三氟甲基化试剂的研究进展

近年来,三氟甲基化成为有机氟化学的研究热点,其主要驱动力是含有三氟甲基基团的有机分子常常表现出独特的物理和化学性质,具有广泛的应用。三氟甲基试剂是向目标分子中引入三氟甲基基团的重要方法之一。综述了三氟甲基化试剂的类型、特点、适用范围等,并对三氟甲基试剂的应用前景作出了展望。     

对氨基三氟甲苯合成工艺的进展

本文对重要的医药、农药中间体 ,即对氨基三氟甲苯的主要合成工艺进行了评述 ,其中着重评述了对氯三氟甲苯的氨解 ,对三卤甲基苯异腈或N -对三卤甲基苯基卤代酰胺的氟解 ,以及苯胺的三氟甲基化三种主要的合成工艺     

三氟单体系列产品发展现状浅析

三氟单体系列产品在高端氟材料领域具有重要的应用,对三氟单体系列产品中的主要产品三氟氯乙烯（CTFE）、三氟乙烯（Tr FE）、三氟溴乙烯（BTFE）,以及三氟溴乙烯主要下游产品如氟溴油、六氟-1,3-丁二烯、三氟苯乙烯的发展现状进行综述和分析,包括制备工艺、主要应用领域以及当前生产和市场现状等。     

三氟甲磺酸酐纯化工艺研究

对三氟甲磺酸酸酐的纯化工艺进行了研究。通过向三氟甲磺酸酐粗品中加入适量的五氧化二磷,反应除去粗品中大部分三氟甲磺酸;接着进行间歇减压精馏,进一步除去三氟甲磺酸酐中的杂质。试验结果表明,反应法可将酸酐中的三氟甲磺酸质量分数降至0.5%以下,间歇减压精馏提纯三氟甲磺酸酐的效果较好,得到的三氟甲磺酸酐的质量分数可达到99.5%以上,收率可达70%。     

项目市场

对氨基三氟甲苯/对溴三氟甲苯及对三氟甲基苯酚/芴甲氧羰酰琥珀酰亚胺     

三氟乙醇的合成

本文介绍了三氟乙醇的基本特性，并详细介绍了三氟乙醇的合成方法。     

三氟丁烯腈及三氟丁烯酸的合成与应用

介绍了三氟丁烯酸和三氟丁烯腈的合成概况,并对其参与的反应及应用进行了详细综述。     

催化氧化三氟乙醇制备三氟乙醛和三氟乙酸

对三氟乙醇气相催化氧化制备三氟乙醛和三氟乙酸的工艺进行了研究,确定了以分子氧为氧化剂 、负载型V₂O₅为催化剂,采用固定床反应器进行反应,气相色谱法检测产品中的三氟乙醛和三氟乙酸的含量,并采用XRD和BET等分析方法对催化剂的性能进行了探讨。     

三氟甲基苯的研究进展

三氟甲基苯是三氟甲基芳香化合物中最为重要的有机中间体之一,在含氟农药、含氟医药及含氟染料等方面有着重要的应用。选取三氟甲基苯作为对象,总结和阐述了近年来三氟甲基苯制备的研究进展。其制备可以通过苯环或卤代苯化合物与氟化试剂的三氟甲基化反应来实现。     

三氟丙酮酸酯的合成与应用研究

综述了分别以六氟环氧丙烷和三氟溴甲烷为原料合成三氟丙酮酸酯类化合物以及三氟丙酮酸酯化合物的应用研究进展。     

First Trimester Prediction of Preterm Delivery in the Absence of Other Pregnancy-Related Complications Using Cardiovascular-Disease Associated MicroRNA Biomarkers

The aim of the study was to determine if aberrant expression profile of cardiovascular disease associated microRNAs would be able to predict within 10 to 13 weeks of gestation preterm delivery such as spontaneous preterm birth (PTB) or preterm prelabor rupture of membranes (PPROM) in the absence of other pregnancy-related complications (gestational hypertension, preeclampsia, fetal growth restriction, or small for gestational age). In addition, we assessed if aberrant expression profile of cardiovascular disease associated microRNAs would be able to predict preterm delivery before and after 34 weeks of gestation. The retrospective study was performed within the period November 2012 to March 2020. Whole peripheral blood samples were collected from 6440 Caucasian individuals involving 41 PTB and 65 PPROM singleton pregnancies. A control group, 80 singleton term pregnancies, was selected on the base of equal sample storage time. Gene expression of 29 selected cardiovascular disease associated microRNAs was studied using real-time RT-PCR. Downregulation of miR-16-5p, miR-20b-5p, miR-21-5p, miR-24-3p, miR-26a-5p, miR-92a-3p, miR-126-3p, miR-133a-3p, miR-145-5p, miR-146a-5p, miR-155-5p, miR-210-3p, miR-221-3p and miR-342-3p was observed in pregnancies with preterm delivery before 37 (≤36 + 6/7) weeks of gestation. Majority of downregulated microRNAs (miR-16-5p, miR-24-3p, miR-26a-5p, miR-92a-3p, miR-133a-3p, miR-145-5p, miR-146a-5p, miR-155-5p, miR-210-3p, and miR-342-3p) was associated with preterm delivery occurring before 37 (≤36 + 6/7) weeks of gestation. The only miR-210-3p was downregulated in pregnancies with preterm delivery before 34 (≤33 + 6/7) weeks of gestation. The type of preterm delivery also had impact on microRNA gene expression profile. Downregulation of miR-24-3p, miR-92a-3p, miR-155-5p, and miR-210-3p was a common feature of PTB and PPROM pregnancies. Downregulation of miR-16-5p, miR-20b-5p, miR-26a-5p, miR-126-3p, miR-133a-3p, miR-146a-5p, miR-221-3p, and miR-342-3p appeared just in PTB pregnancies. No microRNA was uniquely dysregulated in PPROM pregnancies. The combination of 12 microRNAs (miR-16-5p, miR-20b-5p, miR-21-5p, miR-24-3p, miR-26a-5p, miR-92a-3p, miR-133a-3p, miR-145-5p, miR-146a-5p, miR-155-5p, miR-210-3p, and miR-342-3p, AUC 0.818, p < 0.001, 74.53% sensitivity, 75.00% specificity, cut off > 0.634) equally as the combination of 6 microRNAs (miR-16-5p, miR-21-5p, miR-24-3p, miR-133a-3p, miR-155-5p, and miR-210-3p, AUC 0.812, p < 0.001, 70.75% sensitivity, 78.75% specificity, cut off > 0.652) can predict preterm delivery before 37 weeks of gestation in early stages of gestation in 52.83% pregnancies at 10.0% FPR. Cardiovascular disease associated microRNAs represent promising biomarkers with very good diagnostical potential to be implemented into the current routine first trimester screening programme to predict preterm delivery.     

A Single Amino Acid Substitution Changes Antigenicity of ORF2-Encoded Proteins of Hepatitis E Virus

Extensive genomic diversity has been observed among hepatitis E virus (HEV) strains. However, the implication of the genetic heterogeneity on HEV antigenic properties is uncertain. In this study, monoclonal antibodies (Mabs) against truncated ORF2-encoded proteins (aa452-617, designated p166 proteins) derived from HEV strains of Burma (genotype 1a, p166Bur), Pakistan (1b, p166Pak) and Morocco (1c, p166Mor) were raised and used for identification of HEV antigenic diversity. Six Mabs reacted to these 3 p166 proteins as well as p166 proteins constructed from strains derived from Mexico (genotype 2), US (genotype 3) and China (genotype 4), indicating the existence of pan-genotypic epitopes. Two Mabs, 1B5 and 6C7, reacted with p166Bur and p166Mor, but not p166Pak or p166s derived from genotypes 2, 3, and 4, indicating that these 2 Mabs recognized strain-specific HEV epitopes. Both the common and specific epitopes could not be mapped by 23 synthetic peptides spanning the p166Bur sequence, suggesting that they are confirmation-dependent. Comparative sequence analysis showed that p166Bur and p166Mor shared an identical aa sequence along their entire lengths, whereas for p166Pak the aas occupying positions 606 and 614 are different from aas at corresponding positions of p166Bur and p166Mor. Reactivity between 1B5 and p166Bur was abrogated with mutation of p166Bur/A606V, whereas p166Pak acquired the reactivity to 1B5 with mutation of p166Pak/V606A. However, mutations of p166Bur/L614M and P166Pak/M614L did not affect the immunoreactivity. Therefore, the aa occupying position 606 plays a critical role in maintaining the antigenicity of the HEV p166 proteins.     

Exclusion of NUMB Exon12 Controls Cancer Cell Migration through Regulation of Notch1-SMAD3 Crosstalk

NUMB is an endocytic adaptor protein that contains four isoforms (p65, p66, p71 and p72) due to alternative splicing regulation. Here, we show that NUMB exon12 (E12)-skipping isoforms p65/p66 promote epithelial to mesenchymal transition (EMT) and cancer cell migration in vitro, and facilitate cancer metastasis in mice, whereas E12-included p71/p72 isoforms attenuate these effects. Mechanistically, p65/p66 isoforms significantly increase the sorting of Notch1 through early endosomes (EEs) for enhanced Notch1 activity. In contrast, p71/p72 isoforms act as negative regulators of Notch1 by ubiquitylating the Notch1 intracellular domain (N1ICD) and promoting its degradation. Moreover, we observed that the interaction between N1ICD and SMAD3 is important for their own stabilization, and for NUMB-mediated EMT response and cell migration. Either N1ICD or SMAD3 overexpression could significantly recuse the migration reduction seen in the p65/p66 knockdown, and Notch1 or SMAD3 knockdown rescued the migration advantage seen in the overexpression of p66. Taken all together, our study provides mechanistic insights into the opposite regulation of Notch1-SMAD3 crosstalk by NUMB isoforms and identifies them as critical regulators of EMT and cancer cell migration.     

对氯苯甲醛的生产和应用

对氯苯甲醛可通过对氯甲苯氯化水解法、对氯甲苯氧化水解法、对氯甲苯电化学氧化法和对硝基甲苯氧化还原法４种方法制得。对氯苯甲醛可广泛应用于医药、农药、染料工业等方面,具有良好开发前景     

气相色谱-质谱法测定防腐涂料中滴滴涕(DDT)含量

提出了用气质联用法(GC-MS)在特定保留时间窗内选择性离子法(SIM)测定油性防腐涂料和水性防腐涂料中四种滴滴涕p,p’-DDE、o,p’-DDT、p,p’-DDD(TDE)、p,p’-DDT(DDT)含量。此方法对滴滴涕的检出限(S/N=3)均小于50μg/kg,测得方法的回收率在70%～130%之间,相对标准偏差(n=10)均小于20%。     

Electrochemical behaviour of viologen-cyclodextrin inclusion complexes. The case of non-alkyl group substituted viologen

The electrochemical behavior of non-alkyl substituted viologen, 4,4-dibenzyl bipyridinium (BzV), 4,4-dicyanophenyl bipyridinium (CyV) and -,-,-cyclodextrin (, , -CD) was studied using cyclic voltammetry and a spectroelectrochemical method. It was found that BzV and Fe(CN) ₆ ^4– formed a charge-transfer (CT) complex with a ratio of 21 and the colour of the solution faded with the addition of an electrolyte. This behaviour is the same as in then-heptyl viologen and ferrocyanide system [1]. BzV, -CD and -CD formed an inclusion complex only in the reduced state, whilst BzV and -CD formed an inclusion complex in both the oxidized and the reduced state. An EC scheme in which a chemical reaction follows an electrochemical reaction was considered to predominate in the BzV and -, -CD systems, while a CE scheme in which a chemical reaction preceded an electrochemical reaction predominated in the BzV and -CD system. On the other hand, CyV was found to form an inclusion complex with -, -, -CD in both the oxidized and the reduced states. therefore a CE scheme was considered to predominate in the CyV--, -, -CD systems.     

Evaluation of the Role of p53 Tumour Suppressor Posttranslational Modifications and TTC5 Cofactor in Lung Cancer

Mutations in the p53 tumor suppressor are found in over 50% of cancers. p53 function is controlled through posttranslational modifications and cofactor interactions. In this study, we investigated the posttranslationally modified p53, including p53 acetylated at lysine 382 (K382), p53 phosphorylated at serine 46 (S46), and the p53 cofactor TTC5/STRAP (Tetratricopeptide repeat domain 5/ Stress-responsive activator of p300-TTC5) proteins in lung cancer. Immunohistochemical (IHC) analysis of lung cancer tissues from 250 patients was carried out and the results were correlated with clinicopathological features. Significant associations between total or modified p53 with a higher grade of the tumour and shorter overall survival (OS) probability were detected, suggesting that mutant and/or modified p53 acts as an oncoprotein in these patients. Acetylated at K382 p53 was predominantly nuclear in some samples and cytoplasmic in others. The localization of the K382 acetylated p53 was significantly associated with the gender and grade of the disease. The TTC5 protein levels were significantly associated with the grade, tumor size, and node involvement in a complex manner. SIRT1 expression was evaluated in 50 lung cancer patients and significant positive correlation was found with p53 S46 intensity, whereas negative TTC5 staining was associated with SIRT1 expression. Furthermore, p53 protein levels showed positive association with poor OS, whereas TTC5 protein levels showed positive association with better OS outcome. Overall, our results indicate that an analysis of p53 modified versions together with TTC5 expression, upon testing on a larger sample size of patients, could serve as useful prognostic factors or drug targets for lung cancer treatment.     

Generation and Characterization of Site-Specifically Mono-Ubiquitylated p53

The tumor suppressor p53 is regulated by various posttranslational modifications including different types of ubiquitylation, which exert distinct effects on p53. While modification by ubiquitin chains targets p53 for degradation, attachment of single ubiquitin moieties (mono-ubiquitylation) affects the intracellular location of p53 and/or its interaction with chromatin. However, how this is achieved at the molecular level remains largely unknown. Similarly, since p53 can be ubiquitylated at different lysine residues, it remains unclear if the eventual effect depends on the position of the lysine modified. Here, we combined genetic code expansion with oxime ligation to generate p53 site-specifically mono-ubiquitylated at position 120. We found that mono-ubiquitylation at this position neither interferes with p53 ubiquitylation by the E3 ligases HDM2 and E6AP in complex with the viral E6 oncoprotein nor affects p53 binding to a cognate DNA sequence. Thus, ubiquitylation per se does not affect physiologically relevant properties of p53.