Search Results (3,439)

Accumulation of stem non-structural carbohydrates (NSC) at heading is crucial for mitigating grain-setting defects in large-panicle rice. While traditional panicle nitrogen fertilizer application at the emergence of the fourth leaf from the flag leaf stage (TL4) may weaken stem sink strength, delaying application to the emergence of the third leaf from the flag leaf stage (TL3) significantly enhances NSC accumulation. This study aimed to elucidate the molecular mechanisms through which TL3 remodels stem sink strength to promote NSC storage. Using two large-panicle rice varieties (Huiliangyou 280 and Yangliangyou 228), we compared stem NSC dynamics under TL4 and TL3 treatments and integrated sugar-related metabolite profiling with transcriptome analysis during the critical NSC accumulation phase. The results showed that TL3 treatment significantly increased stem NSC content and NSC per spikelet at heading, leading to a higher percentage of filled grains. The period from 5 days before heading (DBH) to heading showed the highest NSC accumulation rate. At the molecular level, TL3 treatment specifically up-regulated eight key genes in the sucrose–starch metabolism pathway, increasing the activities of sucrose phosphate synthase, sucrose synthase, and ADP–glucose pyrophosphorylase, and thereby promoting the accumulation of sucrose, trehalose, and D-fructose. In summary, delaying panicle nitrogen application to TL3 enhances stem NSC storage by remodeling sink strength via coordinated regulation of the sucrose–starch metabolic network. Full article

Multiple myeloma (MM) is a clonal plasma cell neoplasm characterized by autonomous immunoglobulin overproduction. Despite associations between serum metabolites and MM, causal mechanisms remain unclear. Here, we employed bidirectional Mendelian randomization (MR) using 452 serum metabolites to elucidate causal associations with MM risk. The inverse variance-weighted (IVW) method was prioritized, complemented by MR-Egger and weighted median (WM) analyses to address horizontal pleiotropy. Sensitivity analyses—including Cochran’s Q test, MR-Egger intercept evaluation, and leave-one-out (LOO) robustness checks—confirmed result stability. Pathway enrichment was performed using MetaboAnalyst 6.0. RNA-seq data were integrated to identify transcriptional regulators and signaling pathways mediating serum metabolite-driven MM. Among 21 metabolites significantly associated with MM, 8 exhibited protective inverse correlations, while 13 showed risk-enhancing effects. Sensitivity analyses further confirmed the validity of the observed relationships, while bidirectional MR confirmed no reverse causality. Pathway enrichment highlighted valine/leucine/isoleucine biosynthesis and biotin metabolism as pivotal pathways. Integrating transcriptomic data revealed 11 overlapping genes enriched in metal ion transmembrane transporter activity and glycosaminoglycan biosynthesis—chondroitin sulfate/dermatan sulfate. This study established a causal relationship between specific serum metabolites and MM and revealed that key genes may affect the development of MM through metabolic-epigenetic crosstalk, providing preliminary insights into potential therapeutic targets. Full article

Primary cutaneous lymphomas (PCLs) are a heterogeneous group of extranodal T- and B-cell neoplasms confined to the skin at diagnosis, characterised by distinct biological drivers, clinical behaviour, and therapeutic challenges compared with systemic lymphomas. Over the past decade, advances in genomic profiling, single-cell and spatial transcriptomics, and tumour microenvironment analysis have substantially refined the understanding of PCL pathogenesis, highlighting immune evasion, clonal heterogeneity, and compartment-specific disease dynamics as key determinants of outcome and treatment response. These insights have coincided with a rapidly evolving therapeutic landscape that includes immunomodulatory agents, targeted therapies, and ADCs, while also exposing persistent limitations related to diagnostic delay, response heterogeneity, resistance, and lack of validated predictive biomarkers. In this review, we provide a dermatology-focused synthesis of primary cutaneous lymphomas, integrating contemporary classification and clinicopathologic features with molecular pathogenesis and tumour microenvironmental insights of direct clinical relevance. We discuss current diagnostic and staging approaches, critically appraise established and emerging therapeutic strategies in cutaneous T- and B-cell lymphomas, and highlight unresolved clinical challenges and unmet needs, including biomarker integration, longitudinal disease monitoring, and translation of molecular advances into routine practice. Full article

Renal fibrosis (RF) represents a major pathological outcome of chronic kidney disease, currently accompanied by extremely limited therapeutic strategies. To decipher key cellular and molecular drivers, we integrated single-cell and bulk transcriptomic profiles for comprehensive analysis. Based on the RF-related single-cell and bulk transcriptomic data, key cell subtypes were identified through Scissor analysis, custom signature matrix construction via CIBERSORTx, and Weighted Gene Co-Expression Network Analysis (WGCNA). Subsequently, key subtype-related biomarkers were identified through the expression analysis, and functional enrichment analysis for biomarkers was conducted to elucidate the potential mechanisms by which biomarkers regulate RF. Through comprehensive profiling, thick ascending limb (TAL) cells were predominant and displayed marked heterogeneity in renal fibrosis (RF), with cortical TAL (CTAL) and adaptive TAL (aTAL) identified as principal subtypes. A set of candidate biomarkers was identified. Quantitative polymerase chain reaction (qPCR) validation in mouse models confirmed aberrant expression of these biomarkers, with STAT1 and PARP8 upregulated and HS6ST2, PTGER3, and TMEM207 downregulated in RF. Furthermore, functional enrichment analyses indicated that these biomarkers were associated with pathways underlying metabolic reprogramming and immune perturbation. Our study implicates CTAL and aTAL as central cellular players in RF and identifies their associated biomarkers. These experimentally validated biomarkers provide novel targets and repurposing opportunities for RF therapeutic intervention. Full article

Marbling, or intramuscular fat (IMF), is a primary determinant of high-quality beef, defining key sensory attributes and nutritional value. Yunling (YL) cattle, an indigenous breed from Yunnan, China, are renowned for their superior marbling, yet the underlying molecular mechanisms remain unclear. This study employed an integrated transcriptomic, lipidomic, and amino acid metabolomic approach to systematically compare the multi-omics profiles of the longissimus dorsi muscle among YL, Angus (AGS), and Simmental (XMTE) cattle. Transcriptome analysis identified 2053 and 2156 differentially expressed genes (DEGs) in XMTE vs. YL and AGS vs. YL, respectively. These DEGs were primarily enriched in the PI3K-Akt and MAPK signaling pathways, as well as oxidative phosphorylation. Lipidomic analysis revealed a distinct lipid profile in YL cattle, identifying 27 characteristic lipid molecules (e.g., SM(d20:0/24:1), DG(16:0/18:1(11Z)/0:0)) compared to XMTE and 17 differential lipids compared to AGS. The amino acid metabolome showed that Beta-Alanine and L-Aspartic acid levels in YL were 42.6% and 54.8% lower than in XMTE, respectively (p < 0.01), and levels of several functional amino acids were significantly reduced compared to AGS. Weighted Gene Co-expression Network Analysis (WGCNA) constructed a gene-metabolite network, identifying key modules strongly correlated with lipid and amino acid metabolism (|r| > 0.6). Within these modules, energy metabolism-related genes such as NDUFB1, COX7C, and IDH3B, along with signal transduction genes including ITGB3, PDGFRA, and FN1, were found to synergistically regulate marbling formation in YL cattle. This study systematically elucidates the molecular mechanisms underlying both marbling formation and the nutritional characteristics of meat in Yunling cattle. This provides a theoretical foundation for genetic improvement and offers potential molecular targets to enhance both marbling and overall meat quality in other indigenous cattle breeds worldwide. Full article

Aluminum chloride (AlCl₃), a widely used inorganic polymeric coagulant in everyday products and industrial materials, has been associated with male reproductive toxicity, though its molecular mechanisms remain poorly understood. To investigate the complex molecular mechanisms underlying GC-1spg cells’ responses to AlCl₃ exposure, transcriptome and small RNA (sRNA) sequencing analyses were performed. Transcriptome sequencing identified 1168 differentially expressed genes (DEGs), while sRNA sequencing detected 65 differentially expressed microRNAs (DEMs). An mRNA–miRNA regulatory network was established, and functional enrichment analysis showed that its target genes were significantly associated with multiple signaling pathways, particularly the p53 pathway. Further validation via Western blot and Hoechst 33342 staining assays confirmed that GC-1spg cells underwent apoptosis upon AlCl₃ exposure via the p53 signaling pathway. Among the identified DEMs, mmu-miR-503-5p was found to enhance GC-1spg cells’ tolerance to AlCl₃-induced stress. Moreover, dual-luciferase reporter assays and RT-qPCR confirmed that mmu-miR-503-5p directly binds to the Islr gene, which plays a role in modulating GC-1spg cell tolerance to AlCl₃-induced stress. These findings provide critical insights into the molecular mechanisms governing GC-1spg cells’ responses to AlCl₃ exposure. Full article

MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression and play important roles in plant development and reproduction. Liriodendron chinense, a representative woody species of Magnoliaceae, produces a large quantity of pollen but exhibits low natural seed set. Despite numerous studies on factors influencing its low seed production, the molecular mechanisms underlying this reproductive limitation remain poorly understood. Here, we performed small RNA sequencing and transcriptome analyses across five tissues of L. chinense, including leaf, calyx, petal, pistil, and pollen. Genome-wide identification yielded 688 miRNAs, comprising both conserved and species-specific members. Expression-based clustering revealed that miRNAs are organized into distinct, tissue-associated modules rather than being uniformly expressed across organs. Among these, a pollen-enriched miRNA module was clearly separated from those associated with leaves and other floral tissues. By integrating sRNA-seq and RNA-seq data, we identified miRNA–target pairs displaying anticorrelated expression patterns, providing expression-level support for miRNA mediated regulation. In pollen, two complementary regulatory modes were observed: low-abundance miRNAs associated with highly expressed target genes, and highly expressed miRNAs associated with repressed targets. The predicted targets of pollen-associated miRNAs were enriched in biological processes central to pollen development, including signal transduction, polarity establishment, vesicle trafficking, and cell wall biogenesis. Overall, this study provides a comprehensive, tissue-resolved view of miRNA expression and pollen-associated miRNA–target relationships in L. chinense, offering candidate regulatory modules for future functional studies of pollen development. Full article

MADS-box transcription factors are key regulators of plant development and environmental responses. Here, we performed an integrated phylogenomic and expression analysis of the MADS-box gene family in Capsicum annuum, identifying 97 members that fall into 52 Type I and 45 Type II genes. Comparative phylogeny, exon–intron organization, conserved motifs, and chromosomal mapping allowed classification into 15 subfamilies. Gene duplication analysis revealed that segmental duplication has been a major driver of family expansion. Expression profiling across multiple tissues, together with promoter cis-element prediction and stress-responsive transcriptome data, demonstrated that Type II genes exhibit broad and dynamic expression patterns, particularly under ABA treatment and temperature stress. A key finding of this study is the complete absence of the Mβ lineage, a Type I subfamily typically associated with gametophyte and endosperm development in other angiosperms. No Mβ-like sequences were detected in the pepper genome, and Type I genes overall showed extremely low expression, suggesting that the Mβ lineage has undergone lineage-specific evolutionary loss and that its functions may be compensated by other Type I members or by expanded Type II regulatory modules. Together, this study provides the first evidence for the evolutionary disappearance of the Mβ subfamily in Capsicum and offers a comprehensive resource for dissecting the developmental and stress-responsive roles of MADS-box genes in pepper. Full article

Extrachromosomal circular DNA (eccDNA) has emerged as a pivotal contributor to cancer progression, facilitating oncogene amplification, dysregulated gene expression, and tumor heterogeneity. Despite its significance in cancer, the interplay between eccDNA and key epigenetic regulators such as EZH2 remains largely unexplored. In this study, we systematically investigate the correlation between Tazemetostat, a highly selective EZH2 inhibitor, and alterations in the eccDNA landscape and transcriptional programs in ovarian cancer. Through integrated profiling using Circle-seq and RNA sequencing, we demonstrate that EZH2 inhibition is associated with markedly reprogrammed eccDNA dynamics. Furthermore, multi-omics integration identified that 67 genes exhibited concordant changes in both eccDNA abundance and transcript expression. Subsequent analyses also pinpointed 11 genes as putative effectors of drug response. Notably, spatial single-cell transcriptomics identified SFRP1 as the most consistently reactivated tumor suppressor across eccDNA, bulk expression, and spatial datasets, based on predefined statistical and biological criteria, by Tazemetostat. Moreover, SFRP1 was one of the genes that varied the most within cancer-associated fibroblast populations, exhibiting distinct spatial expression patterns. Taken together, this study establishes the first potential evidence that EZH2 inhibition may reprogram eccDNA dynamics to potentially restore SFRP1 tumor suppressor expression in ovarian cancer. By integrating multi-omics and spatial single-cell transcriptomics, we uncovered a novel epigenetic–eccDNA axis that may contribute to oncogenic plasticity and therapeutic resistance. This could result in a paradigm shift in targeting eccDNA-driven malignancies. Full article

Fibromyalgia is a complex chronic pain condition characterized by pervasive pain, persistent fatigue, and cognitive disturbances. Despite advances in understanding its neurobiological mechanisms, diagnosis largely relies on subjective symptom assessment and exclusion criteria, contributing to underdiagnosis and treatment delays. Recent research has increasingly focused on identifying objective biomarkers and leveraging digital phenotyping to improve diagnostic precision. Promising biomarkers include neuroimaging indicators of altered pain processing, neuroinflammatory signatures in cerebrospinal fluid and blood, and dysregulated neuroendocrine and autonomic patterns. In addition, metabolomics and transcriptomics have revealed molecular profiles associated with fibromyalgia pathophysiology. Concurrently, digital health tools (e.g., wearable sensors, ecological momentary assessment, and machine learning-based symptom clustering) offer opportunities for continuous, real-world data collection and individualized disease characterization. This body of work suggests that integrating biological and digital metrics could enable a transition from subjective to objective data-driven fibromyalgia classification, facilitating earlier diagnosis and improved therapeutic outcomes. Full article

Cytoplasmic male sterility (CMS) provides a natural model for studying nuclear–cytoplasmic interactions, although the details of nuclear–cytoplasmic communication remain poorly understood. In this study, transcriptomic and metabolomic data were integrated to elucidate the molecular and metabolic regulatory networks underlying stamen developmental defects in the tobacco CMS K326 (Nicotiana tabacum). Disrupted energy metabolism, auxin pathways, and floral development gene expression were identified in CMS K326. Metabolites such as glucose-6-phosphate, fructose-6-phosphate, and oxalosuccinic acid decreased, while an accumulation of succinate was observed and auxin IAA was deficient. Our study revealed that disrupted nuclear–cytoplasmic interactions in CMS K326 are associated with concurrent disruptions in early auxin homeostasis and energy metabolism, which collectively lead to the disturbance of the stamen development program. This study provides multiomics-level evidence for understanding stamen identity defects in CMS. Full article

Thyroid hormones profoundly modulate hepatic fatty acid and cholesterol synthesis and turnover. Although nonalcoholic fatty liver disease (NAFLD) shows epidemiological links to hypothyroidism, the genetic substrates of this relationship remain unresolved. Integrating large-scale genome-wide association studies with single-cell transcriptomics, spatial transcriptomics, and single-cell chromatin accessibility via state-of-the-art computational approaches, we interrogated the association between NAFLD and hypothyroidism across organ systems, cellular expression landscapes, and molecular–genetic strata. We uncovered pronounced spatial specificity in genetic risk within the liver, prioritized hepatocytes as the principal shared cell type affected, and, leveraging spatial transcriptomics, advanced a dynamic spatiotemporal two-hit model. We further nominated MAGI3, RRNAD1, and PRCC as high-confidence candidate genes and pinpointed a key risk locus, rs926103. These findings deliver a dynamic, testable framework for the full pathophysiological continuum linking NAFLD and hypothyroidism and yield new targets and leads for precision intervention. Full article

Low temperature is a major abiotic stress that affects maize across its entire growth cycle, with the germination stage being particularly sensitive. To investigate the genetic basis of early-stage cold tolerance, we used quantitative trait locus mapping and identified ZmbHLH30 as a candidate gene regulating maize responses to low temperature. The ZmbHLH30 protein is localized in the cytoplasm of maize protoplasts, and ZmbHLH30 promoter drives β-glucuronidase (GUS) expression in Arabidopsis thaliana leaves. The promoter region of ZmbHLH30 contains multiple environmental stress-responsive elements, including motifs associated with cold and auxin responses. Overexpression of ZmbHLH30 significantly enhanced cold tolerance at the germination, bud, and seedling stages, with the strongest effect observed during germination, where the cold-tolerance D-value increased by 0.366 relative to the control. In contrast, CRISPR/Cas9 knockout lines showed a 0.399 decrease in D-value. Under cold stress, ZmbHLH30 expression was markedly induced in overexpression lines but suppressed in knockout lines. Integrated transcriptomic and metabolomic analyses further identified ZmbHLH30 as a key regulator of cold tolerance in maize. Full article

The Bactrian camel (Camelus bactrianus), with its unique physiological adaptations and immune characteristics, represents a highly valuable model for innate immunity research. However, a systematic dissection of its innate immune gene repertoire and the key functional drivers within its immune response remains limited. This study integrated CRISPR-Cas9 knockout screening with time-resolved transcriptomic profiling to systematically unveil the immune regulatory mechanisms in camel dermal fibroblasts challenged with the viral mimic poly(I:C) and the bacterial mimic LPS. The CRISPR screen successfully identified 59 key genes conferring a survival advantage under lethal pathogenic challenge. The gene sets required for resisting viral versus bacterial mimics were entirely distinct, revealing divergent genetic underpinnings. Transcriptomic analysis further delineated a dynamic reprogramming of gene expression, uncovering a shared core immune response program alongside significant stimulus-specific regulation. Integrative analysis pinpointed pivotal genes, such as HSP90AA1 in the antiviral process and CSF1 in the antibacterial process, which played critical roles at both the functional screening and transcriptional regulatory levels. These key genes exhibited dynamic and evolving co-expression networks across different time points, indicating their temporally specific regulatory roles throughout the immune response. By combining functional genomics and transcriptomics, this study provides the first systematic mapping of the innate immune landscape and its dynamic regulation in the Bactrian camel, not only deepening the understanding of camelid immunobiology but also offering a new framework and insights for evolutionary studies of immune adaptation mechanisms in mammals. Full article

Background: Three-finger toxins (3FTxs) are a major axis of functional diversification in advanced snake venoms, with canonical paralytic activity mediated through muscle-type nicotinic acetylcholine receptors (nAChRs) and a broader set of non-nicotinic targets. This review integrates evidence bearing on coevolution between 3FTxs and target receptors, spanning toxin origin, diversification, receptor evolution, and ecological context. Methods: The synthesis draws on comparative genomic and transcriptomic studies of 3FTx gene-family evolution, codon-model analyses of selection, structural characterisation of toxin–receptor interfaces, and functional assays (including receptor-mimicking peptide binding) that link sequence variation to binding and toxicity. Results: Across lineages, 3FTx diversification is repeatedly structured by strong constraint on the disulphide-rich scaffold with accelerated change concentrated in solvent-exposed loops, alongside birth–death dynamics and exon/segment-level innovation that expand binding specificity. On the receptor side, resistance-associated variation is most intensively characterised for the nAChR α₁ orthosteric site and includes convergent, mechanistically distinct solutions such as electrostatic repulsion and glycosylation-mediated steric interference. Within the predominantly elapid systems currently examined, integrative datasets indicate that prey-selective binding and geographically variable susceptibility can arise from modest substitutions at toxin–receptor interfaces, but they also reveal substantial taxonomic and target-specific biases. Conclusions: Current evidence supports adaptive diversification in both toxins and receptors, while broader evolutionary interpretations are limited by uneven sampling and the frequent lack of matched toxin and receptor variants analysed within a common evolutionary framework. Development of predictive models will require joint pipelines linking genomics, structure-informed evolutionary inference, scalable functional assays, and explicit ecological network context. Full article