SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target

Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of excessive damages caused by SARS-CoV-2 remains largely unknown. Here we show that the SARS-CoV-2 envelope (2-E) protein alone is able to cause acute respiratory distress syndrome (ARDS)-like damages in vitro and in vivo. 2-E proteins were found to form a type of pH-sensitive cation channels in bilayer lipid membranes. As observed in SARS-CoV-2-infected cells, heterologous expression of 2-E channels induced rapid cell death in various susceptible cell types and robust secretion of cytokines and chemokines in macrophages. Intravenous administration of purified 2-E protein into mice caused ARDS-like pathological damages in lung and spleen. A dominant negative mutation lowering 2-E channel activity attenuated cell death and SARS-CoV-2 production. Newly identified channel inhibitors exhibited potent anti-SARS-CoV-2 activity and excellent cell protective activity in vitro and these activities were positively correlated with inhibition of 2-E channel. Importantly, prophylactic and therapeutic administration of the channel inhibitor effectively reduced both the viral load and secretion of inflammation cytokines in lungs of SARS-CoV-2-infected transgenic mice expressing human angiotensin-converting enzyme 2 (hACE-2). Our study supports that 2-E is a promising drug target against SARS-CoV-2.Subject terms: Cell death, Molecular biology     

夜间温度升高对双季早晚稻产量的影响

温度是影响水稻生长发育的重要因素,但夜间温度升高对双季水稻产量的影响还不清楚。利用两间玻璃室内夜间不同的温度条件,研究了水稻生长期间夜温升高对双季早、晚稻产量的影响。结果表明,夜间最低温度每升高1℃早稻产量降低5.42%-9.48%,而夜间最低温度每升高1℃晚稻产量提高8.99%-11.28%。夜温升高有利于早、晚稻的分蘖,增加有效穗数,但不利于颖花分化,使每穗粒数减少;夜温升高使早稻结实率下降,但提高晚稻的结实率。     

Sulfated glycosaminoglycans and low-density lipoprotein receptor mediate the cellular entry of Clostridium novyi alpha-toxin

Dear Editor, Clostridium novyi(C.novyi)is a spore-forming anaerobic bacterium and opportunistic pathogen causing severe infectious diseases in humans and animal...     

大型水生植物对重金属的富集与转移

通过野外调查和室内分析,研究了云南阳宗海南北两区域自然生长的17种水生植物的生长状况及植物和对应水样、根区底泥中重金属(As、Zn、Cu、Cd、Pb)的含量。结果表明:植物长势良好,未发现受害症状。水体As严重污染,Pb轻度污染,Zn、Cu和Cd均未超标。9种沉水植物同时对As、Zn、Cu、Cd、Pb的富集系数(植物全株重金属含量与水中该元素含量的比值)远大于1,具有共富集特征。在平均含As0.175mg/L的水中,金鱼藻、黑藻、小眼子菜、八药水筛全株As平均含量分别为(150±7.3)、(179±35)、(92±31)、(265±21)mg/kg(干重),对As具有较强富集能力;对于8种湿生和挺水植物,北部采样点的喜旱莲子草、田栖稗、细叶小苦荬和长芒稗对As,长芒稗、细叶小苦荬、圆果雀稗、水蓼和风车草对Cd,海芋和圆果雀稗对Zn的富集系数(植物地上部重金属含量与底泥中该元素含量的比值)以及圆果雀稗对Cd和Zn转移系数(植物地上部重金属含量与根中该元素含量的比值)均大于1。聚类分析结果表明,金鱼藻、黑藻、八药水筛、小眼子菜、穗状狐尾藻5种水生植物同时对As、Zn、Cu、Cd、Pb具有较强的吸收和富集能力,在重金属复合污染水体修复中具有较大潜力。     

Lithocholic acid inhibits dendritic cell activation by reducing intracellular glutathione via TGR5 signaling

Dendritic cells (DCs) are the major antigen-presenting cells and play an important role in autoimmune uveitis. Emerging evidence suggests that bile acids (BAs) regulate DCs maturation. However, the underlying mechanisms by which BAs regulate the function of DCs still need to be clarified. Here, we demonstrate that lithocholic acid (LCA) inhibits the production of pro-inflammatory cytokines and the expression of surface molecules in bone marrow-derived dendritic cells (BMDCs). LCA attenuates the severity of EAU by modulating the maturation of splenic CD11C⁺MHCII^high DCs. Notably, Takeda G-protein coupled receptor 5 (TGR5) deficiency partially reverses the inhibitory effect of LCA on DCs in vitro and in vivo. TGR5 activation also downregulates the NF-κB and MAPK pathways by inhibiting glutathione production and inducing oxidative stress in DCs, which leads to apoptosis and autophagy in DCs. In addition, LCA or INT-777 treatment increases the TGR5 expression in monocyte-derived dendritic cells (MD-DCs) of patients with active BD, whereas both LCA and TGR5 agonists inhibit the activation of MD-DCs. These results suggest that LCA and TGR5 agonists might be potential therapeutic drugs for the treatment of autoimmune uveitis.     

重金属离子对酵母影响的研究

本文探讨了培养基中不同浓度的重金属离子（Ｃｒ^＋２、Ｐｂ^＋２）对酵母的影响。实验结果表明,重金属离子的浓度越高,酵母菌的一系列生理生化指标：如每个培养皿的菌落数、细胞直径、蛋白质、核酸及可溶性糖的含量都有不同程度的降低。     

Design,synthesis, and biological evaluation of novel carbazole derivatives as potent DNMT1 inhibitors with reasonable PK properties

The DNA methyltransferases (DNMTs) were found in mammals to maintain DNA methylation. Among them, DNMT1 was the first identified, and it is an attractive target for tumour chemotherapy. DC_05 and DC_517 have been reported in our previous work, which is non-nucleoside DNMT1 inhibitor with low micromolar IC₅₀ values and significant selectivity towards other S-adenosyl-_L-methionine (SAM)-dependent protein methyltransferases. In this study, through a process of similarity-based analog searching, a series of DNMT1 inhibitors were designed, synthesized, and evaluated as anticancer agents. SAR studies were conducted based on enzymatic assays. And most of the compounds showed strong inhibitory activity on human DNMT1, especially WK-23 displayed a good inhibitory effect on human DNMT1 with an IC₅₀ value of 5.0 µM. Importantly, the pharmacokinetic (PK) profile of WK-23 was obtained with quite satisfying oral bioavailability and elimination half-life. Taken together, WK-23 is worth developing as DNMT1-selective therapy for the treatment of malignant tumour.