高温及络合稳定剂存在下水热晶化合成TS-2分子筛

在TS-2分子筛胶液制备过程中,添加了络合稳定剂H₂O₂。实验分析表明：钛酸四丁酯与H₂O₂形成过氧化钛物种,可以有效避免锐钛矿TiO₂形成,提高骨架钛含量,在高温条件下晶化仍能得到催化性能较好的TS-2分子筛。利用丙烯环氧化反应对TS-2分子筛进行了考评,H₂O₂的转化率可达94％,H₂O₂生成PO的选择性可达97％。反应体系的酸碱性对环氧化产物分布影响显著,碱性物质的加入可以显著提高PO的选择性,抑制PO和溶剂发生的副反应,但是过量的碱性添加物会造成TS-2分子筛的失活。     

高分子精密过滤工艺的工程应用设计探讨

采用新型刚性高分子微孔精密过滤工艺对合成氨净化装置脱碳液、铜氨液过滤进行改造,取得良好的节能降耗效果。     

介孔分子筛负载杂多酸催化剂催化合成邻苯二甲酸二辛酯

采用介孔分子筛负载杂多酸为催化剂,在釜式反应器内对苯酐和正辛醇的酯化反应进行了研究,考察了催化剂的活性、选择性和稳定性,结果表明,在组成适宜的催化剂和适当的反应条件下,苯酐转化率可达98%,DOP选择性可达100%,且催化剂可重复多次使用。     

Utilizing Genomically Targeted Molecular Data to Improve Patient-Specific Outcomes in Autism Spectrum Disorder

Molecular biology combined with genomics can be a powerful tool for developing potential intervention strategies for improving outcomes in children with autism spectrum disorders (ASD). Monogenic etiologies rarely cause autism. Instead, ASD is more frequently due to many polygenic contributing factors interacting with each other, combined with the epigenetic effects of diet, lifestyle, and environment. One limitation of genomics has been identifying ways of responding to each identified gene variant to translate the information to something clinically useful. This paper will illustrate how understanding the function of a gene and the effects of a reported variant on a molecular level can be used to develop actionable and targeted potential interventions for a gene variant or combinations of variants. For illustrative purposes, this communication highlights a specific genomic variant, SHANK3. The steps involved in developing molecularly genomically targeted actionable interventions will be demonstrated. Cases will be shared to support the efficacy of this strategy and to show how clinicians utilized these targeted interventions to improve ASD-related symptoms significantly. The presented approach demonstrates the utility of genomics as a part of clinical decision-making.     

Discovery of SARS-CoV-2 3CLPro Peptidomimetic Inhibitors through the Catalytic Dyad Histidine-Specific Protein–Ligand Interactions

As the etiological agent for the coronavirus disease 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenges the ongoing efforts of vaccine development and drug design. Due to the accumulating cases of breakthrough infections, there are urgent needs for broad-spectrum antiviral medicines. Here, we designed and examined five new tetrapeptidomimetic anti-SARS-CoV-2 inhibitors targeting the 3C-Like protease (3CL^Pro), which is highly conserved among coronaviruses and essential for viral replications. We significantly improved the efficacy of a ketoamide lead compound based on high-resolution co-crystal structures, all-atom simulations, and binding energy calculations. The inhibitors successfully engaged the catalytic dyad histidine residue (H41) of 3CLPro as designed, and they exhibited nanomolar inhibitory capacity as well as mitigated the viral loads of SARS-CoV-2 in cellular assays. As a widely applicable design principle, our results revealed that the potencies of 3CL^Pro-specific drug candidates were determined by the interplay between 3CL^Pro H41 residue and the peptidomimetic inhibitors.     

抗坏血酸对猴头菇β-葡聚糖表观黏度及结构特征的影响

采用碱提醇沉法制备猴头菇 β-葡聚糖(Hericium erinaceus alkali-extracted polysaccharide,HEAEP),系统研究了不同条件(抗坏血酸浓度、金属离子、温度、pH值等)下抗坏血酸对HEAEP表观黏度的影响,并深入分析了抗坏血酸对HEAEP结构特征的影响.研究结果表明:猴头菇...     

基于网络药理学探讨水红花子抗肝硬化机制

为进一步研究水红花子的药用物质基础,利用网络药理学和分子对接技术探讨了水红花子治疗肝硬化的作用机制.首先利用中药系统药理学数据库与分析平台(TCMSP)、人类基因数据库(GeneCards)、蛋白质-蛋白质相互作用网络功能富集分析平台(STRING)建立了水红花子有效成分-肝硬化的靶点基因网络,然后利用基因本体(gene ontology,GO)、京都基因和基因组百科全书(Kyoto encyclopedia of genes and genomes, KEGG)富集分析和分子对接手段研究了水红花子的抗肝硬化机制.研究结果显示：水红花子治疗肝硬化的成分可能是具有保肝功能的β-谷甾醇、山奈酚、儿茶素、圣草酚、槲皮素,作用靶点可能为IL-6、VEGFA、AKT1、TP53、CXCL8、TNF;水红花子参与抗肝硬化的生物学过程可能有凋亡负调控、程序性细胞死亡负调控、细胞增殖调控等,相关信号通路可能包括癌症通路、细胞因子-细胞因子受体相互作用、Toll样受体信号通路等;槲皮素、山奈酚与AKT1的结合能和呋塞米与AKT1的结合能相似.该研究结果可为后续研究水红花子抗肝硬化的机制提供理论依据.     

Fractionation of oligomers of linear alphaolefins in a molecular evaporator

Oligomers of higher alphaolefins, mainly of 1-decene and 1-octene have important applications as synthetic lubricating oils or their components. The results of fractionation of polydecene, polyoctene, and polybutene oils in a wiped-film molecular evaporator, for the purpose of preparing narrow distillate cuts, are presented in the paper. Characteristics and properties of the fractions obtained are shown, and the possibilities for this distillation method in the fractionation of polyolefin oils discussed.     

Molecular Networking for Drug Toxicities Studies: The Case of Hydroxychloroquine in COVID-19 Patients

Using drugs to treat COVID-19 symptoms may induce adverse effects and modify patient outcomes. These adverse events may be further aggravated in obese patients, who often present different illnesses such as metabolic-associated fatty liver disease. In Rennes University Hospital, several drug such as hydroxychloroquine (HCQ) have been used in the clinical trial HARMONICOV to treat COVID-19 patients, including obese patients. The aim of this study is to determine whether HCQ metabolism and hepatotoxicity are worsened in obese patients using an in vivo/in vitro approach. Liquid chromatography high resolution mass spectrometry in combination with untargeted screening and molecular networking were employed to study drug metabolism in vivo (patient’s plasma) and in vitro (HepaRG cells and RPTEC cells). In addition, HepaRG cells model were used to reproduce pathophysiological features of obese patient metabolism, i.e., in the condition of hepatic steatosis. The metabolic signature of HCQ was modified in HepaRG cells cultured under a steatosis condition and a new metabolite was detected (carboxychloroquine). The RPTEC model was found to produce only one metabolite. A higher cytotoxicity of HCQ was observed in HepaRG cells exposed to exogenous fatty acids, while neutral lipid accumulation (steatosis) was further enhanced in these cells. These in vitro data were compared with the biological parameters of 17 COVID-19 patients treated with HCQ included in the HARMONICOV cohort. Overall, our data suggest that steatosis may be a risk factor for altered drug metabolism and possibly toxicity of HCQ.