MicroRNAs (miRNAs) are important post-transcriptional regulators during adipocyte adipogenesis. MiR-206-3p, a tissue-specific miRNA, is absent in white adipocytes. In this study, we examined the roles of mmu-miR-206-3p in the adipogenic differentiation of 3T3-L1 preadipocytes. The miR-206-3p expression has shown an apparent decreasing trend after induction, and sustained low expression throughout the differentiation of 3T3-L1 cells. miR-206-3p blocked the adipogenic differentiation of 3T3-L1 cells by attenuating c-Met expression; the inhibition effect of miR-206 to the adipogenic differentiation can be counteracted by restoring c-Met expression. In addition, miR-206-3p decreased the phosphorylation of Akt, which is the downstream effector of c-Met in the PI3K/Akt signaling pathway. These data indicate that miR-206-3p inhibits adipocyte adipogenesis through silencing c-Met and subsequently inactivating the PI3K/Akt signaling pathway.

Folic acid (FA) is an antioxidant that can reduce reactive oxygen species generation and can blunt cardiac dysfunction during ischemia. We hypothesized that FA supplementation prevents cardiac fibrosis and cardiac dysfunction induced by obesity. Six-week-old C57BL6/J mice were fed a high-fat diet (HFD), normal diet (ND), or an HFD supplemented with folic acid (FAD) for 14 weeks. Cardiac function was measured using a transthoracic echocardiographic exam. Phenotypic analysis included measurements of body and heart weight, blood glucose and tissue homocysteine (Hcy) content, and heart oxidative stress status. HFD consumption elevated fasting blood glucose levels and caused obesity and heart enlargement. FA supplementation in HFD-fed mice resulted in reduced fasting blood glucose, heart weight, and heart tissue Hcy content. We also observed a significant cardiac systolic dysfunction when mice were subjected to HFD feeding as indicated by a reduction in the left ventricular ejection fraction and fractional shortening. However, FAD treatment improved cardiac function. FA supplementation protected against cardiac fibrosis induced by HFD. In addition, HFD increased malondialdehyde concentration of the heart tissue and reduced the levels of antioxidant enzyme, glutathione, and catalase. HFD consumption induced myocardial oxidant stress with amelioration by FA treatment. FA supplementation significantly lowers blood glucose levels and heart tissue Hcy content and reverses cardiac dysfunction induced by HFD in mice. These functional improvements of the heart may be mediated by the alleviation of oxidative stress and myocardial fibrosis.

Wilms’ tumor is also called nephroblastoma and is the most common pediatric renal cancer. Several genetic and epigenetic factors have been found to account for the development of Wilms’ tumor. MiRNAs play important roles in this tumorigenic process. In the present study, we aimed to investigate the role of miR-140-5p in nephroblastoma by identifying its targets, as well as its underlying molecular mechanism of action. The miRNA expression profile of nephroblastoma samples was investigated and the targets of miR-140-5p were predicted and validated using the miRNA luciferase reporter method. Moreover, the roles of miR-140-5p in regulating nephroblastoma cell proliferation, migration and cell cycle were analyzed by the CCK8, migration and flow cytometry assays, respectively. The downstream protein of the direct target of miR-140-5p was also identified. miR-140-5p was downregulated in Wilms’ tumor tissues, whereas in the nephroblastoma cell lines G401 and WT-CLS1 that exhibited high levels of miRNA-140-5p, inhibition of cellular proliferation and metastasis were noted as well as cell cycle arrest at the G1/S phase. TGFBRI and IGF1R were identified as direct target genes for miRNA-140-5p. In addition, SMAD2/3 and p-AKT were regulated by TGFBRI and IGF1R separately and participated in the miRNA-140-5p regulatory network. Ectopic expression of TGFBR1 and IGF-1R could abrogate the inhibitory effect of miR-140-5p. We demonstrated that miRNA-140-5p participates in the progression of Wilms’ tumor by targeting the TGFBRI/SMAD2/3 and the IGF-1R/AKT signaling pathways.

Physical activity (PA) serves as a modifiable determinant of bone mineral density (BMD). However, sex- and site-specific dose–response relationships remain poorly defined. Leveraging data from the National Health and Nutrition Examination Survey (NHANES 2011–2014), this cross-sectional study investigated sex-specific associations between accelerometer-derived PA (volume and intensity) and site-specific BMD in 2,659 children and adolescents aged 8–19 years. BMD assessment was conducted via dual-energy X-ray absorptiometry, and PA was quantified using monitor-independent movement summary units (MIMS). Linear and nonlinear analyses revealed distinct patterns: boys exhibited stronger linear associations between PA volume and BMD at weight-bearing sites (e.g., pelvis, arms, and legs; β = 0.003–0.004, P < 0.05), and girls demonstrated nonlinear thresholds (e.g., volume threshold: 15.0 × 10³ MIMS/day). Both sexes had intensity-driven thresholds (~ 45–49 MIMS/min), with diminishing returns above these values (β = 0.010 in boys; stagnation in girls). Directional trends suggest the greater BMD gains per standard deviation (SD) increase in PA for boys compared with that for girls across most skeletal regions (e.g., total body less head: 0.131 SD vs. 0.106 SD for intensity). However, statistical significance (P < 0.05) was observed only for arm BMD responses. Mechanistic analyses highlighted the corresponding biomechanical principles, with weight-bearing regions showing stronger PA-BMD links than nonweight-bearing sites (e.g., spine). These findings underscore the importance of prioritizing high-intensity, weight-bearing activities, particularly for girls, to optimize skeletal health during growth. Public health strategies should focus on achieving, rather than exceeding, the identified daily 60 min intensity thresholds (~ 45–49 MIMS/min) through school- and community-based interventions.

Pulmonary arterial hypertension (PAH) is a life‐threatening condition characterized by elevated pulmonary vascular resistance. Despite recent advances, early diagnosis remains challenging due to nonspecific symptoms. By utilizing RNA sequencing (RNA‐seq) data from the GEO database, we conducted bioinformatics analyses to identify potential diagnostic biomarkers. Differentially expressed genes (DEGs) were screened in blood from PAH patients, followed by functional enrichment and protein‐protein interaction (PPI) network analyses. Thirteen overlapping DEGs were identified, which were enriched in erythrocyte development, heme biosynthesis, and chloride transport. Five hub genes (SLC4A1, AHSP, ALAS2, FECH, and CA1), exhibited strong diagnostic potential, with an area under the curve (AUC) ≥ 0.7 in training datasets (GSE38267, GSE22356). External validation using datasets GSE33463 and GSE117261 confirmed their efficacy in blood samples, although AHSP showed reduced performance in lung tissue. Experimental validation in hypoxic human pulmonary artery smooth muscle cells (hPASMCs) supported the bioinformatics findings. These results underscore SLC4A1, AHSP, ALAS2, FECH, and CA1 as promising noninvasive diagnostic biomarkers for PAH, linking transcriptional dysregulation to clinical application.

Diabetic cardiomyopathy (DCM) is a critical pathological driver of heart failure in diabetic patients, primarily characterized by progressive myocardial fibrosis. Nevertheless, the core molecular network linking upstream metabolic dysregulation to the aberrant activation of downstream cardiac fibroblasts remains largely elusive. In this study, we combined in vivo and in vitro approaches with bioinformatics analysis. A high‐fat diet‐induced mouse model of diabetic myocardial fibrosis was established, and transcriptome sequencing was performed to screen for hub genes, which were subsequently validated in two independent DCM datasets. Single‐cell RNA sequencing revealed that PDK4 and ACOT1 were upregulated in cardiac fibroblasts under pathological conditions. In vitro experiments confirmed that high glucose induced the expression of PDK4, ACOT1, and fibrotic markers in human primary cardiac fibroblasts. Molecular docking predicted a potential interaction between PDK4 and ACOT1. Collectively, our findings identify PDK4 and ACOT1 as evolutionarily conserved metabolic hub genes associated with myocardial fibrosis in DCM, suggesting a putative “metabolism–fibrosis axis” and providing potential therapeutic targets.