Stoichiometry of Nucleotide Binding to Proteasome AAA+ ATPase Hexamer Established by Native Mass Spectrometry

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Highlights

• •All six binding sites in PAN^WT are occupied by ADP- or ATP-type nucleotides.
• •PAN^KA Walker A mutant substoichiometrically binds ATP- but not ADP-type nucleotides.
• •PAN hexamer dissociation of the solution origin characteristics was observed in MS.
• •We posit that the PAN hexamer dissociation proceeds within the ESI droplets.

     

Correction to: Microcella flavibacter sp. nov., isolated from marine sediment,and reclassification of Chryseoglobus frigidaquae,Chryseoglobus indicus,and Yonghaparkia alkaliphila as Microcella frigidaquae comb. nov., Microcella indica nom. nov., and Microcella alkalica nom. nov.

Antonie van Leeuwenhoek -     

The contribution of atmospheric deposition of cadmium and lead to their accumulation in rice grains

Plant and Soil - Over-accumulation of cadmium and lead in rice grain is a global concern as it has adverse health impacts. Atmospheric deposition is an important source of heavy metal accumulation...     

Correction to: An integrated strategy for polyploidization of Cerastigma willmottianum Stapf based on tissue culture and chemical mutagenesis and the carbon dioxide fixation ability of tetraploids

Plant Cell, Tissue and Organ Culture (PCTOC) -     

AntiV-SGN: a universal antiviral strategy to combat both RNA and DNA viruses by destroying their nucleic acids without sequence limitation

Numerous viral outbreaks have threatened us throughout history. Here, we demonstrated a nucleic acid-based antiviral strategy named AntiV-SGN. Unlike those CRISPR-mediated methods, AntiV-SGN has advantages of no targets' sequence limitation, such as protospacer adjacent motif (PAM) or protospacer flanking sequence (PFS), being universal for both DNA and RNA viruses. AntiV-SGN was composed of a FEN1 protein and specific hpDNAs targeting viruses' nucleic acid. Its antiviral ability was tested on SARS-CoV-2 and HBV respectively. Reporter assays in human cells first illustrated the feasibility of AntiV-SGN. Then, it was verified that AntiV-SGN destroyed about 50% of live RNAs of SARS-CoV-2 in Vero cells and 90% cccDNA of HBV in HepG2.2.15 cells. It was also able to remove viral DNA integrated into the host's genome. In the mouse model, AntiV-SGN can be used to significantly reduce HBV expression at a level of 90%. Actually, in some cases, when viruses mutate to eliminate PAM/PFS or hosts were infected by both DNA and RNA viruses, AntiV-SGN could be a choice. Collectively, this study provided a proof-of-concept antiviral strategy of AntiV-SGN, which has potential clinical value for targeting a wide variety of human pathogens, both known and newly identified.     

黄芪甲甙对急性心肌梗死大鼠心室重构和NOX/ROS/TNF⁃α信号通路的影响

研究旨在探究黄芪甲甙对急性心肌梗死大鼠心室重构的作用及其机制。选取36只Wistar大鼠随机分为假手术组、模型组、黄芪甲甙低剂量组、黄芪甲甙中剂量组、黄芪甲甙高剂量组和阳性对照组,每组6只。除假手术组外,其余大鼠手术建立急性心肌梗死模型,假手术组大鼠开胸后仅分离冠状动脉左前降支,不做结扎处理便逐层缝合,造模后第2天开始药物干预：黄芪甲甙低、中、高剂量组分别给予20、40、60 mg·kg^-1黄芪甲甙灌胃处理,阳性对照组给予100 mg·kg^-1阿司匹林灌胃处理。比较各组治疗第0、2、4周心功能指标[左心室射血分数（left ventricular ejection fractions,LVEF）、左心室短轴缩短率（left ventricular fractional shortening,LVFS）、左心室质量指数（left ventricular mass index,LVMI）]的变化情况。采用心脏血流动力学监测系统监测心脏血流动力学指标[左心室舒张末压（left ventricular end diastolic pressure,LVEDP）、左心室收缩压（left ventricular systolic pressure,LVSP）和左心室等容收缩/舒张压上升最大速率（maximal rate of left ventricular pressure increase/decrease,±dp/dt_max）]的变化情况,采用酶联免疫吸附法测定血清血管紧张素Ⅱ（angiotensin Ⅱ,AngⅡ）、内皮素1（endothelin-1,ET-1）、脑钠肽（brain natriuretic peptide,BNP）含量,试剂盒检测心肌组织活性氧（reactive oxygen species,ROS）含量,实时荧光定量PCR和Western blot检测大鼠心肌组织NADPH氧化酶（reduced nicotinamide adenine dinucleotide phosphate oxidase,NOX）、肿瘤坏死因子α（tumor necrosis factor α,TNF-α）mRNA相对表达量和蛋白表达水平。结果显示,治疗4周后,黄芪甲苷高剂量组和阳性对照组LVEF、LVFS随着治疗时间延长不断升高（P<0.05）;与相同治疗时间假手术组比较,模型组LVEF、LVFS均显著降低（P<0.05）;与治疗第0周模型组比较,各治疗组LVEF、LVFS差异无统计学意义（P>0.05）;治疗第2、4周与模型组比较,黄芪甲苷中剂量组、黄芪甲苷高剂量组和阳性对照组LVEF、LVFS显著升高（P<0.05）;与模型组比较,黄芪甲苷中剂量组、黄芪甲苷高剂量组和阳性对照组LVMI显著降低（P<0.05）,LVSP、LVEDP、±dp/dt显著升高（P<0.05）,血清AngⅡ、ET-1、BNP显著降低（P<0.05）,心肌组织ROS含量显著降低（P<0.05）,NOX、TNF-α基因和蛋白表达量显著降低。研究结果表明,黄芪甲甙可改善AMI大鼠心功能和血流动力学紊乱,抑制心室重构,可能与下调NOX/ROS/TNF-α信号通路表达有关。