Search Results (12,609)

Training not only enhances the athletic performance of horses but also improves cardiac structure and function, strengthens cardiovascular adaptability, and reduces the risk of cardiovascular diseases. However, the consequences of training on equine cardiac structure and function remain unclear. This study investigated the morphological, functional, genetic, and metabolic changes in the hearts of Yili horses divided into three groups: high athletic performance (agility group, AG), low athletic performance (ordinary group, OG), and untrained (untrained group, UN). The results showed remodeling of the cardiac structure and physiological adaptations in AG and OG compared to UN groups, with differences between AG and OG primarily in the left ventricle. To explore the molecular mechanisms underlying these phenotypic changes, transcriptomic and metabolomic analyses (particularly GO and KEGG pathway analyses) were performed to assess differences in gene expression and metabolite levels among the three groups. Our results show that miR-1842, miR-671, miR-106b and miR-18a were differentially expressed in the trained groups (AG group and OG group) compared with the control group that did not receive training. These regulatory factors would regulate PFKFB3 to affect the glycolytic activity mediated by HIF-1, there by promoting glycolysis and changing lactate level. This, in turn, would positively feedback to stabilize HIF-1, thus forming a closed loop for the reprogramming of myocardial energy metabolism. In the AG group, positive effects of cAMP signaling were noticeable. In conclusion, our findings offer new insights into physiological cardiac remodeling in Yili horses by highlighting genetic and metabolomic changes resulting from exercise training. Full article

Background: Cardiorenal syndrome (CRS) reflects bidirectional heart–kidney injury whose mechanisms extend far beyond hemodynamics. High-throughput genomics and multi-omics now illuminate the molecular circuits that couple cardiac and renal dysfunction. Methods: We narratively synthesize animal and human studies leveraging transcriptomics, proteomics, peptidomics, metabolomics, and non-coding RNA profiling to map convergent pathways in CRS and to highlight biomarker and therapeutic implications. Results: Across acute and chronic CRS models, omics consistently converge on extracellular matrix (ECM) remodeling and fibrosis (e.g., FN1, POSTN, collagens), immune–inflammatory activation (IL-6 axis, macrophage/complement signatures), renin–angiotensin–aldosterone system hyperactivity, oxidative stress, and metabolic/mitochondrial derangements in both organs. Single-nucleus and bulk transcriptomes reveal tubular dedifferentiation after cardiac arrest-induced AKI and myocardial reprogramming with early CKD, while quantitative renal proteomics in heart failure demonstrates marked upregulation of ACE/Ang II and pro-fibrotic matricellular proteins despite near-normal filtration. Human translational data corroborate these signals: urinary peptidomics detects CRS-specific collagen fragments and protease activity, and circulating FN1/POSTN and selected microRNAs (notably miR-21) show diagnostic potential. Epigenetic and microRNA networks appear to integrate these axes, nominating targets such as anti-miR-21 and anti-fibrotic strategies; pathway-directed repurposing exemplifies dual-organ benefit. Conclusions: Genomics and multi-omics recast CRS as a systems disease driven by intertwined fibrosis, inflammation, neurohormonal and metabolic programs. We propose a translational framework that advances (i) composite biomarker panels combining injury, fibrosis, and regulatory RNAs; (ii) precision, pathway-guided therapies; and (iii) integrated, longitudinal multi-omics of well-phenotyped CRS cohorts to enable prediction and personalized intervention. Full article

Shale gas extraction releases significant quantities of organic iodides of “unknown origin”, which generally pose high ecological and health risks, yet their toxic mechanisms remain unclear. In this study, the human hepatocellular carcinoma (HepG2) cell line was employed as an in vitro cell model to assess the cytotoxic effects of three typical organic iodides (1,2-diiodoethane, 1,3-diiodopropane, and 1,4-diiodobutane) identified in shale gas extraction wastewater from Chongqing, China. The results demonstrated that all three diiodoalkanes exhibited significant toxic effects on HepG2 cells at a concentration of 25 µM, and this effect demonstrated a dose-dependent pattern. As the concentration of diiodoalkanes increased, the viability of HepG2 cells decreased significantly, while cell mortality increased markedly. The transcriptomic analysis indicated that exposure to these three diiodoalkanes induced abnormal expression of genes associated with the extracellular space, extracellular matrix (ECM), and endoplasmic reticulum (ER) in HepG2 cells, which was presumed to be linked to the disruption of the intracellular redox-antioxidant system homeostasis by the diiodoalkanes. Furthermore, assays of intracellular reactive oxygen species (ROS) and antioxidant enzyme/molecule levels suggested that diiodoalkane exposure triggered excessive intracellular ROS production, induced oxidative stress, and ultimately resulted in cell death. Full article

Estrogen is a key regulator of skeletal muscle growth and metabolism in birds, yet its specific roles in female chickens remain poorly defined. To address this gap, we established an estrogen-deficient model by surgically removing the ovaries of Wuding hens, a Chinese indigenous slow-growing breed. Growth traits, carcass yield, and meat quality were evaluated across different ages, complemented by histological examination, serum biochemical analysis, and multi-omics approaches (transcriptomics, proteomics, and lipidomics). Ovariectomized hens maintained somatic growth for a longer period and reached greater body weight and carcass yield at 330 days compared with intact controls. Thigh muscle tenderness was also enhanced in the absence of estrogen, despite no long-term differences in muscle fiber morphology. Lipidomic analysis revealed a transient increase in intramuscular triglyceride content at mid-growth (240 days), pointing to altered lipid storage and distribution. Integrated omics profiling further demonstrated significant changes in the mitogen-activated protein kinase (MAPK) and mechanistic target of rapamycin (mTOR) signaling pathways, accompanied by differential expression of key metabolic and structural genes, including mitogen-activated protein kinase 8 (MAPK8), fatty acid binding protein 4 (FABP4), ankyrin 1 (ANK1), and coenzyme Q6 monooxygenase (COQ6). These molecular adjustments suggest that estrogen withdrawal triggers broad reprogramming of muscle signaling and lipid metabolism. Overall, this study highlights the multifaceted role of estrogen in coordinating growth, muscle quality, and lipid homeostasis in hens and provides a functional model for studying estrogen deficiency in poultry with implications for meat quality improvement. Full article

Soil salinization threatens global food security, necessitating the development of saline–alkaline-tolerant crops. This study investigated the molecular mechanisms of alkali stress tolerance in maize. Screening 369 inbred lines identified two alkali-resistant and two alkali-sensitive varieties. Systematic analysis revealed that resistant varieties rapidly lowered rhizosphere pH and maintained root architecture, whereas sensitive varieties suffered reduced lateral roots and severe biomass loss. Metabolomic profiling showed that all varieties secreted malonic acid via the pyrimidine pathway to modulate rhizosphere pH, with resistant varieties exhibiting stronger accumulation. Transcriptome and RT-qPCR analysis identified two key genes: Zm00001eb396990 (asparagine synthetase), upregulated in resistant varieties and linked to organic acid synthesis, and Zm00001eb370000 (cytokinin dehydrogenase), downregulated in resistant varieties, potentially aiding root maintenance. Multi-omics correlation confirmed the association between Zm00001eb396990 expression and malonic acid content. This study demonstrates that maize roots can alleviate alkali stress through the secretion of malonic acid and the regulation of related genes, providing potential genetic targets and a theoretical basis for cultivating alkali-tolerant maize. Full article

Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious epidemic caused by the porcine reproductive and respiratory syndrome virus (PRRSV). Characterized by reproductive disorders in pregnant sows and respiratory symptoms in pigs of all ages, it poses a severe threat to the global swine industry. In recent years, the high mutation rate of PRRSV has increasingly limited the effectiveness of vaccines against it, prompting the search for new anti-PRRSV drugs. scutellarin (SCU), a natural flavonoid compound extracted from the medicinal plant Scutellaria baicalensis, possesses multiple biological activities. Its antiviral effects have been demonstrated in numerous studies; however, its inhibitory activity against PRRSV and the underlying mechanism remain unknown. In this study, through in vitro cell experiments, we found that scutellarin significantly inhibits PRRSV infection in PAMs. Furthermore, it directly acts on PRRSV to exert antiviral effects. Transcriptomic analysis suggests that scutellarin may exert its anti-PRRSV effects by regulating host immunity and anti-inflammation through immune-related signaling pathways, including the complement and coagulation cascades, ECM-receptor interaction, Rap1 signaling pathway, and PI3K-Akt signaling pathway. Full article

Chamazulene (CHA) is a brilliant blue compound present in Artemisia sieversiana Ehrhart ex Willd. essential oil (AEO). We have previously reported that both CHA and AEO can shield the skin from UVB damage, exhibiting significant anti-photoaging effects. However, the molecular mechanisms underlying CHA’s photoprotective properties are still unclear. Herein, we integrated transcriptomics, targeted fatty acid profile, and untargeted metabolomics analyses on the dorsal skin of mice exposed to UVB with or without 0.4% CHA topical treatment. The results showed that CHA upregulated key genes involved in fatty acid metabolism, including two peroxisome proliferator-activated receptor (PPAR) subtypes, i.e., PPARα and PPARγ, in mouse skin. The CHA treatment elevated levels of various saturated, monounsaturated, and polyunsaturated fatty acids, and it especially restored n-3/n-6 polyunsaturated fatty acid homeostasis and downregulated the p38 MAPK/COX-2 pathway. Additionally, CHA enhanced skin non-essential amino acid metabolism, likely via PPARα. In conclusion, our study indicates that CHA may mitigate UVB-induced photoaging by inducing metabolic reprogramming and suppressing inflammation, and the findings suggest that the activation of PPARα/γ may play a vital role in these observed effects, thereby establishing CHA as a promising topical agent against UVB-induced photoaging. Full article

The Bactrian camel exemplifies mammalian adaptation to deserts, but the spatial organization of its innate immune system remains uncharacterized. This study integrated transcriptomes from 110 samples across 11 major tissues and organs to resolve tissue-specific gene expression and innate immune modularity. Through differential expression analysis, Tau specificity index (τ > 0.8), and machine learning validation (Random Forest F1-score = 0.86 ± 0.11), we identified 4242 high-confidence tissue-specific genes (e.g., LIPE/PLIN1 in adipose). Weighted gene co-expression network analysis (WGCNA) of 1522 innate immune genes revealed 11 co-expression modules, with six exhibiting significant tissue associations (FDR < 0.01): liver-specific (r = 0.96), spleen-adipose-enriched (r = 0.88), muscle-associated (r = 0.82), and blood-specific (r = 0.80) modules. These networks demonstrated multifunctional coordination of immune pathways—including Pattern Recognition, Cytokine Signaling, and Phagocytosis—rather than isolated functions. Our results establish that camel innate immunity is organized into spatially modular networks tailored to tissue microenvironments, providing the first systems-level framework for understanding immune resilience in desert-adapted mammals and may inform strategies for enhancing livestock resilience in arid regions. Full article

Acne Vulgaris is a chronic inflammatory skin disorder driven by a combination of microbial colonization, immune dysregulation, and disruption of the epidermal barrier. Although isotretinoin remains the most effective treatment, the molecular mechanisms underlying its anti-inflammatory effects are incompletely understood. This study integrates transcriptomic meta-analysis and computational drug screening to identify novel therapeutic targets and candidate compounds for acne management. Three publicly available GEO datasets (GSE6475, GSE10433, GSE11792) were analyzed to identify differentially expressed genes (DEGs) associated with isotretinoin response. Among these, Spectrin beta, non-erythrocytic 1 (SPTBN1) and Signal-induced proliferation-associated 1-like protein 1 (SIPA1L1) emerged as consistently regulated genes with known roles in cytoskeletal organization and immune signaling, respectively. To assess the druggability of these targets, molecular docking was conducted using gentamicin and natural compounds derived from Cymbopogon winterianus, including citronellol, citral, citronellal, and geraniol. Gentamicin demonstrated the strongest binding affinity to SIPA1L1 (−8.6 kcal/mol) and SPTBN1 (−5.9 kcal/mol), forming multiple hydrogen bonds and hydrophobic contacts. Subsequent 100 ns molecular dynamics (MD) simulations confirmed the stability of the gentamicin–protein complexes, as evidenced by favorable RMSD, RMSF, and energy profiles. Interaction energy decomposition revealed strong contributions from electrostatic and van der Waals forces. These findings highlight the potential of gentamicin, and possibly structurally related natural compounds, as modulators of host inflammatory pathways implicated in acne. The study further underscores the utility of integrating transcriptomics, molecular docking, and MD simulation for early-phase therapeutic discovery targeting inflammation and barrier dysfunction in dermatological diseases. Full article

In vitro maturation (IVM) of oocytes is a pivotal step in assisted reproductive technologies for livestock. However, oxidative stress (OS) and mitochondrial dysfunction during in vitro culture often lead to oocyte aging, thereby limiting the efficiency of the technologies. To address these challenges, this study investigated the regulatory effects of 1-Palmitoyl-2-Oleoyl-sn-Glycero-3-Phosphocholine (POPC) on bovine oocyte IVM, aging, and developmental competence to determine the optimal concentration and explore underlying mechanisms. Cumulus–oocyte complexes (COCs) were collected from abattoir-derived bovine ovaries and cultured in IVM medium supplemented with 0 (control), 50, 100, 150, or 200 μmol/mL of POPC (n = 300 per group) at 38.5 °C under 5% CO₂ for 22 h. The optimal concentration was determined based on the first polar body extrusion rate, followed by in vitro fertilization (IVF), fluorescence staining, Smart-seq2 transcriptome sequencing, and quantitative PCR (qPCR) analysis. The results demonstrated that 150 μmol/mL of POPC yielded the highest maturation rate, significantly exceeding the control group (p < 0.05), and enhanced 2-4-cell cleavage rates after IVF. Furthermore, POPC markedly reduced intracellular reactive oxygen species (ROS) levels, increased glutathione (GSH) content, improved mitochondrial function, and restored normal spindle morphology. Transcriptomic analysis identified 350 upregulated and 280 downregulated differentially expressed genes (DEGs), which were enriched in pathways related to OS. qPCR validation confirmed upregulation of SIRT1/2 and BCL-2, along with downregulation of BAX and Caspase-1/3. Collectively, these findings suggest that 150 μmol/mL of POPC alleviates OS and activates the “SIRT–antioxidant–antiapoptotic” signaling axis, thereby providing valuable insights for optimizing assisted reproductive technologies in livestock. Full article

The study of molecular mechanisms underlying late-life depression (LLD) is increasingly important in light of population aging. To date, LLD-related molecular brain changes remain poorly understood. Furthermore, environmental factors such as climate change and geography contribute to LDD risks. One overlooked factor might be deuterium—a stable hydrogen isotope—whose concentration in drinking water can vary geographically (~90–155 ppm) and alter the incidence of mood disorders. Conversely, potential effects of natural variations in deuterium content in drinking water on LLD symptoms and brain gene expression remain unknown. We conducted Illumina gene expression profiling in the hippocampi and prefrontal cortexes of 18-month-old C57BL/6J mice, a model of LLD-like behaviors, compared to 3-month-old controls. Separately, aged mice were allowed to consume deuterium-depleted (DDW, ~90 ppm) or control (~140 ppm) water for 21 days and were studied for LLD-like behaviors and Illumina gene expression of the brain. Naïve old mice displayed ≥2-fold significant changes of 35 genes. Housing on DDW increased their hedonic sensitivity and novelty exploration, reduced helplessness, improved memory, and significantly altered brain expression of Egr1, Per2, Homer1, Gadd45a, and Prdx4, among others. These genes revealed significant alterations in several GO-BP and KEGG pathways implicated in inflammation, cellular stress, synaptic plasticity, emotionality, and regeneration. Additionally, we found that incubation of primary neuronal cultures in DDW-containing buffer ameliorated Ca²⁺ influx and mitochondrial potential in a toxicity model, suggesting the involvement of mitochondrial mechanisms in the effects of decreased deuterium levels. Thus, aging induced profound brain molecular changes that may at least in part contribute to LLD pathophysiology. Reduced deuterium intake exerted modest but significant effects on LLD-related behaviors in aged mice, which can be attributed to, but not limited by ameliorated mitochondrial function and changes in brain gene expression. Full article

Targeted therapies, including treatment with inhibitors of BRAF^V600 and MEK kinases, have improved outcomes in advanced melanoma. However, most patients relapse due to acquired resistance, underscoring the need for new drug targets. This study evaluated PRI-724, a CBP/β-catenin inhibitor, in patient-derived drug-naïve melanoma cells and their trametinib- or vemurafenib-resistant counterparts. While PRI-724 has demonstrated efficacy in preclinical models and clinical trials in different cancer types, its potential in melanoma has not been previously assessed. We found that treatment with PRI-724 downregulated survivin and other CBP/β-catenin target proteins, reduced invasiveness, and induced apoptosis in drug-naïve and trametinib- and vemurafenib-resistant cells. Trametinib-resistant melanoma cells showed the greatest sensitivity to PRI-724, indicating that CBP/β-catenin transcriptional activity may represent a new therapeutic vulnerability. Transcriptomic and immunoblotting analyses revealed the highest survivin levels in vemurafenib-resistant cells, which may underlie their reduced responsiveness to PRI-724. Bioinformatic analyses (TCGA and GSE50509) confirmed that a high survivin level predicts poor prognosis and reduced response to treatment. The results of the study point to the potential of PRI-724 as a chemotherapeutic agent for the treatment of melanoma. Its efficacy might depend on CBP/β-catenin transcriptional activity in melanoma cells, and further evaluation of this signaling with survivin as a biomarker is therefore warranted. Full article

Non-bagging apple cultivation, which is time-saving, labor-saving, and cost-effective, represents the future direction of apple cultivation in China. However, compared with bagging cultivation, it degrades fruit appearance quality, characterized by rough peels and dull colors, with the underlying physiological and molecular mechanisms remaining unclear. This study used ‘Tianhong 2’ Fuji apples, grafted onto SH dwarfing rootstock, and integrated transcriptomics–metabolomics to explore these mechanisms. Results showed that non-bagging-cultivated apple peels had higher chlorophyll and carotenoid contents but lower anthocyanin content than those of bagging-cultivated ones. Transcriptome sequencing identified 1571 differentially expressed genes (DEGs: 1269 upregulated, 302 downregulated). Functional analysis revealed that the decline in fruit appearance quality was primarily associated with secondary metabolite biosynthesis, lipid metabolism, and carbohydrate metabolism, and 34 candidate genes were identified. Metabolomic analysis detected 394 differentially expressed metabolites (DEMs), 38 of which were closely related to the non-bagging-induced appearance degradation, mainly lipids, organic oxygen compounds, and organic acids and their derivatives. Integrated analysis of DEGs and DEMs indicated the involvement of multiple critical metabolic pathways, including cutin, suberin and wax biosynthesis; starch and sucrose metabolism; cyanoamino acid metabolism; and phenylpropanoid and flavonoid biosynthesis. Compared with bagging-cultivated apples, non-bagging-cultivated apples exhibited faster starch degradation and higher soluble sugar accumulation. Additionally, the accumulation of specific metabolites [e.g., quercetin (HMDB0005794, HMDB03249, LMPK12112097), and suberin components (LMFA01170020, LMFA01050437, HMDB0031885)], along with elevated organic acid levels, contributed to peel roughness and dull coloration. These findings further enrich the theoretical basis for the formation of fruit quality in Fuji apples under non-bagging cultivation and provide valuable theoretical guidance for the practical application of this cultivation mode. Full article

Background: Protein arginine deiminase 4 (PAD4) has emerged as a promising therapeutic target for acute promyelocytic leukemia (APL) because of its role in epigenetic regulation and leukemogenesis. All-trans retinoic acid, a standard differentiation agent in APL therapy, has been shown to upregulate PAD4 expression during leukemic cell maturation. Interestingly, first-generation PAD4 inhibitors also promote differentiation, but simultaneously trigger compensatory PAD4 overexpression, underscoring the unresolved complexity of PAD4 modulation in leukemia therapy. Methods: In this study, we employed mass cytometry and transcriptomic–proteomic integrated analysis to investigate the underlying mechanisms of YW3-56, a dual-function PAD4 inhibitor against protein expression and enzymatic function, in NB4 leukemia cells. Functional validation was conducted using Western blot and metabolic assays. Results: Mass cytometry analysis revealed that YW3-56 reduced leukemia stemness (CD44/CD133), while enhancing myeloid differentiation (CD11b/CD14) and immunogenic activation (CD80/CD86). Multiomics analysis revealed a YW3-56-induced metabolic shift characterized by downregulation of glycolytic enzymes and upregulation of the tricarboxylic acid cycle and pentose phosphate pathway components, indicating a reversal of the Warburg effect. Mechanistically, this metabolic reprogramming was driven by reduced AKT expression and phosphorylation at Thr308, impaired GLUT1 expression and membrane localization, and decreased glucose uptake, which collectively promoted the differentiation of NB4 cells. Additionally, YW3-56 suppressed the downstream mTOR pathway, inducing caspase-3/PARP-mediated apoptosis and inhibiting cell proliferation. Conclusions: Our study demonstrated that YW3-56 exerts multimodal antileukemic effects in APL by simultaneously targeting PAD4-mediated epigenetic regulation, AKT-driven metabolic reprogramming and cellular differentiation, highlighting PAD4-AKT signaling as a promising target for APL combination therapy. Full article

Background/Objectives: Ovarian cancer is a heterogeneous malignancy with molecular subtypes that strongly influence prognosis and therapy. High-dimensional mRNA data can capture this biological diversity, but its complexity and noise limit robust subtype characterization. Furthermore, current classification approaches often fail to reflect subtype-specific transcriptional programs, underscoring the need for computational strategies that reduce dimensionality and identify discriminative molecular features. Methods: We designed a multi-stage feature selection and network analysis framework tailored for high-dimensional transcriptomic data. Starting with ~65,000 mRNA features, we applied unsupervised variance-based filtering and correlation pruning to eliminate low-information genes and reduce redundancy. The applied supervised Select-K Best filtering further refined the feature space. To enhance robustness, we implemented a hybrid selection strategy combining recursive feature elimination (RFE) with random forests and LASSO regression to identify discriminative mRNA features. Finally, these features were then used to construct a gene co-expression similarity network. Results: This pipeline reduced approximately 65,000 gene features to a subset of 83 discriminative transcripts, which were then used for network construction to reveal subtype-specific biology. The analysis identified four distinct groups. One group exhibited classical high-grade serous features defined by TP53 mutations and homologous recombination deficiency, while another was enriched for PI3K/AKT and ARID1A-associated signaling consistent with clear cell and endometrioid-like biology. A third group displayed drug resistance-associated transcriptional programs with receptor tyrosine kinase activation, and the fourth demonstrated a hybrid profile bridging serous and endometrioid expression modules. Conclusions: This pilot study shows that combining unsupervised and supervised feature selection with network modeling enables robust stratification of ovarian cancer subtypes. Full article