Roles of Twist1 in lipid and glucose metabolism.

The abnormal lipid and glucose metabolisms are linked to the metabolic disorders, tumorigenesis, and fibrotic diseases, which attracts the increasing attention to find out the key molecules involved in the lipid and glucose metabolism as the possible therapeutic targets on these diseases. A transcriptional factor Twist1 has been associated with not only the embryonic development, cancer, and fibrotic diseases, but also the regulation of lipid and glucose metabolism. In this review, we will discuss the roles and mechanisms of Twist1 in the obesity-associated white adipose tissue inflammation and insulin resistance, brown adipose tissue metabolism, fatty acid oxidation, and glucose metabolism in skeletal muscle to provide a rational perspective to consider Twist1 as a potential treatment target in clinic. Video Abstract.

Construction and evaluation of an integrated predictive model for chronic kidney disease based on the random forest and artificial neural network approaches.

Chronic kidney disease (CKD) is recognized as a serious global health problem due to its high prevalence and all-cause mortality. The aim of this research was to identify critical biomarkers and construct an integrated model for the early prediction of CKD. By using existing RNA-seq data and clinical information from CKD patients from the Gene Expression Omnibus (GEO) database, we applied a computational technique that combined the random forest (RF) and artificial neural network (ANN) approaches to identify gene biomarkers and construct an early diagnostic model. We generated ROC curves to compare the model with other markers and evaluated the associations of selected genes with various clinical properties of CKD. Moreover, we highlighted two biomarkers involved in energy metabolism pathways: pyruvate dehydrogenase kinase 4 (PDK4) and zinc finger protein 36 (ZFP36). The downregulation of the identified key genes was subsequently confirmed in both unilateral ureteral obstruction (UUO) and ischemia reperfusion injury (IRI) mouse models, accompanied by decreased energy metabolism. In vitro experiments and single-cell sequencing analysis proved that these key genes were related to the energy metabolism of proximal tubule cells and were involved in the development of CKD. Overall, we constructed a composite prediction model and discovered key genes that might be used as biomarkers and therapeutic targets for CKD.