Search Results (2,814)

Antimony (Sb) is a toxic metalloid and has become an increasingly prevalent contaminant in ecosystems. Previous studies have reported that Sb has severe toxic effects on plant growth. However, the molecular mechanisms of the response to Sb stress in plants still remain unclear. In the present study, common bermudagrass (Cynodon dactylon [L.] Pers.), ‘Yangjiang’ cultivar, was treated with 200 mg/mL of antimony potassium tartrate solution. Integrated metabolomic and transcriptomic analysis was conducted to investigate the mechanisms of the Sb stress response of bermudagrass. The results showed that, after Sb stress treatment, soluble protein content, malondialdehyde (MDA) content, and catalase (CAT) activity increased by 180.56%, 280%, and 112.61%, respectively, compared to the control. Meanwhile, transcriptomic and metabolomic analyses identified numerous differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) that were involved in the Sb stress response of bermudagrass, and many pathways, such as the carbon metabolism, photosynthesis and alanine, aspartate, and glutamate metabolism pathways, were also identified to be related to the Sb stress response of the bermudagrass plant by KEGG and GO enrichment. Overall, the present study revealed that photosynthesis and amino acid metabolism pathways play important roles in the Sb stress response of bermudagrass. Full article

Late spring frosts represent a major threat to grapevine (Vitis vinifera L.), a risk increasingly exacerbated by climate change-driven shifts in phenology. To explore sustainable strategies for frost mitigation, this study investigated the effect of a natural polysaccharide-based biogel, derived from carob (Ceratonia siliqua L.), on the molecular response of grapevine buds exposed to severe cold stress. To this aim, a preliminary RNA-Seq analysis was carried out to compare the transcriptomes of biogel-treated frozen buds (BIOGEL), untreated frozen buds (NTF), and unstressed controls (TNT). The transcriptomic analysis revealed extensive reprogramming of gene expression under freezing stress, highlighting the involvement of pathways related to membrane stabilization, osmotic adjustment, and metabolic regulation. Interestingly, the biogel treatment appeared to attenuate the modulation of several cold-responsive genes, particularly those associated with membrane functionality. Based on these preliminary transcriptomic data, twelve candidate genes, representative of the functional classes affected by biogel treatment, were selected for qRT-PCR validation. The expression patterns confirmed the RNA-Seq trends, further suggesting that biogel application might mitigate the typical transcriptional activation induced by frost, while supporting genes involved in cellular protection and integrity maintenance. The overall analyses suggest that the biogel may act through a dual mechanism: (i) providing a physical barrier that reduces cold-induced cellular damage and stress perception, and (ii) promoting a selective adjustment of gene expression that restrains excessive defense activation while enhancing membrane stability. Although further field validation is required, this natural and biodegradable formulation represents a promising and sustainable tool for mitigating late frost injuries in viticulture. Full article

Gastric diseases represent a significant challenge to global health. A comprehensive understanding of their complex molecular mechanisms, particularly the pathways of molecular progression in precancerous lesions, is essential for enhancing diagnosis and treatment. StomachDB, the first comprehensive multi-omics database dedicated to gastric diseases, has been developed to address these research needs. This database integrates 6 types of biological data: genomics, transcriptomics, emerging single-cell and spatial transcriptomics, proteomics, metabolomics, and therapeutic-related information. It encompasses 44 gastric-related pathologies, including various forms of gastric cancer, gastric ulcers, and gastritis, primarily involving humans and mice as model organisms. The database compiles approximately 2.5 million curated and standardized profiles, along with 268,394 disease-gene associations. The user-friendly analytics platform provides tools for browsing, querying, visualizing, and downloading data, facilitating systematic exploration of multi-omics features. This integrative approach addresses the limitations of single-omics analyses, such as data heterogeneity and insufficient analytical dimensions. Researchers can investigate the clinical significance of target genes (e.g., CDH1) across different omics levels and explore potential regulatory mechanisms. Furthermore, StomachDB emphasizes the discovery of therapeutic targets by cataloging interactions among chemical drugs, traditional herbal medicines, and probiotics. As an open-access resource, it serves as a powerful tool for studying complex biological interactions and regulatory mechanisms. Full article

CaMK4, a calcium/calmodulin-dependent protein kinase, is an important mediator of cellular signal transduction, yet its role in the regulation of skeletal muscle satellite cells (MuSCs) in goats has remained unclear. In this study, CaMK4 overexpression and knockdown models were established, and integrated transcriptomic and proteomic analyses were performed to systematically elucidate its regulatory network. CaMK4 overexpression altered key pathways associated with cell proliferation and muscle development, including cAMP, PI3K-Akt, and actin cytoskeleton regulation, while proteomic data highlighted calcium signaling and JAK-STAT pathways. Conversely, CaMK4 knockdown enhanced MuSC proliferation by upregulating cell cycle-related genes and proteins. Integrated analyses further identified that Galectin-9 (LGALS9), Collagen triple helix repeat containing-1 (CTHRC1), Hyaluronan Synthase 1 (HAS1), and L-Threonine Dehydrogenase (TDH) may serve as potential key nodes regulating cell cycle, apoptosis, and metabolic control. This suggests a regulatory role for CaMK4. Collectively, these findings provide a mechanistic framework for understanding CaMK4 function in ruminant muscle development and may offer insights for improving goat muscle growth, meat quality traits, and production efficiency. Full article

Porcine extraintestinal pathogenic Escherichia coli (ExPEC) is a significant zoonotic pathogen with escalating antimicrobial resistance, underscoring the urgent need for novel therapeutics. This study aimed to investigate the therapeutic potential and mechanism of action of the antimicrobial peptide Protegrin-1 (PG-1) against a multidrug-resistant porcine ExPEC strain, PCN033. The minimal inhibitory concentration (MIC) was determined, and resistance stability was assessed through serial induction and withdrawal passages. Hemolytic activity was evaluated to gauge selectivity. A murine infection model was utilized to assess in vivo efficacy, bacterial load reduction, cytokine modulation, and histopathology. Comparative spleen transcriptomic analysis was performed to elucidate global host responses. PG-1 exhibited potent bactericidal activity (MIC = 32 μg/mL) and maintained its efficacy over multiple passages, demonstrating no induced resistance. It showed acceptable hemolytic activity and significantly improved survival, reduced bacterial loads in multiple organs, and mitigated tissue damage in mice. Transcriptomics revealed PG-1 treatment broadly tempered infection-induced hyperinflammatory responses, including NF-κB, MAPK, and TNF signaling pathways, and counteracted metabolic reprogramming. The findings conclude that PG-1 effectively integrates direct, resistance-resistant bactericidal activity with multimodal immunomodulation, representing a superior therapeutic strategy that simultaneously eliminates pathogens and restores immune homeostasis, offering a promising alternative to conventional antibiotics against MDR ExPEC infections. Full article

(1) Background: This study aims to systematically identify key candidate genes and the regulatory networks governing ovarian development in sheep breeds with divergent fecundity. Focusing on elucidating the central regulatory roles of these factors during distinct ovarian developmental stages in highly prolific breeds, the research seeks to reveal the mechanism by which multilevel regulatory networks synergistically determine ewe reproductive capacity. (2) Methods: This study utilized the ovaries from the low-fecundity sheep breed Ujumqin sheep, the high-fecundity breed small-tailed Han sheep, and various developmental stages of small-tailed Han sheep as research subjects. Through whole-transcriptome sequencing analysis, differentially expressed mRNAs(DEGs) and non-coding RNAs (ncRNAs) were screened, and a ceRNA regulatory network was constructed and subjected to bioinformatic analysis. The dual-luciferase reporter gene detection system was employed to validate the targeting relationships within the obtained key circRNA-miRNA-mRNA networks. Finally, qRT-PCR was used to verify the accuracy of the sequencing results. (3) Results: Our analysis constructed two distinct ceRNA networks: one from different fecundity groups (116 DECs, 46 DEMs, 82 DEGs) and another from different ovarian stages (186 DECs, 143 DEMs, 338 DEGs). Functional enrichment revealed key reproduction-related pathways, including Mitogen-Activated Protein Kinase(MAPK), Janus Kinase-Signal Transducer and Activator of Transcription(JAK-STAT), and WNT signaling in the fecundity comparison, and MAPK, Ras, WNT, Hippo signaling in the developmental stage comparison. Integrated analysis identified a core circRNA-miRNA-mRNA network, pinpointing circRNA2058-miR-9226-5p-MET as a central regulatory axis. The dual-luciferase assay confirmed that circRNA2058 acts as a sponge for miR-9226-5p, thereby mediating MET expression. qRT-PCR validation of randomly selected RNAs confirmed the sequencing reliability. (4) Conclusions: this study deciphers a synergistic regulatory network and identifies, for the first time, the pivotal circRNA2058-miR-9226-5p-MET ceRNA axis as an potential critical molecular switch driving follicular dominance in sheep. This discovery provides a molecular foundation for targeting core regulators of ovine reproductive efficiency and offers significant insights for innovative strategies in enhancing sheep reproduction. Full article

The pericarp of Macadamia integrifolia represents a promising but underexplored source of functional flavonoids. To systematically elucidate their biosynthesis and enhance the industrial potential of this by-product, we conducted integrated transcriptomic and metabolomic profiling of pericarps across five developmental stages (50, 80, 110, 140, and 170 days after flowering). Our analysis reveals, for the first time, a distinct temporal shift in both gene expression and metabolite accumulation. Early stages were characterized by high expression of PAL, 4CL, CHS, and FLS, coupled with abundant flavonols and anthocyanins. In contrast, late stages exhibited upregulation of CHI and F3’5’H, redirecting the metabolic flux toward flavanones and isoflavones. This dynamic profile was closely associated with jasmonate and gibberellin signaling pathways and was likely regulated by key transcription factors (MYB, NAC, bHLH). These findings provide a multi-omics framework that elucidates the temporal flavonoid biosynthesis in macadamia pericarp, thereby laying the groundwork for its future industrial valorization. Full article

Hepatocellular carcinoma (HCC) is the most prevalent primary malignancy of the liver. Characterized by rapid progression and poor overall survival rates, HCC requires effective and streamlined treatment regimens. It predominantly occurs in East Asia and sub-Saharan Africa, where it has historically been managed with herbal formulas. We previously observed that the herbal formula HO-1089 exerts potent anti-HCC effects both in vitro and in vivo. In this study, we investigated the anticancer efficacy and mechanisms of HO-1197, a reconstituted herbal formulation derived from HO-1089. HO-1197 selectively inhibited the viability of HCC cell lines without hepatotoxicity and demonstrated superior anticancer activity compared with both HO-1089 and sorafenib. Mechanistically, HO-1197 induced apoptosis and G2/M arrest through reactive oxygen species-mediated DNA damage, independent of p53 status. Transcriptomic analysis revealed downregulation of mitosis-related genes, particularly those regulated by FOXM1, a key driver of HCC proliferation and metastasis. HO-1197 suppressed FOXM1 expression and nuclear translocation, reducing its downstream targets and diminishing angiogenic and metastatic potential. Furthermore, HO-1197 modulated the tumor immune microenvironment by promoting pro-inflammatory macrophage polarization and enhancing natural killer cell-mediated cytotoxicity. HO-1197 exhibited potent antitumor efficacy, and combination therapy with HO-1197 and sorafenib exhibited synergistic effects in both two-dimensional and immune-activated multicellular spheroid models. These findings suggest that HO-1197 is a promising multifunctional therapeutic candidate with antitumor, antiangiogenic, antimetastatic, and immunomodulatory properties. Its combination with sorafenib may offer effective treatment for HCC. HO-1197, which demonstrated strong efficacy, is a novel herbal medicine developed by H&O Biosis and is referred to as an Integrated Natural Medicine. Full article

Aroma is a crucial quality trait in ornamental flowers; however, the molecular mechanisms by which hormones regulate fragrance in Rhododendron remain poorly understood. In this study, Gibberellin (GA₃)-treated petals of Rhododendron fortunei Lindl were used as experimental materials to integrate volatile metabolomics with RNA-seq analysis, aiming to investigate aroma changes and their underlying molecular regulatory mechanisms. We cloned and characterized RfHMGR1, which encodes a key enzyme in the Mevalonate (MVA) pathway, and verified its function. Subcellular localization analysis showed that the Green Fluorescent Protein (GFP) signal of the RfHMGR1-GFP fusion protein was mainly distributed in the cytoplasm. Transient overexpression of RfHMGR1 in petals of two Rhododendron species (R. fortunei and Rhododendron hybrida) significantly increased the accumulation of the terpenoid linalool, whereas gene silencing reduced linalool accumulation. Furthermore, the purified recombinant RfHMGR1 protein exhibited HMGR-specific reductase activity in vitro. Our results confirmed that GA₃ regulates the terpenoid fragrance of R. fortunei by targeting the MVA pathway gene RfHMGR1. Collectively, these findings provide new insights into the fragrance regulation mechanisms in R. fortunei and identify molecular targets for breeding strategies aimed at improving floral scent. Full article

Radiomics has emerged as a promising tool for non-invasive tumour phenotyping in breast cancer, providing valuable insights into tumour heterogeneity, response prediction, and risk stratification. However, traditional radiomic approaches often rely on correlative patterns of image analysis to clinical data and lack direct biological interpretability. Combining information provided by radiomics with genomics or other multi-omics data can be important to personalise diagnostic and therapeutic work up in breast cancer management. This review aims to explore the current progress in integrating radiomics with multi-omics data—genomics and transcriptomics—to establish biologically grounded, multidimensional models for precision management of breast cancer. We will review recent advances in integrative radiomics and radiogenomics, highlight the synergy between imaging and molecular profiling, and discuss emerging machine learning methodologies that facilitate the integration of high-dimensional data. Applications of radiogenomics, including breast cancer subtype and molecular mutation prediction, radiogenomic mapping of the tumour immune microenvironment, and response forecasting to immunotherapy and targeted therapies, as well as lymph nodes involvement, will be evaluated. Challenges in technical limitations including imaging modalities harmonization, interpretability, and advancing machine learning methodologies will be addressed. This review positions integrative radiogenomics as a driving force for next-generation breast cancer care. Full article

Background and Objectives: Siglec-XII, encoded by SIGLEC12, is a unique sialic acid-binding immunoglobulin-like lectin. It lacks a highly conserved R122 residue for sialic acid recognition in humans. Although it is upregulated in bladder cancer (BCa), its role in tumorigenesis remains largely unexplored. This study aims to investigate the expression patterns of SIGLEC12 in BCa and its correlation with disease features. Materials and Methods: An integrated analysis of transcriptomic data and clinical profiles was conducted using various databases and tools, including UALCAN, GEPIA, TIMER, CAMOIP, and CPADs. The analyses encompassed SIGLEC12 expression, survival rates, immune infiltration levels, promoter methylation, and correlation with drug response. Results: SIGLEC12 expression was higher in both low-grade papillary and high-grade invasive non-papillary BCa. Higher SIGLEC12 expression resulting from low promoter hypomethylation was detected at the stage II-IV of BCa, and was unrelated to disease stages and metastatic stages. Elevated SIGLEC12 expression correlated with increased immune cell infiltration, higher expression of oncogenic and immune checkpoint blockade-related genes, and drug resistance signatures. Mutation analysis confirmed the absence of the canonical R122 missense mutation, indicating that the structural integrity and potential functionality of Siglec-XII are preserved in BCa. Conclusions: SIGLEC12 may have sialic acid recognition functions and serve as a potential early biomarker of BCa. Full article

Drought stress severely limits peanut productivity, highlighting the urgent need to understand the molecular mechanisms that underlie drought adaptation. While microRNAs (miRNAs) are known to play essential roles in plant stress responses, their functional contributions in polyploid crops like peanut remain insufficiently explored. This study provides the first integrated transcriptomic analysis of drought-responsive miRNAs in tetraploid peanut (Arachis hypogaea). We performed high-throughput sRNA sequencing on a drought-tolerant cultivar Fenhua 8 under PEG6000-simulated drought stress, identifying 10 conserved drought-responsive miRNAs. Among these, ahy-miR398 and ahy-miR408 were significantly downregulated under drought conditions. Degradome sequencing revealed that ahy-miR398 targets copper chaperones for superoxide dismutase (CCSs), potentially reducing SOD activation and amplifying oxidative stress. In contrast, ahy-miR408 targets laccase 12 (LAC12), P-type ATPase copper transporters (COPAs), and a blue copper protein-like (PCL) gene. These targets are involved in copper homeostasis and the regulation of reactive oxygen species (ROS), suggesting that ahy-miR408 plays a role in oxidative stress management. Functional validation in transgenic Arabidopsis lines overexpressing ahy-miR398 or ahy-miR408 showed significantly reduced drought tolerance, with impaired seed germination, shorter primary roots, and exacerbated growth suppression during water deprivation. Taken together, these findings highlight a novel miRNA-mediated regulatory network in peanut drought adaptation, centered on copper-associated oxidative stress management. This study provides new insights into miRNA-based regulation in polyploid crops and offers potential molecular targets for breeding climate-resilient peanut varieties, especially in arid regions where yield stability is crucial. Full article

Tacrolimus-induced chronic nephrotoxicity (TACN) represents a major barrier to long-term graft survival in kidney transplantation, yet its molecular pathogenesis remains incompletely understood. We have previously reported metabolic abnormalities, including carnitine deficiency, nicotinamide adenine dinucleotide depletion, and elevated asymmetric dimethyl arginine (ADMA), in TACN. To identify upstream regulators associated with these metabolic disturbances, we conducted a comprehensive trans-omic analysis, integrating transcriptomics and proteomics of kidney tissues from male ICR mice with TACN (n = 5/group). Differentially expressed genes and proteins were subjected to functional enrichment and transcription factor binding motif analyses, followed by upstream master regulator identification using the Genome Enhancer platform. A total of 785 genes and 2472 proteins were differentially expressed, with partially discordant regulation between transcriptomic and proteomic profiles, underscoring the limitations of single-omic approaches. Upstream analysis identified protein arginine methyltransferase-1 (PRMT1) and integrins, particularly αVβ6, as potential master regulators and therapeutic targets. PRMT1 is implicated in ADMA-mediated nitric oxide inhibition and fibrosis, whereas integrin αVβ6 is associated with tubular injury and renal fibrogenesis. Notably, PRMT1 may activate STAT3, which in turn regulates integrin β6 expression, suggesting a novel PRMT1–STAT3–integrin αVβ6 axis in TACN pathogenesis. This study represents the first trans-omic approach to TACN, providing a foundation for mechanistic validation and therapeutic exploration of PRMT1 and integrins in both preclinical and clinical settings. Full article

Background/Objectives: Ultrasound-guided transvaginal follicular aspiration is a central procedure in in vitro fertilisation (IVF), aiming to collect oocytes necessary for the success of assisted reproduction treatments. Follicular flushing, proposed in the absence of cumulo-oocyte complex (COC) at initial aspiration, remains controversial regarding its real impact on oocyte quality and pregnancy rates. Methods: In this controlled study, conducted in 274 patients, we evaluated the effects of systematic follicular flushing up to 10 washes with a standardised medium (pH 7.3 ± 0.1; 37.2 ± 0.2 °C) on oocyte yield, oocyte morphology, embryo kinetics and clinical outcomes. Results: Flushing resulted in an additional 38% recovery of COCs, mostly between the second and fifth flush, with no significant increase in oocyte dysmorphisms or major embryonic abnormalities. A slight increase in slow cleavages was observed (27% vs. 23%, p = 0.04), as well as a lower oocyte maturation rate when ovulation was triggered by Ovitrelle alone. Clinically, pregnancy rates per transfer were comparable between groups (33.27% without flushing vs. 32.86% with flushing; p = 0.67), as were miscarriage rates (9.11% vs. 8.69%; p = 0.81). Conclusions: These results indicate that follicular flushing, when applied according to a standardised protocol, significantly increases oocyte yield without compromising oocyte morphological quality or embryonic development potential. Although the observed clinical benefits remain modest, this approach could constitute a relevant complementary strategy, particularly in patients with poor ovarian response or in the context of poor initial recovery. However, the controlled but non-randomised nature of this study requires cautious interpretation of the findings. Larger randomised trials, integrating dynamic assessment technologies, such as time-lapse imaging or oocyte transcriptomic analysis, are needed to refine the clinical indications of this technique and explore its underlying biological mechanisms. Full article

The growing emergence of multidrug-resistant bacterial pathogens drives the need for new antibacterial agents. Punicalagin exhibits efficacy against methicillin-resistant Staphylococcus aureus (MRSA), but its specific antibacterial mechanisms remain unclear. This study unveiled the specific antibacterial mechanism of punicalagin against MRSA via phenotypic and transcriptomic analyses. Punicalagin was found to induce severe cell wall damage and membrane disruption. Competitive binding assays identified lipoteichoic acid (LTA) as a potential target, and transcriptomic analysis further revealed that punicalagin downregulated key genes involved in cell wall synthesis (murA, murE) and LTA biosynthesis (dltA-D), consistent with the disruption of the cell wall. Additionally, punicalagin disrupted membrane homeostasis by inhibiting fatty acid synthesis (fabD, fabZ) and amino acid metabolism (dapA, dapB), leading to increased membrane permeability, which aligned with the phenotypic manifestations of membrane damage. Collectively, this work links phenotypic changes to specific gene expression patterns, unveiling that punicalagin inactivates MRSA via the multi-pathway regulation of the cell wall (LTA) and membrane function—providing insights for combating antibiotic-resistant pathogens in food safety and clinical settings. Full article