Endothelial cell autophagy in chronic intermittent hypoxia is impaired by miRNA-30a-mediated translational control of Beclin-1

Chronic intermittent hypoxia (CIH) in obstructive sleep apnea causes damage of aortic endothelial cells, which predisposes the development of many cardiovascular diseases. Recently, both altered expression of microRNAs (miRNAs) and impaired autophagy were found to be associated with endothelial cell dysfunction in CIH. However, the exact molecular regulatory pathway has not been determined. Here, we address this question. In a mouse model of CIH, we detected significant upregulation of miR-30a, a miRNA that targets 3′-untranslated region of autophagy-associated protein 6 (Beclin-1) messenger RNA (mRNA) for suppressing the protein translation, which subsequently attenuated the endothelial cell autophagy against cell death. Indeed, unlike Beclin-1 mRNA, the Beclin-1 protein in endothelial cells did not increase after CIH. Suppression of miR-30a by expression of antisense of miR-30a significantly increased Beclin-1 levels to enhance endothelial cell autophagy in vitro and in vivo, which improved endothelial cell survival against CIH. Together, these data suggest that endothelial cell autophagy in CIH may be attenuated by miR-30a-mediated translational control of Beclin-1 as an important cause of endothelial cell dysfunction and damage.     

Ascorbic acid induced TET2 enzyme activation enhances cancer immunotherapy efficacy in renal cell carcinoma

Exploring the regulatory mechanism of PD-L1 in renal cancer is one of the key strategies to improve the response of renal cancer patients to checkpoint blockade therapy. In this study, the synergistic effect of ascorbic acid (vitamin C) supplementation and the impact of TET2 depletion on anti-PD-L1 therapy were determined in xenograft model experiments. Lymphocyte infiltration and chemokine expression were determined using flow cytometry and qRT-PCR. To determine the downstream targets of TET2, we performed hMeDip-seq and RNA-seq analyses. The molecular mechanism was further confirmed by hMeDip-qPCR, MeDip-qPCR, bisulfite sequencing, Western blotting, qRT-PCR and xenograft model experiments in vitro and in vivo. The present study demonstrated that ascorbic acid enhanced the efficacy of immunotherapy and that the loss of TET2 function enabled renal cancer cells to evade antitumor immunity. Ascorbic acid treatment significantly increased the intratumoral infiltration of T cells and the expression of cytokines and chemokines, while the loss of TET2 impaired the infiltration of T cells and the expression of cytokines and chemokines. TET2 was recruited to IRF1 by IFN-γ-STAT1 signaling, thereby maintaining IRF1 demethylation and ultimately inducing PD-L1 expression. These results suggest a new strategy of stimulating TET activity to improve immunotherapy for renal cell carcinoma.     

河流着生藻类多样性对城镇化的响应——以深圳市为例

着生藻类是河流生态状况的重要指示生物,然而关于城镇化对着生藻类多样性影响的研究还较缺乏。基于深圳市9条主要河流74个样点2020年雨、旱季的调查数据,对比了城区、郊区河流样点的着生藻类α、β多样性。两次调查共鉴定出着生藻类301个分类单元,其中硅藻门种类最多。谷皮菱形藻(Nitzschia palea)、隐头舟形藻(Navicula cryptocephala)、平庸菱形藻(Nitzschia inconspicua)等污染指示种在城区组相对丰度更高,而清洁指示种微小曲丝藻(Achnanthidium minutissimum)在郊区组相对丰度更高。城镇化对着生藻类物种丰富度、香农维纳多样性指数、Pielou均匀度指数等α多样性指数均无显著影响,但对着生藻类群落结构有显著影响。城区组样点的着生藻类β多样性(用主坐标分析质心指示)低于郊区组,城区组与郊区组藻类β多样性差异在旱季更为显著。两组样点的藻类β多样性差异主要来源于物种周转组分。与城区组着生藻类群落显著相关的环境因子包括总氮、高锰酸钾指数、电导率、pH、浊度和水深,而与郊区组着生藻类群落显著相关的是总氮、溶解性无机磷和电导率。研究...     

基于Bioperl实现远程自动获取抗逆基因序列

BioPerl对于现今大量的生物数据来说,具有很好的获取和处理能力,并且NCBI提供了可以直接访问它下属的Entrez数据库（包括PubMed）的编程接口,即E-Utilities。为了从NCBI中自动获取大量抗逆基因序列,使得生物抗逆基因二次数据库得以搭建,该文基于BioPerl设计了远程自动获取大量抗逆基因序列的程序。此程序灵巧、精悍,Perl语言强大的文本处理功能使程序能实现不同类型基因序列的远程获取。