PubMed

BMC Genomics. 2026 Mar 3. doi: 10.1186/s12864-026-12702-1. Online ahead of print.NO ABSTRACTPMID:41776392 | DOI:10.1186/s12864-026-12702-1

NPJ Cardiovasc Health. 2025 Oct 30;2(1):55. doi: 10.1038/s44325-025-00091-5.ABSTRACTLipoproteins, synthesized in the liver and secreted into the bloodstream, play a central role in lipid transport. Although their quality affects cardiovascular outcomes, conventional markers do not fully explain the disease risk. We characterized the lipoprotein composition during coronary atherosclerosis progression in myocardial infarction-prone rabbits, which consistently develop severe aortic lesions but show variable coronary stenosis at 20 months. This variation allowed for the exploration of coronary-specific factors that are often masked by other models. Using quantitative lipidomics and proteomics, we profiled 237 lipids and four apolipoproteins in lipoproteins every four months. Coronary severity was positively correlated with long-chain saturated ceramide levels in very-low- and low-density lipoprotein particles, specifically at eight months, reflecting an early disease stage. This correlation was independent of apolipoproteins and classical risk factors, such as cholesterol and triacylglycerol. Network analysis revealed that lipid class-specific clusters were associated with disease severity. This unbiased multi-omics approach provides novel insights into the contribution of lipoprotein composition to coronary atherosclerosis.PMID:41776359 | DOI:10.1038/s44325-025-00091-5

Nat Aging. 2026 Mar 3. doi: 10.1038/s43587-026-01069-3. Online ahead of print.ABSTRACTThe decline in ovarian function with age affects fertility and is associated with increased risk of age-related diseases, including osteoporosis and dementia. Notably, earlier menopause is linked to shorter lifespan, yet the molecular mechanisms underlying ovarian aging remain poorly understood. Recent evidence suggests the gut microbiota may influence ovarian health. Here we show that ovarian aging is associated with distinct gut microbial profiles in female mice and that the gut microbiome can directly influence ovarian health. Using fecal microbiota transplantation from young or estropausal female mice, we demonstrate that heterochronic microbiota transfer remodels the ovarian transcriptome, reduces inflammation-related gene expression and induces transcriptional features consistent with ovarian rejuvenation. These molecular changes are accompanied by enhanced ovarian health and increased fertility. Integrating metagenomics-based causal mediation analyses with serum untargeted metabolomics, we identify candidate microbial species and metabolites that may contribute to the observed effects. Our findings reveal a direct link between the gut microbiota and ovarian health.PMID:41776310 | DOI:10.1038/s43587-026-01069-3

Commun Biol. 2026 Mar 3. doi: 10.1038/s42003-026-09780-y. Online ahead of print.ABSTRACTGliomas, the most common primary brain tumors, exhibit profound metabolic alterations that can be non-invasively probed using magnetic resonance spectroscopy (MRS). Compared to upfield signals in traditional MRS, downfield signals exhibit complex composition with limited understanding of their metabolite origins. Correlating high-throughput metabolic profiles provided by untargeted metabolomics with MRS signals can help elucidate the origins of metabolites in MRS. In this study, upfield and downfield MRS spectra are obtained from control and glioma-bearing male Wistar rats, followed by correlation analysis with untargeted metabolomics from corresponding brain tissues. Here, we show that multiple downfield MRS peaks are significantly elevated in glioma rats and correlate with metabolomic features. Notably, downfield MRS demonstrate the capability of capturing adenosine triphosphate (ATP)-associated nucleotide metabolism. Furthermore, MRS signatures exhibit predictive potential for tumor growth parameters. This work establishes an integrated MRS-metabolomics framework, providing a basis for non-invasively monitoring dynamic metabolic reprogramming and predicting glioma progression.PMID:41776305 | DOI:10.1038/s42003-026-09780-y

Nat Commun. 2026 Mar 3. doi: 10.1038/s41467-026-69979-9. Online ahead of print.ABSTRACTAicardi-Goutières syndrome (AGS) is a genetic type I interferon (IFN)-mediated disease characterized by neurological involvement with onset in utero or in childhood. Here, we analyze peripheral blood samples from patients bearing AGS-causing mutations in ADAR1, RNASEH2B or SAMHD1 using single-cell transcriptomics and targeted metabolomics. Using machine-learning approaches and differential gene expression analysis, we identified a loss of transcription factor hypoxia induced factor 1 α (HIF-1α) expression and activity associated with features of a metabolic switch favoring oxidative phosphorylation and glutathione metabolism over glycolysis in monocytes and dendritic cells. Evidences of mitochondrial stress and accumulation of cytosolic double-stranded DNA and RNA were also found. The energy metabolic switch was confirmed at the metabolic level in primary peripheral blood mononuclear cells of AGS patients. Chemical stabilization of HIF-1α using a synthetic drug in in vitro cellular models of AGS, reversed the energy metabolic switch towards glycolysis, attenuated mitochondrial stress, and markedly reduced the IFN response and IP-10 production. We therefore propose that an energy metabolic switch contributes to chronic inflammation in AGS and that targeting this pathway might represent a potential therapeutic approach.PMID:41776196 | DOI:10.1038/s41467-026-69979-9

Appl Microbiol Biotechnol. 2026 Mar 3. doi: 10.1007/s00253-026-13774-5. Online ahead of print.ABSTRACTAcute-on-chronic liver failure (ACLF) is a severe condition arising from chronic liver disease, characterized by acute decompensation, organ failure, and high short-term mortality. Poor outcomes have also been observed in patients with ACLF after liver transplantation (LT). Emerging evidence, including a study from our center, suggests that gut microbiota plays an important role in ACLF. Patients who underwent LT at our center between October 2022 and June 2024 were included. Fecal samples were collected within 1 month post-LT for 16S rRNA and untargeted metabolomic sequencing. In this study, 144 samples from 69 patients with ACLF, cirrhosis, or hepatocellular carcinoma (HCC) were analyzed. Distinct microbiota and metabolic profiles were observed among the groups. ACLF patients exhibited significantly altered beta diversity, with notable depletion of g__Anaerostipes. Metabolomic analysis revealed substantial differences, including enrichment of tangeritin and depletion of candesartan in the ACLF group. Network analysis identified g__Anaerostipes as a key node linking differential taxa and metabolites. A random forest model based on these features effectively distinguished patient groups, with the highest classification accuracy observed in HCC. Multi-omic signatures were also associated with early allograft dysfunction (EAD), particularly g__Lachnoclostridium. Several microbial and metabolic features, including g__Lachnoclostridium, showed significant correlations with clinical indicators. The gut microbiome after LT is closely associated with ACLF. This study offers valuable insights for further investigation into the pathogenesis and post-LT prognosis. KEY POINTS: • ACLF patients have a unique gut microbiota and metabolic profile after LT • g__Anaerostipes is the prominent biomarker of ACLF's multi-omics signature • g__Lachnoclostridium is a promising indicator of recovery after LT.PMID:41776098 | DOI:10.1007/s00253-026-13774-5

NPJ Cardiovasc Health. 2024 Jun 3;1(1):5. doi: 10.1038/s44325-024-00003-z.ABSTRACTPostoperative atrial fibrillation (POAF) is a common complication after coronary artery bypass grafting (CABG) surgery. Gut microbiota and its metabolites have been implicated in the development of AF. However, whether the gut-host metabolic interaction contributes to POAF is still unknown. This study aimed to investigate the POAF-associated gut microbiota metabolism biomarkers and related risk model. The POAF (N = 30) patients and non-POAF (N = 60) patients from the discovery cohort exhibited significantly different microbiome and metabolome profiles. The differentiated features were mainly implicated in the bile acids (BAs) and short-chain fatty acids metabolism, inflammation, and oxidative stress. Random forest analysis identified the combination of five secondary BAs showed a powerful performance on predicting POAF in the discovery cohort, highlighting significant values of area under the curve (AUC = 0.954) and correct classification rate (CCR, 93.3%). In addition, the five secondary BAs-based risk model also exhibited good performance in differentiating the POAF (N = 114) and non-POAF individuals (N = 253) in an independent validation cohort (AUC = 0.872; CCR = 90.4%). This work revealed perturbed microbial and metabolic traits in POAF, providing potential avenues for the prediction and prevention of POAF after CABG.PMID:41775960 | DOI:10.1038/s44325-024-00003-z

Commun Med (Lond). 2026 Mar 3;6(1):132. doi: 10.1038/s43856-025-01227-5.ABSTRACTBACKGROUND: Development of therapies for CLN3 disease, a rare pediatric lysosomal storage disorder, has been hindered by the lack of etiological insights and translatable biomarkers to clinics.METHODS: We used a deep multi-omics approach to discover blood-based biomarkers using longitudinal serum samples from a porcine model of CLN3 disease. Comprehensive metabolomics was combined with a nanoparticle-based LC-MS-based proteomic profiling coupled with TMTpro 18-plex to generate quantitative data on 769 metabolites and 2634 proteins, collectively the most exhaustive multi-omics profile conducted on serum from a porcine model. This was previously impossible due to lack of efficient deep serum proteome profiling technologies compatible with model organisms.RESULTS: Here we show that the presymptomatic disease state is characterized by elevations in glycerophosphodiester species and lysosomal proteases, while later timepoints are enriched with species involved in immune cell activation and sphingolipid metabolism. Cathepsin S (CTSS), Cathepsin B (CTSB), glycerophosphoinositol, and glycerophosphoethanolamine captured a large portion of the genotype-correlated variation between healthy and diseased animals, suggesting that an index score based on these analytes could have great utility in the clinic.CONCLUSIONS: This study's findings demonstrate the potential of deep multi-omics profiling for uncovering disease-specific biomarkers, providing valuable insights for understanding disease and facilitating the identification of potential drug targets, thus offering valuable insights for therapeutic interventions.PMID:41775934 | DOI:10.1038/s43856-025-01227-5

NPJ Precis Oncol. 2026 Mar 4. doi: 10.1038/s41698-026-01342-z. Online ahead of print.ABSTRACTLung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality worldwide, highlighting the urgent need for non-invasive strategies for early detection. Here, we present a machine learning-assisted metabolomics approach for the early detection of LUAD. Untargeted metabolomic profiling was performed on 199 serum samples from healthy individuals, patients with lung precancerous lesions, and those with stage I LUAD. An ensemble machine learning workflow was developed to identify metabolite panels capable of discriminating clinical status with high accuracy. We observed progressive metabolic alterations in bile acid, lipid, amino acid, and purine metabolism during LUAD initiation and stepwise progression. Notably, ensemble learning identified a six-metabolite panel, including 12-hydroxydodecanoic acid, hypoxanthine, xanthosine, cholic acid, agmatine, and paraxanthine, for accurate detection of early-stage LUAD, and a distinct four-metabolite panel, comprising 7-α,27-dihydroxycholesterol, 11-undecanedicarboxylic acid, biliverdin, and Prolyl-Valine, for precise differentiation between pre-invasive and invasive lesions. Both panels demonstrated promising diagnostic potential, with performance metrices comparing favorably to established methodologies within the current study cohort. This study delineates the evolutionary trajectory of the serum metabolome associated with early LUAD pathogenesis and provides promising biomarkers for non-invasive early detection.PMID:41775866 | DOI:10.1038/s41698-026-01342-z

NPJ Biol Timing Sleep. 2025 Oct 1;2(1):34. doi: 10.1038/s44323-025-00052-2.ABSTRACTThe circadian oscillator is an innate timing mechanism present in most organisms, including plants. In this study, Populus tremula × P. tremuloides (Populus) trees with reduced expression of circadian clock components were exposed to gradually increases in the osmotic and ionic components of salt stress. Reduced levels of the morning components PttLATE ELONGATED HYPOCOTYL 1 and 2 (PttLHY1,2) or of the evening components PttPSEUDO-RESPONSE REGULATOR 7a and b (PttPRR7a,b) and PttGIGANTEA1,2 (PttGI1,2) affected growth adaptation under stress conditions. PttLHY1,2 regulated growth under NaCl treatment via the control of PttCyclin D3 expression. PttPRR7a,b and PttGI1,2 were instrumental in maintaining growth in roots by enabling effective adaptation of the metabolome. Major changes in the root metabolome under prolonged stress included alterations in carbohydrate, amino acids, and fatty acids. This study places the circadian clock at the centre of adaptation to adverse conditions in trees and will help the development of stress-resistant trees.PMID:41775820 | DOI:10.1038/s44323-025-00052-2

Sci Rep. 2026 Mar 3. doi: 10.1038/s41598-026-41850-3. Online ahead of print.ABSTRACTSalinity stress severely limits barley (Hordeum vulgare L.) growth and productivity. This study examined the effects of chitosan (Cs), selenium (Se), and chitosan-selenium nanoparticles (Cs-Se NPs) on salt tolerance of two barley cultivars, Mv Initium and Tectus, exposed to 0, 100, and 200 mM NaCl. Salinity reduced plant height, biomass, and chlorophyll content. Foliar application of Cs and especially Cs-Se NPs significantly improved these traits. Cs-Se NPs enhanced proline (PRO) accumulation and activities of ascorbate peroxidase (APX) and catalase (CAT) under salt stress in both cultivars, which supports improved ROS scavenging capacity. The significant upregulation of antioxidant enzyme genes (HvAPX, HvSOD, HvCAT) following Cs-Se NPs treatment under salinity strongly indicates enhanced reactive oxygen species (ROS) detoxification. Key ion homeostasis genes (HvSOS1, HvSOS3, HvNHX1 and HvHKT2) were also upregulated, supporting improved salt stress tolerance. Strong correlations were found between antioxidant activity, chlorophyll content, and growth. These findings suggest that Cs-Se NPs effectively boost barley's physiological and molecular defenses against salinity.PMID:41775817 | DOI:10.1038/s41598-026-41850-3

NPJ Parkinsons Dis. 2026 Mar 4. doi: 10.1038/s41531-026-01306-x. Online ahead of print.ABSTRACTPrevious metabolomic studies have reported significant alterations in circulating amino acids in Parkinson's disease (PD). However, it remains unclear whether these changes reflect central nervous system pathology or are restricted to peripheral metabolism. To address this issue, here we measured the levels of a panel of amino acids in post-mortem brain samples from MPTP-intoxicated monkeys, with and without L-DOPA treatment, and from PD patients at different Braak Lewy body (LB) stages through targeted UPLC-MS. In untreated MPTP monkeys, the putamen showed significant increases in glutamate, aspartate, GABA, phenylalanine, branched-chain amino acids, and serine. L-DOPA treatment further altered this profile, increasing glycine, threonine, and citrulline levels. In contrast, no amino acid changes were detected in the superior frontal gyrus (SFG) of MPTP monkeys, regardless of treatment. In PD patients, caudate-putamen analysis revealed consistent serine upregulation at Braak LB stages 3-4 and 6, with stage 6 additionally showing increased proline and reduced phosphoethanolamine. No amino acid changes were observed in the PD SFG, whereas Alzheimer's disease SFG samples showed marked amino acid increases. Together, these findings demonstrate region-specific amino acid dysregulation in PD, preferentially affecting nigrostriatal targets and supporting disease-specific metabolic signatures across neurodegenerative disorders.PMID:41775741 | DOI:10.1038/s41531-026-01306-x

Nat Commun. 2026 Mar 3. doi: 10.1038/s41467-026-70336-z. Online ahead of print.ABSTRACTThiols serve indispensable biochemical functions across catalysis, redox homeostasis and energy metabolism. However, profiling multiple thiols at the single-cell level remains challenging due to their trace amount and susceptibility to oxidation. Herein, we report an integrated strategy for thiol profiling at the single-cell level which combines live-cell labeling with organic mass cytometry. The live-cell labeling strategy facilitates the comprehensive measurement of intrinsic thiols with expanded coverage and improved sensitivity, while organic mass cytometry enables simultaneous quantification of 27 labeled thiols and 355 other metabolites from single cells. Assessment of metabolic fluctuation upon stimulation demonstrates practicability and accuracy of this integrated methodology which is capable of pathway activity monitoring, metabolic network mapping and untargeted metabolome profiling. Further application of this method in investigating RSL3-triggered ferroptosis reveals that RSL3 inhibits glutathione synthesis via nuclear factor E2-related factor 2- glutathione axis and results in heterogenous glutathione metabolism between subtypes.PMID:41775714 | DOI:10.1038/s41467-026-70336-z

J Diabetes Sci Technol. 2026 Mar 3:19322968261426026. doi: 10.1177/19322968261426026. Online ahead of print.ABSTRACTBACKGROUND: Hemoglobin A1c (HbA1c) interpretation can be affected by genetic and hematologic factors that alter erythrocyte turnover. This study investigated red blood cell (RBC) profiles and metabolomic alterations linked to glycemic variability in type 2 diabetes (T2D) and evaluated the effects of common RBC genetic disorders on HbA1c interpretation.METHODS: Participants were recruited in Nakhon Si Thammarat, Thailand. In Phase 1, 244 normoglycemic participants and 447 individuals with T2D were enrolled. In Phase 2, 45 participants from each group were analyzed for hematologic and biochemical parameters. In Phase 3, liquid chromatography-mass spectrometry (LC-MS)-based RBC metabolomics were performed in 10 individuals without diabetes and 14 individuals with diabetes.RESULTS: Fasting blood glucose, fructosamine, and ferritin showed no significant differences, whereas HbA1c was significantly lower in those with RBC disorders for both individuals without diabetes (P = .001) and individuals with diabetes (P < .001) groups. Red blood cells with hypochromic microcytosis in β-thalassemia heterozygote (BTH) were used as a model to explore metabolomic changes associated with normal and high HbA1c levels. Multivariate analyses revealed distinct clustering patterns in high-HbA1c cases. Interestingly, 5-oxo-L-proline exhibited the highest fold change (FC = 6.90, P = .0004), followed by 5-aminolevulinate and D-gluconic acid, along with increased oxidized/reduced glutathione and decreased NADH and sphingomyelin.CONCLUSIONS: Distinct RBC metabolic signatures were observed in BTHs with elevated HbA1c, highlighting alterations in redox and heme metabolism. These findings provide a basis for future investigations into RBC-derived metabolites as complementary tools for glycemic assessment in individuals with thalassemia and hemoglobinopathies.PMID:41775457 | DOI:10.1177/19322968261426026

J Immunother Cancer. 2026 Mar 3;14(3):e011864. doi: 10.1136/jitc-2025-011864.ABSTRACTBACKGROUND: B-cell maturation antigen (BCMA) is the main target for chimeric antigen receptor (CAR)-T cells in multiple myeloma (MM), demonstrating promising outcomes. However, unlike what happens with CART19 in lymphoblastic leukemia and non-Hodgkin's lymphoma, a high proportion of patients will relapse after CAR-T BCMA therapy due to insufficient antigen expression, low CAR-T cell persistence and/or T-cell exhaustion. In other B cell malignancies, second-generation anti-CD19 4-1BB CARs with CD28-transmembrane domain (TMD) have shown high efficacy and a favorable toxicity profile. We have developed a second-generation CD8α-TM BCMA-4-1BBζ CAR-T product, ARI0002h (Cesnicabtagene-autoleucel) for patients with relapsed/refractory MM. We hypothesized that replacing the TMD of ARI0002h with a CD28-TMD could increase efficacy and reduce tumor escape while maintaining a tolerable toxicity profile.METHODS: We generated CAR-T cells using T-cells isolated from buffy coats and evaluated the efficacy and fitness of CAR-Ts at day 8-10 of expansion against several MM cell lines. In vitro analyses included cytotoxicity, proliferation, cytokine secretion, T-cell subset markers, activation and exhaustion profiling, metabolomic assays, and RNA-seq after multiple tumor challenges. In in vivo xenograft studies using NSG mice, with tumor cells expressing GFP-ffLuc, disease progression was monitored weekly via bioluminescence imaging.RESULTS: Despite showing similar in vitro performance regarding cytotoxicity, proliferation and cytokine production, ARI2h-TM28 outperforms ARI0002h in a low BCMA expression setting and achieves superior in vivo tumor control and survival in relapse models with antigen downregulation. Furthermore, ARI2h-TM28 showed an optimized metabolic profile, more oxidative and energetic compared with ARI0002h, with downregulation of proinflammatory genes in CD8 T cells, contributing altogether both to reduced exhaustion and increased persistence of the CARs, improving their efficacy in preclinical models.CONCLUSIONS: Incorporating a CD28-TMD into the ARI0002h CAR enhances tumor control even in relapse models with downregulation of the target antigen, offering improved long-term disease management. This modification increases potency against MM tumor cell lines with both normal and reduced BCMA expression, demonstrating superior metabolic endurance and in vivo activity.PMID:41775430 | DOI:10.1136/jitc-2025-011864

J Adv Res. 2026 Mar 1:S2090-1232(26)00186-4. doi: 10.1016/j.jare.2026.02.052. Online ahead of print.ABSTRACTINTRODUCTION: Acute liver injury (ALI) is a severe clinical syndrome with high mortality, often triggered by toxins, viruses, or immune-mediated injury. The gut-liver axis serves as a key mediator in the progression of hepatic disorders, and probiotics are considered viable treatment options owing to their impact on modulating intestinal microbiota, reduce inflammation, and alleviate oxidative stress.OBJECTIVES: This study was designed to elucidate the hepatoprotective mechanisms of L. paracasei 36 against D-GalN/LPS-induced ALI in mice, with a specific focus on its roles in inflammation, oxidative stress, apoptosis, and intestinal microbiota regulation.METHODS: The mice were pretreated with L. paracasei 36 for three weeks prior to the D-GalN/LPS challenge. Serum biomarker, oxidative damage indicators, inflammatory cytokines, and apoptosis-related genes were measured. Intestinal microbiota composition was analyzed via 16S rRNA sequencing, and hepatic transcriptomics and metabolomics were performed to identify key pathways and metabolites.RESULTS: L. paracasei 36 pretreatment significantly reduced serum AST, ALT, and TBil levels, alleviated histopathological damage, and decreased oxidative stress and inflammatory cytokine production. It inhibited hepatocyte apoptosis by modulating Bcl-2/Bax expression and suppressed NLRP3 inflammasome activation. L. paracasei 36 restored intestinal microbiota balance, increasing beneficial genera (Ligilactobacillus, Akkermansia) and reducing harmful ones (Alistipes, Parasutterella). Multi-omics analysis revealed suppression of NF-κB/MAPK pathways along with an increase in hepatoprotective metabolites like berberine and flavin nucleotides.CONCLUSION: L. paracasei36 exerts potent hepatoprotective effects against D-GalN/LPS-induced ALI by mitigating inflammation, oxidative damage, and apoptosis, and by restoring intestinal microbiota homeostasis. Collectively, these results suggest that L. paracasei 36 represents a potential therapeutic strategy for ALI.PMID:41775324 | DOI:10.1016/j.jare.2026.02.052

J Environ Manage. 2026 Mar 2;402:129171. doi: 10.1016/j.jenvman.2026.129171. Online ahead of print.ABSTRACTThere is a need to explore alternative phosphorus (P) delivery strategies to improve P use efficiency for minimizing the related environmental damage and achieving Sustainable Development Goals (SDGs). In this study, foliar application of nanoscale hydroxyapatite (nHAP) exhibited greater potential to promote rice (Oryza sativa L.) growth than NaH2PO4 with equivalent P mass under controlled experimental conditions. Specially, the rice shoot and root biomass promotion induced by the application of nHAP at 200 mg/L was 2.1- and 2.4-fold of that by NaH2PO4 with equivalent P mass with 200 mg/L nHAP, respectively. Mechanistically, (1) nHAP exhibited greater adhesion and lower rebound on rice leaves than NaH2PO4, leading to more effective P supply; (2) nHAP application facilitated the recruitment of phosphate-solubilizing bacteria in phyllosphere. The abundance of Pseudomonas and Bacillus on rice phyllosphere was 203.9 and 12.3% higher than that in control; and (3) metabolomic analyses revealed that nHAP markedly upregulated rice metabolism, particularly in pathways such as inositol phosphate metabolism, the TCA cycle, starch and sucrose metabolism. The content of jasmonic acid and indole acetic acid in rice shoots after foliar application of nHAP was 156 and 11.5% greater than that in NaH2PO4 treatment, respectively. Full life-cycle pot experiment, a proof of concept rather than field-scale validation, further indicated that nHAP application was associated with improved yield-related performance and enhanced grain nutritional quality, with starch and protein levels increasing by 56.3% and 24.3%, respectively. These findings suggest that nHAP can potentially serve as an effective alternative of P fertilizer, offering a promising approach for achieving SDG2 (zero hunger).PMID:41775236 | DOI:10.1016/j.jenvman.2026.129171

J Hazard Mater. 2026 Feb 28;506:141644. doi: 10.1016/j.jhazmat.2026.141644. Online ahead of print.ABSTRACTMicroplastics (MPs), as emerging pollutants, have been increasingly detected in aquatic ecosystems, where their interactions with microalgae critically influence pollutant transport and ecological risks. This study aimed to elucidate how different nutrition levels and MPs types regulate extracellular polymeric substance (EPS) secretion and hetero-aggregation behavior of Scenedesmus sp. A combination of experimental observations and density functional theory (DFT) simulations was used to investigate the interfacial interactions between Scenedesmus sp. and two representative microplastics, polystyrene (PS) and polyvinyl chloride (PVC), while metabolomic profiling was conducted to examine the corresponding biochemical responses. Results showed that PS exposure induced the formation of larger and looser flocs with a maximum sedimentation efficiency of 99.63%, whereas PVC resulted in smaller and denser aggregates (93.57%). DFT analysis further demonstrated that PS-EPS interactions were dominated by delocalized van der Waals and hydrogen-bonding forces, whereas PVC-EPS complexes involved localized polar interactions mediated by proteinaceous EPS. Metabolomic analysis indicated that both PS and PVC disturbed purine metabolism and lipid remodeling, with PVC additionally activating amino acid and nitrogen metabolic pathways. Overall, nutrition levels and MPs types jointly modulated EPS composition, interfacial coupling, and aggregation characteristics. This study provides molecular-level evidence for understanding the interfacial mechanisms between microplastics and microalgae. The resulting hetero-aggregation could be further utilized for biodiesel production, enabling the valorization and conversion of waste materials.PMID:41775205 | DOI:10.1016/j.jhazmat.2026.141644

J Hazard Mater. 2026 Mar 1;506:141652. doi: 10.1016/j.jhazmat.2026.141652. Online ahead of print.ABSTRACTGestational diabetes mellitus (GDM) is a heterogeneous pregnancy complication comprising insulin-resistant and insulin-deficient subtypes with distinct pathophysiology. Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) has been implicated in gestational glucose disturbances, yet congener-specific effects on subtypes of GDM and underlying metabolic mechanisms remain unknown. In the Shanghai Birth Cohort, 1789 women had plasma concentrations of 9 PFAS congeners and untargeted serum metabolomics measured in early pregnancy, and GDM subtypes were defined at 24-28 weeks' gestation using a 75 g oral glucose tolerance test with indices of insulin sensitivity and secretion. Associations of individual and mixture PFAS exposures with GDM subtypes were evaluated using multivariable, weighted quantile sum, quantile-based g-computation, and Bayesian kernel machine regression models. Metabolome-wide and meet-in-the-middle analyses identified metabolites jointly related to key PFAS and GDM subtypes, followed by pathway enrichment and mediation analyses. Across modeling approaches, perfluorooctane sulfonate (PFOS) was associated with insulin-deficient GDM, whereas perfluoroheptanoic acid (PFHpA) was associated with insulin-resistant GDM. Metabolomic analyses revealed that metabolites shared by PFOS and insulin-deficient GDM enriched in fatty-acid metabolism and hormone signaling, and those shared by PFHpA and insulin-resistant GDM enriched in transmembrane transport and amino-acid metabolism. Mediation analyses further indicated divergent metabolic signatures, with polyunsaturated fatty acids and glycerophospholipids mediating the association between PFOS and insulin-deficient GDM, and medium- to long-chain acylcarnitines, bile acids, and glucogenic amino acids primarily mediating the association between PFHpA and insulin-resistant GDM. This prospective study provides the first evidence that specific PFAS congeners differentially influence GDM subtypes through distinct metabolic disruptions.PMID:41775189 | DOI:10.1016/j.jhazmat.2026.141652

Plant Physiol Biochem. 2026 Feb 28;232:111185. doi: 10.1016/j.plaphy.2026.111185. Online ahead of print.ABSTRACTStylosanthes guianensis (stylo), an important tropical and subtropical green manure crop, shows remarkable adaptation to acidic soils with low phosphate (Pi) availability. Nevertheless, the specific mechanisms underlying its high phosphorus (P) utilization efficiency (PUE) in acidic soils are not fully understood. This study combined a field experiment conducted in low-Pi acidic soils with multifaceted analyses to compare the physiological and molecular responses of two stylo genotypes differing in PUE. The high-PUE genotype P457 was superior to the low-PUE genotype Reyan No.2 in acidic soils, exhibiting significantly greater biomass, P content, and PUE. Notably, P457 displayed higher leaf acid phosphatase (APase) activity than Reyan No.2. Untargeted metabolomic and lipidomic analyses further revealed significantly lower phospholipid levels in P457 leaves than in Reyan No.2. Transcriptomic analysis identified significantly elevated expression of a purple APase gene (SgPAP10b) in P457 leaves than in those of Reyan No.2. Functional characterization of SgPAP10b via heterologous overexpression in Arabidopsis demonstrated that it not only enhanced shoot biomass, PUE, and APase activity but also reduced shoot phospholipid levels relative to wild-type plants. Recombinant SgPAP10b exhibited phosphatase activity and high hydrolytic activity toward phospholipids, including phosphatidylethanolamine and lysophosphatidylcholine. Taken together, our results suggest that SgPAP10b-mediated lipid remodeling and P recycling are associated with the superior low-Pi adaptability of P457, thereby contributing to improved PUE. These findings uncover a previously unrecognized role of SgPAP10b in stylo adaptation to low-Pi conditions and highlight it as a promising target for enhancing PUE in crops grown on acidic soils.PMID:41775164 | DOI:10.1016/j.plaphy.2026.111185