Search Results (250)

Body color is the most prominent phenotypic trait in animals. To investigate the molecular regulatory mechanisms underlying skin pigmentation and body color in Channa argus, single-nucleus RNA sequencing technology was employed to analyze cell diversity and functional changes in the skin of normal and albino C. argus. Three pigment-related cell types, seven immune-related cell types, and nine other skin-related structural and functional cell types were identified. The skin of albino C. argus, which appears white to the naked eye, contains numerous melanocytes and iridophores with reflective silver properties. Compared to normal C. argus, melanocytes in albino individuals contained fewer melanin granules, while iridophores exhibited increased chromogenic substances. Melanocyte-specific genes—kitlg, myo5a, and scarb1—were significantly downregulated in albino melanocytes (p < 0.05). Conversely, iridophore-specific genes alk, pnp, and gpnmb were significantly upregulated in albino skin, whereas mlph was significantly downregulated (p < 0.05). Weighted gene co-expression network analysis revealed that scarb1 was associated with the melanocyte module, alk was identified as a core gene, and pnp was linked to the iridophore module. Functionally, scarb1 is involved in pigment transport, pnp in purine synthesis, and alk is essential for iridophore development. Therefore, scarb1, pnp, and alk may be correlated to albinism in C. argus. Overall, this study constructed a single-cell transcriptional atlas of C. argus skin, providing valuable reference data for further research into the regulatory mechanisms governing body color formation and maintenance in this species. Full article

Uric acid (UA), a key end-product of human purine metabolism, serves as an important biomarker linked to multiple disorders. This study developed a novel enzyme-free colorimetric sensing platform based on starch-derived nitrogen-doped biochar (NC) for the highly sensitive and selective detection of UA in human body fluids. The NC material with a high specific surface area and abundant nitrogen active sites was prepared via a two-step strategy involving hydrothermal synthesis followed by high-temperature pyrolysis, using starch and urea as raw materials. Under mild conditions, the NC effectively catalyzes dissolved oxygen to produce reactive oxygen species (·O₂⁻ and ¹O₂), which oxidize 3,3′,5,5′-tetramethylbenzidine (TMB) to a blue-colored oxidation product (TMBox). The presence of UA reduces TMBox to colorless TMB, leading to a measurable decrease in absorbance at 652 nm and enabling quantitative UA detection. Key reaction conditions were systematically optimized. Material characterization and mechanistic investigations confirmed the catalytic performance of the NC. The method demonstrated a wide linear response from 10 to 500 μmol·L⁻¹, with a detection limit of 4.87 μmol·L⁻¹, and demonstrated outstanding selectivity, stability, and reproducibility. Practical application in human serum and urine samples yielded results consistent with clinical reference ranges, and spike-recovery rates ranged from 95.5% to 103.6%, indicating great potential for real-sample analysis. Full article

Background: Polysaccharides modulate host health by interacting with gut microbiota and reshaping the host–microbial metabolome, potentially facilitating immune regulation. Methods: This study evaluated the modulatory effect of Artocarpus heterophyllus Lam. (jackfruit) polysaccharide (JFP-Ps) against cyclophosphamide (Cy)-induced immunosuppression in mice, focusing on gut microbiota modulation and metabolite changes. Results: JFP-Ps effectively increased the beneficial bacteria ratio, such as Lactobacillus and Lachnospiraceae, while inhibiting some species like Akkermansia. Metabolomic analysis showed that JFP-Ps notably regulated gut microbe-associated metabolites, including short-chain fatty acids (SCFAs), amino acids, bile acids, indoles, and derivatives. These metabolites were involved in various metabolic pathways, including primary bile acid synthesis and biosynthesis of phenylalanine, tyrosine, and tryptophan, along with tryptophan catabolism, purine metabolic processes, and unsaturated fatty acid production. Additionally, significant correlations between microbial groups and functional metabolites were identified. Overall, JFP-Ps exerted an immuno-modulatory effect by reshaping gut microbiota and enhancing co-metabolism with the host. Conclusions: These results provided valuable insights into host–microbiota interactions and gut microbiota-targeted intervention strategies of tropical natural bioactive polysaccharides. Full article

Early-life development of immune functions is crucial for calf health, growth, and future productivity. Galacto-oligosaccharides (GOSs) have been reported to facilitate ruminal microbial establishment and improve growth in Holstein dairy calves, but their prolonged influence on immunoglobulin levels, hindgut microbiota, and metabolic regulation remains insufficiently understood. This study evaluated the effects of early-life GOS supplementation on immune-related indicators, intestinal microbial ecology, and metabolic profiles in Holstein calves. Twenty-four newborn Holstein female dairy calves were randomly assigned to a control group (CON, n = 12) or a GOS group (GOS, n = 12; 10 g/day from birth to day 28). After supplementation ceased on day 28, calves previously receiving GOS were referred to as the GOSS group (n = 6). Immunoglobulin levels, gut microbiota, and fecal and serum metabolomes were evaluated during supplementation and six weeks after withdrawal. GOS supplementation significantly increased serum IgA and IgG levels during the treatment, with IgG levels remaining elevated for six weeks after discontinued supplementation. Although overall microbial diversity was not markedly altered, GOS selectively enriched bacterial taxa and function pathways linked to amino acid synthesis, unsaturated fatty acid production, and coenzyme-related metabolism. On day 70, GOSS group displayed distinct fecal and serum metabolomic profiles, with altered metabolites primarily associated with vitamin B6, folate, cobalamin metabolism, branched-chain amino acid biosynthesis, and purine and arginine pathways. These results demonstrate that early-life GOS supplementation promotes sustained immune and metabolic alterations following supplementation cessation, potentially mediated by modulation of gut microbial functions. These findings suggest that early dietary GOS supplementation may support physiological maturation in calves and could be useful as a nutritional strategy in calf-rearing systems. Full article

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

Objective: To explore the association between uric acid and the prevalence of hyperlipidemia via the NHANES database, a combined hyperuricemia–hyperlipidemia (HUA-HLP) quail model was subsequently established to investigate the pathological characteristics of the model. Methods: In the NHANES database, information on patients with hyperuricemia is collected, and the association between serum uric acid levels and the prevalence of hyperlipidemia is analyzed by adjusting for confounding variables. A high-purine and high-fat diet was prepared with a ratio of regular feed–yeast extract powder–lard = 15:2:3. By measuring uric acid and blood lipid levels, and observing the activities of uric acid-producing enzymes and enzymes related to lipid metabolism synthesis and decomposition, the metabolic disorder and pathological characteristics of the model were evaluated. Results: By adjusting for confounding variables, it is found that as serum uric acid levels increase, the prevalence of hyperlipidemia rises significantly. The high-purine and high-fat diet successfully induced a quail model of hyperuricemia combined with hyperlipidemia. During the first week, serum uric acid, triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels were significantly elevated and remained high until the end of the experiment. Serum free fatty acid levels were significantly increased from the second week and remained at a high level. Serum high-density lipoprotein cholesterol levels were significantly reduced from the third week and remained stable thereafter. In addition, the enzymes involved in uric acid synthesis as well as those related to lipid metabolism (including synthesis and decomposition) also exhibited significant abnormalities. Conclusions: In the human body, uric acid and lipid metabolism interact with each other and exacerbate one another’s abnormalities. A high-purine and high-fat diet can induce a quail model of hyperuricemia combined with hyperlipidemia. Uric acid and lipid metabolism are simultaneously disturbed, and the activities of uric acid-producing enzymes as well as enzymes related to lipid metabolism synthesis and decomposition are also altered. Full article

Key intermediate azidodiols were synthesized according to literature from commercially available (+)- and (−)-α-pinene in a four-step sequence, including epoxidation with mCPBA, allylic rearrangement, a second epoxidation and, finally, a regioselective azidolysis of the resulting epoxide by sodium azide, yielding the enantiomerically pure azidodiols. The pyrimidine-based alkyne building blocks were prepared from dichloropyrimidines following our method reported previously, while the purine-containing alkyne analogues were synthesized in a procedure of two or three steps. Click reactions were carried out in the presence of Cu(OAc)₂ and sodium ascorbate. The obtained pinane-coupled 2,4-diaminopyrimidines were screened for antiproliferative activity by MTT assay on HeLa, MD231, SiHa, MCF-7, and A2780 human cancer cell lines compared with fibroblast cells (NIH/3T3), on Gram-positive and Gram-negative pathogenic bacteria, and two yeasts, and the SAR was explained in detail. The prepared compounds showed moderate antiproliferative activity. While the starting azidodiols (+)-2 and (−)-2 exhibited excellent and selective antibacterial activities against S. aureus with a moderate antimycotic effect on C. krusei, only the (−)-enantiomer was active against P. aeruginosa. In a similar manner, most pyrimidine and purine derivatives also expressed moderate antimycotic effect against C. krusei. One of the purine-based derivatives (−)-30 possessed remarkable and selective antibacterial effect against P. aeruginosa. Full article

Although the digestion of dietary and endogenous proteins by the exocrine pancreatic proteases and peptidases in the small intestine luminal fluid is highly efficient for most proteins, it has been roughly approximated that between 3 and 11 g of alimentary proteins and peptides are moving from the small intestine to the large intestine in humans. Here, this nitrogenous material is degraded by the bacterial protease and peptidase activities, releasing amino acids. These amino acids are utilized by the abundant population of bacteria, notably amino acids that the bacteria are unable to synthesize, and which can thus be considered as indispensable for these microorganisms. The anabolism of amino acids by colonic bacteria is related to the synthesis of proteins while some specific amino acids are used for the synthesis of the purine and pyrimidine rings in DNA and RNA. Catabolism of specific amino acids allows for ATP synthesis and results in the production of metabolites with documented roles in the metabolism and physiology of commensal and pathogenic microorganisms among the intestinal microbiota. In the present narrative review, we examine the recycling of the undigested host’s proteins by large intestine bacteria and the metabolism of released amino acids. In addition, we describe how these metabolic pathways are involved in bacterial growth and communication, as well as in bacterial physiology in terms of virulence, resistance to detrimental environmental conditions, and capacity to form biofilms. Full article

The viable bacterial count is a crucial quality indicator for lactic acid bacteria (LAB) starters and fermented foods. Metabolic activity is an integral component of stress tolerance pathways. Lacticaseibacillus rhamnosus exhibits enhanced heat and oxidative stress tolerance in tryptone-free media. To investigate the stress tolerance mechanisms from a metabolic perspective, the heat and oxidative stress tolerance and transcriptomic changes in L. rhamnosus hsryfm 1301 and its ccpA deficient strain (ΔccpA) were analyzed under different nitrogen source conditions. Slower growth, decreased heat stress tolerance, and enhanced oxidative stress tolerance were observed in ΔccpA in MRS. Compared to the wild-type strain, 260 genes were upregulated and 55 genes were downregulated in ΔccpA, mainly including carbon source transport and metabolism genes, but no typical stress tolerance genes. The regulation of pfk, pyk, dnaK, and groEL was different from that in other lactic acid bacteria. The pathways related to acetate production were regulated solely by ccpA deletion, while dnaK, groEL, and de novo pyrimidine synthesis genes were only regulated by tryptone. Fatty acid and purine synthesis genes and glmS were co-regulated by ccpA and tryptone. The deletion of ccpA eliminated the nitrogen source-induced oxidative stress tolerance changes. It was found that ccpA in L. rhamnosus can affect both carbon and nitrogen source metabolism, altering stress tolerance. Full article

Changes in the homeostatic balance between purine nucleotide synthesis, degradation, and salvage are caused by disruptions in ATP supply and/or demand in the heart. These disruptions may affect myocardial energetics and, consequently, cardiac function and mechanics. Increased cardiac inorganic phosphate levels and decreased myocardial ATP levels are the outcomes of this decrease in purine nucleotide levels. Both modifications can immediately affect cellular mechanical work and tension development. Depletion of cardiac nucleotides and compromised myocardial mechanical function are linked to both acute myocardial ischemia and decompensatory remodelling of the myocardium in heart failure. Theoretically, in both acute ischemia and chronic high-demand situations associated with the development of heart failure, an imbalance in the breakdown, salvage, and synthesis of purine nucleotides results in a net loss of purine nucleotides. It was found that the use of nucleotide precursors can be a potentially effective approach to diminishing ischemia–reperfusion damage. The scope of this article is to review knowledge of the effect of purine nucleotide precursors such as D-ribose, AICAR, inosine, hypoxanthine, and adenine on myocardial ischemia–reperfusion injury and highlight potential targets for treating myocardial metabolic and mechanical dysfunction associated with ischemia–reperfusion injury by these molecules. Full article

Rice blast, caused by Magnaporthe oryzae (M. oryzae), severely threatens global rice production with substantial yield losses, endangering food security and driving demand for resistant varieties. Fuhui2165 (FH2165), an elite restorer line with stable blast resistance, superior agronomic traits, and high grain quality, is valuable for hybrid breeding, but its resistance mechanisms remain unclear. In this study, we investigated the rice blast resistance and underlying mechanisms in FH2165 and its parental lines (Huahangsimiao/HHSM, Minghui86/MH86, and Shuhui527/SH527) using transcriptome sequencing analysis. Phenotypic analysis revealed that FH2165 and HHSM exhibited stronger resistance compared to MH86 and SH527. Differential expression analysis identified 3886, 2513, 3390, and 4678 differentially expressed genes (DEGs) in FH2165, HHSM, MH86, and SH527, respectively. Gene Ontology (GO) enrichment analysis highlighted DEGs associated with chloroplasts, plastids, thylakoids, and related cellular components. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified significant enrichment in pathways such as carbon metabolism, amino acid biosynthesis, and photosynthesis. This suggested that defense strategies could involve energy reprogramming and the synthesis of secondary metabolites. Additionally, the DEGs co-expressed specifically in FH2165 and HHSM were enriched in functions related to RNA processing, GTP binding, and L-ascorbic acid binding, with purine metabolism playing a role in the regulation of energy and signaling. These findings elucidated the critical metabolic and signaling networks that underlie the blast resistance of FH2165 and offered potential targets for breeding high-yield, disease-resistant hybrid rice varieties. Full article

Comets are chemically rich and thermally extreme, spanning surface temperatures from ~50 K in the Oort Cloud to >1000 K for sungrazing bodies. These conditions may support key steps of prebiotic chemistry, including the synthesis of nucleic acid precursors. This study present a thermodynamic evaluation of seven candidate reactions, producing nitrogenous bases, sugars, nucleosides, and nucleotides, across the cometary temperature spectrum, 50–1000 K. Purine nucleobase synthesis, including adenine formation via aminoacetonitrile polymerization and HCN polymerization, is strongly exergonic at all temperatures. Sugar formation from formaldehyde is also exergonic, while intermediate pathways, e.g., 2-aminooxazole synthesis, become thermodynamically viable only above ~700 K. Nucleoside formation is thermodynamically neutral at low T but becomes favorable at elevated temperatures, whereas phosphorylation to AMP, i.e., adenosine-monophosphate, a nucleotide serving as a critical regulator of cellular energy status, remains highly endergonic under the entire T range studied. My analysis suggests that, under standard-state assumptions, comets can thermodynamically support formation routes of nitrogenous bases and simple sugars but not a complete nucleotide assembly. This supports a dual-phase origin scenario, where comets act as molecular reservoirs, with further polymerization and biological activation occurring post-delivery on planetary surfaces. Importantly, these findings represent purely thermodynamic assessments under standard-state assumptions and do not address kinetic barriers, catalytic influences, or adsorption effects on ice or mineral surfaces. The results should therefore be viewed as a baseline map of feasibility, subject to modifications in more complex chemical environments. Full article

Hyperuricemia (HUA) is a metabolic disorder characterized by abnormal purine metabolism within the body. Ampelopsis japonica (Thunb.) Makino has traditionally been utilized in the treatment of various kidney diseases; however, its specific anti-hyperuricemic effects and the underlying mechanisms warrant further investigation. This study investigates the mechanism of action by which A. japonica extract (AJE) addresses HUA using a combination of pharmacology techniques, including network pharmacology and metabolomics. A HUA mouse model was established using potassium oxonate and hypoxanthine. AJE intervention significantly reduced serum uric acid and creatinine levels in HUA mice and markedly decreased glomerular atrophy and renal tubular degeneration. Metabolic profiling revealed distinct metabolic profiles between AJE-intervention and control groups, further demonstrating that AJE corrected disruptions in arginine biosynthesis, purine metabolism, pyrimidine metabolism, and arachidonic acid metabolism. The results of the network pharmacology-based study indicate that AJE can alleviate HUA by modulating the TNF pathway and the Toll-like receptor pathway. The mechanisms of action of AJE in HUA involve the inhibition of xanthine oxidase (XOD) to reduce uric acid synthesis, downregulation of URAT1 and GLUT9 to decrease uric acid reabsorption, and suppression of the TLR4/NF-κB pathway to mitigate inflammation in the HUA mouse model. Therefore, AJE demonstrates significant potential as a therapeutic intervention for HUA and its associated renal complications. Full article

Mitochondria play a pivotal role in fungal growth, development, and metabolic regulation, yet their significance has often been overlooked in traditional breeding programs. Auricularia heimuer, the second most widely cultivated edible fungus in China, has attracted increasing attention due to its nutritional and health-promoting properties, underscoring the urgent need for the development of functional cultivars and the elucidation of mitochondrial regulatory mechanisms. In this study, we constructed isonuclear alloplasmic strains with identical nuclear genotypes but distinct mitochondrial backgrounds. Comparative analyses of mycelial growth, fruiting body morphology, and nutritional composition were conducted, alongside transcriptomic profiling. The results showed no significant morphological differences on sawdust-based medium; however, on PDA medium, the strains exhibited notable differences in growth rate, melanin content, β-glucan levels, iron ion concentration, and amino acid content. Transcriptomic analysis identified 3385 differentially expressed genes (DEGs), which were enriched in pathways related to lysine biosynthesis, purine metabolism, DNA replication, and repair. Key DEGs involved in lysine biosynthesis were found to encode aminoadipate reductase (AAR) and saccharine dehydrogenase (SDH), with AAR localized in the cytoplasm and potentially regulating lysine synthesis through its enzymatic activity. This study highlights the critical influence of mitochondrial genes on the metabolic composition and transcriptional landscape of A. heimuer, providing a theoretical foundation for genetic improvement and the development of functional fungal cultivars. Full article

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