PubMed

Nat Commun. 2025 Mar 19;16(1):2651. doi: 10.1038/s41467-025-58107-8.ABSTRACTAnti-programmed death 1 (αPD1) immune checkpoint blockade is used in combination for cancer treatment but associated with cardiovascular toxicity. Leflunomide (Lef) can suppress the growth of several tumor and mitigate cardiac remodeling in mice. However, the role of Lef in αPD1-induced cardiotoxicity remains unclear. Here, we report that Lef treatment inhibits αPD1-related cardiotoxicity without compromising the efficacy of αPD1-mediated immunotherapy. Lef changes community structure of gut microbiota in αPD1-treated melanoma-bearing mice. Moreover, mice receiving microbiota transplants from Lef+αPD1-treated melanoma-bearing mice have better cardiac function compared to mice receiving transplants from αPD1-treated mice. Mechanistically, we analyze metabolomics and identify indole-3-propionic acid (IPA), which protects cardiac dysfunction in αPD1-treated mice. IPA can directly bind to the aryl hydrocarbon receptor and promote phosphoinositide 3-kinase expression, thus curtailing the cardiomyocyte response to immune injury. Our findings reveal that Lef mitigates αPD1-induced cardiac toxicity in melanoma-bearing mice through modulation of the microbiota-IPA-heart axis.PMID:40108157 | DOI:10.1038/s41467-025-58107-8

J Cardiovasc Comput Tomogr. 2025 Mar 18:S1934-5925(25)00048-6. doi: 10.1016/j.jcct.2025.03.001. Online ahead of print.ABSTRACTBACKGROUND: Air pollution is associated with mortality and major adverse cardiovascular events (MACE) in the general population. However, little is known about the relationship between air pollution and coronary artery disease (CAD) and how this relates to MACE.METHODS: This study utilized data from the computed tomography (CT) arm of the PROMISE trial investigating symptomatic individuals with suspected CAD. We linked levels of air pollutants (PM2·5, PM10, NO2, and ozone) at U.S. zip codes of residence CT-derived CAD and adjudicated MACE (all-cause death, myocardial infarction, and hospitalization for unstable angina). Multivariable analyses were adjusted for the ASCVD risk score and socioeconomic determinants of health. Mediation analyses were used to test putative pathways.RESULTS: In 4343 individuals (48 ​% males; age: 61 ​± ​8 years), elevated exposures to PM2.5 (≥9.4 ​μg/m3) and NO2 (≥5.3 ​ppb) were independently associated with obstructive CAD (aOR ​= ​1.23, 95%CI: 1.03-1.48, p ​= ​0.024; aOR ​= ​1.56, 95%CI: 1.02-2.40, p ​= ​0.042), while there were no significant associations with PM10 (≥15 ​μg/m3) or ozone (≥51 ​ppb). Increased PM2.5, PM10 and ozone were independently associated with MACE (aHR ​= ​1.56, 95%CI: 1.12-2.18, p ​= ​0.008; aHR ​= ​2.09, 95%CI: 1.18-3.70, p ​= ​0.011, aHR ​= ​1.96, 95%CI: 1.20-3.21, p ​= ​0.008). In the mediation analysis, obstructive CAD accounted for 9 ​% of the total effect (p ​= ​0.012) between PM2.5 and MACE.CONCLUSION: Exposure to air pollution, particularly PM2.5, was independently associated with obstructive CAD and MACE, with obstructive CAD mediating a small but significant portion of the association between air pollution and MACE.PMID:40107947 | DOI:10.1016/j.jcct.2025.03.001

Korean J Pain. 2025 Mar 20. doi: 10.3344/kjp.24355. Online ahead of print.ABSTRACTBACKGROUND: Chrysin is a natural flavonoid that exhibits various pharmacological activities including pain relief. However, the effects of chrysin on changes of metabolic profiles during pain remain unclear. The aim of this study was to analyze the biomarkers related to pain in serum and to evaluate the analgesic properties of chrysin in a rat model of pain.METHODS: Male Wister rats were divided into four groups (n = 5). Pain was induced by injecting 50 μL of formalin into the hind paw. Chrysin and diclofenac (10 mg/kg, intraperitoneal injection) was administered to the intact and pain groups. All injections were given 30 minutes before pain induction. Immediately, the behavioral test was performed. Then the serum sample was separated for 1HNMR-based metabolite analysis.RESULTS: Chrysin treatment alleviated the paw licking events, flinching response, and pain score. The integrated analyses further revealed three major metabolic changes including glycine-serine-threonine, taurine-hypotaurine, and arginine by comparing the serums from intact operated rats, pain rats, and pain rats treated with chrysin, and suggested that chrysin may improve pain by regulating the biosynthesis of these metabolic pathways.CONCLUSIONS: These findings provide insights into metabolic pathways involved in pain and the analgesic effects of chrysin and may help to identify potential targets for the anti-pain properties of chrysin.PMID:40107856 | DOI:10.3344/kjp.24355

Metabolism. 2025 Mar 17:156195. doi: 10.1016/j.metabol.2025.156195. Online ahead of print.ABSTRACTMetabolome-based biomarkers contribute to identify mechanisms of disease and to a better understanding of overall mortality. In a long-term follow-up subsample (n = 1878) of the PREDIMED trial, among 337 candidate baseline plasma metabolites repeatedly assessed at baseline and after 1 year, 38 plasma metabolites were identified as predictors of all-cause mortality. Gamma-amino-butyric acid (GABA), homoarginine, serine, creatine, 1-methylnicotinamide and a set of sphingomyelins, plasmalogens, phosphatidylethanolamines and cholesterol esters were inversely associated with all-cause mortality, whereas plasma dimethylguanidino valeric acid (DMGV), choline, short and long-chain acylcarnitines, 4-acetamidobutanoate, pseudouridine, 7-methylguanine, N6-acetyllysine, phenylacetylglutamine and creatinine were associated with higher mortality. The multi-metabolite signature created as a linear combination of these selected metabolites showed a strong association with all-cause mortality using plasma samples collected in PREDIMED also at 1-year follow-up. This association was subsequently confirmed in 4 independent American cohorts, validating the signature as a consistent predictor of all-cause mortality across diverse populations.PMID:40107652 | DOI:10.1016/j.metabol.2025.156195

Clin Chim Acta. 2025 Mar 17:120246. doi: 10.1016/j.cca.2025.120246. Online ahead of print.ABSTRACTOvarian cancer (OC), a leading cause of gynecological cancer mortality, is frequently detected at advanced stages due to asymptomatic early progression. This study investigates plasma-based untargeted metabolomics for identifying biomarkers to screen and differentiate ovarian tumors (OT). Plasma samples from OC, benign ovarian tumors (BOT), and healthy controls (HC) were analyzed. Samples were randomized into train and test sets, with differential metabolites screened via two-tailed Student's t-test and partial least squares discriminant analysis. ROC models evaluated discriminatory capacity. Key metabolites demonstrated high predictive value: TMAO and hippuric acid distinguished OT from HC (AUC > 0.95), while linoleic acid, alpha-linolenic acid, and arachidonic acid (AUC > 0.9) further supported OT screening. Kynurenine differentiated OC from BOT (AUC = 0.808). Reduced levels of specific lysophosphatidylcholines (LPC (17:0/0:0), LPC (15:0/0:0)) also distinguished OT from HC (AUC = 0.771-0.89). These findings suggest plasma metabolomics holds promise for noninvasive biomarker discovery in OT screening and distinguishing between malignant and benign cases, though further validation of metabolite quantification is warranted prior to clinical application.PMID:40107594 | DOI:10.1016/j.cca.2025.120246

Hum Reprod. 2025 Mar 19:deaf040. doi: 10.1093/humrep/deaf040. Online ahead of print.ABSTRACTSTUDY QUESTION: What are the plasma metabolomics profiles associated with endometriosis in adolescents and young adults?SUMMARY ANSWER: Our findings show dysregulation of plasma metabolomic profiles in adolescents and young adults with endometriosis, revealing systemic elevation of fatty acyls and ceramides in endometriosis cases compared to controls.WHAT IS KNOWN ALREADY: Endometriosis is a gynecologic disease often presenting with severe pelvic pain impacting around 200 million reproductive-aged women worldwide. However, little is known about the pathophysiology and molecular features of endometriosis diagnosed during adolescence and young adulthood.STUDY DESIGN, SIZE, DURATION: We conducted a cross-sectional analysis including 190 laparoscopically confirmed endometriosis cases and 120 controls who participated in The Women's Health Study: From Adolescence to Adulthood, which enrolled participants from 2012 to 2018. Control participants were females without a diagnosis of endometriosis enrolled from the same clinics as the cases or recruited from the general population. Among the cases, 81 had blood samples collected before and after surgery.PARTICIPANTS/MATERIALS, SETTING, METHODS: Plasma metabolites were measured in blood collected at enrollment using liquid chromatography-tandem mass spectrometry, and a total of 430 known metabolites were evaluated in our analysis. We used linear regression adjusting for age at blood draw, BMI, hormone use, and fasting status at blood draw. Metabolite set enrichment analysis (MSEA) was used to identify metabolite classes. Number of effective tests (NEF) and false discovery rate (FDR) were used for multiple testing correction.MAIN RESULTS AND THE ROLE OF CHANCE: The median age was 17 years for endometriosis cases and 22 years for controls. The majority of endometriosis cases had rASRM stage I or II (>95%). We identified 63 plasma metabolites associated with endometriosis (NEF < 0.05). Endometriosis cases had higher levels of plasma metabolites associated with proinflammatory response [e.g. eicosatrienoic acid (β = 0.61, 95% CI = 0.37, 0.86)], increased oxidative stress response [e.g. xanthine (β = 0.64, 95% CI = 0.39, 0.88)], and downregulation of metabolites related to apoptosis [glycocholic acid (β = -0.80, 95% CI = -1.04, -0.56)]. MSEA revealed increased fatty acyls (FDR = 2.3e-4) and ceramides (FDR = 6.0e-3) and decreased steroids and steroid derivatives (FDR = 1.3e-4) in endometriosis cases compared to controls. When we examined the changes in plasma metabolite profiles before and after surgery among endometriosis cases, 55 endometriosis-associated metabolites significantly changed from before to after surgery. MSEA revealed steroids and steroid derivatives (FDR = 8.1e-4) significantly increased after surgery, while fatty acyls (FDR = 1.2e-4) significantly decreased after surgery. Ceramides did not change from pre- to post-surgery and were elevated in post-surgical blood compared to controls (FDR = 3.9e-3).LIMITATIONS, REASONS FOR CAUTION: Our study population mainly consists of self-reported non-Hispanic, white individuals and endometriosis cases with superficial peritoneal lesions only, so the generalizability may be limited. Furthermore, despite our large study population of adolescents and young adults with endometriosis, sample size was limited to conduct detailed stratified analyses of plasma metabolomic profiles, especially by post-surgical pelvic pain outcomes.WIDER IMPLICATIONS OF THE FINDINGS: Our study includes the utilization of state-of-the-art metabolomics technology with high reproducibility to comprehensively investigate the metabolites that were associated with endometriosis diagnosed in adolescents and young adults. Our results suggest a positive impact of endometriosis-related surgery for some, but not all, on systemic metabolic dysregulation in young patients with endometriosis. These results warrant further investigation on whether and how persistent systemic changes despite treatment may lead to long-term chronic disease risk among those diagnosed with endometriosis.STUDY FUNDING/COMPETING INTEREST(S): Financial support for establishment of and data collection within the A2A cohort was provided by the J. Willard and Alice S. Marriott Foundation, and support for assay costs was in part provided by the Peery family. This project was funded by Eunice Kennedy Shriver National Institute of Child Health and Human Development R21HD107266. S.A.M., A.L.S., and K.L.T. were supported by Eunice Kennedy Shriver National Institute of Child Health and Human Development R01HD094842. S.A.M. received grant funding from AbbVie, National Institutes of Health, Department of Defense, and Marriott Family Foundation; received honoraria from WERF, Huilun Shanghai, and University of Kansas Medical Center; travel support from SRI, ESHRE, FWGBD, University of Michigan, MIT, ASRM, LIDEA Registry, Taiwan Endometriosis Society, SEUD, Japan Endometriosis Society, NASEM, Endometriosis Foundation of America, Gedeon Richter Symposium at ESHRE; Board member receiving financial remuneration from AbbVie, Roche, LIDEA Registry, Editor of Frontiers in Reproductive Health, Roundtable participation for Abbott; Board member without financial remuneration from NextGen Jane and Statistical Advisory Board member of Human Reproduction; leadership role in Society for Women's Health Research, World Endometriosis Society, World Endometriosis Research Foundation, ASRM, ESHRE. N.S. and K.L.T. receive grant funding from Aspira Women's Health unrelated to this project. The remaining authors have no disclosures relevant to this manuscript.TRIAL REGISTRATION NUMBER: N/A.PMID:40107296 | DOI:10.1093/humrep/deaf040

Ecotoxicol Environ Saf. 2025 Mar 18;294:118056. doi: 10.1016/j.ecoenv.2025.118056. Online ahead of print.ABSTRACTAs an emerging environmental pollutant, microplastics have attracted increasing attention to their potential health hazards. However, the current understanding about the toxicity and health implications, especially about developmental toxicity with exposure to microplastics is quite limited. In the current study, we aimed to scrutinize the deleterious effects of polystyrene microplastics (PSMPs) with different sizes (0.1 and 5 μm) on the placenta that plays crucial role in fetal development, following oral exposure during gestational stages. The results showed that two sizes of PSMPs could distribute in mouse placental tissues, and nanosized PSMPs (0.1 μm) exhibited greater capability to penetrate the placenta and deposit in the liver and brain of fetuses than microsized PSMPs (5 μm). Importantly, only 0.1 μm PSMPs induced a decrease in the junctional area, a reduction in the labyrinthine vascularization and an increase in cell apoptosis in the placenta, accompanied by fetal developmental impairments. The results of metabolome and transcriptome uncovered that 0.1 μm PSMP exposure caused changes in metabolic and gene profiles of placental tissues, across multiple pathways such as vascular supply, nutrient absorption and transportation and amino acid metabolism. Overall, our results confirmed that maternal PSMP exposure led to placental damages associated with metabolic and gene expression disorders. This study would provide new insights into the developmental impacts of microplastic consumption during gestation.PMID:40107219 | DOI:10.1016/j.ecoenv.2025.118056

J Chromatogr B Analyt Technol Biomed Life Sci. 2025 Mar 16;1256:124563. doi: 10.1016/j.jchromb.2025.124563. Online ahead of print.ABSTRACTDendrobium huoshanense (DH) belongs to the Dendrobium genus of the Orchidaceae family and is a herbaceous plant that protects the liver and nourishes the Yin according to traditional Chinese Medicine (TCM) theory. This research aimed to determine the therapeutic effect and mechanisms of DH on a nonalcoholic fatty liver disease (NAFLD) mouse model and its chemical composition. For pharmacological research, the pathological damage and lipid accumulation in liver tissues were evaluated using HE and oil red staining, respectively. The differential proteins between the model and DHH groups were screened using 4D label-free quantitative proteomics, and the proteomic results were verified using Western blot. The potential mechanism was validated by metabolomic analysis. The main active ingredients in a DH aqueous extract were identified using UHPLC-Q Exactive HF HRMS. Pathological staining results showed that DH can reverse liver pathological damage and lipid accumulation in the NAFLD model. Quantitative proteomics revealed that the differential proteins were mainly associated with liver lipid deposition (LAL, AMPK, TM7SF2, SBCAD, and SIRT1), insulin resistance (GYS1, GYS2, PYGL, FoxO1, and PPAR-γ), and inflammation (TLR2 and MAPKAPK). Western blot verified the above-mentioned results. Metabolomic analysis also indicated that the DH aqueous extract ameliorated NAFLD in mice by affecting cholesterol metabolism and AMPK signaling pathway, proving its significant therapeutic effects on the NAFLD model. Sixty-five compounds were identified from DH aqueous extract by analyzing the precise molecular weight and MS/MS fragmentation pathway. The pharmacological mechanism of DH in treating NAFLD mainly involved the TLR2-NF-κB and AMPK-SREBP1-SIRT1 signaling pathways.PMID:40107184 | DOI:10.1016/j.jchromb.2025.124563

Biophys Chem. 2025 Mar 15;322:107436. doi: 10.1016/j.bpc.2025.107436. Online ahead of print.ABSTRACTSevere Acute Pancreatitis (SAP) is characterized by an abrupt onset of pancreatic inflammation, which may induce damage to other organs, and is associated with significant morbidity and mortality. Despite the considerable disease burden, specific treatments to stop progression or prevent occurrence are limited. Currently, there is a paucity of comprehensive studies that thoroughly explore metabolic dysregulation in SAP, particularly those that emphasize changes in outcomes. Nuclear magnetic resonance (NMR) based metabolomics coupled with multivariate analysis was applied to serum samples of 20 survivors and 30 non-survivors of SAP to identify metabolic changes linked to different outcomes. The discriminant analysis of serum samples of SAP survivors and non-survivors revealed isoleucine, leucine, valine, arginine, lactate, and 3-hydroxybutyrate as significant metabolites elevated in the non-survivors. These identified metabolites had shown a significant positive correlation with clinical severity scores in the Pearson correlation analysis. Pathway analysis revealed disruptions in amino acid metabolism, driven by protein catabolism to fulfill the patient's energy requirements. This study highlights the importance of metabolomics in unraveling the molecular and physiological mechanisms underlying SAP. These findings offer valuable insights for clinicians to develop treatment strategies that target metabolic pathways in SAP, potentially for improving patient outcomes.PMID:40107078 | DOI:10.1016/j.bpc.2025.107436

J Pharm Biomed Anal. 2025 Mar 12;260:116806. doi: 10.1016/j.jpba.2025.116806. Online ahead of print.ABSTRACTThe leaves of Annona muricata Linn. have long been utilized in traditional medicine for diabetes treatment, and there is no study that has employed a metabolomics approach to investigate the plant's effects in managing the disease. We aimed to explore the antidiabetic effects of the standardised A. muricata leaf extract on diabetes-induced rats by alloxan monohydrate (Ax) and nicotinamide (NA) using a proton nuclear magnetic resonance (¹H-NMR)-based metabolomics approach. Absolute quantification was performed on the leaf extract using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Two different doses of the extract were administered orally for four weeks to diabetic rats induced with Ax + NA, and physical evaluations, biochemical analyses, and ¹H-NMR metabolomics of urine and serum were assessed. The results showed that quercetin 3-rutinoside was the most abundant compound in the 80 % ethanolic extract of A. muricata leaf. The induction of type 2 diabetes mellitus (T2DM) in the rat model was confirmed by the clear metabolic distinction between normal rats, diabetic rats, and metformin-treated diabetic rats. The low-dose of A. muricata leaf extract (200 mg/kg) was found to exhibit better results, significantly reducing serum urea levels in diabetic rats, with effects comparable to those of metformin. Additionally, metabolite analysis from ¹H-NMR metabolomics of serum and urine showed a slight shift toward normal metabolic profiles in the treated diabetic rats. Pathway analysis revealed alterations in the tricarboxylic acid cycle (TCA), pyruvate metabolism, and glycolysis/gluconeogenesis pathways in the diabetic rat model, which were improved following treatment with the A. muricata leaf extract. Overall, this study provides scientific support for its traditional use in diabetes management and offers new insights into the underlying molecular mechanisms.PMID:40106911 | DOI:10.1016/j.jpba.2025.116806

Environ Sci Technol. 2025 Mar 19. doi: 10.1021/acs.est.4c11949. Online ahead of print.ABSTRACTFerroferric oxide nanoparticles (Fe3O4 NPs) are widely utilized as nanoenabled agrochemicals and soil remediation agents, with functional modification significantly enhancing their stability and biocompatibility. However, excessive use of Fe3O4 NPs may pose unassessed ecological risks in soils, particularly concerning the regulatory role of two most common surface modifiers as polyvinylpyrrolidone (PVP) and citric acid (CA) which influence the interactions of NPs with soil organisms and potential toxicity. This study evaluated the nanotoxic effects of bare Fe3O4 NPs (B-Fe3O4 NPs), CA-Fe3O4 NPs, and PVP-Fe3O4 NPs on Eisenia fetida in soil ecosystems. After 7 days of exposure, the B-, CA- and PVP-Fe3O4 NPs decreased the weight of the earthworms, caused oxidative stress and tissue damage. Functional Fe3O4 NPs showed increased accumulation in earthworms while alleviating oxidative stress and homeostatic imbalance by accelerating the activation of related enzymes. Moreover, hyperspectral and pathological observations indicated that CA and PVP modifications effectively alleviated tissue damage caused by Fe3O4 NPs via an improvement in NP biocompatibility, dispersion and stability evidenced by the levels of inositol metabolites, which has been upregulated more significantly by B-Fe3O4 NPs. Significant metabolic disturbances were observed, indicating that functional modifications forced earthworms to adjust amino acid metabolism and consume more energy to detoxify and repair damage. This work supplements the toxic assessment of Fe3O4 NPs and provides crucial insights for optimizing the safety of NPs through functionalization.PMID:40106728 | DOI:10.1021/acs.est.4c11949

J AOAC Int. 2025 Mar 19:qsaf025. doi: 10.1093/jaoacint/qsaf025. Online ahead of print.ABSTRACTBACKGROUND: Dendrobium nobile is an edible orchid with diverse therapeutic properties. In north-eastern Himalayan states of India, the extract of this flower is consumed by tribal populations for the treatment of diabetes, cancer, and cardiovascular diseases. However, the profile of biologically active compounds in the colored varieties of D. nobile orchid flowers cultivated in the north-eastern Himalayan region is not well-established, necessitating a thorough investigation.OBJECTIVE: This study aims to establish and compare the metabolite profile of three types of D. nobile flowers (white, light-pink, and dark pink) using liquid chromatography-high resolution mass spectrometry (LC-HRMS).METHODS: The homogenized and cryoground flower samples were extracted with aqueous methanol. After LC-MS data acquisition through full-scan (untargeted) and MS/MS (targeted) modes, data processing involved peak alignment, adduct identification, and integration. Results were compared by multivariate statistics using Independent Component Analysis.RESULTS: A total of 73 metabolites was identified, each with mass error of less than 5 ppm for both precursor and fragment ions. From anthocyanin classes, the chemometric analysis revealed 11 distinguishing biomarker metabolites, with variable influence on projection values above 1. Across the test accessions, three compounds, viz. cyanidin-3-diglucoside, delphinidin-3-sophoroside, and delphinidin-3-gentiobioside revealed their discriminatory presence.CONCLUSION: The study identified the therapeutically important anthocyanins for metabolomic discrimination of three different D. nobile flower accessions. The study will be useful for authenticating D. nobile accessions, derived products, and selecting candidate traits for future breeding programs for varietal improvements.HIGHLIGHTS: This study identified and profiled the bioactive anthocyanin compounds in D. nobile orchid flowers grown in the north-eastern Himalayan region of India, based on color variations using a non-target metabolomics approach.PMID:40106708 | DOI:10.1093/jaoacint/qsaf025

Cell Rep. 2025 Mar 17;44(3):115411. doi: 10.1016/j.celrep.2025.115411. Online ahead of print.ABSTRACTThe recent global pandemic illustrates the importance of understanding the host cellular infection processes of emerging zoonotic viruses. Nipah virus (NiV) is a deadly zoonotic biosafety level 4 encephalitic and respiratory paramyxovirus. Our knowledge of the molecular cell biology of NiV infection is extremely limited. This study identified changes in cellular components during NiV infection of human cells using a multi-platform, high-throughput transcriptomics, proteomics, lipidomics, and metabolomics approach. Remarkably, validation via multi-disciplinary approaches implicated viral glycoproteins in enriching mitochondria-associated proteins despite an overall decrease in protein translation. Our approach also allowed the mapping of significant fluctuations in the metabolism of glucose, lipids, and several amino acids, suggesting periodic changes in glycolysis and a transition to fatty acid oxidation and glutamine anaplerosis to support mitochondrial ATP synthesis. Notably, these analyses provide an atlas of cellular changes during NiV infections, which is helpful in designing therapeutics against the rapidly growing Henipavirus genus and related viral infections.PMID:40106432 | DOI:10.1016/j.celrep.2025.115411

Mycorrhiza. 2025 Mar 19;35(2):23. doi: 10.1007/s00572-025-01195-7.ABSTRACTPanax quinquefolius L, a medicinal plant of the family Araliaceae, has been used in China for more than 300 years. The quality of its medicinal materials is a significant concern. Our previous studies have shown that arbuscular mycorrhizal fungi (AMF) promote the growth of P. quinquefolius and facilitate the accumulation of the active ingredient ginsenosides. However, these beneficial effects are limited by the low AMF colonization rate in production settings, requiring interventions to improve the colonization rate. Biochar is considered an effective soil amendment. Our preliminary experiments indicate that biochar can enhance the inter-root microecology of P. quinquefolius, as well as increase the AMF colonization rate, but the mechanism was not clear. Therefore, we propose using biochar to increase the AMF colonization rate. In this study, we explore the use of biochar to promote the AMF infestation rate of P. quinquefolius and its potential mechanisms. The mechanism was explored by setting up eight treatments. The colonization rate and intensity of AMF in P. quinquefolius roots were assessed using a Trypan Blue solution. Rhizosphere soil microorganisms were analyzed by 16S and ITS sequencing, and secondary metabolites were identified via non-targeted metabolomics. The results showed that the AMF and 2% biochar combined (AMF + BC2) treatment significantly increased both the colonization rate and colonization intensity of AMF, which were 53.58% and 195.95% higher than that of AMF, respectively. The colonization and rhizosphere AMF data indicate that the application of biochar promotes AMF colonization from outside to inside the root. In addition, biochar attracted potentially beneficial microorganisms such as Sphingobium, Sphingomonas, and Novosphingobium, which are positively correlated with AMF and promote AMF colonization. These microorganisms are closely linked with active secondary metabolites, such as Sphingobium, which is positively correlated with L-malic acid. In conclusion, biochar can improve the quality of P. quinquefolius by promoting the formation of mycorrhizae. This finding provides a theoretical basis for the observed effect of the co-application of biochar and AMF on the growth and active ingredient accumulation of P. quinquefolius.PMID:40106050 | DOI:10.1007/s00572-025-01195-7

Plant Mol Biol. 2025 Mar 19;115(2):47. doi: 10.1007/s11103-025-01566-w.ABSTRACTIn recent years, abiotic stresses, including droughts, floods, high temperatures, and salinity, have become increasingly frequent and severe. These stresses significantly hinder crop yields and product quality, posing substantial challenges to sustainable agriculture and global food security. Simultaneously, the rapidly growing global population exacerbates the need to enhance crop production under worsening environmental conditions. Consequently, the development of effective strategies to strengthen the resilience of crop plants against high temperatures, water scarcity, and extreme environmental conditions is critical for mitigating the impacts of abiotic stress. Plants respond to these environmental challenges by reprogramming their transcriptome and metabolome. Common strategies for developing stress-tolerant plants include screening germplasm, generating transgenic crop plants, and employing genome editing techniques. Recently, chemical treatment has emerged as a promising approach to enhance abiotic stress tolerance in crops. This technique involves the application of exogenous chemical compounds that induce molecular and physiological changes, thereby providing a protective shield against abiotic stress. Forward and reverse genetic approaches have facilitated the identification of chemicals capable of modulating plant responses to abiotic stresses. These priming agents function as epigenetic regulators, agonists, or antagonists, playing essential roles in regulating stomatal closure to conserve water, managing cellular signaling through reactive oxygen species and metabolites to sustain plant growth, and activating gluconeogenesis to enhance cellular metabolism. This review summarizes recent advancements in the field of chemical priming and explores strategies to improve stress tolerance and crop productivity, thereby contributing to the enhancement of global food security.PMID:40105987 | DOI:10.1007/s11103-025-01566-w

Arch Toxicol. 2025 Mar 19. doi: 10.1007/s00204-025-03998-1. Online ahead of print.NO ABSTRACTPMID:40105957 | DOI:10.1007/s00204-025-03998-1

Appl Microbiol Biotechnol. 2025 Mar 19;109(1):67. doi: 10.1007/s00253-025-13446-w.ABSTRACTStrong sugar tolerance and high bioethanol yield of yeast under high-gravity fermentation have caused great attention in the bioethanol industry. In this study, Clustered Regularly Interspaced Short Palindromic Repeats Cas9 (CRISPR-Cas9) technology was used to knock out S. cerevisiae GPD2, FPS1, ADH2, DLD3, ERG5, NTH1, and AMS1 to construct engineering strain S. cerevisiae GFADENA. Under high-gravity fermentation with 400 g/L of sucrose, S. cerevisiae GFADENA produced 135 g/L ethanol, which increased 17% compared with the wild-type strain. In addition, S. cerevisiae GFADENA produced 145 g/L of ethanol by simultaneous saccharification and fermentation (SSF) using 400 g/L of corn syrup with a sugar-ethanol conversion rate of 41.1%. Further, the targeted metabolomics involving energy, amino acid, and free fatty acid metabolisms were performed to unravel its molecular mechanisms. The deletion of seven genes in S. cerevisiae GFADENA caused a more significant effect on energy metabolism compared with amino acid and free fatty acid metabolisms based on the significantly different metabolites. Two metabolites α-ketoglutaric acid and fructose-1,6-bisphosphate were the most significantly different upregulation and downregulation metabolites, respectively (p < 0.05). Functions of metabolism, environmental information processing, and genetic information processing were related to sucrose tolerance enhancement and ethanol production increase in S. cerevisiae GFADENA by the regulation of significantly different metabolites. This study provided an effective pathway to increase ethanol yield and enhance sucrose tolerance in S. cerevisiae through bioengineering modification. KEY POINTS: • S. cerevisiae GFADENA with gene deletion was constructed by the CRISPR-Cas9 approach • S. cerevisiae GFADENA could produce ethanol using high-gravity fermentation condition • The ethanol yield of 145 g/L was produced using 400 g/L corn syrup by the SSF method.PMID:40105951 | DOI:10.1007/s00253-025-13446-w

Rapid Commun Mass Spectrom. 2025 Apr 15;39(11):e10024. doi: 10.1002/rcm.10024.ABSTRACTRATIONALE: In traditional Chinese medicine, Semen Ziziphi Spinosae (SZS) is employed for alleviating conditions such as neurasthenia, sleep disorders, and anxiety. Its therapeutic effects are attributed to an abundance of biologically active compounds. The main objective of this study was the comparative profiling of SZS from different harvest times using a widely targeted metabolomics approach.METHODS: First, UPLC-Q Trap-MS/MS was used for identification of metabolic profile. Then, multivariate statistical analysis and KEGG enrichment analysis were performed to screen out the differential metabolites and related metabolic pathways among different growth stages.RESULTS: In total, 466 metabolites were identified at three different growth and development stages (T1, T2, and T3) of SZS using UPLC-Q Trap-MS/MS, including 83 flavonoids, 80 phenolic acids, 67 amino acids and derivatives, 56 lipids, 39 nucleotides and derivatives, 38 organic acids, 1 quinone, 6 lignans and coumarins, 53 other metabolites, 10 tannins, 20 alkaloids, and 13 terpenoids. The result of clustering and PCA analyses showed that there was a great difference in metabolites between SZS at three growth stages. Differential metabolites in three comparison groups (T1 vs. T2, T2 vs. T3, and T1 vs. T3) were 195, 104, and 96, respectively. There were 29 common differential metabolites among the three different growth stages of SZS. The contents of important active ingredients (flavonoids and terpenoids) gradually increased during the T1, T2, and T3 stages, indicating that SZS harvested during T3 period was suitable for medicinal use. All the differential metabolites screened were enriched in 11 metabolic pathways, including glycerolipid metabolism, glycerophospholipid metabolism, phenylalanine metabolism, and phenylpropanoid biosynthesis pathway.CONCLUSIONS: This study provides a more comprehensive understanding of the dynamic changes in the metabolic profile of SZS, laying a foundation for subsequent development and utilization.PMID:40105258 | DOI:10.1002/rcm.10024

Electrophoresis. 2025 Mar 19. doi: 10.1002/elps.8120. Online ahead of print.ABSTRACTProstate cancer is the second most common cancer among men globally, with over 1.4 million new cases and nearly 400000 deaths reported in 2022. Despite the availability of diagnostic tools such as the Prostate Specific Antigen (PSA) test, its low sensitivity reinforces the need for the exploration of more reliable biomarkers. In this context, metabolomics offers a promising approach for identifying sensitive biomarkers to improve cancer diagnosis and treatment. Therefore, this study aimed to conduct a targeted metabolomic analysis of the extracellular environment of In Vitro non-tumoral and cancer prostate cells to compare the levels of eight nucleosides using micellar electrokinetic capillary chromatography with UV detection (MEKC-UV). The method was adapted from a previously optimized protocol for blood serum, with minor adjustments to meet the Brazilian National Health Surveillance Agency (ANVISA) standards. Nucleosides were extracted via solid-phase extraction (SPE), and cell cultures were maintained under controlled conditions at 37°C with 5% CO2 until reaching 80% confluence. The optimized MEKC-UV method demonstrated precision and accuracy, although the Youden test indicated some lack of robustness. Statistical analysis using a two-tailed t-test revealed significantly higher adenosine levels in non-tumoral cells, whereas uridine and 5-methyluridine concentrations were elevated in cancer cells. Inosine was detected exclusively in the non-tumoral cell line. Nevertheless, the method's innovative and cost-effective nature underscores its potential as a tool for cancer biomarker identification, with distinct nucleoside patterns in cancer cells offering valuable insights for disease recognition.PMID:40105252 | DOI:10.1002/elps.8120

Eur J Endocrinol. 2025 Mar 19:lvaf055. doi: 10.1093/ejendo/lvaf055. Online ahead of print.ABSTRACTOBJECTIVE: Metabolic flexibility, a key hallmark of cancer, reflects aberrant tumor changes associated with metabolites. The metabolic plasticity of pancreatic neuroendocrine tumors (pNETs) remains largely unexplored. Notably, the heterogeneity of pNETs complicates their diagnosis, prognosis, and therapeutic management. Here, we compared the plasma metabolomic profiles of patients with pNET and non-cancerous individuals to understand metabolic dysregulation.DESIGN AND METHODS: Plasma metabolic profiles of 76 patients with pNETs and 38 non-cancerous individuals were analysed using LC-MS/MS and FIA-MS/MS (Biocrates AbsoluteIDQ p180 kit). Statistical analyses, including univariate and multivariate methods, were performed along with the generation of receiver operating characteristic (ROC) curves for metabolomic signature identification.RESULTS: Compared to non-cancerous individuals, patients with pNET exhibited elevated levels of phosphoglyceride metabolites and reduced acylcarnitine levels, indicating an upregulation of fatty acid oxidation (FAO), which is crucial for the energy metabolism of pNET cells and one-carbon metabolism metabolites. Elevated glutamate levels and decreased lipid metabolite levels have been observed in patients with metastatic pNETs. Patients with the germline MEN1 mutations showed lower amino acid metabolites and FAO, with increased metabolites related to leucine catabolism and lipid metabolism, compared to non-MEN1 mutated patients. The highest area under the ROC curve (AUC) was observed in patients with pNET harbouring MEN1 mutations.CONCLUSION: This study highlights the distinct plasma metabolic signatures of pNETs, including the critical role of FAO and elevated glutamate levels in metastasis, supporting the energy and biosynthetic needs of rapidly proliferating tumour cells. Mapping of these dysregulated metabolites may facilitate the identification of new therapeutic targets for pNETs management.PMID:40105057 | DOI:10.1093/ejendo/lvaf055