Multi-dimensional analyses unveil strain-specific metabolic perturbations and flavour deterioration traits induced by spoilage bacteria in cold-stored chicken breast.

Unraveling the metabolic fingerprinting and improved properties of wheat dough co-fermented with Lactiplantibacillus plantarum and Saccharomyces cerevisiae at different ratios.

Integrated transcriptomic and metabolomic analysis of intestinal responses of Litopenaeus vannamei under acute freshwater stress.

Niche adaptation of marine heterotrophic nitrification-aerobic denitrification bacterium in mariculture wastewater treatment: Synergistic mechanism of nitrogen removal and sulfamethoxazole biotransformation.

Untargeted metabolomics reveals bovine viral diarrhea virus infection reprogram host nucleotide and amino acid metabolism in MDBK Cells.

Multi-omics association analysis of the toxicity mechanism differences of typical veterinary antibiotics on tomatoes: From physiological inhibition to metabolic reprogramming.

Nucleotide (NT) supplementation is an efficient practice for enhancing growth and immune performance in farmed aquatic species. However, the NT mode of use, optimal dosage and metabolic effects in different species remain poorly understood. This study investigated the effects of exposing zebrafish ( Danio rerio ) and gilthead seabream ( Sparus aurata ) embryos and larvae to different concentrations of a blend of NTs directly through the water. Embryos and larvae were exposed for 96 h, starting at 24 h post fertilisation. The developmental and physiological parameters assessed included survival, hatching rate, morphology, swimming behaviour, expression of growth-related genes, and macrophage cell status. In zebrafish, survival and hatching rate were unaffected up to 200 mg L −1 (>90%). Morphological analysis revealed that zebrafish exposed to NT at 20–40 mg L −1 exhibited the most significant enhancements in growth (+5% compared to controls), while behavioural tests and gene expression analysis indicated increased swimming activity and significant modulation of key growth-related genes at 10 mg L −1 . Furthermore, immunological assays demonstrated a significant increase in the prevalence of pro-healing M2 macrophages in the gut of larvae at this NT concentration. In gilthead seabream, NT-treated larvae at 10 mg L −1 exhibited a significant increase in standard body length (+4% compared to controls), with no adverse effects on survival or hatching rate up to this level (>75%). Overall, these findings demonstrate that NT exposure promotes larval growth and modulates immune and metabolic activity in zebrafish and gilthead seabream, supporting the application of NT blends as sustainable bioactive additives in aquaculture. • Waterborne nucleotide enhance zebrafish and gilthead seabream larval growth. • Nucleotide exposure boosts zebrafish swimming activity and expression of growth-related genes. • Nucleotides increase pro-healing M2 macrophages in the gut of transgenic zebrafish. • Zebrafish serves as an efficient model for testing bioactive compounds in aquaculture.

NME2-driven epigenetic control of inflammasome-activated microglial lineage dynamics promotes sepsis-associated encephalopathy.

Grape seed proanthocyanidin extract suppresses bladder cancer by dual blockade of IMPDH1/2-mediated purine and pyrimidine nucleotide biosynthesis.

Dual metabolic reprogramming by metal-polyphenol nanoplatform enhances ferroptotic therapy for triple-negative breast cancer.

The genus Acinetobacter is recognized for its metabolic versatility, which contributes to environmental persistence, virulence, and antimicrobial resistance. This study aimed to elucidate the metabolic pathways, particularly those associated with virulence and antimicrobial resistance (AMR), in non-baumannii Acinetobacter species. Genome-scale metabolic prediction of 19 Acinetobacter isolates identified 104 distinct pathways spanning 32 metabolic categories. Ninety-six pathways were conserved across all genomes, whereas a small subset exhibited species- or strain-specific distributions: four pathways occurred in 18 isolates, three were restricted to five A. junii isolates, and one was unique to 14 A. nosocomialis genomes. Amino acid metabolism was the most diverse (29 pathways), followed by lipid metabolism (14 pathways) and energy metabolism (8 pathways). The 96 conserved pathways supported essential cellular functions, including protein synthesis, energy production, and nucleotide metabolism. Notably, 20 pathways were associated with virulence, pathogenicity, and AMR, spanning lipid metabolism, siderophore biosynthesis, and nucleotide metabolism, among others. Eighteen of these pathways were conserved across all isolates and encompassed diverse metabolic functions, including protein N-glycosylation, heme biosynthesis, lipid IVA synthesis, fatty acid β-oxidation, tRNA maturation, triclosan resistance, and superoxide degradation. Interestingly, all A. junii isolates uniquely encoded siderophore biosynthesis systems. In silico analysis of the whole-genome sequences from the five A. junii isolates revealed the presence of genes sharing > 91% sequence identity with the acinetoferrin biosynthetic cluster (acbABCD) from Acinetobacter haemolyticus. Additionally, genes homologous to the acinetoferrin transport genes (actB, actC, actA, and actD) were identified. However, genes associated with the desferrioxamine E biosynthetic pathway were not detected in these isolates. The high degree of conservation of the acinetoferrin biosynthetic cluster in A. haemolyticus and A. junii suggests that A. junii likely produces acinetoferrin. These findings highlight the high degree of conservation of metabolic pathways in non-baumannii Acinetobacter species and represent the first report of the putative acinetoferrin biosynthetic gene cluster in A. junii.

The diatom Cymbella janischii is an invasive species in Japan, causing nuisance blooms by forming thick mats in rivers. To date, there are no documented studies on the microbiome associations in C. janischii mats or the processes that drive bloom formation. This study used metabarcoding of diatoms, bacteria, and fungi to identify key species and assess the effects of C. janischii blooms on the benthic microbial communities. C. janischii blooms reduced diatom and bacterial species diversity, while fungal diversity remained stable. In addition, the diatom Nitzschia paleacea and the bacterium Flavobacterium sp. were observed to co-occur and vary in abundance, indicating a possible ecological link that may affect mat structure or function. Metagenomic predictions of bacterial functions showed that compared to benthic stones without visible C. janischii mats, mat-associated bacteria had enriched pathways related to the metabolism of carbohydrates, nucleotides, and amino acids, along with zeatin biosynthesis. Zeatin is a cytokinin phytohormone that stimulates plant growth and development. Invitro exposure of C. janischii to varying zeatin concentrations confirmed its growth-promoting effects, inducing cell proliferation and stalk formation. This study shows that zeatin stimulates the growth of C. janischii. The findings of this study provide new insights into microbiome diversity, identifying key taxa associated with C. janischii mats to help better understand bloom formation.

Multi-omics characterization of radiation-induced cerebellar remodeling and tumorigenic transcriptional programs.

Osteoporosis is characterized by an imbalance between bone formation and resorption, and the dysregulated differentiation of bone marrow mesenchymal stem cells (BMSCs) plays a central role. Our previous study identified Bhlhe22 as a key negative regulator of osteogenic differentiation; here, we further validate its role in osteoporotic BMSCs (OP-BMSCs) and investigate its therapeutic potential. Knocking down Bhlhe22 enhanced osteogenesis by upregulating key osteogenic markers (RUNX2, ALP, OPN) and suppressing the PI3K-Akt signaling pathway. To enable targeted delivery of siBhlhe22, we designed an aptamer-functionalized tetrahedral framework nucleic acid-based nanocarrier (Apt19S-tFNA-siBhlhe22, ATS). The ATS system exhibited well-defined nanostructure, excellent biocompatibility, and high cellular uptake efficiency in OP-BMSCs. In vitro, ATS-mediated Bhlhe22 knockdown significantly promoted osteogenic differentiation and matrix mineralization. This effect depended on the inhibition of PI3K-Akt signaling, as demonstrated by rescue experiments using the agonist Recilisib. Non-targeted metabolomics revealed that osteoporosis was associated with disruption of nucleotide and purine metabolism, which was effectively reversed by ATS treatment. Functional studies confirmed that intact purine metabolism, which was essential for ATP production and redox balance, was required for the pro-osteogenic effect of ATS. In an osteoporotic rat bone defect model, ATS delivered via GelMA hydrogel promoted bone regeneration. This was accompanied by in vivo suppression of PI3K-Akt signaling and upregulation of OCN and OPN. Our findings establish a novel gene therapy strategy that targets Bhlhe22 to simultaneously modulate pro-osteogenic signaling and metabolic reprogramming, offering a promising anabolic approach for osteoporosis treatment.

Ectonucleoside triphosphate diphosphohydrolase 2 (ENTPD2), an enzyme involved in extracellular nucleotide metabolism and purinergic signaling, has been linked to tumor-immune interactions, although its role in colorectal cancer (CRC) remains unclear. This study examined the expression pattern and regulatory context of ENTPD2 through integrative analysis of transcriptomic, proteomic, microRNA (miRNA), and single-cell transcriptomic datasets. Transcriptomic analyses showed that ENTPD2 mRNA levels are elevated in colorectal tumors compared with normal tissues and that higher expression is associated with shorter relapse-free survival. In contrast, proteomic analyses indicated reduced ENTPD2 protein abundance in tumor samples, suggesting a divergence between transcript and protein expression. Analysis of candidate miRNAs identified miR-708-5p as a potential post-transcriptional regulator, supported by its increased expression in CRC and a predicted binding site within the ENTPD2 3'-untranslated region (UTR). Single-cell transcriptomic datasets further indicated that ENTPD2 transcripts are mainly detected in malignant epithelial cells. We performed a functional validation using dual-luciferase reporter assays, qRT-PCR, and Western blot analysis in CRC cell lines. Experimental analyses demonstrated that miR-708-5p directly targets the ENTPD2 3'UTR in HCT116 cells and suppresses ENTPD2 expression in both HCT116 and HT-29 cells. These findings support a potential contribution of miR-708-5p to ENTPD2 regulation in CRC.

Polyphyllin V (PPV) is a pharmaceutically valuable steroidal saponin with extremely low natural abundance, severely limiting its research and application. Here we established an efficient plant-based production platform for PPV in Nicotiana benthamiana through systematic optimization of glycosyltransferases and UDP-sugar metabolism. By comparing five candidate enzymes from Paris polyphylla and Dioscorea zingiberensis, we identified optimal combinations: PpUGT73CR1 with AtUGP1 (UDP-glucose pyrophosphorylase) for trillin synthesis (442.20 μg/g dry weight), and DzGT1 with AtRHM2 (rhamnose synthase) for PPV production (284.92 μg/g dw)─representing an ∼30-fold improvement over natural levels. Metabolite profiling revealed that UDP-sugar availability is a critical bottleneck, with AtUGP1 and AtRHM2 coexpression enhancing trillin and PPV yields by 1.27-fold and 1.45-fold, respectively. Scale-up production yielded 21.1 mg of purified PPV from 118 g of biomass in a 6 day production cycle. This work establishes a rapid, scalable platform for producing low-abundance steroidal saponins and demonstrates the importance of engineering both glycosyltransferases and sugar nucleotide metabolism for efficient heterologous biosynthesis.

Colorectal cancer (CRC) exhibits profound molecular heterogeneity according to primary tumor location, but spatially resolved assessment is limited by interindividual variability. Here, to minimize interindividual genetic confounding, we performed an exploratory single-case spatial metabolomics study (MALDI-MSI) on a rare case of synchronous bilateral tumors from one patient. This was complemented by untargeted metabolomics (UHPLC-HRMS/MS) on tumor and matched normal tissues from a cohort of 30 CRC patients with different anatomical sites and histologies. As an observational finding in this single case, the left-sided colon cancer (LCC) showed distinct metabolite distribution features from the tumor core to the invasive margin, whereas in right-sided colon cancer (RCC), metabolic differences were more closely associated with a histological subtype. UHPLC-HRMS/MS showed that, among tubular adenocarcinomas, LCC exhibited enrichments in ether lipid and phosphatidylcholine metabolism, whereas RCC preferred nucleotide and fatty acid metabolism. Furthermore, right-sided mucinous adenocarcinomas displayed unique sphingolipid alterations, consistent with a possible desaturase-associated shift from apoptosis-promoting pathways toward structural functions compared with the tubular subtype. Collectively, these findings underscore the potential influence of primary tumor location and histology on a microenvironmental metabolic architecture, offering exploratory insights for future hypothesis testing on location- and histology-dependent tumor adaptation.

Chitosan-induced delay in quality deterioration of sturgeon fillets: insights from untargeted metabolomics and microbial diversity profiling under refrigeration.

SUMMARYBacteria are constantly exposed to changing environmental conditions, and to survive they need to adapt quickly, adjusting their gene expression and metabolism to make the most of the resources available. One of the mechanisms involved is the stringent response, characterized by production of specific guanosine derivatives-ppGpp and pppGpp (collectively called (p)ppGpp). These regulators exert their action and coordinate a global response at many different levels, for example, transcription, translation, nucleotide metabolism, DNA replication, and carbon and lipid metabolism. In this review, we discuss how (p)ppGpp is synthesized and degraded, how it controls different cellular processes and their interplay with other second messengers. A description of differences in (p)ppGpp regulation in Gram-negative and Gram-positive bacteria, along with recent findings and some historical perspectives, is provided. We argue that although much is known about the stringent response and the novel discoveries are definitely advancing the (p)ppGpp field, they are not exhaustive. Instead, they seem to constantly point to aspects that are still waiting to be uncovered-thus, the (p)ppGpp magic goes on.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a major global health challenge, characterised by a heterogeneous clinical spectrum. While metabolomic studies have identified disruptions in amino acid, lipid, nucleotide, and energy metabolism during COVID-19, these investigations often lack fine-grained clinical stratification. In this study, we performed untargeted metabolomic profiling of plasma from 25 participants, including five healthy controls and twenty COVID-19 patients classified into four severity groups (COV1–COV4) based on pulmonary involvement and the need for respiratory support. Using ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS), 541 metabolites were detected and analysed across all samples. Principal component analysis revealed a progressive metabolic divergence corresponding to disease severity. Monocarboxylic acid dysregulation was predominant in early to moderate cases (COV1–COV3), whereas severe disease (COV4) demonstrated a shift toward pyrimidine metabolism enrichment, consistent with heightened nucleotide turnover driven by viral replication and immune cell proliferation. Phenylalanine metabolism emerged as a consistently enriched pathway in COV1–COV3, suggesting aromatic amino acid perturbations as early markers of metabolic stress and immune activation. In contrast, pyrimidine pathway activation in COV4 could reflect profound systemic metabolic reprogramming associated with critical illness. These findings provide novel insights into COVID-19 pathophysiology, highlighting stage-specific metabolic signatures and potential biomarkers for disease monitoring. Our results support the concept of metabolomics-guided precision medicine, offering a rationale for targeted therapeutic interventions based on disease stage and metabolic phenotype.