Search Results (1,982)

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

MicroRNA-211 (miR-211) is a versatile regulatory molecule that plays critical roles in cellular homeostasis and disease progression through the post-transcriptional regulation of gene expression. This review comprehensively examines miR-211’s multifaceted functions across various biological systems, highlighting its context-dependent activity as both a tumor suppressor and oncogene. In physiological contexts, miR-211 regulates cell cycle progression, metabolism, and differentiation through the modulation of key signaling pathways, including TGF-β/SMAD and PI3K/AKT. miR-211 participates in retinal development, bone physiology, and protection against renal ischemia–reperfusion injury. In pathological conditions, miR-211 expression is altered in various diseases, particularly cancer, where it may be a useful diagnostic and prognostic biomarker. Its stability in serum and differential expression in various cancer types make it a promising candidate for non-invasive diagnostics. The review also explores miR-211’s therapeutic potential, discussing both challenges and opportunities in developing miRNA-based treatments. Understanding miR-211’s complex regulatory interactions and context-dependent functions is crucial for advancing its clinical applications for diagnosis, prognosis, and targeted therapy in multiple diseases. Full article

Global warming has resulted in an increase in the frequency of extreme high-temperature events. High temperatures can increase cell membrane permeability, elevate levels of osmotic adjustment substances, reduce photosynthetic capacity, impair plant growth and development, and even result in plant death. Under high-temperature stress, plants mitigate damage through physiological and biochemical adjustments, heat signal transduction, the regulation of transcription factors, and the synthesis of heat shock proteins. However, different plants exhibit varying regulatory abilities and temperature tolerances. Investigating the heat-resistance and regulatory mechanisms of plants can facilitate the development of heat-resistant varieties for plant genetic breeding and landscaping applications. This paper presents a systematic review of plant physiological and biochemical responses, regulatory substances, signal transduction pathways, molecular mechanisms—including the regulation of heat shock transcription factors and heat shock proteins—and the role of plant hormones under high-temperature stress. The study constructed a molecular regulatory network encompassing Ca²⁺ signaling, plant hormone pathways, and heat shock transcription factors, and it systematically elucidated the mechanisms underlying the enhancement of plant thermotolerance, thereby providing a scientific foundation for the development of heat-resistant plant varieties. Full article

Grapholita molesta is a globally significant fruit pest. Females achieve maximal reproductive output through efficient sperm utilization following a single copulation. Post-mating maturation of eupyrene sperm is a critical step in reproductive success. Here, we report that a male accessory gland-derived serine protease (named GmAGSP1) is essential for this process. GmAGSP1 was only distantly related to other identified sperm-activating SPs, and its transcript was highly expressed in the AG at 48 h after emergence. RNAi-mediated knockdown of GmAGSP1 in males did not affect courtship rate, copulation duration, or mating frequency, whereas male fertility decreased significantly. Mating with GmAGSP1-knockdown males markedly impaired eupyrene sperm maturation in the spermatophores, with phenotypes including failure of eupyrene sperm bundles to dissociate normally and marked reduction in viability of the dissociated eupyrene sperm. Finally, untargeted metabolomic analysis preliminarily demonstrated marked alterations in multiple metabolic pathways within the spermatophore following mating with GmAGSP1-knockdown males. This study advances our understanding of the regulatory mechanism of “sperm activation in the spermatophore’s metabolic microenvironment mediated by male AG-derived SP” while providing critical insights for the development of novel genetic control strategies targeting G. molesta. Full article

Nuclear receptors (NRs) are ligand-activated transcription factors that regulate gene expression and are involved in diverse physiological and pathological processes, including carcinogenesis. In bladder cancer (BCa), dysregulation of NR signaling pathways has been linked to tumor initiation, progression, therapy resistance, and immune evasion. Recent evidence highlights the intricate crosstalk between NRs and microRNAs (miRNAs), which are small non-coding RNAs that posttranscriptionally modulate gene expression. This review provides an integrated overview of the molecular interactions between key NRs and miRNAs in BCa. We investigated how miRNAs regulate NR expression and function and, conversely, how NRs influence miRNA biogenesis, thereby forming regulatory feedback loops that shape tumor behavior. Specific miRNA–NR interactions affecting epithelial-to-mesenchymal transition, metabolic reprogramming, angiogenesis, and chemoresistance are discussed in detail. Additionally, we highlight therapeutic strategies targeting NR–miRNA networks, including selective NR modulators, miRNA mimics and inhibitors, as well as RNA-based combinatorial approaches focusing on their utility as diagnostic biomarkers and personalized treatment targets. Understanding the molecular complexity of NR–miRNA regulation in BCa may open new avenues for improving therapeutic outcomes and advancing precision oncology in urological cancers. Full article

Background: Gastric cancer (GC) represents a significant global health burden with considerable heterogeneity in clinical and molecular behavior. The anatomical site of tumor origin—proximal versus distal—has emerged as a determinant of prognosis and response to therapy. The aim of this paper is to elucidate the transcriptional and regulatory differences between proximal gastric cancer (PGC) and distal gastric cancer (DGC) through master regulator (MR) analysis. Methods: We analyzed RNA-seq data from TCGA-STAD and microarray data from GEO (GSE62254, GSE15459). Differential gene expression and MR analyses were performed using DESeq2, limma, corto, and RegEnrich pipelines. A harmonized matrix of 4785 genes was used for MR inference following normalization and batch correction. Functional enrichment and survival analyses were conducted to explore prognostic associations. Results: Among 364 TCGA and 492 GEO patients, PGC was associated with more aggressive clinicopathological features and poorer outcomes. We identified 998 DEGs distinguishing PGC and DGC. PGC showed increased FOXM1 (a key regulator of cell proliferation), STAT3, and NF-κB1 activity, while DGC displayed enriched GATA6, CDX2 (a marker of intestinal differentiation), and HNF4A signaling. Functional enrichment highlighted proliferative and inflammatory programs in PGC, and differentiation and metabolic pathways in DGC. MR activity stratified survival outcomes, reinforcing prognostic relevance. Conclusions: PGC and DGC are governed by distinct transcriptional regulators and signaling networks. Our findings provide a biological rationale for location-based stratification and inform targeted therapy development. Full article

The worldwide agriculture industry is facing increasing problems due to rapid population increase and increasingly unfavorable weather patterns. In order to reach the projected food production targets, which are essential for guaranteeing global food security, innovative and sustainable agricultural methods must be adopted. Conventional approaches, including traditional breeding procedures, often cannot handle the complex and simultaneous effects of biotic pressures such as pest infestations, disease attacks, and nutritional imbalances, as well as abiotic stresses including heat, salt, drought, and heavy metal toxicity. Applying phytohormonal approaches, particularly those involving hormonal crosstalk, presents a viable way to increase crop resilience in this context. Abscisic acid (ABA), gibberellins (GAs), auxin, cytokinins, salicylic acid (SA), jasmonic acid (JA), ethylene, and GA are among the plant hormones that control plant stress responses. In order to precisely respond to a range of environmental stimuli, these hormones allow plants to control gene expression, signal transduction, and physiological adaptation through intricate networks of antagonistic and constructive interactions. This review focuses on how the principal hormonal signaling pathways (in particular, ABA-ET, ABA-JA, JA-SA, and ABA-auxin) intricately interact and how they affect the plant stress response. For example, ABA-driven drought tolerance controls immunological responses and stomatal behavior through antagonistic interactions with ET and SA, while using SnRK2 kinases to activate genes that react to stress. Similarly, the transcription factor MYC2 is an essential node in ABA–JA crosstalk and mediates the integration of defense and drought signals. Plants’ complex hormonal crosstalk networks are an example of a precisely calibrated regulatory system that strikes a balance between growth and abiotic stress adaptation. ABA, JA, SA, ethylene, auxin, cytokinin, GA, and BR are examples of central nodes that interact dynamically and context-specifically to modify signal transduction, rewire gene expression, and change physiological outcomes. To engineer stress-resilient crops in the face of shifting environmental challenges, a systems-level view of these pathways is provided by a combination of enrichment analyses and STRING-based interaction mapping. These hormonal interactions are directly related to the United Nations Sustainable Development Goals (SDGs), particularly SDGs 2 (Zero Hunger), 12 (Responsible Consumption and Production), and 13 (Climate Action). This review emphasizes the potential of biotechnologies to use hormone signaling to improve agricultural performance and sustainability by uncovering the molecular foundations of hormonal crosstalk. Increasing our understanding of these pathways presents a strategic opportunity to increase crop resilience, reduce environmental degradation, and secure food systems in the face of increasing climate unpredictability. Full article

Gibberellins (GAs) are essential phytohormones that regulate seed dormancy release and germination. Lomatogonium rotatum (L.) Fries ex Nym is a traditional medicinal plant whose seed germination is often hindered by physiological dormancy. In this study, we systematically investigated the effects of exogenous GA₃ on the seed germination of L. rotatum and elucidated the underlying molecular regulatory mechanisms via transcriptomic analysis. GA₃ treatment (500 mg/L for 24 h) significantly improved the germination rate, vigor index, and other germination traits. RNA-seq analysis identified time-dependent transcriptional changes in GA₃-treated seeds across three developmental stages (24 h, 72 h, and 96 h). KEGG enrichment and K-means clustering revealed dynamic actiSvation of hormonal signaling, secondary metabolism, and DNA replication pathways. WGCNA uncovered two hormone-responsive co-expression modules (Red and Lightcyan) corresponding to early and late stages of germination, respectively. Key genes related to ABA and GA biosynthesis and signal transduction showed phase-specific expression, highlighting the coordinated hormonal regulation during seed germination. Our findings provide new insights into the molecular basis of GA₃-regulated seed germination and offer theoretical support for the cultivation and utilization of L. rotatum. Full article

Flammulina velutipes is a widely cultivated edible mushroom in East Asia, recognized for its nutritional benefits and distinct morphology characterized by a long stipe and a compact, hemispherical pileus. The pileus not only plays a critical biological role in reproduction through spore formation but also serves as a key commercial trait influencing consumer preference and market value. Despite its economic importance, pileus development in F. velutipes is highly sensitive to environmental factors, among which carbon dioxide (CO₂) concentration is particularly influential under indoor cultivation conditions. While previous studies have reported that elevated CO₂ levels can inhibit pileus expansion in other mushroom species, the molecular mechanisms by which CO₂ affects pileus growth in F. velutipes remain poorly understood. In this study, we investigated the impact of CO₂ concentration on pileus morphology and gene expression in F. velutipes by cultivating fruiting bodies under two controlled atmospheric conditions: low (1000 ppm) and high (10,000 ppm) CO₂. Morphometric analysis revealed that elevated CO₂ levels significantly suppressed pileus expansion, reducing the average diameter by more than 50% compared to the low CO₂ condition. To elucidate the underlying genetic response, we conducted RNA sequencing and identified 102 differentially expressed genes (DEGs), with 78 being downregulated under elevated CO₂. Functional enrichment analysis highlighted the involvement of cyclin-dependent protein kinase regulatory pathways in this response. Two cyclin genes were found to be significantly downregulated under elevated CO₂ conditions, and their suppression was validated through quantitative real-time PCR. These genes, possessing conserved cyclin_N domains, are implicated in the regulation of the eukaryotic cell cycle, particularly in mitotic growth. These results indicate that CO₂-induced downregulation of cyclin genes may underlie cell cycle arrest, contributing to inhibited pileus development. This study is the first to provide transcriptomic evidence that elevated CO₂ concentrations specifically repress PHO80-like cyclin genes in F. velutipes, revealing a molecular mechanism by which CO₂ stress inhibits pileus development. These findings suggest that elevated CO₂ triggers a morphogenetic checkpoint by repressing PHO80-like cyclins, thereby modulating cell cycle progression during fruiting body development. This study provides the first evidence of such a transcriptional response in edible mushrooms and offers promising molecular targets for breeding CO₂-resilient strains and optimizing commercial cultivation conditions. Full article

Background: Preeclampsia (PE) is a pregnancy-specific disease and hypertensive disorder with a multifactorial pathogenesis involving complex molecular regulatory networks. Recent studies highlight the critical role of non-coding RNAs, particularly miRNAs and lncRNAs, in PE development. This study investigates the molecular interaction between miR-7151-5p and the lncRNA KCNQ1OT1 and their functional contributions to PE pathogenesis. Methods: An integrative approach combining RNAhybrid-based bioinformatics, dual-luciferase reporter assays, qRT-PCR, Transwell migration and invasion assays, and RNA sequencing was employed to characterize the binding between miR-7151-5p and KCNQ1OT1 and assess their influence on trophoblast cell function and gene expression. Results: A bioinformatic analysis predicted a stable binding site between miR-7151-5p and KCNQ1OT1 (minimum free energy: –37.3 kcal/mol). The dual-luciferase reporter assay demonstrated that miR-7151-5p directly targets KCNQ1OT1, leading to suppressed transcriptional activity. In HTR8/SVneo cells, miR-7151-5p overexpression significantly downregulated both KCNQ1OT1 and Notch1 mRNA, whereas its inhibition showed no significant changes, suggesting additional regulatory mechanisms of Notch1 expression. Transwell assays indicated that miR-7151-5p overexpression suppressed trophoblast cell migration and invasion, whereas its inhibition enhanced these cellular behaviors. RNA-seq analysis further revealed that miR-7151-5p overexpression altered key signaling pathways, notably the TGF-β pathway, and significantly modulates PE-associated genes, including PLAC1, ANGPTL6, HIRA, GLA, HSF1, and BAG6. Conclusions: The regulatory effect of miR-7151-5p on KCNQ1OT1, along with its influence on trophoblast cell dynamics via Notch1 and TGF-β signaling pathways, highlights its role in PE pathogenesis and supports its potential as a biomarker in early PE screening. Full article

B-box (BBX) transcription factors are critical regulators of light-mediated anthocyanin biosynthesis, influencing peel coloration in plants. To explore their role in red mango cultivars, we identified 32 BBX genes (MiBBX1–MiBBX32) in the mango (Mangifera indica L.) genome using a genome-wide analysis. Phylogenetic and structural analyses classified these genes into five subfamilies based on conserved domains. A collinearity analysis revealed segmental duplication as the primary mechanism of MiBBX gene family expansion, with purifying selection shaping their evolution. A promoter analysis identified numerous light- and hormone-responsive cis-elements, indicating regulatory roles in the light and hormonal signaling pathways. Expression profiling in the ‘Sensation’ cultivar revealed organ-specific patterns, with several MiBBX genes showing higher expression in the peel than in the flesh. Many of these genes also consistently exhibited elevated expression in the peel of red-skinned cultivars (‘Sensation’ and ‘Guifei’) compared to yellow and green cultivars, suggesting their role in red peel pigmentation. Furthermore, postharvest light treatment of ‘Hongmang No. 6’ fruit significantly upregulated multiple MiBBX genes, suggesting their involvement in light-induced anthocyanin accumulation in red mango peel. These findings provide valuable insights into the molecular mechanisms governing light-regulated peel coloration in mango and establish a foundation for functional studies of MiBBX genes in fruit pigmentation. Full article

Background/Objectives: Moso bamboo (Phyllostachys edulis), the most widely distributed bamboo species in China, is valued for both its shoots and timber. This species often faces challenges from high-temperature stress. To cope with this stress, Moso bamboo has evolved various adaptive mechanisms at the physiological and molecular levels. Although numerous studies have revealed that a large number of transcription factors (TFs) and genes play important roles in the regulatory network of plant heat stress responses, the regulatory network involved in heat responses remains incompletely understood. Methods: In this study, Moso bamboo was placed in a high-temperature environment of 42 °C for 1 h and 24 h, and transcriptome sequencing was carried out to accurately identify key molecules affected by high temperature and their related biological pathways. Results: Through a differential expression analysis, we successfully identified a series of key candidate genes and transcription factors involved in heat stress responses, including members of the ethylene response factor, HSF, WRKY, MYB, and bHLH families. Notably, in addition to traditional heat shock proteins/factors, multiple genes related to lipid metabolism, antioxidant enzymes, dehydration responses, and hormone signal transduction were found to play significant roles in heat stress responses. To further verify the changes in the expression of these genes, we used qRT-PCR technology for detection, and the results strongly supported their key roles in cellular physiological processes and heat stress responses. Conclusions: This study not only deepens our understanding of plant strategies for coping with and defending against extreme abiotic stresses but also provides valuable insights for future research on heat tolerance in Moso bamboo and other plants. Full article

Insect metamorphosis is a complex developmental process regulated by hormonal signaling and gene transcription. To elucidate its transcriptional regulatory mechanisms, we examined chromatin accessibility dynamics during metamorphosis in two holometabolous insects, Harmonia axyridis and Drosophila melanogaster, using ATAC-seq. Our analysis revealed distinct stage-specific chromatin accessibility patterns, with peak accessibility during the prepupal stage in H. axyridis and the wandering larval to prepupal transition in D. melanogaster. Through analysis of differential accessibility regions (DARs), we identified enrichment of metamorphosis-related processes including cell morphogenesis, tissue remodeling, and hormone signaling pathways via Gene Ontology and KEGG pathway analyses. Integration of chromatin accessibility with gene expression data revealed 608 conserved genes exhibiting coordinated accessibility and expression changes across both species. Additionally, we constructed a regulatory network centered around four key transcription factors (dsx, E93, REPTOR, and Sox14) that form core regulatory modules controlling metamorphosis. This study provides novel insights into the epigenetic landscape of insect metamorphosis and establishes a foundation for understanding the transcriptional regulatory mechanisms governing this critical developmental process. Full article

Background/Objectives: In gastric cancer, only a subset of patients benefit clinically from neoadjuvant chemoimmunotherapy, underscoring the need for robust biomarkers that can predict treatment responses and guide personalized immunotherapy. This study aimed to characterize the immune microenvironment of gastric tumors and identify predictive markers associated with therapeutic efficacy. Methods: We prospectively enrolled 16 patients with histologically confirmed, PD-L1–positive (CPS ≥ 1) gastric adenocarcinoma (T_2–4N_0–1M₀). All patients received eight cycles of FLOT chemotherapy combined with pembrolizumab. Treatment response was assessed by Mandard tumor regression grading. Spatial transcriptomic profiling (10x Genomics Visium) and multiplex immunofluorescence were used to evaluate tumor-infiltrating immune cell subsets and PD-1 expression at baseline and after treatment. Results: Transcriptomic analysis differentiated the immune landscapes of responders from non-responders. Responders exhibited elevated expression of IL1B, CXCL5, HMGB1, and IFNGR2, indicative of an inflamed tumor microenvironment and type I/II interferon signaling. In contrast, non-responders demonstrated upregulation of immunosuppressive genes such as LGALS3, IDO1, and CD55, along with enrichment in oxidative phosphorylation and antigen presentation pathways. Multiplex immunofluorescence confirmed a higher density of FoxP3⁺ regulatory T cells in non-responders (median 5.36% vs. 2.41%; p = 0.0032). Notably, PD-1⁺ CD8⁺ T cell and PD-1⁺ FoxP3⁺ Treg frequencies were significantly elevated in non-responders, suggesting that PD-1 expression within cytotoxic and regulatory compartments may contribute to immune evasion. No substantial differences were observed in PD-L1 CPS or PD-1⁺ B cells and PD-1⁺ macrophages. Conclusions: Our findings identify PD-1⁺ CD8⁺ T cells and PD-1⁺ FoxP3⁺ Tregs as potential biomarkers of resistance to neoadjuvant chemoimmunotherapy in gastric cancer. Transcriptional programs centered on IL1B/CXCL5 and LGALS3/IDO1 define distinct immune phenotypes that may guide future combination strategies targeting both effector and suppressive arms of the tumor immune response. Full article

Background/Objectives: Doxorubicin (DOX), a widely used anthracycline chemotherapeutic agent, is recognized for its efficacy in treating various malignancies. However, its clinical application is critically limited due to dose-dependent cardiotoxicity, predominantly induced by oxidative stress and compromised antioxidant defenses. Photobiomodulation (PBM), a non-invasive intervention that utilizes low-intensity light, has emerged as a promising therapeutic modality in regenerative medicine, demonstrating benefits such as enhanced tissue repair, reduced inflammation, and protection against oxidative damage. This investigation sought to evaluate the cardioprotective effects of PBM preconditioning in human-induced pluripotent stem cell-derived ventricular cardiomyocytes (hiPSC-vCMs) subjected to DOX-induced toxicity. Methods: Human iPSC-vCMs were allocated into three experimental groups: control cells (untreated), DOX-treated cells (exposed to 2 μM DOX for 24 h), and PBM+DOX-treated cells (preconditioned with PBM, utilizing 660 nm ±10 nm LED light at an intensity of 10 mW/cm² for 500 s, delivering an energy dose of 5 J/cm², followed by DOX exposure). Cell viability assessments were conducted in conjunction with evaluations of oxidative stress markers, including antioxidant enzyme activities and malondialdehyde (MDA) levels. Furthermore, transcriptional profiling of 40 genes implicated in cardiac dysfunction was performed using TaqMan quantitative polymerase chain reaction (qPCR), complemented by analyses of protein expression for markers of cardiac stress, inflammation, and apoptosis. Results: Exposure to DOX markedly reduced the viability of hiPSC-vCMs. The cells exhibited significant alterations in the expression of 32 out of 40 genes (80%) after DOX exposure, reflecting the upregulation of markers associated with apoptosis, inflammation, and adverse cardiac remodeling. PBM preconditioning partially restored the cell viability, modulating the expression of 20 genes (50%), effectively counteracting a substantial proportion of the dysregulation induced by DOX. Notably, PBM enhanced the expression of genes responsible for antioxidant defense, augmented antioxidant enzyme activity, and reduced oxidative stress indicators such as MDA levels. Additional benefits included downregulating stress-related mRNA markers (HSP1A1 and TNC) and apoptotic markers (BAX and TP53). PBM also demonstrated gene reprogramming effects in ventricular cells, encompassing regulatory changes in NPPA, NPPB, and MYH6. PBM reduced the protein expression levels of IL-6, TNF, and apoptotic markers in alignment with their corresponding mRNA expression profiles. Notably, PBM preconditioning showed a diminished expression of BNP, emphasizing its positive impact on mitigating cardiac stress. Conclusions: This study demonstrates that PBM preconditioning is an effective strategy for reducing DOX-induced chemotherapy-related cardiotoxicity by enhancing cell viability and modulating signaling pathways associated with oxidative stress, as well as inflammatory and hypertrophic markers. Full article