Study of spatial and temporal evolution of Ar and F atoms in SF6/Ar microsecond pulsed discharge by optical emission spectroscopy

The study of sulfur hexafluoride(SF6) discharge is vital for its application in gas-insulated equipment. Direct current partial discharge(PD) may cause SF6 decomposition, and the decomposed products of SF6, such as F atoms, play a dominant role in the breakdown of insulation systems. In this study, the PD caused by metal protrusion defects is simulated by a needle-plate electrode using pulsed high voltage in SF6/Ar mixtures. The spatial and temporal characteristics of SF6/Ar plasma are analyzed by measuring the emission spectra of F and Ar atoms, which are important for understanding the characteristics of PD. The spatial resolved results show that both F and Ar atom spectral intensities increase first from the plate anode to the needle and then decrease under the conditions of a background pressure of400 Pa, peak voltage of-1000 V, frequency of 2 kHz, pulse width of 60 μs, and electrode gap of 5-9 mm. However, the distribution characteristics of F and Ar are significantly different. The temporal distribution results show that the spectral intensity of Ar decreasesfirst and then increases slowly, while the spectral intensity of F increases slowly for the duration of the pulsed discharge at the electrode gap of 5 mm and the pulse width of40-80 μs.

Enhanced protective immunity against SARS-CoV-2 elicited by a VSV vector expressing a chimeric spike protein

SARS-CoV-2 and SARS-CoV are genetically related coronavirus and share the same cellular receptor ACE2.By replacing the VSV glycoprotein with the spikes(S)of SARS-CoV-2 and SARS-CoV,we generated two replication-competent recombinant viruses,rVSVSARS-CoV-2 and rVSV-SARS-CoV.Using wild-type and human ACE2(hACE2)knock-in mouse models,we found a single dose of rVSV-SARS-CoV could elicit strong humoral immune response via both intranasal(i.n.)and intramuscular(i.m.)routes.Despite the high genetic similarity between SARS-CoV-2 and SARS-CoV,no obvious cross-neutralizing activity was observed in the immunized mice sera.In macaques,neutralizing antibody(NAb)titers induced by one i.n.dose of rVSV-SARS-CoV-2 were eight-fold higher than those by a single i.m.dose.Thus,our data indicates that rVSV-SARS-CoV-2 might be suitable for i.n.administration instead of the traditional i.m.immunization in human.Because rVSV-SARS-CoV elicited significantly stronger NAb responses than rVSV-SARS-CoV2 in a route-independent manner,we generated a chimeric antigen by replacing the receptor binding domain(RBD)of SARS-CoV S with that from the SARS-CoV-2.rVSV expressing the chimera(rVSV-SARS-CoV/2-RBD)induced significantly increased NAbs against SARS-CoV-2 in mice and macaques than rVSV-SARS-CoV-2,with a safe Th1-biased response.Serum immunized with rVSV-SARS-CoV/2-RBD showed no cross-reactivity with SARS-CoV.hACE2 mice receiving a single i.m.dose of either rVSV-SARS-CoV-2 or rVSV-SARSCoV/2-RBD were fully protected against SARS-CoV-2 challenge without obvious lesions in the lungs.Our results suggest that transplantation of SARS-CoV-2 RBD into the S protein of SARS-CoV might be a promising antigen design for COVID-19 vaccines.

Design, synthesis, and in vitro activity of methylisoxazole/isothiazole amides as BACE1 inhibitors

Based on the structure of compound B51（IC_（50） = 37.4 μM）, which was discovered as hit in a previous virtual screen, a series of methylisoxazole/isothiazole amide derivatives were designed and synthesized as BACE1 inhibitors. The methoxyphenylpyrimidone fragment of B51 was transformed into a methoxyphenylmethylisoxazole/isothiazole moiety to reduce the molecular weight while retaining the ability to fit into the S1＇ and S2＇ subpocket of BACE1 as predicted by docking studies. The effects of BACE1 inhibition and the structure-activity relationships were analyzed. Among all 20 designed compounds, 5t exhibited almost 10-fold improved potency（IC_（50） = 5.33 μM） compared to B51 in the BACE1 inhibition assay. Additionally, it has exhibited ＂rapid binding, slow dissociation＂ kinetics in SPR analysis, suggesting a longer inhibitory effect than B51. All acquired methylisoxazole/isothiazole derivatives were small in size and safe to normal cells, which allow them represent a novel scaffold for BACE1 inhibitor design.

毛乌素沙地沙障固沙机制与效益评估

沙障是沙区广泛应用的一种固沙工程措施,准确理解沙障的固沙机制并优化其配置模式有助于防风固沙技术的完善.本文以毛乌素沙地腹地发育的4个新月形沙丘作为研究载体,通过对9类(3种材料×3种规格)沙障措施下的沙丘开展地形测量、风沙观测、沉积物采样、植被调查和室内分析等研究,揭示了沙障环境下沙丘的表面过程,评估了各类型沙障防风固沙效果及生态恢复效应.结果表明,沙障具有降低沙丘高度、重塑微地貌形态、降低近地表风速、拦阻沙物质输移以及促进植被恢复的作用,其作用强度大小受控于沙障材料、规格配置及铺设坡位;沙柳沙障是该区防风固沙和促进植被恢复的最佳选择,草绳沙障其次,聚乳酸(polylactic acid,PLA)纤维沙袋沙障最差;沙柳和草绳沙障在1 m×1 m规格下的固沙效益最佳,而PLA沙障在2 m×2 m规格下的固沙效益最佳.此外,本文认为,沙障的防风固沙效益受多个要素的共同影响,单以近地表风速大小或微地貌形态作为衡量标准是不充分的;沙障工程应依据区域固沙需求和实地环境,立足重点目标或需求,因地制宜选择出最适宜的沙障配置模式.

Structure-based design and synthesis of 5-benzyl-2-phenylpyrimidin-4(3H)-one derivatives as novel MEK1 inhibitors

Previous studies have shown that Ras/Raf/MEK/ERK signaling pathway is up-regulated in almost all cancer cells.Blocking of this pathway by MEK inhibition is an efficient therapeutic approach of cancer.In the present study,we described the discovery of 5-benzyl-2-phenylpyrimidin-4（3 H）-one as a novel skeleton of allosteric MEK inhibitor.All acquired target compounds exhibited modest potency to inhibit MEK1 in Raf-MEK cascading assay,and docking studies revealed that the binding mode of the most potent compound（SJ3） was very similar to that of the well known diarylamine-based inhibitor（PD0325901）.The results provided valuable guidance for further optimizations on this novel scaffold to achieve druggable molecules.