m6A positional remodeling and parallel transcriptional reprogramming.

Nitric oxide (NO) is a pleiotropic free radical that functions as a master regulator of gene expression, and its sustained production within the tumor microenvironment reshapes the epitranscriptomic state of cancer cells. We previously demonstrated that NO inhibits the m6A mRNA demethylases FTO and ALKBH5 through dinitrosyliron complex formation while leaving the methyltransferase METTL3 intact, a demethylase-specific perturbation that increases global m6A on mRNA. Here, integrating m6A-RIP-seq and RNA-seq from triple-negative breast cancer cells, we show that chronic NO does not produce the uniform hypermethylation anticipated from demethylase inhibition. Instead, it redistributes m6A on mRNA, enriching the 5'UTR and coding sequence while depleting the 3'UTR and departing from the canonical stop-codon and 3'UTR topology. We found that the position of m6A, rather than its intensity or mere presence, shapes the outcome, in part by determining which reader protein is predicted to recognize it. In parallel, NO drives a canonical NF-&#x3ba;B and inflammatory transcriptional program. The transcriptional program is independent of the m6A methylome in both which genes respond and how strongly they respond, ruling out a linear methylome-to-transcriptome cascade; even so, m6A position remains associated with the direction of change among responding transcripts. The 3'UTR is the primary site of m6A loss and shows a suggestive computational link to miRNA-mediated regulation. Sense-antisense coordination reinforces the transcriptional response without bridging the two programs. These findings demonstrate that NO not only increases m6A abundance, but it also rewrites the m6A positional code, establishing spatial reprogramming of the epitranscriptome as a previously unrecognized mode of gene regulation.

RNA Methylation

Multi-dimensional profiling of primary metabolites in Heuchera micrantha varieties reveals potential for functional food development.

Heuchera micrantha is a horticultural plant with emerging pharmacological value, yet its primary metabolites remain underexplored. This study comprehensively profiled nutrient metabolites in four H. micrantha varieties using LC-MS/MS. We identified 285 metabolites, with amino acid derivatives being predominant. Multivariate analysis revealed distinct varietal accumulation patterns and 204 differential accumulated metabolites (DAMs). Integrative network pharmacology and molecular docking suggested &#x3b3;-glutamyltyrosine and L-prolyl-L-phenylalanine as potential bioactive dipeptides that may interact with core hubs (MAPK1, EGFR, SRC) involved in cancer and inflammation pathways, though these predictions require experimental validation. Transcriptomics identified 39 differentially expressed genes regulating the biosynthesis of their precursor amino acids. Antioxidant assays showed varietal differences: some excelled in free radical scavenging (DPPH/ABTS) while others demonstrated superior reducing power (FRAP). This multi-omics study suggests that H. micrantha may be a rich source of therapeutically relevant primary metabolites, providing a preliminary scientific basis for its development as a functional food or nutraceutical pending further validation.

Functional Food

Whole-genome sequencing identifies a c.1282C > T missense variant in Taurine Transporter (TauT) associated with taurine-mediated dilated cardiomyopathy in a family of domestic shorthair cats.

Taurine is a cytoprotectant amino acid critical for a variety of cellular functions, including cell volume and intracellular calcium regulation, bile salt formation, free radical protection, and mitochondrial biogenesis. In most mammals, taurine is synthesized via methionine transsulfuration; albeit, in cats, taurine biosynthesis is blunted due to low enzymatic activity of their encoded cysteine sulfonic acid decarboxylase and, therefore, is an essential amino acid in the species. Taurine deficiency in cats results in retinopathy, coagulopathy, growth retardation, impaired immunological function, and most notably dilated cardiomyopathy (DCM). A three-year-old domestic shorthair cat was evaluated for vomiting, anorexia, and lethargy. Severe dilated cardiomyopathy and taurine deficiency were identified, despite eating a commercial, nutritionally balanced, diet with adequate taurine concentrations. A whole-genome association study (WGAS), under the assumptions of an incomplete dominance mode of inheritance (MOI), was performed on this case and two related cats with mild taurine and echocardiographic abnormalities (i.e., queen and littermate) compared to 18 previously whole-genome sequenced echocardiographically-normal geriatric controls (>10&#xa0;years-of-age; n&#xa0;=&#xa0;21). A 'MODERATE' c.1282C&#xa0;>&#xa0;T; p.Arg428Trp variant harbored in Solute Carrier Family 6 Member 6/Taurine Transporter (SLC6A6/TauT) was identified. The variant segregated to the postulated MOI and was not observed in any of the control or in an expanded population of cats (n&#xa0;=&#xa0;422). Functional analyses involving wildtype and mutant SLC6A6 overexpression in HEK293-derived cells revealed marked reduction in cellular taurine uptake and decreased plasma membrane expression in those harboring the c.1282C&#xa0;>&#xa0;T variant. This represents the first-ever reported genetic variant explaining taurine deficiency in any domestic animal species.

Dilation

Development of Dual-Cross-Linked AlgMA/HAMA Hybrid Hydrogels for Traumatic Wound Healing.

Traumatic injuries and uncontrolled, intense bleeding caused by surgery remain among today's leading medical problems. Traumatic wounds are not only observed on the skin but also result from internal organ ruptures caused by explosions and firearms. At this point, severe hemorrhaging can lead to hypothermia, hemorrhagic shock, organ failure, and even death due to the loss of more than 40% of blood volume. Therefore, it is crucial to halt bleeding rapidly. In this study, an alginate derivative that supports platelet aggregation and a hyaluronic acid derivative that adheres to wet tissues and induces angiogenesis, thereby promoting vascularization, have been prepared. The derivatives of alginate and hyaluronic acid were subjected to free radical photopolymerization, allowing them to cross-link in the presence of visible light. The study aims to introduce a new biomaterial featuring sodium alginate and hyaluronic acid groups that demonstrates good mechanical strength, a high swelling capacity to stabilize bleeding in the environment, and effective hemostatic properties. The chemical characterization of biopolymers was analyzed using FTIR and NMR techniques. The mechanical properties, swelling behavior, and degradation profiles of visible light cross-linked hybrid hydrogels were systematically characterized. The biocompatibility of the produced hydrogels was also evaluated using MTT and scratch wound healing tests. In addition, hemolysis and blood coagulation tests were performed to investigate the hemocompatibility and hemostatic potential of visible light cross-linked hybrid hydrogels.

Journal Article

Mechanisms of Hexavalent Chromium-Induced Reproductive Toxicity: A Focus on the Ovary and Placenta.

Hexavalent Chromium (Cr(VI)) is a Group A carcinogen, mutagen, and teratogen. Cr(VI) has been used by more than 50 industries, and its contamination of drinking water is widespread across the United States (U.S.). Epidemiological data of women who lived in Willits, California, U.S., indicate that environmental exposure to Cr(VI) adversely affects pregnancy outcomes and the health of their immediate offspring, resulting in a low birth rate, pregnancy loss, and spontaneous abortion, and their children (F1 offspring) experienced birth defects. However, the molecular mechanisms behind Cr(VI)-induced reproductive and developmental toxicity are poorly understood. Cr(VI) enters cells through anion transporters and is rapidly reduced to Cr(III) by endogenous antioxidants within the cell. Cr(III) forms adducts with DNA, which can block DNA replication and transcription; abnormal repair can lead to DNA double-strand breaks, mutations, micronucleus formation, chromosomal abnormalities, and increased genomic instability. Cr(VI) induces oxidative stress via the Fenton reaction, generating free radicals, and depleting antioxidants, thereby promoting apoptosis via p53-dependent and independent pathways, resulting in follicular atresia and accelerated reproductive aging. Antioxidant supplementation with resveratrol, vitamin C, and edaravone mitigates Cr(VI) toxicity in the ovary. Cr(VI) disrupts meiosis in metaphase II oocytes by causing DNA strand breaks, altering F-actin dynamics, disturbing microtubules, and leading to chromosome missegregation. Gestational exposure to Cr(VI) also disrupts placental function through multiple mechanisms by targeting trophoblast lineages. The current review focuses on genotoxicity, oxidative stress, and other mechanisms by which Cr(VI) disrupts the female reproductive and endocrine systems, with particular emphasis on the ovary and placenta.

Hexavalent chromium

Resveratrol in Combination Therapy: Mechanisms and Limitations of Resveratrol in Cancer, Regeneration, and Chronic Disease.

Resveratrol (RSV), a nonflavonoid polyphenol phytoalexin, has considerable therapeutic potential for managing chronic and acute diseases due to its anti-inflammatory, anti-cancer, antimicrobial, and antioxidant properties. It can help protect cells from free radical damage and modulate signaling pathways in the body to promote overall health. RSV can also facilitate the therapeutic effects of mesenchymal stem cells by increasing their self-renewal, survival, anti-aging effects, and lineage commitment. However, the natural form of RSV has limitations, such as poor intestinal absorption and low bioavailability. This review focuses on the potential of RSV to explore its effects and mechanisms of action in cancer, regenerative medicine, and chronic disease. It also discusses how RSV can protect normal tissue against genomic instability and presents findings from combination therapies involving RSV and nanoparticle-based agents. Overall, this review highlights the latest developments regarding RSV as a promising compound, emphasizing the potential to overcome its limitations.

Resveratrol

Molecular Cloning, Recombinant Expression, and In Silico Structural Analysis of Cu/Zn-Superoxide Dismutase from Trachyspermum ammi.

Superoxide dismutase (SOD) is an essential antioxidant metalloenzyme that is critical for the cellular defense against oxidative damage, as it scavenges superoxide radicals and maintains the redox status. Cytosolic Cu/Zn-SOD is particularly important in the regulation of oxidative stress among different isoforms in higher plants. While Cu/Zn-SODs from several plant species have been characterized, molecular information is limited for Trachyspermum ammi, a medicinally important member of a family Apiaceae with antioxidant potential.In the present study, an integrated molecular and in silico approach has been taken to clone and analyze a Cu/Zn type SOD gene from T. ammi to get insight into its structural and evolutionary characteristics. PCR amplification yielded an open reading frame of 456&#xa0;bp encoding a protein of 152 amino acids. Sequence analysis showed that plant Cu/Zn-SODs, especially those from Daucus carota, were highly similar to one another (about 90-95%).Multiple sequence alignment confirmed the presence of conserved catalytic motifs and metal-binding histidine residues, both of which are crucial for enzymatic function. Physicochemical analysis predicted the protein to be stable, hydrophilic and compatible with cytosolic localization. The analysis of secondary structure indicated a predominance of &#x3b2;-strands, consistent with the conserved &#x3b2;-barrel architecture of plant Cu/Zn-SODs.The three-dimensional structure was built by homology modeling using a closely related plant Cu/Zn-SOD template with high sequence identity. Structural validation demonstrated an acceptable stereochemical quality with 86.3% residues in the favored region of Ramachandran plot, satisfactory ERRAT and Verify3D scores, and a low RMSD value of 0.104&#xa0;&#xc5; on structural superimposition. Phylogenetic analysis placed the enzyme in the Apiaceae lineage, suggesting evolutionary conservation among related plant species. In conclusion, this study presents the first molecular and structural characterization of Cu/Zn-SOD from T. ammi and confirms the existence of a conserved structural framework typical of plant Cu/Zn-SODs. These results provide a basis for further studies concerning recombinant expression, enzymatic validation and potential relevance in antioxidant and plant stress biology.

Cloning, Molecular

Birnessite-mediated simultaneous remediation of lead and benzo[a]pyrene co-contaminated soils.

It is currently challenging to remediate soils co-contaminated by heavy metals and polycyclic aromatic hydrocarbons. Birnessite is a naturally ubiquitous manganese oxide mineral with strong oxidation and adsorption capacities, but its specific roles in pollutant transformation and interfacial interaction within co-contaminated systems remain elusive. This study investigated the simultaneous remediation of lead (Pb) and benzo[a]pyrene (BaP) in soils by birnessite through incubation experiments and density functional theory calculation. Birnessite treatment decreased CaCl2- and toxicity characteristic leaching procedure-extractable Pb content by 64.3% and 86.6% and reduced the BaP content by 33.8%. Mechanistically, Pb immobilization was primarily driven by spontaneous adsorption, including ion exchange and surface complexation, which facilitated Pb transformation into Fe-Mn oxide-bound fractions. Concurrently, BaP removal occurred via a synergistic pathway involving reactive species and electron transfer processes. Increasing dosage of birnessite promoted Pb immobilization, but had little effect on BaP oxidation. Moreover, the co-existing Pb affected birnessite-mediated BaP adsorption and oxidation by promoting the formation of [BaP-Pb]2+ and [BaP-Pb(H2O)]2+ complexes via cation-&#x3c0; interactions. These complexes were more preferentially adsorbed on birnessite compared with BaP molecules, but exhibited higher electron transfer barriers. The findings provide critical insights into the remediation of co-contaminated soils and the fate of co-existing contaminants.

Birnessite

Hydroxyl Radical Inactivation of Vesicle-Cloaked and Free Murine Norovirus: Linking Biomolecular Oxidation to Lifecycle Disruption and Infectivity Loss.

Hydroxyl radicals (&#x2022;OH) play a central role in inactivating human viruses during advanced oxidation processes for water and wastewater treatment, solar disinfection, and natural attenuation in sunlit aquatic environments. Human norovirus, a leading cause of gastroenteritis, is efficiently transmitted through water and exhibits strong environmental persistence. The recent discovery of vesicle-cloaked virus clusters (viral vesicles) further challenges water treatment and reuse, particularly for norovirus elimination. We investigated &#x2022;OH inactivation kinetics and mechanisms of murine norovirus 1 (MNV-1), a human norovirus surrogate, in free-virus and vesicle-cloaked forms. &#x2022;OH rapidly inactivated both MNV-1 vesicles and free MNV-1 with second rate constants of &#x223c;1010 M-1 s-1; however, the vesicle membrane provided a 2.24-fold protective effect to cloaked MNV-1, resulting in slower inactivation kinetics than those of free MNV-1. &#x2022;OH oxidized viral capsid proteins and genomes together with vesicle proteins and lipids, resulting in impaired CD300lf receptor and cell-based binding, disrupted genome replication, and diminished viral assembly. Despite these biochemical and functional impairments, most vesicle structures remained largely intact following &#x2022;OH exposure. This study establishes a quantitative framework linking biomolecular damage to viral infectivity loss through functional impairment and lifecycle disruption, providing mechanistic insights into advance water disinfection strategies and public health protection.

Norovirus

Deuteration enhances UV-induced hyperpolarization of [1-13C]pyruvate to trityl-level performance in vitro and in vivo.

Dissolution dynamic nuclear polarization (dDNP) using UV-irradiated, non-persistent radicals has recently emerged as a filtration-free alternative to trityl-based methods; however, its performance for in vivo metabolic imaging remains insufficiently evaluated. Here, we systematically assessed UV-induced hyperpolarized (HP) [1-13C]pyruvate and its deuterated analog in the mouse brain, a technically demanding target for HP 13C MRI, and directly compared the results with conventional OX063-based dDNP. UV-induced HP [1-13C]pyruvate yielded lactate-to-pyruvate and bicarbonate-to-pyruvate ratios equivalent to those obtained with OX063-polarized preparations, and demonstrated good test-retest reproducibility. Deuteration substantially improved the polarization levels of UV-irradiated samples to values comparable to trityl-based dDNP, while preserving comparable in vivo metabolic readouts. Building on this methodological validation, awake 13C MRSI using HP [1-13C, d4]pyruvate, as applied in the present study, was used as a proof-of-concept in an Alzheimer's disease mouse model, where increased pyruvate-to-lactate conversion was detected in hippocampus-including regions of 3-month-old APPNL-G-F knock-in mice. Together, these results support UV-induced, deuterated HP pyruvate as a practical alternative to trityl-based dDNP and demonstrate its feasibility for preclinical HP 13C MRI studies of brain metabolism.

Alzheimer&#x2019;s disease model

Novel insights into retinoblastoma: From oncogenic circuitry to precision diagnosis and eye-preserving therapies.

Retinoblastoma (RB) represents the most common primary intraocular malignancy in childhood and stands as a paradigm for translating molecular oncology into precision clinical management. This review synthesizes the comprehensive evolution in the understanding and treatment of RB. First, we deconstruct the intricate oncogenic circuitry that extends far beyond Knudson's classic "two-hit" RB1 inactivation model, describing non-classical MYCN-driven pathogenesis, multi-layered epigenetic reprogramming (including chromatin, RNA and histone changes), and distinct histological subtypes with defined clinical correlates, such as the favorable-prognosis cavitary RB. Single-cell genomics has elucidated the cellular origin from cone precursor cells and intratumoral heterogeneity. Risk stratification has been refined through well-defined classification systems, from the therapy-guiding International Intraocular Retinoblastoma Classification (IIRC) to the comprehensive American Joint Committee on Cancer Tumor-Node-metastasis (AJCC TNM) staging. Furthermore, the diagnostic paradigm has advanced from conventional anatomical imaging to liquid biopsies, enabling non-invasive molecular staging and monitoring via tumor-derived cell-free DNA analysis. Concurrently, the therapeutic landscape has undergone a radical shift, moving from enucleation and external-beam radiotherapy to an era dominated by local sight-preserving strategies. We provide a critical synthesis of the evidence for intravenous chemotherapy and the transformative role of super-selective intra-arterial chemotherapy (IAC), and describe essential randomized controlled trials, technical innovations, and optimized drug regimens. Finally, we explore emerging targeted molecular therapies and future directions. By integrating cutting-edge molecular insights with robust, high-level clinical evidence, this review offers the framework for achieving patient and eye survival as well as vision preservation in children with Retinoblastoma.

Intra-arterial chemotherapy