CircNet 2.0: an updated database for exploring circular RNA regulatory networks in cancers.

Circular RNAs (circRNAs), which are single-stranded RNA molecules that have individually formed into a covalently closed continuous loop, act as sponges of microRNAs to regulate transcription and translation. CircRNAs are important molecules in the field of cancer diagnosis, as growing evidence suggests that they are closely related to pathological cancer features. Therefore, they have high potential for clinical use as novel cancer biomarkers. In this article, we present our updates to CircNet (version 2.0), into which circRNAs from circAtlas and MiOncoCirc, and novel circRNAs from The Cancer Genome Atlas database have been integrated. In total, 2732 samples from 37 types of cancers were integrated into CircNet 2.0 and analyzed using several of the most reliable circRNA detection algorithms. Furthermore, target miRNAs were predicted from the full-length circRNA sequence using three reliable tools (PITA, miRanda and TargetScan). Additionally, 384 897 experimentally verified miRNA-target interactions from miRTarBase were integrated into our database to facilitate the construction of high-quality circRNA-miRNA-gene regulatory networks. These improvements, along with the user-friendly interactive web interface for data presentation, search, and visualization, showcase the updated CircNet database as a powerful, experimentally validated resource, for providing strong data support in the biomedical fields. CircNet 2.0 is currently accessible at https://awi.cuhk.edu.cn/∼CircNet.

Esaxerenone Inhibits Renal Angiogenesis and Endothelial-Mesenchymal Transition via the VEGFA and TGF-ß1 Pathways in Aldosterone-Infused Mice.

Renal fibrosis is an inevitable process in the progression of chronic kidney disease (CKD). Angiogenesis plays an important role in this process. Vascular endothelial cells are involved in renal fibrosis by phenotypic transformation and secretion of extracellular matrix. Aldosterone stimulates mineralocorticoid receptor (MR) activation and induces inflammation, which is important for angiogenesis. Clinically, MR blockers (MRBs) have a protective effect on damaged kidneys, which may be associated with inhibition of angiogenesis. In this study, we used aldosterone-infused mice and found that aldosterone induced angiogenesis and that endothelial-mesenchymal transition (EndMT) in neovascular endothelial cells was involved in renal fibrosis. Notably, aldosterone induced inflammation and stimulated macrophages to secrete vascular endothelial growth factor (VEGF) A to regulate angiogenesis by activating MR, whereas EndMT occurred in response to transforming growth factor-ß1 (TGF-ß1) induction and participated in renal fibrosis. These effects were antagonized by the MRB esaxerenone. These findings suggest that reducing angiogenesis may be an effective strategy for treating renal fibrosis.

Esaxerenone Inhibits Interferon-γ Induced Pyroptosis of Macrophages in the Lungs of Aldosterone-treated Mice.

Lung immune cells such as lymphocytes and macrophages can induce an inflammatory response due to the activation of mineralocorticoid receptor (MR), which is manifested by the infiltration of inflammatory cells and the secretion of inflammatory cytokines and subsequent apoptosis, pyroptosis and necrosis of intrinsic lung cells and immune cells. Macrophages are immune cells that are abundant in the lung and act as the first line of defense against pathogens but are also aggravating factors of infection. The activation of the renin-angiotensin-aldosterone system (RAAS), especially aldosterone-stimulated MR activation, can induce macrophage and CD8+ T cell aggregation and the secretion of cytokines such as tumor necrosis factor-α (TNF-α) and interferon-gamma (IFN-γ). Increased IFN-γ secretion can induce macrophage pyroptosis and the release of interleukin 1-ß (IL-1ß), aggravating lung injury. In this study, lung injury in C57BL/6 mice was induced by subcutaneous micro-osmotic pump infusion of aldosterone. After 12 weeks of administration, the kidney, heart, blood vessels and lungs all showed obvious inflammatory injury, which manifested as rapid accumulation of macrophages. The overexpression of IFN-γ in the lungs of aldosterone-treated mice and the stimulation of MH-S and RAW264.7 alveolar macrophages (AMs) with aldosterone in vitro showed that IFN-γ induced pyroptosis of macrophages via the activation of the inflammasome, and the MR blocker esaxerenone effectively inhibited this effect and alleviated lung injury. In addition, IFN-γ secreted by CD8+ T cells is associated with macrophage pyroptosis. In conclusion, the inhibition of macrophage pyroptosis can effectively alleviate lung injury.

Improvement in physical properties of single-layer gas diffusion layers using graphene for proton exchange membrane fuel cells.

Gas diffusion layer (GDL) is an important component related to the efficiency of proton exchange membrane fuel cells (PEMFCs). Nevertheless, the preparation cost of the conventional GDL is high. In our previous studies, a single-layer gas diffusion layer (SL-GDL) prepared by a simple and cost-effective process has been used for PEMFCs, and it achieved 85% efficiency of a commonly used commercial GDL. In this study, improvement in physical properties of a series of single-layer gas diffusion layers, SL-GDL-Gx (x = 1-3), via uniform distribution of graphene in the SL-GDL, and the application of SL-GDL-Gx in PEMFCs are studied. The results indicate that the presence of well-distributed graphene layers in SL-GDL-Gxs causes an increase in the surface roughness and the formation of irregular slender interstices, leading to the enhancement of gas permeability while maintaining the microporous layer (MPL)-like microstructure and retaining good loading and efficient utilization of the catalyst. Moreover, the electrical resistivities significantly decreased and the mechanical properties improved. These improvements in physical properties are significantly beneficial for the performance of PEMFC. The single-cell performance tests show that the best performance measured at 80 °C under 99.9% relative humidity (RH) conditions is obtained from the PEMFC (FC-2) fabricated with SL-GDL-G2 and is 46% higher than that from FC-0 with SL-GDL-G0 without graphene and 15% higher than that from FC-3 with the commercial GDL. Furthermore, the performances of FC-2 measured at 50-80 °C under 15% RH are all much higher than those of FC-3. The results indicate that SL-GDL-G2 prepared via a cost-effective method is a potential GDL for PEMFCs.