Search Results (4,114)

Sea buckthorn is a vital woody oil species valued for its role in soil conservation and its bioactive seed oil, which is rich in unsaturated fatty acids and other compounds. However, low seed oil content and small seed size are the main bottlenecks restricting the development and utilization of sea buckthorn. In this study, we tested the seed oil content and seed size of 12 sea buckthorn cultivars and identified the key genes and transcription factors involved in seed development and lipid biosynthesis via the integration of UID RNA-seq (Unique Identifiers, UID), WGCNA (weighted gene co-expression network analysis) and qRT-PCR (quantitative real-time PCR) analysis. The results revealed five cultivars (CY02, CY11, CY201309, CY18, CY21) with significantly higher oil contents and five cultivars (CY10, CY201309, CY18, CY21, CY27) with significantly heavier seeds. A total of 10,873 genes were significantly differentially expressed between the S1 and S2 seed developmental stages of the 12 cultivars. WGCNA was used to identify five modules related to seed oil content and seed weight/size, and 417 candidate genes were screened from these modules. Among them, multiple hub genes and transcription factors were identified; for instance, ATP synthase, ATP synthase subunit D and Acyl carrier protein 1 were related to seed development; plastid–lipid-associated protein, acyltransferase-like protein, and glycerol-3-phosphate 2-O-acyltransferase 6 were involved in lipid biosynthesis; and transcription factors DOF1.2, BHLH137 and ERF4 were associated with seed enlargement and development. These findings provide crucial insights into the genetic regulation of seed traits in sea buckthorn, offering targets for future breeding efforts aimed at improving oil yield and quality. Full article

Ferroptosis is a distinct form of regulated cell death driven by iron-dependent lipid peroxidation participating in various diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a central regulator of cellular redox homeostasis and a key determinant of ferroptosis resistance. Nrf2 activates the expression of downstream antioxidant genes to protect cells from oxidative stress and ferroptosis. Consequently, precise regulation of Nrf2 expression is crucial. Recent studies have revealed that complex epigenetic mechanisms involving DNA methylation, histone modifications, and non-coding RNA networks regulate Nrf2 expression. DNA methylation usually suppresses while histone acetylation promotes Nrf2 expression. The influences of histone methylation on NFE2L2 are site- and methylation degree-dependent. m6A modification stabilizes NFE2L2 mRNA to promote Nrf2 expression and thereby inhibit ferroptosis. This article summarizes current understanding of the epigenetic mechanisms controlling Nrf2 expression and Nrf2-mediated ferroptosis pathways and their implications in disease models. The challenges associated with the epigenetic regulation of Nrf2 and future research directions are also discussed. A comprehensive understanding of this regulatory interplay could open new avenues for intervention in ferroptosis-related diseases by fine-tuning cellular redox balance through the epigenetic modulation of Nrf2. Full article

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a systemic ciliopathy resulting from loss-of-function mutations in the PKD1 and PKD2 genes, which encode polycystin-1 (PC1) and polycystin-2 (PC2), respectively. PC1 and PC2 regulate mechanosensation, calcium signaling, and key pathways controlling tubular epithelial structure and function. Loss of PC1/PC2 disrupts calcium homeostasis, elevates cAMP, and activates proliferative cascades such as PKA–B-Raf–MEK–ERK, mTOR, and Wnt, driving cystogenesis via epithelial proliferation, impaired apoptosis, fluid secretion, and fibrosis. Recent evidence also implicates novel signaling axes in ADPKD progression including, the Hippo pathway, where dysregulated YAP/TAZ activity enhances c-Myc-mediated proliferation; the stimulator of interferon genes (STING) pathway, which is activated by mitochondrial DNA release and linked to NF-κB-driven inflammation and fibrosis; and the TWEAK/Fn14 pathway, which mediates pro-inflammatory and pro-apoptotic responses via ERK and NF-κB activation in tubular cells. Mitochondrial dysfunction, oxidative stress, and maladaptive extracellular matrix remodeling further exacerbate disease progression. A refined understanding of ADPKD’s complex signaling networks provides a foundation for precision medicine and next-generation therapeutics. This review gathers recent molecular insights and highlights both established and emerging targets to guide targeted treatment strategies in ADPKD. Full article

Background/Objectives: Male infertility is a major health concern with a complex etiopathology, yet a substantial proportion of cases remain idiopathic. Mitochondrial dysfunction and non-coding RNA (ncRNA) deregulation have both been implicated in impaired spermatogenesis, but their interplay remains poorly understood. This study aimed to identify infertility-specific variants in ncRNAs that affect mitochondrial dynamics and homeostasis and to explore their roles. Methods: Whole-genome sequencing (WGS) was performed on genomic DNA samples from teratozoospermic, asthenozoospermic, oligozoospermic, and normozoospermic men. Variants uniquely present in infertile individuals and mapped to ncRNAs that affect mitochondrial dynamics were selected and prioritized using bioinformatics tools. An independent transcriptomic validation was conducted using RNA-sequencing data from testicular biopsies of men with non-obstructive azoospermia (NOA) to determine whether the ncRNAs harboring WGS-derived variants were transcriptionally altered. Results: We identified several infertility-specific variants located in lncRNAs known to interact with mitochondrial regulators, including GAS5, HOTAIR, PVT1, MEG3, and CDKN2B-AS1. Transcriptomic analysis confirmed significant deregulation of these lncRNAs in azoospermic testicular samples. Bioinformatic analysis also implicated the disruption of lncRNA–miRNA–mitochondria networks, potentially contributing to mitochondrial membrane potential loss, elevated reactive oxygen species (ROS) production, impaired mitophagy, and germ cell apoptosis. Conclusions: Our integrative genomic and transcriptomic analysis highlights lncRNA–mitochondrial gene interactions as a novel regulatory layer in male infertility, while the identified lncRNAs hold promise as biomarkers and therapeutic targets. However, future functional studies are warranted to elucidate their mechanistic roles and potential for clinical translation in reproductive medicine. Full article

Early blight, caused by the pathogen Alternaria solani, is a major fungal disease impacting potato production globally, with reported yield losses of up to 40% in susceptible varieties. As one of the most common diseases affecting potatoes, its incidence has been steadily increasing year after year. This study aimed to elucidate the molecular mechanisms underlying resistance to early blight by comparing gene expression profiles in resistant (B1) and susceptible (D30) potato seedlings. Transcriptome sequencing was conducted at three time points post-infection (3, 7, and 10 dpi) to identify differentially expressed genes (DEGs). Weighted Gene Co-expression Network Analysis (WGCNA) and pathway enrichment analyses were performed to explore resistance-associated pathways and hub genes. Over 11,537 DEGs were identified, with the highest number observed at 10 dpi. Genes such as LOC102603761 and LOC102573998 were significantly differentially expressed across multiple comparisons. In the resistant B1 variety, upregulated genes were enriched in plant–pathogen interaction, MAPK signaling, hormonal signaling, and secondary metabolite biosynthesis pathways, particularly flavonoid biosynthesis, which likely contributes to biochemical defense against A. solani. WGCNA identified 24 distinct modules, with hub transcription factors (e.g., WRKY33, MYB, and NAC) as key regulators of resistance. These findings highlight critical molecular pathways and candidate genes involved in early blight resistance, providing a foundation for further functional studies and breeding strategies to enhance potato resilience. Full article

Botryosphaeria dothidea is the causative agent of Chinese hickory trunk canker, which poses significant threat to the production of Chinese hickory (Carya cathayensis Sarg.). Previous studies reported that endophytic–pathogenic phase transition, also referred to as latent infection, plays an important role in the interaction of Botryosphaeria dothidea with various host plants, including Chinese hickory. However, the mechanism underlying this phase transition is not well understood. Here, we employed RNA-Seq to investigate transcriptional changes in B. dothidea during its phase transition upon interaction with Chinese hickory. A co-expression network was generated based on 6391 differentially expressed genes (DEGs) identified from different infection stages and temperature treatments. One co-expressed module was found that highly correlated with temperature treatments which simulated conditions of B. dothidea latent infection in the field. Subsequently, 53 hub genes were detected, and gene ontology (GO) enrichment analysis revealed three categories of enriched GO terms: transmembrane transport or activity, ion homeostasis or transport, and carbohydrate metabolism. One PacC transcriptional factor (BDLA_00001555, an ambient pH regulator), and one endo-β-1,3-glucanase (BDLA_00010249) were specifically upregulated under temperature treatments that corresponded with the activation stage of B. dothidea’s pathogenic state. The knockout mutant strain of BDLA_00001555 demonstrated defective capability upon the activation of the pathogenic state. This confirmed that BDLA_00001555, the PacC transcriptional factor, plays an important role in the latent infection phase of B. dothidea. Our findings provide insights into the pathogenic mechanism of Chinese hickory trunk canker disease. Full article

Soil salinization is a major constraint to global crop productivity, highlighting the need to identify salt tolerance genes and their molecular mechanisms. Here, we integrated mRNA and miRNA profile analyses to investigate the molecular basis of salt tolerance of an elite Brassica napus cultivar S268. Time-course RNA-seq analysis revealed dynamic transcriptional reprogramming under 215 mM NaCl stress, with 212 core genes significantly enriched in organic acid degradation and glyoxylate/dicarboxylate metabolism pathways. Combined with weighted gene co-expression network analysis (WGCNA) and RT-qPCR validation, five candidate genes (WRKY6, WRKY70, NHX1, AVP1, and NAC072) were identified as the regulators of salt tolerance in rapeseed. Haplotype analysis based on association mapping showed that NAC072, ABI5, and NHX1 exhibited two major haplotypes that were significantly associated with salt tolerance variation under salt stress in rapeseed. Integrated miRNA-mRNA analysis and RT-qPCR identified three regulatory miRNA-mRNA pairs (bna-miR160a/BnaA03.BAG1, novel-miR-126/BnaA08.TPS9, and novel-miR-70/BnaA07.AHA1) that might be involved in S268 salt tolerance. These results provide novel insights into the post-transcriptional regulation of salt tolerance in B. napus, offering potential targets for genetic improvement. Full article

SnRK kinases, central regulators of plant stress response, remain uncharacterized in Taxus—an ancient gymnosperm valued for paclitaxel production. This study aimed to identify the Taxus SnRK family and elucidate its functional roles. Specifically, we identified SnRK genes through genomic analysis and assessed tissue-specific expression via transcriptomics, while regulatory networks were deciphered using WGCNA. To overcome experimental constraints, a PEG-mediated protoplast transient expression system was developed using calli, followed by dual-luciferase assays. Consequently, 19 SnRK genes (2 SnRK1, 4 SnRK2, 13 SnRK3) were identified, with tissue-specific expression revealing TaSnRK1.2 upregulation under methyl jasmonate (MeJA) and in stress-resilient tissues (bark/root). Subsequently, WGCNA uncovered a bark/root-specific module containing TaSnRK1.2 with predicted TF interactions (TaGRAS/TaERF). Critically, homologous dual-luciferase assays demonstrated TaSnRK1.2 activates TaGRAS and TaERF promoters (4.34-fold and 3.11-fold induction, respectively). This study establishes the Taxus SnRK family and identifies TaSnRK1.2 as a hub integrating stress signals (e.g., MeJA) to modulate downstream TF networks, while the novel protoplast system enables future functional studies in this medicinal plant. Full article

Cucumbers (Cucumis sativus L.) are highly sensitive to cold, but grafting onto cold-tolerant rootstocks can enhance their low-temperature resilience. This study investigates the physiological and molecular mechanisms by which exogenous vitamin C (Vc) mitigates cold stress in grafted cucumber seedlings. Using cucumber ‘Chiyu 505’ as the scion and pumpkin ‘Chuangfan No.1’ as the rootstock, seedlings were grafted using the whip grafting method. In the third true leaf expansion stage, seedlings were foliar sprayed with Vc at concentrations of 50, 100, 150, and 200 mg L⁻¹. Three days after initial spraying, seedlings were subjected to cold stress (8 °C) for 3 days, with continued spraying. After that, morphological and physiological parameters were assessed. Results showed that 150 mg L⁻¹ Vc treatment was most impactive, significantly reducing the cold damage index while increasing the root-to-shoot ratio, root vitality, chlorophyll content, and activities of antioxidant enzymes (SOD, POD, CAT). Moreover, this treatment enhanced levels of soluble sugars, soluble proteins, and proline compared to control. However, 200 mg L⁻¹ treatment elevated malondialdehyde (MDA) content, indicating potential oxidative stress. For transcriptomic analysis, leaves from the 150 mg L⁻¹ Vc and CK treatments were sampled at 0, 1, 2, and 3 days of cold stress. Differential gene expression revealed that genes associated with photosynthesis (LHCA1), stress signal transduction (MYC2-1, MYC2-2, WRKY22, WRKY2), and antioxidant defense (SOD-1, SOD-2) were initially up-regulated and subsequently down-regulated, as validated by qRT-PCR. Overall, we found that the application of 150 mg L⁻¹ Vc enhanced cold tolerance in grafted cucumber seedlings by modulating gene expression networks related to photosynthesis, stress response, and the antioxidant defense system. This study provides a way for developing Vc biostimulants to enhance cold tolerance in grafted cucumbers, improving sustainable cultivation in low-temperature regions. Full article

Anthocyanins, a subclass of flavonoid pigments, impart vivid red, purple, and blue coloration to horticultural plants, playing essential roles in ornamental enhancement, stress resistance, and pollinator attraction. Recent studies have identified B-box (BBX) proteins as a critical class of transcription factors (TFs) involved in anthocyanin biosynthesis. Despite these advances, comprehensive reviews systematically addressing BBX proteins are urgently needed, especially given the complexity and diversity of their roles in regulating anthocyanin production. In this paper, we provide an in-depth overview of the fundamental structures, biological functions, and classification of BBX TFs, along with a detailed description of anthocyanin biosynthetic pathways and bioactivities. Furthermore, we emphasize the diverse molecular mechanisms through which BBX TFs regulate anthocyanin accumulation, including direct activation or repression of target genes, indirect modulation via interacting protein complexes, and co-regulation with other transcriptional regulators. Additionally, we summarize the known upstream regulatory signals and downstream target genes of BBX TFs, highlighting their significance in shaping anthocyanin biosynthesis pathways. Understanding these regulatory networks mediated by BBX proteins will not only advance fundamental horticultural science but also provide valuable insights for enhancing the aesthetic quality, nutritional benefits, and stress adaptability of horticultural crops. Full article

Powdery mildew (PM), caused by Sphaerotheca phaseoli, severely threatens mungbean (Vigna radiata) productivity and quality, yet the molecular basis of resistance remains poorly defined. This study employed transcriptome profiling to compare defense responses in a resistant genotype, SUPER5, and a susceptible variety, CN84-1, following pathogen infection. A total of 1755 differentially expressed genes (DEGs) were identified, with SUPER5 exhibiting strong upregulation of genes encoding pathogenesis-related (PR) proteins, disease resistance proteins, and key transcription factors. Notably, genes involved in phenylpropanoid and flavonoid biosynthesis, pathways associated with antimicrobial compound and lignin production, were markedly induced in SUPER5. In contrast, CN84-1 showed limited activation of defense genes and downregulation of essential regulators such as MYB14. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses highlighted the involvement of plant–pathogen interaction pathways, MAPK signaling, and reactive oxygen species (ROS) detoxification in the resistant response. Quantitative real-time PCR validated 11 candidate genes, including PAL3, PR2, GSO1, MLO12, and P21, which function in pathogen recognition, signaling, the biosynthesis of antimicrobial metabolites, the production of defense proteins, defense regulation, and the reinforcement of the cell wall. Co-expression network analysis revealed three major gene modules linked to flavonoid metabolism, chitinase activity, and responses to both abiotic and biotic stresses. These findings offer valuable molecular insights for breeding PM-resistant mungbean varieties. Full article

Background: The candidate therapeutic peptide TnP demonstrates broad, system-level regulatory capacity, revealed through integrated network analysis from transcriptomic data in zebrafish. Our study primarily identifies TnP as a multifaceted modulator of drug metabolism, wound healing, proteolytic activity, and pigmentation pathways. Results: Transcriptomic profiling of TnP-treated larvae following tail fin amputation revealed 558 differentially expressed genes (DEGs), categorized into four functional networks: (1) drug-metabolizing enzymes (cyp3a65, cyp1a) and transporters (SLC/ABC families), where TnP alters xenobiotic processing through Phase I/II modulation; (2) cellular trafficking and immune regulation, with upregulated myosin genes (myhb/mylz3) enhancing wound repair and tlr5-cdc42 signaling fine-tuning inflammation; (3) proteolytic cascades (c6ast4, prss1) coupled to autophagy (ulk1a, atg2a) and metabolic rewiring (g6pca.1-tg axis); and (4) melanogenesis-circadian networks (pmela/dct-fbxl3l) linked to ubiquitin-mediated protein turnover. Key findings highlight TnP’s unique coordination of rapid (protease activation) and sustained (metabolic adaptation) responses, enabled by short network path lengths (1.6–2.1 edges). Hub genes, such as nr1i2 (pxr), ppara, and bcl6aa/b, mediate crosstalk between these systems, while potential risks—including muscle hypercontractility (myhb overexpression) or cardiovascular effects (ace2-ppp3ccb)—underscore the need for targeted delivery. The zebrafish model validated TnP-conserved mechanisms with human relevance, particularly in drug metabolism and tissue repair. TnP’s ability to synchronize extracellular matrix remodeling, immune resolution, and metabolic homeostasis supports its development for the treatment of fibrosis, metabolic disorders, and inflammatory conditions. Conclusions: Future work should focus on optimizing tissue-specific delivery and assessing genetic variability to advance clinical translation. This system-level analysis positions TnP as a model example for next-generation multi-pathway therapeutics. Full article

Glioblastoma (GBM) is a highly aggressive and heterogeneous brain tumor. Glioma stem-like cells (GSCs) play a central role in tumor progression, therapeutic resistance, and recurrence. Although immune cells are known to shape the GBM microenvironment, the impact of antigen-presenting-cell (APC) signature genes on tumor-intrinsic phenotypes remains underexplored. We analyzed both bulk- and single-cell RNA sequencing datasets of GBM to investigate the association between APC gene expression and tumor-cell states, including stemness and metabolic reprogramming. Signature scores were computed using curated gene sets related to APC activity, KEGG metabolic pathways, and cancer hallmark pathways. Protein–protein interaction (PPI) networks were constructed to examine the links between immune regulators and metabolic programs. The high expression of APC-related genes, such as HLA-DRA, CD74, CD80, CD86, and CIITA, was associated with lower stemness signatures and enhanced inflammatory signaling. These APC-high states (mean difference = –0.43, adjusted p < 0.001) also showed a shift in metabolic activity, with decreased oxidative phosphorylation and increased lipid and steroid metabolism. This pattern suggests coordinated changes in immune activity and metabolic status. Furthermore, TNF-α and other inflammatory markers were more highly expressed in the less stem-like tumor cells, indicating a possible role of inflammation in promoting differentiation. Our findings revealed that elevated APC gene signatures are associated with more differentiated and metabolically specialized GBM cell states. These transcriptional features may also reflect greater immunogenicity and inflammation sensitivity. The APC metabolic signature may serve as a useful biomarker to identify GBM subpopulations with reduced stemness and increased immune engagement, offering potential therapeutic implications. Full article

Ribosome biogenesis is a highly coordinated, multi-step process that assembles the ribosomal machinery responsible for translating mRNAs into proteins. It begins with the rate-limiting step of RNA polymerase I (Pol I) transcription of the 47S ribosomal RNA (rRNA) genes within a specialised nucleolar region in the nucleus, followed by rRNA processing, modification, and assembly with ribosomal proteins and the 5S rRNA produced by Pol III. The ribosomal subunits are then exported to the cytoplasm to form functional ribosomes. This process is tightly regulated by the PI3K/RAS/MYC oncogenic network, which is frequently deregulated in many cancers. As a result, ribosome synthesis, mRNA translation, and protein synthesis rates are increased. Growing evidence supports the notion that dysregulation of ribosome biogenesis and mRNA translation plays a pivotal role in the pathogenesis of cancer, positioning the ribosome as a promising therapeutic target. In this review, we summarise current understanding of dysregulated ribosome biogenesis and function in cancer, evaluate the clinical development of ribosome targeting therapies, and explore emerging targets for therapeutic intervention in this rapidly evolving field. Full article

Bone metastasis remains a significant cause of morbidity and diminished quality of life in patients with advanced breast, prostate, and lung cancers. Emerging research highlights the pivotal role of reversible epigenetic alterations, including DNA methylation, histone modifications, chromatin remodeling complex dysregulation, and non-coding RNA networks, in orchestrating each phase of skeletal colonization. Site-specific promoter hypermethylation of tumor suppressor genes such as HIN-1 and RASSF1A, alongside global DNA hypomethylation that activates metastasis-associated genes, contributes to cancer cell plasticity and facilitates epithelial-to-mesenchymal transition (EMT). Key histone modifiers, including KLF5, EZH2, and the demethylases KDM4/6, regulate osteoclastogenic signaling pathways and the transition between metastatic dormancy and reactivation. Simultaneously, SWI/SNF chromatin remodelers such as BRG1 and BRM reconfigure enhancer–promoter interactions that promote bone tropism. Non-coding RNAs, including miRNAs, lncRNAs, and circRNAs (e.g., miR-34a, NORAD, circIKBKB), circulate via exosomes to modulate the RANKL/OPG axis, thereby conditioning the bone microenvironment and fostering the formation of a pre-metastatic niche. These mechanistic insights have accelerated the development of epigenetic therapies. DNA methyltransferase inhibitors (e.g., decitabine, guadecitabine) have shown promise in attenuating osteoclast differentiation, while histone deacetylase inhibitors display context-dependent effects on tumor progression and bone remodeling. Inhibitors targeting EZH2, BET proteins, and KDM1A are now advancing through early-phase clinical trials, often in combination with bisphosphonates or immune checkpoint inhibitors. Moreover, novel approaches such as CRISPR/dCas9-based epigenome editing and RNA-targeted therapies offer locus-specific reprogramming potential. Together, these advances position epigenetic modulation as a promising axis in precision oncology aimed at interrupting the pathological crosstalk between tumor cells and the bone microenvironment. This review synthesizes current mechanistic understanding, evaluates the therapeutic landscape, and outlines the translational challenges ahead in leveraging epigenetic science to prevent and treat bone metastases. Full article