PubMed

Front Artif Intell. 2026 Aug 24;9:1901969. doi: 10.3389/frai.2026.1901969. eCollection 2026.ABSTRACTUntargeted metabolomics, anchored in high-resolution mass spectrometry, has matured into the central analytical platform of human exposomics. It can capture endogenous biology, diet, drugs, microbial chemistry, environmental contaminants, and their transformation products from a single biological sample. Yet exposome science remains stubbornly single-study: most untargeted exposomics publications stand alone, featuring tables, partial annotations, and semi-quantitative intensities that cannot be combined across cohorts. The bottleneck is no longer instrumentation or annotation; it is interoperability. Existing standards, including MSI, mQACC, BP4NTA, NORMAN, MERIT, mzML, mzTab-M, ISA-Tab, the Universal Spectrum Identifier, RefMet, ChEBI, MetaboLights, Metabolomics Workbench, GNPS/MassIVE, and the emerging GA4GH human exposome data standards, cover the necessary ingredients but do not yet compose a single, executable profile. I argue that the next stage of exposomics must move from FAIR deposition to meta-analysis-ready evidence: a four-layer stack of acquisition comparability, machine-readable reporting, evidence-aware annotation, and standardized summary statistics, validated by a living community benchmark. Cumulative exposome science depends on it.PMID:42707398 | PMC:PMC13547244 | DOI:10.3389/frai.2026.1901969

Front Nutr. 2026 Aug 24;13:1795141. doi: 10.3389/fnut.2026.1795141. eCollection 2026.ABSTRACTBACKGROUND: Aortic aneurysm (AA) is a life-threatening cardiovascular condition with a strong genetic component, however, its molecular mechanisms remain poorly understood. Although genome-wide association studies (GWAS) have identified numerous risk loci, most prior studies have investigated genetic and metabolic factors separately, leaving the causal pathways from genetic variants to disease largely unexplored.METHODS: We established an integrative framework combining cross-tissue transcriptome-wide association studies (TWAS) with metabolomic mediation analysis. First, we integrated GWAS data from FinnGen R12 with multi-tissue expression quantitative trait loci (eQTL) data from Genotype-Tissue Expression Project (GTEx) V8, then performed cross-tissue TWAS using the Unified Test for MOlecular SignaTures (UTMOST) and single-tissue validation with the Functional Summary-based Imputation (FUSION) to prioritize susceptibility genes. Second, we applied Mendelian randomization (MR), colocalization, and Fine-mapping Of CaUsal gene Sets (FOCUS) to assess causality and identify high-confidence genes. Third, we performed metabolite mediation analysis to uncover metabolic pathways linking genetic variants to disease risk. Finally, we validated key findings in mouse models of thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA) using Quantitative Real-Time Reverse Transcription Polymerase Chain Reaction (RT-qPCR) and Western blotting.RESULTS: We identified multiple novel susceptibility genes for AA and its subtypes. Key genes included ADH family members (ADH1A, ADH1B, ADH4, ADH6) and ZNF827, which showed cross-subtype associations with strong colocalization evidence in vascular tissues. Metabolite mediation analysis revealed significant pathways involving N-acetylphenylalanine and methionine sulfoxide. Functional enrichment revealed distinct biological mechanisms: AA and AAA were primarily associated with metabolic pathways, whereas TAA-related genes were enriched in developmental and contractile processes. PheWAS indicated no significant off-target associations. Critically, experimental validation in mouse models confirmed significant upregulation of ZNF827 in TAA and ADH6 in AAA at both mRNA and protein levels, corroborating the genetic predictions.CONCLUSION: This integrated cross-omics analysis identifies novel genetic loci and, crucially, uncovers specific nutrient-related metabolic pathways that mediate genetic risk. These findings provide a mechanistic basis for future nutritional and metabolic intervention studies in AA and its subtypes.PMID:42707359 | PMC:PMC13547935 | DOI:10.3389/fnut.2026.1795141

Front Nutr. 2026 Aug 24;13:1849329. doi: 10.3389/fnut.2026.1849329. eCollection 2026.ABSTRACTBACKGROUND: Metabolically dysfunction-associated steatotic liver disease (MASLD) is the most prevalent liver disease worldwide and is increasing in parallel with metabolic syndrome and obesity. In this exploratory, cross-sectional study, we analysed metabolic changes in the blood and urine of patients with early-stage MASLD (fibrosis grades 0, 1, and 2) to identify metabolites associated with disease presence and the prevalent fibrosis stage and to develop machine learning models for case discrimination and fibrosis-stage stratification.METHODS: Fifty-one metabolites, including17 urinary organic acids, 14 blood amino acids, 19 blood acylcarnitines/free carnitine, and glucose, were quantified in 232 participants (100 controls and 132 patients with MASLD: 68 F0, 34 F1, and 30 F2) using gas chromatography-mass spectrometry (GC/MS) and tandem mass spectrometry (MS/MS). MASLD-associated metabolites were visualised using volcano plots, cluster heatmaps, and a metabolic network diagram. Three machine learning approaches, namely, orthogonal partial least squares discriminant analysis (OPLS-DA), random forest (RF), and support vector machines (SVM), were implemented within a strictly leakage-free pipeline (feature selection and preprocessing performed within training folds only), with performance evaluated on independent test sets and validated by permutation testing and repeated cross-validation.RESULTS: A case-discrimination panel comprised β-hydroxy butyrate, adipic acid, acylcarnitines (C0, C2, C3, C10:1, C14:1, and C18:1), formiminoglutamate, glucose, glycine, citric and lactic acids, Leu/Ile, pyroglutamate, sebacic and suberic acids, tiglylglycine, and valine. A stage-stratification panel comprising valine, ethylmalonate, glycine, acylcarnitines (C0, C8:1, C2, C5, C16, C10, C18, and C18:1), Leu/Ile, alanine, glutamine, pyroglutamate, 3-hydroxybutyrate, succinate, vanillylmandelate, and citrulline was associated with MASLD severity. Metabolite-based models discriminated disease status more effectively than FIB-4 (AUC 0.74) and APRI (AUC 0.70) in this cohort; permutation testing (OPLS-DA permutation p ≤ 0.001; random-forest empirical p ≈ 0.01) confirmed the models captured genuine biological structure rather than random patterns.CONCLUSION: Machine learning applied to targeted blood and urinary metabolomics identified candidate metabolite signatures associated with early-stage MASLD and fibrosis stage. These findings are exploratory and hypothesis-generating; prospective, externally validated studies with metabolically matched comparators are required before clinical application.PMID:42707340 | PMC:PMC13547064 | DOI:10.3389/fnut.2026.1849329

Front Endocrinol (Lausanne). 2026 Aug 24;17:1901830. doi: 10.3389/fendo.2026.1901830. eCollection 2026.ABSTRACTAIMS: Despite growing evidence implicating FN3K in the pathogenesis of cancer and diabetes, its precise role in modulating renal tubular injury within the context of diabetic nephropathy has yet to be fully elucidated.MATERIALS AND METHODS: FN3K expression was examined in DKD model mice, human kidney biopsy samples, and high glucose-treated HK-2 cells via immunohistochemistry (IHC) and Western blotting. Associations between serum FN3K levels and DKD risk were analyzed in the Kidney Precision Medicine Project cohort via multivariable logistic regression, restricted cubic spline modelling, and receiver operating characteristic (ROC) analysis. Regional proteomics, single-cell RNA sequencing, untargeted metabolomics, and joint pathway analyses were integrated to delineate FN3K-associated pathways and cell type-specific metabolic alterations. The effect of FN3K on mitochondrial function was evaluated using Mitochondrial respiratory chain activity assays.RESULTS: FN3K expression was significantly reduced in the renal tubular compartments of DKD mice and patients and was downregulated by high glucose in HK-2 cells. Low circulating FN3K levels were independently associated with increased DKD risk and improved diagnostic performance when combined with conventional biomarkers. Proteomic and single-cell analyses revealed the activation of PI3K/AKT signaling and the suppression of mitochondrial metabolic pathways in DKD tubules, whereas FN3K-high proximal tubule cells presented increased oxidative phosphorylation and reduced inflammatory and apoptotic signaling. Metabolomic profiling demonstrated that FN3K overexpression restored the levels of mitochondrial- and nitrogen-related metabolites and attenuated injury-associated lipid remodeling. Joint pathway analysis highlighted nitrogen and glutathione metabolism as convergent FN3K-related signatures. Over-expression of FN3K would improves the function of mitochondrial respiratory chain I and III activity.CONCLUSIONS: FN3K deficiency is associated with tubular injury and DKD progression, potentially through increased glycation stress, mitochondrial metabolic dysfunction.PMID:42707184 | PMC:PMC13546999 | DOI:10.3389/fendo.2026.1901830

Clin Transl Med. 2026 Sep;16(9):e70796. doi: 10.1002/ctm2.70796.ABSTRACTBACKGROUND: Lung adenocarcinoma (LUAD) remains a leading cause of cancer mortality, and current therapies are limited by drug resistance and toxicity. Ferroptosis offers an attractive strategy for cancer therapy, but classical ferroptosis is iron‑dependent. Repurposing approved drugs offers a rapid strategy to identify novel anti‑LUAD agents, yet the mechanism by which 4‑Hydroxytamoxifen (4‑OHT) exerts estrogen receptor-independent anti‑tumour effects remains unclear.METHODS: We performed a drug repurposing screen of 950 endogenous metabolites in LUAD cells. Anti‑tumour activity was validated in vitro and in vivo using LUAD cell lines and mouse models. Target identification and mechanistic studies employed LiP‑MS, pull-down SPR, CETSA, metabolomics, and enzyme activity assays. Clinical relevance was assessed via tissue microarrays and TCGA analysis. Drug synergy was quantified using the Chou-Talalay method.RESULTS: 4‑OHT inhibited LUAD cell proliferation with IC50 values of 3.86 ± 0.26 µM to 13.58 ± 0.55 µM independent of estrogen receptor. It triggered noncanonical ferroptosis characterised by GSH depletion (reduced by about 60%), GPX4 downregulation, lipid peroxidation (about 2.5-fold increase), and iron independence. Mechanistically, 4‑OHT directly bound AKR1B10 (KD(M) was 7.98e-06) and inhibited its enzymatic activity, leading to ACC1 degradation, lipid deficiency, and accumulation of toxic lipid‑derived carbonyls. AKR1B10 knockout abolished 4‑OHT‑induced cell death, while rescue restored sensitivity. Nanatinostat similarly targeted AKR1B10 and induced the same cell death modality. AKR1B10 upregulation in LUAD tissues correlated with reduced overall survival rates.CONCLUSION: This study demonstrates that 4‑OHT directly inhibits AKR1B10 enzymatic activity to induce a noncanonical ferroptosis in LUAD. AKR1B10 overexpression correlates with poor prognosis and chemoresistance in LUAD patients. Nonetheless, AKR1B10 inhibition warrants further investigation as a therapeutic strategy.HIGHLIGHTS: 4‑OHT directly inhibits AKR1B10 enzymatic activity to induce noncanonical ferroptosis in LUAD. AKR1B10 sustains LUAD survival by stabilising ACC1 and detoxifying reactive carbonyl species (RCSs). Nanatinostat similarly targets AKR1B10 and elicits the same cell death modality. AKR1B10 overexpression correlates with poor prognosis and chemoresistance in LUAD.PMID:42707018 | DOI:10.1002/ctm2.70796

J Exp Bot. 2026 Sep 8:erag448. doi: 10.1093/jxb/erag448. Online ahead of print.ABSTRACTGrapevine cultivars vary widely in monoterpenoid content, yet the genetic and regulatory mechanisms underlying this variation remain poorly characterized beyond highly aromatic Muscat types. We profiled free volatiles and monoterpenoid glycosides in a Riesling × Cabernet Sauvignon F1 mapping population, revealing extensive variation and transgressive segregation consistent with multigenic control. QTL mapping identified 70 significant loci associated with 48 volatile compounds and monoterpene glycosides, including two major QTLs explaining 33.6% and 33.4% of phenotypic variance in (3S)-linalool accumulation. Integration of haplotype-resolved transcriptomics with metabolite data, enabled by a chromosome-scale diploid Riesling genome assembly, resolved a (3S)-linalool/nerolidol synthase cluster on chromosome 10 and identified VviTPS54 as the strongest candidate underlying linalool variation. VviTPS54 exhibited haplotype-specific expression strongly correlated with (3S)-linalool accumulation across genotypes, while no QTL was detected at the 1-deoxy-D-xylulose-5-phosphate synthase 1 (VviDXS1) locus previously identified in Muscat cultivars. In addition, VviDXS1 expression was not correlated with terpene levels, indicating that regulatory variation within terpene synthase clusters, rather than methylerythritol phosphate (MEP) pathway flux, drives monoterpenoid composition in this population. These results establish regulatory variation of terpene synthases as a key mechanism underlying monoterpenoid diversity in grapevine and demonstrate that resolving such variation requires haplotype-phased genome assemblies coupled with haplotype-resolved transcriptomics to detect allele-specific expression differences at complex, heterozygous loci.PMID:42706918 | DOI:10.1093/jxb/erag448

J Sci Food Agric. 2026 Sep 8. doi: 10.1002/jsfa.71036. Online ahead of print.ABSTRACTBACKGROUND: Pigeon albumen exhibits superior gel properties and a characteristic translucent appearance, yet substantial variation in albumen transparency exists among individual eggs. The molecular basis underlying this quality difference remains poorly understood, particularly regarding protein and metabolite compositional profiles.RESULTS: We employed label-free quantitative proteomics and untargeted metabolomics to compare transparent and opaque pigeon egg albumen. A total of 55 differentially expressed proteins and 34 differential metabolites were identified. Transparent albumen showed marked upregulation of endoplasmic reticulum-resident chaperones (BiP, calreticulin) and protein disulfide isomerases, whereas vesicle-trafficking proteins (RAB7A, ACTR2) were downregulated. Metabolically, lysophospholipids were the most substantially increased compounds (LysoPA, fold change [FC] = 2.22; LysoPI, FC = 2.14), while l-carnitine (FC = 0.48) and 2-methyl-5-vinylpyrazine (FC = 0.46) were the most decreased. Integrated correlation network analysis revealed 99 significant protein-metabolite associations, predominantly involving polyphenolic compounds.CONCLUSION: These compositional profiles suggest that enhanced endoplasmic reticulum protein folding capacity, altered lipid composition, and redox-related modifications collectively distinguish transparent from opaque albumen. Our findings provide quantitative molecular evidence for albumen quality variation in pigeon eggs and inform composition-based strategies for quality grading, feed optimization, and processing innovation in the poultry industry. © 2026 Society of Chemical Industry.PMID:42706888 | DOI:10.1002/jsfa.71036

Plant Cell Environ. 2026 Sep 7. doi: 10.1111/pce.70869. Online ahead of print.ABSTRACTGall induction by hymenopteran gall wasps is one of the most sophisticated forms of plant-insect interaction, in which insects manipulate plant development to produce specialized, nutrient-rich structures that support their growth and reproduction. Despite substantial advances, the biochemical and molecular mechanisms underlying gall formation remain incompletely understood. This review synthesizes current knowledge on gall induction, focusing insect-derived signals, phytohormonal regulation, host developmental reprogramming, nutrient manipulation, and defense modulation. Evidence from physiological, transcriptomic, proteomic, and metabolomic studies indicates that gall development involves extensive reprogramming of host cellular, developmental, metabolic, and defense-related pathways. Altered auxin and cytokinin dynamics are associated with abnormal cell proliferation, tissue differentiation, vascular reorganization, and nutrient sink establishment, while gall-inducing wasps modulate host defenses through changes in oxidative signaling, secondary metabolism, and gene expression. Host genotype influences gall outcomes, with resistant plants exhibiting stronger defenses and restricted gall development. Collectively, available evidence suggests that gall formation results from the coordinated interaction of developmental, hormonal, metabolic, and defense-related processes. However, candidate insect-derived effectors may trigger phytohormonal alterations, nutrient sink formation, and defense modulation, collectively contributing to the reprogramming of host tissues into specialized organs that support insect development. Future multi-omics and functional studies are needed to identify key drivers of gall induction and host manipulation.PMID:42706810 | DOI:10.1111/pce.70869

Zool Res. 2026 Sep 18;47(5):1691-1702. doi: 10.24272/j.issn.2095-8137.2025.447.ABSTRACTHolometabolous insects make cocoons during larval-pupal metamorphosis to protect the pupal phase. The materials used for cocoon construction vary widely. Lepidopteran insects typically secrete silk to form cocoons, which display diverse colors. The eri silkworm, Samia cynthia ricini, is an economically important domesticated species that mostly produces white cocoons, with some varieties producing red cocoons. The enzyme kynureninase (KYNU), acquired from bacteria by horizontal gene transfer, has previously been implicated in insect coloration, while the tryptophan metabolite 3-hydroxyanthranilic acid (3-HAA) has been identified as a red pigment. However, exactly how KYNU is involved in cocoon pigmentation remains unclear. Here, we report that a horizontally transferred bacterial gene encoding KYNU regulates red cocoon formation. Metabolomic analysis revealed a high accumulation of 3-HAA in red cocoons, confirming its role as the primary pigment and associating the coloration with tryptophan metabolism. Quantitative real-time polymerase chain reaction (qPCR) analysis indicated that SrKYNU is highly expressed in the silk glands and significantly downregulated in the red cocoon strain compared to the white cocoon strain. Genomic sequencing identified a 141 bp deletion in the upstream regulatory region of KYNU in the red cocoon strain compared to the white cocoon strain. Dual-luciferase assays confirmed that this deletion significantly reduced promoter activity. CRISPR/Cas9 knockout of SrKYNU in the white-cocoon strain resulted in mutants producing red cocoons with elevated 3-HAA content. These findings reveal that the horizontally transferred gene SrKYNU exhibits tissue-specific expression and regulates cocoon coloration in S. ricini, illustrating that horizontal gene transfer can play an important role in regulating an insect physiological process.PMID:42706795 | DOI:10.24272/j.issn.2095-8137.2025.447

J Pediatr Gastroenterol Nutr. 2026 Sep 7. doi: 10.1002/jpn3.70567. Online ahead of print.ABSTRACTOBJECTIVES: Long-chain polyunsaturated fatty acids (LC-PUFAs) are integral components of cell membranes and serve as precursors of bioactive lipid mediators known as oxylipins. Although oxylipins have been identified in human milk (HM), their temporal dynamics and relationships with precursor LC-PUFAs during early lactation, particularly in preterm milk, remain under-examined. This study characterized longitudinal changes in LC-PUFAs and oxylipins in HM from Japanese mothers of moderately preterm infants during the first 3 weeks of lactation.METHODS: HM samples were collected weekly for 3 consecutive weeks from breastfeeding women who delivered infants born moderately preterm (30-34 weeks of gestation). Analyses were performed on 50 HM samples from 21 participants. Selected precursor fatty acids and their derived oxylipins were quantified using liquid chromatography-tandem mass spectrometry.RESULTS: Despite significant declines in milk arachidonic acid (AA) and docosahexaenoic acid (DHA) concentrations over the first 3 weeks of lactation, many corresponding oxylipins remained stable or increased. All measured linoleic acid (LA)-derived oxylipins increased significantly (p < 0.01) despite constant LA concentrations. Several n-3-derived oxylipins, including α-linolenic acid (ALA)-derived 13-hydroxy-9,11,15-octadecatrienoic acid (13-HOTrE), eicosapentaenoic acid (EPA)-derived 15-hydroxyeicosapentaenoic acid (15-HEPE) and DHA-derived protectin DX also increased by Week 3. Although some selected oxylipins were positively associated with their precursor fatty acids, the temporal oxylipin trajectories were not consistently aligned with changes in precursor concentrations.CONCLUSION: These findings highlight the dynamic, pathway-specific regulation of bioactive lipid mediators in preterm HM and provide a biochemical basis for future studies investigating the potential relationship between these mediators and prematurity-related morbidity.PMID:42706736 | DOI:10.1002/jpn3.70567

Autophagy. 2026 Sep 7:1-17. doi: 10.1080/15548627.2026.2719430. Online ahead of print.ABSTRACTTORC1 is a central regulator of cell growth whose inactivation under conditions of nutrient deprivation triggers adaptive responses, including macroautophagy/autophagy, amino acid uptake, and sexual differentiation. Autophagy-deficient fission yeast cells display mating defects and are unable to recover from amino acid starvation, even when external amino acids are available. Here, we investigate how TORC1 signaling and autophagy interact to control these processes. We show that both major phenotypes of autophagy-deficient cells - their inability to resume growth after amino acid starvation and their mating defects - stem from insufficient intracellular amino acid pools. Genetic or environmental enhancement of intracellular amino acid pools alleviates both defects. During leucine starvation, deletion of any1 rescues the growth defect of atg1Δ mutants by maintaining amino acid transporters at the plasma membrane, promoting amino acid uptake. Importantly, we uncover a previously unrecognized role for autophagy in the cell-cycle remodeling required for sexual differentiation. Nitrogen depletion-mediated TORC1 inactivation initiates these cell-cycle rearrangements required to start the mating/meiosis program, but autophagy is specifically required for the final G2-to-G1 arrest that precedes the program. This step correlates with the accumulation of the cyclin-dependent kinase inhibitor Rum1. Metabolomic analyses reveal that intracellular amino acid pools drop sharply during nitrogen starvation, especially in autophagy-deficient cells, and supplementation with trace amino acids restores their ability to complete the final G2-to-G1 transition. Together, our results reveal that autophagy sustains intracellular amino acid pools during prolonged stress, enabling TORC1 reactivation and cell-cycle remodeling necessary for successful mating and meiosis.Abbreviations: DNA: deoxyribonucleic acid; FACS: fluorescence-activated cell sorting; GATOR1: GAP activity toward Rags 1; GATOR2: GAP activity toward Rags 2; GFP: green fluorescent protein; MM: minimal medium; N: nitrogen; PCR: polymerase chain reaction; RNA: ribonucleic acid; S. cerevisiae: Saccharomyces cerevisiae; S. pombe: Schizosaccharomyces pombe; TOR: target of rapamycin; TORC1: target of rapamycin complex 1; TORC2: target of rapamycin complex 2; tRNA: transfer ribonucleic acid; YE5S: yeast extract 5 amino acid supplemented; WT: wild-type.PMID:42706721 | DOI:10.1080/15548627.2026.2719430

J Sci Food Agric. 2026 Sep 7. doi: 10.1002/jsfa.71071. Online ahead of print.ABSTRACTBACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent global health concern with limited therapeutic options. Alpha-lipoic acid (ALA), a naturally occurring organosulfur compound with potent antioxidant activity, shows hepatoprotective potential, but its mechanisms along the gut-liver axis remain poorly understood. This study investigated whether ALA ameliorates high-fat diet (HFD)-induced MASLD by repairing the intestinal barrier and restoring gut microbiota-mediated primary bile acid (BA) signaling.RESULTS: In C57BL/6 mice fed an HFD with or without ALA supplementation (60 mg/kg/d) for 12 weeks, ALA significantly attenuated HFD-induced obesity, dyslipidemia, insulin resistance, and hepatic injury (steatosis, apoptosis, oxidative stress), without altering caloric intake. ALA restored intestinal barrier function by up-regulating tight junction proteins (Occludin, ZO-1) and mucin (Muc2), reducing systemic inflammation and metabolic endotoxemia. Integrated 16S rRNA sequencing and targeted BA metabolomics revealed that ALA selectively enriched beneficial gut bacteria (e.g., Akkermansia, Lactobacillus) and reversed HFD-induced depletion of primary BAs including cholic acid (CA) and chenodeoxycholic acid (CDCA). These restored primary BAs were positively correlated with the enriched microbial taxa.CONCLUSION: These findings elucidate a novel 'gut microbiota-primary bile acid' axis underlying the hepatoprotective effects of dietary ALA, supporting its potential as a functional food component or dietary supplement for MASLD management. © 2026 Society of Chemical Industry.PMID:42706705 | DOI:10.1002/jsfa.71071

J Cell Mol Med. 2026 Sep;30(17):e71354. doi: 10.1111/jcmm.71354.ABSTRACTFurong Tongmai capsule (FRTM) is a traditional Chinese medicine formula with reported lipid-lowering and anti-inflammatory activities, but its mechanisms in atherosclerosis (AS) remain unclear. In ApoE-/- mice fed a high-fat diet, FRTM administration improved serum lipid profiles by reducing total cholesterol, triglycerides and low-density lipoprotein cholesterol and increasing high-density lipoprotein cholesterol. FRTM also attenuated aortic lesion formation, reduced pro-inflammatory cytokines (IL-6, IL-1β and TNF-α), and improved oxidative stress indices. 16S rRNA sequencing showed that FRTM reshaped the gut microbiota, increasing beneficial taxa such as Lactobacillus and Bifidobacterium while decreasing Turicibacter. Functional prediction and untargeted serum metabolomics both suggested that arachidonic acid metabolism was a key pathway affected by FRTM. Furthermore, FRTM was associated with increased p-PPARγ and EP4 expression, decreased p-P65, and increased p-STAT3/STAT3, accompanied by downregulation of M1 markers (iNOS/Nos2) and upregulation of M2 markers (CD206 and ARG1). Faecal microbiota transplantation from FRTM-treated donors partially recapitulated the anti-atherosclerotic and anti-inflammatory effects. Overall, these findings suggest that FRTM may ameliorate AS in a murine model by modulating gut microbiota, arachidonic acid metabolism and macrophage polarization; however, further functional studies are needed to establish causality and assess translational relevance.PMID:42706702 | DOI:10.1111/jcmm.71354

J Sci Food Agric. 2026 Sep 7. doi: 10.1002/jsfa.71062. Online ahead of print.ABSTRACTBACKGROUND: Yunnanopilia longistaminea is an esteemed woody vegetable native to southwestern China, with high culinary desirability and economic value. Its nutritional quality varies markedly across monthly harvests, which may influence market valuation and guide strategies for product development and commercial utilization.RESULTS: This study characterized the monthly variation in nutritional components and metabolomic profiles of Y. longistaminea tender shoots and evaluated their associations with climatic and environmental factors. The results showed that carbohydrate levels remained relatively stable, whereas soluble proteins, chlorophyll, polyphenols and amino acids exhibited significant monthly fluctuations. These variations were closely associated with precipitation, humidity, temperature, and solar radiation. Untargeted liquid chromatography-tandem mass spectrometry metabolomic profiling identified terpenoids and flavonoids as the major differential metabolite classes contributing to monthly discrimination. Integration with environmental data showed that terpenoids were generally associated with higher temperature and lower precipitation and humidity, whereas flavonoids accumulated at higher levels under relatively humid conditions with lower temperature and reduced radiation intensity. These results suggest distinct environment-associated accumulation patterns for terpenoid and flavonoid metabolites.CONCLUSION: Samples harvested in February exhibited the most favorable overall nutritional and metabolomic profiles, with relatively high levels of essential nutrients and bioactive metabolites. These findings provide new insights into the monthly dynamics and environmental associations of nutritional quality in Y. longistaminea, suggesting February as a preliminary optimal harvest period under the single-year study conditions, and offering practical guidance for cultivation management and industrial applications. © 2026 Society of Chemical Industry.PMID:42706678 | DOI:10.1002/jsfa.71062

Pest Manag Sci. 2026 Sep 7. doi: 10.1002/ps.71286. Online ahead of print.ABSTRACTBACKGROUND: Prothioconazole (PTC) is one of the most widely used triazole fungicides worldwide, while its major metabolite, prothioconazole-desthio (dPTC), exhibits enhanced toxicological potential. However, the metabolic perturbations induced by chronic PTC exposure and sensitive biomarkers for exposure monitoring remain poorly understood. This study aimed to elucidate the metabolic toxicity mechanisms of PTC and identify reliable biomarkers using integrated in vitro and in vivo metabolomics.RESULTS: Cytotoxicity assays demonstrated significant differences in the toxicity of eight representative pesticides toward L-02 hepatocytes, with half-maximal inhibitory concentration (IC50) values of 102.8 and 167.3 μmol L-1 for PTC and dPTC, respectively. Untargeted metabolomics revealed that PTC exposure significantly disturbed lipid metabolism, nicotinate metabolism, amino acid metabolism, and mitochondrial energy homeostasis. Corticosterone, equol, and uric acid exhibited excellent discriminatory performance (area under the curve (AUC) > 0.95) and were identified as potential cellular biomarkers of exposure. In C57BL/6J mice, chronic PTC exposure for 28 days induced systemic metabolic disturbances involving the tricarboxylic acid cycle, lysine degradation, and host-microbiota co-metabolism. Targeted metabolomics further validated significant increases in succinic acid, heptanedioic acid, and 2-oxohexanedioic acid, together with a marked decrease in indole-3-propionic acid, consistent with the untargeted metabolomics results. These metabolites demonstrated high sensitivity and specificity for discriminating PTC exposure.CONCLUSIONS: This study demonstrates that chronic PTC exposure disrupts mitochondrial energy metabolism and multiple metabolic pathways, leading to systemic metabolic dysfunction. The identified metabolic biomarkers provide promising tools for pesticide biomonitoring and mechanistic toxicity assessment, improving exposure surveillance and health risk evaluation of triazole fungicides. © 2026 Society of Chemical Industry.PMID:42706637 | DOI:10.1002/ps.71286

Sci Rep. 2026 Aug 5;16(1):27951. doi: 10.1038/s41598-026-63063-4.ABSTRACTMaternal nutrition during gestation can shape offspring skeletal muscle development, but its long-term effects on the beef cattle muscle lipidome remain poorly understood. This study investigated whether gestational protein-energy supplementation is associated with lipidomic signatures in the Longissimus thoracis muscle of Nellore offspring. Targeted multiple reaction monitoring-based lipidomics was applied to 14 samples, including 7 non-programmed (NP) and 7 fetal-programmed (FP) animals. Of 3,437 multiple reaction monitoring transitions evaluated, 408 lipid features were retained for downstream analyses. Lipidomic profiles were explored using multivariate analyses, univariate filtering, pathway enrichment, triacylglycerol chain-length and unsaturation summaries, and correlations with meat-quality traits. Gestational supplementation was associated with subtle but detectable shifts in the skeletal muscle lipidome. Ten lipid features met nominal p-value and fold-change criteria, although none remained significant after false-discovery-rate correction. These features involved membrane-related and bioactive lipid classes, including phosphatidylcholines, phosphatidylethanolamines, sphingomyelins, ceramides, diacylglycerols, phosphatidylglycerols, and selected triacylglycerols, whereas triacylglycerol chain-length and unsaturation distributions remained stable. Overall, this study highlights lipidomics as a promising approach to identify candidate molecular signatures of fetal programming in beef cattle, requiring validation in larger cohorts.PMID:42706303 | DOI:10.1038/s41598-026-63063-4

Sci Rep. 2026 Sep 7;16(1):27970. doi: 10.1038/s41598-026-65449-w.ABSTRACTHeat stress is a major environmental constraint limiting plant growth and productivity, including in mungbean (Vigna radiata). Although physiological, biochemical, and molecular responses of mungbean to elevated temperature have been widely investigated, the role of heat stress-induced leaf lipidome reconfiguration in thermotolerance remains insufficiently understood. In this study, we examined physiological, biochemical, and lipid metabolic responses to heat stress in two contrasting mungbean genotypes: PI425243 (heat-tolerant) and PI223002 (heat-sensitive), grown under non-stress (34/25 °C day/night) and heat stress (42/30 °C day/night) conditions. Heat stress significantly affected physiological traits, including chlorophyll index (SPAD), relative leaf water content, and electrolyte leakage, and altered biochemical responses, including proline accumulation, malondialdehyde content, and antioxidant enzyme activities (superoxide dismutase, peroxidase, and catalase). Lipidomic profiling identified 178 lipid species spanning major membrane lipid classes, including phospholipids and glycolipids, across both genotypes and treatments. Heat stress induced distinct lipid remodeling patterns between genotypes, with the heat-tolerant genotype PI425243 showing reduced membrane lipid unsaturation, reflected by lower proportions of polyunsaturated linolenic acid (18:3)-containing lipid species and increased abundance of less unsaturated and saturated fatty acids, particularly oleic (18:1) and linoleic (18:2)-containing species. Responsive lipid classes included major membrane phospholipids and chloroplast-associated glycolipids, indicating differential membrane adaptation under thermal stress. These findings suggest that heat-associated lipid remodeling is linked with enhanced membrane stability and improved heat adaptation in mungbean and highlight lipid signatures as potential biomarkers for screening climate-resilient genotypes.PMID:42706300 | DOI:10.1038/s41598-026-65449-w

Sci Rep. 2026 Sep 7;16(1):27962. doi: 10.1038/s41598-026-55229-x.ABSTRACTAs coral cover declines worldwide, coral propagation has become a necessary strategy to restore coral reefs. However, predation can negatively affect the survival of coral microfragments used in restoration. While predation in terrestrial plants is reduced via secondary metabolites that deter predators, the effects of secondary metabolites on coral survival and predation in the field are poorly understood. We placed Orbicella faveolata microfragments from ten different colonies in a predator-exclusion cage for 0 to 3 mo. We used untargeted metabolomics methods based on mass spectrometry to analyze metabolic patterns across lengths of time in the predator-exclusion cage. Betaine, a compound previously associated with temperature and predation stress, was found in higher abundance in fragments that experienced lower field survival and higher incidents of predation, suggesting a potential relationship with corallivory. Our results suggest a connection between the metabolome, fish predation, and survival of O. faveolata microfragments, and highlights a promising avenue to use secondary metabolites to enhance survivorship of coral fragments during restoration projects.PMID:42706288 | DOI:10.1038/s41598-026-55229-x

NPJ Sci Food. 2026 Sep 4;10(1):269. doi: 10.1038/s41538-026-01121-x.ABSTRACTCold storage induces flavor deterioration in sweet cherry, while cultivar-specific regulatory mechanisms are poorly understood. In this study, two mainstream commercial cultivars, 'Rainier' and 'Tieton', were stored at 4 °C for 21 days. We comprehensively integrated physiological phenotyping, transcriptomics, metabolomics, and volatile compound profiling to explore their flavor deterioration patterns. Physiological results demonstrated that fruit softening and sugar-acid imbalance were typical deterioration symptoms, and 'Tieton' reached a 100% decay rate at the end of storage, far higher than 51.55% of 'Rainier'. Metabolomic analysis identified 1876 metabolites, and the two cultivars showed asynchronous metabolic reprogramming. 'Tieton' underwent dramatic metabolic changes at the early storage stage, while obvious metabolic shifts occurred in 'Rainier' at the mid stage. "Starch and sucrose metabolism" and "phenylpropanoid biosynthesis" were confirmed as two universally core pathways associated with flavor variation. We also detected 45 differential volatile compounds linked to fruit aroma. Furthermore, a flavor regulatory network was constructed, verifying that PavMYB3/13 as candidate positive regulators and PavC2H2 is a candidate negative regulator of flavor maintenance. This work elaborates on the genotype-specific patterns of cold-induced flavor decay and provides a theoretical foundation for developing variety-targeted postharvest preservation technologies for sweet cherries.PMID:42706278 | DOI:10.1038/s41538-026-01121-x

Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2026 Jul 7;61(7):759-767. doi: 10.3760/cma.j.cn115330-20260120-00044.ABSTRACTObjective: Perineural invasion (PNI) is a critical determinant of poor prognosis in laryngeal squamous cell carcinoma (LSCC), but its underlying mechanisms remain unclear. This study aimed to investigate whether LSCC-derived exosomes induce axonal growth by delivering neuroactive molecules, thereby contributing to tumor perineural invasion. Methods: Clinical data from the laryngeal cancer cohort of The Cancer Genome Atlas Head and Neck Squamous Cell Carcinoma (TCGA-HNSC) dataset were analyzed. Propensity score matching (PSM) and Cox regression were used to evaluate the prognostic value of nerve density, and these findings were validated using 35 pairs of laryngeal cancer and adjacent normal tissue specimens collected at Yantai Yuhuangding Hospital between 2022 and 2026 to assess neural morphological changes. Exosomes were isolated from the human LSCC cell line AMC-HN-8, characterized by quality-control assays, and co-cultured with PC12 cells. A rescue experiment using GW4869, a specific inhibitor of neutral sphingomyelinase, was performed to confirm the exosome-dependent effect. Neurite outgrowth was evaluated by immunofluorescence, and the expression of axonal growth-related genes was measured by RT-qPCR. Targeted metabolomics was employed for the absolute quantification of neuroactive metabolites within the vesicles and for pathway enrichment analysis. Results: After PSM adjustment, high nerve density was identified as an independent poor prognostic factor in LSCC patients (HR=2.10, P=0.035), with particularly pronounced prognostic value in the early-stage node-negative (N0) subgroup (HR=4.07, P=0.001). Pathological sections showed high expression of the neural markers βIII-tubulin and PGP9.5 in LSCC tissues (βIII-tubulin: t=2.234, P<0.05; PGP9.5: t=2.575, P<0.05). Exosomes were successfully isolated from AMC-HN-8 cells and passed quality control. In vitro assays showed that LSCC-derived exosomes significantly promoted neurite extension and branching in PC12 cells (t=4.147, P<0.000 1) and upregulated core axonal growth genes, including GAP-43, NEFL, and NEFM (GAP-43: t=3.698, P<0.05; NEFL: t=5.113, P<0.01; NEFM: t=5.263, P<0.01); this effect was completely reversed by the exosome-release inhibitor GW4869 (t=3.535, P<0.001). Targeted metabolomics revealed a specific enrichment of 12 neurotransmitters and metabolites within LSCC exosomes, centered on glutamine (83.411 μmol/L, FC=1.88) and glutamate (18.461 μmol/L, FC=1.21), which were significantly enriched in signaling pathways such as "central carbon metabolism in cancer" and "glutamatergic synapse". Conclusion: Nerve density is a potential adverse prognostic factor in patients with LSCC. LSCC-derived exosomes can directly induce axonal growth in neuron-like cells, suggesting that tumor cells actively remodel the neural microenvironment and drive axonal growth through exosome-mediated long-range signaling.PMID:42706064 | DOI:10.3760/cma.j.cn115330-20260120-00044