Near-atomic cryo-electron microscopy structures of varicella-zoster virus capsids

VZV是一种广泛存在并且具有高度传染性的人类α-疱疹病毒。初次感染VZV可导致水痘，人群普遍易感（感染率约为61%～100%）。该病毒可在背根神经节潜伏感染，持续终生。夏宁邵教授团队长期开展VZV相关基础与新型疫苗研究，通过系统和精细探索建立了高效的VZV规模化培养和病毒颗粒纯化技术体系，成功获得高质量的VZV颗粒样品。首次揭示了疱疹病毒α家族的水痘-带状疱疹病毒（VZV）不同类型核衣壳的近原子分辨率结构，阐明了VZV核衣壳不同组成蛋白的相互作用网络与衣壳装配机制，可为进一步开展新型载体疫苗设计及抗病毒药物等研究提供重要支持。 我校博士后王玮、高级工程师郑清炳、博士生潘德全和俞海副教授为该论文共同第一作者，我校夏宁邵教授、程通副教授、李少伟教授以及美国罗格斯大学朱桦（Hua Zhu）教授、加利福尼亚大学洛杉矶分校周正洪（Z. Hong Zhou）教授为该论文的共同通讯作者。【Abstract】Varicella-zoster virus (VZV) is a medically important human herpesvirus that causes chickenpox and shingles, but its cell-associated nature has hindered structure studies. Here we report the cryo-electron microscopy structures of purified VZV A-capsid and C-capsid, as well as of the DNA-containing capsid inside the virion. Atomic models derived from these structures show that, despite enclosing a genome that is substantially smaller than those of other human herpesviruses, VZV has a similarly sized capsid, consisting of 955 major capsid protein (MCP), 900 small capsid protein (SCP), 640 triplex dimer (Tri2) and 320 triplex monomer (Tri1) subunits. The VZV capsid has high thermal stability, although with relatively fewer intra- and inter-capsid protein interactions and less stably associated tegument proteins compared with other human herpesviruses. Analysis with antibodies targeting the N and C termini of the VZV SCP indicates that the hexon-capping SCP—the largest among human herpesviruses—uses its N-terminal half to bridge hexon MCP subunits and possesses a C-terminal flexible half emanating from the inner rim of the upper hexon channel into the tegument layer. Correlation of these structural features and functional observations provide insights into VZV assembly and pathogenesis and should help efforts to engineer gene delivery and anticancer vectors based on the currently available VZV vaccine.This research was supported by grants from the National Science and Technology Major Projects for Major New Drugs Innovation and Development (no. 2018ZX09711003-005-003), the National Science and Technology Major Project of Infectious Diseases (no. 2017ZX10304402), the National Natural Science Foundation of China (no. 81871648, 81601762), the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences (no. 2019RU022) and the US National Institutes of Health (DE025567/028583). 该研究获得了国家自然科学基金、新药创制国家科技重大专项和传染病防治国家科技重大专项等资助

Microarray-Based Approach Identifies Differentially Expressed MicroRNAs in Porcine Sexually Immature and Mature Testes

MicroRNAs (miRNAs) are short non-coding RNA molecules which are proved to be involved in mammalian spermatogenesis. Their expression and function in the porcine germ cells are not fully understood.We employed a miRNA microarray containing 1260 unique miRNA probes to evaluate the miRNA expression patterns between sexually immature (60-day) and mature (180-day) pig testes. One hundred and twenty nine miRNAs representing 164 reporter miRNAs were expressed differently (p<0.1). Fifty one miRNAs were significantly up-regulated and 78 miRNAs were down-regulated in mature testes. Nine of these differentially expressed miRNAs were validated using quantitative RT-PCR assay. Totally 15,919 putative miRNA-target sites were detected by using RNA22 method to align 445 NCBI pig cDNA sequences with these 129 differentially expressed miRNAs, and seven putative target genes involved in spermatogenesis including DAZL, RNF4 gene were simply confirmed by quantitative RT-PCR.Overall, the results of this study indicated specific miRNAs expression in porcine testes and suggested that miRNAs had a role in regulating spermatogenesis

Polymer Nanocomposites for Photocatalytic Degradation and Photoinduced Utilizations of Azo-Dyes

Specially designed polymer nanocomposites can photo-catalytically degrade azo dyes in wastewater and textile effluents, among which TiO2-based nanocomposites are outstanding and extensively explored. Other nanocomposites based on natural polymers (i.e., chitosan and kaolin) and the oxides of Al, Au, B, Bi, Fe, Li, and Zr are commonly used. These nanocomposites have better photocatalytic efficiency than pure TiO2 through two considerations: (i) reducing the hole/electron recombination rate by stabilizing the excited electron in the conducting band, which can be achieved in TiO2-nanocomposites with graphene, graphene oxide, hexagonal boron nitride (h-BN), metal nanoparticles, or doping; (ii) decreasing the band energy of semiconductors by forming nanocomposites between TiO2 and other oxides or conducting polymers. Increasing the absorbance efficiency by forming special nanocomposites also increases photocatalytic performance. The photo-induced isomerization is exploited in biological systems, such as artificial muscles, and in technical fields such as memory storage and liquid crystal display. Heteroaryl azo dyes show remarkable shifts in photo-induced isomerization, which can be applied in biological and technical fields in place of azo dyes. The self-assembly methods can be employed to synthesize azo-dye polymer nanocomposites via three types of interactions: electrostatic interactions, London forces or dipole/dipole interactions between azo dyes, and photo alignments

Fault Recovery Control Strategy of a Two-Stroke Free-Piston Linear Generator

This paper proposes a recovery control strategy of a two-stroke free-piston linear generator. The recovery process is implemented through switching the linear electric machine into motoring mode once certain unstable operation like misfire occurs during stable cycles. Various operation states are illustrated. Both the steady operation strategy and the fault recovery strategy are analyzed and simulated. The analysis experiments results show that the proposed recovering strategy is feasible and easy to be implemented. The unstable situation can be effectively recovered during 20ms or less, and has no negative influence on the next stable operation

Study on Breakdown Voltage and Minimum Ignition Energy of Sparking System for Free-Piston Linear Generator

This paper is aimed at studying the breakdown voltage and minimum ignition energy of sparking system for the free-piston linear generator (FPLG). Combing the ignition characteristics and demands specifically for the FPLG system, the breakdown voltage and conduction duration of the primary coil are determined theoretically with the Townsend and Paschen Laws. A computational fluid dynamics (CFD) mode is developed to investigate the in-cylinder pressure and temperature at various igniting moments. The theoretical minimum ignition energy is determined with the laminar combustion theory, which contributes to the design and optimization of the sparking system. The effects of the ignition points and initial in-cylinder temperature on the breakdown voltage and minimum ignition energy are analyzed. The results show that advanced ignition contributes to decreasing the breakdown voltage and the conduction duration of the primary coil, meanwhile has no negative influence on the minimum ignition energy. However, rising initial in-cylinder temperature lowers the breakdown voltage, shortens the conduction duration of the primary coil and reduces the minimum ignition energy

Effects of Initial Temperature on the Performances of Free Piston Linear Generator

This paper investigates the influences of the initial temperature on the performance of free piston linear generator (FPLG). Based on multi-dimensional combustion model, the effects of initial temperature on in-cylinder pressure, in-cylinder temperature and NOx emissions are studied. The cause of NOx in internal combustion engine is introduced and the NOx formation mechanism of gasoline FPLG is explored. It is found that reducing initial temperature can rapidly increase in-cylinder pressure, including transient pressure, peak pressure and the maximum pressure rising rate. However, the in-cylinder temperature linearly rises up with the increasing initial temperature. And the NOx emissions increases accordingly. In order to improve output power and reduce emissions, it is feasible to decrease initial temperature properly

An efficient procedure to predict the dynamic loads for piston liner systems in marine engines

The piston ring-cylinder liner (PRCL) is one of the most important parts of marine diesel engines and contributes 25% to 50% of total friction loss. The lubrication simulation analysis of the PRCL system is a challenging task. Complete understanding and precise prediction of lubrication loads is a key to understanding the friction behavior of PRCL systems as the accuracy of the friction prediction depends upon precise prediction of lubrication loads. Therefore, this paper focuses on the gas pressure calculation which is the primary source of lubrication loads. The procedure presented combines the advantages of two mainstream methods to predict loads in the PRCL system. The result is a significant reduction in the computation time without compromising on accuracy. Firstly, a comparison of both approaches is presented which suggests that each technique has its limitations (one is time-bound, and one is accuracy-bound). Then, the results from both calculation methods are verified against literature and a parametric study is performed to identify the key structural parameters of PRCL system that affect the calculation efficiency. Finally, a correlation coefficient is introduced into the analysis to combine the two approaches which then identifies the conditions under which the use of the faster method becomes invalid and replaces it with the more accurate approach. This ensures optimum performance of the calculation procedure by switching between the fast and the accurate method depending upon the accuracy requirement under given conditions, thereby, simplifying the dynamic and lubrication model of PRCL systems. The study has direct implications for the tribological design of the PRCL interface