Optimizing transient expression systems in fish embryos is crucial for rapid gene function analysis. Here, we established an efficient system in medaka (Oryzias latipes) embryos by evaluating nucleic acid type and injection site. Our results revealed that injecting the elongation factor 1αA (ef1αA) promoter-driven plasmid into the yolk yielded the highest expression on day 1 post-fertilization. Using this optimized system, we investigated cytosolic 5'-nucleotidase 1a (nt5c1a), which is involved in the metabolism of inosine monophosphate (IMP), an umami flavor compound. In silico analysis revealed that medaka had two nt5c1a paralogs: nt5c1aa and nt5c1ab. While nt5c1ab retains conserved substrate-recognition sequences and exhibits significant IMP degradation activity, nt5c1aa has lost these functions. Structural analysis using AlphaFold revealed that the Nt5c1aa L305P mutation causes local conformational changes near the substrate-binding site, potentially altering substrate orientation without disrupting the overall protein fold. Our expression system demonstrated that this single L305P substitution partially restored IMP-degrading activity in Nt5c1aa, confirming that residue 305 is a key determinant of its functional divergence. Our findings provide a robust foundation for molecular breeding to enhance umami flavor in farmed fish. Specifically, the targeted manipulation of these nt5c1a paralogs could facilitate developing breeds with maximized IMP accumulation in muscle tissues.

Bifidobacterium longum subsp. infantis B8762 modulates the infant gut-lung axis via microbial and metabolic reprogramming.

Potential mechanisms of taste changes in surimi gels with typical cross-linking degrees during frozen storage: Based on ice crystals, water migration, and intermolecular interactions.

Metabolic reprogramming and intracellular ATP homeostasis in immunity.

ANKRD9 negatively regulates chicken myogenesis through ubiquitin-mediated regulation of IMPDH2.

Evaluating the safety and efficacy of chemotherapy in patients with relapsed small cell lung cancer combined with allopurinol and MycoPhenolate (CLAMP).

As essential branches of systems biology, metabolomics and lipidomics systematically reveal the composition, dynamic changes, and biological functions of small-molecule metabolites and lipids using high-throughput analytical techniques. This review examines the application of these omics technologies in evaluating livestock and poultry meat and egg quality, focusing on their roles in elucidating the molecular mechanisms behind key traits such as flavor, tenderness, and nutritional value. By identifying key metabolic markers-including glutamic acid, inosine monophosphate, and specific triglycerides-the intrinsic links between these markers and intramuscular fat deposition, flavor precursor formation, and antioxidant capacity are highlighted. Furthermore, this paper emphasizes the transformative impact of integrating multi-omics data with artificial intelligence (AI). AI-driven analytical frameworks are overcoming the limitations of traditional high-dimensional data processing, enabling robust biomarker discovery, predictive modeling for product quality, and reverse design for genetic improvement. Ultimately, the synergistic application of metabolomics, lipidomics, and AI will drive the development of modern animal husbandry toward intelligent, predictable, and precision-based production.

Immunosuppressant drugs may damage the intestinal barrier (IB) either indirectly by promoting dysbiosis, or directly by cytotoxic effects exerted on intestinal cells. This has been demonstrated, for instance, with the inosine monophosphate inhibitor mycophenolic acid (MPA) and with its ester prodrug mycophenolate mofetil (MMF). These two drugs can cause severe gastrointestinal toxicity in transplant patients receiving them for rejection prophylaxis. We investigated whether a multistrain probiotic preparation could protect against MPA- and MMF-induced IB damage using differentiated CaCo-2 cells as in vitro model. We obtained an acellular probiotic conditioned medium by culturing the multistrain probiotic preparation in DMEM + FBS, either with or without MPA or MMF. The probiotic conditioned medium reduced IB permeability when added to the upper compartment of the transwell both in the presence and in the absence of these immunosuppressant drugs, as indicated by an increase in transepithelial electrical resistance. The probiotic conditioned medium also prevented cytotoxicity induced by both MPA and MMF and increased the expression of the tight junction proteins zonulin-1 and claudin-5, both of which contribute to barrier tightness. The protective effects of the probiotic medium may depend on preventing free radical damage, as we found that it reduced free oxygen radicals in cells exposed to either MPA, MMF or to the pro-oxidant compound tert-butyl hydroperoxide (tBHP). Finally, the probiotic conditioned medium reduced the activity of the ABC1B1 pump, though this did not result in changes in transwell IB crossing by MPA or MMF. In conclusion, we demonstrated that a multistrain probiotic preparation can protect the intestinal barrier from toxicity induced by MPA and MMF. The fact that this was a postbiotic effect, as it occurred in the absence of probiotic microorganisms, could be relevant for immunocompromised patients, as probiotic bacteria could potentially induce opportunistic infections in these subjects.

Background/Objectives: Parkinson's disease (PD) is a progressive neurodegenerative disorder that poses a substantial threat to global human health. Yam (Dioscorea opposita Thunb.) is a traditional medicinal and edible plant that has long been used in Asia, Africa, and the Caribbean. Its major bioactive components, such as dioscin and polysaccharides, have been reported to exhibit neuroprotective effects; however, the impact of dietary yam on PD progression remains to be elucidated. Therefore, we sought to evaluate its neuroprotective potential and the underlying mechanisms in 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)-induced PD mice. Methods: Mice received six-week dietary yam supplementation. Behavioral, histological, and neurochemical analyses were performed to assess motor function, dopaminergic neuron integrity, and dopamine levels. Gut microbiota and metabolic profiles were analyzed using 16S rRNA gene sequencing and non-targeted metabolomics. Transcriptomic sequencing and Western blot analysis of the substantia nigra pars compacta (SNc) were conducted to investigate molecular mechanisms, and integrative multi-omics analysis was applied to explore microbiota-metabolite-host interactions. Results: Yam supplementation improved motor function, preserved nigrostriatal dopaminergic neurons, and restored striatal dopamine levels in PD mice. Notably, yam was associated with the maintenance of intestinal homeostasis by strengthening barrier integrity and enriching beneficial taxa, including Ileibacterium, Lachnospiraceae NK4A136 group, and Blautia. Consistently, yam also elevated neuroprotective purines and amino acids, including inosine, xanthine, and succinic acid. At the molecular level, yam treatment modulated mitochondrial oxidative phosphorylation by increasing PGC-1α and COX7c expression, and reduced inflammasome-related neuroinflammatory signaling. Integrative modeling showed significant associations between yam-modulated genes and PD-related indices with microbiota and metabolites. Conclusions: These findings suggest that yam may represent a potential dietary strategy for alleviating PD-related neurodegeneration by modulating the microbiota-gut-brain axis.

Meat quality and metabolism alterations in broiler driven by selective breeding and their associations with gut microbiota.

Brain death in organ donors may trigger tissue injury that can negatively influence transplant outcome. We analyzed plasma metabolomic profiles in heart transplant donors and tested whether any donor metabolite may predict the risk of acute cellular rejection after heart transplantation. Plasma samples from 83 heart transplant donors and 20 healthy volunteers were profiled using quantitative targeted metabolomics of 102 metabolites. Plasma samples from another set of 48 heart transplant donors were used for validation. The plasma levels of 24 metabolites representing 24% of the targeted metabolites were significantly altered in brain-dead heart transplant donors, compared with healthy controls. Alterations in the purine metabolism pathway were most prominent: adenine, xanthosine, allantoin, xanthine, and inosine monophosphate were upregulated, whereas adenosine monophosphate and adenosine were downregulated, indicating an energy metabolism shift and oxidative stress. Donor plasma glycine levels predicted the risk of acute cellular rejection (concordance = 0.74, area under the curve = 0.75; P < .01) in both the training and the validation cohort within 1-year after transplantation. Donor plasma glycine levels moderately correlated with other plasma metabolites linked to collagen formation and extracellular matrix organization. Targeted metabolomics revealed altered purine metabolism in brain-dead heart transplant donors, suggesting increased energy demand and oxidative stress. Donor plasma glycine was identified as a risk predictor for acute cellular rejection after heart transplantation and may serve as a donor-side biomarker to guide posttransplant risk stratification and monitoring.

Regulation of lipid metabolism and flavor formation in Tianfu broiler chickens via the circ_015424/miR-196-1-3p/MOGAT1 axis.

Guanidinoacetic acid improves flesh quality associated with collagen synthesis and nucleotide metabolism in gibel carp CAS V (Carassius gibelio, CAS V).

This study investigated the effects of shortened rearing periods on meat quality and sensory attributes, aiming to identify an appropriate age range to ensure consumer satisfaction. A total of 320 Hanwoo cattle (n=80 per age group) were reared from 6months of age and slaughtered at 24, 26, 28, or 30months. They were fed mixed concentrate and roughage under a three-phase feeding program (crude protein 13-16%; total digestible nutrients 70-75%). Older groups (28-30months) exhibited significantly higher crude fat (+22%) and myofibril fragmentation index (+14%) than the younger groups (24-26months). The 30-month group demonstrated a comparable water-holding capacity to that of the 28-month group (P>0.05), while demonstrating higher values (+6%) than the younger groups (P<0.01). Age-related differences were observed in bioactive compounds. Carnosine and anserine were significantly higher in the 24-month group than the 30-month group (by 25.52 and 14.21mg/100g, respectively), whereas l-carnitine was significantly higher in the 30-month group than the other groups (58.94 vs. 50.41-53.10mg/100g). Older groups also exhibited significantly higher levels of inosine monophosphate, guanosine monophosphate, oleic acid, and volatile compounds (e.g., lactones) than the younger groups (P<0.001). In the sensory evaluation, the tenderness and juiciness scores were significantly higher in the older groups than in the 24-month group (P<0.001). Collectively, these findings suggest that slaughtering Hanwoo at 28-30months, rather than at younger ages, may contribute to improved beef quality and flavor characteristics.

Ubiquitination is a critical regulator of cancer development, yet the role of deubiquitinases in purine metabolism remains largely unexplored. In this study, untargeted metabolomic analysis revealed a significant upregulation of purine metabolism in esophageal cancer (ESCC). Database analysis further identified a strong positive correlation between the deubiquitinase USP5 and purine metabolism. Functional assays demonstrated that USP5 knockdown suppressed cell proliferation in vitro and inhibited tumor growth in vivo, accompanied by a reduction in purine metabolism. Mechanistically, USP5 directly interacts with inosine monophosphate dehydrogenase 2 (IMPDH2), the rate-limiting enzyme in de novo guanine nucleotide biosynthesis, and removes K48-linked polyubiquitin chains at lysine 489. This deubiquitination event stabilizes IMPDH2, prevents its proteasomal degradation, and promotes guanine nucleotide synthesis. Guanine supplementation enhanced ESCC cell proliferation, whereas dietary purine restriction suppressed tumor progression in vivo. Furthermore, we identified mebendazole, an FDA-approved anthelmintic, as a pharmacological inhibitor of USP5. Combination treatment with mebendazole and oxaliplatin significantly enhanced chemosensitivity in ESCC cells. Collectively, these findings establish the USP5-IMPDH2-guanine axis as a critical driver of ESCC progression and highlight its potential as a promising therapeutic target for ESCC.

This study aimed to investigate the changes in the meat quality characteristics of Duolang sheep using rumen metagenomic and muscle metabolomic analyses across different age groups. A total of 24 three-month-old male Duolang sheep were selected and reared, and samples of longissimus thoracis muscle and rumen contents were collected at 4, 6, and 8 months of age to evaluate meat quality, metabolites, rumen metagenome, and volatile fatty acids (VFAs). The results indicated that the lightness (L*45min) and yellowness (b*45min) of the longissimus thoracis muscle at 45 min post-slaughter were significantly higher at 4 and 6 months than at 8 months of age (p < 0.05). In terms of ruminal VFAs, butyrate concentration was significantly higher at 6 months than at 4 months (p < 0.05), and valerate concentration exhibited a quadratic relationship with age (p = 0.02). With increasing age, the relative abundances of Prevotella and Fibrobacter increased, whereas those of Methanobrevibacter and Bacteroides decreased (p < 0.05), leading to shifts in functional pathways related to amino acid, lipid, and carbohydrate and energy metabolism. Untargeted metabolomics revealed that muscle betaine and inosine peaked at 4 months of age, whereas L-arginine, L-proline, and inosinic acid were most abundant at 6 months of age (p < 0.05). Correlation analysis revealed that the b*45min was positively associated with ruminal concentrations of propionate, butyrate, and valerate, as well as with the relative abundances of key Selenomonadales taxa (p < 0.05). Inosinic acid exhibited a positive correlation with the abundance of the genus Sodaliphilus and ruminal butyrate concentration (p < 0.05), while Sodaliphilus abundance was negatively correlated with inosine (p < 0.05). In summary, this study demonstrates that age-related variations in the meat quality of Duolang sheep are closely associated with rumen microbial ecology and muscle metabolites, offering novel insights into the molecular mechanisms underlying meat quality formation and identifying potential biomarkers.

This study aimed to investigate the underlying mechanisms by which replacing soybean meal with different proportions of black soldier fly (BSF) larvae meal affects the antioxidant capacity, immune function, and intestinal health in Xichuan black-bone chickens. After feeding the diets with 0.0%, 3.9%, 7.8%, 11.7%, and 15.6% BSF powder for 56 days, twelve chickens were sampled from each group. The optimal addition group was determined. Compared with the control group, adding 11.7% BSF significantly increased serum T-AOC, SOD, IgA, IgM, IL-4, and IL-10 concentrations, while markedly reducing IL-1β, TNF-α, and IL-6 (p < 0.05) and improving spleen morphology. Adding 11.7% BSF significantly increased the duodenal villus-to-crypt ratio (V/C) and markedly elevated the ileal V/C (p < 0.05), and it significantly increased gene expression levels of duodenal Claudin-1, Occludin, and E-cadherin, jejunal Claudin-1, and ileal Claudin-1, Occludin, and E-cadherin (p < 0.05). Compared with the control group, the 11.7% addition group exhibited significant alterations in caecal microbiota composition (p < 0.05), with 10 distinct bacterial genera identified at the genus level. A total of 424 differentially expressed metabolites were identified. Correlation analyses revealed that adding 11.7% BSF may enhance immune function by regulating intestinal metabolites such as isovaleric acid, inosine, and tazarotenic acid via Akkermansia, Sphaerochaeta, and Blautia in the cecum. It may also improve gut health by modulating inosine through Sphaerochaeta and Blautia. This trial provides feasibility evidence for substituting soybean meal with BSF meal, offering scientific support for sustainable development in animal husbandry.

Investigation of the effects and underlying mechanisms of adenylate kinase 1 on inosine monophosphate deposition in Beijing-You chickens

With the increasing global burden of fatty liver disease (FLD), liver transplantation (LT) recipients face heightened risks of steatosis recurrence in graft livers, necessitating urgent reappraisal of immunosuppressant-associated metabolic effects. The effects of mycophenolic acid (MPA), a commonly used immunosuppressant in LT, on hepatic lipid metabolism following LT remain unclear. This study employed a multifaceted approach encompassing cellular, animal, and molecular biology techniques to systematically evaluate the role of MPA in hepatic lipid metabolism. Our results demonstrated that MPA promoted lipid synthesis in healthy hepatic models by upregulating the expression of genes associated with lipogenesis, including SREBP-1c, FASN, and PPARγ, while paradoxically inhibiting lipid accumulation in steatotic hepatic models. Mechanistically, we identified inosine monophosphate dehydrogenase 2 (IMPDH2) as the molecular switch governing this dichotomy. Notably, significantly increased interaction between IMPDH2 and PPARγ was observed following MPA treatment. Our findings highlight the intricate role of MPA in hepatic lipid homeostasis and underscore the importance of further elucidating the effects of MPA across a spectrum of liver conditions to inform tailored treatment strategies following LT.

Integrated transcriptomic and metabolomic analysis identifies C5NT1AL as a candidate gene influencing inosine monophosphate levels in chicken breast muscle