PubMed

Nature. 2026 Mar 4. doi: 10.1038/s41586-026-10193-4. Online ahead of print.ABSTRACTFerroptosis, a major mechanism of non-apoptotic programmed cell death, critically regulates the homeostasis and functionality of peripheral CD4+ and CD8+ T cells1-6. Here we demonstrate that in mouse, resistance of T cells to ferroptosis depends critically on the composition of standard rodent diets, and that dietary effects on ferroptosis (DEFs) have a crucial role in regulation of T cell homeostasis and immune responses. DEFs are microbiota-independent and are driven by variations in dietary polyunsaturated and monounsaturated fatty acids (PUFAs and MUFAs) that lead to variations in abundance of lipid species in lymphoid tissues and T cells. Consistently, ferroptosis resistance of human T cells also correlated with plasma lipid profiles across multiple healthy cohorts, exhibiting negative associations with PUFA/MUFA ratios in major lipid classes. DEFs dictate T cell resilience in the absence of the essential lipid peroxide scavenger GPX4 and broadly modulate T cell-dependent humoral immunity and T cell-mediated anti-tumour immunity, including in chimeric antigen receptor T cell therapy. Mechanistically, ACSL4, which preferentially biosynthezises PUFA-containing phospholipids7, is highly expressed in T cells and underpins DEF-mediated regulation of follicular helper T (TFH) cell generation and function. Our findings reveal the physiological significance of lipid metabolism in driving DEFs in immunity and suggest strategies targeting lipid metabolism to enhance vaccine efficacy and T cell-mediated immunotherapy.PMID:41781622 | DOI:10.1038/s41586-026-10193-4

Sci Rep. 2026 Mar 4. doi: 10.1038/s41598-026-42524-w. Online ahead of print.ABSTRACTChicken eggs are one of the most consumed foods worldwide. However, the practice of chicken culling in the poultry industry involves unnecessary animal suffering and finding a way to put an end to this has become a societal priority. One approach that has been propagated as acceptable is based on the selection of female eggs early in the incubation process and the devitalization of the male eggs. It is with this objective in mind that we searched for a biomarker for early gender screening in eggs. Applying an untargeted mass spectrometry approach, we profiled allantoic fluid of different day-old eggs and identified the feature 3-[(2-aminoethyl)sulfanyl]butanoic acid (ASBA) as a strong biomarker for in-ovo gender prediction for day-9 old embryos. In the present work, we describe the identification of ASBA as a new biomarker in allantoic fluid for gender screening and the optimization of a high throughput assay using acoustic droplet ejection-mass spectrometry (ADE-MS). Special attention is given to the optimization of ADE-MS compatible liquid handling and the development of the data processing to ensure a reliable gender prediction. We have been able to accurately determine the gender of day-9 eggs in a cohort of 154 samples with a prediction accuracy of 95.5%, with a throughput of 1800 samples per hour for the prototype, which may vary in production systems.PMID:41781573 | DOI:10.1038/s41598-026-42524-w

J Agric Food Chem. 2026 Mar 4. doi: 10.1021/acs.jafc.5c13677. Online ahead of print.ABSTRACTNuclear magnetic resonance (NMR) spectroscopy is widely adopted for assessing biochemical composition in agriculture. This study evaluated the feasibility of 400 MHz NMR to detect biochemical differences in Hass avocados grown under conventional (N = 101) and regenerative (N = 105) farming practices in Southwestern Australia. Phosphite, associated with Phytophthora root rot management, was a key discriminating feature (area under ROC curve = 0.96), being detected in 90% of conventional avocados (mean: 49 mg/kg) and 6 regenerative samples (mean: 24 mg/kg). To assess translational potential, water extracts of five samples were analyzed using 80 MHz benchtop NMR. Phosphite was detectable below the strictest maximum residue limit (25 mg/kg), demonstrating the potential of NMR as a sustainable and cost-effective solution for monitoring phosphite residues. This proof-of-concept benchtop NMR approach demonstrates analytical feasibility but requires further validation before application in field-based traceability or regulatory contexts, with a potential future relevance to environmental monitoring, sustainable agriculture, and other crop systems.PMID:41780928 | DOI:10.1021/acs.jafc.5c13677

Mol Cell Proteomics. 2026 Mar 2:101548. doi: 10.1016/j.mcpro.2026.101548. Online ahead of print.ABSTRACTOxidative stress triggers redox-sensitive post-translational modifications, notably disulfide bond formation involving cysteine residues. However, these bonds are often overlooked in proteomics due to the routine use of reducing agents. Here, we employed liquid chromatography-mass spectrometry (LC-MS) based metabolomics and non-reducing tandem mass tag (TMT) proteomics to investigate the effects of H2O2 on MDA-MB-231 cells. Metabolomic analysis revealed pathway-specific inhibition of major metabolic pathways including glycolysis, the tricarboxylic acid (TCA) cycle, and nucleotide biosynthesis. Proteomic analysis using the DBond algorithm revealed extensive and isoform-specific disulfide crosslinks across more than 1,000 proteins. These linkages were enriched at redox-sensitive cysteines near basic residues and displayed high isoform specificity. Our findings demonstrate that disulfide bond formation serves as a selective mechanism of redox regulation. This study highlights the utility of non-reducing proteomics in elucidating redox-controlled protein networks and structural dynamics under oxidative stress.PMID:41780889 | DOI:10.1016/j.mcpro.2026.101548

J Dairy Sci. 2026 Mar 2:S0022-0302(26)00194-3. doi: 10.3168/jds.2025-27877. Online ahead of print.ABSTRACTFood allergies are a major challenge in current healthcare. Probiotics and human milk oligosaccharides (HMO) are increasingly being used to address food allergies. However, the role of nonfucosylated neutral oligosaccharides in food allergies remains unclear. Moreover, HMO interact positively with probiotics, but the synergistic effects and underlying mechanisms of their combined action in alleviating food allergies remain poorly understood. Consequently, Bifidobacterium longum ssp. infantis (B. infantis), which exhibits the greatest capacity to use HMO, was chosen for this study. The effects of lacto-N-neotetraose (LNnT), B. infantis, and their combination on allergy was assessed using an ovalbumin (OVA)-induced allergic mouse model. The mechanisms underlying the alleviation of food allergies by LNnT + B. infantis were also investigated through genomics and metabolomics. The results demonstrated that LNnT and B. infantis exerted partial modulatory effects on allergic symptoms, BW, mast cell degranulation, cytokine levels, and immune cell populations in mice. Notably, the simultaneous administration of LNnT and B. infantis significantly outperformed the administration of either LNnT or B. infantis alone, indicating a synergistic effect. Furthermore, LNnT + B. infantis was found to alleviate intestinal injury. Gut microbiota analysis revealed that LNnT + B. infantis reduced the abundance of the allergy-associated bacterium Desulfovibrio and significantly increased the levels of beneficial bacteria, including Lactobacillus, Limosilactobacillus, and Blautia. The LNnT + B. infantis treatment also enhanced steroid hormone biosynthesis, ascorbate and aldarate metabolism, and nucleotide metabolism. Some substances in these pathways are produced by the gut microbiota and are linked to allergy amelioration. In conclusion, LNnT + B. infantis alleviates food allergies by modulating the gut microbiota and its associated metabolic functions in OVA mice.PMID:41780875 | DOI:10.3168/jds.2025-27877

J Dairy Sci. 2026 Mar 2:S0022-0302(26)00185-2. doi: 10.3168/jds.2025-27993. Online ahead of print.ABSTRACTPrebiotics promote the proliferation and colonization of probiotics in the intestine; therefore, synergistic application of probiotics and functional oligosaccharides can confer significant health benefits to the host. This study optimized a complex prebiotic combination that enhanced the growth of Lactobacillus paracasei ProSci-92 by measuring the optical density at 600 nm, pH, and viable cell counts. Through response surface optimization, the optimal ratio was determined to be 1.959% trehalose, 1.029% inulin, and 1.582% fructooligosaccharides. Under these conditions, cell density reached 1.629 ± 0.012, and the viable cell count was (6.5 ± 0.28) × 109 cfu/mL, representing increases of 12.3% and 1.67-fold, respectively, compared with the de Man, Rogosa, and Sharpe agar medium control group. The optimized compound was subsequently applied to fermented milk; its rheological properties, texture characteristics, and viable bacterial counts were analyzed using sucrose as the control. The results show that the compound group coagulated 1 h earlier than did the sucrose control, and exhibited higher elasticity and viscosity coefficients. During the 28-d storage period, the pH decreased gradually (final value: 4.16), titratable acidity remained low (final value: 102°T [degrees of titratable acidity]), viable bacterial count remained above 108 cfu/mL, and water-holding capacity averaged 65.86%. Moreover, both textural attributes and sensory evaluation scores improved significantly. Metabolomic analysis identified 87 differential metabolites between the PC92-Oli (experimental) group and the PC92-Suc (control) group, which were primarily associated with the ABC transport system, AA biosynthesis, and carbon metabolism pathways. The compound oligosaccharide mixture activated specific metabolic pathways in the strain, promoted the synthesis of functional metabolites, inhibited fatty acid production, and accelerated extracellular polysaccharide synthesis. These findings provide a strong scientific basis for enhancing the product development and functional properties of probiotic fermented milk, and offer innovative perspectives and strategies for improving its production and storage characteristics.PMID:41780873 | DOI:10.3168/jds.2025-27993

J Dairy Sci. 2026 Mar 2:S0022-0302(26)00164-5. doi: 10.3168/jds.2025-26902. Online ahead of print.ABSTRACTArtificial reproduction technologies (ART) may exert long-term effects on offspring, which have not yet been addressed in dairy cattle. This longitudinal study examined reproductive outcomes and transgenerational effects of embryo recipients conceived by different ART, including artificial insemination (AI) and embryo transfer (ET) with fresh, frozen, and vitrified embryos. For this purpose, in vitro-produced (IVP) embryos were transferred to synchronized recipients (n = 298 ET from AI, and n = 84 ET from IVP-ET origin). Pregnancy on d 40 and 62, birth to term, and gestation length were recorded. From birth until adulthood, calf morphometry (weight, size, and chest perimeter) was monitored (n = 142 animals), and IGF2 methylation and expression were analyzed in peripheral blood lymphocytes (n = 113 samples). The plasma metabolome on d 0 (n = 179 samples) and d 7 (n = 176 samples) and metabolically regulated pathways were compared between estrus-synchronized recipients born by AI and ET. Data were analyzed with generalized mixed models (parametric) and Kruskal-Wallis test (nonparametric). Pregnancy and birth rates did not differ between AI and ET recipients. However, mothers from ET-born recipients were heavier at calving, and their calves showed transgenerational effects, including higher birth weight, size, gestation length, and daily weight gain compared with those from AI recipients. Only calves born from frozen embryos displayed transient IGF2 hypomethylation on d 30, which disappeared later on. In contrast, IGF2 expression decreased on d 0 and 30 in calves born from cryopreserved embryos, and increased in calves aged 2 to14 mo from vitrified embryos, but did not differ thereafter between any group. Among females >6 mo old, those from frozen embryos and AI were heavier and taller than females from vitrified and fresh embryos. Certain metabolite concentrations on d 0 and d 7 differed among recipient groups, mainly in essential amino acids and 1-carbon-generating units metabolites. Overall metabolic differences (Mahalanobis distance matrix) between females were higher in AI than in ET-cryopreserved females on d 0, and in AI versus ET-fresh females on d 7. These findings suggest that ART induces epigenetic and metabolic variations, potentially influencing nutritional efficiency.PMID:41780859 | DOI:10.3168/jds.2025-26902

Cancer Lett. 2026 Mar 2:218393. doi: 10.1016/j.canlet.2026.218393. Online ahead of print.ABSTRACTHepatocellular carcinoma remains a leading cause of cancer mortality worldwide, with peritumoral microenvironment interactions playing a critical role in disease progression. This multi-omics study employed artificial intelligence-pathology, single-nucleus multi-omics, spatial transcriptomics, and metabolomics to characterize peritumoral ductular reactions. Ductular reaction scores strongly predicted poor clinical outcomes and correlated with cirrhosis severity. We identified three functionally distinct cholangiocyte subpopulations, with Small_duct_type_Cho exhibiting robust fibroblast interactions that promote stromal remodeling. Metabolomic profiling revealed tumor margin enrichment of cholic acid, which induced CD8+ T cell dysfunction via NR1H4-dependent PD1 upregulation. Importantly, NR1H4 inhibition synergized with anti-PD1 therapy in murine models, significantly suppressing tumor growth. These results position ductular reactions as both a prognostic biomarker and therapeutic target, with cholic acid/NR1H4 pathway inhibition representing a promising immunotherapeutic strategy for hepatocellular carcinoma patients.PMID:41780844 | DOI:10.1016/j.canlet.2026.218393

Clin Chim Acta. 2026 Mar 2:120937. doi: 10.1016/j.cca.2026.120937. Online ahead of print.ABSTRACTHepatocellular carcinoma (HCC) is frequently diagnosed at an advanced stage due to tumor heterogeneity and chronic liver damage, which reduce the performance of single biomarkers and complicate the clinical interpretation of laboratory results. The genotoxic diethylnitrosamine (DENA)-induced hepatocarcinogenesis model provides a stage-resolved and experimentally controlled framework associated with genotoxic stress, inflammation, and fibrosis, along with metabolic adaptation in target tissues and circulating biofluids. This review summarizes multi-omics data from DENA models and translational cohorts, encompassing genomics/epigenomics, transcriptomics, proteomics, metabolomics, and glycomics, as well as liquid biopsy analytes, including cell-free DNA, extracellular vesicle cargo, and circulating tumor cell markers. We integrated the dynamics of injury progression to fibrosis and tumor development at the pathway scale, highlighting multi-analyte biomarker sets that improve the differentiation between advanced fibrosis/cirrhosis and early hepatocellular carcinoma (HCC). Additionally, we examined enabling technologies in analytical techniques, including targeted mass spectrometry (MS), PCR-based methods, and clinically scalable glycoprofiling. Notably, we propose a stage-aware biomarker selection paradigm that emphasizes mechanistic consistency, analytical viability, and clinical actionability to facilitate earlier identification and longitudinal tracking. Finally, we discuss the practical implications of multicenter validation and a harmonized study design to enhance reproducibility and expedite clinical translation.PMID:41780833 | DOI:10.1016/j.cca.2026.120937

J Nutr. 2026 Mar 2:101453. doi: 10.1016/j.tjnut.2026.101453. Online ahead of print.ABSTRACTBACKGROUND: Independently, diet and exercise can benefit bone health, but they are seldom studied in combination.OBJECTIVE: We investigated how dietary supplementation with tart cherry (TC) alone and in combination with exercise affects bone, and whether this response differs with age.METHODS: Two cohorts of female C57BL/6 mice (6-wk-old;n=12 mice/group & 60-wk-old;n=14 mice/group) were assigned to diets (Control vs. TC diet) and exercise (with vs. without treadmill running) for 8 wks. Bone microarchitecture, biomechanics, and gene expression of regulators of bone cell differentiation and activity were assessed. Data were analyzed using 2-way ANOVA followed by post-hoc testing. Diet effects on serum untargeted metabolomics were analyzed using unpaired t-tests. For all analyses, alpha=0.05.RESULTS: Diet and exercise differentially affected young and aging mice. Both TC (P<0.0001) and exercise (P<0.05) independently increased femoral trabecular bone in young mice. Although exercise failed to increase cortical parameters, it improved bone strength. In the aging cohort, TC treatment improved cortical thickness (P<0.05) and biomechanical properties of the femur. The effects of TC and exercise were not additive in either cohort. Within the bone of young mice, TC increased (P<0.01) the expression of Bmp2, a regulator of osteoblast differentiation and decreased (P<0.01) matrix metalloproteinases (Mmp8 and Mmp9), involved in bone matrix degradation. In the aging mice, TC increased (P<0.05) regulators of osteoblast differentiation (Osx and Bmp2), and TC and exercise independently increased Col1a1, indicative of osteoblast activity. Metabolomics revealed increases in xenometabolites from TC and the gut microbiota (e.g., hippuric acid, methyltyrosine, and methylgalactoside) in both cohorts, which positively correlated with bone parameters.CONCLUSIONS: We conclude there was no added benefit of combining TC with the running protocol used in this study. TC had a pronounced osteogenic effect in both age groups and metabolomic profiling revealed new potential mechanisms by which its bone effects are mediated.PMID:41780825 | DOI:10.1016/j.tjnut.2026.101453

Microb Pathog. 2026 Mar 2:108417. doi: 10.1016/j.micpath.2026.108417. Online ahead of print.ABSTRACTBoesenbergia rotunda (L.) Mansf. rhizome has been traditionally used to treat abscesses, leukoplakia, and leukorrhea. Candida albicans is a major cause of these incidences and can lead to bloodstream infection. This study aimed to evaluate the effectiveness and mechanisms of B. rotunda extract on susceptibility, biofilm formation, and invasion into human endothelial EA.hy926 cells of bloodstream-isolated C. albicans. Their virulence were determined by microdilution, metabolic activity, lactate dehydrogenase release, and internalization assays. Alterations in biomolecule composition were determined by Fourier-transform infrared microspectroscopy. The metabolomic profiles during host-pathogen interactions were assessed with high-resolution accurate-mass spectrometry. The B. rotunda extract consisted of 15.60% (w/w) pinostrobin and 6.02% (w/w) pinocembrin. All strains of C. albicans were not susceptible to the extract at a concentration of 100 μg/mL. The biofilm formation was inhibited only in C. albicans Isolate03 by the B. rotunda extract with IC50 value of 46.03 μg/mL. However, the ability of Isolate03 and Isolate04, invasive phenotypes, to damage the endothelial EA.hy926 cells was significantly inhibited with IC50 values of 27.39 and 30.81 μg/mL, respectively. The extract markedly altered the invasive phenotype's biomolecule composition and metabolomic profiles. The glycogen and carbohydrate compositions were decreased, whereas protein was increased. Moreover, propanoate and glycerolipid metabolism were dramatically regulated. These results suggest that alterations of biomolecule and metabolism could decrease their virulences because metabolic adaptation involved in pathogenic traits of C. albicans. Therefore, the B. rotunda extract might disrupt biomolecule compositions and metabolic pathways of the isolated C. albicans, thereby reducing biofilm formation and tissue invasion.PMID:41780771 | DOI:10.1016/j.micpath.2026.108417

J Control Release. 2026 Mar 2:114774. doi: 10.1016/j.jconrel.2026.114774. Online ahead of print.ABSTRACTExcessive reactive oxygen species (ROS) accumulation and dysregulated inflammation drive acetaminophen (APAP)-induced acute liver injury (ALI), yet the therapeutic effect of the commonly used clinical drug N-acetylcysteine (NAC) still has certain limitations at present. Here, we engineered a multifunctional nanozyme nanocomposite, MPCNH, by in situ deposition of bimetallic PtCu nanoparticles onto UiO-66 metal-organic frameworks (MOFs), loading NAC, and coating with hyaluronic acid (HA) to enhance biocompatibility. MPCNH exhibited cascade superoxide dismutase (SOD)-like and catalase (CAT)-like catalytic activities, enabling rapid ROS clearance and mitochondrial protection in APAP-challenged hepatocytes. Meanwhile, the delivery of the therapeutic drug NAC was achieved. In vivo, MPCNH lowered serum transaminases, activated the Keap1-Nrf2 antioxidant pathway, shifted macrophages polarization toward an anti-inflammatory M2 phenotype and restored metabolic balance. By integrating catalytic and pharmacological functions, MPCNH offers a synergistic strategy to simultaneously eliminate oxidative stress and regulate inflammation, providing a promising therapeutic platform for oxidative stress-driven liver injury.PMID:41780678 | DOI:10.1016/j.jconrel.2026.114774

J Ethnopharmacol. 2026 Mar 2:121460. doi: 10.1016/j.jep.2026.121460. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Aloperine (ALO), an alkaloid derived from Sophora alopecuroides L., demonstrates therapeutic potential against malignant tumors, while the role of ALO and its molecular mechanisms in ovarian cancer remain unclear.AIM OF THE STUDY: This study aims to systematically investigate the efficacy and molecular mechanisms of ALO against ovarian cancer by integrating network pharmacology and metabolomics.MATERIALS AND METHODS: The anti-tumor effect of ALO on ovarian cancer cells was evaluated using CCK-8, colony formation, cell scratch and transwell invasion assay in vitro. An ovarian cancer xenograft mouse model was used to evaluate the anti-ovarian cancer effect of ALO in vivo. Potential targets of ALO in ovarian cancer were predicted via network pharmacology, and the binding affinity of ALO to the potential targets was analyzed using molecular docking techniques. High-performance liquid chromatography-mass spectrometry (HPLC-MS) was used to identify the different metabolites of ALO and their metabolic pathways in ovarian cancer cells, followed by multi-level integrated analysis of network pharmacology and metabolomics results. Metabolite detection kits, western blotting, and qPCR were employed to validate the involved metabolites and their associated target genes.RESULTS: ALO suppressed the proliferation, migration and invasion of ovarian cancer cells SKOV-3 and ES-2 in a dose dependent manner in vitro. Correspondingly, ALO inhibited the growth of ovarian cancer xenografts in vivo. Network pharmacology and molecular docking analysis revealed Mouse double minute 2 homolog (MDM2), Janus kinase 2 (JAK2), Cyclin-dependent kinase 2 (CDK2), Myeloperoxidase (MPO), Janus kinase 1(JAK1) and Androgen receptor (AR) as the potential targets of ALO in ovarian cancer. While metabolomics analysis showed that ALO increases citrate acid and α-ketoglutarate (α-KG) levels in ovarian cancer cells. The integrated metabolomics, network pharmacology, and molecular docking identified that ALO primarily affects the tricarboxylic acid cycle (TCA cycle) and three hub genes, including MDM2, JAK2, and CDK2. In the experimental validation, ALO treatment increased the levels of key metabolites citrate acid and α-KG in the TCA cycle in ovarian cancer cells, while suppressed the levels of pyruvate and lactate, the primary metabolites of glycolysis, ultimately leading to a reduction in cellular ATP content. Moreover, ALO suppressed the glycolytic protein expression of GLUT1, PKM2 and LDHA in ovarian cancer cells. MDM2, JAK2, and CDK2 were identified as the most promising targets of ALO in ovarian cancer.CONCLUSION: ALO demonstrates anti-ovarian cancer effects both in vitro and in vivo through the enhancement of TCA cycle and reversing of aerobic glycolysis in ovarian cancer cells, providing a robust experimental foundation for future investigation of the potential clinical utility of ALO in ovarian cancer therapy.PMID:41780620 | DOI:10.1016/j.jep.2026.121460

J Lipid Res. 2026 Mar 2:101011. doi: 10.1016/j.jlr.2026.101011. Online ahead of print.ABSTRACTOxylipins are oxidized polyunsaturated fatty acids (PUFA) such as hydroxy-PUFA and epoxy-PUFA. Total oxylipins are commonly analyzed following base hydrolysis as non-esterified oxylipins by means of LC-MS/MS. For that, a standard operation procedure has been developed, which was successfully tested in an international interlaboratory comparison (J. Lipid Res. (2020) 61: 1424-1436). Here, we report the concentrations of total oxylipins in NIST SRM 1950 plasma determined by LC-MS/MS analyses in different labs, which are similar to those in other freshly prepared human plasma samples . Hydroxy-PUFA of the long chain PUFA arachidonic acid (ARA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) occur between 1 and 75 nmol/L (0.3-24 ng/mL) and linoleic acid (LA)-derived hydroxy-PUFA up to 400 nmol/L (120 ng/mL). The concentration of ARA, DHA- and EPA-derived epoxy-PUFA ranges between 2 and 20 nmol/L (0.6-6 ng/mL) and LA up to 100 nmol/L (32 ng/mL). We also report 70 oxylipins which cannot be detected (∼<0.5 nmol/L; 0.2 ng/mL), such as multiple hydroxylated PUFA, including so-called SPM (exept for 10,17-DiHDHA), and most isoprostanes. If the plasma is prepared or stored inappropriately, oxylipins are formed by autoxidation, leading to artificially high levels of total oxylipins. This is shown for the concentrations in different commercially available plasma pools of unknown origin, being 100-1000 fold higher. The concentrations provided here for NIST SRM 1950 plasma and freshly prepared plasmathus inform which concentration range of total oxylipins should be expected in human plasma from healthy subjects, and increase the utility of NIST SRM 1950 for analytical quality control protocols.PMID:41780594 | DOI:10.1016/j.jlr.2026.101011

Ecotoxicol Environ Saf. 2026 Mar 3;312:119973. doi: 10.1016/j.ecoenv.2026.119973. Online ahead of print.ABSTRACTAs a widely used triazine herbicide, atrazine (ATR) has been demonstrated to exert neurotoxicity and induce metabolic disorders in organisms. Our previous studies have further revealed that maternal exposure to ATR during pregnancy and lactation can damage dopaminergic neurons in the midbrain of offspring. Current mechanistic investigations into the intergenerational neurotoxic effects of ATR and other environmental factors have mostly focused on regulatory mechanisms at the genetic material level, which present significant limitations. However, there is a lack of relevant experimental evidence to verify whether maternal ATR exposure during these special periods can induce dopaminergic neuronal damage in offspring through alternative pathways, such as altering maternal plasma metabolite levels, and the specific underlying mechanisms remain to be further explored. This study integrated multiple approaches including neurobehavioral assays, plasma metabolomics, bioinformatics, and molecular biology, systematically elucidated the mechanism by which maternal ATR exposure induces intergenerational dopaminergic neurotoxicity in offspring by remodeling the maternal plasma metabolic profile. Furthermore, by combining the analysis of single-cell transcriptomic data from Parkinson's disease patients with molecular docking and molecular dynamics simulation analyses, we revealed for the first time, from the novel perspective of the metabolite-single cell axis, the potential mechanism by which serotonin may mediate dopaminergic neuronal damage in offspring induced by maternal ATR exposure during pregnancy and lactation-specifically by regulating the AKT1/SRC pathway and intercellular crosstalk across multiple cell types. This finding provides new research strategies and directions for understanding the intergenerational neurotoxicity of environmental pollutants and their early prevention.PMID:41780476 | DOI:10.1016/j.ecoenv.2026.119973

Water Res. 2026 Mar 1;296:125672. doi: 10.1016/j.watres.2026.125672. Online ahead of print.ABSTRACTRedox oscillations within riparian ecosystems emerge as a critical threat to carbon sequestration, yet the mechanistic coupling between abiotic drivers and microbial metabolism remains elusive. Through controlled incubation experiments, we demonstrate that redox-oscillating conditions significantly reduce microbial carbon use efficiency (CUE), thus accelerating carbon loss compared to static oxic or anoxic conditions. Mechanistically, redox oscillations drove the cycling of iron (Fe) species, thereby reducing the amorphous Fe pool and liberating mineral-associated organic carbon (MAOC) composed of substantial biodegradable organic substrates (e.g., lipids and proteins). Concurrently, hydroxyl radicals (•OH) generated during Fe(II) oxidation depolymerize complex aromatic organic matter into labile forms. Integrated metagenomic and metabolomic analyses further demonstrated that redox oscillations significantly reshaped soil metabolite profiles and microbial community. In particular, microbial catabolic pathways such as pentose phosphate pathway and the tricarboxylic acid (TCA) cycle were activated to efficiently mineralize newly available substrate. Together, these results identify a coupled abiotic-biotic "prime and burn" mechanism in which Fe-driven substrate reorganization primes microbial differentiation toward enhanced respiration. This study highlights redox-oscillating zones as potential carbon leakage hotpots in the terrestrial carbon sink.PMID:41780450 | DOI:10.1016/j.watres.2026.125672

Food Chem. 2026 Feb 24;509:148525. doi: 10.1016/j.foodchem.2026.148525. Online ahead of print.ABSTRACTThis study revealed the formation mechanism of flavonoid aglycones in Moringa oleifera leaf (MOL) during Monascus anka fermentation via widely targeted metabolomics and data-independent acquisition-based proteomics. Bioactivity assays demonstrated that M. anka fermentation significantly enhanced MOL's bioactivity; total flavonoid and phenolic content, ABTS and DPPH radical scavenging capacities were increased by 226.8%, 45.59%, 1.28-, and 1.25-fold compared with the unfermented control, respectively. Widely targeted metabolomics identified 172 phenolic metabolites, of which flavonoids accounted for 70.9%. Notably, flavonoid aglycones (quercetin and kaempferol) were significantly accumulated during fermentation, being 5.05-, 2.65-, and 5.54-fold higher than the unfermented control. Proteomics analysis identified key carbohydrate-active enzymes associated with cell wall degradation. Importantly, β-glucosidases (GH1, GH3) and α-L-rhamnosidases (GH78) hydrolyzed flavonoid glycosidic linkages, facilitating free aglycone accumulation. Collectively, these findings indicated that M. anka-secreted enzymes exerted catalytic roles in cell wall degradation and flavonoid deglycosylation, providing a theoretical basis for targeted enhancement of MOL bioactivity.PMID:41780433 | DOI:10.1016/j.foodchem.2026.148525

J Environ Manage. 2026 Mar 3;402:129125. doi: 10.1016/j.jenvman.2026.129125. Online ahead of print.ABSTRACTPit bottom wastewater (PBW), a high-strength organic effluent from sauce-flavored Baijiu production, poses considerable environmental challenges. This study explores its valorization as a nutrient medium for biosynthesis of high-value compounds using Monascus purpureus MP-1 isolated from Daqu. Cultivation in 10% PBW-supplemented medium increased biomass by 150% and enhanced hydrolytic enzyme activities. Integrated metabolomic and transcriptomic analyses revealed that PBW supplementation suppressed Monascus pigment biosynthesis but activated the putrescine (Puu) pathway for γ-aminobutyric acid (GABA) synthesis, increasing yield by 50.38% (121.28 μg/mL). Concurrently, organic pollutants were effectively degraded via enhanced lignin catabolism and redox activities. This work establishes a sustainable waste-to-value strategy, demonstrating the potential of Monascus spp. for simultaneous resource recovery and functional metabolite production, offering dual benefits of waste reduction and value creation for the food industry.PMID:41780378 | DOI:10.1016/j.jenvman.2026.129125

Plant Physiol Biochem. 2026 Feb 7;232:111114. doi: 10.1016/j.plaphy.2026.111114. Online ahead of print.ABSTRACTUltraviolet-B (UV-B) radiation in the Qinghai-Tibet Plateau (QTP) is a crucial environmental constraint affecting plant distribution and development. E. sibiricus is an important perennial grass species used for pasture establishment and grassland restoration in the QTP, whose molecular adaptation to UV-B stress remains underexplored. Herein, phenotypic physiology, transcriptomics, and metabolomics were integrated to systematically decipher UV-B response mechanisms in E. sibiricus. Exposure to 288 kJ/m2 UV-B radiation in tolerant (SC020 2-A1, SC) and sensitive (XJ007 22-A5, XJ) E. sibiricus genotypes yielded 21,773 genes, with 5076 and 4541 genotype-specific differentially expressed genes (DEGs), respectively. Temporal profiling of the DEGs revealed 3792 and 6322 DEGs in SC, compared to 4826 and 10,890 DEGs in XJ under short- and long-term stress, respectively. Core findings demonstrated that MYB and WRKY transcription factors (TFs) mediated UV-B responses via phenylpropanoid metabolism and UVR8 signaling. In addition, 20 pivotal TFs, including EsMYB and EsbHLH, coordinated with 30 stress metabolites, such as corticosterone, to regulate the ascorbate and aldarate network, thereby activating 8 crucial pathways, including photosynthetic carbon fixation. Notably, heat shock proteins (HSP702 and HSP704) emerged as novel UV-B resistance components. These results provide molecular insights into UV-B adaptation of members of the Gramineae family and genetic resources for breeding UV-B radiation-resistant grass cultivars.PMID:41780311 | DOI:10.1016/j.plaphy.2026.111114

Cytokine. 2026 Mar 3;201:157135. doi: 10.1016/j.cyto.2026.157135. Online ahead of print.ABSTRACTOBJECTIVE: Cow milk protein allergy (CMPA), a common food allergy in early childhood, involves type 2 immune cells such as group 2 innate lymphoid cells (ILC2s). Linoleic acid (LA) is a polyunsaturated fatty acid with immunomodulatory properties. Although its role in CMPA is not yet clear, previous metabolomics research by our team revealed elevated levels of linoleic acid in the intestinal ILC2s of allergic mice. In this study, the effects of linoleic acid on ILC2 activation and the mechanisms underlying this activation were explored using a mouse model of CMPA.METHODS: The linoleic acid content of intestinal ILC2s from milk protein-allergic mice was measured. Flow cytometry was used to analyse the effects of linoleic acid on the proportion of ILC2s and the release of IL-5/IL-13. The PPARα agonist WY14643 and the NF-κB signalling pathway inhibitor MLN120B were used to study immune regulation, and transcriptomic sequencing was performed to elucidate the underlying molecular mechanism.RESULTS: Compared with control mice, allergic mice presented ILC2s with increased LA levels, increased proportions of ILC2s, and increased IL-5/IL-13 release. PPARα agonists reduced the proportion of ILC2s and decreased inflammation and allergic reactions. Transcriptomic analysis revealed that LA may activate the NF-κB signalling pathway; its inhibition reduced the proportions of ILC2s and the levels of cytokines in CMPA mice.CONCLUSION: Linoleic acid may regulate ILC2s via the NF-κB signalling pathway and thereby promote IL-5/IL-13 release and exacerbate inflammation in CMPA mice. Inhibition of LA enrichment or the NF-κB signalling pathway may be potential therapies for CMPA in early childhood.PMID:41780286 | DOI:10.1016/j.cyto.2026.157135