PubMed

Crop Health. 2025 Jul 1;3(1):15. doi: 10.1007/s44297-025-00055-2.ABSTRACTHerbivore attacks or some pathogen infections typically begin with wounding of plant tissues, yet the transcriptional dynamics of wound-induced responses in the monocot rice remain incompletely understood. Here, we conducted a time-series transcriptome analysis of mechanically wounded rice leaves. Temporal expression patterns were observed even in untreated plants, particularly at dusk. To identify differentially expressed genes (DEGs), we compared wounded and unwounded (control) plants at corresponding time points. Jasmonate-related genes, including 18 biosynthetic and 13 catabolic genes, were significantly up-regulated. Consistently, jasmonic acid (JA) and jasmonoyl-L-isoleucine were rapidly accumulated in wounded tissues within 1 h, followed by JA catabolites after 3 h. Weighted gene co-expression network analysis of upregulated DEGs revealed early- and late-responsive gene modules. Early-expressed genes included putative regulators such as transcription factors, kinases, abscisic acid pathway components, and small peptide-coding genes, while late-responsive genes were primarily involved in specialized metabolite biosynthesis (e.g., phenylpropanoids). Targeted metabolomic analysis showed that most phenolamides were highly accumulated in wounded leaves, whereas flavonoid levels were decreased, likely due to altered metabolic flux in the phenylpropanoid pathway. Comparative analysis of leaf folder (LF) larvae- and wound-induced transcriptomes revealed that only 42% of wound-upregulated DEGs responded to LF feeding, suggesting that LF larvae partially suppress wound responses in rice. This study provides a valuable resource for understanding wound-associated biotic stress responses in rice.PMID:41649643 | DOI:10.1007/s44297-025-00055-2

Plant Mol Biol. 2026 Feb 6;116(2):19. doi: 10.1007/s11103-026-01683-0.NO ABSTRACTPMID:41649591 | DOI:10.1007/s11103-026-01683-0

Environ Sci Technol. 2026 Feb 6. doi: 10.1021/acs.est.5c12691. Online ahead of print.ABSTRACTNon-targeted liquid chromatography tandem high-resolution mass spectrometry (LC-MS/MS) is increasingly applied for the structure-resolved chemical analysis of dissolved organic matter (DOM). With new developments in MS instrumentation and analysis software, the approach has gained substantial momentum over the past decade. However, achieving high-quality analytical data that is reproducible and comparable across laboratories can be a bottleneck in non-targeted metabolomics and organic matter chemical analysis, especially for data reuse in repository-scale analyses. Understanding the capabilities as well as challenges of comparing LC-MS/MS data from different laboratories is necessary for inferring global trends from public data sets. To illuminate instrumentation factors that drive differences and variability, we used a standardized data analysis pipeline, including classical (CMN) and feature-based molecular networking (FBMN), to analyze data from a ring trial by 24 laboratories on identical sample sets of algal and DOM extracts that were mixed in predefined concentrations and spiked with standards. Our results showed that data sets from similar mass spectrometer types with unified instrument parameters were qualitatively comparable, resolving the same general trends and shared mass spectral features. Interlaboratory comparability was best for high-intensity features, while low-intensity features showed greater detection variability. Our analysis also highlights challenges when comparing data from instruments with different acquisition rates or operating with less standardized methods. Lastly, we provide recommendations for data integration, public data sharing, standardization, and best practices for standardized LC-MS/MS data acquisition, which will be critical for long-term time series and intercomparability of DOM chemical analyses.PMID:41649479 | DOI:10.1021/acs.est.5c12691

J Exp Bot. 2026 Feb 6:erag057. doi: 10.1093/jxb/erag057. Online ahead of print.ABSTRACTPhytochrome (phy) A and phyB are red and far-red photoreceptors that play essential roles in modulating seed germination. Despite extensive research on the roles of hormones and light signaling, the metabolic characteristics of phytochromes during the red-light-mediating seed germination remain largely unknown. Using high-throughput non-targeted metabolomics, this study profiled Arabidopsis seeds including the wild-type (Col-0), single mutants (phyA-211, phyB-9), double mutant phyAB, and the pifq mutant during red-light-induced germination, and identified a total of 164 metabolites linked to primary and secondary metabolism. Comparative analysis of the metabolome revealed that the levels of flavonols including quercetin, kaempferol and relevant glycosides were increased in phyA-211, decreased in Col-0 and phyB-9, and exhibited less change in phyAB, demonstrating that phyA and phyB antagonistically regulate flavonoid biosynthesis. Flavonoid biosynthesis was upregulated in pifq under red light. Exogenous quercetin and kaempferol treatment modestly inhibited Col-0 and pifq seed germination. Taken together, these results unveil the comprehensive metabolic networks, highlight the flavonoid metabolism under red light, and elucidate the synergistic and antagonistic roles of phyA and phyB in regulating seed metabolism. This study provides novel insight into the functional mechanisms of flavonoid metabolism and light signaling in plant development.PMID:41649387 | DOI:10.1093/jxb/erag057

Physiol Plant. 2026 Jan-Feb;178(1):e70742. doi: 10.1111/ppl.70742.ABSTRACTSoil contamination by bisphenol A (BPA) has raised considerable ecological and environmental concerns, particularly due to its potential impact on plant growth. However, the interactive effects of BPA and different soil types on soil-plant systems remain poorly understood. Capsicum annuum L., a widely cultivated vegetable crop, was used as a model to systematically investigate the mechanisms of BPA uptake, translocation, and metabolic disruption in roots under varying soil types and BPA dose. Greenhouse experiments showed that BPA accumulation in pepper roots was highest in viscous soil, significantly greater than in sandy or loamy soils. When BPA dose exceeded 10 mg kg-1, root elongation and vitality were markedly suppressed, accompanied by enhanced antioxidant enzyme activity and elevated malondialdehyde content, indicating phytotoxicity was linked to increased oxidative stress. Integrated transcriptomic and metabolomic analyses identified 995 differentially expressed genes and revealed significant disruptions in root metabolic processes. BPA exposure altered the expression of genes related to the biosynthesis of phytohormone precursors and branched metabolites. Key pathways, including indole-3-acetic acid biosynthesis and phytohormone signal transduction, were significantly affected. These findings clarify the soil-dependent uptake and translocation patterns of BPA in pepper roots and provide important molecular insights into the plant's adaptive and defense responses to BPA-induced stress.PMID:41649378 | DOI:10.1111/ppl.70742

mSystems. 2026 Feb 6:e0049325. doi: 10.1128/msystems.00493-25. Online ahead of print.ABSTRACTMicrobes inhabiting soils experience periodic water deprivation. The effects of desiccation on DNA, protein, and membrane integrity are well-described. However, the effects of drying and rehydration on the composition of cellular RNA and metabolites are still poorly understood. Here, we describe how slow drying and rehydration with water vapor influence the composition of RNAs and metabolites in a soil Arthrobacter. While drying reduced cultivability relative to hydrated controls, water vapor rehydration fully restored it. Ribosomal RNA proportions remained constant throughout all treatments, and mRNA profiles showed stable composition during desiccation-changing only during transitions into and out of desiccation-induced dormancy. Six transcriptional modules displayed distinct expression patterns in desiccated-rehydrated samples relative to hydrated controls, including desiccation-rehydration responsive and rehydration-specific profiles. Targeted intracellular metabolomics revealed similarly static profiles during desiccation, with a cluster of ribonucleosides and nucleobases increasing in response to desiccation and returning to baseline levels upon rehydration with water vapor. These findings demonstrate that both mRNA and metabolite profiles remain essentially frozen in desiccated Arthrobacter, with dynamic changes occurring only during state transitions. These results have important implications for environments with frequent drying cycles where stable mRNA in dormant cells combined with intracellular RNA recycling may obscure interpretations of RNA-based environmental analyses that use RNA as a marker of microbial activity. Our results suggest that RNA-based activity assessments in periodically dry environments require careful consideration of dormancy-associated molecular preservation.IMPORTANCEMetabolic activity quickly ceases in drying bacteria as they enter desiccation-induced dormancy. We show that mRNA and metabolite profiles were variable during drying and rewetting but did not change while desiccated. Additionally, water vapor stimulated the shift from the static to active state when exiting desiccation-induced dormancy. These shifts coincided with increased cultivability, indicating water vapor resuscitated dry cells. Because RNAs are transient, labile molecules that are turned over rapidly in growing bacteria, the presence of RNA in the environment is used as a marker for microbial activity. Our research shows this assumption may not hold for desiccated cells, indicating reliance on RNA as a marker of activity in environments that experience drying may obscure estimates of in situ microbial activity.PMID:41649271 | DOI:10.1128/msystems.00493-25

mBio. 2026 Feb 6:e0382925. doi: 10.1128/mbio.03829-25. Online ahead of print.ABSTRACTUsing a selective plating strategy for staphylococci, we surveyed the local community wastewater and purified 16 independent isolates representing the following seven species of Staphylococcus: S. cohnii, S. equorum, S. lentus, S. nepalensis, S. sciuri, S. shinii, and S. xylosus. Staphylococcus aureus was not detected. The wastewater also served as a source to identify a bacteriophage (phage), referred to here as JS1, that could infect all these species of Staphylococcus, as well as a range of clinical S. aureus strains, including methicillin-resistant isolates. The class Caudoviricetes are tailed phages, and classification systems recognize the following three major morphotypes: the Myo-like (medium-to-long, straight, contractile tails), Sipho-like (long, flexible, non-contractile tails), and Podo-like (very short, rigid tails). Electron microscopy showed that JS1 virions have 252 nm long, curved, contractile tails. Curvature analysis showed that this represented a range with a 1/R value of 7.6 ± 1.3 μm-1, where R is the radius of curvature. Phage JS1 also encodes hydrolases that are assembled onto the phage virions. One of these hydrolases, JS1_0224, was biochemically characterized and found to etch regions from the Staphylococcal cell wall. The possibility that these on-board hydrolases and the curvature of the long contractile tails are advantageous to the phage for navigating through the cell wall of these various species of Staphylococcus is discussed.IMPORTANCEPast work has seen over-representation of Staphylococcus aureus clinical isolates in genome and biology studies on staphylococci. Here, we show by a selective plating analysis of municipal wastewater that independent isolates representing seven other species of Staphylococcus were recovered (S. cohnii, S. equorum, S. lentus, S. nepalensis, S. sciuri, S. shinii, and S. xylosus), as readily identified in the samples. Genome sequence analysis revealed some species-specific antibiotic resistance profiles across the strains, and a bacteriophage was isolated that had a cross-species host range. Using this broad biological approach to analyze staphylococci has identified a phage with a broad killing range, and this phage is morphologically distinct from the three known types of tailed phages.PMID:41649268 | DOI:10.1128/mbio.03829-25

Microbiol Spectr. 2026 Feb 6:e0274025. doi: 10.1128/spectrum.02740-25. Online ahead of print.ABSTRACTThe coordinated post-natal development of the gut microbiome and metabolome is essential for preterm infant health, yet its disruption is increasingly linked to adverse outcomes such as bronchopulmonary dysplasia (BPD). In this study, we performed an integrated multiomics analysis of fecal samples collected from preterm infants to characterize temporal changes in gut microbial and metabolic profiles and explore their potential associations with BPD development. This study observed a distinct trajectory of the phylum Bacteroidota as a hallmark of normal gut maturation, with its abundance progressively declining across non-BPD infants. In contrast, infants who later developed BPD exhibited early depletion followed by irregular enrichment of Bacteroidota. Correlation analysis revealed that Streptococcus abundance was positively associated with elevated cysteic acid, a metabolite linked to oxidative stress. Together, these findings suggest that altered Bacteroidota succession and Streptococcus-associated oxidative imbalance may reflect early microbial-metabolic perturbations in infants at risk of BPD. This work provides preliminary, hypothesis-generating insights into gut-associated signatures potentially relevant to BPD pathogenesis.IMPORTANCE: Bronchopulmonary dysplasia (BPD) remains a leading cause of morbidity in preterm infants, yet early biomarkers and targeted preventive strategies are limited. By integrating microbiome and metabolome data from a pilot cohort, this study identified patterns of disrupted Bacteroidota succession and Streptococcus-associated oxidative stress that are associated with BPD risk. These findings highlight the gut as a potential extrapulmonary contributor to disease susceptibility and support early risk assessment and guide future microbiome-targeted interventions in preterm infants.PMID:41649265 | DOI:10.1128/spectrum.02740-25

Microbiol Spectr. 2026 Feb 6:e0110225. doi: 10.1128/spectrum.01102-25. Online ahead of print.ABSTRACTCampylobacteriosis and salmonellosis are the leading bacterial zoonoses in Europe, with poultry meat being the primary source of human contamination. Although both Campylobacter and Salmonella bacteria can coexist asymptomatically in chickens, their reciprocal impact remains underexplored. An in vitro study showed that Campylobacter jejuni survival was positively affected by the presence of Salmonella, but no data are available on this interaction in the animal gut. In this study, an in vivo investigation was carried out to explore the dynamics between Campylobacter and Salmonella colonization in chickens. The results revealed that both Salmonella and Campylobacter maintained significantly higher levels of colonization in the ceca throughout the experiment when co-inoculated compared to when inoculated alone. Additionally, changes in the microbiota were associated with each pathogen inoculated alone, but the simultaneous presence of Campylobacter and Salmonella induced specific modulations that could possibly explain this phenomenon. Significant differences were found in the serum metabolome of the contaminated groups, and partial least squares discriminant analysis models enabled the discrimination of contaminated animals from controls using these metabolic signals. Furthermore, possible links between variations in the microbiota and variations in the metabolome were identified.IMPORTANCEThis study demonstrates a synergistic effect between Salmonella and Campylobacter jejuni in the gut during co-infection in chickens, leading to an increased presence of both pathogens, as well as unique microbiota and metabolome changes. These findings underscore the importance of considering co-infection in poultry control measures and highlight the complex interplay between pathogens, microbiota, and metabolism.PMID:41649264 | DOI:10.1128/spectrum.01102-25

Invest Ophthalmol Vis Sci. 2026 Feb 2;67(2):21. doi: 10.1167/iovs.67.2.21.ABSTRACTPURPOSE: Glaucoma is a leading cause of irreversible blindness, yet the circulating proteins and metabolic pathways that causally contribute to different glaucoma subtypes remain poorly defined.METHODS: We analyzed baseline plasma proteomics in 1485 glaucoma cases (447 primary open‑angle glaucoma [POAG], 177 primary angle-closure glaucoma [PACG], 120 normal-tension glaucoma [NTG]) in the UK Biobank using Cox models with graded adjustment. We then integrated five independent protein quantitative trait loci resources with FINLAND R12 genome-wide association study data to perform two‑sample Mendelian randomization (MR) and cross‑cohort meta‑analysis for overall glaucoma and each subtype. To prioritize effector genes and pathways, we conducted summary-data-based Mendelian randomization (SMR) using eQTLGen and two‑step mediation MR using metabolite quantitative trait loci data for ∼1400 plasma metabolites from the Canadian Longitudinal Study on Aging cohort.RESULTS: In fully adjusted Cox models, 484 proteins were associated with incident glaucoma, 135 with NTG, 59 with POAG, and 1 with PACG (false discovery rate <0.05). Multicohort MR and meta‑analysis identified eight proteins with robust causal effects: NRP2, TSPAN1, and HAVCR2 for overall glaucoma; NRXN3 for PACG; MANSC4 for NTG; and LTBP2, CD69, and SMAD1 for POAG. SMR supported NRP2 (overall glaucoma) and SMAD1 (POAG) as causal genes. Mediation MR revealed that sphingomyelins, acylcarnitines, and bile acid-related metabolites partially mediated the effects of several proteins, defining shared (e.g., sphingolipid) and subtype‑specific metabolic pathways.CONCLUSIONS: By integrating epidemiologic, proteomic, genetic, and metabolomic data, we identify convergent systemic protein and metabolic signatures associated with glaucoma susceptibility and its clinical subtypes. These findings nominate NRP2, SMAD1, and related pathways as promising biomarkers and therapeutic targets and support a systems‑level view of glaucoma pathogenesis beyond intraocular pressure alone.PMID:41649226 | DOI:10.1167/iovs.67.2.21

Plant Cell Physiol. 2026 Feb 6:pcag017. doi: 10.1093/pcp/pcag017. Online ahead of print.ABSTRACTParasitic plants such as witchweeds transition from complete host dependence below ground to partial autotrophy after emergence, yet the mechanisms coordinating this metabolic shift remain poorly understood. Here, we combine fluorescent dye tracing, metabolite profiling, three-dimensional vascular imaging, tissue-specific transcriptomics, and targeted metabolomics to examine metabolic compartmentalisation in Striga hermonthica and Alectra vogelii. We identify a consistent interruption of host-derived transport at a stem-localised "sink equilibrium zone" (SEqZ) positioned below the first green leaves. This zone coincides with vascular reorganisation, the onset of photosynthesis, and a pronounced reconfiguration of carbohydrate gradients along the parasite axis. Using newly designed metabolite indices, we show that tissues below the SEqZ accumulate raffinose-family oligosaccharides and starch near the haustorium, consistent with strong sink activity and carbon storage, whereas tissues above the SEqZ are enriched in monosaccharides and metabolites associated with photosynthetic activity and growth. Transcriptomic analyses reveal that below-ground tissues preferentially express genes involved in sugar unloading, apoplastic barrier formation, Casparian strip development, and carbohydrate storage, while above-ground tissues activate photosynthesis, circadian regulation, and sugar redistribution pathways. Notably, spatially restricted expression of circadian regulators suggests a localised establishment of temporal control following emergence. Together, these findings support a model in which the SEqZ represents a developmentally defined transition zone where transport, unloading, and metabolic priorities shift to coordinate host-derived and self-fixed carbon through combined anatomical and molecular mechanisms. This framework provides mechanistic insight into trophic mode switching in Striga and Alectra and identifies metabolic features that may be exploited for improved parasitic weed control.PMID:41649145 | DOI:10.1093/pcp/pcag017

J Agric Food Chem. 2026 Feb 6. doi: 10.1021/acs.jafc.5c12081. Online ahead of print.ABSTRACTPhosphorus (P) deficiency reduces the crop yield, yet its impact on legume seed quality remains unclear. Herein, we found that phosphate (Pi) starvation led to a significant decrease in soybean (Glycine max) yield. However, seed nitrogen, protein, and amino acid concentrations were significantly increased by Pi starvation. Combined with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and RNA sequencing analyses of developing seeds, a total of 522 differentially accumulated metabolites (DAMs) were identified, particularly increased accumulations of amino acids, such as l-arginine and l-glutamine. Meanwhile, a total of 3793 differentially expressed genes (DEGs) were detected, with 1764 upregulated and 2029 downregulated by Pi starvation. Notably, the integration of metabolomic and transcriptomic analyses revealed a tight connection between DEGs and DAMs in developing seeds, especially for nitrogen translocation and assimilation. Collectively, this study highlights the complex and distinct responses of young soybean seeds to P deficiency, which provides candidate genes for improving the soybean seed protein concentration.PMID:41648942 | DOI:10.1021/acs.jafc.5c12081

bioRxiv [Preprint]. 2026 Jan 21:2026.01.20.700581. doi: 10.64898/2026.01.20.700581.ABSTRACTSpatial Metabolomics (SM) technology is transforming the fine-mapping of metabolic states associated with tissue function, and its power is greatly enhanced if augmented by a matching Spatial Transcriptomics (ST) profile. Several recent tools enable analysis of paired SM and ST data, including alignment and integration of the two modalities. However, there is only rudimentary support for probing biological relationships between the two omics views. We present a computational tool called MANTIS, which analyzes paired and aligned SM+ST profiles of a sample, optionally along with spatial domain or cell type information, to discover metabolite spatial distribution patterns and gene-metabolite relationships. It employs a novel strategy to assess statistical significance of such findings, based on specialized permutation tests that control for spatial autocorrelation of metabolite distribution. It disentangles different sources of spatial patterns and correlations, viz., those arising from regional preferences, cell type associations, or other unknown factors. It also introduces the use of spatial cross-correlation statistics and spatial partial correlation for quantifying gene-metabolite associations. We present the functionalities of MANTIS through application to three data sets spanning different spatial technologies, different tissues and species. We compare our findings to suitable baselines representing existing tools and argue that MANTIS achieves superior specificity in detecting patterns and associations, through its rigorous statistical procedures. To our knowledge, MANTIS is the first toolkit to unify spatial metabolomics, spatial transcriptomics, cell type information and spatial domains within a single framework that emphasizes spatial statistics and rigorous hypothesis testing.PMID:41648596 | PMC:PMC12871805 | DOI:10.64898/2026.01.20.700581

bioRxiv [Preprint]. 2026 Jan 17:2026.01.16.699917. doi: 10.64898/2026.01.16.699917.ABSTRACTBacteria use small molecules to orchestrate collective behaviors in a process called quorum sensing (QS), which relies on the production, release, and group-wide detection of extracellular signal molecules referred to as autoinducers. One QS autoinducer, termed AI-2, is broadly used for inter-species bacterial communication, including in the mammalian gut. AI-2 consists of a family of interconverting compounds and adducts originating from 4,5-hydroxy-2,3-pentanedione. This complex speciation, coupled with the inherent instability of AI-2 congeners, have complicated isolation efforts. It has been known that mammalian epithelial cells produce an AI-2 mimic to which bacteria respond. However, the identity of the AI-2 mimic has remained elusive, presumably due to its instability, similar to that of known AI-2 compounds. Here, we developed a reactivity-based metabolomics approach to capture and identify a mammalian AI-2 mimic. Using a chemical strategy targeted at the α-diketone moiety of known AI-2s, we identify the unusual sugar L-xylosone, as well as the related metabolite L-xylulose, as AI-2 mimics. While L-xylulose is a common and naturally occurring sugar known in human metabolism, L-xylosone is a rare and highly reactive oxidation product. We established a facile synthetic route to access pure enantiomers of xylosone and confirmed that, like AI-2, the L-configuration is required for recognition by the bacterial AI-2 receptor, LuxP, whereas D-xylosone is inactive. L-xylosone is new to the human metabolome, suggesting that other chemically reactive small molecules that mediate host-microbe interactions await discovery. The identification of L-xylosone expands the AI-2 family of molecules and adds a new word to the lexicon of host-bacterial interactions.PMID:41648565 | PMC:PMC12871118 | DOI:10.64898/2026.01.16.699917

bioRxiv [Preprint]. 2026 Jan 14:2026.01.13.699318. doi: 10.64898/2026.01.13.699318.ABSTRACTGene dosage imbalance resulting from an extra copy of human chromosome 21 (Hsa21) contributes to numerous clinical features in Down syndrome (DS). While dysregulated metabolism has long been noted in DS, the underlying cause is poorly understood and vastly understudied. To fill this critical knowledge gap, we conducted a comprehensive metabolic analysis of Dp(16)1Yey/+ mice (abbreviated Dp16), a segmental duplication model carrying a majority of the triplicated Hsa21 gene orthologs. Our multi-tissue transcriptomic analyses reveal shared and sex-specific increases in expression dosage of the triplicated genes in white and brown adipose tissues, liver, skeletal muscle, and hypothalamus. Despite sexual dimorphism in body weight, body temperature, food intake, and physical activity, Dp16 males and females share striking core phenotypes of pronounced insulin resistance, glucose intolerance, impaired lipid clearance, and dyslipidemia. Functional assessments, combined with biochemical, transcriptomic, and metabolomic analyses reveal tissue signatures of immune activation and a pro-inflammatory state, ER and oxidative stress, fibrosis, impaired glucose and fatty acid catabolism, altered lipid and bile acid profiles, and reduced mitochondrial respiration in Dp16 mice. These concerted changes disrupt homeostatic mechanisms that underpin metabolic health, contributing to systemic metabolic dysfunction. An obesogenic diet further exacerbates insulin resistance in Dp16 males and females despite divergent weight gain. The collective phenotypes broadly reflect the metabolic profile of DS. Our extensive molecular, biochemical, and physiological data provide an essential foundation for genetic dissection of dosage-sensitive genes affecting glucose and lipid metabolism, and for testing therapeutic strategies to improve metabolic outcomes in DS.PMID:41648536 | PMC:PMC12871095 | DOI:10.64898/2026.01.13.699318

bioRxiv [Preprint]. 2026 Jan 14:2026.01.13.699280. doi: 10.64898/2026.01.13.699280.ABSTRACTThe role of aromatic gut-derived bacterial metabolites (GDBMs) in shaping immune cell metabolism and function remains poorly explored. Using ex vivo metabolomic profiling of paired plasma and CD4⁺ T-cells from people living with HIV-1 (PLWH), we identified a network of aromatic GDBMs whose cell-associated abundance, rather than systemic levels, was linked to broad alterations in CD4⁺ T-cell metabolic and functional states. Among these metabolites, p-cresol sulfate (PCS) emerged as a mechanistic prototype investigated in depth. Ex vivo flow cytometry and single-cell RNA sequencing of CD4⁺ T-cells stratified by cell-associated PCS levels revealed dose-dependent enrichment of transcriptional programs associated with impaired differentiation capacity, regulatory-like identity, and cellular senescence. Consistently, in vitro transcriptomic and proteomic analyses of PCS-exposed CD4⁺ T cells demonstrated induction of cell-cycle arrest, mitochondrial dysfunction, and senescence-associated programs, including upregulation of p16 and p21. Integration of these immunometabolic features with measurements of HIV-1 reservoir size in PLWH revealed that CD4⁺ T-cell states defined by cell-associated GDBMs track with intact proviral DNA levels in vivo. Together, these findings define a microbiome-derived axis that reshapes CD4⁺ T-cell metabolism and fate and promotes immune aging-associated states in PLWH. Our data suggest that cell-associated GDBMs may foster immunometabolic CD4⁺ T-cell states previously linked to long-term HIV-1 reservoir persistence in vivo.PMID:41648363 | PMC:PMC12871317 | DOI:10.64898/2026.01.13.699280

bioRxiv [Preprint]. 2026 Jan 24:2026.01.23.701345. doi: 10.64898/2026.01.23.701345.ABSTRACTGlial cells maintain the brain's lipid and energy balance, and their breakdown is increasingly recognized as a causal contributor to Alzheimer's disease (AD). While this concept is established, no approach has directly shown how glial homeostatic failure manifests across brain regions and microenvironments or how it links local pathology, such as plaques, to global metabolic imbalance. To address this gap, we developed iMIST, an integrated platform that combines MALDI-based metabolite imaging, histology, and spatial transcriptomics within a single tissue section to align molecular and anatomical information. Using a mouse model of late-onset AD that recapitulates both amyloid deposition and metabolic vulnerability, iMIST revealed that glial lipid dysregulation is widespread but spatially specialized. In gray matter, plaque-associated microglia were associated with upregulated glycerophospholipid-remodeling in cortico-thalamic areas indicating metabolic stress around local pathology. In contrast, white matter tracts rich in lipid-producing oligodendrocytes show plaque-independent deficits in galactosylceramide metabolism reflecting their high myelin demand. Both processes intensify with age, transforming adaptive glial responses into persistent metabolic dysfunction. Together, these findings demonstrate the spatial interplay between global glial metabolic imbalance and local microenvironmental stressors associated with AD pathology. By integrating transcriptomic and metabolomic information in situ , iMIST provides a framework for uncovering how regional glial vulnerability shapes the pathogenesis of neurodegenerative diseases.PMID:41648223 | PMC:PMC12871637 | DOI:10.64898/2026.01.23.701345

bioRxiv [Preprint]. 2026 Jan 14:2026.01.13.699336. doi: 10.64898/2026.01.13.699336.ABSTRACTInsecticide resistance reduces the effectiveness of current malaria vector control interventions. To understand the mechanisms underlying permethrin resistance in field-derived Anopheles gambiae vectors collected from Cameroon, we used Ultra-High Performance Liquid Chromatography coupled with High-Resolution Tandem Mass Spectrometry (UHPLC-HRMS/MS) to comprehensively analyze metabolic changes in resistant and susceptible samples to gain insight into mechanisms driven permethrin resistance. Resistant mosquitoes exhibited upregulated levels of inosine, nicotinic acid, dipeptides, amino acids, fumarate, uracil, and aldopentose. These data suggest that altered metabolic-based detoxification, as well as target site and metabolic shifts, and enhanced energy production contribute to permethrin resistance. Conversely, susceptible mosquitoes showed increased levels of N-acetyl-aspartic acid, xanthurenic acid, 2-hydroxyglutarate, 3-hydroxykynurenine, propanoylcarnitine, and L-pipecolic acid. These metabolites are associated with neurotoxicity, energy disruption, as well as tryptophan and lysine catabolism. These findings elucidate the metabolic pathways of permethrin-resistance and underscore the mechanisms that could lead to the emergence of pyrethroid cross-resistance.PMID:41648180 | PMC:PMC12871309 | DOI:10.64898/2026.01.13.699336

bioRxiv [Preprint]. 2026 Feb 1:2026.01.22.701114. doi: 10.64898/2026.01.22.701114.ABSTRACTAcute systemic inflammation affects brain function, with detrimental consequences in aged individuals. These include delirium, an acute neuropsychiatric syndrome characterized by fluctuating disturbances in attention, perception and cognition. Delirium is associated with disrupted brain energy metabolism but our understanding of this during acute systemic inflammation is limited. Here we hypothesized that LPS-induced systemic inflammation would disrupt brain energy metabolism in aged C57BL6J mice and that the consequent functional impairments would be mitigated by ketone body utilization. We investigated ketone body effects in sickness behaviour, inflammation, energy metabolism and cognitive function. Real-time changes in utilisation of energy sources were quantified by indirect calorimetry and administration of radioisotope-labelled glucose and betahydroxybutyrate. Mass-spectrometry metabolomics was used to index severity of behavioural distrurbances to changes in hippocampal energy metabolism. LPS precipitated hypoglycemia and induced a whole-body switch from carbohydrate to lipid utilisation. Despite this, hippocampal insulin resistance and preserved brain glucose was observed while alternative carbohydrates, mannose and fructose, became depleted. Ketone ester treatment reversed insulin resistance, mitigated sickness behaviour and prevented delirium-like cognitive dysfunction without altering pro-inflammatory responses. Our results show that promoting ketone body usage mitigates systemic inflammation-induced brain energy disruption and prevents delirium-like cognitive deficits in aged mice.PMID:41648100 | PMC:PMC12871820 | DOI:10.64898/2026.01.22.701114

Front Microbiol. 2026 Jan 21;16:1730714. doi: 10.3389/fmicb.2025.1730714. eCollection 2025.ABSTRACTINTRODUCTION: Polycystic ovary syndrome (PCOS) is marked by disruptions in metabolic and reproductive endocrine functions. This study synthesizes systemic metabolic profiles, alterations in gut microbiota, and follicular fluid metabolism to elucidate the reproductive and endocrine metabolic changes associated with PCOS. Furthermore, it aims to elucidate the potential mechanisms through which acupuncture may exert therapeutic effects.METHODS: In this open-label randomized controlled trial conducted in China (November 2021-January 2023), 60 women with PCOS scheduled for In Vitro Fertilization (IVF) were randomized to receive acupuncture combined with IVF treatment or IVF treatment alone, with 30 healthy women serving as controls. Gut microbiota was sequenced and analyzed by 16S rRNA and metagenomics; follicular fluid metabolites were determined by untargeted metabolomics.RESULTS: Compared with healthy controls, PCOS exhibited gut microbiota dysbiosis and metabolic disorders. The specific gut microbiota in PCOS dominated by s_Lachnospiraceae, s_Blautia_sp. and g_Escherichia-Shigella, which correlated with body mass index (BMI), waist circumference, waist-to-hip ratio, and hormone levels. Acupuncture combined with IVF significantly regulated glucose and lipid metabolism, reduced g_Escherichia-Shigell abundance, and showed potential advantages in enhancing oocyte quality and embryonic developmental potential (p = 0.011). Analysis of the correlation between differential metabolites and oocyte and embryo quality demonstrated that methionine sulfoxide and boldione may be key metabolites to affect follicle quality.CONCLUSION: PCOS is associated with systemic multi-pathway metabolic dysregulation and gut microbiota dysbiosis. It described the potential therapeutic benefits of acupuncture combined with IVF for PCOS, laying a foundation for further understanding the disease and the mechanisms of acupuncture for PCOS metabolic disorders, and providing directions for future research.PMID:41648005 | PMC:PMC12868155 | DOI:10.3389/fmicb.2025.1730714