PubMed

Clin Nutr ESPEN. 2025 Apr 4:S2405-4577(25)00263-3. doi: 10.1016/j.clnesp.2025.03.172. Online ahead of print.ABSTRACTBACKGROUND & AIMS: Vitamin D regulates calcium and phosphorus homeostasis, skeletal health, and potentially other aspects of health. There are limitations of existing vitamin D biomarkers. We aimed to discover novel vitamin D biomarkers by investigating serum and urine metabolites associated with vitamin D supplementation.METHODS: We examined cross-sectional associations between vitamin D supplementation and serum and urine metabolites in Atherosclerosis Risk in Communities Study participants at visit 5 (2011-2013). Untargeted metabolomic profiling of serum and spot urine samples was performed by Metabolon, Inc. We analyzed associations between vitamin D supplementation and log2-transformed metabolites using linear regression models adjusted for demographic, lifestyle, and health covariates.RESULTS: Of 5225 participants with serum metabolites analyzed (mean age 76 [SD 5] years, 57% female, 20% Black), 45% reported taking vitamin D supplements. Eighty-two of 933 serum metabolites were associated with vitamin D supplementation (P<0.05/933). Most were lipids (n=36). Of 1565 participants with urine metabolites analyzed, one-third (37%) used vitamin D. Nineteen of 946 urine metabolites were associated with vitamin D supplementation (P<0.05/946). Most were cofactors and vitamins (n=12). After adjusting for other supplement use (multivitamin/mineral, omega-3, B and C vitamins), 5 serum metabolites (pro-hydroxy-pro, pyroglutamine, sulfate, creatine, and 2-hydroxypalmitate) and no urine metabolites were significantly associated with vitamin D supplementation.CONCLUSIONS: Many serum and urine metabolites were associated with vitamin D supplementation. Five serum metabolites remained associated with vitamin D after adjustment for other dietary supplements, including metabolites of bone collagen degradation, glutathione metabolism, and sphingolipid metabolism. These metabolites may reflect physiological activities of vitamin D and, thus, improve assessment of vitamin D adequacy to achieve functional outcomes. These merit further investigation as potential vitamin D biomarkers.PMID:40189143 | DOI:10.1016/j.clnesp.2025.03.172

Environ Res. 2025 Apr 4:121546. doi: 10.1016/j.envres.2025.121546. Online ahead of print.ABSTRACTIn recent years, microplastic (MPs) and pesticide pollution have become prominent issues in the field of soil pollution. This research endeavored to assess the impact of ultraviolet radiation (UV) on the characteristics of microplastics, as well as investigating the toxicological effect on earthworms (Eisenia fetida) when subjected to the dual stressors of microplastics and acetochlor (ACT). This research found that microplastics aged under UV were more prone to wear and tear in the environment, and produced more oxygen-containing functional groups. Chronic exposure experiments were conducted on ACT and aged-MPs. The results revealed that aged-MPs and ACT inhibited earthworm growth, induced oxidative stress, and caused damage to both the body cavity muscles and the intestinal lumen. Compared with individual exposure, combined exposure increased the oxidative products (superoxide dismutase (SOD) and catalase (CAT)) and altered the expression levels of related genes (TCTP and Hsp70) significantly. PE inflicted more significant harm to the earthworm intestinal tissue compared to PBAT. By 1H-NMR metabolomics, the investigation delved into the repercussions of PE and ACT on the metabolic pathways of earthworms. Exposure to ACT and PE can disrupt the stability of intestinal membranes stability, amino acid metabolism, neuronal function, oxidative stress and energy metabolism. Overall, the research revealed that combined exposure of MPs and ACT exacerbated the negative effects on earthworms significantly, and contributed valuable insights to environmental risk assessment of the combined toxicity of microplastics and pesticides.PMID:40189011 | DOI:10.1016/j.envres.2025.121546

Biol Psychiatry. 2025 Apr 4:S0006-3223(25)01106-0. doi: 10.1016/j.biopsych.2025.03.018. Online ahead of print.ABSTRACTBACKGROUND: Although childhood trauma is an important risk factor for various diseases, biological mechanisms remain insufficiently understood. To deepen this understanding, we investigated the wide-spectrum metabolomic signature of childhood trauma exposure in a large adult cohort.METHODS: Baseline and six-year follow-up data from the Netherlands Study of Depression and Anxiety were used (Nparticipants=2,902, Nobservations=4,800). Childhood trauma exposure was retrospectively assessed with the Childhood Trauma Interview. Plasma metabolite levels were measured with the Metabolon mass spectrometry-based untargeted metabolomics platform at both timepoints. Mixed-effect models evaluated the metabolomics associations of childhood trauma while controlling for sociodemographic, lifestyle, health-related, and technical covariates. We examined the overlap between the metabolomic profiles of childhood trauma and depression. External replication was tested in 308 additional participants.RESULTS: Childhood trauma was associated in a dose-response manner with 18 metabolites. Upregulated metabolites were nominally enriched with compounds involved in fatty acid and branched-chain amino acid metabolism (p=3.91e-02, qFDR>.05) while downregulated metabolites were nominally enriched with corticosteroids (p=2.24e-03, qFDR>.05). Six of the 18 metabolites were linked to childhood trauma but not depression. Findings were partially replicated using an alternative measure for childhood trauma (effect sizes correlation r=0.94) and an external sample (r=0.54).CONCLUSIONS: Childhood trauma was linked in a dose-response manner to a biological signature encompassing a wide array of metabolites. Dysregulations were observed in amino acid and fatty acid metabolism as well as hypothalamic-pituitary-adrenal axis function. Further studies should corroborate these findings and develop early-intervention strategies targeting trauma-related biological mechanisms to prevent cardiometabolic and psychiatric diseases.PMID:40189007 | DOI:10.1016/j.biopsych.2025.03.018

Toxicology. 2025 Apr 4:154130. doi: 10.1016/j.tox.2025.154130. Online ahead of print.ABSTRACTBisphenol F (BPF) is one of the main substitutes for Bisphenol A (BPA) and is widely used in the manufacture of household products. In addition, BPF threatens human health through environmental pollution and the food chain. However, the toxicity of BPF to the liver and how it affects glucose metabolism and lipid metabolism is still unclear. This study used male SD rats as an animal model to investigate the hepatotoxicity of BPF and its effects on glucose and lipid metabolism. The results of the HE, serum and liver biochemical indicators show that BPF can damage the basic structure of the liver, cause liver dysfunction and lead to disorders of liver glucose metabolism and lipid metabolism. Furthermore, we conducted metabolomics and proteomics analyses on the livers of the BPF exposed group at 100mg/kg/d in comparison with the control group. The results indicated that BPF exposure had a significant effect on liver metabolism. Combined with biological analysis and the validation of changes in genes and proteins related to glucose and lipid metabolism in the liver, it was elucidated that BPF can promote fatty acid oxidation and inhibit fatty acid synthesis through the AMPK and PPAR signaling pathways, leading to a reduction in fatty acids. Furthermore, it has been demonstrated that BPF can promote glycogen synthesis and gluconeogenesis via the AKT pathway, which can result in disorders of glucose metabolism.PMID:40188933 | DOI:10.1016/j.tox.2025.154130

Poult Sci. 2025 Mar 1;104(6):104958. doi: 10.1016/j.psj.2025.104958. Online ahead of print.ABSTRACTTea polyphenols are a class of natural plant compounds with potent antioxidant properties, and their critical role in regulating lipid metabolism has been demonstrated in numerous studies. However, systematic research on the effects of tea polyphenols on lipid metabolism in lion-head geese remains limited. In this study, we examined the impact of tea polyphenols on lipid metabolism in geese through an integrative analysis of transcriptomics and metabolomics. A total of 240 healthy male lion-head geese with similar body weights at 1 day of age were randomly allocated into two treatment groups (6 replicates per group, with 20 geese per replicate). The control group received a basal diet, while the experimental group was supplemented with 1000 mg/kg of tea polyphenols (50.4 % catechin purity) in the basal diet for 18 weeks. The results indicated that serum total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-Px) activities were significantly increased (P < 0.05), while malondialdehyde (MDA) levels were significantly decreased (P < 0.05) in the tea polyphenol group compared to the control group. Additionally, serum triglycerides (TG), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) activities were significantly lower (P < 0.05) in the tea polyphenol group than in the control group. Hepatic transcriptomic analysis further revealed that tea polyphenols significantly modulated the expression of several genes involved in lipid metabolism, including angiopoietin-like 4 (ANGPTL4), which plays a role in regulating lipid homeostasis, as well as glycerophosphodiester phosphodiesterase domain containing 2 (GDPD2), immunoglobulin heavy chain (IGH), proto-oncogene protein c-fos (FOS), and matrix metallopeptidase 1 (MMP1), etc. Serum metabolomic analysis also demonstrated significant alterations in lipid metabolites induced by tea polyphenols, including the downregulation of fatty acyl metabolites such as L-Palmitoylcarnitine and Hexadecanal. Moreover, the combined analysis revealed a strong positive correlation between ANGPTL4 and the organic compounds of steroidal saponins, such as Glucoconvallasaponin B, and negative correlations with glycerophospholipid metabolites, such as LysoPC (P-16:0). The comprehensive analysis suggests that the inclusion of tea polyphenols in the diet enhances the antioxidant capacity of lion-head geese, improves hepatic lipid profiles, and regulates lipid metabolism via modulating lipid metabolism-related genes and metabolites.PMID:40188624 | DOI:10.1016/j.psj.2025.104958

Nutr Res. 2025 Jan 15;137:1-13. doi: 10.1016/j.nutres.2025.01.004. Online ahead of print.ABSTRACTThis study investigated the metabolic mechanisms underlying the association between malnutrition and poor prognosis in coronary artery disease (CAD). We hypothesized that specific metabolites associated with nutritional status impact all-cause mortality and Major Adverse Cardiovascular Events in CAD patients. To test this hypothesis, we evaluated the nutritional status of 5182 CAD patients from multiple centers using three nutritional risk screening tools and analyzed the impact on CAD outcomes with restricted cubic splines and Cox regression. Poor nutritional status was found to be linked to increased adverse outcomes. Further analysis using multiple linear regression and mediation analysis identified elevated concentrations of β-pseudouridine and dulcitol, and decreased concentrations of l-tryptophan and LPC (18:2/0:0), among other metabolites, as mediators of this association. Employing Least Absolute Shrinkage and Selection Operator for variable selection, we integrated these metabolites with clinical variables, which significantly improved the predictive accuracy for adverse outcomes. Our results highlight significant metabolic disparities in CAD patients based on nutritional status and provide novel insights into the role of nutrition-associated metabolites in CAD prognosis. These findings suggest that customized nutritional interventions targeting these metabolites could positively influence the progression of CAD.PMID:40188579 | DOI:10.1016/j.nutres.2025.01.004

STAR Protoc. 2025 Apr 5;6(2):103745. doi: 10.1016/j.xpro.2025.103745. Online ahead of print.ABSTRACTNanoflow liquid chromatography-tandem mass spectrometry (nLC-MS) benefits untargeted metabolomics by enhancing sensitivity and integrating proteomics for the same sample. Here, we present a protocol to enable nLC-MS for dual metabolomics and proteomics. We describe steps for solid-phase micro-extraction (SPME)-assisted metabolite cleaning and enrichment, which avoids capillary column blockage. We then detail nLC-MS data acquisition and analysis. This protocol has been applied in diverse specimens including biofluids, cell lines, and tissues. For complete details on the use and execution of this protocol, please refer to Lin et al.1.PMID:40188434 | DOI:10.1016/j.xpro.2025.103745

World J Microbiol Biotechnol. 2025 Apr 7;41(4):124. doi: 10.1007/s11274-025-04335-5.ABSTRACTThis study analyzed the secondary metabolite profile of Salicornia europaea inoculated with Brevibacterium casei EB3 and Pseudomonas oryzihabitans RL18 in aquaponic systems, exploring the metabolic mechanisms responsible for the observed shifts. Experiments were conducted in both microcosm and pilot-scale aquaponic setups to evaluate how these metabolic shifts vary across different system scales and their potential contributions to the observed increased accumulation of bioactive compounds with antioxidant and antimicrobial properties, including some phenolic acids, such as caffeic acid (154-fold), flavonoids (2.85-fold), and some unsaturated fatty acids, such as oct-3-enoic acid (32-fold). Metabolic profiling revealed shifts in pathways associated with plant growth and stress resilience, such as amino acid and phenolic biosynthesis. Additionally, differences in metabolic responses observed between microcosm and pilot-scale systems underscored the importance of understanding scaling effects. These findings highlight the potential for optimizing aquaponic systems by leveraging microbial-plant interactions to enhance ecological and economic outcomes. This approach offers valuable applications in nutrient recycling, phytopharmaceutical development, and the advancement of saline agriculture within integrated aquaculture frameworks.PMID:40189660 | DOI:10.1007/s11274-025-04335-5

Sci Rep. 2025 Apr 6;15(1):11777. doi: 10.1038/s41598-025-89755-x.ABSTRACTTrigeminal neuralgia (TN) is a neuropathic facial pain disorder characterized by severe stabbing pain along the trigeminal nerve. While its pathogenesis remains unclear, nerve demyelination and inflammation are likely involved. Current research has primarily focused on various blood-based omics approaches, which do not fully capture the lipid alterations occurring during TN progression in brain. In contrast, our study is the first to investigate cerebrospinal fluid (CSF) lipidomic profiles in TN patients, aiming to elucidate potential disease mechanisms. CSF samples were collected from 22 TN patients and 18 healthy controls, followed by untargeted lipidomic analysis using high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. A pipeline for lipid identification and relative quantification, combined with statistical analysis, revealed 188 lipid species across 21 classes. We found significant upregulation of Cer-NPs, LPCs, PCs, TGs, and OxTGs in TN patients, while stigmasterol hexoside was downregulated. Moderate correlations were observed between lipid species and clinical parameters. These findings highlight considerable CSF lipidome alterations in TN, suggesting roles for nerve demyelination, neuroinflammation, and pain sensitization in its pathogenesis. Our study provides novel insights into lipid targets that may offer therapeutic potential for managing TN.PMID:40189602 | DOI:10.1038/s41598-025-89755-x

Transl Psychiatry. 2025 Apr 6;15(1):128. doi: 10.1038/s41398-025-03362-y.ABSTRACTDespite increasing mental health problems among young people, few studies have examined associations between plasma proteins and mental health. Interactions between proteins and metabolites in association with mental health problems remain underexplored. In 730 twins, we quantified associations between plasma proteins measured at age 22 with 21 indicators of either depressive symptoms or the p-factor and tested for interactions with metabolites. Symptoms were collected from questionnaires and interviews completed by different raters (e.g., self-report, teachers) through adolescence to young adulthood (12 to 22 years). We found 47 proteins associated with depressive symptoms or the p-factor (FDR < 0.2), 9 being associated with both. Two proteins, contactin-1 and mast/stem cell growth factor receptor kit, positively interacted with valine levels in explaining p-factor variability. Our study demonstrates strong associations between plasma proteins and mental health and provides evidence for proteome-metabolome interactions in explaining higher levels of mental health problems.PMID:40189586 | DOI:10.1038/s41398-025-03362-y

J Ethnopharmacol. 2025 Apr 4:119730. doi: 10.1016/j.jep.2025.119730. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Gastric ulcer (GU) is a common multifactorial gastrointestinal disorder, affecting millions of people worldwide. Mu Jin Powder (MJP), a renowned herbal pair, was recorded in Yizong Jinjian by Wu Qian during the Qing dynasty. This combination has been integrated into traditional Chinese medicine (TCM) prescriptions for gastrointestinal diseases, particularly GU, and has demonstrated significant results in modern medicine studies. However, the specific advantages of MJP for GU and its underlying mechanisms remain insufficiently understood, requiring further investigation.AIM OF THE STUDY: To assess the preventive effects of MJP on ethanol-induced gastric mucosal injury and elucidate its underlying mechanisms.MATERIALS AND METHODS: This study was based on ethanol induced SD rat model to elucidate the pharmacological effects of MJP. The chemical components of MJP and the absorbed components in the serum of treated rats were identified by UPLC-Q-TOF-MS. Serum metabolomics and Network pharmacology were applied to investigate the potential mechanisms of MJP against GU, and the mechanistic pathways were verified through PCR and Western blot analyses.RESULTS: In vivo pharmacological experiments demonstrated that MJP significantly reduced ulcer area and improved the histopathological features of gastric tissues. Fifty-three chemical components were determined in MJP, and 18 absorbed components were detected in the serum of treated rats for the first time. Non-targeted serum metabolomics revealed 28 significantly altered differential metabolites, most of which were modulated and normalized by MJP. Comprehensive network pharmacology and metabolomics analyses indicated that MJP exerted anti-GU effects by intervening in 5 key target proteins (PTG2, CHRNA7, CA1, PTG1, CASP3, and AKT1) and regulating differential metabolites. PCR and Western blot analyses suggested that MJP may inhibit the PI3K/Akt/NF-κB pathway to prevent ethanol-induced gastric ulcers.CONCLUSIONS: Mu Jin Powder effectively ameliorates ethanol-induced gastric ulcers in rats, potentially by inhibiting the PI3K/Akt/NF-κB pathway.PMID:40188894 | DOI:10.1016/j.jep.2025.119730

Water Res. 2025 Mar 31;281:123581. doi: 10.1016/j.watres.2025.123581. Online ahead of print.ABSTRACTNitrate is a common co-contaminant with 2,4-dichlorophenol (2,4-DCP) in water, presenting a challenge for environmental remediation. Under anaerobic conditions, the ring cleavage of chlorophenol is inefficient, while under aerobic conditions, nitrate removal is hindered. In this study, a microbial consortium capable of hydrogenotrophic denitrification and 2,4-DCP degradation was cultured, aiming to achieve efficient nitrate removal and 2,4-DCP degradation by alternately switching between hydrogen (H2) and oxygen (O2). Under H2 conditions, nitrate removal exceeded 90 %, while under O2 conditions, 2,4-DCP degradation reached 100 %. Under H2 conditions, the abundance of the Nar gene which was involved in nitrate reduction was higher than that under O2 conditions, promoting hydrogenotrophic denitrification. In contrast, under O2 conditions, 2,4-DCP degradation occurred via hydroxylation, ring-cleavage, dechlorination, and mineralization through the TCA cycle. Metagenomic and metabolomic analysis was performed to explore microbial metabolic pathways and potential synergistic mechanisms involved in hydrogenotrophic denitrification and 2,4-DCP biodegradation. In the H2-atmosphere, microbes (Methylobacillus and Chromobacterium), genes (E3.1.1.45 and speG), and metabolites (Cytosine and Uridine) may play a crucial role in hydrogenotrophic denitrification. In the O2-atmosphere, the functional genus of Paracoccus and Aquamicrobium associated with genes (tfdB and tfdC) may contribute to 2,4-DCP and its metabolites 2-Chloromaleylacetate degradation. These findings confirmed the role of functional microbial communities through H2/O2 regulation. This work provides a promising technological reference for treating industrial wastewater containing phenols and nitrogen.PMID:40188788 | DOI:10.1016/j.watres.2025.123581

EBioMedicine. 2025 Apr 5;115:105690. doi: 10.1016/j.ebiom.2025.105690. Online ahead of print.ABSTRACTBACKGROUND: Excessive hydrogen sulfide in the gut, generated by sulfur-metabolising bacteria from foods, has been linked to intestinal inflammation and human diseases. We aim to investigate the interplay between diet and sulphur-metabolising bacteria in relation to mortality and circulating metabolites in understudied populations.METHODS: In the Southern Community Cohort Study (SCCS), a prospective cohort of primarily low-income American adults, habitual diets were assessed using a food frequency questionnaire at baseline (2002-2009). A sulfur microbial diet score (SMDS) was developed among 514 Black/African American participants by linking habitual dietary intakes with the abundance of sulfur-metabolising bacteria profiled by faecal shotgun metagenomics. The SMDS was then constructed among all eligible SCCS participants (50,114 Black/African American and 23,923 non-Hispanic White adults), and its associations with mortality outcomes were examined by Cox proportional hazards model and Fine-Grey subdistribution hazard model. The association between SMDS and 1110 circulating metabolites was examined by linear regression among 1688 SCCS participants with untargeted metabolomic profiling of baseline plasma samples.FINDINGS: Over an average 13.9-year follow-up, SMDS was associated with increased all-cause mortality (HR [95% CI] for the highest vs. lowest quartiles: 1.21 [1.15-1.27]) and cardiovascular disease (1.18 [1.08-1.29]), cancer (1.13 [1.02-1.25]), and gastrointestinal cancer-specific (1.22 [1.00-1.49]) mortality among Black/African American participants (all P-trend<0.05). The associations were largely consistent across participant subgroups. Similar results were observed among non-Hispanic White participants. The SMDS was associated with 112 circulating metabolites, which mediated 36.15% of the SMDS-mortality association (P = 0.002).INTERPRETATION: A dietary pattern promoting sulfur-metabolising gut bacteria may contribute to increased total and disease mortality in low-income American adults.FUNDING: This study was funded by the National Institutes of Health, United States, to Vanderbilt University Medical Center, United States, and Anne Potter Wilson Chair endowment to Vanderbilt University, United States.PMID:40188743 | DOI:10.1016/j.ebiom.2025.105690

Ecotoxicol Environ Saf. 2025 Apr 5;295:118156. doi: 10.1016/j.ecoenv.2025.118156. Online ahead of print.ABSTRACTAmmonia nitrogen and salinity are critical environmental factors that significantly impact marine organisms and present substantial threats to Penaeus monodon species within aquaculture systems. This study utilized a comprehensive multi-omics approach, encompassing transcriptomics, metabolomics, and gut microbiome analysis, to systematically examine the biological responses of shrimp subjected to low salinity, ammonia nitrogen stress, and their combined conditions. Metabolomic analysis demonstrated that exposure to ammonia nitrogen stress markedly influenced the concentrations of antioxidant-related metabolites, such as glutathione, suggesting that shrimp mitigate oxidative stress by augmenting their antioxidant capacity. The transcriptomic analysis revealed an upregulation of genes linked to energy metabolism and immune responses and antioxidant enzymes. Concurrently, gut microbiome analysis demonstrated that ammonia nitrogen stress resulted in a marked increase in Vibrio populations and a significant decrease in Photobacterium, indicating that alterations in microbial community structure are intricately associated with the shrimp stress response. A comprehensive analysis further indicated that the combined stressors of ammonia nitrogen and salinity exert a synergistic effect on the immune function and physiological homeostasis of shrimp by modulating antioxidant metabolic pathways and gut microbial communities. These findings provide critical systematic data for elucidating the mechanisms through which ammonia nitrogen and salinity influence marine ecosystems, offering substantial implications for environmental protection and ecological management.PMID:40188731 | DOI:10.1016/j.ecoenv.2025.118156

Cell Rep. 2025 Apr 4;44(4):115530. doi: 10.1016/j.celrep.2025.115530. Online ahead of print.ABSTRACTSalmonella causes ∼1 million cases of gastroenteritis annually in the United States. Critical to virulence are secreted effectors that reprogram host functions. We previously discovered the effector SarA facilitates phosphorylation of STAT3, inducing expression of the anti-inflammatory cytokine interleukin-10 (IL-10). This STAT3 activation requires a region of homology with the host cytokine receptor gp130. Here, we demonstrate that a single amino acid difference is critical for the anti-inflammatory bias of SarA-STAT3 signaling. An isoleucine at pY+1 of the YxxQ motif in SarA (which binds the STAT3 SH2 domain) causes increased STAT3 recruitment and phosphorylation, biasing toward anti-inflammatory targets. This isoleucine renders SarA a better substrate for tyrosine phosphorylation by GSK-3. GSK-3 is canonically a serine/threonine kinase that nonetheless undergoes tyrosine autophosphorylation at a motif with isoleucine at the pY+1 position. Our results provide a molecular basis for how a Salmonella effector achieves supraphysiological levels of STAT3 activation to control host genes.PMID:40188438 | DOI:10.1016/j.celrep.2025.115530

J Transl Med. 2025 Apr 5;23(1):403. doi: 10.1186/s12967-025-06258-z.ABSTRACTBACKGROUND: Exposomes are critical drivers of carcinogenesis. However, how they modulate tumor behavior remains unclear. Extensive clinical data show cigarette smoke to be a key exposome that promotes aggressive tumors, higher rates of metastasis, reduced response to chemoradiotherapy, and suppressed anti-tumor immunity. We sought to determine whether smoke itself can modulate aggressive tumor behavior in head and neck squamous cell carcinoma (HNSCC) through reprogramming of the cellular reductive state.METHODS: Using established human and murine HNSCC cell lines and syngeneic mouse models, we utilized conventional western blotting, steady state and flux metabolomics, RNA sequencing, quantitative proteomics and flow cytometry to analyze the impact of smoke exposure on HNSCC tumor biology and anti-tumor immunity.RESULTS: Cigarette smoke persistently activated Nrf2 target genes essential for maintenance of the cellular reductive state and survival under conditions of increased oxidative stress in HNSCC regardless of human papillomavirus (HPV) association. In contrast to e-cigarette vapor, conventional cigarette smoke mobilizes cellular metabolism toward oxidative stress adaptation, resulting in development of cross-resistance to cisplatin. In parallel, smoke exposure modulates expression of PDL1 and the secretory phenotype of HNSCC cells resulting in an altered tumor immune microenvironment (TIME) in syngeneic mouse models and downregulated expression of antigen presentation and costimulatory genes in myeloid cells.CONCLUSION: The cigarette smoke exposome is a potent activator of the Nrf2 pathway and appears to be the primary trigger for a tripartite phenotype of aggressive HNSCC consisting of: (1) reduced chemotherapy sensitivity, (2) enhanced metastatic potential and (3) suppressed anti-tumor immunity.PMID:40188338 | DOI:10.1186/s12967-025-06258-z

Nat Commun. 2025 Apr 6;16(1):3278. doi: 10.1038/s41467-025-58314-3.ABSTRACTLongitudinal multi-view omics data offer unique insights into the temporal dynamics of individual-level physiology, which provides opportunities to advance personalized healthcare. However, the common occurrence of incomplete views makes extrapolation tasks difficult, and there is a lack of tailored methods for this critical issue. Here, we introduce LEOPARD, an innovative approach specifically designed to complete missing views in multi-timepoint omics data. By disentangling longitudinal omics data into content and temporal representations, LEOPARD transfers the temporal knowledge to the omics-specific content, thereby completing missing views. The effectiveness of LEOPARD is validated on four real-world omics datasets constructed with data from the MGH COVID study and the KORA cohort, spanning periods from 3 days to 14 years. Compared to conventional imputation methods, such as missForest, PMM, GLMM, and cGAN, LEOPARD yields the most robust results across the benchmark datasets. LEOPARD-imputed data also achieve the highest agreement with observed data in our analyses for age-associated metabolites detection, estimated glomerular filtration rate-associated proteins identification, and chronic kidney disease prediction. Our work takes the first step toward a generalized treatment of missing views in longitudinal omics data, enabling comprehensive exploration of temporal dynamics and providing valuable insights into personalized healthcare.PMID:40188173 | DOI:10.1038/s41467-025-58314-3

Biomark Res. 2025 Apr 5;13(1):55. doi: 10.1186/s40364-025-00768-0.ABSTRACTHypertrophic cardiomyopathy (HCM) is the common cause of sudden cardiac death in young people and is characterized by cardiac hypertrophy. Non-HCM caused left ventricular hypertrophy (LVH) is more common in the population, especially in people with hypertension, obesity, and diabetes. In order to identify high-risk populations, a screening technique that can rapidly differentiate between HCM and LVH patients should be developed. Plasma metabolomics may help develop useful biomarkers for the disease diagnosis. We performed a comprehensive plasma metabolomic analysis on a total of 720 individuals, included 441 HCM patients, 160 LVH patients, and 119 normal controls (NC) (derivation cohort = 368, validation cohort = 352). Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to construct discriminant models based on metabolomics, and the result showed significant changes in plasma metabolic profiling among the HCM, LVH, and NC. The prospective diagnostic biomarkers for HCM patients have been examined using variable importance in projection, fold change, and FDR. Acylcarnitines efficiently distinguished HCM and LVH patients, with a C14:0-carnitine AUC of 0.937 shown by the reiver operator characteristic (ROC) curve analysis. The biomarkers for the diagnosis of HCM patients was verified in another independent validation cohort. This study is the largest plasma metabolomics analysis of Chinese Han patients with HCM, finding biomarkers that can be used to distinguish between HCM from LVH patients. These results highlight the great potential value of plasma metabolic profiling analysis on HCM diagnoses.PMID:40188144 | DOI:10.1186/s40364-025-00768-0

Sci Rep. 2025 Apr 5;15(1):11713. doi: 10.1038/s41598-025-95867-1.ABSTRACTThe exposure of bacteria to toxic compounds such as polychlorinated biphenyl (PCB) and biphenyl induces an adaptive response at different levels of cell morphology, biochemistry, and physiology. PCB and biphenyl are highly toxic compounds commercially used in the industry. In our previous study, Brucella anthropi MAPB-9 efficiently degraded PCB-77 and biphenyl at a high concentration. In this study, we used metabolomic analyses to understand the metabolic processes occurring in MAPB-9 during exposure to biphenyl. A combination of analytical techniques such as GC-MS/MS and HR-MS study confirmed the complete biphenyl degradation pathway. The intermediate metabolic products identified were cis-2, 3-dihydro-2, 3-dihydroxy biphenyl, 2,3-dihydroxy biphenyl, and 4-dihydroxy-2-oxo-valerate. Further, benzoic acid and 2,3-dihydroxy benzoic acid metabolites identified in the extract revealed the interconnection of biphenyl and benzoic degradation pathways. In addition, the variations in the functioning of the major biochemical pathways in the cells were revealed through changes in the profile of metabolites belonging to glyoxylate, tricarboxylic acid (TCA) cycle, and fatty acid pathways. The exposure to biphenyl inhibited metabolic activity leading to changes in the morphology and metabolism. Despite many adverse changes, the MAPB-9 was able to adapt and grow in the toxic environment undergoing upper and lower biphenyl degradation pathways.PMID:40188133 | DOI:10.1038/s41598-025-95867-1

Nat Commun. 2025 Apr 5;16(1):3267. doi: 10.1038/s41467-025-58666-w.ABSTRACTThe general association between longevity and energy metabolism has been well-documented for some time, yet the specific metabolic processes that regulate longevity remain largely unexplored. In contrast to the common active swimming daphnids (e.g., Daphnia sinensis), Simocephalus vetulus is notable for being sedentary and having a lower metabolic rate, yet it has a longer lifespan than D. sinensis. In this study, metabolomic analysis and drug validation experiments are employed to demonstrate that the lower pyruvate dehydrogenase (PDH) activity reduces the locomotor performance of S. vetulus and to identify PDH activity as a regulator of the lifespan of daphnids. Inhibition of PDH activity in daphnids by CPI-613 attenuates its ATP supply and locomotor performance but significantly induces longevity. The study also determines that the invertebrate neurotransmitter octopamine and temperature have a significant impact on PDH activity and modulate daphnids lifespan. And when the effects of temperature and octopamine on PDH activity are counteracted by inhibitors or agonists, the impact on lifespan becomes ineffective. These results support an important role for PDH in lifespan regulation and locomotor performance in daphnids and provide insights into the metabolic regulation of lifespan.PMID:40188124 | DOI:10.1038/s41467-025-58666-w