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     

Segmental Kinematic Coupling of the Human Spinal Column during Locomotion

As one of the most important daily motor activities, human locomotion has been investigated intensively in recent decades. The locomotor functions and mechanics of human lower limbs have become relatively well understood. However, so far our understanding of the motions and functional contributions of the human spine during locomotion is still very poor and simultaneous in-vivo limb and spinal column motion data are scarce. The objective of this study is to investigate the delicate in-vivo kinematic coupling between different functional regions of the human spinal column during locomotion as a stepping stone to explore the locomotor function of the human spine complex. A novel infrared reflective marker cluster system was constrncted using stereophotogrammetry techniques to record the 3D in-vivo geometric shape of the spinal column and the segmental position and orientation of each functional spinal region simultaneously. Gait measurements of normal walking were conducted. The preliminary results show that the spinal column shape changes periodically in the frontal plane during locomotion. The segmental motions of different spinal functional regions appear to be strongly coupled, indicating some synergistic strategy may be employed by the human spinal column to facilitate locomotion. In contrast to traditional medical imaging-based methods, the proposed technique can be used to investigate the dynamic characteristics of the spinal column, hence providing more insight into the functional biomechanics of the human spine.     

shRNA‑mediated knockdown of KNTC1 inhibits non-small-cell lung cancer through regulating PSMB8

In view of the important roles played by Kinetochore proteins in mitosis, we believed that they may contribute to the development and progression of human cancers, which has been reported recently elsewhere. Kinetochore-associated 1 (KNTC1) participates in the segregation of sister chromatids during mitosis, the effects of which on non-small-cell lung cancer (NSCLC) remain unclear. Here, we sought to identify the biological significance of KNTC1 in NSCLC. KNTC1 protein expression in NSCLC tissues was investigated by immunohistochemistry. Lentivirus delivered short hairpin RNA (shRNA) was utilized to establish KNTC1 silence NSCLC cell lines. The effects of KNTC1 depletion on NSCLC cell proliferation, migration, apoptosis, and tumor formation were analyzed by MTT assay, wound-healing assay, transwell assay, flow cytometry assay, and in nude mouse models in vivo. After KNTC1 reduction, NSCLC cell viability, proliferation, migration, and invasion were restrained. A xenograft tumor model was also provided to demonstrate the inhibited tumorigenesis in NSCLC. In addition, the downstream mechanism analysis indicated that KNTC1 depletion was positively associated with PSMB8. The findings of the present study suggested that KNTC1 may have a pivotal role in mediating NSCLC progression and may act as a novel therapeutic target for NSCLC.Subject terms: Non-small-cell lung cancer, Cell migration     

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基于MODIS数据的中国东部地区海陆温差时空变化特征

海陆温差是海-陆间热力对比的重要表征,对区域乃至全球气候产生重要影响。研究基于2001-2021年中分辨率成像光谱仪(MODIS)遥感数据,研究了中国东部地区地表温度、海表温度以及海陆温差的时空变化及区域差异特征。结果表明:2001-2021年中国东部地区地表温度和海表温度均呈显著上升趋势,上升幅度分别为0.34 ℃/10a和0.32 ℃/10a;夜间地表温度和海表温度的上升态势更突出;各季节中,冬季地表温度和夏季海表温度增幅最大,分别达0.45 ℃/10a和0.43 ℃/10a(P<0.05);空间上,中国东部地表温度总体呈南高北低的格局特征, 海表温度则表现出从东北向西南递增、近岸低于远岸的特征。研究时段内,中国东部地区海陆温差通常为负值,海表温度总体高于地表温度,且离海岸线越近的缓冲区范围内海陆温差越小;100 km、200 km和300 km缓冲区范围内年际海陆温差总体呈减小趋势,其中100 km缓冲区范围内的降幅最大;各季节中,春季和冬季海陆温差呈减小趋势,夏季和秋季的呈增大趋势;空间上,以30°N为界,以北和以南区域的海陆温差分别呈减小和增大趋势。     

用SARS冠状病毒全基因组芯片杂交方法分析SARS-CoV

为从临床样品中检测和分析SARSCoV病毒打基础,并为分析SARSCoV病毒的复制和转录等机理提供一种有效方法。以SARS冠状病毒TOR2株序列作为标准设计和制备一种覆盖SARS冠状病毒全基因组的寡聚核苷酸芯片,探针长度为70nt,每相邻的探针序列重复25nt,共660条。用该芯片分析了细胞培养的SARSCoV病毒总RNA、7个SARSCoV病毒的基因克隆片段。对RNA样品用随机引物进行反转录PCR获得cDNA。对DNA用随机引物扩增和dUTPcy3标记。结果用这种芯片杂交检测SARSCoV病毒RNA可见阳性信号呈全基因组分布,并且有多处连续的阳性信号点;用正常人的白细胞RNA为对照,杂交未出现明显阳性信号。检测7个SARSCoV病毒基因克隆片段,在该片段相应的探针区段出现连续阳性信号点。这种方法可有效地检测和分析样品中SARS冠状病毒全基因组的信息。     

Automics: an integrated platform for NMR-based metabonomics spectral processing and data analysis

Background  

Spectral processing and post-experimental data analysis are the major tasks in NMR-based metabonomics studies. While there are commercial and free licensed software tools available to assist these tasks, researchers usually have to use multiple software packages for their studies because software packages generally focus on specific tasks. It would be beneficial to have a highly integrated platform, in which these tasks can be completed within one package. Moreover, with open source architecture, newly proposed algorithms or methods for spectral processing and data analysis can be implemented much more easily and accessed freely by the public.