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     

LGR5 regulates osteogenic differentiation of human thoracic ligamentum flavum cells by Wnt signalling pathway

Thoracic ossification of the ligamentum flavum (TOLF) is ectopic ossification of the spinal ligaments. Histologically, the development of TOLF can be described as the process of endochondral ossification. However, the underlying aetiology has not been completely clarified. In this investigation, the gene expression profile associated with leucine‐rich repeat‐containing G‐protein‐coupled receptors (LGR) and Wnt signalling pathway in the thoracic ligamentum flavum cells (TLFCs) of different ossification stages was analysed via RNA sequencing. We further confirmed the significant differences in the related gene expression profile by Gene Ontology (GO) enrichment analysis. LGR5 was first identified in primary human TLFCs during osteogenic differentiation. To evaluate the effect of LGR5 on osteogenic differentiation, LGR5 has been knocked down and overexpressed in human TLFCs. We observed that the knockdown of LGR5 inhibited the activity of Wnt signalling and attenuated the potential osteogenic differentiation of TLFCs, while overexpression of LGR5 activated the Wnt signalling pathway and increased osteogenic differentiation. Our results provide important evidence for the potent positive mediatory effects of LGR5 on osteogenesis by enhancing the Wnt signalling pathway in TOLF.     

南极生物粪对汞的生物放大作用

首次报道了南极地区金图企鹅、阿德利企鹅、黑背鸥和巨海燕 4种海鸟 ,以及象海豹、威德尔海豹、毛皮海狮等 3种海豹新鲜粪便中的全 Hg含量 ,并对比了该区风化土壤的 Hg含量 ,其中 Hg含量水平依次为 :土壤背景值 <黑背鸥粪 <金图企鹅粪 <阿德利企鹅粪 <威德尔海豹粪 <象海豹粪 <巨海燕粪 <毛皮海狮粪 ,可见 ,相对于背景土壤生物粪明显富集 Hg元素。此外 ,结合上述粪便样品的 δ15 N测定结果 ,讨论了南极生物粪对 Hg的生物放大作用。研究表明 ,随着 δ15 N升高 ,即生物营养级的升高 ,其粪便的全 Hg含量有逐步增高的趋势 ,这证实了生物粪和生物肌体一样存在对 Hg的生物放大作用。文中还对南极阿德雷岛一个经过企鹅粪污染的 Y2湖泥芯剖面上 15个样品的 2 6种元素进行了聚类分析 ,结果表明 ,沉积物中的汞和企鹅粪的标型元素具有同源性 ,即沉积物中的汞主要是由企鹅粪带入的 ,由于生物粪对汞的生物富集作用 ,生物粪的混入会造成湖泊沉积物中汞含量的增高     

Distinct basolateral amygdala excitatory inputs mediate the somatosensory and aversive-affective components of pain

Pain is a multidimensional perception that includes unpleasant somatosensory and affective experiences; however, the underlying neural circuits that mediate different components of pain remain elusive. Although hyperactivity of basolateral amygdala glutamatergic (BLA^Glu) neurons is required for the somatosensory and emotional processing of pain, the precise excitatory inputs to BLA^Glu neurons and their roles in mediating different aspects of pain are unclear. Here, we identified two discrete glutamatergic neuronal circuits in male mice: a projection from the insular cortex glutamatergic (IC^Glu) to BLA^Glu neurons, which modulates both the somatosensory and affective components of pain, and a projection from the mediodorsal thalamic nucleus (MD^Glu) to BLA^Glu neurons, which modulates only the aversive-affective component of pain. Using whole-cell recording and fiber photometry, we found that neurons within the IC→BLA and MD→BLA pathways were activated in mice upon inflammatory pain induced by injection of complete Freund’s adjuvant (CFA) into their paws. Optical inhibition of the IC^Glu→BLA pathway increased the nociceptive threshold and induced behavioral place preference in CFA mice. In contrast, optical inhibition of the MD^Glu→BLA pathway did not affect the nociceptive threshold but still induced place preference in CFA mice. In normal mice, optical activation of the IC^Glu→BLA pathway decreased the nociceptive threshold and induced place aversion, while optical activation of the MD^Glu→BLA pathway only evoked aversion. Taken together, our results demonstrate that discrete IC^Glu→BLA and MD^Glu→BLA pathways are involved in modulating different components of pain, provide insights into its circuit basis, and better our understanding of pain perception.     

夜间变暖提高荫香叶片的光合能力

研究了不同氮供应的条件下夜间变暖对荫香叶片光合能力的影响。当植株生长在相同的日间温度(25℃),而夜间温度从18℃增至20℃时,叶片的光合速率增高(p<0.05)。高氮供应的植株,夜间变暖下其叶片光合速率较低氮供应的高,氮供应增高能促进夜间变暖提高叶片光合速率的效应。在低氮供给和夜间变暖下,植株叶片的光下呼吸和暗呼吸的增高显著(p<0.05)。无论在高氮或低氮供应下,生长在夜间变暖下的植物,其叶片的R ub isco最大羧化速率(Vcm ax)和光合电子传递最大速率(Jm ax)增高(p<0.05),氮供应能增强夜间变暖对Vcm ax和Jm ax的正向效应。夜间变暖降低植株叶片的比叶重,而增加单位叶干重的氮含量(Nm),单位叶面积的氮含量(Na)没发生明显变化。随着全球气候变化,夜间趋暖将有利于树木叶片光合能力的提高,结合高氮供给将会明显地增高植物的碳固定。     

斑马鱼急性无机砷暴露后肝脏差异表达基因的生物信息学分析

砷是一种致癌物,是心血管、外周血管疾病、神经疾病、糖尿病和各种癌症的致病因素。目的:利用GO数据库和KEGG数据库等生物信息学方法对GEO数据库数据中的差异表达基因进行评价。利用生物信息学分析软件对差异基因进行功能富集、功能注释分析和生存分析。利用Cytoscape上的蛋白-蛋白相互作用网络(Protein-protein interaction network, PPI)软件对179个差异基因进行筛选和分析。结果发现126个基因作用于蛋白靶点,其中有10个基因为关键基因分别为:PSMB3、HSP701、HSPE1、STIP1、HSPD1、HSP70、DNAJB1B、HSP90AA1.1、HSPA9H和TCP1。核心基因主要作用于内质网中的蛋白质加工通路。这可能会为砷对肝脏损伤的潜在生物标志物和生物学机制提供新的思路。     

蜘蛛北国壁钱繁殖生物学特性的观察

为保护利用北国壁钱(Uroctea lesserti),作者从1996年3月~2003年3月在山东日照市沿海地区对其生物学特性进行了观察。结果表明,北国壁钱在该地区一年发生一代,以不同龄的若蛛附着于室内墙壁上、桥洞、山洞内的扁圆钱形巢内越冬。翌年4月上旬出蛰,7月上旬发育至成蛛,开始交配、产卵、孵化。卵期13·5d,若蛛期337·2d,成蛛期106·5d。雌雄比为5∶3。成蛛日食麦蛾(Gelechiidae)5·8头,以多种昆虫为食。     

多胚苗水稻APIV不同颖花的多卵和多胚苗频率研究

ＡＰＩＶ的多卵和多胚苗频率与其颖花和种子的发育季节以及颖花的着生部位有一定关系。在夏季条件下抽穗开花,其多卵频率和多胚苗频率均比较低,而在秋季条件下抽穗开花则比较高。在同一稻穗中的多卵和多胚苗频率,强势颖花要明显地高于弱势颖花。在同一季节抽穗开花的主穗和分蘖穗之间,其颖花内的多卵频率不存在明显差异,多胚苗频率的差异也不明显。     

牙鲆CA/GT微卫星标记的筛选

采用生物素选择杂交法与放射性同位素杂交法相结合的技术,成功地从牙鲆(Paralichthys olivaceus)基因组中分离出含有CA/GT重复类型的微卫星序列。通过两轮淘选,共获得526个阳性菌落。测序其中的119个菌落,结果获得133个含有微卫星座位的序列。除了两个复合型微卫星外(1.5%),完美型63个(47.37%),非完美型68个(51.13%)。设计并合成22对微卫星引物,对8个人工雌核发育家系的亲本进行遗传背景分析。PCR结果表明,4对引物无扩增带或者扩增带不是目的条带,1对引物表现为单态,其余17对引物均呈多态性,平均每个座位产生5.2个复等位基因,杂合度为0.375～0.846,多态信息含量为0.305～0.823。结果表明,所筛选的大部分微卫星标记能够用于牙鲆群体遗传学研究。