PubMed

Plant Cell Environ. 2025 Mar 30. doi: 10.1111/pce.15517. Online ahead of print.ABSTRACTDormancy is a critical adaptive feature for trees to respond effectively to environmental changes. Understanding the comprehensive mechanisms regulating dormancy in poplar is vital for the genetic improvement of forest trees. However, previous studies have typically used mixed-sample extraction, which fail to capture spatial tissue-specific responses. This study provides precise spatial lipidomics analysis of poplar buds during phases of growth and dormancy by employing an innovative technique combining liquid chromatography-tandem mass spectrometry with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) for precise spatial lipidomics analysis of poplar buds during phases of growth and dormancy. MALDI-MSI revealed that most phospholipids were uniformly distributed across all tissues in growing buds but localized in the bud axis during dormancy. Moreover, triacylglycerols, which serve a storage function, were observed to accumulate mainly within the shoot apical meristem tissue during dormancy. These findings highlight the unique spatial distribution patterns of lipids during bud growth and dormancy in poplar, emphasize the role of lipid metabolism in adapting to seasonal changes, and provide new approach for elucidating the lipidomics of seasonal growth patterns in trees.PMID:40159725 | DOI:10.1111/pce.15517

J Agric Food Chem. 2025 Mar 30. doi: 10.1021/acs.jafc.5c00349. Online ahead of print.ABSTRACTThe aim of this study was to evaluate innovative mass spectrometry imaging (MSI) for determining the metabolic potential of selected soil bacteria from the genera Bacillus and Priestia in the presence of the phytopathogen Fusarium. This research marks the first application of direct 3D MSI that to visualize interactions between potential biocontrol agents and plant pathogens on agar medium. The LARAPPI/CI-3D-MSI (Laser-Assisted Remote Atmospheric Pressure Imaging/Chemical Ionization-3D Mass Spectrometry Imaging) setup provided valuable insights into the compounds produced by the tested microorganisms, revealing their spatial distributions and their ability to diffuse into the agar medium. Subsequently, a Pathway Impact Analysis of Metabolites was conducted. Ion images based on ultrahigh resolution mass spectrometry data were obtained, including for potentially bioactive compounds. Statistical analysis of the entire MS data set showed that the metabolites identified for Bacillus licheniformis samples were distinctly separated from the Priestia megaterium samples and could be helpful tools for screening biocontrol strains. The LARAPPI/CI MSI technique offers significant advantages over existing MSI methods. Further research using this technology could help validate the effectiveness of various biopreparations and contribute to enhancing the quality of biological plant protection products available on the market.PMID:40159642 | DOI:10.1021/acs.jafc.5c00349

Gut Microbes. 2025 Dec;17(1):2484386. doi: 10.1080/19490976.2025.2484386. Epub 2025 Mar 30.ABSTRACTMethicillin-resistant Staphylococcus aureus (MRSA) represents a major global health threat due to its resistance to conventional antibiotics. The commensal microbiota maintains a symbiotic relationship with the host, playing essential roles in metabolism, energy regulation, immune modulation, and pathogen control. Mammals harbor a wide range of commensal bacteria capable of producing unique metabolites with potential therapeutic properties. This study demonstrated that M28 family peptidase (M28), derived from commensal bacteria Peribacillus frigoritolerans (P. f), provided protective effects against MRSA-induced pneumonia. M28 enhanced the phagocytosis and bactericidal activity of macrophages by inducing trained immunity. RNA sequencing and metabolomic analyses identified the CFB-C3a-C3aR-HIF-1α axis-mediated phosphatidylcholine accumulation as the key mechanism for M28-induced trained immunity. Phosphatidylcholine, like M28, also induced trained immunity. To enhance M28-mediated therapeutic potential, it was encapsulated in liposomes (M28-LNPs), which exhibited superior immune-stimulating properties compared to M28 alone. In vivo experiments revealed that M28-LNPs significantly reduced bacterial loads and lung damage following MRSA infection, which also provided enhanced protection against Klebsiella pneumoniae and Candida albicans. We first confirmed a link between complement activation and trained immunity, offering valuable insights into the treatment and prevention of complement-related autoimmune diseases.PMID:40159598 | DOI:10.1080/19490976.2025.2484386

Biogerontology. 2025 Mar 30;26(2):84. doi: 10.1007/s10522-025-10225-y.ABSTRACTExercise is widely recognized for improving physical functions, learning, and memory. However, the mechanisms behind these effects are not fully understood. This study aims to investigate the potential mechanisms through which exercise enhances learning and memory in mice using multi-omics analysis. Twenty male C57BL/6J mice were divided into exercise and control groups. The exercise group underwent a 4-month treadmill training regimen (12 m/min). Learning and memory abilities were assessed using the Morris water maze test. Brain, serum, and fecal samples were collected for neurotransmitter analysis, serum metabolomics analysis, and gut microbiota analysis. Data from neurotransmitter and serum metabolomics analyses were integrated with gut microbiota analysis. For comparisons between the two groups, the independent sample t-test was employed. For comparisons involving multiple groups, a repeated measures one-way analysis of variance (ANOVA) with random unit group design was applied. Statistical significance was defined as P < 0.05. The Morris water maze test significantly improved learning and memory in the exercise group (P < 0.05). Neurotransmitter analysis revealed significant differences in cognitive function-related neurotransmitters and pathways between the exercise and control groups (P < 0.05). Serum metabolomics analysis identified differences in serum metabolites between the two groups, which were linked to key pathways involved in neural repair and cognitive function. Microbial sequencing showed greater gut microbiota diversity in the exercise group, with the most notable changes at the genus level, particularly in Allobaculum, A2, and Clostridium_sensu_stricto_1 (P < 0.05). Integrated analysis indicated correlations between changes in gut microbiota and serum metabolites associated with cognitive function. Long-term exercise enhances learning and memory in mice through multiple mechanisms, including neurotransmitter regulation, serum metabolite changes, and modulation of gut microbiota. These findings provide new insights into the neuroprotective effects of exercise.PMID:40159584 | DOI:10.1007/s10522-025-10225-y

BMC Cancer. 2025 Mar 30;25(1):573. doi: 10.1186/s12885-025-13952-0.ABSTRACTBACKGROUND: The high heterogeneity of hepatocellular carcinoma (HCC) poses challenges for precision treatment strategies. This study aims to use multi-omics methodologies to better understand its pathogenesis and discover biomarkers.METHODS: Quantitative proteomics was used to investigate hepatocellular carcinoma tissues (HCT) and their corresponding adjacent non-tumor tissues (DNT), obtained from six HCC patients. Untargeted metabolomics was applied to analyze the metabolic profiles of HCT and DNT of ten HCC patients. Statistical analyses, such as the Student's t-test, were performed to identify differentially expressed proteins (DEPs) and metabolites (DEMs) between the two groups. The functions and metabolic pathways involving DEPs and DEMs were annotated and enriched using the gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) databases. Bioinformatics methods were then utilized to analyze consistency between proteomics and metabolomics results, leading to identification of potential biomarkers along with key altered pathways associated with HCC.RESULTS: This study identified 1556 DEPs between HCT and DNT samples. These DEPs were primarily enriched in crucial biological pathways such as amino acid degradation, fatty acid metabolism, and DNA replication. Subsequently, the analysis of metabolomics identified 500 DEMs that mainly participated in glycerophospholipid metabolism, the phospholipase D signaling pathway, and choline metabolism related to cancer. Integrated analysis of proteomics and metabolomics data unveiled significant dysfunctions in bile secretion, multiple amino acid and fatty acid metabolic pathways among HCC patients. Further investigation revealed that five proteins (PTP4A3, B4GALT5, GAB1, ME2, and PKM) along with seven metabolites (PI(6 keto-PGF1alpha/16:0), 13, 16, 19-docosatrienoic acid, PA(18:2(9Z, 12Z)/20:1(11Z)), Citric Acid, PG(20:3(6, 8, 11)-OH(5)/18:2(9Z, 12Z)), Spermidine, and N2-Acetylornithine) exhibited excellent diagnostic efficiency for HCC and could serve as its potential biomarkers.CONCLUSION: Our integrated proteome and metabolome analysis revealed 10 key HCC-related pathways and proposed 12 potential biomarkers, which may enhance our understanding of HCC pathophysiology and be helpful in facilitating early diagnosis and treatment strategies.PMID:40159482 | DOI:10.1186/s12885-025-13952-0

Tree Physiol. 2025 Mar 30:tpaf038. doi: 10.1093/treephys/tpaf038. Online ahead of print.ABSTRACTPhosphorus (P) deficiency is critical to the renewal barrier of she-oak (Casuarina equisetifolia), an important tree species used for coastal protection. However, the response of she-oak to P deficiency remains unclear. In this study, we compared the phenotypes of two she-oak cultivars, the P deficiency-sensitive 'Chihu219' and the insensitive 'Chihu397', and found that P deficiency significantly increased root growth, P concentration and P absorption efficiency (PAE) in Chihu219, but not in Chihu397. We also analyzed the transcriptome and metabolome of these cultivars under different P conditions and showed that trans-zeatin riboside (tZR) levels were highly suppressed by P deficiency in Chihu219, but not in Chihu397. Furthermore, exogenous tZR suppressed both root P concentration and PAE while promoting phosphorus use efficiency (PUE). We also identified CeIPT5 (isopentenyltransferase 5) as a key regulatory gene of tZR biosynthesis and found that its expression was more highly induced by P deficiency in Chihu219 than in Chihu397. We also showed that overexpression of CeIPT5 in insensitive she-oak lines reduced tZR concentration and increased root P concentration compared to the vector control. Taken together, P deficiency can greatly reduce tZR accumulation in P deficiency-insensitive she-oak at least by activating the tZR accumulation regulatory gene, CeIPT5, thereby promoting root elongation and P concentration. This study not only provides a genetic basis for enhancing PAE in woody plants, but also establishes a theoretical basis for optimizing root structure and improving nutrient utilization efficiency, thereby promoting sustainable forestry development.PMID:40159239 | DOI:10.1093/treephys/tpaf038

Crit Rev Biotechnol. 2025 Mar 30:1-32. doi: 10.1080/07388551.2025.2478094. Online ahead of print.ABSTRACTNatural products and their derivatives have been important for treating diseases in humans, animals, and plants. However, discovering new structures from natural sources is still challenging. In recent years, artificial intelligence (AI) has greatly aided the discovery and development of natural products and drugs. AI facilitates to: connect genetic data to chemical structures or vice-versa, repurpose known natural products, predict metabolic pathways, and design and optimize metabolites biosynthesis. More recently, the emergence and improvement in neural networks such as deep learning and ensemble automated web based bioinformatics platforms have sped up the discovery process. Meanwhile, AI also improves the identification and structure elucidation of unknown compounds from raw data like mass spectrometry and nuclear magnetic resonance. This article reviews these AI-driven methods and tools, highlighting their practical applications and guide for efficient natural product discovery and drug development.PMID:40159111 | DOI:10.1080/07388551.2025.2478094

Biochem Pharmacol. 2025 Mar 28:116905. doi: 10.1016/j.bcp.2025.116905. Online ahead of print.ABSTRACTGastric cancer, a leading cause of cancer-related mortality, has a median survival of just 15 months in advanced stages and currently lacks effective treatment options. Neddylation blockade is a promising therapeutic strategy, yet its clinical application faces challenge with the emergence of drug resistance. Currently, the underlying mechanisms behind the drug resistance are not fully understood. Our study uncovers the link between MLN4924-induced metabolic reprogramming and its antitumor efficacy in gastric cancer cells. We first demonstrated that MLN4924, a neddylation blocker, has multiple effects on gastric cancer cell growth, notably inducing mitochondrial damage. Untargeted metabolomic analysis revealed that MLN4924 enhances glucose utilization in gastric cancer cells in a concentration-dependent manner. Mechanistically, MLN4924 reduces the neddylation of cullin2, thereby inhibiting the degradation of HIF-1α. This leads to the accumulation of HIF-1α, which upregulates GLUT1 levels and facilitates increased glucose uptake. This metabolic adaptation allows gastric cancer cells to maintain their energy supply despite mitochondrial impairment. Based on the increased glucose dependency following neddylation inhibition by MLN4924, we propose a co-targeting strategy with GLUT1 inhibition, which significantly improves therapeutic efficacy in vitro and in vivo models without safety risks. This dual-targeting approach represents a potent new strategy for gastric cancer treatment.PMID:40158819 | DOI:10.1016/j.bcp.2025.116905

Toxicol Lett. 2025 Mar 28:S0378-4274(25)00060-8. doi: 10.1016/j.toxlet.2025.03.011. Online ahead of print.ABSTRACTThe organophosphorus pesticide chlorpyrifos (CPF) is widely utilized in agriculture to protect crops from pests and diseases. Concerns regarding its extensive use have emerged due to the substance's persistence, bioaccumulation, endocrine disruption, and associated toxicity, which may lead to various adverse reactions. In this study, 32 male C57BL/6J mice were orally administered varying doses of CPF over a period of two weeks. Metabolic perturbations resulting from subacute exposure to CPF were assessed using LC-MS/MS-based untargeted metabolomics, alongside biochemical analysis and histopathological techniques. The 16S rRNA gene sequencing method was employed to evaluate changes in the gut microbial community within the cecal contents of mice exposed to CPF. In vivo studies have shown that CPF exposure induced dose-dependent damage and dysregulation of the intestinal microbiota in mouse colonic tissues. This was characterized by significant alterations in the gut microbiota, increased intestinal permeability and elevated levels of lipopolysaccharides. These changes may have compromised intestinal barrier function and facilitated the transfer of intestinal microbial metabolites and endotoxins to the liver, subsequently leading to liver injury. Collectively, this study elucidates a potential mechanism by which CPF triggers liver injury through alterations in the intestinal microbial community and increased intestinal permeability. These findings not only enhance our understanding of the toxicological effects of CPF but also contribute to the assessment of health risks associated with CPF exposure.PMID:40158758 | DOI:10.1016/j.toxlet.2025.03.011

Semin Immunol. 2025 Mar 29;78:101946. doi: 10.1016/j.smim.2025.101946. Online ahead of print.ABSTRACTGlycosylation of antibodies is essential for shaping immune responses, as it contributes significantly to antibody function and diversity. While immunoglobulin G (IgG) Fc glycosylation is well-characterized, variable domain glycosylation (VDG) introduces an additional and less understood layer of complexity. Notably, VDG is associated with rheumatoid arthritis, where disease-specific IgG autoantibodies abundantly express this modification. Moreover, its presence on these antibodies correlates with disease progression in at-risk individuals and therapeutic outcomes. Emerging evidence links increased VDG levels to other autoimmune diseases and B-cell malignancies, highlighting its potential as both a marker and modulator in disease onset and progression. Importantly, VDG on IgG is now recognized to influence antigen binding, enhance antibody stability, and modulate interactions with the human neonatal Fc receptor. In addition, glycans in the antigen-binding domains of autoreactive B-cell receptors (BCRs) can significantly impact B cell activation. In follicular lymphoma and other B-cell malignancies, the presence of N-glycosylation sites in the immunoglobulin variable domains leads to the introduction of oligomannose glycans, which are postulated to bind to mannose-specific lectins. This interaction might promote antigen-independent activation of BCRs, thereby supporting malignant B cell survival and proliferation. Here, we explore the regulatory pathways of VDG and its functional roles across both physiological and pathological conditions, underscoring its prevalence and significance in various autoimmune diseases and B-cell malignancies. Ultimately, advancing our understanding of the regulatory factors influencing VDG and its functional implications could be highly rewarding for identifying potential therapeutic targets and strategies to prevent and treat autoimmune diseases and B-cell malignancies.PMID:40158366 | DOI:10.1016/j.smim.2025.101946

Sci Total Environ. 2025 Mar 29;975:179262. doi: 10.1016/j.scitotenv.2025.179262. Online ahead of print.ABSTRACTIn the contemporary era, named plasticene, the extensive presence of micro- and nanoplastics (MPs/NPs) in all environmental matrices constitutes a global challenge that impacts on living beings, including humans. Regardless of the route of exposure, the internalized MPs/NPs may reach the central nervous system and cause cytotoxicity. The effects of nano- and micro- polystyrene particles (n/mPS; 100 μg/mL), both in virgin (v) and home oxidized (ox) form, were assessed on the human neuroblastoma cells SH-SY5Y, treated for 24 h, using toxicological endpoints and 1H NMR-based metabolomics. A pro-oxidant effect was shown by reactive oxygen species (ROS) overproduction, present in virgin and oxidized particles, albeit 27.6 % and 29.5 % higher in ox-nPS and ox-mPS. DNA damage, mitochondrial impairment, and lipid peroxidation were found to be directly related to particle size and oxidation state (v-nPS < ox-nPS < v-mPS < ox-mPS). The metabolic changes induced by v- and ox- n/mPS in neuroblastoma cells involved the amino acid and energy metabolism, osmoregulation, oxidative stress, and neurotransmission. Interestingly, it was highlighted the ability of SH-SY5Y cells exposed to ox-nPS to counteract more effectively oxidative damage by reshaping metabolic pathways. Overall, the combination of toxicological assays and metabolic profiling confirmed the harmful effects induced by n/mPS to SH-SY5Y cells, always enhanced by the in home-oxidized counterpart, that led to cytotoxic effects and changes in cell metabolism. Despite a variable capacity for cellular homeostasis, the results shed light on the potential risks that these ubiquitous xenobiotics pose to human health, acting also as "triggers" for neurodegenerative diseases.PMID:40158331 | DOI:10.1016/j.scitotenv.2025.179262

Redox Biol. 2025 Mar 25;82:103617. doi: 10.1016/j.redox.2025.103617. Online ahead of print.ABSTRACTAdolescent depression is a significant global health challenge, with many patients responding inadequately to antidepressant treatments. Omega-3 polyunsaturated fatty acids (ω3 PUFAs) have been proposed as a potential adjunctive treatment, but their precise mechanisms remain poorly understood. This study aimed to explore the mechanisms through which ω3 PUFAs exert their antidepressant effects and to identify potential biomarkers for their therapeutic response. A comprehensive assessment of plasma metabolomic and erythrocyte membrane lipidomic was performed on 51 depressed adolescents who were randomly assigned to received either ω3 PUFAs plus paroxetine (n = 27) or paroxetine alone (n = 24) for 12 weeks. Following ω3 PUFA supplementation, phospholipid metabolism emerged as the most significantly altered pathway. ω3 PUFAs markedly influenced the composition of membrane fatty acids, significantly increasing the ω3 PUFA content, decreasing the ω6/ω3 PUFA ratio, and increasing membrane fluidity. Notably, ω3 PUFAs reduced lipid peroxidation in both plasma and cell membranes while enhancing antioxidant capacity in the membranes. Moreover, alterations in phospholipids and membrane function were significantly correlated with improvements in depressive symptoms and cognitive function. Importantly, ω3 PUFA supplementation resulted in greater improvement in clinical symptoms compared to the non-supplemented group exclusively in the subgroup with high baseline oxidative damage levels. This study suggests that ω3 PUFAs promoted phospholipid integration and alleviated oxidative stress, which may account for their antidepressant effects. Lipid oxidation biomarkers could help identify patients likely to benefit from ω3 PUFA supplementation. These findings advance our understanding of the mechanism and clinical application of ω3 PUFAs in treating adolescent depression.PMID:40158256 | DOI:10.1016/j.redox.2025.103617

J Ethnopharmacol. 2025 Mar 28:119690. doi: 10.1016/j.jep.2025.119690. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Ershen Wan (ESW), a classic traditional Chinese medicine (TCM) prescription composed of Psoralea corylifolia Linn. and Myristica fragrans Houtt., has been applied to treat gastrointestinal disorders in clinical practices for thousands of years. However, its potential molecular mechanism in alleviating ulcerative colitis (UC) remains to be elusive.AIM OF THE STUDY: The purpose of the study is to explore the underlying mechanism of ESW in treating UC.MATERIALS AND METHODS: The protective effect of ESW on dextran sodium sulfate (DSS)-induced UC mice was assessed by body weight, disease activity index (DAI), colon length, colon tissue pathology, and colonic inflammatory factors. Furthermore, network pharmacology was applied to dissect the possible targets and biological pathways regulated by ESW. The plasma and fecal metabolomics were comprehensively analyzed by UPLC-Q-TOF/MS. Subsequently, an efficient and feasible approach integrating network pharmacology, metabolomics, and molecular docking was used to explore the key targets obtained from the metabolite-reaction-enzyme-gene network. And the effect of ESW on the MAPK signaling mediated intestinal epithelial cell apoptosis was further investigated by in vitro and in vivo experiments.RESULTS: ESW could notably alleviate colon injury and inflammation of UC mice. Network pharmacology suggested that the bioactive components of ESW could mainly modulate signaling pathways associated with inflammation and metabolism. Consistently, plasma and fecal metabolomics further indicated that ESW could regulate the metabolic pathways of arachidonic acid, linoleic acid, sphingolipid, tryptophan, and glycerophospholipid. And the combined analysis of network pharmacology and metabolomics revealed that 14 pivotal targets were modulated by ESW, including PTGS1, PTGS2, CYP1A1, FADS1, CBR1, ALOX5, EPHX1, EPHX2, HPGD, PLA2G1B, PLA2G7, MGLL, ACHE, and SPHK1. Additionally, molecular docking suggested that bioactive components of ESW could bind well to these potential targets. And in vitro and in vivo experiments further verified that ESW could markedly ameliorate pathological symptoms of UC mice through inhibiting MAPK signaling mediated colonic epithelial cell apoptosis.CONCLUSION: Collectively, these findings indicated that ESW could effectively alleviate the pathological symptoms of UC mice, mainly involving in the modulation of lipid and amino acid metabolism pathways, and the suppression of MAPK signaling-mediated apoptosis. In this study, the potential mechanism of ESW for the treatment of UC was first clarified, which provided a solid scientific foundation for its clinical application. Notably, the proposed strategy facilitated a comprehensive prediction and validation of the efficacy and molecular mechanism of TCMs, and also provided a novel approach for revealing the intricate biological pathogenesis of diseases.PMID:40158827 | DOI:10.1016/j.jep.2025.119690

Biochem Pharmacol. 2025 Mar 28:116904. doi: 10.1016/j.bcp.2025.116904. Online ahead of print.ABSTRACTMetabolic dysregulation is closely related to hepatocellular carcinoma (HCC) progression. Aberrant proline metabolism plays crucial roles in HCC onset and development. However, the detailed molecular mechanisms of proline metabolism in HCC remain unclear. In this study, we reported that hydroxyproline, a metabolite of proline, is a key causal factor of HCC progression using Mendelian randomization analysis. An elevated level of hydroxyproline promotes HCC cell growth, migration, and invasion. Using a non-targeted metabolomics approach, we found that USP10 increases the amount of proline and hydroxyproline in HCC cells. We subsequently proved that USP10 stabilizes Yes-associated protein 1 (YAP1), enhancing YAP1/TEA domain transcription factor 4 (TEAD4)-mediated transcription of prolyl 4-hydroxylase subunit alpha 1 (P4HA1). This leads to increased expression of P4HA1, which alters the proline catabolic profile. In contrast, knocking down USP10 or suppressing its activity reduced the expression of P4HA1. Given the crucial roles of USP10 in HCC progression, we further validated ginkgolic acid, a hit compound that targets USP10, leading to potential anti-HCC efficacy in xenograft mouse models. Overall, our study provides novel insights into the role and potential molecular mechanisms of USP10 on proline metabolism in HCC for the first time, as well as offers a promising therapeutic strategy of targeting USP10 for HCC treatment.PMID:40158816 | DOI:10.1016/j.bcp.2025.116904

Cell Signal. 2025 Mar 28:111775. doi: 10.1016/j.cellsig.2025.111775. Online ahead of print.ABSTRACTSmall extracellular vesicles (sEVs) from tumour cells mediate intercellular communication and signalling to regulate the progression of pancreatic ductal adenocarcinoma (PDAC). While we and others have shown that PDAC-derived sEVs comprise oncogenic protein and nucleic acid cargo, understanding the lipid landscape of these sEVs remains unknown. Lipids influence both the composition of sEVs and their roles in lipid metabolism and signalling pathways within the tumour microenvironment and tumorigenesis. We hypothesised that specific lipids in oncogenic sEVs might provide insights into PDAC. Comprehensive mass spectrometry-based lipidomic analysis was performed using liquid chromatography-electrospray ionisation-tandem mass spectrometry on sEVs isolated from PDAC and non-malignant pancreatic cell lines, patient-derived xenograft cell lines and plasma from the PDAC transgenic mouse model KPC (KRASWT/G12D/ TP53WT/R172H/Pdx1-Cre+/+). The sEV lipidomic analyses identified over 700 lipid species from 25 lipid classes and subclasses. Our results showed that, compared to non-malignant cells, PDAC-derived sEVs were enriched in specific lysophospholipids, particularly sphingosine-1-phosphate (S1P), a lipid known for its pivotal role in cancer pathogenesis. S1P enrichment was validated in plasma-derived sEVs from KPC mice compared to WT. To explore the functional implications of S1P enrichment, we conducted assays demonstrating that S1P in sEVs facilitated tubule formation in human microvascular endothelial cells and promoted cancer-associated fibroblast cell migration. We show that PDAC-derived sEVs are differentially enriched in specific lipids associated with cancer phenotype. Our findings highlight that PDAC-derived sEVs are enriched in specific lipids, particularly S1P, which plays a crucial role in promoting cancer progression.PMID:40158707 | DOI:10.1016/j.cellsig.2025.111775

Metab Eng. 2025 Mar 28:S1096-7176(25)00050-3. doi: 10.1016/j.ymben.2025.03.014. Online ahead of print.ABSTRACTMethanol is a promising sustainable alternative feedstock for green biomanufacturing. The yeast Yarrowia lipolytica offers a versatile platform for producing a wide range of products but it cannot use methanol efficiently. In this study, we engineered Y. lipolytica to utilize methanol by overexpressing a methanol dehydrogenase, followed by the incorporation of methanol assimilation pathways from methylotrophic yeasts and bacteria. We also overexpressed the ribulose monophosphate (RuMP) and xylulose monophosphate (XuMP) pathways, which led to significant improvements in growth with methanol, reaching a consumption rate of 2.35 g/L in 24 hours and a 2.68-fold increase in biomass formation. Metabolomics and Metabolite Flux Analysis confirmed methanol assimilation and revealed an increase in reducing power. The strains were further engineered to produce the valuable heterologous product resveratrol from methanol as a co-substrate. Unlike traditional methanol utilization processes, which are often resource-intensive and environmentally damaging, our findings represent a significant advance in green chemistry by demonstrating the potential of Y. lipolytica for efficient use of methanol as a co-substrate for energy, biomass, and product formation. This work not only contributes to our understanding of methanol metabolism in non-methylotrophic organisms but also paves the way for achieving efficient synthetic methylotrophy towards green biomanufacturing.PMID:40158687 | DOI:10.1016/j.ymben.2025.03.014

Plant Physiol Biochem. 2025 Mar 26;223:109835. doi: 10.1016/j.plaphy.2025.109835. Online ahead of print.ABSTRACTIn early spring, bleeding is a common occurrence in A. arguta when local temperatures reach 8 °C-10 °C. In this study, changes in the composition of bleeding sap and effect of bleeding on A. arguta were determined by analyzing the variation in the composition of bleeding sap from different periods. Accordingly, the bleeding sap was analyzed by gas chromatography-mass spectrometry (GC-MS), and the related physiological indexes in the stem were measured. The results revealed that in annual early spring, bleeding seriously affected A. arguta. In addition, annual branches had a stronger capacity for scavenging free radicals than biennial or barren branches. The metabolomics analysis identified a total of 153 differential metabolites, mainly involved in glycolysis and the tricarboxylic acid cycle. Bleeding decreased the number and length of new shoots and basal stems, as well as the size of the phloem, phloem fibers, and xylem. In contrast, the proline, soluble protein, soluble sugar, and malondialdehyde contents, as well as the activities of superoxide dismutase, catalase, and peroxidase, increased in treated stems compared with untreated controls. This study was the first to analyze the metabolomic profile of bleeding sap in A. arguta and investigate the effects of bleeding on its growth and development. The results will provide a theoretical basis for explaining the physiological changes occurring in stems after bleeding and lay a foundation for further research on understanding the underlying mechanism and repairing bleeding.PMID:40158483 | DOI:10.1016/j.plaphy.2025.109835

Plant Physiol Biochem. 2025 Mar 24;223:109828. doi: 10.1016/j.plaphy.2025.109828. Online ahead of print.ABSTRACTLight quality exerts a vital influence on the accumulation of secondary metabolites in medicinal plants. Atropa belladonna L. serves as a primary source plant of tropane alkaloids (TAs). Nevertheless, in agricultural production, its application is restricted due to the relatively low content of alkaloids. This study explored the impacts of red, yellow, blue, and white light on the growth of A. belladonna and the biosynthesis of TAs. Through phenotypic and physiological analyses, it was found that red-light had the most significant effect on A. belladonna. Red-light remarkably increased the content of TAs, enlarged the leaf area, extended the stomatal length, and elevated the ammonium nitrogen level. It also enhanced the activities of ornithine decarboxylase, nitrate reductase, and glutamine synthetase, which are essential for nitrogen assimilation. Transcriptomic analysis identified GDHA, At2g42690, and PAO5 as key genes with upregulated expression in the putrescine biosynthesis pathway, where putrescine is an important precursor of TAs. Metabolomic data confirmed that the levels of scopolamine, hyoscyamine, and their precursors increased under red-light. Subsequent qPCR verification under red/white light treatments consistently showed the upregulation of these genes, further confirming their roles in the synthesis of TAs. Moreover, red-light activated photosynthesis-related genes and transcription factors, indicating a coordinated regulatory relationship between light signal transduction and metabolic pathways. This study has preliminarily elucidated the potential mechanism by which red-light promotes the accumulation of TAs through enhancing nitrogen metabolism and precursor synthesis, providing a theoretical basis for improving the quality of A. belladonna and optimizing agricultural production.PMID:40158482 | DOI:10.1016/j.plaphy.2025.109828

Environ Health. 2025 Mar 29;24(1):14. doi: 10.1186/s12940-025-01162-x.ABSTRACTBACKGROUND: Prenatal exposure to air pollution has been associated with an increased risk of low birth weight. Disrupted metabolism may serve as an underlying mechanism, but the specific metabolic pathways involved remain unclear.METHODS: In the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) study, 382 third-trimester maternal serum samples were analyzed for untargeted metabolomics using liquid chromatography with Fourier transform high-resolution mass spectrometry. Ambient concentrations of fine particulate matter (PM2.5), particulate matter ≤ 10 μm in diameter (PM10), nitrogen dioxide (NO2), and ozone (O3) were estimated using inverse-distance-squared weighted spatial interpolation based on daily residential histories. Birth weight was retrieved from medical records. Linear regression identified metabolomic features associated with air pollution exposure or birth weight, followed by Mummichog pathway enrichment and mediation analyses for the selected features.RESULTS: Second-trimester PM2.5 exposure was associated with lower birth weight. Fourteen metabolic pathways were significantly associated with second-trimester PM2.5 exposure, with C21-steroid hormone biosynthesis and metabolism showing the most significant association. Sixteen metabolic pathways were significantly associated with birth weight, with vitamin A (retinol) metabolism being the most significantly enriched pathway. Seven pathways were associated with both PM2.5 exposure and birth weight, including C21-steroid hormone biosynthesis and metabolism, bile acid biosynthesis, tyrosine metabolism, ascorbate (vitamin C) and aldarate metabolism, vitamin D3 (cholecalciferol) metabolism, vitamin A (retinol) metabolism, and pyrimidine metabolism. Overweight or obese women exhibited more metabolomic features and metabolic pathways associated with PM2.5 exposure compared to underweight or normal-weight women. No associations were observed between PM10, NO2, or O3 and birth weight.CONCLUSIONS: Maternal metabolic pathways involving steroid metabolism, oxidative stress and inflammation, vitamin metabolism, and DNA damage may link prenatal PM2.5 exposure to lower birth weight, with overweight or obese women potentially more susceptible to these metabolic disruptions.PMID:40158186 | DOI:10.1186/s12940-025-01162-x

Nutr J. 2025 Mar 29;24(1):50. doi: 10.1186/s12937-025-01116-6.ABSTRACTThe gut microbiome can modulate nutrient metabolism to produce many metabolites interacting with the host. However, the intricate interactions among dietary intake, the gut microbiome and metabolites, and host metabolites need to be further explored although some studies have been devoted to it. Here, in a cross-sectional studies, 88 children aged 2-12 years were enrolled from northwestern China. The dietary intake data were collected via a designed food frequency questionnaire to calculate plant-based diet indices (PDIs). Stool and plasma samples were collected for metagenomic and broad-targeted metabolomic analysis. Spearman's rank correlation was used to describe the associations between nutrients/PDIs and the gut microbiota and metabolites. PDI was significantly positively associated with Bilophila wadsworthia, Bacteroides thetaiotaomicron, and Alistipes indistinctus, etc., but was obviously negatively correlated with Roseburia intestinalis, Faecalibacterium prausnitzii, etc. However, these species showed no significant associations with either healthy PDI (hPDI) or unhealthy PDI (uPDI). Interestingly, hPDI was significantly positively related to species, including Ruminococcus bicirculans, and was significantly negatively associated with uPDI, and vice versa. The above correlation trends were also observed between PDIs and predicted gut microbial functional pathways, microbial metabolites and the host metabolome. Notably, the significantly related pathways were focused mainly on substances and energy metabolism. PDI was significantly positively associated with the fecal contents of P-aminobenzoate, chenodeoxycholic acid, 4,6-dihydroxyquinoline, quinoline-4,8-diol, etc., but was significantly negatively associated with those of TMAO, FFA, creatine phosphate, etc. In plasma, PDI was significantly positively associated with sarcosine, ornithine, L-histidine, etc., but was distinctly negatively correlated with FFAs, carnitine C2:0, etc. Strikingly, the healthy plant-based diet index (hPDI) is correlated with increased levels of metabolites related to tryptophan metabolism, whereas the unhealthy PDI (uPDI) is linked to increased levels of metabolites associated with tyrosine and sphingolipid metabolism, which are pathways commonly associated with Western diets. Our studies provide reliable data support and a comprehensive understanding of the effects of dietary intake on the gut microbiome and microbial and host metabolites and lay a foundation for further studies of the diet-gut microbiota-microbial metabolites and host metabolism.PMID:40158160 | DOI:10.1186/s12937-025-01116-6