针对鼠伤寒沙门氏菌致病性岛Ⅲ筛选中药活性成分作为鼠伤寒沙门氏菌潜在毒力抑制剂

目的:筛选中药活性成分作为鼠伤寒沙门氏菌致病性岛III(Salmonella pathogenicity island III,SPI-3)潜在毒力抑制剂。方法:通过分子对接技术明确中药成分与SPI-3中的MgtC蛋白的潜在结合关系。使用β-半乳糖苷酶测定法评估中药成分对mgtC转录的影响。最后,通过评估细菌生长曲线和关键代谢基因的转录水平研究药物对细菌生长的影响。结果:所有27个候选中药成分均显示出与MgtC结合的潜力。阿魏酸、对羟基肉桂酸、牛蒡子苷和掌叶防己碱使mgtC的转录活性降低了15%以上。这四个成分对mgtC转录的最低抑制浓度分别为:阿魏酸16μM;对羟基肉桂酸40μM;牛蒡子苷80μM;掌叶防己碱160μM。此外,我们证实这四种成分均未抑制细菌生长。结论:在本研究中,我们建立了一种基于β-半乳糖苷酶测定法的鼠伤寒沙门氏菌毒力抑制剂筛选方法。以SPI-3为靶标,筛选了27种中药成分,发现有4种对鼠伤寒沙门氏菌毒力具有潜在的强效抑制作用。这为未来从草药中开发新型抗生素提供了先导化合物。这种方法也可用于筛选其他致病菌的毒力抑制剂。

Online pharmaceutical process analysis of Chinese medicine using a miniature mass spectrometer: Extraction of active ingredients as an example

The automation of traditional Chinese medicine(TCM)pharmaceuticals has driven the development of process analysis from offline to online.Most of common online process analytical technologies are based on spectroscopy,making the identification and quantification of specific ingredients still a challenge.Herein,we developed a quality control(QC)system for monitoring TCM pharmaceuticals based on paper spray ionization miniature mass spectrometry(mini-MS).It enabled real-time online qualitative and quantitative detection of target ingredients in herbal extracts using mini-MS without chromatographic separation for the first time.Dynamic changes of alkaloids in Aconiti Lateralis Radix Praeparata(Fuzi)during decoction were used as examples,and the scientific principle of Fuzi compatibility was also investigated.Finally,the system was verified to work stably at the hourly level for pilot-scale extraction.This mini-MS based online analytical system is expected to be further developed for QC applications in a wider range of pharmaceutical processes.

Application of Chinese Herbal Medicine in the Inhibition of Salmonella and its virulence

Salmonellosis poses a serious challenge to public health and poultry industries worldwide.With the emergence of multi-drug resistant Salmonella,the burden caused by Salmonella infections has increased steadily.Enhancing the understanding of the Salmonella infection process may aid the development of new treatments and effective preventive strategies against the disease.This review outlined the Salmonella infection process and introduced the pathogenesis of Salmonella and its virulence factors,such as Type III Secretion Systems effectors.The author summarized the recent advances in the application of Chinese herbal medicine(CHM)in the inhibition of drug-resistant Salmonella and its virulence and discussed the possible mechanisms of CHM inhibiting Salmonella growth and affecting its virulence.CHM has been shown to be effective in inhibiting bacterial growth and alter the virulence properties of pathogens.It is shown that CHM is much less likely to produce drug resistance to bacteria comparing to conventional antibiotics.One reason for this is that CHM may enhance host immunity to control the bacterial infection indirectly whereas conventional antibiotics directly kill the bacteria or inhibit their growth.At present,the percentage of antibiotic-resistant Salmonella isolates is increasing globally.CHM shows great potential for the development of new medicines.It may be an alternative solution to preventing and treating Salmonellosis caused by antibiotic-resistant strains.Further studies on the molecular mechanisms of the active ingredients of CHM may help the future development of novel antibacterial drug designs to contain bacterial infections.

Role of temperature in tribolayers in fretting wear ofγ-TiAl alloy

The formation of tribolayers may play significant influences on fretting wear.At elevated temperature,the adhesion among wear debris and the increased diffusion rate facilitate the formation of tribolayers.However,the intensification of oxidation at elevated temperature and the low diffusion rate in oxides may play an adverse role.The present study aims to investigate the role of temperature in tribolayers in fretting wear using aγ-TiAl alloy.Scanning electron microscope,energy dispersive spectrometer,Raman spectrometer,transmission electron microscope and nanoindentation were utilized to investigate the wear debris,tribolayers,and wear scars.The fretting tests showed that,compared with that at room temperature(RT)and 350℃,significant reduction in wear rate and decrease in the fluctuation of friction coefficient occurred at 550 and 750℃.It was further revealed that when temperature raised from room temperature(RT)to 750℃,the oxidation of the wear debris increased slightly and the diffusion coefficients increased prominently,which facilities the formation of well tribo-sintered tribolayers.The well tribo-sintered tribolayers presented homogenous structure,nanocrystalline grains with excellent mechanical properties,and resulted in the improvement in the fretting wear resistance of theγ-TiAl alloy at 550 and 750℃.

Rapid differentiation of simple saccharides based on cluster ions by paper spray tandem mass spectrometry

Simple saccharides have a variety of biological functions,but their structural diversity and inherent structural features pose a major challenge for rapid analysis.In this work,we developed a derivative-free and ion mobility-free method for the rapid analysis of monosaccharides and disaccharides using paper spray tandem mass spectrometry.Trimeric cluster ions consisting of saccharide analytes,ligands and transition metal ions are used as precursor ions.We defined the R-value as the ratio of the intensity of the product ion that loses one molecule of ligand over the intensity of the product ion that loses one molecule of saccharide via collision induced dissociation(CID).The species and conformation of simple saccharides can be easily differentiated by calculating this R-value.With the capability of directly analyzing clinical samples using paper spray ionization,our method can be used to rapidly quantify the molar ratio of galactose to glucose in dried plasma samples to aid in the diagnosis of galactosemia.The analytical strategy provided herein has good potential to be applied to a wide range of saccharide analysis applications in the future.

Mutations of Desmoglein‑2 in Sudden Unexplained Death in the Chinese Han Population

Sudden unexplained death(SUD)remains a puzzle in forensic medicine.Desmoglein‑2(DSG2)has been linked to arrhythmogenic right ventricular cardiomyopathy which may cause life‑threatening ventricular arrhythmias and sudden death.Fatal arrhythmias resulting in sudden death also occur in the absence of morphologic cardiac abnormalities at autopsy.We hypothesized that DSG2 mutations may be responsible for certain Chinese SUD cases.We sequenced all 15 exons of DSG2 in DNA extracted from postmortem heart tissues of 25 Chinese patients dying from SUD.The primers were designed using the Primer Express 3.0 software.Direct sequencing for both sense and antisense strands was performed with a BigDye Terminator DNA sequencing kit on a 3130 Xl Genetic Analyzer.Mutation damage prediction was made using Mutation Taster,PolyPhen,and SIFT software.In 2 of 25 cases of Chinese SUD samples,two DSG2 heterozygous mutations(p.P927 L and p.T1070M)were identified,and one is probably damaging.We concluded that DSG2 mutations may be related to the occurrence of part of SUD cases in the Chinese Han population.