Search Results (31,446)

Background: Spinal cord injury (SCI) triggers secondary injury processes involving neuroinflammation and systemic immune remodeling. The endocannabinoid system (ECS) has been implicated in neuroimmune regulation, but its transcriptional relationship with immune remodeling and its translational relevance in human SCI blood remain incompletely defined. Methods: A cross-species discovery–validation–translation framework was applied using a rat spinal cord discovery cohort (GSE45006), an independent mouse validation cohort (GSE171441), and a human peripheral white blood cell cohort (GSE151371). Analyses included differential expression profiling, ECS-focused assessment, cross-species comparison, immune-cell signature scoring, ECS–immune correlation analysis, receiver operating characteristic (ROC) analysis, LASSO-based biomarker prioritization, network analysis, disease enrichment, drug–gene interaction querying, and transcription factor/microRNA regulatory annotation. Results: ECS-related transcriptional remodeling was identified across rodent and human datasets in a compartment-dependent manner. In human SCI blood, CNR2, PTGS2, and DAGLB were significantly altered and showed biomarker-prioritization potential. Human SCI blood also showed innate immune enrichment, adaptive immune depletion, and significant ECS–immune correlations. The integrated 28-gene SCI–ECS immune panel formed a functionally coherent protein–protein interaction (PPI) network enriched in immune-response pathways. Disease enrichment supported an immune/inflammatory pathological context, whereas DGIdb identified hypothesis-generating drug–gene relationships involving ECS-related targets. ChEA 2022 revealed nominal transcription factor annotations that did not survive multiple-testing correction, and miRNet identified database-derived miRNA regulators of panel genes. In a secondary sensitivity analysis, the combined ECS signature also retained discriminatory performance against non-CNS trauma controls, suggesting that the observed transcriptional pattern was not fully attributable to generalized trauma-related responses. Conclusions: This study proposes an ECS-associated immune remodeling signature in SCI with translational biomarker-prioritization and pharmacologic target-annotation context in human peripheral blood. These findings are exploratory and require prospective and functional validation. Full article

Anoplophora glabripennis is a destructive forest pest. Elaeagnus angustifolia attracts A. glabripennis for feeding and oviposition, but its gum encapsulates and kills the eggs, functioning as a dead-end trap tree. However, the olfactory mechanisms by which A. glabripennis recognizes E. angustifolia volatiles remain unclear. In this study, we analyzed the antennal transcriptome of female adult A. glabripennis exposed to E. angustifolia volatiles. Ten OBP genes were significantly up-regulated in response to the volatiles, including six Classic OBPs and four Minus-C OBPs (log₂ fold changes: 1.02–3.01). qRT-PCR showed AglaOBP1/2/3 were highly and specifically expressed in the antennae, suggesting key olfactory roles. Static molecular docking showed that all three OBPs bound 22 E. angustifolia volatiles, each displaying the highest affinity for (+)-Longifolene, with AglaOBP1 exhibiting the strongest binding. Nevertheless, 200 ns MD simulations revealed a shift: the AglaOBP3–(+)-Longifolene complex displayed the greatest structural stability, not AglaOBP1. MM/PBSA corrected the initial docking screen and confirmed that AglaOBP3 had the strongest thermodynamic binding affinity for (+)-Longifolene (ΔG_bind = −30.94 ± 2.57 kcal·mol⁻¹). This study provides novel molecular insights into the olfactory recognition of E. angustifolia volatiles in A. glabripennis, laying a foundation for future functional validation and sustainable pest management. Full article

Inflorescence degeneration in Areca catechu L. is characterized by growth arrest, tissue shrinkage and browning, ultimately compromising functional inflorescence formation and yield stability. To investigate its developmental window and regulatory basis, inflorescences from different leaf positions at the full-bloom stage were analyzed using anatomical observation, morphological measurements, carbohydrate and hormone assays, and RNA-seq-based transcriptomic analysis with qRT-PCR validation. Inflorescence degeneration was mainly concentrated in axillary inflorescences at the third and fourth leaf positions (BY3 and BY4). Compared with adjacent normal inflorescences, degenerated inflorescences showed reduced sucrose, starch and trehalose contents, increased ABA, JA and MeJA levels, and decreased cZR levels. Transcriptomic analysis revealed clear separation between degenerated and normal inflorescences, and differentially expressed genes were enriched in starch and sucrose metabolism, plant hormone signal transduction and transcriptional regulation. Co-expression network analysis identified modules associated with the degeneration window and key physiological traits, highlighting six candidate hub genes: AcAHP2, AcTIFY4B, AcTPS9-2, AcHXK2, AcWRKY3 and AcMPK1. These findings suggest that inflorescence degeneration is closely associated with carbon metabolic imbalance, hormone network remodeling and co-expression network reprogramming within a specific developmental window, providing a basis for future mechanistic studies and control strategies. Full article

Epitranscriptomic modifications, particularly RNA methylations, have emerged as regulators of gene expression, with their dysregulation acting as a key factor in tumorigenesis and metastatic progression. This review evaluates the therapeutic landscapes of N⁶-methyladenosine (m⁶A) and N¹-methyladenosine (m¹A) modifications in cancer. While the m⁶A machinery predominantly dictates mRNA turnover and stability, the m¹A network is uniquely positioned to drive translational reprogramming, allowing malignant cells to endure severe microenvironmental stress and evade cell death. Despite positional and chemical differences, these modifications exhibit profound epitranscriptomic crosstalk through shared regulatory proteins. Here, we comprehensively analyze current pharmacological strategies targeting the m⁶A axis, highlighting the transition from classical small-molecule inhibitors of regulatory proteins of these methylations, such as methyltransferase-like 3 (METTL3), fat mass and obesity-associated protein (FTO), and AlkB homolog 5 (ALKBH5), to the novel event-driven approach of proteolysis-targeting chimeras (PROTACs). Furthermore, we assess the emerging therapeutic potential of the m¹A regulatory machinery, positioning tRNA methyltransferase 6/61A (TRMT6/61A) writers and AlkB homolog 1 to 3 (ALKBH1-3) erasers as promising therapeutic targets. Finally, we discuss clinical successes and current translational obstacles, including off-target toxicity, pharmacokinetic limitations, and epitranscriptomic escape, emphasizing that site-specific modulation and smart precision therapies will dictate the future of oncology. Full article

A comprehensive analysis of the microcin J25 (MccJ25) biosynthetic gene cluster revealed a previously uncharacterized 96-base pair overlapping gene, designated mcjX. This gene features a +1 reading frame shift relative to the primary sequence and encodes a 31-amino acid peptide. Notably, 53 nucleotides overlap with the 3′ terminus of the structural gene mcjA. Such significant overlaps are rare features in the Escherichia coli genome, highlighting the hidden complexity of microbial operon architectures. In this study, we demonstrate that mcjX is actively translated. Functional assays, including green fluorescent protein reporter systems, suggest that McjX acts as a negative regulator of the mcjA promoter, modulating MccJ25 expression. This discovery represents the first report of a regulatory mechanism mediated by an overlapping gene within a lasso peptide operon, providing new perspectives on how microbial genomes fine-tune the production of antimicrobial peptides through compact genetic organization. Full article

The YABBY family consists of plant-specific transcription factors that regulate organ polarity and reproductive development. As a member of this family, CRABS CLAW (CRC) plays crucial roles, but its molecular mechanism in oilseed rape stigma development remains unclear. In this study, we identified YABBY genes in four Brassicaceae species. The results showed that CRC proteins are highly conserved in structure, but their cis-acting elements vary among species. To explore its function, we performed transcriptome sequencing on an oilseed rape CRC-deficient mutant (sd). The transcriptome data revealed multiple changes in the sd mutant. Specifically, brassinosteroid (BR) signaling factors were downregulated. Sugar transporters and auxin-related genes showed abnormal expression. Furthermore, pro-senescence and programmed cell death (PCD) genes were upregulated, whereas the classic senescence pathway remained unchanged. Based on these findings, we propose a potential mechanism. The loss of CRC disrupts BR signaling, sugar transport, and calcium homeostasis. This disruption triggers non-classic death of stigma papilla cells, which hinders pollen tube penetration and reduces seed set. Notably, increasing environmental humidity partially rescued the seed set, likely by delaying cell death. Although these transcriptomic insights warrant further experimental validation, this study provides valuable clues and genetic resources for future research on reproductive development in oilseed rape. Full article

Juvenile hormone (JH) analog insecticides are widely used in pest management because of their ability to disrupt insect growth and metamorphosis; however, the molecular mechanisms linking endocrine disruption to metabolic dysregulation remain incompletely understood. In addition to their established roles in diapause and developmental regulation, JH signaling pathways have also been implicated in carbohydrate and lipid metabolism. In the present study, we investigated the effects of two JH analogs, pyriproxyfen and hydroprene, on the migratory locust, Locusta migratoria, with particular emphasis on lipid metabolic regulation and the function of midgut-enriched fatty acid-binding protein gene (Mg-FABP). Bioassays were performed to evaluate insecticidal activity, and transcriptomic analyses were conducted to identify differentially expressed genes associated with endocrine signaling and lipid metabolism. Functional characterization of Mg-FABP was further performed using RNA interference (RNAi) and Oil Red O staining assays. In addition, the tertiary structure of LmMg-FABP was predicted using AlphaFold 3, and molecular docking analyses were carried out to investigate its interactions with fatty acid ligands. Both pyriproxyfen and hydroprene caused approximately 70% mortality in locust nymphs and induced significant transcriptional changes in pathways related to hormone signaling and lipid metabolism. Transcriptomic analysis revealed pronounced downregulation of Mg-FABP following JH analog exposure. RNAi-mediated silencing of Mg-FABP significantly reduced lipid droplet accumulation in the fat body, indicating that Mg-FABP plays an essential role in lipid transport and metabolic homeostasis in L. migratoria. Structural analyses further demonstrated that LmMg-FABP possesses a conserved tertiary structure highly similar to FABP homologs from other insect species. Molecular docking identified key amino acid residues involved in fatty acid binding and suggested that hydrophobic interactions are critical for ligand stabilization within the binding cavity. Collectively, our findings demonstrate that pyriproxyfen and hydroprene disrupt insect development not only through endocrine imbalance but also through perturbation of Mg-FABP-associated lipid metabolic pathways. This study provides new mechanistic insight into the coordinated interaction between hormonal signaling and lipid metabolism during JH analog exposure and identifies FABP-mediated lipid transport as a potential molecular target for the development of more selective insect growth regulators. Full article

Cardamine hupingshanensis (C. hupingshanensis) is an important dietary source of selenium for humans due to its remarkable capacity for selenium hyperaccumulation. As core components of the SCF (SKP1–Cullin–F-box) ubiquitin ligase complex, F-box proteins play vital roles in plant responses to environmental stress, such as salt and drought. However, information regarding the F-box gene family in C. hupingshanensis and its potential functions in regulating responses to abiotic stress remains limited. In this study, members of the F-box gene family in C. hupingshanensis were identified through sequence alignment. Comprehensive bioinformatic analyses, including analyses of physicochemical properties, phylogenetic relationships, subcellular localization, conserved motifs and domains, gene structure, chromosomal distribution, promoter cis-elements, and gene duplication events, were performed using TBtools and associated online resources. In particular, a total of 548 F-box genes were identified and classified into nine distinct groups based on phylogenetic analysis. Protein sequence analysis predicted 15 conserved motifs and 18 distinct domains across the identified F-box proteins. Promoter analysis suggested the presence of 32 different cis-elements that may be potentially associated with growth, development, hormone signaling, and abiotic stress responses. Furthermore, 283 collinear gene pairs were detected within the C. hupingshanensis genome, providing insights into the possible expansion of this gene family. Quantitative real-time PCR was employed to examine the tissue-specific expression levels of F-box genes in various organs, as well as their expression profiles in response to exogenous selenium, salt, osmotic stress, and abscisic acid treatment. The results indicated that 11 ChFBX genes responded to exogenous selenium, salt, osmotic stress, or abscisic acid. Notably, transgenic plants overexpressing ChFBX171 displayed heightened sensitivity to salt stress during seed germination. In conclusion, this study provides a comprehensive identification and characterization of 548 F-box genes in C. hupingshanensis and offers valuable insights into the potential role of ChFBX genes, particularly ChFBX171, in mediating responses to abiotic stress. Full article

N-acetylserotonin methyltransferase (ASMT) is among the key enzymes involved in the final steps of melatonin biosynthesis. Here, we have shown that inactivation of ASMT in A. thaliana results in reduced endogenous melatonin levels, modulating other plant hormone pathways and affecting stress-related responses. Transcriptomic analysis of the asmt-null mutant revealed that the differentially expressed genes were predominantly enriched in terms associated with auxin responses and signalling, as well as with abscisic acid (ABA)-mediated stress responses. In addition, the expression of genes involved in the ethylene, salicylic acid, jasmonic acid and brassinosteroid pathways was altered in the mutant. Assays of a β-glucuronidase (GUS) construct in which a fragment containing 1000 bp upstream of the ASMT start codon was fused to the GUS reporter gene confirmed that ASMT is involved in the responses to ABA, gibberellic and indole acetic acids, trans-zeatin, ethylene and epibrassinolide, which is consistent with the results of the in silico analysis of the ASMT promoter. Furthermore, the expression of a number of genes, such as SLG1, HIS1-3, AtAIRP1 and several LEA genes, whose transcriptional regulation is associated with water management and contributes to impaired tolerance to dehydration stress, was altered in the mutant. The pleiotropic effects of ASMT gene disruption facilitate the identification of new potential melatonin targets and provide insights into the specific mechanisms of melatonin action. Full article

MicroRNAs are important regulators of skeletal muscle development and regeneration; however, the molecular basis by which exercise-induced miRNAs preserve middle-aged muscle function remains to be elucidated. This study aimed to investigate how aerobic exercise delays skeletal muscle attenuation by reversing age-related miRNAs dysregulation in male mice. Twelve-month-old male C57BL/6J mice (MC) (n = 8/group) were randomly assigned to a sedentary control group (OC) or an aerobic exercise group (OE) (12 m/min, 40 min/session, three sessions/week, for 12 weeks). miRNA sequencing identified differentially expressed miRNAs (DEmiRNAs), followed by miRNA–mRNA network construction. The results demonstrated that aerobic exercise improved muscle strength and mass while attenuating early atrophy and fibrosis. Four atrophy-associated DEmiRNAs (miR-150-5p, miR-199a-5p, miR-3535, and miR-329-5p) were reversed after aerobic exercise intervention. GO and KEGG profiling demonstrated that target genes were predominantly involved in protein binding and the Wnt signaling pathway. miR-199a-5p and miR-150-5p, with the most predicted targets, were selected as candidate mechanistic contributors, and FZD4 was confirmed as a common downstream target. Further analysis confirmed that miR-199a-5p and miR-150-5p inhibition attenuated D-galactose-induced C2C12 myotube atrophy, reducing Atrogin-1 and increasing MyoD1, FZD4, and β-catenin expression. These findings suggest that the exercise-induced miR-150-5p/miR-199a-5p axis may alleviate muscle aging in middle age via the restoration of key proteins in Wnt signaling and contribute preliminary observational evidence relevant to the understanding of aerobic exercise intervention in sarcopenia. Full article

Inhibin, a water-soluble protein emitted by the gonads, plays a pivotal role in regulating the release of follicle-stimulating hormone (FSH) from the pituitary gland, which, in turn, influences follicular growth, gamete production, and the secretion of associated hormones. We performed high-throughput sequencing of the nanobody gene in the lymphocytes of Bactrian camels before and after inhibin α protein immunization followed by mass spectrometry analysis of specific antibodies to this protein in the serum following immunization to screen for inhibin α subunit-specific nanobodies. Seven inhibin α-specific nanobodies, namely Nb-1712, Nb-1971, Nb-2000, Nb-799, Nb-2004, Nb-1737, and Nb-338, were identified through high-throughput sequencing and mass spectrometry. Following the construction and expression of a prokaryotic expression vector, five of these nanobody proteins were successfully produced. These proteins demonstrated high affinity for inhibin α in the indirect enzyme-linked immunosorbent assay. Notably, nanobodies Nb-1737, Nb-1971, and Nb-2004 significantly downregulated Inha and upregulated Fshb gene expression, enhancing follicle-stimulating hormone secretion. In female mice, these three nanobodies promoted follicular development and led to a numerical increase in litter size (average ~10%, with Nb-2004 showing a 14.93% increase), although the differences were not statistically significant. These findings demonstrate their potential to regulate reproductive function. We identified 7 inhibin α subunit-specific nanobody genes from a Xinjiang Bactrian camel’s lymphocyte genome through high-throughput sequencing and mass spectrometry. We also compared their relative binding affinities and characterized their biological functions, thereby providing key theoretical guidance and technical support for increasing FSH levels. Full article

Background: Cell division plays a crucial role in plant growth and development. Cyclin-dependent kinase inhibitors (ICK/KRP) negatively regulate the cell cycle, thereby affecting cell elongation and organ development. This study aimed to systematically identify and characterize the ICK/KRP gene family in pepper, and to explore their roles in growth, development, and stress responses. Methods: Bioinformatics approaches were used for genome-wide identification, chromosomal localization, collinearity analysis, sequence characterization, promoter element prediction, and tissue-specific expression profiling of pepper ICK genes. Phylogenetic analysis was performed with homologs from Arabidopsis, tomato, maize, and rice. Quantitative real-time PCR and virus-induced gene silencing (VIGS) were applied to validate gene expression patterns and gene function, respectively. Subcellular localization assays were also conducted. Results: A total of six ICK genes were identified in pepper. They were classified into three subfamilies and distributed on different chromosomes, with one pair showing evidence of duplication. All ICK/KRPs contain the conserved Motif 1 (amino acid sequence: KIPTTREIEEFFATAEKQQQRRFIEKYNFDPVNEKPL) and were predicted to localize to the nucleus. Promoter analysis revealed cis-acting elements associated with plant development, stress responses, and hormone signaling. Expression pattern analysis indicated tissue-specific divergence and significant induction/repression under temperature stress. qRT-PCR results were consistent with transcriptome data, and expression differences were observed in materials with different stigma lengths. Subcellular localization confirmed that Caz03g38750.1 and Caz12g03790.1 proteins localize to both the nucleus and plasma membrane. Silencing of CazICK1 significantly repressed stigma elongation and altered stigma morphogenesis. Conclusions: The six pepper ICK/KRP genes display distinct diversity in distribution, structure and expression, and function in plant growth, development and stress adaptation. This work not only lays a solid basis for exploring the cell cycle regulatory network of pepper and contributes to relevant theoretical research, but it also identifies key gene resources for improving stigma traits. It has great potential for application in molecular breeding to promote high yield and efficient hybrid seed production in pepper. Full article

Endothelial dysfunction is an early event in the development of cardiovascular diseases and is characterized by impaired barrier function, inflammatory activation of endothelial cells (ECs), and alterations in lipid metabolism. In addition to typical (mononuclear) endothelial cells (TECs), multinucleated variant endothelial cells (MVECs) are present within the vascular wall; however, their functional role remains poorly understood. The aim of the present study was to investigate the molecular and functional characteristics of MVECs and their potential contribution to the development of endothelial dysfunction. Primary human umbilical vein endothelial cells (HUVECs) were used, and multinucleated cells were generated by polyethylene glycol-induced fusion. Cells were incubated under control conditions or exposed to low-density lipoproteins (LDL; 100 µg/mL, 24 h). A comprehensive analysis was performed, including transcriptomic and proteomic (secretome) profiling using gene set enrichment analysis (GSEA), as well as functional assays assessing transendothelial LDL transport, intracellular cholesterol accumulation, macrophage migration, and the expression and secretion of pro-inflammatory cytokines (IL-6, IL-8). MVECs exhibited pronounced differences compared to TECs. GSEA revealed reduced enrichment of pathways related to canonical nuclear factor kappa B (NF-κB) signaling and negative regulation of NF-κB transcription factor activity, actin cytoskeleton organization, focal adhesion assembly, basement membrane organization, and vesicle-mediated transport in MVECs relative to TECs, indicating impaired cytoskeletal integrity, altered cell–matrix interactions, dysregulated inflammatory signaling, and reduced vesicular trafficking activity. Functionally, MVECs demonstrated an increased capacity for cholesterol accumulation and enhanced transendothelial migration of macrophages. Notably, transendothelial LDL transport across the MVEC monolayer was not increased, suggesting a predominance of intracellular lipid accumulation. MVECs also exhibited a pronounced pro-inflammatory phenotype, characterized by elevated expression and secretion of IL-6 and IL-8. Taken together, these findings indicate that MVECs represent a functionally altered endothelial phenotype with impaired barrier function, dysregulated lipid metabolism, and enhanced inflammatory activity. Local accumulation of MVECs within the vascular wall may contribute to the formation of pro-atherogenic regions and play a role in the initiation and progression of endothelial dysfunction. Full article

Abiotic stresses severely restrict plant growth, development, and crop yield. Histone modification functions as a key epigenetic regulator in plant stress adaptation. This review systematically summarizes the major types of histone modifications (e.g., acetylation, methylation) and their catalytic enzyme systems. It clarifies the regulatory patterns of chromatin remodeling and gene expression under diverse abiotic stress conditions, like extreme temperature changes, persistent drought, elevated salinity, and heavy metal exposure, and reveals the crosstalk networks between histone modifications and ABA, CBF/DREB, and ROS signaling pathways. It also discusses the transgenerational inheritance of stress-induced histone modification variations and their molecular basis, and introduces the application of CRISPR/Cas9 and dCas9-based epigenetic editing in improving crop stress resistance. Currently, research on histone modification in plateau crops remains fragmented: studies mostly focus on single stress rather than combined multiple abiotic stresses, lack tissue-specific epigenetic regulatory maps for native plateau plants, and the field application of epigenetic breeding technologies is seriously insufficient. Considering the compound stresses, including low temperature, drought, salinization, and heavy metals, on the Qinghai–Tibet Plateau, this review identifies current research gaps, such as tissue specificity, multi-stress crosstalk, and field application, and proposes future directions, including multi-omics analysis, stress adaptation mechanisms of plateau plants, and precise epigenetic breeding. Overall, this review fills the research gap of systematic collation on histone-mediated stress tolerance epigenetics under plateau combined abiotic stresses, and provides a theoretical reference for epigenetic research on plant stress resistance and for the improvement of plateau crops. Full article

Pubertal initiation critically determines reproductive performance in female pigs. Histone H3 lysine 27 trimethylation (H3K27me3) has been implicated in ovarian development. However, its genome-wide regulatory landscape during the pubertal transition remains unexplored. Here, we obtained transcriptomes of GCs treated with the pharmacological H3K27me3 agonist GSK-J4 or H3K27me3 inhibitor EPZ005687. We found that H3K27me3 substantially remodels the transcriptomic landscape of porcine GCs, with differentially expressed genes significantly enriched in pathways governing cell proliferation and apoptosis. Mechanistically, H3K27me3 suppressed GC proliferation by downregulating the expression of PCNA and promoting apoptosis through upregulation of CASP3, thereby delaying pubertal initiation. Furthermore, genome-wide ChIP-seq analysis on porcine ovaries from pre-pubertal and in-pubertal gilts revealed higher H3K27me3 enrichment around transcription start sites in the In-puberty stage than in the Pre-puberty stage. Genes with promoters exhibiting reduced H3K27me3 occupancy during the pubertal transition were enriched in pathways related to sex differentiation and serine-type endopeptidase inhibitor activity. Notably, secretory leukocyte peptidase inhibitor (SLPI) was identified by ChIP-qPCR as a direct target repressed by H3K27me3. Functional validation demonstrated that SLPI promoted GC proliferation and inhibited GC apoptosis in vitro. Intraperitoneal injection of LV-Slpi or sh-Slpi into C57BL/6J mice showed that Slpi accelerated pubertal initiation of mice in vivo. Collectively, our findings confirmed that developmental stage-specific loss of H3K27me3 at the SLPI promoter derepressed SLPI transcription, which in turn promoted porcine GC proliferation, suppressed apoptosis, and facilitated pubertal initiation in mice. These results provided valuable insights into the epigenetic regulation of pubertal initiation in mammals. Full article