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     

张家界武陵源风景区自然景观价值评估

自然景观提供给人们观赏、娱乐和休闲的效用和价值,长期以来,人们对自然景观的价值忽略并低估,导致在开发利用自然资源过程中出现资源浪费和生态破坏的问题.如果赋予自然景观合适的经济价值,能为其开发利用提供决策支持.为评价张家界武陵源风景区的景观价值,构建了相应的指标体系.自然景观价值乃使用价值与非使用价值之和,并对这两种价值分别运用旅行费用法和条件价值法进行评估.结果表明:2011年武陵源风景区的自然景观价值为89.01亿元,其中使用价值为79.30亿元,非使用价值为9.71亿元.分析表明,武陵源风景区的自然景观价值要远高于以往的研究及近年的旅游收入,建议景区当局全面认识其景观价值,在旅游人次不断攀升的形势下,全力保护该地生态环境,探究武陵源风景区的可持续发展道路.     

金合欢根瘤菌的几种酶活特性

金合欢根瘤菌Rhizobium sp.(Acacia farnesiana)的氧化酶、过氧化氢酶、脲酶、青霉素酶和β-半乳糖苷酶均呈阳性。经过酶活性定量测定表明金合欢根瘤菌有葡萄糖酸-6-磷酸脱氢酶(6PGD)和β-半乳糖苷酶的酶活性,而慢生型大豆根瘤菌未测到上述两种酶活性。根据聚丙烯酰胺凝胶电泳酯酶图谱,6株金合欢根瘤菌可分成两群:酋株AF1、AF2和AF3的酯酶图谱中有A带,AF4、AF5和AF6的酯酶图谱中没有A带。     

茄子果实相关农艺性状全基因组关联分析研究进展与展望

茄子是重要的园艺作物,也是茄科植物中种植最广泛的蔬菜之一。茄子果实相关农艺性状是一种复杂的数量性状,传统育种选育效率低、周期长。高通量测序技术与生物信息学技术的快速发展,使得全基因组关联分析(genome-wide association study, GWAS)在解析茄子果实相关复杂农艺性状的遗传规律方面展现出巨大的应用前景。本文对全基因组关联分析在茄子的果形、果色等果实相关农艺性状中的研究进展进行了综述;针对茄子数量性状遗传研究中普遍存在的“丢失遗传力”(missing heritability)问题,从4个GWAS策略在茄子果实相关农艺性状研究中的应用热点出发,提出了未来茄子GWAS的发展对策;并结合当前茄子遗传改良的实践需求,展望了GWAS策略在茄子分子育种领域的广阔应用前景。本文为今后利用GWAS解析各种茄子果实相关性状的遗传基础以及选育符合消费者需求的果实材料提供了理论依据和参考。     

鸟粪对同里湿地公园土壤重金属及其形态的影响

为了解鸟粪对同里湿地公园土壤重金属全量及形态转化的影响,测定了公园内有鸟粪土壤、无鸟粪土壤、鸟粪沉积物的理化性质,Co、Cr、Cu、Ni、Zn全量及其形态分布,并进行统计分析。结果显示:同里湿地公园土壤及沉积物p H值平均含量达4.5,N、C、H、S和TP平均含量分别达到3.69、38.07、10.97、0.52、1.43g/kg,有鸟粪土壤中N、C、H和S含量显著高于无鸟粪土壤。Cu、Zn、Co平均含量呈现出鸟粪沉积物有鸟粪土壤无鸟粪土壤;Cr的平均含量表现为鸟粪沉积物无鸟粪土壤有鸟粪土壤;Ni呈现出有鸟粪土壤鸟粪沉积物无鸟粪土壤。总体上,鸟粪的进入增加了土壤Cu、Zn、Co、Ni含量。因此应及时清理土壤上覆鸟粪,降低对当地重金属污染风险。相对于无鸟粪土壤中不同重金属形态的分布,有鸟粪土壤中Co、Cr、Cu、Zn的活性态占全量的百分比均略有下降,非活性态呈上升趋势。鸟粪的加入,虽然会在一定程度上降低活性态重金属占总量的比例,但因总量和活性态含量均上升,向植物系统的迁移量会呈现增加趋势,因此对鸟粪施肥再利用应慎重。     

基于人工掩蔽物法的若尔盖湿地中华蟾蜍种群生态研究

近几十年来,全球两栖动物种群衰减显著,两栖动物的生存现状引起了越来越多的生态学家和保护生物学家的关注。若尔盖湿地不仅是世界上最大的一块高原泥炭沼泽湿地,也是我国生物多样性保护的热点地区之一。该地区分布有3种两栖类:高原林蛙(Rana kukunoris)、倭蛙(Narorana pleskei)和中华蟾蜍岷山亚种(Bufo gargarizans minshanica)。已有研究发现该3种两栖动物种群数量均有不同程度的下降。采用人工掩蔽物法,在2011—2014年对该地区中华蟾蜍种群生态做了连续追踪。结果表明:该区域中华蟾蜍种群数量逐年波动较大,年龄结构数据显示该种群处于增长期;中华蟾蜍为聚集分布,且发现率与水体距离呈显著的线形关系(P0.01),在样地范围内离水体越远,发现的个体越多;线形样方比方形样方捕获动物的效率更高(P=0.018);中华蟾蜍亚成体的肥满度季节间无明显差异;中华蟾蜍具有较强的迁徙能力,可能沿着固定的线路周而复始的迁徙。对于家域范围大,迁徙距离远的中华蟾蜍这类物种,应加强最适栖息地的保护并防止栖息地破碎化。     

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.