Search Results (3,338)

Background: Coronary heart disease (CHD) has a high global disease burden. According to traditional Chinese medicine theory, the main syndrome type of CHD is the syndrome of intermingled phlegm and blood stasis (SI-GPBS). Tanyu Tongzhi Decoction (TYTZD) exerts clear cardioprotective effects on CHD patients with SI-GPBS, while its specific regulatory mechanism remains unclear. Methods: Clinical serum proteomics and network pharmacology were used to screen key targets and pathways for CHD with SI-GPBS. An APOE^−/− mouse model of CHD complicated with SI-GPBS was established and treated with TYTZD. Transcriptomics, proteomics and WGCNA were combined to screen core genes, with Western blotting, immunofluorescence, co-localization analysis and Carstairs staining for target verification and observation of coronary microthrombosis and endothelial injury. Results: A total of 754 differentially expressed proteins were identified in CHD patients with SI-GPBS, significantly enriched in the platelet activation pathway, with ITGA2B as the upregulated core hub protein. Network pharmacology found 94 active ingredients and 144 therapeutic targets of TYTZD for CHD with SI-GPBS, and key components bound well with ITGA2B. In APOE^−/− mice with SI-GPBS, TYTZD improved cardiac function, reduced blood lipids, myocardial enzymes, aortic lipid deposition and myocardial damage, downregulated ITGA2B, F2RL2, FGA and FGB, inhibited integrin αIIbβ3 signaling, restrained endothelial activation and reduced coronary microthrombosis. Conclusions: TYTZD treats CHD with SI-GPBS mainly by inhibiting platelet activation, improving endothelial dysfunction, and reducing coronary microthrombosis. This study provides experimental basis for TYTZD’s clinical application in CHD with SI-GPBS and new ideas for TCM syndrome–disease combination research. Full article

For the first time, a regulatory network linking melanin, genes, pathways, and edible quality was constructed for 138 Auricularia cornea strains sourced domestically and internationally. This marks the inaugural study of A. cornea spanning from cellular to physical-mechanical properties. Correlation analysis between melanin and edible quality traits (hardness, springiness, cohesiveness, gumminess, chewiness, and resilience) revealed that hardness, cohesiveness, and gumminess increased with rising melanin content, while springiness correspondingly decreased. Genome-wide association analysis identified 15,597,589 SNP loci. A total of 39 genes related to food quality were annotated, including one melanin-related lacquer enzyme gene, ACW004924. Real-time quantitative PCR validation of key genes identified for melanin and edible quality traits revealed results consistent with those from correlation analysis. The lacquer enzyme genes ACW004736, ACW006232, which regulate melanin synthesis, and the tyrosinase genes ACW001451, ACW002443, and ACW001003 were also identified in edible quality traits. These genes perform similar functions in GO-enriched metabolic processes, catalytic activity, and cellular structural complexes, as well as in KEGG-enriched pathways such as carbon metabolism and polysaccharide synthesis. They catalyze melanin synthesis and promote interactions between melanin and cell wall polysaccharides, chitin, and structural proteins, thereby stabilizing the cellular scaffold structure, jointly mediating the effect of melanin on the edible quality of A. cornea. The results supplement the downstream regulatory chain of catalytic enzymes and edible quality in the γ-L-glutaminyl-3,4-dihydroxybenzene (GDHB) pigment synthesis pathway, and form an information network of melanin synthesis, cell wall structure optimization, and edible quality regulation. Full article

Powdery mildew in wheat, caused by the biotrophic fungus Blumeria graminis f. sp. tritici (Bgt), is a major threat to global wheat production, yet the molecular mechanisms underlying differential cultivar resistance remain largely unresolved. In this study, tandem mass tag (TMT)-based quantitative proteomics was employed to investigate protein dynamics in resistant (Yannong37) and susceptible (Yannong1766) wheat cultivars at 0 and 24 h following Bgt inoculation. A total of 276 proteins exhibited significant changes in abundance after infection, with enrichment in cell wall and plasmodesmata-associated proteins. Comparative analysis further identified 456 differentially expressed proteins between the two cultivars at 24 h post-inoculation. Protein–protein interaction network analysis indicated that proteins involved in secondary metabolism and immune responses form coordinated regulatory networks contributing to disease resistance. RT–qPCR validation supported the reliability of the proteomic data. Notably, TaCAD-A1 displayed higher transcript abundance in the resistant cultivar and was associated with reduced fungal biomass accumulation. Silencing of TaCAD-A1 resulted in decreased expression of multiple defense-related genes. Collectively, these findings suggest that TaCAD-A1 may positively contribute to wheat resistance against Bgt infection and may be associated with defense responses and monolignol biosynthesis-related processes. Full article

Precision nano-fertilization offers transformative potential for sustainable improvement of grape quality, yet the underlying molecular mechanisms remain poorly understood. Here, we investigated the effects of foliar-applied nano zero-valent iron (nZVI) and potassium dihydrogen phosphate (KH₂PO₄), in combination, on berry quality and secondary metabolic reprogramming in Vitis vinifera cv. Marselan. The combined nZVI/KH₂PO₄ treatment improved photosynthetic capacity, Fe/P co-accumulation, and berry quality traits including soluble solid content, sugar–acid ratio, and phenolic and aroma metabolite profiles. Crucially, integrated transcriptomic and metabolomic profiling identified 631 differentially expressed genes and 838 differentially accumulated metabolites, converging on flavonoid biosynthesis and glutathione metabolism as the dominant regulatory axes. Correlation network analysis pinpointed five hub regulatory genes—VvHCT, VvFLS1, VvLAR1/2, VvUGT88F5, and VvODC—as central orchestrators of nanomaterial-driven metabolic reprogramming: VvHCT and VvFLS1 coordinately redirected carbon flux toward hydroxycinnamic acid conjugates and flavonol accumulation, while VvLAR1/2 governed proanthocyanidin polymerization, and VvUGT88F5 modulated glycosylation-dependent metabolite stabilization. Notably, VvODC linked polyamine metabolism to glutathione-mediated stress buffering, revealing a previously uncharacterized crosstalk between nano-iron signaling and antioxidant reprogramming. These findings establish a mechanistic framework in which nZVI and KH₂PO₄ synergistically remodel the secondary metabolome through discrete yet interconnected transcriptional nodes, providing molecular targets for nano-enabled precision viticulture and broader applications of engineered nanomaterials in high-value crop improvement. Full article

Heat stress (HS) is among the most economically consequential environmental challenges to global dairy production, causing progressive declines in milk yield, compositional quality, and mammary cellular integrity. The temperature–humidity index (THI) is the primary thermal load metric, with performance-impairment thresholds typically beginning at THI 68 in Holstein cattle, with severe impacts manifesting beyond THI 72; breed-specific thresholds for Jersey, Brown Swiss, and Simmental cows differ owing to their lower metabolic heat load and greater inherent thermotolerance. At the molecular level, HS activates heat shock protein networks—notably HSPA1A, HSP90B1, and HSPH1—through HSF1/HSF4 transcriptional activation, while simultaneously suppressing casein genes (CSN1S1, CSN2, CSN3), lipogenic genes (FASN, SCD, CD36), amino acid transporters (SLC7A5, SLC38A2), and mTOR-AKT-STAT5 translational machinery, collectively impairing milk biosynthetic capacity. Pro-apoptotic signaling (BAX, CASP3 upregulation; BCL2 downregulation) and mitochondrial dysfunction further compromise mammary epithelial viability. Post-transcriptional regulation through miRNA, circRNA, and lncRNA competing endogenous RNA networks, alongside epitranscriptomic m6A modifications, adds further regulatory complexity. Genome-wide association studies have identified SNPs in HSP70A1A, HSPA4, TLR4, and PRLR as thermotolerance candidates compatible with sustained milk production. Nutritional supplementation with methionine, arginine, and taurine partially restores cellular synthetic capacity. Integrating multi-trait genomic selection with Bos indicus introgression, precision cooling, and targeted nutrition offers the most viable path toward climate-resilient, high-producing dairy cattle. Full article

Despite decades of therapeutic advances, cardiovascular diseases remain the leading cause of global mortality, underscoring the need for strategies that move beyond untargeted systemic pharmacotherapy. Synthetic biology introduces a programmable therapeutic paradigm in which engineered gene circuits can sense, compute, and respond to pathological signals with spatiotemporal precision. This review examines the current progress of synthetic gene circuits for cardiovascular therapy, organized across three domains of clinical relevance. The first domain comprises circuits engineered for direct cardiac applications, from inducible switches to classifier systems. This discussion is further expanded by exploring circuits that indirectly target cardiovascular disease; these circuits address upstream risk factors such as cholesterol dysregulation and chronic inflammation. Looking ahead, the focus shifts to orthogonal architectures pioneered in other therapeutic contexts that hold promise for future cardiac applications. This review further discusses the emerging role of computational tools, including gene regulatory network inference and foundation models, in accelerating target discovery. Finally, a modified Design-Build-Test-Learn framework is proposed to overcome translational bottlenecks, thus paving the way for next-generation cardiac therapeutics. Full article

Background/Objectives: Tree peony (Paeonia suffruticosa) has a short flowering period, and its regulatory mechanisms remain poorly understood. These limitations have severely constrained its industrial development. Expansins (EXPs) are key proteins that mediate cell wall loosening associated with petal expansion, yet they remain uncharacterized in tree peony. Methods: This study utilized gene family identification, key gene screening and functional research, as well as regulatory network analysis to reveal the role of the EXP family in the regulation of flower opening. Results: This study presents the first genome-wide identification of 36 PsEXP genes in tree peony, classifying them into four evolutionarily conserved subfamilies (PsEXPA, PsEXPB, PsEXLA, and PsEXLB). Promoter analysis revealed that 28 out of 36 PsEXP promoters contain gibberellin (GA)-responsive elements. Exogenous GA₃ treatment significantly promoted flower opening and upregulated eight PsEXPs, with PsEXPA4-1 showing the highest expression level and promoter GA-responsive element abundance. Subcellular localization confirmed that PsEXPA4-1 was targeted to the cell wall. Overexpression of PsEXPA4-1 in Arabidopsis led to early flowering and enlarged petals, indicating that PsEXPA4-1 had the potential to promote cell expansion, consistent with its proposed role in tree peony flower opening. Mechanistically, we identified a bHLH transcription factor, PsbHLH25, whose expression was induced by GA. Y1H and dual-luciferase assays indicated that PsbHLH25 can bind to the PsEXPA4-1 promoter. Conclusions: This study systematically characterized the EXP gene family in tree peony, revealed PsEXPA4-1 as a key effector downstream of GA promoting flower opening, and discovered PsbHLH25 as a transcriptional activator linking GA signaling to PsEXPA4-1. These findings provided important insights into GA-mediated floral opening and genetic resources for understanding the molecular mechanisms and enabling precise flowering time regulation in tree peony. Full article

RNA N⁶-methyladenosine (m⁶A) is a prevalent epitranscriptomic modification that governs plant growth, development, and environmental adaptation. This review synthesizes recent advances in understanding the molecular mechanisms and biological functions of m⁶A in plants. The m⁶A landscape is dynamically regulated by methyltransferases (writers), demethylases (erasers), and m⁶A-binding proteins (readers), which collectively influence mRNA stability, translation efficiency, alternative polyadenylation (APA), and chromatin crosstalk. Functionally, m⁶A integrates diverse developmental processes—including embryogenesis, organogenesis, flowering, fruit ripening, and leaf senescence—with abiotic stress responses such as salt, drought, cold, and heat. Notably, m⁶A modification exhibits remarkable species-, cultivar-, and tissue-specific plasticity, enabling precise spatiotemporal gene regulation. Recent breakthroughs have revealed bidirectional crosstalk between m⁶A and histone modifications, forming a multi-layered regulatory network, while emerging concepts including phase separation, RNA structure dynamics, and stress memory further expand the functional repertoire of m⁶A. Despite significant progress, plant epitranscriptomics remains mechanistically underexplored, with critical gaps persisting in our understanding of translation initiation mechanisms, upstream regulatory signals controlling writers/erasers activities, and the functional significance of individual m⁶A sites. This review provided systematic insights into the complexity and specificity of m⁶A regulation in plants, offering a theoretical foundation for future efforts to decipher and ultimately manipulate this epitranscriptional layer for crop improvement. Full article

Transcriptome profiling has been widely used to dissect the molecular mechanisms underlying plant responses to environmental stresses, yet the extent to which RNA changes reflect functional protein levels remains unclear. Here, we performed an integrated multi-omics analysis of the transcriptome, proteome, phosphoproteome, and acetylome in rice during a drought–rewatering cycle. We first identified 5449 differentially expressed genes (DEGs) and 525 differentially expressed proteins (DEPs) under drought stress, followed by 4340 DEGs and 328 DEPs upon rewatering, which underpinned an extensive remodeling of photosynthetic and metabolic pathways. Temporal clustering of transcriptomic and proteomic data then delineated five distinct expression patterns for both transcripts and proteins, uncovering transcriptional and translational strategies ranging from rapid reversal to persistent stress adaptation. Despite the observed coherence in some expression clusters, we nonetheless uncovered widespread transcriptome–proteome discordance, with a substantial fraction of gene–protein pairs exhibiting uncorrelated abundance changes. Remarkably, the observed discordance is quantitatively associated with the dynamic nature of post-translational modifications, including phosphorylation and acetylation, which act as key post-transcriptional tuners to independently regulate protein abundance—particularly for components of photosynthesis and energy metabolism—enabling plants to dynamically balance stress tolerance with the maintenance of core physiological functions. Our research delves into the intricate and often distinct regulatory networks that span transcriptional, translational, and post-translational levels, extending beyond a singular transcriptional focus. Full article

Soil salinity is a major constraint on crop productivity, and plants rely on multilayered regulatory mechanisms to adapt to stress. Alternative splicing (AS) enhances transcriptome plasticity, yet how light modulates AS under salt stress remains unclear. Here, we performed a transcriptome-wide analysis to investigate light-dependent AS dynamics in sweet potato under salt stress. Plant treatments were initiated during daytime (SD) and nighttime (SN) conditions, and samples were collected at five time points (0–8 h). Intron retention (IR) was the predominant AS type (~36–37%), followed by A3SS, A5SS, and exon skipping (SE). Notably, light enhanced both the magnitude and temporal dynamic of AS, with a pronounced early response (0–2 h) under SD, where differential AS (DAS) events were nearly doubled compared with SN. This early AS response was accompanied by an increased prevalence of IR events and upregulation of spliceosome-related genes, suggesting dynamic splicing regulation under light. Enrichment of the mRNA surveillance pathway further indicates that IR-derived transcripts may be subject to RNA quality control. Although enriched pathways were largely conserved between SD and SN, including spliceosome and mRNA surveillance, more DAS genes under SD indicate enhanced responsiveness of conserved regulatory networks. These findings demonstrate that light reshapes the temporal dynamics of AS under salt stress, primarily through IR and its coupling with RNA surveillance, providing new insights into post-transcriptional regulation in crop stress adaptation. Full article

Oocyte maturation is a pivotal event in teleost reproduction that directly determines egg quality, fertilization success, and the developmental competence of early embryos. However, the transcriptional and post-transcriptional regulatory mechanisms operating within oocytes during maturation in marine teleosts remain poorly understood. In the present study, the orange-spotted grouper (Epinephelus coioides), an economically important marine aquaculture species, was used as a model. Oocytes at four distinct maturation stages were obtained by microscopically removing the surrounding follicular layers, followed by integrated mRNA-seq and miRNA-seq analyses to characterize the molecular regulatory landscape underlying oocyte maturation and hydration. The results showed that, as maturation progressed, oocyte diameter and wet weight increased significantly, accompanied by a marked decrease in Na⁺ content, a significant increase in K⁺ content, and the continuous accumulation of most free amino acids, indicating the gradual establishment of an osmotic basis favorable for oocyte hydration. Transcriptomic analysis further revealed extensive transcriptional remodeling during both the early and late phases of maturation. Differentially expressed genes were significantly enriched in pathways related to oocyte meiosis, cytokine signaling, lipid metabolism, DNA replication, cell cycle regulation, ribosome biogenesis, spliceosome function, oxidative phosphorylation, and mitochondrial activity, suggesting that oocyte maturation is a dynamic process characterized by a shift from basal growth maintenance to metabolic reprogramming, maternal transcript remodeling, and terminal maturation responses. miRNA profiling identified a large number of stage-specific differentially expressed miRNAs, including let-7d-5p, miR-22a-3p, and novel-miR-20/27/118, whose predicted target genes were mainly enriched in ribosome-related pathways, oxidative phosphorylation, DNA replication, transcriptional regulation, and signal transduction. Moreover, the miRNA–TF–mRNA regulatory network demonstrated that miRNAs may not only directly repress target genes, but also mediate hierarchical regulatory cascades through transcription factors, thereby coordinately participating in cell cycle progression, cytoskeletal remodeling, vesicular transport, and immune- and cell communication-related responses. Collectively, this study provides the first systematic temporal atlas of mRNA and miRNA regulation during oocyte maturation and hydration at the oocyte level in a marine teleost, thereby deepening our understanding of the molecular basis of meiotic resumption and egg quality formation, and offering valuable theoretical support for the optimization of artificial breeding and the identification of key molecular targets in grouper reproduction. Full article

Vairimorpha ceranae (formerly Nosema ceranae) is an obligate intracellular parasite that poses a major threat to the health of the honey bee. Circular RNAs (circRNAs) have been recognized as key regulators in gene expression and pathogen–host interactions. However, their expression patterns and regulatory roles in V. ceranae infection remain largely unexplored. In this study, we performed circRNA profiling in V. ceranae spores (NcCK) and the midguts of Apis mellifera ligustica workers at 7 d post inoculation (dpi) and 10 dpi (Nc7T and Nc10T) based on transcriptome sequencing, followed by in-depth investigation of the regulatory roles of differentially expressed circRNAs (DEcircRNAs). In total, 243 circRNAs were identified in V. ceranae, with lengths predominantly ranging from 201 to 400 nucleotides. Comparative analysis screened 70 and 192 DEcircRNAs in the NcCK vs. Nc7T and NcCK vs. Nc10T comparison groups, respectively, with a significant majority being downregulated. The parental genes of these DEcircRNAs were significantly enriched in fundamental cellular processes and critical pathways such as protein processing in the endoplasmic reticulum and ribosome biogenesis. Additionally, we constructed a competing endogenous RNA network, suggesting that DEcircRNAs could potentially interact with DEmiRNAs to modulate mRNAs associated with fungal proliferation-relevant signaling pathways like MAPK, PI3K–Akt, and cAMP. Moreover, numerous DEcircRNAs were predicted to contain internal ribosome entry site elements, indicative of their potential for protein coding. The back-splicing junctions and expression trends of selected DEcircRNAs were successfully validated by RT-PCR and qRT-PCR. Our data not only offer a valuable resource for future functional studies but also provide a basis for elucidating the circRNA-mediated mechanisms underlying microsporidian pathogenesis and host–pathogen interactions. Full article

Fruit endocarp and seed coat are essential protective structures that influence key agronomic and mechanical traits in species with lignified protective tissues, yet their regulatory mechanisms remain incompletely understood. Here, we conducted a comprehensive genome-wide analysis of the MADS-box gene family in four angiosperm species: Juglans sigillata, Carya illinoinensis, Macadamia integrifolia, and Ricinus communis. A total of 58, 55, 57, and 57 MADS-box genes were identified, respectively, and systematically characterized through phylogenetic, structural, and evolutionary analyses. Comparative results revealed that MIKCc-type genes are highly conserved and primarily expanded via segmental duplication under strong purifying selection. Co-expression network analysis identified MADS-box genes as high-connectivity hub candidates that are strongly associated with genes involved in tissue specification, hormone signaling, and secondary cell wall biosynthesis. Promoters analysis indicated that these genes contain diverse cis-regulatory elements; however, these results are based on sequence prediction and do not demonstrate functional regulatory interactions. Across species, MADS-box genes exhibited analogous temporal expression dynamics during lignified endocarp and seed coat development, consistent with a potentially conserved transcriptional framework. Collectively, this study provides new insights into the evolutionary diversification and putative functions of MADS-box genes, and proposes a putative hierarchical regulatory framework for lignified endocarp and seed coat development. These findings supply valuable candidate target genes for future molecular breeding aimed at improving shell thickness, hardness, and related agronomic traits in woody nut and oilseed species. Full article

Fusarium graminearum infection of maize induces complex transcriptional reprogramming, yet existing differential-expression and local graph convolutional approaches struggle to capture long-range and multi-scale regulatory dependencies. We propose DC-FusionGNN, a dual-channel fusion graph neural network for key resistance-gene identification. Based on the transcriptome dataset GSE174508, we first construct a comprehensive gene interaction network by integrating a WGCNA co-expression network with a STRING-based interaction network. The left channel combines structure-aware propagation with a Transformer-based global self-attention mechanism to model long-range cross-module dependencies, while the right channel couples GraphSAGE with a GCN to capture local topology and neighborhood heterogeneity. Embeddings from the two channels are concatenated to form a unified gene representation, trained via self-supervised link prediction. Compared with baseline graph neural networks, DC-FusionGNN achieves competitive and overall improved performance across multiple metrics, and robustness and independent cross-species (rice, GSE39635) experiments further confirm its stability and generalization ability. GO and KEGG enrichment analyses show that the top-ranked candidate genes are significantly enriched in plant defense responses, hormone signaling, and secondary metabolism, supporting the biological relevance of the model’s predictions. Full article

Soil salinity is a major environmental constraint limiting plant productivity and modulating secondary metabolism. Triterpenoid saponins play crucial roles in plant stress adaptation, yet their biosynthetic regulation in Cyclocarya paliurus under salt stress remains poorly understood. This research integrated transcriptomic and metabolomic analyses to investigate triterpenoid saponin metabolism in C. paliurus leaves at four NaCl concentrations and two sampling times. Salt stress altered ion homeostasis, suppressed growth, and induced distinct triterpenoid saponins accumulation patterns, with cyclocaric acid B and oleanolic acid showing significant increases. Weighted gene co-expression network analysis identified two modules significantly correlated with triterpenoid saponin accumulation and highlighted transcription factors including WRKY18, bHLH121, ERF4, and ERF1 as regulators of key biosynthetic genes (DXS, SQS, and HMGR). Molecular docking further validated these regulatory interactions, demonstrating that bHLH35, MYC2, ERF113, and MED26B form stable complexes with target gene promoters through extensive hydrogen-bond networks. These findings elucidate the regulatory framework of triterpenoid saponin metabolism under salinity and provide a foundation for molecular breeding and cultivation of C. paliurus in saline regions. Full article