ACE2, the Receptor that Enables Infection by SARS-CoV-2: Biochemistry,Structure, Allostery and Evaluation of the Potential Development of ACE2 Modulators

Angiotensin converting enzyme 2 (ACE2) is the human receptor that interacts with the spike protein of coronaviruses, including the one that produced the 2020 coronavirus pandemic (COVID-19). Thus, ACE2 is a potential target for drugs that disrupt the interaction of human cells with SARS-CoV-2 to abolish infection. There is also interest in drugs that inhibit or activate ACE2, that is, for cardiovascular disorders or colitis. Compounds binding at alternative sites could allosterically affect the interaction with the spike protein. Herein, we review biochemical, chemical biology, and structural information on ACE2, including the recent cryoEM structures of full-length ACE2. We conclude that ACE2 is very dynamic and that allosteric drugs could be developed to target ACE2. At the time of the 2020 pandemic, we suggest that available ACE2 inhibitors or activators in advanced development should be tested for their ability to allosterically displace the interaction between ACE2 and the spike protein.     

（S）-噻吗洛尔半水合物的合成及表征

为了开发β受体阻断剂新药（S）-噻吗洛尔半水合物，采用3-吗啉-4-氯-1，2，5-噻二唑为起始原料，经水解反应得到中间体1（3-吗啉-4-羟基-1，2，5-噻二唑）。中间体1与R-环氧氯丙烷发生醚化反应，经后处理及重结晶得到中间体2 {（R）-4-［4-（环氧乙烷-2-基甲氧基）-1，2，5-噻二唑-3-基］吗啉}。中间体2经胺化反应、马来酸成盐及重结晶得到（S）-马来酸噻吗洛尔。（S）-马来酸噻吗洛尔经游离、纯水转晶得到符合药典标准的（S）-噻吗洛尔半水合物，总收率14.05%且e.e.值为99.66%。最终成品经IR、1H-NMR、13C-NMR、MS、TGA、DSC表征，并优化各步反应条件。结果表明:以三乙胺为醚化反应缚酸剂75 ℃反应最佳；以乙醇为胺化反应溶剂46 ℃反应16 h最佳；S-噻吗洛尔的转晶拆分以水作溶剂，比传统不对称合成工艺安全稳定，操作简单，适合工业化生产。     

Cheese fortification using saturated monoglyceride self‐assembly structures as carrier of omega‐3 fatty acids

The purpose of this research was to study the capacity of emulsions containing saturated monoglyceride self‐assembly structures to deliver omega‐3 fatty acids in fresh soft cheese. To this aim, fortified emulsions containing different ratios of milk, saturated monoglycerides (MGs) and cod liver oil were added to milk before cheese‐making. These emulsions were characterised by distinct microstructural features observed by polarised light microscopy and apparent viscosity values. The omega‐3 delivery performance of MG emulsions highlighted that this strategy allowed a good retention of the omega‐3‐rich oil in the curd (up to 75%). The fortified cheeses showed yield value and fat content higher than those of control samples. The enriched cheese showed hardness and cohesiveness obtained by texture profile analysis similar to those of the unfortified product. Only a slight decrease in gumminess was detected in fortified cheese.     

Effects of SO2 on selective catalytic reduction of NO with NH3 over a TiO2 photocatalyst

The effect of SO₂ gas was investigated on the activity of the photo-assisted selective catalytic reduction of nitrogen monoxide (NO) with ammonia (NH₃) over a TiO₂ photocatalyst in the presence of excess oxygen (photo-SCR). The introduction of SO₂ (300 ppm) greatly decreased the activity of the photo-SCR at 373 K. The increment of the reaction temperature enhanced the resistance to SO₂ gas, and at 553 K the conversion of NO was stable for at least 300 min of the reaction. X-ray diffraction, FTIR spectroscopy, thermogravimetry and differential thermal analysis, x-ray photoelectron spectroscopy (XPS), elemental analysis and N₂ adsorption measurement revealed that the ammonium sulfate species were generated after the reaction. There was a strong negative correlation between the deposition amount of the ammonium sulfate species and the specific surface area. Based on the above relationship, we concluded that the deposition of the ammonium sulfate species decreased the specific surface area by plugging the pore structure of the catalyst, and the decrease of the specific surface area resulted in the deactivation of the catalyst.     

不同晶相结构ZrO2负载铜基催化剂用于二乙醇胺脱氢反应

通过制备不同晶相结构〔单斜相(m-ZrO_2)、四方相(t-ZrO_2)和无定型(a-ZrO_2)〕ZrO_2载体,再通过沉积沉淀法制得Cu/m-ZrO_2、Cu/t-ZrO_2和Cu/a-ZrO_2催化剂,分别用于催化二乙醇胺脱氢合成亚氨基二乙酸反应。采用XRD、氮气物理吸附脱附、XPS、H_2-TPR、CO_2-TPD对催化剂的结构进行了表征。结果表明,Cu/m-ZrO_2催化剂界面更加有利于Cu~+/Cu~0稳定存在,具有更多的碱性位点,且抗氧化性较好。在二乙醇胺脱氢反应中,Cu/m-ZrO_2催化剂性能最好,反应时间为2.5 h,亚氨基二乙酸收率为97.64%。     

CAN-BUS系统应用一例

CAN-BUS系统自问世以来,已将近30年,当代各品牌车辆纷纷采用,但大部分技术人员对CAN总线系统既熟悉又陌生。经常能听到,但具体操作又显得有些力不从心。本文通过对奇瑞A3品牌轿车CAN总线的巧妙应用,引导大家进一步理解和应用CAN总线。     

共享交通的时空轨迹检索与群体发现

为解决共享交通下的共乘用户群体发现效率低、准确率不高问题，依据R-树原理建立GeoOD-Tree索引，并在此基础上提出以最大化共乘率为目标的群体发现策略。首先，对原始时空轨迹数据进行特征提取与标定处理，挖掘有效出行起讫点（OD）轨迹；其次，针对用户起讫点轨迹的特征，建立GeoOD-Tree索引进行有效的存储管理；最后，给出以最大化共乘行程为目标的群体发现模型，并运用K最近邻（KNN）查询对搜索空间剪枝压缩，提高群体发现效率。采用西安市近12000辆出租车营运轨迹数据，选取动态时间规整（DTW）等典型算法与所提算法在查询效率与准确率上进行性能对比分析。与DTW算法相比，所提算法的准确率提高了10.12%，查询效率提高了约15倍。实验结果表明提出的群体发现策略能有效提高共乘用户群体发现的准确率和效率，可有效提升共乘出行方式的出行率。     

Investigation on phase shifting for a 4 K Stirling pulse tube cryocooler with He-3 as working fluid

He-3 is generally recognized for its ability to provide more excellent thermophysical performance than He-4, especially in the 4 K temperature range. However, this was not always the case in our preliminary experiments on a three-stage Stirling-type pulse tube cryocooler (SPTC). Our ongoing studies, as reported in this paper, demonstrate that the different working fluids also affect the performance through their phase shifting capability. This feature has been passed over in large part by researchers considering refrigerant substitution. Unlike previous theoretical analyses that focus primarily on regenerator losses, this report investigates the effects of the working fluid on the phase angle at the cold end in order to quantitatively reveal the relationship between the lowest attainable temperature and the cooling capacity. The analysis agrees well with our experimental results on a three-stage SPTC. While running with the operating parameters optimized for He-3, the lowest temperature of the SPTC decreased from 5.4 K down to 4.03 K. This is the lowest refrigeration temperature ever achieved with a three-stage SPTC.     

Barium titanate‐based nanodielectrics of two chemically recyclable thermosets

In this work was investigated the effect of the addition of barium titanate (BaTiO₃) on electrical properties of two chemically recyclable thermosets, polyhemiaminal (PHA) and polyhexahydro‐s‐triazine (PHT), both fabricated from 4,4′‐oxydianiline (ODA), an ether derivative of aniline and paraformaldehyde. Thermal and mechanical properties as well as chemical recyclability of the two polymers and their nanocomposites/nanodielectrics were also investigated. In addition, a quantitative analysis was conducted of the nanoparticle dispersion in the PHA‐/PHT‐based BaTiO₃‐containing nanocomposites using transmission electron microscopy imaging and the nearest‐neighbor distance index and this index was used to analyze the investigated properties in connection with the proper mechanisms. Regarding the electrical properties for both neat polymers, conductivity values of the order of 10^?8 S m^?1 at 100 Hz were observed and dielectric constant values close to 2.80 for both polymers at 1 kHz. The addition of 0.5 wt% of BaTiO₃ ferroelectric nanoparticles increased by about 44% the dielectric constant (1 kHz) and conductivity (10² Hz) of the PHA‐based nanocomposite. PHA and PHT exhibited glass transition temperature (T_g) values in the range 125–180 °C. An increase of 7 °C in T_g was observed after the incorporation of 0.5 wt% of BaTiO₃ into PHA. Concerning the mechanical properties, values in the range 4.00–4.45 GPa for reduced modulus and 0.30–0.43 GPa for nanohardness for PHA and PHT polymers were observed. Independently of filler content or polymer matrix, both mechanical properties were enhanced after the addition of BaTiO₃. The chemical recycling of PHA/PHT and all nanocomposites in the initial ODA reagent after sulfuric acid treatment was successfully characterized using the NMR and Fourier transform infrared spectroscopic techniques. © 2018 Society of Chemical Industry