Search Results (271)

Glutamine synthetase (GS; EC 6.3.1.2) is a key enzyme for primary assimilation and re-assimilation of ammonium in higher plants. Although several GS gene families have been reported for several cereal crops, systematic studies for barley (Hordeum vulgare) under different nitrogen treatment conditions are still lacking. In this study, we combined genome-wide bioinformatics mining with transcriptome analysis to characterize the HvGS gene family in two different genotypes of barley (nitrogen-efficient W26 and nitrogen-sensitive W20) and their responses to low nitrogen stress. Four HvGS genes were retrieved from the barley genome and named HvGS1–HvGS4. These genes were comprehensively analyzed in terms of chromosomal distribution, physicochemical properties, subcellular localization, intron-exon structure, conserved motifs, promoter cis-acting elements, evolutionary relationships, and predicted protein–protein interactions. Leaves and roots were sampled and subjected to RNA-seq analysis at 3, 18, and 21 days of low-nitrogen stress, which revealed significant expression differences among genotypes and tissues. In W26, low nitrogen (0.4 mmol·L⁻¹) induced synergistic expression of HvGS1 and HvGS4 and suppressed expression of plastidic HvGS2, whereas W20 up-regulated the expression of HvGS1 and HvGS3 mainly in the root system. Combined GO/KEGG enrichment analysis and metabolomic characterization of the differentially expressed genes highlighted nitrogen metabolism, glutathione turnover, and amino acid biosynthesis as key hubs in the tolerant genotypes. Our results provide a genome-wide analysis of the barley GS family and highlight HvGS1 and HvGS4 as candidate genes for functional validation toward improved nitrogen use efficiency. Full article

Background/Objectives: Carvacrol, a major active component of oregano oil and common feed additive, has been widely studied for its effects on fish growth, immunity, and intestinal health. But its transcriptional/metabolic impacts on fish liver remain unclear. This study investigated these effects in Pengze crucian carp (Carassius auratus var. Pengze). Methods: Fish were fed a basal diet (control) or basal diet supplemented with 10% microencapsulated carvacrol (600 mg/kg) for 56 days; liver samples were analyzed via transcriptomics and metabolomics. Results: Transcriptomic analysis revealed 482 differentially expressed genes (DEGs) in the liver of Pengze crucian carp following carvacrol supplementation, with 158 upregulated and 324 downregulated genes. Functional annotation highlighted enrichment in translation, signal transduction, amino acid metabolism, and posttranslational modification pathways. GO analysis further identified key processes, including carboxylic acid transport, tRNA aminoacylation, and mitochondrial nucleoid function, while KEGG pathways were implicated in amino acid biosynthesis, lipid metabolism (e.g., alpha-linolenic acid), and insulin signaling. Metabolomic profiling identified 679 significantly altered metabolites, including 113 upregulated and 566 downregulated ones. Among these, upregulated compounds like L-asparaginyl-L-lysine (Log₂FC = 4.36) and 2′-Deoxyadenosine-5′-diphosphate (Log₂FC = 4.31) are linked to nucleotide metabolism, and downregulated peptides (e.g., Ala-Phe-Tyr-Arg) suggesting modulated protein turnover. Joint omics analysis revealed convergent pathways in glycerophospholipid metabolism, aminoacyl-tRNA biosynthesis, and autophagy. Notably, the chaperone gene dnaja3b was correlated strongly with neuroactive metabolites (e.g., normetanephrine), potentially implicating carvacrol in stress response regulation. Conclusions: Our findings demonstrate that carvacrol modulates liver gene expression and metabolic profiles, primarily influencing amino acid and lipid metabolism pathways, autophagy, and stress responses. The observed correlations between dnaja3b and specific metabolites offer mechanistic insights into the action of carvacrol in fish liver. Full article

Pediatric inflammatory bowel disease (pIBD), comprising ulcerative colitis (UC) and Crohn’s disease (CD), involves complex mechanisms that include non-coding RNAs (ncRNAs), such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), alongside enzymes regulating serotonin metabolism. Tryptophan hydroxylase 1 (TPH1) and monoamine oxidase A (MAOA) play critical roles in serotonin turnover and may contribute to intestinal inflammation. We investigated the expression of TPH1, MAOA, hsa-miR-194-5p, hsa-miR-1276, and the lncRNA Nuclear Enriched Abundant Transcript 1 (NEAT1) in intestinal tissue biopsies and peripheral blood from pIBD patients and controls. TPH1 was significantly elevated in the inflamed transverse colon (p = 0.034), whereas MAOA was reduced in the ileum (p = 0.041) and descending colon (p = 0.001), with further decreases in inflamed ileum (p < 0.001), ascending (p = 0.008), and descending colon (p = 0.001). Subgroup analysis revealed decreased MAOA in the ascending colon of UC patients (p = 0.011). hsa-miR-194-5p was upregulated in the transverse colon (p = 0.015), inflamed transverse (p = 0.013) and descending colon (p = 0.015), and in blood of UC patients (p = 0.01). NEAT1 expression increased in the ascending colon (p = 0.042) but decreased in the ileum (p = 0.006). Correlation analysis showed strong positive associations between TPH1 and NEAT1 in the ileum (r = 0.945, p < 0.01) and transverse colon (r = 0.609, p < 0.01). These results highlight region-specific dysregulation of serotonin-related genes and ncRNAs in pIBD, with the TPH1/miR-194-5p/NEAT1 axis potentially contributing to disease pathophysiology and warranting further mechanistic investigation. Full article

Pepino mosaic virus (PepMV) is a highly infectious potexvirus that poses a significant threat to tomato cultivation in greenhouses worldwide. The threat posed by this virus is attributed to by its genetic complexity, characterized by the presence of multiple genotypes in circulation, mixed infections, and ongoing genotype turnover. Surveys of wild Solanum species have identified promising sources of resistance; however, this resistance is often incomplete, manifesting as symptomless, yet virus-positive, plants. When resistance is identified, introgressing of these traits into elite backgrounds is frequently impeded by reproductive barriers and linkage drag. Consequently, there are currently no commercially available cultivars with durable resistance to PepMV. Current control measures rely on stringent hygiene practices, seed health protocols, and the use of mild isolate cross-protection, which can mitigate fruit symptoms when carefully genotype-matched and closely monitored. Looking forward, achieving durable control will likely require host-centered strategies. Loss-of-susceptibility mutations and RNA interference-based approaches have demonstrated strong potential in experimental studies. Future solutions may involve the integration of genome editing with RNA-based technologies, supported by regulatory harmonization and socioeconomic viability considerations. Full article

Inherited retinal degenerations (IRDs), driven by pathogenic mutations, often involve primary dysfunction of the retinal pigment epithelium (RPE)—a pathogenic feature shared with atrophic age-related macular degeneration (aAMD), despite aAMD’s multifactorial etiology. Prominin-1 (Prom1), traditionally linked to photoreceptor pathology, has an unclear role in RPE homeostasis. We assessed Prom1 expression in C57BL/6J mouse retina sections and RPE flat mounts using immunohistochemistry and generated Prom1-knockout (KO) mouse RPE cells via CRISPR/Cas9. Bulk RNA sequencing with DESeq2 and gene set enrichment analysis (GSEA) revealed Prom1-regulated pathways. Prom1-KO cells exhibited upregulation of Grem1, Slc7a11, Serpine2, Il1r1, and IL33 and downregulation of Ablim1, Cldn2, IGFBP-2, BMP3, and OGN. Hallmark pathway interrogation identified reduced expression of PINK1 (mitophagy) and MerTK (phagocytosis), implicating defects in mitochondrial quality control and outer segment clearance. Enrichment analysis revealed activation of E2F/MYC targets, mTORC1 signaling, oxidative phosphorylation, and TNFα/NF-κB signaling, alongside suppression of apical junctions, bile acid metabolism, and Epithelial-Mesenchymal Transition (EMT) pathways. These findings suggest Prom1 safeguards RPE integrity by modulating stress responses, mitochondrial turnover, phagocytosis, metabolism, and junctional stability. Our study uncovers Prom1-dependent signaling networks, providing mechanistic insights into RPE degeneration relevant to both IRD and aAMD, and highlights potential therapeutic targets for preserving retinal health. Full article

Residential radon is a leading environmental cause of lung cancer, but circulating biomarkers linking home exposure to pathogenic biology are not well defined. We conducted an exposure-contrast study in Hang Dong District, Chiang Mai, measuring indoor radon in 48 homes and enrolling adults from <50 Bq/m³ (low) and ≥100 Bq/m³ (high) households for serum profiling. Mean indoor radon was 61.8 ± 18.4 Bq/m³ (range 34–126), with 6.2% of homes ≥100 Bq/m³. Small RNA sequencing identified 55 differentially expressed miRNAs (12 up, 43 down) in high-radon serum. Notably, miR-200b-3p, miR-200c-3p, and miR-194-5p were increased, while miR-3913-5p, miR-584-5p, miR-30a-3p, miR-22-3p, and miR-125a-5p were decreased. Target enrichment (KEGG/GO) implicated PI3K–Akt and MAPK hubs with Ras/Wnt/VEGF alongside focal adhesion/ECM–receptor/actin–cytoskeleton and immune-regulatory modules. Untargeted LC–MS metabolomics showed exposure-aligned shifts: higher PUFAs and oxylipins (e.g., AA, EPA; 9-HEPE, 8-HETE, 5,12-DiHETE), elevated acyl-carnitines (β-oxidation), and increased inosine/hypoxanthine, consistent with lipid/steroid remodeling, mitochondrial fuel reprogramming, oxidative stress, and nucleotide turnover. Integrated interpretation supports DDR/ATM → PI3K/Akt–MAPK activation with EMT/adhesion remodeling, angiogenic signaling, and immune modulation—linking residential radon to lung cancer mechanisms. Given the small sample size (n = 10), these findings should be interpreted as preliminary and hypothesis-generating, warranting validation in larger cohorts. Nevertheless, findings support household testing, remediation at ≥100 Bq/m³, and integrated exposure studies considering PM2.5 co-exposures. Full article

The conversion of agricultural residues into high-value organic amendments is fundamental to sustainable farming systems. Corn cobs represent a widely available lignocellulosic resource; however, their rigid structural properties often hinder efficient biodegradation during composting. This study evaluated whether optimizing corn cob particle size could improve aerobic composting performance by enhancing humification and compost quality. Corn cobs were ground into three particle sizes (6-mesh, 10-mesh, and 20-mesh) and composted with a commercial microbial inoculant for up to 51 days. Physicochemical properties, humic substance fractions (HSC, HAC, FAC), microbial community dynamics (16S rRNA and ITS sequencing), and maturity indicators were monitored. The 10-mesh treatment (M10) exhibited the most favorable composting outcomes, achieving the greatest degree of humification (HA/FA = 2.85; HAC = 48.30 g/kg) and the most pronounced aromatic condensation in humic acids. M10 also supported a more diverse and metabolically specialized microbial consortium, with notable enrichment of lignocellulose-degrading and humus-forming genera (e.g., Streptomyces, Thermobifida). Consequently, M10 produced the most mature compost, reflected by the highest germination index (93.63%) and the lowest heavy-metal accumulation, meeting agricultural safety standards. Structural equation modeling revealed that particle size influenced humification primarily by modulating microbial community structure (path coefficient = 0.86), highlighting particle size as a key environmental selector in composting systems. Overall, 10-mesh particle size created an optimal aeration–moisture balance that stimulated microbial metabolism, accelerated organic matter degradation, and enhanced stable organic matter formation. These findings demonstrate that corn cob particle size significantly governs composting efficiency and final product quality. Selecting a 10-mesh size presents a practical pretreatment strategy to accelerate biomass turnover and produce safe, nutrient-rich compost, providing an effective approach for sustainable bioconversion of agricultural residues. Full article

The pathological loss of nuclear TDP-43 is a hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), leading to extensive alterations in RNA metabolism and a broad number of neuronal transcripts. However, the key effectors linking TDP-43 dysfunction to synaptic defects remain unclear. In this study, using Drosophila and human iPSC-derived motoneurons, we identify Rab4 as a direct and conserved target of TDP-43, whose expression is necessary and sufficient to recover synaptic vesicle recycling, neuromuscular junction growth, and locomotor function in TDP-43-deficient motoneurons. Moreover, Rab4 activity promotes the presynaptic recruitment of futsch/MAP1B, a microtubule-associated protein also regulated by TDP-43, which autonomously supports synaptic growth and vesicle turnover. Together, these findings define a TDP-43/Rab4/futsch/MAP1B regulatory axis that couples endosomal dynamics to cytoskeletal assembly. Furthermore, this functionally coherent module provides a mechanistic basis for understanding how synaptic vulnerability is amplified in disease and offers a framework to identify key compensatory targets capable of sustaining neuronal function in the absence of TDP-43. Full article

Inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic immune-mediated disorders characterized by mucosal injury, cycles of inflammation and repair, and tissue damage. Persistent inflammation accelerates epithelial turnover, generates oxidative and replication stress, and remodels the stromal niche, contributing to the risk of colorectal cancer (CRC). Systematic dysplasia surveillance remains essential. Cellular senescence has emerged as a unifying mechanism linking inflammation, impaired epithelial repair, fibrosis, and neoplasia. In UC, p16/p21 upregulation, telomere erosion, and loss of lamin B1 accumulate and adopt a senescence-associated secretory phenotype (SASP) that perpetuates barrier dysfunction. In CD, senescence within stem and stromal compartments limits regeneration, promotes pro-fibrotic remodeling, and sustains cycles of injury and repair via chronic SASP signaling. IBD prevalence continues to rise from environmental factors, dietary changes, antibiotic exposures, and gut microbiota alterations. Pathogenesis integrates genetic factors (e.g., NOD2, IL23R, HLA, and ATG16L1 mutations), environmental modifiers, dysbiosis characterized by loss of short-chain fatty-acid-producing Gram-positive bacteria and expansion of Proteobacteria, and a dysregulated immune system. Therapeutic strategies have shifted toward targeted biologics and small molecules to promote mucosal healing. In this review, we recapitulate the mechanistic axes of inflammation, oxidative stress, and senescence in IBD and then critically evaluate emerging targeted therapies. Topics include anti-TNFα, integrin blockade, IL-12/23 and IL-23 inhibition, JAK inhibitors, S1P receptor modulators, microRNA modulation, senomorphics, mesenchymal cell therapy, and microbiome interventions. We endorse biomarker-guided therapy and propose future directions to break the SASP-driven inflammatory loop and mitigate long-term carcinogenic risk. Full article

Pluripotent stem cells (PSCs) exhibit remarkable self-renewal capacity and differentiation potential, necessitating tight regulation of gene expression at both transcriptional and post-transcriptional levels. Among post-transcriptional mechanisms, RNA turnover and degradation together play pivotal roles in maintaining transcriptome homeostasis and controlling RNA stability. RNA degradation plays a pivotal role in determining transcript stability for both messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs), thereby influencing cell identity and fate transitions. The core RNA decay machinery, which includes exonucleases, decapping complexes, RNA helicases, and the RNA exosome, ensures timely and selective decay of transcripts. In addition, RNA modifications such as 5′ capping and N6-methyladenosine (m⁶A) further modulate RNA stability, contributing to the fine-tuning of gene regulatory networks essential for maintaining PSC states. Recent single-cell and multi-omics studies have revealed that RNA degradation exhibits heterogeneous and dynamic kinetics during cell fate transitions, highlighting its role in preserving transcriptome homeostasis. Conversely, disruption of RNA decay pathways has been implicated in developmental defects and disease, underscoring their potential as therapeutic targets. Collectively, RNA degradation emerges as a central regulator of PSC biology, integrating the decay of both mRNAs and ncRNAs to orchestrate pluripotency maintenance, lineage commitment, and disease susceptibility. Full article

Abdominal aortic aneurysms (AAAs) are progressive, life-threatening vascular disorders characterized by focal dilation of the abdominal aorta due to chronic weakening of the arterial wall. The condition often remains asymptomatic until rupture, which carries mortality rates exceeding 70–85%. Among the various etiological theories of AAA development, degradation of the extracellular matrix (ECM) has emerged as the most widely accepted paradigm, with the breakdown of elastin representing a central and irreversible hallmark event. Elastin, a highly cross-linked and durable structural protein, provides elasticity and recoil to the aortic wall. In human AAA specimens, reduced elastin content, impaired cross-linking, and extensive fiber fragmentation are consistently observed, while experimental studies across multiple animal models confirm that elastin degradation directly correlates with aneurysm initiation, expansion, and rupture risk. Elastin loss is driven by a complex interplay of proteolytic enzymes coupled with inflammatory cell infiltration and oxidative stress. Furthermore, elastin-derived peptides perpetuate immune cell recruitment and matrix degradation, creating a vicious cycle of wall injury. Genetic and epigenetic factors, including variants in ECM regulators and dysregulation of non-coding RNAs, further modulate elastin homeostasis in AAA pathobiology. Clinically, biomarkers of elastin turnover and elastin-targeted molecular imaging techniques are emerging as tools for risk stratification. Therapeutically, novel strategies aimed at stabilizing elastin fibers, enhancing cross-linking, or delivering drugs directly to sites of elastin damage have shown promise in preclinical models and early translational studies. In parallel, regenerative approaches employing stem cells, exosomes, and bioengineered elastin scaffolds are under development to restore structural integrity. Collectively, these advances underscore the pivotal roles of elastin not only as a structural determinant of aneurysm development but also as a diagnostic and therapeutic target. This review summarizes and integrates recent discoveries on elastin biology in AAA, with a particular emphasis on molecular mechanisms of elastin degradation and the translational potential of elastin-centered interventions for the prevention and treatment of AAA. Full article

Cid1 protein is a crucial component in the RNA interference pathway and abnormal nuclear RNA turnover processes, primarily responsible for adding uridine to the 3′ end of RNA. Cid1 exhibits selective polymerization of UTP over other nucleoside triphosphates. To explore the mechanism of this selectivity, five systems: free-Cid1, Cid1-ATP, Cid1-UTP, Cid1-CTP, and Cid1-GTP with 500 ns Gaussian accelerated molecular dynamics (GaMD) simulations were performed to investigate conformational changes and binding affinities between substrates and Cid1. The results showed that UTP formed stronger and more numerous non-covalent interactions with Cid1 compared to the other three substrates. The Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) binding energy analysis revealed a substrate preference for Cid1 polymerase in the order of UTP, followed by ATP, CTP, and GTP. These findings provide theoretical insights into the substrate selectivity mechanism of Cid1 and provide theoretical clues for the design and modification of Cid1 polymerase. Full article

Salinity is a pivotal environmental factor that governs crustacean survival and development through its regulatory effects on key physiological processes, including osmoregulation and metabolic homeostasis. In the mud crab Scylla paramamosain, salinity tolerance of the megalopa plays an important role in larval survival rates and aquaculture yield. Here, we employed a combined transcriptomic and proteomic strategy to comprehensively dissect the molecular adaptive mechanisms of S. paramamosain megalopa exposed to acute and prolonged low-salinity stress (8‰) compared to control condition (17‰). Illumina-based transcriptome sequencing generated 81.71 Gb of high-quality clean data, which were assembled into 42,210 unigenes. LC-MS/MS-based proteomic profiling identified 51,390 unique peptides, corresponding to 5909 confidently quantified proteins. Transcriptomic profiling identified 2627 differentially expressed genes (DEGs) under acute low-salinity stress, comprising 1332 upregulated and 1295 downregulated genes compared to the control group. In contrast, a total of 733 DEGs were identified under prolonged low-salinity exposure, including 390 upregulated and 343 downregulated genes. Parallel proteomic analysis identified 199 differentially expressed proteins (DEPs) in the acute stress group, with 105 upregulated and 94 downregulated relative to the control group. Under prolonged stress, 206 DEPs were detected, including 124 upregulated and 82 downregulated proteins compared to the control group. Significant GO term and KEGG pathway enrichments contained metal ion binding, oxidoreductase activity, nucleus, apoptotic process, innate immune response, and amino acid metabolism, suggesting that megalopa employ coordinated regulatory mechanisms involving metabolic reprogramming, immunity system modulation, ion homeostasis maintenance and cell cycle regulation to adapt to hypoosmotic stress. Integrated multi-omics analysis identified 17 genes displaying significant concordant differential expression at both mRNA and protein levels during acute hypoosmotic stress, versus only 5 gene-protein pairs during prolonged stress exposure, indicating extensive post-transcriptional regulation and protein turnover mechanisms in sustained hypoosmotic condition. To the best of our knowledge, this study established the first integrative transcriptome-proteome framework elucidating hypoosmotic adaptation (8‰) mechanisms in S. paramamosain megalopa. The identified molecular signatures offer actionable targets for selective breeding of salinity-tolerant strains and precision management of megalopa culture under suboptimal salinity condition, while fundamentally advancing our mechanistic understanding of osmoregulatory plasticity across decapod crustaceans. Full article

Drought-tolerant cactus Opuntia stricta sustains livestock in Brazil’s semi-arid Northeast but suffers yield losses from the armored scale insect Diaspis echinocacti. Symbiotic bacteria are thought to underpin scale fitness; however, their response to pest pressure remains unexplored. We characterized the bacterial communities of D. echinocacti collected from cladodes displaying low, intermediate, and high infestation (n = 3 replicates per level) using 16S-rRNA amplicon sequencing, processed with nf-core/ampliseq. Shannon diversity declined from low to high density, and Bray–Curtis ordination suggested compositional shifts, although group differences were not significant (Kruskal–Wallis and PERMANOVA, p > 0.05). The obligate endosymbiont “Candidatus Uzinura” dominated all samples (>85% relative abundance) irrespective of density, indicating a resilient core microbiome. PICRUSt2 predicted a contraction of metabolic breadth at higher infestations, with convergence on energy- and amino acid biosynthesis pathways. Taken together, increasing pest density was associated with modest loss of diversity and functional streamlining, rather than wholesale turnover. These baseline data can guide future work on microbiome-based strategies to complement existing scale-insect control in dryland cactus systems. Full article

Transfer RNA-derived small RNAs (tDRs) are increasingly being recognized as versatile regulators, yet their physiological landscape remains poorly charted. We analyzed tDR expression in seven adult mouse tissues to explore tissue-specific tDR enrichment using a tDR-optimized library preparation methodology. We catalogued 26,901 unique nuclear tDRs (ntDRs) and 5114 mitochondrial tDRs (mtDRs). Clustering analysis segregated the tissues, with the spleen and lungs forming a distinct immune cluster. Tissue-versus-all and pairwise differential analysis showed the spleen harboring unique ntDRs and mtDRs. Tissue-enriched tDRs arose from specific isoacceptor and isodecoder tRNAs, independent of mature tRNA abundance, suggesting selective biogenesis rather than bulk turnover. G-quadruplex prediction revealed a pronounced enrichment of potentially quadruplex-forming ntDRs in the kidneys, heart, and spleen, predominantly derived from i-tRFs and tRF3 fragments, suggesting structure-dependent functions in immune regulation. We also benchmarked our library strategy against the PANDORA-seq method. Despite comparable or lower sequencing depth, our method detected ~3–10-fold more unique ntDRs and we observed a clearer representation of tRF-3 fragments and greater isotype diversity. Our tissue atlas and improved tDR sequencing method reveal extensive tissue-specific heterogeneity in tDR biogenesis, sequencing, and structure, providing a framework for understanding the context-dependent regulatory roles of tDRs. Full article