Background: The nuclear receptor Rev-erbα/β, a key component of the circadian clock, emerges as a drug target for heart diseases, but the function of cardiac Rev-erb has not been studied in vivo. Circadian disruption is implicated in heart diseases, but it is unknown whether cardiac molecular clock dysfunction is associated with the progression of any naturally occurring human heart diseases. Obesity paradox refers to the seemingly protective role of obesity for heart failure, but the mechanism is unclear. Methods: We generated mouse lines with cardiac-specific Rev-erbα/β knockout (KO), characterized cardiac phenotype, conducted multi-omics (RNA-seq, ChIP-seq, proteomics, and metabolomics) analyses, and performed dietary and pharmacologic rescue experiments to assess the time-of-the-day effects. We compared the temporal pattern of cardiac clock gene expression with the cardiac dilation severity in failing human hearts. Results: KO mice display progressive dilated cardiomyopathy (DCM) and lethal heart failure. Inducible ablation of Rev-erbα/β in adult hearts causes similar phenotypes. Impaired fatty acid oxidation in the KO myocardium, particularly in the light cycle, precedes contractile dysfunctions with a reciprocal overreliance on carbohydrate utilization, particularly in the dark cycle. Increasing dietary lipids or sugars supply in the dark cycle does not affect cardiac dysfunctions in KO mice. However, obesity coupled with systemic insulin resistance paradoxically ameliorates cardiac dysfunctions in KO mice, associated with rescued expression of lipid oxidation genes only in the light cycle in phase with increased fatty acids availability from adipose lipolysis. Inhibition of glycolysis in the light cycle and lipid oxidation in the dark cycle, but not vice versa, ameliorates cardiac dysfunctions in KO mice. Altered temporal patterns of cardiac Rev-erb gene expression correlate with the cardiac dilation severity in human hearts with DCM. Conclusions: The study delineates temporal coordination between clock-mediated anticipation and nutrient-induced response in myocardial metabolism at multi-omics levels. The obesity paradox is attributable to increased cardiac lipids supply from adipose lipolysis in the fasting cycle due to systemic insulin resistance and adiposity. Cardiac molecular chronotypes may be involved in human DCM. Myocardial bioenergetics downstream of Rev-erb may be a chronotherapy target in treating heart failure and DCM.

Dermal papilla (DP) cells play a vital role in hair follicle (HF) development and postnatal hair cycling. However, the abilities are lost on further culture. Recent studies have demonstrated significant influences of posttranscriptional regulation by microRNA (miRNA) on HF development. The current study aims to investigate how miRNAs regulate Wnt/β-catenin to control HF inductivity of DP cells by performing microarray analysis in early- and late-passage DP cells and transfecting with miRNAs inhibitor or mimic. Results showed early-passage DP cells strongly expressed miRNAs related to inhibition of noncanonical Wnt pathways. In late-passage DP cells, miRNAs capable of inhibiting the canonical Wnt/β-catenin pathway were upregulated, in addition to the miRNAs targeting the noncanonical Wnt pathway. Moreover, we verified thatβ-catenin expression was downregulated by miR-195-5p overexpression in dose manner. Meanwhile LRP6 expression was downregulated in both protein and mRNA as well as the genes involved in the hair inductivity of DP cells. These results suggest that the appearance of miRNAs that suppress the Wnt/β-catenin pathway may be responsible for the loss of ability of DP cells in culture and miR-195-5p is the potential key factor involved in regulating HF inductivity of DP cells.

The pandemic has fundamentally altered the way that medical students acquire knowledge, making blended learning the predominant student-centered teaching model. This approach has demonstrated positive effects on developing key competencies in clinical medical students. Furthermore, research indicates that case-based learning (CBL) and integrated teaching are beneficial attempts to achieve the above educational goals. In this study, students from the grades of 2020 and 2021 were provided with Massive Open Online Course (MOOC) resources. A blended learning approach combining CBL with cross-chapter integration in Pathophysiology was implemented to construct an effective post-pandemic teaching model, with the aim of enhancing the comprehensive abilities of medical students. Results showed that this case-based, integrated blended teaching model led to an increase in final exam scores, particularly in the proportion of high-scoring students across both cohorts. A significant score improvement was also observed in integrated module assessments. Survey results revealed that most students agreed the new model enhanced their self-directed learning, motivation, and classroom engagement, supporting personalized learning and knowledge integration. Consequently, this model may serve as a valuable template for post-pandemic course design in local medical universities.

The conventional experimental methods can no longer satisfy the requirements of modern higher education in medical sciences. As a result, the integration of scientific research into experimental curricula has become more common in medical education in China. However, the teaching efficacy of integrating scientific research into experimental curricula in local medical universities remains unclear. This study investigated the educational impact of the integrated course model at Basic Medical School of Guilin Medical University. A total of 70 students (2019 cohort) were enrolled in a scientific research-based pathophysiology course, with 77 students (2020 cohort) taking conventional experiments as the control group. Besides regular experiments, this course guided students to conduct a scientific research project on “Acute alcoholic liver injury”, which enabled them to gain a deep understanding of the principles of pathophysiology. Compared with the control group, the scientific research-based experiment improved students’ performance in pathophysiology. Moreover, notable improvements were recorded in students’ scientific literacy, self-learning ability, and teamwork proficiency. Notably, this scientific research-based course is highly appreciated by both students and teachers. Therefore, this innovative teaching model merits wider application in experimental teaching at local medical universities.’