Search Results (167)

This study aimed to investigate the effects of dietary Herba Epimedii Folium (HEF) supplementation on semen quality, reproductive hormones, immune parameters, gut microbiota, and seminal plasma metabolites in aged boars, and to evaluate its potential for extending their reproductive lifespan. A total of 18 Bama boars (approximately 3 years of age) were randomly assigned to three groups (n = 6 per group). The control group received a basal diet, while the treatment groups were fed the basal diet supplemented with 3 g/kg or 5 g/kg of HEF for 8 weeks. The results showed that adding HEF to the diet of aged boars increased the motility and concentration of their sperm and reduced the proportion of abnormal sperm. Treatment with 3 g/kg HEF increased serum LH and IgG levels, whereas the 5 g/kg dose elevated IgA levels in both serum and seminal plasma, as well as IgG levels in seminal plasma. Furthermore, 16S rRNA sequencing revealed that dietary HEF supplementation reduced the relative abundance of Streptococcus and Oscillospiraceae UCG-002 in the gut of aged boars. PICRUSt2 analysis predicted that pathways involved in lysine biosynthesis, arginine and proline metabolism, glycine, serine and threonine metabolism, and amino acid-related enzymes were enriched in the HEF treatment group. Semen metabolite profiling showed that the HEF treatment enriched several key metabolites, including 5-hydroxytryptophan, acetylcarnitine, tretinoin, methyltestosterone, prostaglandin A3, and prostaglandin B2. Spearman correlation analysis revealed a negative association between Streptococcus abundance and sperm motility, whereas acetylcarnitine, 5-hydroxytryptophan, and prostaglandin A3 were positively associated with motility. Furthermore, 5-hydroxytryptophan levels were positively linked to both sperm concentration and serum LH. In summary, our study demonstrates that Epimedii Folium may enhance the semen quality of aged Bama boars by improving the intestinal microbiota and the metabolic profile of seminal plasma. These findings may offer a theoretical basis for optimizing reproduction and conserving germplasm resources in aged Bama miniature pigs. Full article

Cysteine biosynthesis is increasingly recognized as a critical determinant of bacterial virulence, highlighting this pathway as a promising reservoir of novel antimicrobial targets. In Pseudomonas aeruginosa, however, the molecular basis of cysteine production has only recently begun to emerge. Here, we identify PA3816 as the major P. aeruginosa serine acetyltransferase (PaCysE), the enzyme responsible for generating the activated serine intermediate that feeds O-acetylserine sulfhydrylase-mediated cysteine synthesis. Through a combination of biochemical and genetic approaches, we demonstrate that PaCysE efficiently catalyzes L-serine acetylation in vitro, and in turn, deletion mutants exhibit cysteine auxotrophy, underscoring its essential contribution to O-acetylserine production. Notably, PaCysE is less sensitive to feedback inhibition by cysteine and does not appear to form the canonical cysteine synthase complex, suggesting a regulatory architecture that diverges from well-characterized orthologs. Loss of PaCysE function has broad physiological consequences, including enhanced biofilm formation, reduced pyocyanin production, and attenuated infectivity in an animal model, linking cysteine biosynthesis directly to pathogen fitness. Finally, we identify a thiazole derivative that inhibits PaCysE activity (IC₅₀ ≈ 30 µM) and suppresses bacterial growth in a cysteine-dependent manner, providing a proof-of-concept for therapeutically targeting this pathway. Full article

Background: Nitrous oxide (N₂O) is increasingly used as a recreational drug, leading to neurological and systemic toxicities. However, due to the rapid elimination and minimal alteration of nitrogen oxides, the short direct detection window complicates the assessment of N₂O exposure. Method: In this study, we investigated the effects of chronic N₂O exposure on plasma metabolites using an untargeted metabolomics approach in a mouse model. C57BL/6 mice were exposed to 90,000 ppm N₂O (1 h, twice daily for 28 days) or room air. Plasma samples were analyzed via UHPLC -Triple TOF -MS. Orthogonal partial least squares discriminant analysis (OPLS-DA) and receiver operating characteristic (ROC) curves were used to identify differential metabolites. Result: A total of 35 differential metabolites were identified. Eight metabolites with an area under the curve (AUC) > 0.90 were selected as candidate biomarkers, including up-regulated SOPC and PC(16:0/16:0) (suggesting disrupted phospholipid remodeling and membrane integrity), and down-regulated DL-tryptophan, creatine, ectoine, indole, His-Ser, and Ile-Pro. Pathway enrichment analysis revealed significant alterations in glycine, serine and threonine metabolism; phenylalanine, tyrosine and tryptophan biosynthesis; protein digestion and absorption; and tryptophan metabolism. Conclusions: Our data indicate that chronic N₂O exposure disrupts multiple amino acid-related metabolic pathways (e.g., tryptophan-kynurenine pathway) and phospholipid homeostasis. The identified metabolite changes, along with vitamin B₁₂, homocysteine, and methylmalonic acid, may constitute a specific metabolic fingerprint for N₂O exposure. These findings help reveal the intrinsic mechanistic links underlying metabolic disorders induced by N₂O exposure. Full article

An integrated approach combining metabolomics, network pharmacology, and molecular docking was employed to systematically explore the serum-absorbed components of jujube, their potential targets, and regulatory pathways. UPLC-MS/MS was used to characterize the absorbed components, while network pharmacology was applied to predict potential targets associated with alcoholic liver disease (ALD). A total of 10 absorbed components and 323 common targets were identified. Among the key components, quercetin, (-)-epigallocatechin, and methyl gallate exhibited strong binding affinities to eight core targets, including AKT serine/threonine kinase 1 (AKT1) and mitogen-activated protein kinase 1 (MAPK1), with quercetin showing the highest content. Jujube intervention significantly altered the serum metabolic profiles of healthy rats, with distinct differences observed between the control and jujube-treated groups. Bioinformatics analysis revealed that the differential metabolites were mainly enriched in the diterpenoid biosynthesis pathway. These findings provide a systematic and preliminary characterization of the serum-absorbed components of jujube, their potential ALD-related targets, and their regulatory effects on serum metabolism in healthy rats. This study provides a preliminary theoretical reference and direction for further research on the potential role of jujube in ALD. Full article

Faba bean-fed crispy tilapia represents a commercially valuable aquaculture product, renowned for its exceptional muscle firmness. However, the dynamic changes in muscle metabolite profiles during the tilapia crisping process remain largely unelucidated. In this study, proton nuclear magnetic resonance spectroscopy (¹H-NMR) combined with multivariate statistical analysis was employed to characterize and compare the muscle metabolomes of tilapia subjected to different crispness grades (CD0, CD2, CD4). A total of 11 differential metabolites were successfully identified, among which glycine, threonine, and trans-4-hydroxy-L-proline were demonstrated to be potential crispness-related biomarkers. Specifically, as the crispness grade increased from 0 to 4, the muscle contents of these key metabolites exhibited a consistent downward trend: glycine decreased significantly from 19.86 mM to 7.15 mM, threonine from 1.21 mM to 0.58 mM, and trans-4-hydroxy-L-proline from 2.25 mM to 0.89 mM. Subsequent metabolic pathway enrichment analysis further revealed that the glycine-serine-threonine metabolic pathway represented the most significantly perturbed pathway associated with the crisping process. Collectively, our findings demonstrate that faba bean-based feeding regimens enhance tilapia muscle crispness by orchestrating metabolite signatures involved in collagen biosynthesis and lipid metabolism. These results not only provide novel insights into the intrinsic molecular mechanisms underlying tilapia crisping but also establish a solid theoretical framework for the precise quality control and standardized production of high-quality crispy tilapia. Full article

This study investigates the mechanisms underlying drought adaptability in Duolang sheep, a local breed from two distinct habitats in Xinjiang—an arid southern region and a grassland northern region—aiming to identify key factors driving differential environmental adaptation. Integrated multi-omics analyses were performed, including serum biochemical assays, untargeted metabolomics of perirenal and tail fat tissues, and transcriptomic profiling of lung, liver, and kidney samples. Our results revealed notable differences: (1) serum levels of GSH-Px, IL-2, and IgG were significantly higher in the southern group (p < 0.01); (2) metabolomic analysis identified key differential metabolites, including EPA (involved in unsaturated fatty acid biosynthesis), choline (glycerophospholipid metabolism), L-serine and glutathione (cofactor biosynthesis), and taurine (sulfur metabolism); and (3) transcriptomic analysis revealed significant differential expression of genes such as FGF21 (thermogenesis), CD14 and DUSP2 (MAPK signaling pathway), GOT1 (arginine biosynthesis), and AVPR2 (vasopressin-regulated water reabsorption). Integrative correlation analysis further indicated that glutathione, EPA, GOT1, and CD14 are involved in energy and lipid metabolism, while taurine, AVPR2, and DUSP2 contribute to oxidative stress resistance and immune regulation. These molecular and metabolic adjustments collectively enhance drought adaptability in southern Xinjiang Duolang sheep. In conclusion, adaptation to arid environments requires enhanced antioxidant capacity and immune function, with metabolites such as EPA supporting lipid metabolism and genes such as FGF21 regulating fatty acid oxidation to limit triglyceride accumulation. Full article

This study provides a systematic and multidimensional evaluation of flesh quality differences between triploid (T-PZ) and allotetraploid (A-PZ) Pengze crucian carp, addressing a significant gap in genetic improvement of this economically important aquaculture species. By integrating proximate composition analysis, detailed amino acid and fatty acid profiling, volatile flavor compounds, texture characteristics, and non-targeted muscle metabolomics, we delineated the distinct quality attributes associated with each cytotype. The results showed that T-PZ possessed significantly higher crude protein and histidine content, along with a superior flavor profile characterized by lower relative levels of fishy odor-associated aldehydes such as hexanal, heptanal, and nonanal. In contrast, A-PZ exhibited significantly elevated crude lipid, total fatty acid, SFA, MUFA, PUFA, and EPA + DHA contents; a higher essential amino acid index; and improved tenderness indicated by significantly lower hardness and chewiness. Metabolomic analysis identified 216 significantly different metabolites, notably enriched in key pathways including glycine, serine, and threonine metabolism; arginine biosynthesis; and glycerophospholipid metabolism. These comprehensive findings elucidate the complementary nutritional and sensory strengths of the two ploidy forms, thereby establishing a crucial scientific foundation for targeted, quality-driven breeding programs aimed at optimizing flesh quality in Pengze crucian carp for the aquaculture industry. Full article

Background: Broodiness is a major limiting factor for reproductive efficiency in indigenous avian breeds, a phenomenon underpinned physiologically by granulosa cell (GC) apoptosis and subsequent follicular atresia. While Serine Protease 23 (PRSS23) has been implicated in mammalian ovarian remodeling, its specific regulatory function in avian follicular dynamics remains elusive. Methods: Utilizing the Wuding chicken—an indigenous breed distinguished by robust environmental adaptability but compromised by high broodiness frequency—as a biological model, this study dissected the molecular mechanism of PRSS23-mediated follicular regression. We cloned the complete coding sequence of the Wuding chicken PRSS23 gene, characterized its spatiotemporal expression profile, and interrogated its function in primary GCs via gain- and loss-of-function assays. Results: RT-qPCR analysis revealed that PRSS23 is differentially expressed across the hypothalamic–pituitary–ovarian (HPO) axis, with ovarian expression being significantly upregulated during the broody period compared to the laying period. Mechanistically, PRSS23 overexpression significantly downregulated the expression of follicle-stimulating hormone receptor (FSHR) and key steroidogenic enzymes (STAR, CYP19A1, HSD3β1), thereby suppressing the expression of genes governing the biosynthesis potential of progesterone and estradiol. Concurrently, PRSS23 overexpression was associated with transcriptional repression of components of the PI3K/AKT/mTOR signaling cascade; this transcriptional regulation further induced cell cycle arrest at the G0/G1 phase, and activated the mitochondrial apoptotic pathway characterized by BAX upregulation and BCL2 downregulation. Conversely, siRNA-mediated knockdown of PRSS23 alleviated these inhibitory effects, promoting GC proliferation and survival. Conclusions: These findings establish PRSS23 as a pivotal pro-atretic factor in Wuding chickens, driving ovarian atrophy through the dual transcriptional-level inhibition of steroidogenesis and survival signaling pathways. This study identifies a potential molecular target for marker-assisted selection programs aimed at attenuating broodiness while preserving the superior meat quality traits of indigenous poultry. Full article

Metabolic reprogramming is a defining feature of breast cancer, enabling tumor cells to sustain rapid proliferation, survive under stress, and resist therapy. Key pathways including glycolysis, glutaminolysis, lipid metabolism, and one-carbon metabolism, play central roles in meeting the energetic and biosynthetic demands of malignant cells. Enhanced glycolytic flux supports ATP generation and lactate production, while glutamine metabolism fuels the tricarboxylic acid cycle and provides nitrogen for nucleotide synthesis. Lipid metabolic pathways, particularly fatty acid synthesis, contribute to membrane biogenesis and signaling, and one-carbon metabolism driven by serine and glycine supplies methyl groups for epigenetic regulation and nucleotide production. These metabolic adaptations not only promote tumor growth but also create vulnerabilities that can be exploited therapeutically. Inhibiting these pathways has shown promise in preclinical models; however, challenges such as metabolic plasticity, tumor heterogeneity, and potential toxicity in normal tissues underscore the need for biomarker-driven strategies and rational combination therapies. Herein, we describe current knowledge of the role of these pathways in breast cancer progression, highlighting the role of key enzymes in promoting breast cancer tumor cell growth and in breast cancer prognoses. Full article

Several strains of Lysobacter have demonstrated keratin-degrading capabilities, positioning them as promising candidates for the degradation and utilization of wool waste. In our previous study, a novel strain, Lysobacter brunescens YQ20, exhibiting highly efficient keratin degradation capabilities, was isolated. In this study, transcriptomic and proteomic analyses were conducted to elucidate the underlying mechanisms of keratin degradation. Our findings revealed that several metabolic pathways, specifically, valine, leucine, and isoleucine biosynthesis; phenylalanine, tyrosine, and tryptophan biosynthesis; glycine, serine, and threonine metabolism; and histidine metabolism, were highly active during keratin degradation, thereby supporting the growth and metabolism of L. brunescens YQ20. Additionally, the upregulation of genes related to sulfur metabolism, cysteine and methionine metabolism, and glutathione metabolism pathways facilitated the cleavage of disulfide bonds in keratin. Moreover, keratinases identified among the differentially expressed genes and proteins (DEGs/DEPs) were classified into the S8, M14, and M28 families, whose synergistic activity contributed to the efficient hydrolysis of keratin. Collectively, these results provide valuable insights into the molecular mechanisms by which L. brunescens YQ20 contributes to keratin degradation. Full article

Background: Drug-induced liver injury (DILI), a major type of adverse drug reaction, has become one of the leading causes of acute liver injury and liver failure worldwide. Its clinical significance lies not only in acute hepatocyte necrosis and functional failure but also in its role as a key initiating factor for liver cancer progression. Therefore, early diagnosis of DILI is of great importance. Methods: This study employed ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) to perform widely targeted metabolomics analysis on acetaminophen (APAP)-induced liver injury mice and healthy mice. Results: UPLC-QTRAP-MS/MS identified 41 differentially expressed metabolites primarily involved in glycerophospholipid metabolism, arginine and proline metabolism, primary bile acid biosynthesis, and glutathione metabolism pathways. The significant elevation of serum and hepatic alanine aminotransferase (ALT) and aspartate aminotransferase (AST) confirmed the successful establishment of the drug-induced liver injury (DILI) model. ROC curve analysis indicated 11 metabolites with AUC values exceeding 0.90 as potential biomarkers, including (R)-2-Hydroxybutyric acid, Glu-Gln, γ-Glu-Gln, 2-Methyllactic acid, L-Serine, Hyodeoxycholic acid, 3-Epideoxycholic acid, and Glycochenodeoxycholic acid 7-sulfate. Conclusions: We propose that these differential metabolites may serve as candidate biomarkers for DILI. Our findings provide a novel metabolomic signature derived directly from the injured tissue and offer a theoretical foundation for further research into early diagnosis of drug-induced liver injury. Full article

Betaphycus gelatinus, a member of the Eucheumatoideae, serves as the primary source for carrageenan extraction and has significant economic value. The growth and reproduction of B. gelatinus are significantly impacted by seasonal fluctuations in seawater temperature. To explore its adaptive mechanisms under temperature stress, we cultured the algae at 15 °C (Low temperature, LT), 27 °C (Medium temperature, MT), and 36 °C (High temperature, HT) for 2 h and conducted subsequent physiological, transcriptomics, and metabolomics analyses. The photosynthetic performance of B. gelatinus significantly declined under both LT and HT stress conditions. Carotenoid content increased significantly under LT conditions, while chlorophyll a showed no significant change. Phycocyanin and phycoerythrin decreased significantly under LT conditions, but there was no significant difference under HT conditions. Under LT stress, glutathione (GSH) levels, ascorbate peroxidase (APX) activity, and catalase (CAT) activity all increased significantly. Under HT stress, APX and CAT activities increased significantly, while superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels remained unchanged. Transcriptomics and metabolomics analyses suggested that photosynthesis, carbohydrate metabolism, amino acid biosynthesis, porphyrin metabolism, and vitamin B6 metabolism are involved in the acute temperature stress response of B. gelatinus. Under both HT and LT, most genes in the targeted metabolic pathways were significantly downregulated (p < 0.05), while only a few were upregulated. Specifically, in carbohydrate metabolism, only nine genes were upregulated, while all others were downregulated. Moreover, all the genes involved in photosynthesis, photosynthetic carbon fixation, arginine biosynthesis, and porphyrin metabolism were downregulated. In contrast, only four genes involved in GSH metabolism, alanine, aspartate, and glutamate metabolism, and glycine, serine, and threonine metabolism were upregulated. These results suggest that temperature stress markedly suppresses the transcription of key genes in these pathways and that the few upregulated genes in these pathways may contribute to compensatory mechanisms or regulatory network reprogramming during stress responses. These findings help clarify how B. gelatinus adapts to different temperature stresses and provide a basis for developing improved germplasm to support stable production under climate variability. Full article

Inhibition of respiratory chain complex I (NADH dehydrogenase) is a widely encountered biochemical consequence of drug intoxication and a primary consequence of mtDNA mutations and other mitochondrial defects. In an organ-selective form, it is also deployed as antidiabetic pharmacological treatment. Complex I inhibition evokes a pronounced metabolic reprogramming of uncertain purposefulness, as in several cases, anabolism appears to be fostered in a state of bioenergetic shortage. A hallmark of complex I inhibition is the enhanced biosynthesis of serine, usually accompanied by an induction of folate-converting enzymes. Here, we have revisited the differential transcriptional induction of these metabolic pathways in three published models of selective complex I inhibition: MPP-treated neuronal cells, methionine-restricted rats, and patient fibroblasts harboring an NDUFS2 mutation. We find that in a coupled fashion, serinogenesis and circular folate cycling provide an unrecognized alternative pathway of complete glucose oxidation that is mostly dependent on NADP instead of the canonic NAD cofactor (NADP:NAD ≈ 2:1) and thus evades the shortage of oxidized NAD produced by complex I inhibition. In contrast, serine utilization for anabolic purposes and C₁-folate provision for S-adenosyl-methionine production and transsulfuration cannot explain the observed transcriptional patterns, while C₁-folate provision for purine biosynthesis did occur in some models, albeit not universally. We conclude that catabolic glucose oxidation to CO₂, linked with NADPH production for indirect downstream respiration through fatty acid cycling, is the general purpose of the remarkably strong induction of serinogenesis after complex I inhibition. Full article

Exercise performance is a critical trait for evaluating the economic and breeding value of working and athletic horses, with cardiac structure and function serving as essential physiological determinants of athletic capacity. This study aimed to investigate the multi-omics response mechanisms associated with varying degrees of cardiac remodeling under identical exercise intensity. Twenty 2-year-old Yili horses were selected and categorized based on echocardiographic parameters into a high cardiac remodeling group (BH; EDV > 500 mL, SV > 350 mL, EF > 66%) and a low cardiac remodeling group (BL; EDV < 450 mL, SV < 330 mL, EF < 64%). Blood samples were collected before and after the 1000 m constant-speed test (pre-test high cardiac remodeling group (BH, n = 10), post-test high cardiac remodeling group (AH, n = 10), pre-test low cardiac remodeling group (BL, n = 10), post-test low cardiac remodeling group (AL, n = 10)), and integrated metabolomic, transcriptomic, and miRNA profiling were conducted to systematically characterize molecular responses to exercise-induced stress. Metabolomic analysis identified a total of 1936 lipid metabolites, with the BH group exhibiting stronger post-exercise lipid mobilization and significant enrichment of sphingolipid signaling pathways. Transcriptomic and miRNA analyses further revealed that key miRNAs in the BH group, including miR-186, miR-23a/b, and the let-7 family, along with their target genes (e.g., GNB4, RGS5, ALAS2), were involved in fine regulation of cardiac electrophysiology, oxidative stress, and energy metabolism. Integrated analysis indicated that the AH vs. BH comparison uniquely enriched pathways related to glycine-serine-threonine metabolism and glycosylphosphatidylinositol (GPI)-anchor biosynthesis, whereas the AL vs. BL comparison showed unique enrichment of α-linolenic acid and arachidonic acid metabolism pathways. Ultimately, multi-omics integration identified that in the BH group, eca-let-7d, eca-let-7e, eca-miR-196b, eca-miR-2483, and eca-miR-98 regulate ALAS2 and, together with GCSH, influence the enrichment of lipids such as PS(17:0_16:1), PS(18:0_18:1), and PS(20:0_18:1). These lipids participate in glycine, serine, and threonine metabolism through complex pathways, collectively modulating energy supply, inflammatory responses, and muscle function during exercise. This study reveals the molecular mechanisms by which horses with high cardiac remodeling maintain energy homeostasis and myocardial protection during exercise. Full article

Follicular atresia is mainly driven by the oxidative stress-induced apoptosis of granulosa cells (GCs). Oxidative stress mediated by H₂O₂ is the predominant form of stress in cells and plays a key role in the death of porcine GCs. In the present study, using integrated transcriptomic and untargeted metabolomic approaches, we explored the mechanisms underlying the regulation of oxidative stress in porcine follicular GCs. Per the transcriptomic analysis, compared with the control group, we identified 328 differentially expressed mRNAs (260 upregulated, 68 downregulated) in the H₂O₂-treatment group; these mRNAs were significantly enriched in apoptosis-related pathways, including the tumour necrosis factor (TNF) and p53 signalling pathways. Furthermore, via untargeted metabolomic analysis, we identified 150 differentially expressed metabolites (101 positive, 49 negative). The pathways associated with protein digestion and absorption, glycine, serine, and threonine metabolism, amino acid biosynthesis, and carbon metabolism were enriched with these metabolites. The integrated transcriptomic and metabolomic analyses revealed taurine, creatine, L-serine, and hypoxanthine as the key metabolites under H₂O₂-induced oxidative stress. Both the differential genes and metabolites were notably enriched in the FOXO and mineral absorption pathways. In the present study, we elucidated the regulatory mechanism underlying H₂O₂-induced oxidative stress in porcine follicular GCs via transcriptomic and metabolomic analyses. Our findings offer novel insights into the alleviation of oxidative stress in GCs. Full article