ABSTRACT
OBJECTIVE: Aberrant glucolipid metabolism in the heart is a characteristic factor in diabetic cardiomyopathy (DbCM). Super-enhancers-driven noncoding RNAs (seRNAs) are emerging as powerful regulators in the progression of cardiac diseases. However, the functions of seRNAs in DbCM have not been fully elucidated. METHODS: Super enhancers and their associated seRNAs were screened and identified by H3K27ac ChIP-seq data in the Encyclopedia of DNA Elements (ENCODE) dataset. A dual-luciferase reporter assay was performed to analyze the function of super-enhancers on the transcription of peroxisome proliferator-activated receptor α-related seRNA (PPARα-seRNA). A DbCM mouse model was established using db/db leptin receptor-deficient mice. Adeno-associated virus serotype 9-seRNA (AAV9-seRNA) was injected via the tail vein to evaluate the role of seRNA in DbCM. The underlying mechanism was explored through RNA pull-down, RNA and chromatin immunoprecipitation, and chromatin isolation by RNA purification. RESULTS: PPARα-seRNA was regulated by super-enhancers and its levels were increased in response to high glucose and palmitic acid stimulation in cardiomyocytes. Functionally, PPARα-seRNA overexpression aggravated lipid deposition, reduced glucose uptake, and repressed energy production. In contrast, PPARα-seRNA knockdown ameliorated metabolic disorder in vitro. In vivo, overexpression of PPARα-seRNA exacerbated cardiac metabolic disorder and deteriorated cardiac dysfunction, myocardial fibrosis, and hypertrophy in DbCM. Mechanistically, PPARα-seRNA bound to the histone demethylase KDM4B (Lysine-specific demethylase 4B) and decreased H3K9me3 levels in the promoter region of PPARα, ultimately enhancing its transcription. CONCLUSIONS: Our study revealed the pivotal function of a super-enhancer-driven long noncoding RNA (lncRNA), PPARα-seRNA, in the deterioration of cardiac function and the exacerbation of metabolic abnormalities in diabetic cardiomyopathy, which recruited KDM4B to the promoter region of PPARα and repression of its transcription. This suggests a promising therapeutic strategy for the treatment of DbCM.
ABSTRACT
The digital image method of monitoring structural displacement is receiving more attention today, especially in non-contact structure health monitoring. Some obvious advantages of this method, such as economy and convenience, were shown while it was used to monitor the deformation of the bridge structure during the service period. The image processing technology was used to extract structural deformation feature information from surveillance video images containing structural displacement in order to realize a new non-contact online monitoring method in this paper. The influence of different imaging distances and angles on the conversion coefficient (η) that converts the pixel coordinates to the actual displacement was first studied experimentally. Then, the measuring and tracking of bridge structural displacement based on surveillance video images was investigated by laboratory-scale experiments under idealized conditions. The results showed that the video imaging accuracy can be affected by changes in the relative position of the imaging device and measured structure, which is embodied in the change in η (actual size of individual pixel) on the structured image. The increase in distance between the measured structure and the monitoring equipment will have a significant effect on the change in the η value. The value of η varies linearly with the change in shooting distance. The value of η will be affected by the changes in shooting angle. The millimeter-level online monitoring of the structure displacement can be realized using images based on surveillance video images. The feasibility of measuring and tracking structural displacement based on surveillance video images was confirmed by a laboratory-scale experiment.
ABSTRACT
Liquid-liquid phase separation (LLPS) is a biophysical process that mediates the precise and complex spatiotemporal coordination of cellular processes. Proteins and nucleic acids are compartmentalized into micron-scale membrane-less droplets via LLPS. These droplets, termed biomolecular condensates, are highly dynamic, have concentrated components, and perform specific functions. Biomolecular condensates have been observed to organize diverse key biological processes, including gene transcription, signal transduction, DNA damage repair, chromatin organization, and autophagy. The dysregulation of these biological activities owing to aberrant LLPS is important in cardiovascular diseases. This review provides a detailed overview of the regulation and functions of biomolecular condensates, provides a comprehensive depiction of LLPS in several common cardiovascular diseases, and discusses the revolutionary therapeutic perspective of modulating LLPS in cardiovascular diseases and new treatment strategies relevant to LLPS.
