PubMed

J Ovarian Res. 2026 Feb 10. doi: 10.1186/s13048-026-02019-8. Online ahead of print.NO ABSTRACTPMID:41668062 | DOI:10.1186/s13048-026-02019-8

Cancer Cell Int. 2026 Feb 10. doi: 10.1186/s12935-026-04215-4. Online ahead of print.ABSTRACTBACKGROUND: Although androgen receptor (AR)-targeted therapies have shown notable clinical efficacy in prostate cancer (PCa), the emergence of drug resistance remains a critical factor driving the clinical prognosis in castration-resistant prostate cancer (CRPC). Aberrant tumor lipid metabolism not only fulfills the energetic and biosynthetic requirements of rapidly proliferating cancer cells but also contributes to the development of therapeutic resistance.METHODS: We examined SOX8 expression in enzalutamide resistance (EnzR) cell lines and validated its association with tumor progression and clinical outcome. The malignant phenotypes related to EnzR were assessed in vitro using PCa cell lines with stable SOX8 overexpression or knockdown. Tumor xenografts were subsequently generated by inoculating the corresponding cell lines into nude mice. To elucidate the underlying mechanisms, we conducted RNA-seq, CUT&Tag, non-targeted metabolomics, and a series of molecular and biochemical assays.RESULTS: SOX8 expression was elevated in EnzR prostate cancer cell lines and positively correlated with poor patient prognosis. Reduced SOX8 expression enhanced cellular sensitivity to enzalutamide, whereas elevated SOX8 expression decreased drug responsiveness. Chromatin immunoprecipitations (ChIP) assays revealed that AR was enriched at the SOX8 promoter region and transcriptionally repressed SOX8. In vivo, stable SOX8 knockdown markedly suppressed tumor growth in nude mouse xenografts. Mechanistically, SOX8 promotes the EnzR by reprograming lipid metabolism and we identified carnitine palmitoyltransferase 2 (CPT2), a key enzyme in lipid metabolism, as a novel downstream target of SOX8. SOX8-driven lipid metabolic reprogramming promoted enzalutamide resistance through the SOX8/CPT2 axis.CONCLUSIONS: High SOX8 expression promotes EnzR in PCa, suggesting SOX8 as a potential therapeutic target. Our findings demonstrate that SOX8 drives EnzR by activating the SOX8/CPT2 axis, thereby inducing lipid metabolic reprogramming in PCa cells.PMID:41668040 | DOI:10.1186/s12935-026-04215-4

BMC Plant Biol. 2026 Feb 11. doi: 10.1186/s12870-026-08293-4. Online ahead of print.ABSTRACTBACKGROUND: Postharvest pepper fruits undergo quality deterioration including water loss, shrinkage and nutritional decline, which limits their commercial value. Notably, nano-silicon (SiNPs) improves postharvest vegetable quality, but its regulatory mechanism on pepper storage quality, especially metabolic changes, remains unclear. Therefore, this study explored SiNPs effects on P70 pepper phenotype, storage quality and metabolism to optimize postharvest preservation.RESULTS: SiNPs treatment significantly improved P70 pepper fruits storage quality. Under roomtemperature (RT) and low temperature (LT) storage conditions, SiNPs treatment (RT-NP, LT-NP) effectively alleviated shrinkage, water loss, and hardness decline. After 6 days of storage, LT-NP group had 1.09-fold higher hardness than LT group, while LT group weight loss was 1.46-fold that of LT-NP. For nutritional quality indicators, SiNPs treatment maintained higher contents of vitamin C, flavonoids, soluble solids and soluble sugar. In terms of antioxidant capacity, SiNPs treatment enhanced the activities of superoxide dismutase, peroxidase and catalase; LT-NP had 1.11-fold higher SOD at 6 days and 1.54-fold higher POD at 4 days than LT. Metabolomic analysis detected1041 metabolites, mainly including flavonoids (22.1%) and phenolic acids (13.7%). Compared with LT group, LT-NP had 164 up- and 79 down-regulated differential metabolites, enriched in flavonoid biosynthesis, starch-sucrose and amino acid metabolism. LT-NP up-regulated flavonoids (Galangin, Apigenin), D-Sucrose and activated polyamine biosynthesis.CONCLUSIONS: SiNPs improves P70 pepper postharvest quality by reducing water loss, maintaining hardness and nutrients. Collectively, the mechanism involves enhanced antioxidant enzyme activity and regulated key metabolites in flavonoid, sugar and amino acid pathways, supporting SiNPs application in pepper postharvest preservation.PMID:41667972 | DOI:10.1186/s12870-026-08293-4

BMC Plant Biol. 2026 Feb 10. doi: 10.1186/s12870-026-08325-z. Online ahead of print.NO ABSTRACTPMID:41667958 | DOI:10.1186/s12870-026-08325-z

Nat Methods. 2026 Feb 10. doi: 10.1038/s41592-025-02976-w. Online ahead of print.NO ABSTRACTPMID:41667878 | DOI:10.1038/s41592-025-02976-w

Sci Rep. 2026 Feb 10. doi: 10.1038/s41598-026-39332-7. Online ahead of print.ABSTRACTTaste is one of the important factors for evaluating the quality of tea. Smart tongue and metabolomics were used to analyze the difference in taste of Gongou black teas from three different varieties. In this study, 564 non-volatile metabolites (NVMs) were identified in the black teas. The quality difference between Shuyong 3 black tea (SY-T) and Fuding Dabai black tea was the greatest, followed by SY-T and Sichuan Small and Medium-leaf black tea. Specially, the differential NVMs primarily influenced the astringency, sourness, umami, and bitterness taste attributes of black teas, rather than sweetness. Based on the correlation results between differential NVMs and the taste of black tea, and in combination with the VIP value ≥ 1.5, 24 characteristic differential NVMs that might have a significant impact on the formation of different taste qualities were successfully screened out. In the withering process, the differential metabolic pathways of three different varieties were primarily concentrated in flavonoid and carbohydrate metabolic pathways, which was potentially explaining the main cause of alterations in the characteristic metabolites and the taste profiles of the black teas. Our findings provide a theoretical basis for the taste variations among different varieties, as well as a new insights into the quality formation of black tea during the withering process.PMID:41667800 | DOI:10.1038/s41598-026-39332-7

NPJ Metab Health Dis. 2026 Feb 10;4(1):7. doi: 10.1038/s44324-025-00098-7.ABSTRACTDeveloping cells undergo extensive metabolic adaptations to support growth and differentiation. Here, using spatially resolved mass spectrometry imaging and stable isotope tracing, we systematically investigate metabolic remodeling in mouse brains at postnatal day 14 and day 28, a period coinciding with the transition from a maternal milk diet to solid food. Untargeted metabolomics reveals global shifts in lipid composition, and region-specific remodeling of central energy metabolism, including increased glycolytic intermediates in grey matter-enriched regions and a global decrease in tricarboxylic acid (TCA) cycle metabolites after weaning. Despite these marked changes in metabolite levels, the glucose incorporation rate remains constant across these developmental stages. Notably, weaning mice onto a milk-replacement diet demonstrates that the observed metabolic adaptations are largely diet-independent. Together, our data suggest that postnatal brain metabolic remodeling is an intrinsically programmed feature of maturation providing region-specific metabolic reorganization to support developmental demands.PMID:41667725 | DOI:10.1038/s44324-025-00098-7

Commun Biol. 2026 Feb 10. doi: 10.1038/s42003-026-09673-0. Online ahead of print.ABSTRACTFungi that live in deep-sea sediments experience extreme environmental conditions, yet little is known about how they adapt their growth and metabolism to these stresses. This study explores the morphogenetic and metabolomic responses of three black yeasts-Salinomyces thailandicus, Neophaeotheca triangularis, and N. salicorniae-isolated from deep-sea sediments of the Gulf of Mexico under varying salinities and exposure to the melanin inhibitor pthalide. Each species displays distinct growth adaptations: S. thailandicus shifts from filamentous to yeast-like forms as salinity increases, N. triangularis exhibits the opposite trend, and N. salicorniae remains dimorphic but grows more slowly at high salinities. Phthalide inhibits hyphal development in all three species. An exploratory metabolic analysis, conducted on pooled samples, indicates that metabolomic profiles change with salinity, with fatty acids dominating across species, suggesting membrane remodeling as an adaptation to osmotic stress. N. triangularis uniquely accumulates amino acids and peptides, a response previously reported mainly in plants. Additional metabolites, including aminocyclitols and compounds associated with extracellular polymeric substances, suggest the involvement of uncharacterized adaptive mechanisms contributing to stress protection. These findings advance our understanding of how black yeasts adapt to osmotic stress and provide a foundation for future studies.PMID:41667606 | DOI:10.1038/s42003-026-09673-0

Sci Rep. 2026 Feb 10. doi: 10.1038/s41598-026-38283-3. Online ahead of print.ABSTRACTDiet influences plaque stability through its potential to modulate inflammation, a process that involves complex interactions among various lipid metabolites. This study aims to utilize metabolomics to identify key metabolites involved in this pathway and to elucidate the mechanisms by which dietary factors affect plaque stability. The Dietary Inflammatory Index (DII), derived from dietary data, was used to assess the inflammatory potential of individual diets. Propensity score matching categorized serum samples from coronary heart disease (CHD) patients into an anti-inflammatory group (n = 108) and a pro-inflammatory group (n = 108). A comprehensive analysis of lipid profiles was performed using an UPLC-MS/MS detection platform combined with the broad-targeted lipid metabolomics technique, and lipid metabolites with significant differences were screened out. Concurrently, we measured serum levels of inflammatory factors and plaque stability. A Bayesian network model was then applied to elucidate the causal relationships among DII, lipid metabolites, inflammatory factors, and plaque stability. A lipidomics analysis identified 22 differentially expressed lipid metabolites, which were associated with sphingolipid metabolism pathways in the KEGG (Kyoto Encyclopedia of Genes and Genomes) database, particularly involving nine ceramide species. The Bayesian network model exploring the impact of DII on plaque stability comprises 16 nodes and 23 directed arcs. It revealed multiple causal relationships among DII, ceramide species, inflammatory factors, and plaque stability. Specifically, six ceramide species [Cer(d16:0/20:1), Cer(d24:3/15:1), Cer(t14:1/21:0), Cer(t20:0/18:2), Cer(t22:1/16:1), Cer(t26:1/12:1)] and five inflammatory factors (IFN-γ, IL-1β, IL-8, IL-12, IL-13) were found to be involved in these associations. Ceramide species emerged as differential lipid metabolites that distinguish between the anti-inflammatory and pro-inflammatory groups, simultaneously serving as key lipid metabolic products through which diet exerts its influence on plaque stability.PMID:41667563 | DOI:10.1038/s41598-026-38283-3

Sci Rep. 2026 Feb 10. doi: 10.1038/s41598-026-36993-2. Online ahead of print.NO ABSTRACTPMID:41667557 | DOI:10.1038/s41598-026-36993-2

Cell Death Dis. 2026 Feb 10. doi: 10.1038/s41419-026-08445-2. Online ahead of print.ABSTRACTThe microtubule-stabilizing drug paclitaxel remains the standard of care for various solid malignancies but frequently leads to chemotherapy-induced peripheral neuropathy (CIPN). CIPN is a leading cause for premature treatment termination and a significantly reduced quality of life in long-term cancer survivors. The molecular mechanisms of neuro-axonal degeneration, neuroinflammation, and pain in patients treated with paclitaxel remain incompletely understood, and there are currently no predictive biomarkers or preventive treatments. We used human iPSC-derived sensory neurons exposed to paclitaxel to comprehensively model the pathophysiology of CIPN. Neurotoxicity was assessed over time using viability assays and sequential RNA sequencing, as well as deep proteome and lipidomic analyses. We observed a time and dose-dependent decline of cell viability at clinically relevant paclitaxel doses. Sequential RNA sequencing defined JUN as an early immediate gene, followed by the overexpression of genes of the neuronal stress response (e.g., ARID5A, WEE1, DUSP16, GADD45A), neuronal injury and apoptotic pathways (e.g., ATF3, HRK, BBC3 [PUMA], BCL2L11 [BIM], CASP3), neuroinflammation and nociception (CALCB, MMP10, IL31RA, CYSLTR2, C3AR1, TNFRSF12A) and neuronal transduction (e.g., CAMK2A, STOML3, PIRT), while key enzymes of lipid biosynthesis were markedly downregulated (e.g., LSS, HMGCS1, HMGCR, DHCR24). Deep proteome analyses following 48 h of exposure to 100 nM paclitaxel revealed a strong correlation of differentially expressed RNA with proteins, and a marked degradation of essential axonal transport proteins such as kinesins, stathmins, and scaffold proteins. Consistent with the downregulation of rate-limiting enzymes of lipid biosynthesis, lipidome analysis confirmed deregulation of neuronal lipid homeostasis. In summary, paclitaxel induces transcriptomic and proteomic signatures of the neuronal stress response, neuroinflammation, nociception, and disturbed metabolism. These may explain, in part, the clinical phenotype of sensory loss, hypersensitivity, and neuropathic pain frequently observed in patients suffering from CIPN, but constitute pharmacologically addressable targets.PMID:41667428 | DOI:10.1038/s41419-026-08445-2

BMJ Open. 2026 Feb 10;16(2):e099348. doi: 10.1136/bmjopen-2025-099348.ABSTRACTINTRODUCTION: Young children and children living with HIV are at high risk of progressing to tuberculosis (TB) disease following Mycobacterium tuberculosis (Mtb) exposure and infection, and also of developing severe forms of disease and TB-related mortality. Identifying children who have very early (sub-clinical) TB disease, prior to progression to clinically apparent TB, would mean that TB preventive treatment (TPT) could be more efficiently targeted to this group. Identifying biomarker changes on drug therapy in children with Mtb infection or very early disease could pave the way for the development of tests that can identify which children have viable bacilli and are therefore at increased risk of disease progression.METHODS AND ANALYSIS: The INTREPID study will use already collected samples taken from well-phenotyped paediatric cohorts in three clinical studies conducted in South Africa in children <5 years, including a drug-resistant TPT trial (TB-CHAMP), an observational household contact study (interferon-gamma release assay studies) and a prospective diagnostic study (Umoya), all conducted in a setting with a high burden of TB and HIV. We will employ transcriptomic, proteomic, metabolomic and serology approaches to analyse changes in host blood profiles at every stage along the TB continuum, from Mtb exposure to disease and from children treated for Mtb infection and early TB disease, as well as targeted Mtb antibody analysis. Data on viral co-infections and relevant clinical and epidemiological parameters will be integrated and evaluated to identify the optimal biosignatures that can predict future progression to clinically overt disease in children below 5 years of age, including those living with HIV.ETHICS AND DISSEMINATION: The study protocol received ethical approval from the Stellenbosch University Health Research Ethics Committee (N23/03/025). The study findings will be disseminated through peer-reviewed publications, scientific conferences and formal presentations to healthcare professionals and to local communities, in collaboration with the Desmond Tutu TB Centre Community Advisory Board.PMID:41667177 | DOI:10.1136/bmjopen-2025-099348

Neurospine. 2026 Jan;23(1):145-158. doi: 10.14245/ns.2551560.780. Epub 2026 Jan 31.ABSTRACTBiomarkers are becoming pivotal in understanding the complex pathophysiology of disc herniation and guiding novel therapeutic strategies. Recent research highlights the value of molecular and cellular biomarkers in delineating disease progression, treatment monitoring and patient stratification. This review summarizes current advances in the identification and validation of emerging biomarkers across genomic, transcriptomic, proteomic, and metabolomic domains, emphasizing their potential to bridge basic mechanistic insights with clinical translation. Particular attention is given to the interplay between inflammatory mediators, extracellular matrix turnover, and immune cell activity as indicators of lumbar disc herniation diagnosis and prognosis. Despite encouraging progress, standardization of biomarker validation protocols, inter-study comparability, and large-scale clinical implementation remain major challenges. Future directions include the integration of multi-omics technologies and bioinformatic tools to identify predictive biomarker panels with diagnostic and prognostic utility towards personalized medicine.PMID:41666868 | DOI:10.14245/ns.2551560.780

Neurospine. 2026 Jan;23(1):3-28. doi: 10.14245/ns.2551584.792. Epub 2026 Jan 31.ABSTRACTLumbar disc herniation (LDH) is one of the most common causes of low back and leg pain. While mechanical and degenerative factors have long been considered the main contributors, persistent or recurrent symptoms in many patients suggest additional biological mechanisms. Recent research has highlighted the microbiome as a potential modulator of inflammation, immune response, and pain sensitization, introducing the "gut-spine axis" concept. This scoping review summarizes the current evidence on the role of both gut and local disc microbiota in LDH. A systematic search of PubMed/MEDLINE and Scopus was conducted up to June 2025, following PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. Twenty-six studies were included, encompassing preclinical and clinical investigations. Animal models showed that LDH may alter gut microbial composition and that microbiome-targeted interventions can reduce inflammation, neuroinflammatory signaling, and pain sensitivity. In human studies, low-virulence bacteria, particularly Cutibacterium acnes, were frequently detected in surgically excised intervertebral discs, although results were inconsistent due to methodological heterogeneity and potential contamination. Some studies reported associations between bacterial colonization and Modic changes, disc height loss, or chronic pain. Additionally, genetic and metabolomic data suggest that gut dysbiosis and related microbial metabolites may influence systemic immune and metabolic pathways implicated in disc degeneration and pain perception. Overall, the current evidence suggests the biological plausibility of microbiome involvement in LDH pathophysiology, acting through both systemic and local mechanisms. However, the available data remain preliminary, and no mechanistic study has confirmed the observed correlations to date. Further standardized, contamination-aware studies are required to clarify causality and explore microbiome-targeted therapeutic strategies.PMID:41666856 | DOI:10.14245/ns.2551584.792

Tuberculosis (Edinb). 2026 Feb 5;157:102745. doi: 10.1016/j.tube.2026.102745. Online ahead of print.ABSTRACTBACKGROUND/OBJECTIVES: Tuberculous pleuritis (TP), a common manifestation of Mycobacterium tuberculosis infection, poses challenges in differentiating microbiologically positive (PEMP-MT) from negative (PEMN-MT) pleural effusions due to the limited sensitivity of traditional diagnostic methods.METHODS: Proteomics analysis using iTRAQ, non-targeted metabolomics, parallel reaction monitoring (PRM), and machine learning were employed to diagnose PEMN-MT or PEMP-MT. A validation cohort of 63 PEMN-MT and 28 PEMP-MT patients underwent ELISA experiments. Receiver operating characteristic (ROC) curves evaluated the predictive value of LDH and LV218 individually and in combination.RESULTS: Differentially expressed proteins (DEPs) and metabolites (DEMs) were identified using bioinformatics tools and pathway enrichment analyses. A machine learning model utilizing six biomarkers (LV218, F13A, RET4, LV321, TBA1C, and LDH) demonstrated excellent diagnostic performance with an AUROC of 0.987 and an AUPR of 0.974, distinguishing PEMP-MT from PEMN-MT. ROC curve analysis showed that both LDH and LV218, alone and in combination, provided strong predictive value for distinguishing the two groups.CONCLUSION: LDH and LV218 are promising biomarkers for differentiating microbiologically positive and negative pleural effusions in tuberculous pleuritis. These biomarkers, particularly when combined, could improve diagnostic accuracy and clinical management.PMID:41666853 | DOI:10.1016/j.tube.2026.102745

Environ Int. 2026 Feb 5;208:110126. doi: 10.1016/j.envint.2026.110126. Online ahead of print.ABSTRACTUbiquitous environmental nano-plastics (NPs) can enter organisms via multiple pathways, posing potential health risks; however, the adverse effects of gestational polystyrene NPs (PS-NPs) exposure on adult offspring reproductive function and underlying mechanisms remain unclear. The adverse outcome pathway (AOP) framework models toxic events from molecular to organismal levels. This study employed multi-omics analysis to construct a putative partial-AOP network, revealing insights into the mechanism of intergenerational reproductive impairment of PS-NPs in adult offspring. Gestational PS-NPs exposure induced testicular structural damage and abnormal spermatogenesis in adult male offspring. The testicular transcriptomic and serum metabolomic data integration, validation and the omics-anchored AOP network construction highlighted four molecular events in adult male offspring following gestational PS-NPs exposure: increased arachidonic acid release, elevated reactive oxygen species levels, increased palmitic acid levels, and decreased lysophosphatidyl choline levels. These molecular events might be implicated in a series of cellular key events (KEs), ranging from cellular damage and impaired proliferation to cell death. These cellular KEs could contribute to testicular cell reduction and organ-level KEs-testicular injury, reduced androgen secretion, and impaired spermatogenesis-culminating in the adverse outcome of reproductive dysfunction. This putative network characterizes the molecular and histopathological landscape of reproductive impairment in adult male offspring associated with gestational PS-NPs exposure, and provides clues for elucidating the intergenerational toxicity mechanisms of PS-NPs.PMID:41666845 | DOI:10.1016/j.envint.2026.110126

Plant Physiol Biochem. 2026 Jan 30;232:111084. doi: 10.1016/j.plaphy.2026.111084. Online ahead of print.ABSTRACTShade could improve the medicinal quality of Zhebeimu (Fritillaria thunbergii Miq.) bulb, but lead to decreased yield resulting from leaf senescence. Although potassium application can mitigate such yield loss by delaying leaf senescence, the underlying mechanism remains largely unknown. In this two-year field experiment, the widely cultivated variety 'Zhebei 3' was subjected to shade (around 50% shading) from the squaring stage, along with potassium application of 22.5 kg K2O ha-1. Shade treatment elevated the levels of senescence-inducing phytohormones [abscisic acid (ABA), salicylic acid (SA), jasmonic acid (JA), and 1-aminocyclopropanecarboxylic acid (ACC, the direct precursor of ethylene)], and reduced anti-senescence phytohormones [auxin (IAA) and cytokinin (CTK)]. It also suppressed the active oxygen scavenging system by lowering the activities of antioxidant enzymes [superoxide dismutase (SOD), peroxidase (POD), catalase (CAT) and glutathione peroxidase (GPX)] and the concentrations of non-enzymatic antioxidants [phenolics, flavonoids, flavones, and ascorbic acid (AsA)], leading to increased accumulation of O2- and malondialdehyde (MDA). Furthermore, shade impaired nitrogen assimilation via inhibiting the activities of nitrate reductase (NR), glutamine synthetase (GS), and glutamate synthase (GOGAT), thereby decreasing amino acid and soluble protein contents. These combined effects resulted in reduced chlorophyll contents and early leaf senescence. By contrast, potassium application increased IAA and CTK levels, enhanced activities of antioxidant enzymes (SOD, POD, CAT, and GPX) and contents of non-enzymatic antioxidant including flavonoids [(+)-gallocatechin, aromadendrin, kaempferol, quercetin, and myricetin] and flavones (kaempferol 3-sophorotrioside, astragalin, rutin, nictoflorin, quercetin 3-sophorotrioside, and isoquercitrin), and improved nitrogen assimilation. These changes collectively elevated chlorophyll contents and delayed shade-induced leaf senescence. Overall, this study broadened the understanding of the mechanism of potassium application in alleviating leaf senescence under shade.PMID:41666827 | DOI:10.1016/j.plaphy.2026.111084

Food Chem. 2026 Feb 8;508(Pt A):148336. doi: 10.1016/j.foodchem.2026.148336. Online ahead of print.ABSTRACTResearch has demonstrated that solid-state fermentation of foxtail millet with Pleurotus geesteranus can enhance its nutritional value and improve its antioxidant properties. However, studies exploring the changes in metabolites and metabolic pathways during fermentation are lacking. Untargeted metabolomics approaches can be used to reveal alterations in metabolites and metabolic pathways during foxtail millet fermentation. In this study, 584 differential secondary metabolites were identified, including 198 lipids, 111 organic compounds, 105 organic acids, and 45 benzenoids. Among these differential metabolites, 371 were upregulated, and 213 were downregulated. Kyoto Encyclopedia of Genes and Genomes enrichment analysis of the differential pathways revealed that they were primarily enriched in amino acid metabolism, biosynthesis of other secondary metabolites, lipid metabolism, and carbohydrate metabolism, with amino acid metabolism being the most significantly enriched. Taken together, these findings provide a foundation for deeper understanding of the nutritional and bioactive components of fermented foxtail millet.PMID:41666584 | DOI:10.1016/j.foodchem.2026.148336

Food Chem. 2026 Feb 6;508(Pt A):148317. doi: 10.1016/j.foodchem.2026.148317. Online ahead of print.ABSTRACTExisting biomarkers for fruit intake have not been well validated owing to the limited coverage of metabolomic platforms and lack specificity when used individually. In a highly controlled cross-over intervention study with 19 healthy volunteers on orange biomarker discovery, metabolomics analysis was performed on orange fruit, its in vitro digested samples, and postprandial urine using dual-column (Amide and T3) ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). Based on an intensive statistical strategy that incorporated the urinary kinetic curve (T0 h, T2 h, T4 h, T6 h, T24 h) of over 30,000 features, we confirmed three previously reported biomarkers (achillein, hesperetin, ferulic acid), and identified nine novel candidates that remained elevated after 24 h of consumption. Multi-biomarker panels using XGBoost achieved high predictive performance in classifying orange consumers after 1-2 days free diet background (single: 0.72 vs. panel: 0.85-0.90). Further application of dual-column UHPLC-MS and multi-biomarkers may accelerate the discovery and application of food biomarkers.PMID:41666577 | DOI:10.1016/j.foodchem.2026.148317

Comp Biochem Physiol Part D Genomics Proteomics. 2026 Feb 6;58:101775. doi: 10.1016/j.cbd.2026.101775. Online ahead of print.ABSTRACTThe sipunculid worm Sipunculus nudus is a dioecious marine invertebrate with ecological and aquaculture importance. To investigate the metabolic features underlying gamete specialization and thermal response, we performed untargeted metabolomic analysis of spermatozeugmata and oocytes under control conditions, as well as oocytes exposed to acute heat stress (37 °C for 24 h; n = 6 males, 6 females, and 4 heat-stressed females) using ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). Combined multivariate and univariate statistical analyses, applied with fold-change and significance thresholds, revealed 894 putatively annotated metabolites that differed between oocytes and spermatozeugmata, and 1749 that changed significantly under heat stress. Oocytes were enriched in lipid species (e.g., phospholipids such as PI and LPC) and nucleotide derivatives (e.g., putatively annotated uridine monophosphate, deoxynucleosides), whereas spermatozeugmata showed higher levels of lipids (e.g., PE and PC species), amino acid derivatives (e.g., putatively annotated N-acetyl-DL-serine), and small peptides. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that metabolites mapped to neurotransmitter and energy metabolism pathways were more prominent in oocytes, while metabolites associated with antioxidant and nucleotide biosynthesis pathways were comparatively enriched in spermatozeugmata. Under heat stress, oocytes exhibited significant metabolic changes, with increased organic acids and lipid metabolites (fatty acids and glycerophospholipids) and decreased nucleotide- and amino acid-related compounds. Most KEGG-mapped metabolic pathways showed an overall reduction in associated metabolites, including amino sugar, nucleotide, and amino acid metabolism, whereas metabolites mapped to Fc epsilon RI signaling and bile secretion KEGG pathways were relatively enriched. This study provides the first comprehensive metabolomic profile of S. nudus germ cells, revealing sex-specific metabolic patterns and heat-induced reprogramming of oocyte metabolism. These findings enhance our understanding of gamete physiology and acute thermal stress responses in marine invertebrates and may contribute to the development of reproductive health biomarkers.PMID:41666562 | DOI:10.1016/j.cbd.2026.101775