Search Results (684)

The aim of this study was to isolate Weizmannia spp. that produce lactic acid from xylose and use an experimental design to optimize the production of the metabolite. After isolation, the experiments were conducted in xylose-yeast extract-peptone medium. The identification of isolates was performed using the 16S rDNA PCR technique, followed by sequencing. A central composite rotatable design (CCRD) was used to optimize the concentrations of the carbon source (xylose), nitrogen source (yeast extract and peptone), and sodium acetate. Two strains were considered promising for lactic acid production, with W. coagulans BLMI achieving greater lactic acid production under anaerobic conditions (21.93 ± 0.9 g.L⁻¹) and a yield of 69.18 %, while the strain W. ginsengihumi BMI was able to produce 19.79 ± 0.8 g.L⁻¹, with a yield of 70.46 %. CCRD was used with the W. ginsengihumi strain due to the lack of records in the literature on its use for lactic acid production. The carbon and nitrogen sources influenced the response, but the interactions of the variables were nonsignificant (p < 0.05). The response surface analysis indicated that the optimal concentrations of carbon and nitrogen sources were 32.5 and 3.0 g.L⁻¹, respectively, without the need to add sodium acetate to the culture medium, leading to the production of 20.02 ± 0.19 g.L⁻¹, productivity of 0.55 g/L/h after 36 hours of fermentation, and a residual sugar concentration of 12.59 ± 0.51 g.L⁻¹. These results demonstrate the potential of W. ginsengihumi BMI for the production of lactic acid by xylose fermentation since it is carried out at 50 °C, indicating a path for future studies Full article

Background/Objectives: Blunt cardiac injury (BCI) is a severe medical condition that may arise as a result of various traumas, including motor vehicle accidents and falls. The main objective of this study was to explore the role and underlying mechanisms of the TRPV4 gene in BCI. Elucidating the function of TRPV4 in BCI may reveal potential novel therapeutic targets for the treatment of this condition. Methods: Rats in each group, including the SD control group (SDCON), the SD blunt-trauma group (SDBT), the TRPV4 gene-knockout control group (KOCON), and the TRPV4 gene-knockout blunt-trauma group (KOBT), were all freely dropped from a fixed height with a weight of 200 g and struck in the left chest with a certain energy, causing BCI. After the experiment, the levels of serum IL-6 and IL-1β were detected to evaluate the inflammatory response. The myocardial tissue structure was observed by HE staining. In addition, cardiac transcriptome analysis was conducted to identify differentially expressed genes, and metabolomics studies were carried out using UHPLC-Q-TOF/MS technology to analyze metabolites. The results of transcriptomics and metabolomics were verified by qRT-PCR and Western blot analysis. Results: Compared with the SDCON group, the levels of serum IL-6 and IL-1β in the SDBT group were significantly increased (p < 0.001), while the levels of serum IL-6 and IL-1β in the KOBT group were significantly decreased (p < 0.001), indicating that the deletion of the TRPV4 gene alleviated the inflammation induced by BCI. HE staining showed that myocardial tissue injury was severe in the SDBT group, while myocardial tissue structure abnormalities were mild in the KOBT group. Transcriptome analysis revealed that there were 1045 upregulated genes and 643 downregulated genes in the KOBT group. These genes were enriched in pathways related to inflammation, apoptosis, and tissue repair, such as p53, apoptosis, AMPK, PPAR, and other signaling pathways. Metabolomics studies have found that TRPV4 regulates nucleotide metabolism, amino-acid metabolism, biotin metabolism, arginine and proline metabolism, pentose phosphate pathway, fructose and mannose metabolism, etc., in myocardial tissue. The combined analysis of metabolic and transcriptional data reveals that tryptophan metabolism and the protein digestion and absorption pathway may be the key mechanisms. The qRT-PCR results corroborated the expression of key genes identified in the transcriptome sequencing, while Western blot analysis validated the protein expression levels of pivotal regulators within the p53 and AMPK signaling pathways. Conclusions: Overall, the deletion of the TRPV4 gene effectively alleviates cardiac injury by reducing inflammation and tissue damage. These findings suggest that TRPV4 may become a new therapeutic target for BCI, providing new insights for future therapeutic strategies. 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

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common enzymatic disorder, affects over 500 million people worldwide and is often linked to exercise intolerance due to oxidative stress, but its true impact on physical performance remains unclear. This study aimed to evaluate the physiological and metabolic effects of G6PD deficiency on endurance capacity. Using humanized mice carrying the African G6PD variant [V68M; N126D] (hG6PD_A−), we show that despite reduced pentose phosphate pathway activity, these mice exhibit a 10.8% increase in treadmill critical speed (CS)—suggesting enhanced endurance capacity. Multi-omics profiling across red blood cells, plasma, skeletal muscle, spleen, kidney, and liver reveals metabolic adaptations, including elevated glycolysis, fatty acid oxidation, and increased mitochondrial activity, alongside heightened oxidative phosphorylation in muscle and accelerated red blood cell turnover in the spleen and liver. These findings indicate that systemic metabolic reprogramming may offset antioxidant deficiencies, potentially conferring a performance advantage. Given that G6PD deficiency affects up to 13% of African Americans and is associated with cardiovascular health disparities, our results challenge conventional exercise restrictions and highlight the need for personalized exercise guidelines for affected individuals. Full article

In the swine industry, artificial insemination (AI) primarily uses chill-stored semen, making sperm preservation crucial for reproductive success. However, sperm quality declines at varying rates during chilled storage at 17 °C, distinguishing high-survival semen from low-survival semen. This study investigates the metabolomic profiles of boar sperm with different abilities to survive liquid storage. We analyzed sperm motility, kinematics, and morphology in freshly extended (Day 0) and 7-day stored AI semen doses. The AI semen doses were classified as high-motile (HM) or low-motile (LM) based on sperm motility after 7 days of storage (Day 7). Metabolomic data were collected in positive (ESI+) and negative (ESI−) ion modes using a Vanquish Flex UPLC coupled with a Q Extractive Plus. We consistently detected 442 metabolites (251 in ESI+, 167 in ESI−, and 24 in both) across samples and storage durations. In freshly extended and 7-day stored AI doses, we identified 42 and 56 differentially expressed metabolites (DEMs), respectively. A clustering analysis showed significant changes in DEMs between the HM and LM samples. These DEMs were mainly enriched in amino acid metabolism, the pentose phosphate pathway, glycerolipid metabolism, glyoxylate and dicarboxylate metabolism, terpenoid backbone biosynthesis, etc. In summary, this study highlights the metabolomic differences between semen doses with varying abilities to survive liquid storage. Glyceric acid and lysoPC(20:3) emerged as potential markers for sperm preservation. 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

Cordycepin, a bioactive adenosine analog, holds promise in pharmaceutical and health product development. However, large-scale production remains constrained by the limitations of natural producers, Cordyceps spp. Herein, we report the reconstruction of the first genome-scale metabolic model (GSMM) for a cordycepin-producing strain of recombinant Aspergillus oryzae. The model, iNR1684, incorporated 1684 genes and 1947 reactions with 93% gene-protein-reaction coverage, which was validated by the experimental biomass composition and growth rate. In silico analyses identified key gene amplification targets in the pentose phosphate and one-carbon metabolism pathways, indicating that folate metabolism is crucial for enhancing cordycepin production. Nutrient optimization simulations revealed that chitosan, D-glucosamine, and L-aspartate preferentially supported cordycepin biosynthesis. Additionally, a carbon-to-nitrogen ratio of 11.6:1 was identified and experimentally validated to maximize production, higher than that reported for Cordyceps militaris. These findings correspond to a faster growth rate, enhanced carbon assimilation, and broader substrate utilization by A. oryzae. This study demonstrates the significant role of GSMM in uncovering rational engineering strategies and provides a quantitative framework for precision fermentation, offering scalable and sustainable solutions for industrial cordycepin production. Full article

The “milky disease” in Chinese mitten crabs (Eriocheir sinensis), caused by Metschnikowia bicuspidata, poses significant threats to aquaculture, though its pathogenic mechanisms remain poorly understood. This study employs transcriptomic sequencing to analyze gene expression changes in Metschnikowia bicuspidata under hemocyte challenge, iron overload (1 mmol/mL), and combined stress, with functional validation through Common in Fungal Extracellular Membrane (CFEMgene) overexpression strains. Key findings reveal that (1) hemocyte challenge activated base excision repair (−log₁₀[P] = 7.58) and ribosome biogenesis pathways, indicating fungal adaptation through DNA repair and enhanced protein synthesis to counter host immune attacks (e.g., ROS-mediated damage). (2) Iron overload induced glutathione metabolism and pentose phosphate pathway enrichment, demonstrating mitigation of ferroptosis through NADPH/GSH antioxidant systems and autophagy/proteasome coordination. (3) Under combined stress, ribosome biogenesis (−log₁₀[P] = 1.3) and non-homologous end-joining pathways coordinated DNA repair with stress protein synthesis, complemented by vacuolar V-ATPase-mediated iron compartmentalization. (4) CFEM genes showed significant upregulation under hemocyte stress, with overexpression strains exhibiting enhanced biofilm formation (35% increased MTT cytotoxicity) and infectivity (40% higher infection rate), confirming CFEM domains mediate pathogenesis through iron homeostasis and virulence factor production. This work elucidates how M. bicuspidata employs metabolic reprogramming, oxidative stress responses, and CFEM-mediated iron regulation to establish infection, providing critical insights for developing targeted control strategies against milky disease. Full article

Salmonella colonization in the gastrointestinal tract of turkeys presents a risk to the safety of products derived from them. Lactobacillus-based probiotics and a plant-derived compound, trans-cinnamaldehyde, have previously been found to be effective in reducing multidrug-resistant Salmonella enterica subsp. enterica serovar Heidelberg (S. Heidelberg) in turkey poults. However, the effect of the challenge and the application of the treatments on the cecal metabolome has yet to be elucidated. Thus, the objective of the present study was to characterize alterations in the metabolic profiles of cecal contents collected from poults following S. Heidelberg challenge and treatment with Lactobacillus salivarius UMNPBX2 and L. ingluviei UMNPBX19 (LB), trans-cinnamaldehyde (TC), or a combination of both (CO) using untargeted gas chromatography–mass spectrometry (GC-MS). Poults in the challenged control (PC) group had the most distinct and convergent metabolome profiles, with the most pronounced disparity observed compared to the unchallenged control (NC), indicating the effect of the S. Heidelberg challenge. Perturbations in metabolites in the primary bile acid biosynthesis, pentose and glucuronate interconversions, and steroid biosynthesis were the most prominent. The greater abundance of metabolites, such as primary bile acids and sugars, in the PC group may be associated with S. Heidelberg colonization or potential shifts in microbiota. The treatments yielded varying effects on the metabolome profiles, with the TC and CO groups exhibiting the closest similarity, although TC was more similar to NC. The findings revealed alterations to ceca-associated metabolites, which are likely a response to the S. Heidelberg challenge and the application of the TC and LB treatments. Additional studies are needed to validate the possible causal relationship between the observed shifts. Gaining insight into the alterations to the metabolic microenvironment in the avian cecum will help elucidate the mechanisms by which they facilitate Salmonella persistence. Understanding these relationships can aid in designing more effective pre-harvest Salmonella control strategies and enhancing the efficacy of interventions within the flock. Full article

Androgenetic alopecia (AGA), the most prevalent form of hair loss worldwide, faces significant therapeutic challenges due to high costs and limited efficacy of current interventions, necessitating safer and more effective solutions. Periplaneta americana (L.)-derived PA-011, endowed with anti-inflammatory and antioxidant properties, has demonstrated notable hair growth-promoting effects in AGA mouse models. This study employed LC-MS/MS, peptidomics, and network pharmacology to characterize PA-011’s chemical composition and predict its potential targets in AGA pathogenesis. Using Western blot and RT-qPCR, PA-011 intervention significantly inhibited inflammatory responses and oxidative stress levels in mouse skin tissues. Concurrently, PA-011 activated the proliferative potential of hair follicle stem cells, as demonstrated by upregulated expression of the cell proliferation marker Ki67, and activated the Wnt/β-catenin signaling pathway in DHT-induced AGA mice. Transcriptomic and metabolomic analyses revealed multi-target effects of PA-011, including modulation of PI3K-Akt/MAPK pathways, pentose phosphate metabolism, and amino acid biosynthesis. 16S rRNA sequencing and metagenomic analysis showed that AGA disrupts skin microbial homeostasis, while PA-011 intervention normalized the microbiota composition. Topical application of PA-011 promoted robust hair regrowth without detectable toxicity in safety assessments. This preclinical study establishes PA-011 as a promising candidate for AGA therapy, warranting further translational investigation. Full article

Traumatic brain injury (TBI) is a major neurological condition affecting millions of individuals each year. Mild TBI (mTBI) manifests differently, with some individuals experiencing persistent, debilitating symptoms while others recover more rapidly. Despite its classification as “mild,” mTBI leads to both short- and long-term neurological effects, many of which occur due to functional changes in the brain. TBI-induced environmental changes within the brain play a critical role in shaping these functional outcomes. The importance of astrocytes in maintaining central nervous system (CNS) homeostasis has been increasingly recognized for their pivotal role in the brain’s response to TBI. Previous studies showed significant TBI-associated metabolic dysregulations. Therefore, we sought to analyze how astrocytes might adapt to persistent metabolic stressors in the post-injury microenvironment and identify injury-induced shifts occurring in vivo that may contribute to chronic metabolic dysfunction. We used an astrocyte-specific genome-scale metabolic model that allowed for the input of biologically relevant uptake rates corresponding to healthy astrocytes to analyze how the activity of metabolic pathways differed in hypoxic and acidic conditions. Additionally, these fluxes were integrated with mass spectrometry-based proteomics from male Sprague-Dawley rats subjected to mTBI to identify chronic adaptive neural responses post-injury. Comparison of modeled metabolic fluxes and experimental proteomic data demonstrated remarkable alignment, with both predicting significant changes in key metabolic processes including glycolysis, oxidative phosphorylation, the TCA cycle, and the Pentose Phosphate Pathway. These overlapping signatures may represent core survival strategies, offering insight into metabolic priorities and potentially serving as biomarkers of injury adaptation or recovery capacity. Full article

Monascus produces various bioactive compounds, including monacolin K (MK), γ-aminobutyric acid (GABA), and Monascus pigments (MPs). Studies have shown that overexpressing genes within the MK biosynthetic cluster significantly enhances MK production. Additionally, MK synthesis in Monascus is regulated by other genes. Based on previous transcriptomic analyses conducted in our laboratory, a significant positive correlation was identified between the expression level of the GAD gene and MK production in M. pilosus. In this study, the GAD gene from M. pilosus was selected for overexpression, and a series of engineered M. pilosus strains were constructed. Among the 20 PCR-positive transformants obtained, 13 strains exhibited MK production increases of 12.84–52.50% compared to the parental strain, while 17 strains showed GABA production increases of 17.47–134.14%. To elucidate the molecular mechanisms underlying the enhanced production of MK and GABA, multi-omics analyses were performed. The results indicated that GAD overexpression likely promotes MK and GABA synthesis in M. pilosus by regulating key genes (e.g., HPD, HGD, and FAH) and metabolites (e.g., α-D-ribose-1-phosphate, β-alanine) involved in pathways such as tyrosine metabolism, phenylalanine metabolism, the pentose phosphate pathway, propanoate metabolism, and β-alanine metabolism. These findings provide theoretical insights into the regulatory mechanisms of MK and GABA biosynthesis in Monascus and suggest potential strategies for enhancing their production. Full article

Objectives: To explore the metabolic changes in zebrafish larvae after infection with Mycobacterium marinum, this study adopted a widely targeted metabolomic approach to analyze the changes in the overall metabolic profiles of zebrafish larvae infected for 5 days. Methods: Data were collected by liquid chromatography–tandem mass spectrometry (LC-MS/MS). Mass spectrometry data were processed using Analyst 1.6.3 and MultiQuant 3.0.3 software, and multivariate statistical analysis was carried out. The KEGG database, HMDB database, and CHEBI database were used to screen and identify differential metabolites, and metabolic pathway enrichment analysis was performed through KEGG pathways. Results: A total of 329 metabolites were detected, among which 61 differential metabolites were screened. Specifically, 41 metabolites, such as kynurenine, isoallolithocholic acid, 2′-deoxyguanosine, indole-3-carboxaldehyde, and L-lactic acid, were downregulated, while 20 metabolites, such as L-palmitoylcarnitine, myristoyl-L-carnitine, dodecanoylcarnitine, 2-isopropyl-malic acid, and 2-methylsuccinic acid, were upregulated. KEGG metabolic pathway enrichment analysis indicated that these differential metabolites were mainly involved in metabolic pathways such as pyrimidine metabolism, nucleotide metabolism, the pentose phosphate pathway, and purine metabolism. Conclusions: This study demonstrated that significant changes occurred in multiple metabolites and metabolic pathways in zebrafish larvae after infection with M. marinum. The research results have improved the understanding of zebrafish as a model organism in the field of Mycobacterium research and laid a solid foundation for subsequent metabolomic-related research using zebrafish. Full article

Thiamine (vitamin B1) is key in maintaining cellular health and energy metabolism. Thiamine is required for proper functioning of enzymes involved in glucose metabolism, which is critical for providing energy to cells. This energy is essential for various cellular processes, including DNA repair mechanisms. In addition, it is a prerequisite for the functioning of key enzymes in the biosynthesis of pentose sugars, which are essential in the synthesis of nucleic acids. Additionally, thiamine has antioxidant properties that help reduce oxidative stress in cells; thus, by relieving this stress, thiamine indirectly supports the maintenance of DNA integrity. Ensuring adequate thiamine intake through diet or supplements can support overall cellular health and potentially aid in DNA repair processes. This review aims to highlight the essential role of vitamin B1 in supporting metabolic health, especially given that deficiencies can develop in patients with disease-related malnutrition as well as in those with an inadequate diet. Full article

Nitrite is a common pollutant in aquaculture systems and can pose serious threats to fish health, especially under high-temperature conditions. This study aimed to investigate the impact of nitrite stress on the growth, glycolipid metabolism, and hepatic metabolomic profiles in the spotted seabass fry (Lateolabrax maculatus) under elevated temperature conditions at 33 °C. A total of 450 fish (28.52 ± 0.84 g) were randomly distributed into nine tanks and exposed to three nitrite concentrations (0, 8, and 16 mg/L), with samples collected on days 1, 3, 7, 14, 21, and 28. Results showed that higher nitrite levels significantly reduced final body weight, weight gain, survival rate, hepatosomatic index, and viscerosomatic index. Blood glucose and triglyceride levels, whole-body crude lipid, liver total cholesterol, and hepatic glycogen content also declined significantly under higher nitrite stress. In contrast, hepatic lactate and lactate dehydrogenase increased in the high-nitrite group. Gene expression analysis revealed suppressed lipid synthesis and enhanced lipolysis under nitrite exposure. Metabolomic analysis further demonstrated disruptions in key energy-related pathways, including the TCA cycle, pentose phosphate pathway, and insulin signaling. These findings indicate that nitrite stress impairs growth and energy metabolism in spotted seabass, which respond by mobilizing energy reserves to cope with combined stress of high temperature and nitrite. Full article