Search Results (1,740)

Training induces sweat morphology changes in horses from muddy sweat (MS) to foamy sweat (FS) and clear sweat (CS), reflecting physiological adaptation. However, the metabolic mechanisms linking sweat phenotypes to systemic amino acid dynamics remain unclear. This study integrated sweat untargeted metabolomics and plasma amino acid targeted metabolomics to reveal coordinated metabolic remodeling. Six 2-year-old Yili horse stallions underwent 10-week training. Plasma and sweat were sampled pre- and post-race at each stage. LC-MS/MS and UHPLC-MS/MS were used for sweat metabolome and plasma amino acid analysis, followed by multivariate statistics, KEGG enrichment, and correlation network (CNet) analysis. Differential sweat metabolites decreased across stages (45, 127, and 38 for MS vs. FS, MS vs. CS, and FS vs. CS). Pre-race BCAA concentrations were higher in MS than in FS and CS, while glycine was lower. Post-race valine, histidine, and aspartate were elevated only in MS. Pre-race plasma amino acids positively correlated with sweat lipids and organic acids, shifting to negative post-race. ABC transporters, mTOR signaling, and BCAA metabolic pathways were key co-regulators. The MS-to-CS transition reflects metabolic remodeling from acute stress to homeostatic adaptation. Plasma BCAAs and sweat cortisol are potential biomarkers, with ABC transporters and mTOR pathways mediating sweat-plasma metabolic coordination. Full article

Background/Objectives: Chromium contamination represents a major environmental challenge due to its detrimental effects on plant growth and agricultural productivity. Since dichromate uptake in plants occurs mainly through sulfate and phosphate transporters, identifying natural compounds capable of competitively inhibiting these transport pathways may provide an eco-friendly strategy for reducing chromium accumulation. This study aimed to investigate the inhibitory potential of phytochemicals from Djiboutian medicinal plants against sulfate and phosphate transporters using an integrated computational approach. Methods: 49 phytochemicals identified by GC–MS from ten Djiboutian medicinal plants were screened against the sulfate transporter (7LHV) and phosphate transporter (7SP5) using molecular docking. Binding interactions were compared with sulfate, phosphate, and dichromate ions to evaluate potential competitive inhibition. The most promising compounds were further assessed through ADMET prediction and 100 ns molecular dynamics simulations to evaluate their pharmacokinetic properties and complex stability. Results: Molecular docking revealed binding energies ranging from −7.04 to −2.91 kcal/mol for 7LHV and from −6.50 to −0.62 kcal/mol for 7SP5, indicating variable binding affinities among the screened phytochemicals. Several compounds exhibited favorable interactions with key amino acid residues involved in anion transport, suggesting their potential to compete with dichromate uptake. ADMET analysis identified multiple compounds with favorable toxicity and drug-likeness profiles. Among them, cyclohexanepropanoic acid from Aloe djiboutiensis demonstrated the strongest binding affinity toward both transporters. Molecular dynamics simulations confirmed the structural stability of the protein–ligand complexes throughout the 100 ns simulation. Conclusions: This study identifies naturally occurring phytochemicals, particularly cyclohexanepropanoic acid, as promising competitive inhibitors of dichromate transport in plants. These findings provide a theoretical foundation for developing sustainable phytochemical-based strategies to mitigate chromium accumulation in crops and support future experimental validation. Full article

Staphylococcus aureus is an important zoonotic pathogen. In recent years, it has been isolated from diseased aquatic animals, causing skin ulcers and septicemia, establishing itself as an emerging pathogen in aquaculture. Rampant antibiotic use has accelerated antimicrobial resistance, a trend that has gradually curtailed the potency of conventional antibiotic therapies, underscoring the urgent need for novel therapies. Here, we screened 20 amino acids and found that exogenous proline significantly enhances the bactericidal activity of amikacin against S. aureus. This synergistic effect extends to other aminoglycoside antibiotics, including neomycin sulfate and gentamicin, and is also effective against drug-resistant strains such as MRSA USA300. Furthermore, we evaluated the efficacy of this combination in eradicating persisters and biofilms. Mechanistically, exogenous proline potentiates amikacin-mediated killing by modulating two key bactericidal pathways. On one hand, it enhances antibiotic uptake by augmenting the proton motive force via the electron transport chain. On the other hand, it amplifies oxidative stress through a multi-pronged mechanism involving the suppression of ROS-scavenging enzymes, activation of the Fenton reaction, and reduction in intracellular nitric oxide (NO) levels, ultimately culminating in bacterial cell death. This study proposes a promising strategy for combating S. aureus in aquaculture and healthcare-associated infections. Full article

Juvenile hormone (JH) analog insecticides are widely used in pest management because of their ability to disrupt insect growth and metamorphosis; however, the molecular mechanisms linking endocrine disruption to metabolic dysregulation remain incompletely understood. In addition to their established roles in diapause and developmental regulation, JH signaling pathways have also been implicated in carbohydrate and lipid metabolism. In the present study, we investigated the effects of two JH analogs, pyriproxyfen and hydroprene, on the migratory locust, Locusta migratoria, with particular emphasis on lipid metabolic regulation and the function of midgut-enriched fatty acid-binding protein gene (Mg-FABP). Bioassays were performed to evaluate insecticidal activity, and transcriptomic analyses were conducted to identify differentially expressed genes associated with endocrine signaling and lipid metabolism. Functional characterization of Mg-FABP was further performed using RNA interference (RNAi) and Oil Red O staining assays. In addition, the tertiary structure of LmMg-FABP was predicted using AlphaFold 3, and molecular docking analyses were carried out to investigate its interactions with fatty acid ligands. Both pyriproxyfen and hydroprene caused approximately 70% mortality in locust nymphs and induced significant transcriptional changes in pathways related to hormone signaling and lipid metabolism. Transcriptomic analysis revealed pronounced downregulation of Mg-FABP following JH analog exposure. RNAi-mediated silencing of Mg-FABP significantly reduced lipid droplet accumulation in the fat body, indicating that Mg-FABP plays an essential role in lipid transport and metabolic homeostasis in L. migratoria. Structural analyses further demonstrated that LmMg-FABP possesses a conserved tertiary structure highly similar to FABP homologs from other insect species. Molecular docking identified key amino acid residues involved in fatty acid binding and suggested that hydrophobic interactions are critical for ligand stabilization within the binding cavity. Collectively, our findings demonstrate that pyriproxyfen and hydroprene disrupt insect development not only through endocrine imbalance but also through perturbation of Mg-FABP-associated lipid metabolic pathways. This study provides new mechanistic insight into the coordinated interaction between hormonal signaling and lipid metabolism during JH analog exposure and identifies FABP-mediated lipid transport as a potential molecular target for the development of more selective insect growth regulators. Full article

This study evaluated the effects of adding zinc oxide nanoparticles (ZnNP), L-arginine (L-Arg), or a combination of both to the diets of growing rabbits to mitigate the physiological and productive consequences of heat stress. Two hundred and eighty 35-day-old New Zealand White rabbits were randomly assigned to four experimental treatments, with 70 rabbits per treatment and seven replicates (10 rabbits/replicate). The control group (Ctr) received the base diet without additives, while the diets of the other groups were fortified with arginine (L-Arg; 3 g/kg), zinc oxide nanoparticles (ZnNP; 40 mg/kg), or a combination of both (Arg-Zn). The results showed that the combined Arg-Zn significantly improved weight gain rate, feed conversion rate, carcass weight, and nutrient digestibility compared to the control group (p < 0.05). At the physiological level, we observed increased serum levels of total antioxidant capacity (T-AOC), glutathione peroxidase (GPx), superoxide dismutase (SOD), immunoglobulin G (IgG), immunoglobulin A (IgA), and triiodothyronine (T3), along with decreased levels of malondialdehyde (MDA), alanine aminotransferase (ALT), and aspartate aminotransferase (AST, p < 0.05) in Arg-Zn-fed rabbits. However, adding the Arg-Zn mixture contributed to a reduction in pathogenic bacteria counts and increased the volatile fatty acid (VFA) levels. At the molecular level, the gene expression of the inflammatory cytokines IL-6 and tumor necrosis factor alpha (TNF-α) decreased; however, the gene expression of claudins-1 (CLDN-1), cationic amino acid transporter-1 (CAT-1), mucin-2 (MUC-2), sodium-glucose co-transporter-1 (SGLT-1), and interferon gamma (IFNγ) increased (p < 0.05) in Arg-Zn-fed rabbits. These results suggest that dietary supplementation with ZnNP and L-Arg may serve as an effective nutritional strategy for improving growth performance, antioxidant status, immune function, and intestinal integrity in rabbits exposed to high ambient temperatures. Full article

Leucine, an essential branched-chain amino acid, serves not only as a substrate for protein synthesis but also as a key regulator of placental function and fetal development. This study investigated the effects of dietary supplementation with RP-Leu during late gestation on placental development and offspring performance in Hu sheep. Sixty twin-pregnant ewes at day 80 of pregnancy were randomly assigned to either a control group (fed a basal diet) or an RP-Leu group (fed a basal diet supplemented with 19 g/day RP-Leu). The feeding trial lasted for 60 d. The ewes were slaughtered at day 140 of gestation. Maternal slaughter traits and fetal organ weights were recorded. Blood and milk samples were collected for milk composition analysis and targeted metabolomic profiling. Leucine supplementation significantly increased the percentage of milk fat content, total solid content, and the birth weight of lambs (p < 0.05). Improvements in placental morphology and antioxidant capacity were observed, including a significant increase in cotyledon density and a significant enhancement of catalase (CAT) activity (p < 0.05). Gene expression analysis indicated that the NOS3, SLC38A1 and FABP4 genes in the placental cotyledons (p < 0.05), and the VEGFA, NOS3, SLC27A1 and FABP4 genes were significantly upregulated in the maternal caruncles (p < 0.05). Plasma metabolomic profiling revealed increased L-glutamic acid levels and alterations in several amino acids, with pathway enrichment indicating involvement in amino acid metabolism and membrane transport processes. Transcriptomic analysis identified 739 differentially expressed genes, which were mainly enriched in the PI3K/Akt signaling pathway, ECM–receptor interaction pathway, and cytokine–cytokine receptor interaction pathway. Collectively, these findings suggest that RP-Leu supplementation during late gestation may enhance offspring growth by modulating amino acid metabolism, promoting placental development, and improving placental nutrient transport capacity, thereby supporting fetal growth and development. Full article

The plastid stroma-localized chaperone HSP90C is essential for maintaining chloroplast proteostasis and facilitating protein translocation. Prior research has established HSP90C’s imperative role in the SEC translocase-dependent transport of the photosystem II subunit PsbO1 and its interaction with the SEC1 translocase motor protein SecA1. However, the exact mechanism of this interaction remains to be explored. In this study, we delineated the interactional mode of HSP90C and SecA1 with the model client protein. Yeast two-hybrid and in vitro ATPase activity analyses with purified proteins revealed PsbO1 may bind to HSP90C at multiple sites, including the DPW motif within the C-terminal extension (CTE) region, suggesting a possible client-loading mechanism unique to plastid orthologs. We also confirmed that glycine-646 is important in mediating substrate interaction, though it conferred a much weaker binding than the CTE region, thereby elucidating a critical role for the amino acid whose mutation resulted in visible plant phenotypes. Our in vitro biochemical assays also demonstrated that the stromal intermediate form of PsbO1 with the thylakoid signal peptide (tSP) significantly enhanced SecA1 ATPase activity, suggesting a preferential binding to the motor protein. On the other hand, the mature domain of the PsbO1, excluding the tSP sequence, inhibited HSP90C ATPase activity. We also observed the HSP90C-PsbO1-SecA1 ternary complex was stabilized by the presence of the client tSP. This work therefore provides new insights into the functional mechanisms of HSP90C and its contribution to chloroplast stromal protein stabilization and thylakoid protein transport. Full article

The use of agricultural by-products as feed is essential for sustainable animal husbandry. This study assessed the effects of substituting whole-plant corn silage with a mixed silage of cotton stalks and grape pomace on growth, serum biochemistry, and jejunal metabolomics in Suffolk rams. In this experiment, 135 rams (6-mo, 30.55 kg BW) were allocated to 0%, 50%, or 100% replacement (CG, EG50, EG100) and fed for 120 d after a 15-d adaptation. Compared with the CG, average daily gain improved by 27.3% and 17.5%, and feed conversion improved by 30.8% and 15.4% in EG50 and EG100 (p < 0.01). Compared with CG, the levels of BUN, TNF-α and IL-1β in serum of EG50 and EG100 were significantly decreased. The levels of IgG, IgM, IL-4, antioxidant enzymes and total antioxidant capacity were significantly increased (p < 0.05). Subsequently, the slaughter performance and jejunal content metabolome of CG and EG50 were further detected and analyzed. The results indicated that the live weight, eye area and muscle crude protein content of EG50 were extremely significantly higher than those of CG (p < 0.01). In jejunal contents, 31 differential metabolites (EG50 vs. CG) were enriched in ABC transporters, branched-chain amino acid biosynthesis, mineral absorption, purine and biotin metabolism, and glucagon signaling. In conclusion, substituting corn silage with the mixed silage promotes growth, improves antioxidant and immune status, reduces serum urea nitrogen, enhances muscle protein deposition (EG50), modulates intestinal nitrogen, purine, lipid, and carbohydrate metabolism (EG50), and supports sustainable meat sheep production. Full article

Carbon dioxide (CO₂) is essential in beekeeping practices but its optimal dosage and physiological effects on honey bees remain unclear. This study examined CO₂ tolerance and molecular responses across three developmental stages: newly emerged, nurse, and forager bees, using gradient exposure and proteomic analysis. Newly emerged bees demonstrated the highest CO₂ tolerance. Hemolymph and brain exhibited distinct responses: the cytochrome P450 pathway dominated in hemolymph, while the brain displayed stage-specific strategies. Newly emerged bees activated metabolic reorganization and clearance pathways. Nurse bees strengthened antioxidant defenses, while foragers enhanced amino acid metabolism to produce antioxidant precursors. All stages showed role-specific energy metabolism reprogramming to meet increased post-exposure demands. These findings provide critical data and theoretical foundations for honey bee colony management, transportation, and handling practices. The results also contribute valuable insights to the fundamental biology of other insects. Full article

In the present study, we investigated how soybean yield is enhanced upon editing of the gene GmJAG1 and the consequent influence on the structure and function of the rhizosphere microbiome. Field trials revealed that gene-edited (GE) soybeans had a 55.22% increase in yield without concomitant changes in root length. Metagenomic sequencing of the rhizosphere soil microbiome showed that, compared with the corresponding non-edited line (CK), the alpha diversity of the GE groups remained unaltered, whereas beta diversity differed significantly at the soybean reproductive (R2) stage. Notably, the rhizosphere microbiome of GE soybeans at the R2 stage exhibited enrichment of functional pathways related to transport, amino acid biosynthesis, and central metabolism. These findings suggest that GmJAG1 editing may shape the functional profile of the rhizosphere microbiome, which could potentially contribute to yield gains. This work offers a novel microbiological perspective for understanding the mechanisms by which yield may be improved in GE crops. Full article

Adult bone marrow-derived mesenchymal stem cells (BMSCs) are multipotent progenitors capable of differentiating into diverse cell lineages, including osteogenic, chondrogenic, adipogenic, and neuronal lineages. In BMSCs, intracellular glutathione (GSH) is a critical determinant of stemness maintenance and differentiation outcomes. However, how intracellular GSH homeostasis is regulated during BMSC-to-neuron differentiation remains unclear. In neurons, GSH synthesis critically depends on cysteine uptake mediated by the excitatory amino acid carrier 1 (EAAC1). Here, we investigated the expression, subcellular localization, and functional contribution of EAAC1 and its regulatory protein, glutamate transporter-associated protein 3-18 (GTRAP3-18) in mouse BMSCs and neuron-like BMSCs generated by Notch intracellular domain-based induction (NICD-3F BMSCs). BMSCs exhibited higher intracellular GSH levels than NICD-3F BMSCs, despite comparable levels of EAAC1 protein. In contrast, EAAC1-dependent cysteine uptake and plasma membrane localization of EAAC1 were markedly reduced in BMSCs, indicating differentiation-dependent regulation of EAAC1 trafficking. Treatment with the xCT inhibitor erastin reduced intracellular GSH levels in both BMSCs and NICD-3F BMSCs. GTRAP3-18 expression was high in BMSCs and significantly reduced in NICD-3F BMSCs. Notably, GTRAP3-18 knockout decreased intracellular GSH levels in BMSCs without altering total EAAC1 protein or intracellular cysteine levels, whereas in NICD-3F BMSCs, both GSH and EAAC1 protein levels were increased. These findings demonstrate lineage-dependent divergence in GSH regulatory mechanisms and reveal previously unrecognized functions of GTRAP3-18 in redox control during stem–to–neuron differentiation. Full article

Fat deposition in laying hens involves lipid synthesis, transport, storage, and allocation across multiple tissues, yet the metabolic links between abdominal fat (AF) and egg yolk (EY) lipid deposition remain unclear. Here, we integrated whole-genome resequencing data with untargeted metabolomic profiles from the liver, duodenum, ileum, cecum, and serum of 248 purebred Rhode Island Red hens at 100 weeks of age. We estimated metabolite-explained variance (me²) for 22 fat deposition-related traits, evaluated metabolite heritability, and combined Spearman correlation analysis with bidirectional generalized summary-data-based Mendelian randomization (GSMR) to identify shared metabolites and pathways associated with AF and EY traits. The me² showed clear tissue specificity, with the liver, serum, and duodenum showing significant explanatory signals for 77.3% (17/22), 72.7% (16/22), and 68.2% (15/22) of fat-related traits. Liver-, AF-, and body weight-related traits showed stronger metabolomic explanatory signals, with significant proportions of 71.4–100.0%, 28.6–100.0%, and 100.0% across tissues, respectively, whereas EY-related traits showed more restricted and tissue-specific associations (0–33.3%). Correlation analysis identified liver-enriched AF–EY shared metabolites (e.g., NADPH, cholesteryl sulfate, N6,N6,N6-trimethyllysine), most of which showed opposite association patterns between AF- and EY-related traits. Bidirectional GSMR prioritized 20 candidate metabolites with opposite putative effects on AF and EY traits, including CDP-choline, phosphorylcholine, and allantoin. Pathway integration highlighted fructose/mannose metabolism, glycerophospholipid metabolism, ABC transporters, folate/one-carbon metabolism, amino acid metabolism, and energy metabolism as core components of the AF–EY shared network. These findings reveal tissue-specific and shared metabolic bases of fat deposition and identify candidate metabolic signatures associated with lipid partitioning between abdominal fat and egg yolk in laying hens. Full article

This study aims to investigate the effects of cysteamine zinc supplementation on milk production, composition, amino acid profile, and metabolites in mares. Building on prior experimental findings, a dose of 7 mg/kg body weight of CS-Zn was selected for the experimental group, which was compared with a control group. Milk samples were collected at various time points, and milk yield was recorded each time. Routine analysis of milk components, as well as the determination of milk metabolites and amino acids, were performed. The results indicated that, compared to the control group, the experimental group exhibited increases in milk yield and the content of milk fat, lactose, and non-fat solids (p < 0.05), with an extremely significant increase in milk protein (p < 0.01). Conversely, the levels of L-glutamine and L-proline in milk were significantly reduced (p < 0.05). Metabolomic analysis revealed that differentially expressed metabolites were enriched in pathways such as ABC transporters, D-aminoadipate metabolism, aminoacyl-tRNA biosynthesis, and protein digestion and absorption. Notably, milk metabolites including cAMp, biotin, and taurine showed a tendency to be upregulated, while oxoglutaric acid, methionine, and diacetyloxyxanthone were downregulated. Based on evidence from the literature other species, it is speculated that CS-Zn supplementation may be associated with alterations in endocrine and amino acid metabolism pathways, potentially influencing lactation performance in mares. However, because no hormones were directly measured in this study, such a mechanism remains speculative and requires direct experimental validation. Full article

All-trans retinoic acid (atRA) is known to regulate lipid metabolism, adipocyte differentiation, and the immune system in mammals and other aquatic species. However, studies on atRA in crustaceans, especially in Eriocheir sinensis, are still scarce. The present study aimed to investigate the regulatory effects of dietary or injected atRA on female crabs during the fattening period. In the dietary regulation experiment, 270 female crabs were fed diets containing different doses of atRA (0, 150, 300, 600, 1200, and 2400 mg/kg) for a total of 49 days. In the in vivo injection experiment, 90 females were divided into an experimental group (injected with a 0.3 μg/g dose of atRA) and a control group (injected with the same amount of DMSO solvent). Injections were given weekly throughout the 35-day experimental period. Results: Both dietary atRA and atRA injection promoted ovarian development, as evidenced by increased GSI, elevated serum Vg levels, decreased GIH, and upregulated expression of vg, vgr, and rxr genes. In terms of mechanism, dietary atRA promoted ovarian development via the upregulation of pyrimidine nucleotides and dehydroepiandrosterone, which supplied nucleic acid precursors and hormonal support. Furthermore, RXR was identified as a potential key target of atRA in inducing ovarian development, as molecular docking revealed that atRA could spontaneously bind to RXR. Moreover, following atRA injection, the expression of rxr, along with key genes involved in ovarian development, lipid synthesis, and lipid transport, was significantly upregulated. In addition, the atRA diet created a favorable microenvironment for ovarian development by reducing pro-inflammatory lipid levels in the ovary. Transcriptomic and metabolomic analyses revealed that atRA modulates energy and lipid metabolism by activating the AMPK pathway. In terms of the bacterial community structure, the atRA diet significantly decreased Fusobacterium abundance and enriched Parabacteroides as the signature beneficial bacterium. In terms of nutritional quality, the atRA diet markedly reduced saturated and trans-fatty acids while increasing monounsaturated fatty acids and various key essential amino acids. Conclusions: This study revealed that atRA plays a key role in promoting ovarian development, improving nutritional quality, and modulating the structure of the microbiota, thereby providing theoretical support for healthy aquaculture of female crabs during the fattening period. Full article

Messenger RNA (mRNA) therapeutics are redefining treatment approaches in vaccines, cancer immunotherapy, protein replacement, and gene editing. Lipid nanoparticles have enabled early clinical successes, but they can be limited by liver-dominant biodistribution, long-term storage stability, and systemic tolerability. Polymeric delivery systems offer a versatile alternative, with tunable physicochemical properties enabling precise control over mRNA complexation, protection, release, and targeting. This review examines recent progress across polyethyleneimine derivatives, poly(β-amino ester)s, poly(amino acid)s, polyesters, dendrimers, charge-altering releasable transporters, and lipid-polymer hybrids. We highlight strategies such as structural modification, stimuli-responsive designs, and high-throughput polymer screening that enhance stability, reduce cytotoxicity, and enable organ- or cell-specific delivery. Addressing challenges in immunogenicity, biodistribution, and manufacturing scalability will be pivotal to translating these innovations into safe and effective mRNA therapeutics. Full article