Understanding and targeting erythroid cell metabolism.

Linking soil organic carbon mineralization to microbial interactions during alpine grassland degradation.

Metabolic network divergence: polyamine and ethylene biosynthesis dynamics in Arabidopsis thaliana and Solanum lycopersicum

Integrated multi-omics unravels bioactive metabolic networks during red chicory heading.

Integrated Tn-seq and MAGE-assisted rapid genome engineering targeting in Escherichia coli.

Metabolic modelling: Insights into the machine room of plant metabolism.

Reprogramming Corynebacterium glutamicum metabolism to efficiently synthesis protocatechuic acid from flask to pilot scale.

Cold stress is one of the major environmental challenges faced by plants, severely affecting their growth, development, and yield. With the intensification of global climate change, the impact of cold stress on plants is becoming increasingly significant. Plants respond to cold stress through complex metabolic regulatory networks, including the accumulation of protective metabolites, modulation of antioxidant defenses, and activation of secondary metabolic pathways. This study aims to explore the dynamic metabolic and transcriptomic responses of T. ambiguum under long-term cold stress, and to reveal its adaptive mechanisms. By integrating metabolomics and transcriptomics, this study provides an indepth analysis of gene expression and metabolic responses of T. ambiguum under different cold stress treatments (2 h, 6 h, 12 h), focusing on key metabolic pathways and signal transduction mechanisms involved in cold stress adaptation. To further investigate the relationship between genes and metabolites, weighted gene co-expression network analysis (WGCNA) was applied to construct the gene-metabolite coexpression network under cold stress. Several functional modules that play significant roles in cold response were identified. Notably, the pink module was found to be associated with lipid metabolism, sugar metabolism, and signal transduction pathways, while the black module was closely linked to plant hormone signaling and antioxidant responses. Additionally, KEGG enrichment analysis revealed that key pathways such as glycerophospholipid metabolism, proline metabolism, and plant hormone signal transduction work synergistically in cold stress adaptation, regulating cellular homeostasis and maintaining energy supply under prolonged cold stress. The results indicate that T. ambiguum enhances its cold tolerance through dynamic coordination between its transcriptomic and metabolic responses. This study provides new molecular biological evidence for the cold adaptation mechanisms of T. ambiguum and offers theoretical support for improving cold tolerance in related crops.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-22148-2.

This study establishes that Lactobacillus plantarum Lac16 alleviates DSS-induced colitis through gut microbiota-dependent mechanisms. Lac16 administration significantly ameliorated colitis symptoms while restoring intestinal barrier integrity, promoting anti-inflammatory macrophage polarization, and suppressing NLRP3 inflammasome overactivation. The pseudo-germ-free mouse model provided definitive evidence that Lac16's suppression of NLRP3 inflammasome overactivation requires gut microbiota. Fecal microbiota transplantation verified the causal role of microbiota in mediating Lac16's therapeutic benefits. Notably, Lac16 reshaped microbial composition, elevating beneficial genera (Alloprevotella and Dubosiella) while suppressing pathogenic genera (Bacteroides and Helicobacter). Crucially, Lac16 increased microbiota-derived short-chain fatty acids, particularly isobutyric acid. Both in vivo and in vitro experiments confirmed that isobutyric acid significantly contributes to anticolitic effects and suppresses NLRP3 activation. These findings elucidate a novel mechanism by which Lac16 ameliorates colitis via (i) microbiota-dependent NLRP3 inflammasome modulation and (ii) isobutyric acid-mediated protective effects. This work provides important insights into probiotic mechanisms and supports targeting microbial metabolic networks for IBD intervention.

African swine fever (ASF) is a highly contagious disease of pigs caused by the African swine fever virus (ASFV), posing a significant threat to global swine production. As an obligate intracellular parasite, ASFV relies on host metabolic networks to fulfill its replication requirements. However, the precise mechanisms by which it manipulates nucleotide metabolism remain unclear. In this study, untargeted metabolomic analysis of ASFV-infected porcine alveolar macrophages revealed significant perturbations in purine and pyrimidine metabolism, glycolysis, the pentose phosphate pathway (PPP), and the glutamate and aspartate metabolic pathways. Functional validation demonstrated that ASFV depends on de novo pyrimidine biosynthesis for viral genome replication. Notably, ASFV employs a dual strategy to sustain the supply of nucleotide precursors: (i) it hijacks the PPP to generate ribose-5-phosphate and NADPH for redox balance, and (ii) it enhances glutamine uptake and catabolism to provide the nitrogen and carbon needed for nucleotide biosynthesis and tricarboxylic acid cycle replenishment. Furthermore, although aspartate is essential for pyrimidine synthesis, ASFV circumvents dependence on extracellular aspartate by activating a cytosolic GOT1-mediated synthesis pathway. Collectively, these findings elucidate how ASFV reprograms host nucleotide metabolism to support its replication, offering new insights into virus-host metabolic interactions and identifying potential targets for antiviral therapy.IMPORTANCEAfrican swine fever (ASF) is a devastating disease that causes substantial economic losses in the global pig industry. This study demonstrates that the African swine fever virus (ASFV) reprograms host cell metabolism to produce the essential building blocks required for its replication. Specifically, ASFV manipulates host nucleotide biosynthetic pathways to secure both the substrates for DNA synthesis and the reducing power necessary to mitigate oxidative stress. Elucidating these metabolic interactions not only deepens understanding of ASFV pathogenesis but also highlights promising metabolic targets for antiviral therapy. By elucidating how ASFV hijacks nucleotide biosynthesis within infected cells, our findings pave the way for innovative strategies to combat ASF.

Progressive supranuclear palsy (PSP) is a clinically heterogeneous neurodegenerative disorder with unclear pathophysiology. This study aimed to uncover clinically relevant metabolic networks derived from 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in PSP. FDG and dopaminergic transporter PET data from 72 PSP patients and 70 healthy controls were analyzed, with an independent test set of 24 PSP patients. All patients underwent comprehensive neuropsychiatric assessments. Using spatial independent component analysis, the study identified independent metabolic networks and examined their correlations with clinical features and striatal dopaminergic binding. Three distinct metabolic networks were identified in PSP: The first network demonstrated hypometabolism in dorsomedial thalamus (dmT), medial prefrontal cortex (mPFC) and midbrain, termed the dmT-mPFC network, negatively correlating with disease severity, functional disability and duration, and associating with gait/midline disturbances and ocular dysfunction. The second network displayed posterior cingulate cortex (PCC) and lateral prefrontal hypometabolism (LPFC), named the PCC-LPFC network, linking to disease severity, cognitive impairment, and parkinsonism. The third network exhibited preserved putamen metabolism with ventrolateral thalamus and sensorimotor cortex hypermetabolism, inversely relating to disease duration. Both dmT-mPFC and PCC-LPFC networks strongly correlated with striatal dopaminergic degeneration. The test set showed strong associations between cognitive impairment and the PCC-LPFC network, and between functional disability and the dmT-mPFC network, along with potential trends linking disease severity to these networks. The robust clinical and dopaminergic-related independent metabolic networks offer novel insights into disease pathophysiology, whereas their qualitative weighting offers a potential tool for staging disease severity. © 2025 International Parkinson and Movement Disorder Society.

Targeting lactate metabolism in the tumor microenvironment: Immunomodulation and prospects for antitumor therapy.

Genome-scale CRISPRi and base-editing libraries for genetic decoding and strain engineering in Shewanella.

BackgroundThis study aimed to investigate the preventive effects of dietary linarin supplementation on Enterotoxigenic coli (ETEC) induced small intestinal barrier dysfunction in weaned piglets via gut microbiota modulation.ResultsTwenty-four weaned piglets were randomly assigned to four experimental groups. The four treatments were as follows: BD + NB (basal diet and orally administered nutrient broth), LN + NB (basal diet supplemented with 150 mg/kg linarin, and orally administered nutrient broth), BD + ETEC (basal diet and orally administered ETEC), LN + ETEC (basal diet supplemented with 150 mg/kg linarin, and orally administered ETEC). The results showed that linarin lowers the serum levels of diamine oxidase (DAO), endotoxin, and D-lactate (P < 0.05). Linarin significantly increased villus height and villus/crypt ratio (P < 0.01), while decreasing crypt depth in the duodenum. jejunum, and ileum (P < 0.05). Additionally, Linarin increased the number of goblet cells within villus-crypt units in the duodenum. jejunum, and ileum (P < 0.05). Linarin significantly enhanced intestinal barrier function, upregulated detoxification pathways, reduced epithelial apoptosis, and improved nutrient transporter expression in the small intestine." Linarin decreased the relative abundances of Actinobacillus, Romboutsia, Enterococcus, and Terrisporobacter, consequently modulating key metabolic pathways, including arginine and proline metabolism, steroid biosynthesis, and cysteine and methionine metabolism.ConclusionsDietary linarin supplementation mitigates ETEC-induced intestinal mucosal barrier dysfunction and enhances nutrient assimilation via targeted modulation of microbial communities and associated metabolic networks, thereby providing a new strategy for the prevention and treatment of ETEC diarrhea.Supplementary InformationThe online version contains supplementary material available at 10.1186/s42523-025-00446-4.

Mass spectrometry imaging (MSI) enables the visualization of hundreds to thousands of analytes in biological tissues. MSI is also capable of mapping time-dependent processes that, combined with these static metabolite profiles, provides a clearer picture of the molecular underpinnings of tissue function. This perspective is organized into sections demonstrating how MSI-based methods can provide unique functional data on systems ranging from single step enzyme-catalyzed transformations to complex metabolic network activities and cellular dynamics. This multisystem capability can be exploited to provide detailed descriptions of the molecular mechanisms contributing to tissue function. An aspect missing in many studies are corresponding maps of tissue microenvironments including oxygenation and pH which influence functional activities. Some progress has been made to map hypoxic and acidic tissue using MSI methods, but further development is needed. This includes pairing in vivo MSI functional studies to in vitro models. Additionally, integrating the capabilities of other imaging methods, such as magnetic resonance and vibrational spectroscopy, that are proven to detect tissue microenvironments, with dynamic MSI methods offer a route to match environment with functional activities. The combination of static molecular profiles, metabolic and cellular dynamics, and environmental mapping will provide the most detailed understanding of tissue function.

BackgroundThe candidate phyla radiation (CPR) comprises a widespread but poorly understood group of bacteria with limited cultured representatives, largely due to their metabolic dependencies on microbial hosts. In laboratory incubations, CPR often decline sharply in relative abundance, even when samples originate from natural environments where they dominate, such as groundwater, where they can represent over 50% of the microbiome. Suitable enrichment conditions and host interactions remain poorly defined.ResultsHere, we analyzed 16S rRNA gene amplicon data from 397 groundwater incubation samples across 31 treatments, including 22 under oxic conditions, to identify factors that promote CPR survival and growth. Despite an initial decline, CPR abundances recovered over longer incubation times, reaching up to 11–30% of the microbial community. In total, we detected 1410 CPR amplicon sequence variants (ASVs), spanning six major CPR classes commonly found in groundwater. Enrichment success was treatment-specific: Cand. Saccharimonadia dominated in incubations with polysaccharides (up to 31.4%), while Cand. Parcubacteria were enriched (> 23%) in treatments stimulating methylotrophs and autotrophs. ASV-specific growth rates based on quantitative PCR showed that some CPR doubled within 1–2 days, comparable to faster-growing non-CPR groundwater bacteria, while most CPR had doubling times around 15 days.Strikingly, although the relative abundance of many CPR ASVs showed positive correlation with anoxic conditions, overall CPR reached higher absolute abundances under oxic conditions than under anoxic conditions. Metabolic network analysis based on metagenome-assembled genomes revealed that up to 62% of annotated genes were associated with functions linked to oxic conditions. In fact, 25 CPR genomes encoded enzymes that directly utilize oxygen, challenging the long-standing view of CPR as strictly anaerobic, fermentative organisms.ConclusionsOur findings demonstrate that diverse CPR lineages not only survive but actively grow in groundwater incubations, even under oxic conditions. The discovery of genes for oxygen-dependent reactions and substantial CPR enrichment in oxic treatments reveals unexpected metabolic flexibility, helping to explain their persistence and ecological success across a wide range of environments. Supplementary InformationThe online version contains supplementary material available at 10.1186/s40168-025-02244-1.

BackgroundSjögren’s syndrome (SS) is a chronic autoimmune disorder marked by lymphocytic infiltration of exocrine glands, leading to xerostomia, keratoconjunctivitis sicca, and systemic involvement including fatigue, arthralgia, and visceral organ impairment. Its pathogenesis reflects a multifactorial interaction of genetic, environmental, and hormonal influences that collectively disrupt immune homeostasis and drive tissue injury. Extensive investigations remain essential to clarify molecular pathways and establish reliable biomarkers that can enable early detection and precision therapy in SS. Detailed characterization of metabolic and molecular disturbances associated with SS is indispensable for advancing both pathophysiological insight and clinical management.Material and methodsRigorous quality control, batch adjustment, and data normalization were applied to untargeted metabolomics to ensure consistency and analytical reliability. Serum metabolite profiling in SS was assessed through unsupervised principal component analysis (PCA) to distinguish intergroup variations. Quantitative evaluation of metabolite abundance, machine learning–based metabolite selection, and functional enrichment analyses using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed to identify candidate biomarkers. Differential gene expression and enrichment analyses, construction of protein–protein interaction (PPI) networks in the SS group, and orthogonal partial least squares discriminant analysis (OPLS-DA) were subsequently performed to investigate underlying molecular mechanisms. Correlations among metabolites, key genes, and immune cell subsets were also examined.ResultsQuality control confirmed the reliability and precision of the untargeted metabolomics data. Differential metabolite analysis highlighted significant alterations, with PC O-36:5, 4-Aminobutyric acid, and PC 16:0_16:1 exhibiting the most marked changes. Machine learning algorithms further identified metabolites including PC O-36:5, Prostaglandin B1, and L-Ergothioneine as candidates with diagnostic potential for SS. Functional enrichment revealed altered KEGG pathways including arginine and proline metabolism, pyrimidine metabolism, and nucleotide metabolism. Sequencing data analysis indicated enriched GO terms related to viral response, KEGG pathways such as Influenza A, and Gene Set Enrichment Analysis (GSEA) pathways including HUNTINGTONS_DISEASE. Two-way orthogonal partial least squares (O2PLS) delineated metabolites central to metabolic networks, such as PC O-36:5, along with genes critical to gene interaction networks, including GZMA. Correlation analysis demonstrated tight associations between metabolites, genes, and immune cell subsets in SS.ConclusionThis integrative analysis identified molecular markers with diagnostic relevance for SS and advanced the understanding of metabolic and molecular alterations underlying the disease.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12920-025-02256-8.

ABSTRACT As fundamental components of metabolic networks, metabolites act as both energy carriers and signaling molecules, orchestrating a wide range of physiological functions. Consequently, the abundance of metabolites within tissues and cells is typically under tight regulation, with any perturbation of this metabolic equilibrium frequently triggering diverse stress responses and diseases. Recent studies demonstrated that nutritional, environmental, and pathogenic stimuli factors during aquaculture may lead to the remodeling of the fatty acid oxidation pathway in aquatic animals, altering the abundance of fatty acid oxidation‐related metabolites and subsequently triggering stress response cascades. Thus, elucidating the functional roles and regulatory mechanisms of these metabolites is critical for developing targeted strategies to mitigate these stress responses. However, the current progress of research on metabolites related to fatty acid oxidation in aquatic animals is not well summarized. Therefore, in this study, we characterize the fundamental pathways of fatty acid oxidation in aquatic animals and summarize the mechanisms by which these metabolic pathways respond to diverse aquaculture‐related stressors. Furthermore, we systematically elucidate the mechanisms through which these metabolites mediate their regulatory functions, highlighting the distinct physiological roles of the key metabolites. Additionally, we provide our perspectives on the potential applications and future research priorities of fatty acid oxidation‐related metabolites in aquaculture. This review contributes to a better understanding of the dynamics and functions of fatty acid oxidation‐related metabolites in aquatic animals and will facilitate the development of metabolites‐based therapeutic strategies, thereby increasing the sustainability of aquaculture.

Metabolic network modeling, especially Flux Balance Analysis (FBA), plays a critical role in systems biology by providing insights into cellular behaviors. Although FBA is the main tool for predicting flux distributions, it can face challenges capturing flux variations under different conditions. Selecting an appropriate objective function is therefore important for accurately representing system performance. To address this, we introduce a novel framework (e.g., TIObjFind) that imposes Metabolic Pathway Analysis (MPA) with Flux Balance Analysis (FBA) to analyze adaptive shifts in cellular responses throughout different stages of a biological system. This framework determines Coefficients of Importance (CoIs) that quantify each reaction's contribution to an objective function, aligning optimization results with experimental flux data. By examining Coefficients of Importance, TIObjFind enhances the interpretability of complex metabolic networks and provides insights into adaptive cellular responses.

BackgroundThe rapid development of intensive layer breeding has intensified odor pollution that must be paid attention to for the green transformation of the industry. This study used Jingfen No.6 laying hens as the model to systematically evaluate the regulatory effect of compound microalgal powder (Chlorella vulgaris:Spirulina platensis:Haematococcus pluvialis = 3:1:1, 1:3:1, 1:1:3) on ammonia (NH3) emissions from laying hen manure.ResultsThrough analysis of the static NH3 production in manure, it was found that the NH3 emissions within 24 h in the experimental group with 0.50% compound microalgal powder added were reduced to 6.27–16.84 mg (vs. control: 28.29 mg), achieving a 40.47%–77.84% reduction. GC/MS and 16S rRNA sequencing analyses indicated that the compound microalgal powder intervened in the remodeling of the microbial community and nitrogen metabolism network in manure, driving the transformation from inorganic nitrogen to organic nitrogen, mitigated the proliferation of NH3-producing bacteria (such as Escherichia coli, Klebsiella pneumoniae, Kurthia, and Proteus), and increased the abundance of acid-producing bacteria (such as Leuconostocaceae and Lactobacillaceae). The Spirulina platensis powder group had the best emission reduction effect (reduced by 77.84%), and its mechanism was closely related to the mitigation of Gram-negative bacteria activity by phycocyanin and increased synthesis of aromatic compounds, such as 2,3,5-trimethyl-6-ethylpyrazine.ConclusionsThis study revealed the mechanism by which the compound microalgal powder reduces NH3 emissions by regulating the proliferation of acid-producing bacteria, reshaping the nitrogen metabolism network, and mitigating the activity of NH3-producing bacteria, while providing theoretical and data support for the development of environmentally friendly feed.Graphical Supplementary InformationThe online version contains supplementary material available at 10.1186/s40104-025-01264-z.