Search Results (59)

Antibiotic-resistant bacteria are widely distributed and threaten public health. Photocatalytic antimicrobial technology can effectively inactivate multidrug-resistant bacteria without readily inducing resistance. We previously showed that oxygen-rich vacancy Bi₂MoO₆ (OBM) exhibits excellent activity against methicillin-resistant Staphylococcus aureus (MRSA), but the underlying molecular mechanisms remain poorly understood. Here, we employed integrated transcriptomics and metabolomics, with qRT-PCR validation, to systematically elucidate the antibacterial mechanism of OBM against MRSA. OBM treatment induced profound transcriptional and metabolic alterations: 231 differentially expressed genes and 206 differentially abundant metabolites were identified. Functional enrichment analysis revealed cooperative involvement in multiple critical pathways, including inhibition of amino acid biosynthesis and protein translation, disruption of cell wall and membrane integrity, induction of oxidative stress, collapse of energy metabolism (suppression of oxidative phosphorylation and impaired ATP synthesis), and imbalance in nucleotide metabolism (down-regulation of DNA helicase and mismatch repair genes, dysregulation of purine/pyrimidine metabolism). These findings demonstrate that OBM photocatalytically inactivates MRSA through a multi-target systemic attack at both the transcriptional and metabolic levels, providing a novel theoretical foundation for the development of photocatalytic materials aimed at controlling MRSA and other drug-resistant bacteria. Full article

This study evaluated how graded dietary nucleotide supplementation (0, 0.25, 0.5, 0.75, 1.0, and 2.0 g/kg) affects growth performance, antioxidant capacity, intestinal morphology, and gut microbiota in swamp eel (Monopterus albus) (initial body weight 10.07 ± 0.92 g). Three hundred sixty fish were randomly assigned to six diets, each in triplicate, for eight weeks. Compared with the control, nucleotide addition significantly increased final body weight, weight gain rate, and specific growth rate, and decreased feed conversion ratio (p < 0.05), with optimal results at 0.75 g/kg (HS3). Survival was 100% in all groups. Supplemented fish showed lower serum and intestinal malondialdehyde levels and higher superoxide dismutase and catalase activities (p < 0.05). Serum total protein, albumin, and triglycerides increased, whereas alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transpeptidase decreased (p < 0.05), pointing to improved hepatic and lipid metabolism. Intestinal trypsin, lipase, and amylase activities also rose markedly (p < 0.05), peaking in HS3. Histological examination revealed greater mucosal thickness and villus height (p < 0.05); in HS3, these values reached approximately 0.95 mm and 0.87 mm, respectively. Metagenomic analysis showed that 0.75–1.0 g/kg nucleotides increased alpha diversity and restructured the microbial community, enriching Bacteroidetes- and Prevotella-related taxa while reducing Proteobacteria, including Acinetobacter baumannii and Escherichia coli. LEfSe identified dose-specific discriminant taxa, and refined KEGG Level 3 pathway analysis predicted enhanced butyrate and propanoate biosynthesis, starch utilization, and purine/pyrimidine interconversion at moderate doses. Genus-level abundances of Prevotella and Bacteroides correlated inversely with serum oxidative and hepatic stress markers. Quadratic regression estimated the optimal dietary nucleotide level at 764 mg/kg (0.76 g/kg), consistent with the best-performing 0.75 g/kg group. Collectively, 0.75–0.76 g/kg dietary nucleotides optimize growth and intestinal health in M. albus through coordinated improvements in antioxidant status, digestive function, mucosal architecture, and beneficial gut microbiota remodeling. Full article

The utilization of sugarcane molasses as a low-cost carbon source for riboflavin production is hindered by the reactive oxygen species (ROS) stress induced by its complex components, which suppresses microbial metabolism. To address this, we employed adaptive laboratory evolution (ALE) under progressively increasing stress to develop a sugarcane molasses-tolerant and high-yielding Ashbya gossypii. The adapted strain achieved a riboflavin titer of 298.39 ± 2.01 mg/L, representing a 99.4% increase over the parental strain (149.66 ± 4.97 mg/L), accompanied by a 96% increase in biomass (dry cell weight). Notably, the specific riboflavin production per unit biomass showed no significant difference between the two strains, indicating that the improved total yield was primarily driven by enhanced biomass accumulation. Transcriptomic analysis revealed the molecular basis for this enhanced biomass accumulation—the elevated expression of antioxidant enzymes (SOD1, PRDX5) mitigated ROS levels to support cellular growth, while the coordinated upregulation of the pentose phosphate pathway (E2.2.1.1) and purine metabolism genes (PPAT, ADE5, PFAS, ADSL) enhanced the supply of biosynthetic precursors, ribulose-5-phosphate (Ru5P) and GTP, for nucleotide biosynthesis and cell proliferation. These metabolic adjustments collectively enabled the adapted strain to achieve robust growth under sugarcane molasses stress, thereby driving the overall increase in riboflavin production. This study elucidates the molecular mechanism underlying ALE-improved riboflavin production and provides a promising strategy for its industrial fermentation using sugarcane molasses. Full article

Cordyceps militaris, a medicinal and edible mushroom, is renowned for its bioactive constituents and health-promoting effects. This study investigated the effects of vacuum freeze drying (VF), vacuum drying (VD), oven drying (OV), and sun drying (SU) on the metabolite profiles and antioxidant activities of C. militaris. VF showed the highest levels of total phenolics, total carotenoids, cordycepin, and N⁶-(2-hydroxyethyl)-adenosine, whereas VD better preserved total flavonoids. VF- and VD-treated samples also exhibited stronger antioxidant capacities than those processed by OV and SU in 1,1-diphenyl-2-picrylhydrazyl radical (DPPH•), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS^•+), hydroxyl radical (•OH), and ferric reducing antioxidant power (FRAP) assays. Metabolomics analysis identified 193 significantly altered metabolites after drying treatments. VF, VD, and SU increased carbohydrates, vitamins, and phenolic acids, while leading to reductions in amino acids, nucleotides, and fatty acids. KEGG analysis revealed that drying significantly affected pathways related to purine and pyrimidine metabolism, amino acid biosynthesis, and phenylpropanoid biosynthesis. Network pharmacology further identified 8 key compounds potentially associated with antioxidant effects through interactions with 37 core targets. These findings highlight the importance of selecting appropriate drying methods to preserve the bioactive compounds and functional quality of C. militaris. Full article

Slaughter performance is a critical economic trait that varies across breeds, yet the rumen metabolic mechanisms driving these phenotypic differences remain unclear. The study involved 30 healthy 12-month-old beef cattle, with 10 animals from each of the three breeds: Chinese Simmental (ST), Taihang Yun (TY), and Charolais (CL). The cattle were randomly assigned into three groups using a completely randomized design, and the average initial body weight was 549.78 ± 59.45 kg. A 130-day feeding trial (10-day pre-feeding period, 120-day main trial period) was conducted. By comparing the slaughter performance, relative organ weight, and rumen fluid metabolomic profiles, the study investigated breed-specific differences in meat quality and potential underlying metabolic patterns. The results showed that CL exhibited a superior carcass yield, with a significantly higher dressing percentage (62.38%, p = 0.013) and net meat percentage (56.54%, p = 0.028) than ST and TY, and a significantly lower backfat thickness (p = 0.006); ST had the highest proportion of premium cuts, relative to carcass weight (72.97%, p = 0.014), with prominent economic value, while TY had significantly higher weights of visceral organs, such as liver, kidney, small intestine and omasum, than CL (p < 0.05). Metabolomic analysis revealed that CL and ST had elevated levels of purine metabolism, nucleotide synthesis and cofactor biosynthesis compared to TY. In conclusion, CL and ST possess advantages in carcass yield supported by upregulated anabolic metabolism in the rumen, whereas TY prioritizes visceral organ development. These findings provide valuable insights into the physiological and metabolic divergences regulating the slaughter performance and regional adaptability across cattle breeds. Full article

Postmortem aging is a crucial process for improving meat quality; however, the metabolic mechanisms underlying the postmortem maturation of Yili horsemeat remain unclear. In this study, untargeted metabolomics was employed to investigate the dynamic changes in metabolites during postmortem aging of Yili horse longissimus dorsi muscle. Samples from six Yili horses were subjected to aging at 4 °C for 0, 14, and 28 days. Intramuscular Environment and metabolic profiles were analyzed using UHPLC-QTOF-MS. Results showed that meat pH initially decreased and then increased over the aging period (p < 0.05), whereas muscle fiber diameter and cross-sectional area gradually declined (p < 0.05). Metabolomic analysis revealed significant differences in metabolic profiles among different aging stages. KEGG pathway enrichment analysis indicated that the differentially expressed metabolites (DEMs) were predominantly involved in purine metabolism, nucleotide metabolism, and amino acid biosynthesis pathways. Notably, the degradation of AMP and IMP into inosine and hypoxanthine and the accumulation of free amino acids such as tryptophan and phenylalanine were closely associated with the development of umami taste and overall flavor of horsemeat. These findings elucidate the key metabolic pathways regulating postmortem meat quality in Yili horses and provide a theoretical basis for its production and application. Full article

Inosine is a key intermediate in many cellular pathways, and our RT-qPCR data showed that DNA polymerase eta (polη) was upregulated upon the repeated treatment of inosine and inosine monophosphate (IMP) in HCT116 cells, which suggests that polη is actively involved in the incorporation and bypass of inosine in cells. To gain novel insight into mutagenic potential of inosine incorporation into DNA and its implication on cell cycle arrest, we conducted structural, biochemical, and cell biological studies of human polη on the incorporation and bypass of inosine. Our nucleotide insertion assay showed that polη incorporated inosine triphosphate (ITP) opposite dC just 18-fold more efficiently than opposite dT, indicating that ITP incorporation by polη is promutagenic. Our three polη crystal structures showed that ITP formed Watson–Crick base pair with dC and that ITP adopted both syn- and anti-conformations across dT, increasing the promutagenicity. Our flow cytometry data showed that only excessive treatment of inosine and IMP caused S- and G2-phase arrest, suggesting that polη’s lesion bypass activity might resolve the cell cycle arrest. Our results give us novel insights into the role of polη in the mutagenic incorporation and bypass of DNA lesions, which might affect cell cycle arrest. Full article

Yellow fever virus (YFV) recurrently causes severe outbreaks in tropical regions of South America and Africa and an average of 30 to 40 thousand deaths worldwide each year. An effective vaccine is available but the coverage of the population in countries at risk is not optimal. No antivirals are currently approved for YFV treatment. Herein, we describe the evaluation of 6-MMPr, a de-novo-purine-nucleotide biosynthesis inhibitor, as a potentiator for enhanced activity of the broad-spectrum antiviral drug favipiravir in a hamster model of yellow fever. Administration of 6-MMPr was well-tolerated and a combination of favipiravir and 6-MMPr did not cause overt toxicity as indicated by normal weight gain of treated hamsters. Treatment with a combination of a suboptimal dose of favipiravir with 6-MMPr was significantly more effective in improving survival, weight change and virus replication when compared with monotherapy. The initiation of treatment two days after virus challenge was also effective in improving survival when compared with monotherapy. Our results demonstrate the safety and efficacy of such a combination either as a preventive or delayed treatment. Full article

Staphylococcus aureus is a leading cause of skin and soft tissue infections (SSTIs), yet the bacterial genomic adaptations underlying the transition from nasal colonization to invasive infection remain incompletely defined. We sequenced and analyzed 157 S. aureus isolates (126 from SSTIs and 31 from asymptomatic nasal colonization) from a primary care network in South Texas. Using genome-wide association studies, non-synonymous single-nucleotide variant (NSNV) profiling, and machine learning, we identified strain-specific adaptations in metabolic and regulatory pathways. SSTI isolates exhibited significant enrichment of nitrogen assimilation, purine biosynthesis, menaquinone production, and anaerobic respiration genes. Elevated copy number and colocalization of phage-linked metabolic genes—including nirB, narH, and nifR3—suggest a pathoadaptive genomic island supporting infection-specific energy generation. The enrichment of α/β-hydrolase domain-encoding genes was associated with clinical severity. To quantify severity, we developed the Purulent Ulcer Skin (PUS) score, which integrates wound size, drainage, and erythema. The α/β-hydrolase and lipoprotein genes were significantly associated with higher PUS scores (higher SSTI severity) and phage-encoded virulence gene products were linked to larger wound size. Machine learning prioritized purL and other metabolic loci as key infection classifiers. NSNVs and unitig-level changes co-localized within nutrient transport, stress resistance, and cytolytic genes, supporting a model of multi-layered genomic selection. Metagenomic assemblies of nasal microbiota were enriched for Staphylococcus, Enterococcus, and Micrococcus species, core metabolic pathways, and taxon-specific virulence determinants. This underscores the roles of metabolic and virulent co-networks within nasal commensals and their adaptive capacity for pathogenic transition. These findings provide a potential genomic blueprint of S. aureus pathoadaptation during SSTI and are a step towards the development of novel therapeutic targets. Full article

Phosphine (PH₃) is a fumigant often used to control insect pests, but its metabolic effects on insect physiology remain unclear. In this study, a comparative metabolomics analysis was performed to elucidate the physiological metabolic pathways affected by PH₃ exposure in Planococcus citri, and significant changes in the metabolic profiles induced by PH₃ treatment were identified. Principal component analysis and correlation analysis revealed different metabolic changes, and a total of 45 metabolites were identified and mapped to metabolic pathways using the KEGG database. PH₃ exposure inhibited energy metabolism by down-regulating riboflavin and flavin adenine dinucleotide, which are important cofactors in oxidative phosphorylation and reactive oxygen species generation. In addition, purine and pyrimidine metabolism, essential for nucleotide synthesis and cellular energy homeostasis, were also suppressed. Notably, lipid metabolism was significantly altered, and the juvenile hormone biosynthesis pathway was down-regulated. These results suggest that PH₃ inhibits electron transport chain activity, induces oxidative stress, and disrupts lipid homeostasis. This study enhances our understanding of the potential biomarkers of PH₃ exposure, the metabolic processes involved, and the resistance mechanisms that pests may develop in response to such exposure. Full article

Background: Salmonella infections pose a serious threat to both animal and human health worldwide. Notably, there is an increasing trend in the resistance of Salmonella to fluoroquinolones, the first-line drugs for clinical treatment. Methods: Utilizing Salmonella Typhimurium CICC 10420 as the test strain, ciprofloxacin was used for in vitro induction to develop the drug-resistant strain H1. Changes in the minimum inhibitory concentrations (MICs) of various antimicrobial agents were determined using the broth microdilution method. Transcriptomic and metabolomic analyses were conducted to investigate alterations in gene and metabolite expression. A combined drug susceptibility test was performed to evaluate the potential of exogenous metabolites to restore antibiotic susceptibility. Results: The MICs of strain H1 for ofloxacin and enrofloxacin increased by 128- and 256-fold, respectively, and the strain also exhibited resistance to ceftriaxone, ampicillin, and tetracycline. A single-point mutation of Glu469Asp in the GyrB was detected in strain H1. Integrated multi-omics analysis showed significant differences in gene and metabolite expression across multiple pathways, including two-component systems, ABC transporters, pentose phosphate pathway, purine metabolism, glyoxylate and dicarboxylate metabolism, amino sugar and nucleotide sugar metabolism, pantothenate and coenzyme A biosynthesis, pyrimidine metabolism, arginine and proline biosynthesis, and glutathione metabolism. Notably, the addition of exogenous glutamine, in combination with tetracycline, significantly reduced the resistance of strain H1 to tetracycline. Conclusion: Ciprofloxacin-induced Salmonella resistance involves both target site mutations and extensive reprogramming of the metabolic network. Exogenous metabolite supplementation presents a promising strategy for reversing resistance and enhancing antibiotic efficacy. Full article

Temperature is the most critical factor in fish preservation. Superchilled storage represents a novel technology that effectively retards quality deterioration in aquatic products. This study investigated the flavor variation patterns and deterioration mechanisms in 16 northern pike (Esox lucius) samples during superchilled storage (−3 °C) based on analysis using gas chromatography-ion mobility spectrometry (GC-IMS) and ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). The results indicate that GC-MS analysis identified 25 key volatile flavor compounds. These comprised seven ketones, thirteen alcohols, aldehydes including 2-methylbutanal, esters such as 2-heptyl acetate and methyl butyrate, as well as nitrogen-containing compounds, exemplified by pyrazines and indole. Non-targeted metabolomics further revealed four pivotal metabolic pathways, glycerophospholipid metabolism, purine metabolism, the pentose phosphate pathway, and arginine biosynthesis. These metabolic pathways were found to regulate flavor changes through modulation of lipid oxidation, nucleotide degradation, and amino acid metabolism. Notably, the arginine biosynthesis pathway exhibited significant correlations with the development of characteristic cold-storage off-flavors, mediated by glutamate accumulation and fumarate depletion. This investigation provided a theoretical foundation for optimizing preservation strategies in cold-water fish species at the molecular level. Full article

Nitrogen (N) critically regulates wheat growth and grain quality, yet the molecular mechanisms underlying foliar nitrogen application remain unclear. This study evaluated the effects of foliar nitrogen application (12.25 kg ha⁻¹) on the growth, grain yield, and quality of spring wheat, as well as its molecular mechanisms. The results indicated that N was absorbed within 3 h post-application, with leaf nitrogen concentration peaking at 12 h. The N treatment increased whole-plant dry matter accumulation and grain protein content by 11.34% and 6.8%, respectively. Amino acid content peaked 24 h post-application, increasing by 25.3% compared to the control. RNA-sequencing analysis identified 4559 and 3455 differentially expressed genes at 3 h and 24 h after urea treatment, respectively, these DEGs being primarily involved in nitrogen metabolism, photosynthetic carbon fixation, amino acid biosynthesis, antioxidant systems, and nucleotide biosynthesis. Notably, the plastidic glutamine synthetase gene (GS2) is crucial in the initial phase of urea application (3 h post-treatment). The pronounced downregulation of GS2 initiates a reconfiguration of nitrogen assimilation pathways. This downregulation impedes glutamine synthesis, resulting in a transient accumulation of free ammonia. In response to ammonia toxicity, the leaves promptly activate the GDH (glutamate dehydrogenase) pathway to facilitate the temporary translocation of ammonium. This compensatory mechanism suggests that GS2 downregulation may be a key switch that redirects nitrogen metabolism from the GS/GOGAT cycle to the GDH bypass. Additionally, the upregulation of the purine and pyrimidine metabolic routes channels nitrogen resources towards nucleic acid synthesis, and thereby supporting growth. Amino acids are then transported to the seeds, culminating in enhanced seed protein content. This research elucidates the molecular mechanisms underlying the foliar response to urea application, offering significant insights for further investigation. Full article

Growth traits are the most important economic traits in red tilapia (Oreochromis spp.) production, and are the main targets for its genetic improvement. Increasing salinity levels in the environment are affecting the growth, development, and molecular processes of aquatic animals. Red tilapia tolerates saline water to some degree. However, few credible genetic markers or potential genes are available for choosing fast-growth traits in salt-tolerant red tilapia. This work used genome-wide association study (GWAS) and RNA-sequencing (RNA-seq) to discover genes related to four growth traits in red tilapia cultured in saline water. Through genotyping, it was determined that 22 chromosomes have 12,776,921 high-quality single-nucleotide polymorphisms (SNPs). One significant SNP and eight suggestive SNPs were obtained, explaining 0.0019% to 0.3873% of phenotypic variance. A significant SNP peak associated with red tilapia growth traits was located on chr7 (chr7-47464467), and plxnb2 was identified as the candidate gene in this region. A total of 501 differentially expressed genes (DEGs) were found in the muscle of fast-growing individuals compared to those of slow-growing ones, according to a transcriptome analysis. Combining the findings of the GWAS and RNA-seq analysis, 11 candidate genes were identified, namely galnt9, esrrg, map7, mtfr2, kcnj8, fhit, dnm1, cald1, plxnb2, nuak1, and bpgm. These genes were involved in ‘other types of O-glycan biosynthesis’, ‘glycine, serine and threonine metabolism’, ‘glycolysis/gluconeogenesis’, ‘mucin-type O-glycan biosynthesis’ and ‘purine metabolism signaling’ pathways. We have developed molecular markers to genetically breed red tilapia that grow quickly in salty water. Our study lays the foundation for the future marker-assisted selection of growth traits in salt-tolerant red tilapia. Full article

Background: Including Chronic Myeloid Leukemia (CML) patients with deep molecular responses (MR4.5) and those with suboptimal responses provides valuable insights into treatment-associated metabolic changes. This study aimed to characterize the metabolomic alterations associated with CML and identify potential biomarkers for treatment response, particularly in patients achieving a deeper molecular response versus those with poorer responses. Methods: Plasma samples were collected from 51 chronic-phase CML patients and 24 healthy controls. CML patients were classified into two groups based on molecular responses: T1 (BCR-ABL1 IS ≤ 0.0032%) and T2 (BCR-ABL1 IS > 0.0032%, <1%). Metabolomic profiling was conducted using quadrupole time-of-flight liquid chromatography/mass spectrometry. The data analysis involved a partial least squares discriminant analysis, variable importance in projection (VIP) scores, and a pathway enrichment analysis. Significant metabolites were identified. Results: The PLS-DA revealed distinct metabolomic profiles between CML patients and healthy controls as well as between the T1 and T2 groups. Key differentiating metabolites with VIP scores > 1.5 included glutamate, hypoxanthine, and D-galactonic acid. In the T2 group, significant increases in malate and 5-aminoimidazole-4-carboxamide ribonucleotide were observed, reflecting disruptions in purine metabolism, the tricarboxylic acid cycle, and amino acid metabolism. The pathway enrichment analysis highlighted significant alterations in CML energy metabolism, nucleotide synthesis, and amino acid biosynthesis. Conclusions: CML patients exhibit pronounced metabolic changes, particularly in energy and nucleotide metabolism, which are linked to treatment response. These findings provide novel insights into CML biology and suggest potential biomarkers for monitoring treatment efficacy and predicting outcomes and therapeutic targets for improving treatment outcomes and overcoming tyrosine kinase inhibitor resistance. Full article