Search Results (160)

As nutrient allocation trade-offs occur between reproductive and vegetative development in crops, optimizing their partitioning holds promise for improving agricultural productivity and quality. Herein, we characterize the phenotypic diversity of the fruitfulness trait and identify associated genes in tea plants (Camellia sinensis). Over three consecutive years, we monitored the fruitfulness of an F₁ hybrid population (n = 206) derived from crosses of ‘Emei Wenchun’ and ‘Chuanmu 217’. A marked variation was observed in the yield of individual plants, ranging from complete sterility (zero fruits) to exceptionally high fertility (1612 fruits). Using the high-resolution genetic linkage map and the fruitfulness data, we identified a stable major QTL designated as qFN5. To fine-map the underlying gene(s), artificial pollination experiments were conducted with extreme phenotype individuals (with the highest vs. lowest fruit numbers). Bulked segregant RNA sequencing (BSR-Seq) with ovules collected at two and seven days post-pollination (DPP) identified the genomic intervals that exhibit a high degree of overlap with qFN5. Analysis of expression dynamics combined with functional genomics data revealed a prominent candidate gene, CsETR2 (TGY048509), which encodes an ethylene receptor protein. When CsETR2 was overexpressed in Arabidopsis thaliana, the transgenic lines exhibited significantly decreased reproductive performance relative to the wild-type plants. Relative to the wild type, the transgenic lines exhibited a significant decline in several key traits: the number of effective panicles decreased by 72.5%, the seed setting rate dropped by 67.7%, and the silique length shortened by 38%. These findings demonstrate its role in regulating plant fruitfulness. Furthermore, yeast one-hybrid and dual-luciferase assays verified that CsMYB15 (TGY110225) directly binds to the CsETR2 promoter, thus repressing its transcription. In summary, our findings expand the understanding of genetic regulation underlying fruitfulness in tea plants and provide candidate target loci for breeding. Full article

Introduction: Neuroinflammation is a common pathological hallmark of Coronavirus Disease 2019 (COVID-19) and epilepsy; however, their shared immunogenomic mechanisms remain poorly defined. This study explores shared immune-inflammatory transcriptomic signatures and identifies potential repositioning therapeutics. Methods: We integrated single-cell RNA-seq data from peripheral blood mononuclear cells (PBMCs) of COVID-19 patients and healthy donors (GSE149689), and bulk RNA-seq data from hippocampal tissue of patients with Temporal Lobe Epilepsy with Hippocampal Sclerosis (TLE-HS) and healthy controls (GSE256068). Common Differentially Expressed Genes (DEGs) were identified and subjected to GO/KEGG enrichment, a PPI network, hub gene detection (cytoHubba), and transcriptional regulation analysis (ENCODE-based TF/miRNA networks). Drug repositioning was performed using the LINCS L1000 database. Results: We identified 25 DEGs shared across datasets, including 22 upregulated genes enriched in cytokine–cytokine receptor interaction, NF-κB, and Toll-like receptor pathways. PPI analysis revealed a CX3CR1–TLR4-centered immune module. Gabapentin emerged as a promising repositioning candidate with potential to downregulate CX3CR1, TLR4, and selectin P ligand (SELPLG). Receiver Operating Characteristic (ROC) analysis confirmed the diagnostic value of these targets (AUC > 0.90 in epilepsy). A mechanistic model was proposed to illustrate Gabapentin’s dual action on microglial polarization and cytokine suppression. Conclusions: Our results reveal a shared CX3CR1–TLR4–NF-κB inflammatory axis in COVID-19 and epilepsy, supporting Gabapentin as a potential dual-action immunomodulator. These findings reveal a previously underappreciated immunomodulatory role for Gabapentin, providing mechanistic rationale for its repositioning in neuroinflammatory conditions beyond seizure control. Full article

Plant heat shock proteins (Hsps) are from a diverse and ancient protein family, with small Hsps of ~20 kDa molecular weight classified as Hsp20s. As a key transcription factor in the jasmonic acid (JA) pathway, myelocytomatosis protein 2 (MYC2) plays a vital role in stamen development. In this study, we identified six genes with significantly altered expression levels using previous RNA-Seq data from PhMYC2a-overexpressing and methyl jasmonate (MeJA)-treated petunia. Interestingly, five of these are Hsp20 family members (PhHsp16.0A, PhHsp16.1, PhHsp16.8, PhHsp21.9, and PhHsp40.8). Yeast one-hybrid (Y1H) and dual-luciferase assays demonstrated that PhMYC2a directly binds their promoters, indicating a collective effect. Thus, a genome-wide analysis was conducted and a total of 38 genes encoding Hsp20s were identified in the reference genome of Petunia axillaris. Phylogenetic analysis revealed that 38 members of Hsp20s were irregularly distributed on 34 chromosome scaffolds and separated into 13 subfamilies, with only PaHsp16.0A and 16.1, among the five selected Hsp20s, being in the same Cytosol IV (CIV) subfamily. Conserved motif analysis suggested that the PaHsp20 gene family members may have a high degree of conservation. The promoter sequence analysis suggested that the promoter regions of PaHsp20 genes contained multiple light- and hormone-related cis-regulatory elements. Subsequently, spatiotemporal expression patterns, analyzed by qRT-PCR, showed that PhHsp16.0A and PhHsp16.1 had relatively high expression levels in flowers, with similar expression patterns at various stages of flower bud and anther development. Furthermore, virus-induced gene silencing (VIGS) of PhHsp16.0A and PhHsp16.1 resulted in significantly reduced pollen fertility, indicating their regulation in the process of flower development and echoing the role of PhMYC2a. This study highlights the pivotal role of Hsp20s in MYC2a-mediated regulatory mechanisms during petunia pollen development. Full article

Ankylosing spondylitis (AS) displays wide inter-patient variability that is not accounted for by HLA-B27 alone, suggesting that additional immune and metabolic modifiers contribute to disease severity. Using a genetically matched design, we profiled peripheral blood mononuclear cells from two brother pairs discordant for AS severity and one healthy brother pair. Strand-specific RNA-seq was analyzed with a family-blocked DESeq2 model, while untargeted metabolites were quantified using gas chromatography–mass spectrometry (GC-MS) and liquid chromatography–mass spectrometry (LC-MS). Differential features were defined as follows: differentially expressed genes (DEGs) (|log₂FC| ≥ 1 and FDR < 0.05) and metabolites (VIP > 1, FC ≥ 1.2, and BH-adjusted p < 0.05). Pathway enrichment was performed with KEGG and Gene Ontology (GO). A total of 325 genes were differentially expressed. Type I interferon and neutrophil granule transcripts (e.g., IFI44L, ISG15, S100A8/A9) were markedly up-regulated, whereas mitochondrial β-oxidation genes (ACADM, CPT1A, ACOT12) were repressed. Metabolomics revealed 110 discriminant features, including 25 MS/MS-annotated metabolites. Primary bile acid intermediates were depleted, whereas oxidized fatty acid derivatives such as 12-Z-octadecadienal and palmitic amide accumulated. Spearman correlation identified two antagonistic modules (i) interferon/neutrophil genes linked to pro-oxidative lipids and (ii) lipid catabolism genes linked to bile acid species that persisted when severe and mild siblings were compared directly. Enrichment mapping associated these modules with viral defense, neutrophil degranulation, fatty acid β-oxidation, and bile acid biosynthesis pathways. This sibling-paired peripheral blood mononuclear cell (PBMC) dual-omics study delineates an interferon-driven lipid–bile acid axis that tracks AS severity, supporting composite PBMC-based biomarkers for future prospective validation and highlighting mitochondrial lipid clearance and bile acid homeostasis as potential therapeutic targets. Full article

Background: Bladder cancer is a common and heterogeneous malignancy of the urinary tract. Traditional chemotherapy using bivalent platinum drugs such as cisplatin(CDDP) is often limited by severe side effects and acquired resistance. To overcome these limitations, we explored a novel Pt(IV) prodrug, DNP, designed to release both cytotoxic cisplatin and the anti-inflammatory cyclooxygenase-2 (COX-2) inhibitor naproxen(NPX). Methods: We evaluated the cytotoxic activity of DNP using both two-dimensional (2D) monolayer and three-dimensional (3D) spheroid models of bladder cancer cells. Transcriptomic analysis via RNA-seq identified apoptosis- and inflammation-related signaling pathways modulated by DNP. RNA-seq-based transcriptomic profiling revealed that DNP regulates signaling pathways associated with apoptosis and inflammation. The anti-inflammatory effects were evaluated using a lipopolysaccharide (LPS)-induced macrophage model, while the in vivo antitumor efficacy was assessed in an orthotopic MB49 bladder cancer model. Results: Compared with CDDP, DNP significantly increased intracellular platinum accumulation and exhibited superior cytotoxicity. It effectively inhibited tumor proliferation, induced apoptosis, and attenuated inflammation both in vitro and in vivo. Conclusions: These findings suggest that DNP exerts dual antitumor effects through enhanced delivery of cytotoxic and anti-inflammatory agents, offering a promising strategy for bladder cancer therapy. Full article

Chrysanthemum morifolium Ramat. is an important ornamental plant, holding dual economic value as a medicinal and edible plant. Jinsi Huangju is a popular healthy tea drink prepared from the large and elegant shaped flowers of C. morifolium. However, the suboptimal accumulation of bioactive flavonoids during conventional harvest (full bloom stage) limits its commercial potential. To elucidate the molecular mechanisms governing flavonoid biosynthesis in Jinsi Huangju flowers and identify key genetic regulators for metabolic engineering, we performed integrated metabolomic and transcriptomic analyses of flowers at distinct developmental stages using ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) and RNA-seq. Differential metabolites were screened, and candidate genes were validated via transient transformation assays. Among 2146 identified metabolites, flavonoids were the predominant differential compounds, with accumulation patterns being strongly stage dependent. Thirty-eight flavonoid biosynthetic genes and key transcription factors from the MYB, bHLH, and WD40 families exhibited dynamic expression. The CmMYB8a was confirmed as a positive regulator of flavonoid biosynthesis through transient overexpression. This study deciphers the stage-specific flavonoid accumulation in Jinsi Huangju and identifies CmMYB8a as a pivotal regulatory target. Our findings provide genetic resources for breeding high-flavonoid cultivars via molecular design. Full article

Melanoma is a highly aggressive skin cancer with limited therapeutic response. Targeting intracellular signaling pathways and promoting tumor cell differentiation are promising therapeutic strategies. Pentoxifylline (PTX) and norcantharidin (NCTD) have demonstrated antitumor properties, but their combined mechanisms of action in melanoma remain poorly understood. The effects of PTX (30 and 60 mg/kg) and NCTD (0.75 and 3 mg/kg), administered alone or in combination, in a DBA/2J murine B16-F1 melanoma model via intraperitoneal and intratumoral (IT) routes were evaluated. Tumor growth was monitored, and molecular analyses included RNA sequencing and immunofluorescence quantification of PI3K, AKT1, mTOR, ERBB2, BRAF, and MITF protein levels, and molecular docking simulations were performed. In the final stage of the experiment, combination therapy significantly reduced tumor volume compared to monotherapies, with the relative tumor volume decreasing from 18.1 ± 1.2 (SD) in the IT Control group to 0.6 ± 0.1 (SD) in the IT combination-treated group (n = 6 per group; p < 0.001). RNA-seq revealed over 3000 differentially expressed genes in intratumoral treatments, with enrichment in pathways related to oxidative stress, immune response, and translation regulation (KEGG and Reactome analyses). Minimal transcript-level changes were observed for BRAF and PI3K/AKT/mTOR genes; however, immunofluorescence showed reduced total and phosphorylated levels of PI3K, AKT1, mTOR, BRAF, and ERBB2. MITF protein levels and pigmentation increased, especially in PTX-treated groups, indicating enhanced melanocytic differentiation. Docking analyses predicted direct binding of both drugs to PI3K, AKT1, mTOR, and BRAF, with affinities ranging from −5.7 to −7.4 kcal/mol. The combination of PTX and NCTD suppresses melanoma progression through dual mechanisms: inhibition of PI3K/AKT/mTOR signaling and promotion of tumor cell differentiation. 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

Soil moisture (SM) is a key variable in agricultural ecosystems and is crucial for drought prevention and control management. However, SM is influenced by underlying surface and meteorological conditions, and it changes rapidly in time and space. To capture the changes in SM and improve the accuracy of short-term and medium-to-long-term predictions on a daily scale, an LSTMseq2seq model driven by both observational data and mechanism models was constructed. This framework combines historical meteorological elements and SM, as well as the SM change characteristics output by the VIC model, to predict SM over a 90-day period. The model was validated using SMAP SM. The proposed model can accurately predict the spatiotemporal variations in SM in Jiangxi Province. Compared with classical machine learning (ML) models, traditional LSTM models, and advanced transformer models, the LSTMseq2seq model achieved R² values of 0.949, 0.9322, 0.8839, 0.8042, and 0.7451 for the prediction of surface SM over 3 days, 7 days, 30 days, 60 days, and 90 days, respectively. The mean absolute error (MAE) ranged from 0.0118 m³/m³ to 0.0285 m³/m³. This study also analyzed the contributions of meteorological features and simulated future SM state changes to SM prediction from two perspectives: time importance and feature importance. The results indicated that meteorological and SM changes within a certain time range prior to the prediction have an impact on SM prediction. The dual-driven LSTMseq2seq model has unique advantages in predicting SM and is conducive to the integration of physical mechanism models with data-driven models for handling input features of different lengths, providing support for daily-scale SM time series prediction and drought dynamics prediction. Full article

Background/Objectives: Degenerative joint diseases (DJDs) involve intricate molecular disruptions within bone, cartilage, and synovial tissues, often preceding overt radiographic changes. These tissues exhibit complex biomolecular architectures and their degeneration leads to microstructural disorganization and inflammation that are challenging to detect with conventional imaging techniques. This review aims to synthesize recent advances in imaging, computational modeling, and sequencing technologies that enable high-resolution, non-invasive characterization of joint tissue health. Methods: We examined advanced modalities including high-resolution MRI (e.g., T1ρ, sodium MRI), quantitative and dual-energy CT (qCT, DECT), and ultrasound elastography, integrating them with radiomics, deep learning, and multi-scale modeling approaches. We also evaluated RNA-seq, spatial transcriptomics, and mass spectrometry-based proteomics for omics-guided imaging biomarker discovery. Results: Emerging technologies now permit detailed visualization of proteoglycan content, collagen integrity, mineralization patterns, and inflammatory microenvironments. Computational frameworks ranging from convolutional neural networks to finite element and agent-based models enhance diagnostic granularity. Multi-omics integration links imaging phenotypes to gene and protein expression, enabling predictive modeling of tissue remodeling, risk stratification, and personalized therapy planning. Conclusions: The convergence of imaging, AI, and molecular profiling is transforming musculoskeletal diagnostics. These synergistic platforms enable early detection, multi-parametric tissue assessment, and targeted intervention. Widespread clinical integration requires robust data infrastructure, regulatory compliance, and physician education, but offers a pathway toward precision musculoskeletal care. Full article

The DNA mismatch repair (MMR) system plays a crucial role in repairing DNA damage and regulating cell cycle arrest induced by cadmium (Cd) stress. To elucidate the mechanism by which miRNAs target AtMSH2 in regulating Arabidopsis’ response to Cd stress, the wild-type Arabidopsis, Atmsh2 mutant, and three miRNA-overexpressing transgenic lines were grown hydroponically in half-strength MS solution containing cadmium (Cd) at concentrations of 0, 0.5, 1, 2, and 3 mg/L for 5 days. miRNA-seq analysis, bioinformatics prediction, dual-luciferase reporter assays, and qRT-PCR results demonstrated that miR5651, miR170-3p, and miR171a-3p specifically targeted AtMSH2 and their expression levels showed a significant negative correlation. Compared to wild-type (WT) Arabidopsis, Cd stress tolerance was significantly enhanced in miRNA-overexpressing transgenic lines. Moreover, exogenous application of these three miRNAs in half-strength MS liquid medium also markedly improved Cd stress tolerance in wild-type Arabidopsis. Furthermore, the expression of these three miRNAs expression was further upregulated by Cd stress in a dose-dependent manner. Additionally, DNA damage response in miRNA-overexpressing transgenic lines was promoted based on the expression of DNA repair, DNA damage signaling, and cell cycle genes, which differed from both wild-type and Atmsh2 plants. Taken together, miR5651, miR170-3p, and miR171a-3p participated in Cd stress response and improved plant Cd tolerance by mediating the expression of AtMSH2. Our study provides novel insights into the epigenetic mechanisms of Cd tolerance in plants, which sheds light on breeding for stress resilience in phytoremediation. Full article

Background: Lung cancer, predominantly NSCLC (80%), has a poor prognosis due to late diagnosis and limited treatment efficacy. DMRTA2 (DMRT5), a transcription factor linked to neural/germ cell development, is overexpressed in NSCLC per TCGA data, indicating its potential role in tumorigenesis and as a therapeutic target. Methods: Conduct a comprehensive search of the relevant theoretical foundations. Based on this, differential expression analysis will be performed using the DESeq2 package in R on RNA-seq data from lung adenocarcinoma and lung squamous cell carcinoma in the TCGA database. The research will then employ various methods, including CRISPR genome editing, MTS assay, flow cytometry, Western blot, co-immunoprecipitation, immunofluorescence, and qRT-PCR. Results: Through experimental validation, we found that DMRTA2 mRNA is highly expressed in non-small-cell lung cancer (NSCLC) tissues and is negatively correlated with poor prognosis. DMRTA2 binds to HSP90β, inhibiting the interaction between HSP90β and p53, thereby suppressing p53 ubiquitination and nuclear export. This activates the p53 pathway, inhibiting the proliferation and invasion of lung cancer cells. Conclusions: In NSCLC, DMRTA2 acts as a context-dependent regulator, stabilizing wild-type p53 through competitive HSP90β binding to suppress tumors, while in p53-compromised cells, potentially engaging HSP90β or alternative pathways to promote malignancy. Its dual localization and transport interactions reveal multifunctional, stress-responsive roles beyond transcription. Full article

Phalaenopsis pulcherrima are known for their captivating floral morphology and diverse colors, demonstrate exceptional resilience to adverse environmental conditions, and exhibit significant potential for hybrid breeding. However, current research on flower coloration is still limited. The data from this study indicates that variations in anthocyanin levels are the primary determinants of the difference between white and purple colors. Through RNA-seq, we identified 469 genes that were differentially expressed. Furthermore, our bioinformatics exploration uncovered two potential transcription factors, PpMYB1 and PpbHLH1, which play regulatory roles in anthocyanin accumulation. Y2H assays demonstrated that these two TFs could form heterodimers and interact with each other. Afterwards, transient expression assays were conducted for the first time in P. pulcherrima flowers, revealing that overexpression of PpMYB1 alone or in combination with PpbHLH1 resulted in purple petal pigmentation. Overexpressing PpMYB1 in tobacco resulted in more purple-colored corollas, stamens, pistils, and pods compared to control plants. Y1H and dual-luciferase assays provided further evidence that PpMYB1 and PpbHLH1 interact with the promoters of the structural genes PpF3H, PpDFR, and PpANS in the anthocyanin biosynthesis pathway, thereby driving their robust expression. This study not only enhances our understanding of the molecular mechanisms underlying anthocyanin synthesis but also holds significant practical implications for advancing plant hybrid breeding and genetic engineering applications in flower color regulation. Full article

Background/Objectives: The regulatory SNPs (rSNPs) that disturb the binding of transcription factors (TFs) and alter the transcription levels of genes play a paramount role in the formation of different traits and are associated with many pathologies. The search for allele-specific events in RNA-seq and ChIP-seq data is a powerful genome-wide approach to detect rSNPs. Using this approach, we have identified the T → A rs2072580 substitution in the bidirectional SART3/ISCU promoter as a potential rSNP and demonstrated its association with colorectal cancer, relying on International Cancer Genome Consortium data. The goal of this work was to identify the TF binding site that is affected by the T → A substitution and to study the effect of this substitution on reporter gene expression in different plasmid constructs. Methods: Electrophoretic mobility shift assay (EMSA), cross-competition analysis and supershift assay, plasmid construction, and dual luciferase reporter assay. Results: The T → A rs2072580 substitution is shown to damage the binding site for ubiquitous TF CREB1 and to significantly decrease the activity of the heterologous promoter carrying the cassettes of two or three repeated CREB binding sites inserted upstream of it. However, the substitution disturbing the CREB1 binding site within the bidirectional promoter shared by SART3 and ISCU inhibits the promoter activity of only the SART3 gene but has no effect on the activity of the ISCU promoter. Conclusions: The performed comprehensive functional analysis of the T → A rs2072580 in the bidirectional SART3/ISCU promoter unambiguously implies it is an rSNP. These results form the background for further studies of this rSNP and its potential significance for various pathologies. Full article

Anthocyanins, as natural pigments belonging to the flavonoid group, play a crucial role in plant reproduction, stress resistance and human fitness. Kiwifruit, which is rich in anthocyanins, demonstrates significant potential for promoting health benefits. Although light is widely recognized as an inducer of anthocyanin accumulation, we observed that kiwifruit accumulates more anthocyanin after bagging treatment. This unexpected finding suggests that anthocyanin biosynthesis in kiwifruit may also be regulated by other environmental or physiological factors influenced by bagging, such as humidity, temperature, or gas exchange. This implies that bagging may trigger specific regulatory pathways that promote anthocyanin accumulation through multiple environmental cues beyond light. Therefore, RNA-seq was performed to find the potential pathway. A total of 260 differentially expressed genes were found, including 8 transcription factors and 1 anthocyanin biosynthesis gene F3GT1 (glucosyltransferase). Dual-luciferase reporter assays revealed that bHLH transcription factors could activate the promoter of F3GT1 by 2.45-fold. We infer that bagging treatment increases the kiwifruit anthocyanin content through the bHLH291-F3GT1 pathway. This study not only highlights the potential agricultural applications and commercial value of bagging treatment but also provides new theoretical support for improving fruit coloration and optimizing breeding strategies. Full article