Search Results (2,077)

Tryptophan (TRP) is a proteinogenic and nutritionally essential amino acid involved in the formation of numerous bioactive substances. A crucial role in the TRP molecule is played by indole, a bicyclic ring formed by benzene and pyrrole, which confers hydrophobic and antioxidant properties and the ability to act as a ligand for aryl hydrocarbon and pregnane X receptors. The first parts of the article examine sources, nutritional requirements, and three pathways of TRP catabolism. Physiologically, ~5% of dietary TRP is catabolized through the pathway forming serotonin and melatonin in the brain and enterochromaffin cells of the gut, ~85% through the pathway resulting in the formation of nicotinamide nucleotides and kynurenine and its derivatives in the liver and immune cells, and ~10% in gut microbiota to indole derivatives. Alterations of individual TRP catabolism pathways in aging, alcoholism, inflammatory bowel disease, metabolic syndrome, renal insufficiency, liver cirrhosis, cancer, and nervous diseases, e.g., depression, Alzheimer’s and Parkinson’s diseases, multiple sclerosis, and schizophrenia, are examined in the central section. The final sections are devoted to the benefits and adverse effects of TRP supplementation, the therapeutic use of various TRP metabolites, and the pharmacological targeting of enzymes, transporters, and receptors involved in TRP catabolism. It is concluded that all pathways of TRP catabolism are altered across a broad spectrum of human illnesses, and further investigation is needed to understand their role in disease pathogenesis better. The goal for clinical research is to explore options for TRP-targeted therapies and their integration into new therapeutic strategies. Full article

Non-traumatic osteonecrosis of the femoral head (ONFH) is a multifactorial disorder in which genetic susceptibility is thought to play an important role, yet the contribution of many candidate genes remains unclear. The catenin beta-1 (CTNNB1) gene encodes β-catenin, a key regulator of the Wnt/β-catenin signaling pathway involved in bone homeostasis and vascular regulation, and may therefore influence susceptibility to non-traumatic ONFH. In this case–control study, genotype data from China Medical University Hospital were analyzed to evaluate the association between CTNNB1 polymorphisms and the risk of ONFH. A total of 609 patients with ONFH and 2436 age- and sex-matched controls were included. Fourteen CTNNB1 single-nucleotide polymorphisms (SNPs) with a minor allele frequency greater than 5% were selected and analyzed using logistic regression under multiple genetic models, with Hardy–Weinberg equilibrium assessed in controls. Two SNPs, rs3774370 and rs11564478, showed significant differences in allele frequencies between cases and controls, with lower minor allele frequencies observed in the ONFH group. Both variants were associated with a reduced risk of ONFH, and these associations remained significant under dominant genetic models. These findings suggest that specific CTNNB1 polymorphisms may confer a protective effect against non-traumatic ONFH and provide further insight into the genetic architecture of this disease. Full article

The microevolutionary pathways and molecular mechanisms by which the important pathogen Vibrio parahaemolyticus acquires resistance in the aquatic environment under continuous selective pressure from quinolone antibiotic residues are still unknown. Here, the study successfully simulated the long-term pressure of antibiotic residues in aquaculture by susceptible V. parahaemolyticus (VPD14) which was isolated from seafood, to a 30-day in vitro induction with sublethal concentrations of levofloxacin, which yielded the mutants (VPD14M). A phenotypic analysis revealed that VPD14M exhibited resistance to ampicillin, levofloxacin and ciprofloxacin, compared to VPD14. These changes were accompanied by adaptations, including a decreased growth rate and an enhanced biofilm formation capacity. Whole-Genome Sequencing identified that the acquired resistance was primarily attributable to key point mutations in three Quinolone Resistance-Determining Regions (QRDRs). Specifically, a G → T substitution at nucleotide position 248 in the gyrA gene, leading to a serine-to-isoleucine substitution at the 83rd amino acid position (Ser83Ile) of the DNA gyrase subunit A; a C → T substitution at position 254 in the parC gene, resulting in a serine-to-phenylalanine substitution at position 85 (Ser85Phe) of the topoisomerase IV subunit A; and a C → T substitution at position 2242 in the gyrB gene, causing a proline-to-serine substitution at position 748 (Pro748Ser) of the DNA gyrase subunit B. Collectively, the study demonstrated that sublethal antibiotic levels rapidly drive quinolone resistance in V. parahaemolyticus, and the specific mutations identified offer critical support for resistance monitoring and seafood safety alerts. Full article

Hibernation profoundly alters host–pathogen dynamics by suppressing metabolism and immune function, posing unique challenges for infection control. In this study, we examined how genomic variation modulates infection and physiological traits in temperate bats during hibernation. We combined infection screening, haematology, blood biochemistry, and whole-genome sequencing across five vespertilionid species, identifying over 170,000 single nucleotide variants (SNVs) and assessing their associations with 23 health-related variables. Using the phylogenetically informed treeWAS framework, we detected 515 significant SNVs linked to traits including fungal, protozoan and bacterial infections, acid–base balance, and blood cell indices. These SNVs mapped to 137 unique genes, which were enriched for functional domains related to cytoskeletal dynamics, membrane trafficking, and intracellular signalling (e.g., SH3, C2, BAR, semaphorin). Notably, canonical immune effector genes were underrepresented, and several trait-associated SNVs appeared in blocks across multiple scaffolds, pointing to regulatory loci as key modulators of hibernator health. Our findings support the hypothesis that bats rely on infection tolerance rather than resistance during hibernation, with genomic variation in regulatory and signalling pathways shaping their physiological responses to infection under energy-limited conditions. Full article

Orf virus (ORFV) is a member of the Parapoxvirus genus of the Poxviridae family causing contagious diseases in sheep, goats, and wild ungulates, with zoonotic potential in humans. Although many viruses, including poxviruses, are known to utilize the host cellular machinery to reproduce viral particles, the metabolic changes induced by ORFV remain unclear. In the present study, non-targeted metabolomics and proteomics were employed to investigate the impact of ORFV infection on the host cellular metabolism network. A total of 301 metabolites and 802 proteins were significantly altered during the early stages of ORFV infection, and most of them were involved in cellular lipid metabolism, amino acid metabolism, nucleotide metabolism, and glucose metabolism. We further determined the effect of the host’s metabolic system on ORFV replication using the TCID₅₀ assay. Virus titers were significantly decreased in the absence of glucose or when treated with the de novo fatty acid synthesis inhibitor, indicating that glucose metabolism and de novo fatty acid synthesis pathway were required for ORFV replication. However, glutamine did not affect viral titers. Our findings provide insights into ORFV–host interactions, which are critical for developing new preventive or therapeutic strategies against ORFV by targeting altered metabolic pathways. Full article

Abiotic stress of cold is one of the limitation factors that hinder the production of alfalfa (Medicago sativa). Although there are a large number of studies suggesting that non-coding RNAs (ncRNAs) play an important role in plant response to abiotic stress, the mechanism by which ncRNAs and competing endogenous RNAs (ceRNAs) influence the low-temperature tolerance of alfalfa remains understudied. In this study, we integrated whole-transcriptome RNA-seq and genome-wide association studies (GWASs) to identify cold stress-related metabolic pathways and candidate genes, differentially expressed (DE) mRNAs, microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Degradome sequencing was used to verify the ceRNA network under cold stress. A total of 46,936 DEmRNAs were identified. Ribosome (ko03010), amino sugar and nucleotide sugar metabolism (ko00520), ribosome biogenesis in eukaryotes (ko03008), circadian rhythm–plant (ko00270), and starch and sucrose metabolism (ko00500) were the top five KEGG terms with the highest p-value, enriching the most number of DEmRNAs. MS.gene53818 (MsUAM1) was considered to be the critical candidate gene for alfalfa response to cold stress by conjoint analysis of GWASs and DEmRNAs. A total of 223 DEmiRNAs, 1852 DElncRNAs, and 13 DEcircRNAs were identified under cold stress. Functional analysis indicates that they play important roles in GO terms such as leaf development (GO:0048366), DNA-binding transcription factor activity (GO:0003700), central vacuole (GO:0042807), response to auxin (GO:0009733), and water channel activity (GO:0015250), as well as in KEGG pathways such as plant hormone signal transduction, starch and sucrose metabolism, and flavone and flavonol biosynthesis (ko00944). A ceRNA network comprising 28 DElncRNAs, 8 DEcircRNAs, 11 DEmiRNAs, and 23 DEmRNA triplets was constructed. In this study, mRNAs and ncRNAs were identified that may be involved in alfalfa’s response to cold stress, and a ceRNA regulatory network related to cold stress was established, providing valuable genic resources for further research on the molecular mechanisms underlying alfalfa cold stress. Full article

Background: Melanoma outcomes have improved in recent years as a result of modern systemic therapies. A major molecular feature of melanoma is abnormal telomerase activation; this is most often caused by telomerase reverse transcriptase (TERT) promoter mutations, which occur in 50–82% of cases and are the most common noncoding alteration in this cancer. Telomerase maintains telomere length, allowing melanoma cells to avoid senescence and continue dividing. However, how telomerase activity influences melanoma cell doubling time remains unclear, and the pathways linking TERT expression to faster cell-cycle progression require further study. Although telomerase inhibitors show promise in preclinical models, their clinical use is limited by delayed cytotoxicity and resistance. Materials and Methods: A scoping review was conducted using Scopus, ScienceDirect, MEDLINE/PubMed, and CINAHL (Cumulative Index to Nursing and Allied Health Literature). Keywords included “telomerase,” “melanoma,” “cancer,” “cell proliferation,” and “doubling time,” using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Telomerase-related biomarkers were found to correlate with disease stage and survival. Suggested therapeutic strategies include enzyme inhibitors, cytotoxic nucleotide incorporation, telomere destabilization, and immunotherapies such as peptide or dendritic cell vaccines, etc. Conclusions: Understanding both telomere-dependent and -independent TERT functions is essential for developing effective biomarkers and therapies that overcome resistance and slow melanoma progression. Full article

This study systematically characterized functional compartmentalization along the intestinal tract of New Zealand rabbits by analyzing mucosal tissue and luminal contents from distinct segments, including the duodenum, jejunum, ileum, cecum, and colon, using RNA-seq and 16S rRNA sequencing. Transcriptomic analysis revealed that differentially expressed genes identified between the small and large intestines were mainly enriched in digestion, absorption, and immune functions. Genes associated with the transport of amino acids, sugars, vitamins, and bile salts showed significantly higher expression in the small intestine, whereas genes related to water absorption, short-chain fatty acids (SCFAs), nucleotides, and metal ion transport were preferentially expressed in the large intestine. From an immunological perspective, genes involved in fungal responses were enriched in the small intestine, while bacterial response pathways and pattern recognition receptor (PRR) signaling genes were upregulated in the large intestine. Microbiota analysis demonstrated significantly greater diversity and abundance in the large intestine compared with the small intestine. Specifically, Proteobacteria and Actinobacteria were enriched in the small intestine, whereas Firmicutes, Verrucomicrobia, and Bacteroidetes dominated the large intestine. Correlation analysis further identified significant associations between gut microbiota composition and host genes involved in nutrient digestion and absorption. Together, these findings provide transcriptome-based evidence for regional specialization of nutrient transport, immune responses, and microbial ecology along the rabbit intestine. Full article

Endophytic fungi enhance plant growth and stress resilience, yet their molecular roles in the roots of the endangered tree Phoebe bournei remain unclear. A comparative RNA-seq analysis was performed on root transcriptomes from wild, endophyte-colonized adult trees (OT) and axenically grown seedlings (ST). Unmapped reads were analyzed against the NCBI nucleotide (NT) database using BLASTN (v2.17.0), revealing Rhizophagus irregularis as the predominant endophytic fungus. Differential expression analysis identified 5891 DEGs, which were significantly enriched in pathways related to plant–pathogen interactions, phenylpropanoid biosynthesis, plant hormone signal transduction, and MAPK signaling. Key upregulated genes included PbMPK3, PbCML42, PbCML41.2, and PbGSTU28, suggesting enhanced ROS scavenging, calcium signaling, and defense activation. RT-qPCR validation confirmed the transcriptomic trends for selected genes. Our findings reveal that root endophytic fungi modulate a coordinated network involving immune priming, phytohormone regulation, and redox homeostasis, thereby supporting root development and enhancing resistance to biotic and abiotic stresses in P. bournei. This study provides foundational molecular insights into beneficial plant–endophyte interactions and identifies candidate genes that are valuable for the conservation and breeding of this threatened species. Full article

Tea is produced from the fresh leaves of the tea plant (Camellia sinensis), and the quality of tea is directly dictated by its raw material. Although factors such as tea cultivar, fertilization, and cultivation practices are known to affect fresh leaf quality, the specific influence of altitude remains poorly understood. In this present study, ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed to investigate the non-volatile metabolites in fresh tea leaves grown at two different altitudes (350 m and 600 m). A total of 2323 metabolites were identified, with flavonoids and phenolic acids representing the dominant classes. Orthogonal partial least squares-discriminant analysis (OPLS-DA) further revealed 116 differential metabolites between groups. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis indicated that several key pathways were differentially activated, including those related to the biosynthesis of kaempferol, luteolin, and flavones, as well as nucleotides and jasmonic acid metabolism. In addition, marked differences were observed in the accumulation patterns of lipids, phenolic acids, and flavonoids between leaves grown at the two altitudes. These findings provide valuable insights into the role of altitude in shaping the metabolic composition and flavor formation of tea. Full article

Interferon-stimulated genes (ISGs) are classically recognized for their direct antiviral functions, such as viral genome degradation or replication blockade. However, emerging evidence reveals that ISGs orchestrate a broader landscape of host defense by rewiring cellular metabolism. These mechanisms are still not fully understood in the context of antiviral immunity. This review synthesizes recent advances in understanding how ISGs modulate metabolic pathways (e.g., glycolysis, lipid metabolism, amino acids, and nucleotide metabolism) to create an antiviral cellular environment. However, viruses have developed strategies to evade or counteract ISG-encoded proteins, and some even hijack certain ISGs to their advantage. Therefore, we further explore how viruses subvert these ISG-driven metabolic to evade host defenses. Overall, we summarize the current state of knowledge on the interactions between viruses and ISGs and propose that ISGs act as “protective” or “pathogenic” regulators at the dimensions of metabolism, offering new perspectives for targeting host-centered pathways to combat viral infections. Full article

Helicobacter pylori is a prevalent gastric pathogen that establishes chronic infection and contributes to gastritis, peptic ulcer disease, and gastric cancer. Its persistence depends on immune evasion strategies that promote sustained low-grade inflammation in the gastric mucosa. Nucleotide-binding oligomerization domain-like receptors (NLRs) are cytosolic pattern recognition receptors that play key roles in innate immune responses against H. pylori. Nod1 and Nod2 detect bacterial peptidoglycan delivered via the type IV secretion system or outer membrane vesicles, activating NF-κB, MAPK, and interferon signaling pathways that regulate inflammatory cytokine production, epithelial barrier function, autophagy, and antimicrobial defense. The NLRP3 inflammasome mediates the maturation of IL-1β and IL-18 primarily in myeloid cells, thereby shaping inflammatory and immunoregulatory responses during infection. In contrast, NLRC4 functions in a context-dependent manner in epithelial cells and is largely dispensable for myeloid IL-1β production. Emerging evidence also implicates noncanonical NLRs, including NLRP6, NLRP9, NLRP12, NLRX1, and NLRC5, in regulating inflammation, epithelial homeostasis, and gastric tumorigenesis. In addition, genetic polymorphisms in NLR genes influence host susceptibility to H. pylori-associated diseases. This review highlights the interplay between NLR signaling, bacterial virulence, and host immunity and identifies potential therapeutic targets. Full article

Chemical complexity is not a nuisance to be minimized in origin of life research, it is an enabling condition. This second edition of the Special Issue on the Origin of Life in Chemically Complex Messy Environments gathers contributions that embrace multicomponent mixtures, dynamic geochemical settings, and nonequilibrium processes. The papers collected here survey surface hydrothermal routes to reactive nitriles, groundwater evolution of alkaline lakes, and transition metal sulfide-driven amino acid and amide formation without cyanide. They report one pot nucleoside and nucleotide synthesis from formamide over cerium phosphate, review non aqueous organophosphorus pathways, and probe peptide rich mixtures and formose type networks under serpentinization associated minerals. The issue also advances conceptual frameworks, including atmospheric photochemical signatures for biosignature discrimination, the role of chiral mineral surfaces in enantioseparation, and computational simulations of the origin of LUCA. Together, these studies position messy chemistry as a crucible that turns chemical diversity and environmental heterogeneity into routes toward organization and function. Full article

Flammulina filiformis is a widely cultivated edible mushroom valued for its taste and nutrition. However, its stipe often develops a fibrous and stringy texture that unpleasantly lodges between teeth during chewing. Texture analysis confirmed a distinct toughness gradient, with the upper stipe being more brittle and less tough than the lower part. UHPLC-MS/MS-based metabolomics of these regions identified 953 metabolites, predominantly spanning lipids and lipid-like molecules, organic acids and derivatives, and nucleosides, nucleotides, and analogues. Comparative analysis revealed that the tender upper stipe was characterized by a widespread downregulation of primary metabolites, including severe depletion of key signaling molecules (cAMP, cGMP) and amino acids such as L-tryptophan. In contrast, the tough lower stipe was enriched with metabolites indicative of an oxidative environment, notably a broad spectrum of oxidized lipids and phenolic compounds. KEGG pathway analysis attributed this dichotomy to distinct metabolic programs. While the upper stipe exhibited downregulation in tryptophan and purine metabolism, the lower stipe was enriched for pathways associated with redox homeostasis and lipid peroxidation, including glutathione metabolism and lipid peroxidation. The co-accumulation of oxidized lipids and phenolics suggests a potential mechanism for oxidation-driven tissue fortification. This study reveals a spatially programmed metabolic basis for the textural differentiation in F. filiformis stipes, providing a framework for understanding tissue development and highlighting potential regulatory targets for breeding varieties with improved eating quality. Full article

Growing evidence suggests that persistent oral infectious diseases (OIDs) contribute to systemic disease, highlighting the importance of understanding their pathogenic mechanisms. Conventional dental treatments, primarily mechanical debridement, surgical intervention, or antimicrobial therapy, often struggle to fully control inflammation or prevent progressive tissue destruction. The nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing 3 (NLRP3) inflammasome is a key regulator of innate immunity, mediating the maturation of proinflammatory cytokines (IL-1β and IL-18) and the pyroptosis-inducing protein gasdermin D. Dysregulated or excessive activation of NLRP3 contributes to the initiation and progression of major oral diseases, including periodontitis, peri-implantitis, pulpitis, and oral mucosal inflammation. Despite growing interest in NLRP3, comprehensive and up-to-date reviews integrating its pathogenic mechanisms and therapeutic potential remain limited. This review summarizes current and past evidence on the role of the NLRP3 inflammasome in oral disease development, highlights emerging pharmacological strategies, and outlines future research directions. Existing studies demonstrate that microbial components and danger signals from injured tissues activate NLRP3, thereby amplifying inflammation, tissue degradation, and bone resorption. Preclinical studies indicate that inflammasome inhibitors and several natural compounds reduce tissue damage; however, their clinical translation remains limited. These findings emphasize the need for deeper understanding of NLRP3-mediated pathways, with translational and clinical research offering promising therapeutic opportunities for oral diseases. Full article