Diversity of arterial cell and phenotypic heterogeneity induced by high-fat and high-cholesterol diet.

Lipid metabolism disorder is the basis of atherosclerotic lesions, in which cholesterol and low-density lipoprotein (LDL) is the main factor involved with the atherosclerotic development. A high-fat and high-cholesterol diet can lead to this disorder in the human body, thus accelerating the process of disease. The development of single-cell RNA sequencing in recent years has opened the possibility to unbiasedly map cellular heterogeneity with high throughput and high resolution; alterations mediated by a high-fat and high-cholesterol diet at the single-cell transcriptomic level can be explored with this mean afterward. We assessed the aortic arch of 16-week old Apoe-/- mice of two control groups (12 weeks of chow diet) and two HFD groups (12 weeks of high fat, high cholesterol diet) to process single-cell suspension and use single-cell RNA sequencing to anatomize the transcripts of 5,416 cells from the control group and 2,739 from the HFD group. Through unsupervised clustering, 14 cell types were divided and defined. Among these cells, the cellular heterogeneity exhibited in endothelial cells and immune cells is the most prominent. Subsequent screening delineated ten endothelial cell subsets with various function based on gene expression profiling. The distribution of endothelial cells and immune cells differs significantly between the control group versus the HFD one. The existence of pathways that inhibit atherosclerosis was found in both dysfunctional endothelial cells and foam cells. Our data provide a comprehensive transcriptional landscape of aortic arch cells and unravel the cellular heterogeneity brought by a high-fat and high-cholesterol diet. All these findings open new perspectives at the transcriptomic level to studying the pathology of atherosclerosis.

Galectin-1-induced skeletal muscle cell differentiation of mesenchymal stem cells seeded on an acellular dermal matrix improves injured anal sphincter.

According to recent studies, mesenchymal stromal cells (MSCs) transplanted via local or tail vein injection can improve healing after anal sphincter injury (ASI) in animal models. However, the transplanted MSCs do not generate skeletal muscle that completely resembles the natural anal sphincter structure. In the present study, we investigated whether bone marrow (BM)-derived MSCs could be induced by Galectin-1 (Gal-1) to differentiate into skeletal muscle and whether the recellularization of an acellular dermal matrix (ADM) with skeletal muscle-differentiated MSCs represents a promising approach to restore ASI in a rat model. BM-MSCs subjected to adenovirus-mediated transfection with Gal-1-GFP (Ad-GFP-Gal-1) displayed increased Gal-1 and desmin expression and differentiated into skeletal muscle cells. MSCs transfected with Ad-GFP-Gal-1 (MSC-Gal-1) were seeded onto an ADM (ADM-MSC-Gal-1) via co-culture, and fusion was observed using a confocal laser scanning microscope. ADM-MSC-Gal-1, ADM-MSC, ADM-MSC-Ad, ADM, or a saline control was applied to a rat ASI model, and injury healing was evaluated via histological examination 6 weeks following treatment. ADM-MSC-Gal-1 treatment promoted significant healing after ASI and improved external anal sphincter contraction curves compared with the other treatments and also led to substantial skeletal muscle regeneration and neovascularization. Our results indicate that repair using ADMs and differentiated MSCs may improve muscle regeneration and restore ASI.

The direct electrocatalysis of phenazine-1-carboxylic acid excreted by Pseudomonas alcaliphila under alkaline condition in microbial fuel cells.

In this paper, we reported a kind of exoelectrogens, Pseudomonas alcaliphila (P. alcaliphila) strain MBR, which could excrete phenazine-1-carboxylic acid (PCA) to transfer electron under alkaline condition in microbial fuel cells (MFCs). The electrochemical activity of strain MBR and the extracellular electron transfer mechanism in MFCs were evaluated by cyclic voltammetry (CV) and electricity generation curve measurement. The results indicated a soluble mediator was the key factor for extracellular electron transfer of strain MBR under alkaline condition. The soluble mediator was PCA detected by gas chromatography-mass (GC-MS) analyses.