Complete ¹H-NMR and <SUP>13</SUP>C-NMR spectral assignment of five malonyl ginsenosides from the fresh flower buds of Panax ginseng

Yu-Shuai Wang,Yin-Ping Jin,Wei Gao,Sheng-Yuan Xiao,Yu-Wei Zhang,Pei-He Zheng,Jia Wang,Jun-Xia Liu,Cheng-He Sun,Ying-Ping Wang 고려인삼학회 2016 Journal of Ginseng Research Vol.40 No.3

Background: Ginsenosides are the major effective ingredients responsible for the pharmacological effects of ginseng. Malonyl ginsenosides are natural ginsenosides that contain a malonyl group attached to a glucose unit of the corresponding neutral ginsenosides. Methods: Medium-pressure liquid chromatography and semipreparative high-performance liquid chromatography were used to isolate purified compounds and their structures determined by extensive one-dimensional- and two-dimensional nuclear magnetic resonance (NMR) experiments. Results: A new saponin, namely malonyl-ginsenoside Re, was isolated from the fresh flower buds of Panax ginseng, along with malonyl-ginsenosides Rb1, Rb2, Rc, Rd. Some assignments for previously published ¹H- and <SUP>13</SUP>C-NMR spectra were found to be inaccurate. Conclusion: This study reports the complete NMR assignment of malonyl-ginsenoside Re, Rb₁, Rb₂, Rc, and Rd for the first time.

Simultaneous Determination of Mycophenolic Acid and Its Metabolites by HPLC and Pharmacokinetic Studies in Rat Plasma and Bile

Jun-wei Gao,Zhi-hai Peng,Xiao-yu Li,Bo Sun,Yan-kun Guo,Gao-lin Liu 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.1

In this study, we determined the pharmacokinetics of mycophenolic acid (MPA) and its metabolites mycophenolic acid glucuronide (MPAG) and acyl glucuronide (AcMPAG) in rat plasma and bile, using a newly developed HPLC method. Protein precipitation and liquid-liquid extraction were employed in sample preparation of plasma and bile, respectively. The HPLC methods included a gradient elution consisting of acetonitrile and phosphate buffer at a flow rate of 1.2 mL/min, with UV detection at 254 nm. The HPLC method was found to be sensitive and linear (r^2 ≥ 0.9991, 1.0-128.0 and 0.25-32.0 mg/L for MPA; 1.0-128.0 and 0.5-64.0 mg/L for MPAG; 0.25-32.0 and 1.0-128.0 mg/L for AcMPAG in rat plasma and bile, respectively), precise (both the intra- and inter-day variability were ≤ 6.8%), and accurate (both the intra- and inter-day accuracy were between 92.2% and 105.4%). The average extraction efficiencies for MPA, MPAG and AcMPAG were 85.3%, 100.1%, and 94.7% in plasma, and 88.0%, 67.3%, and 68.3% in bile, respectively. The method was successfully employed for pharmacokinetic studies in plasma and bile after oral administration of mycophenolate mofetil (prodrug of MPA) in rats.

Discovery and Characterization of the Tuberculosis Drug Lead Ecumicin

Gao, Wei,Kim, Jin-Yong,Chen, Shao-Nong,Cho, Sang-Hyun,Choi, Jongkeun,Jaki, Birgit U.,Jin, Ying-Yu,Lankin, David C.,Lee, Ji-Ean,Lee, Sun-Young,McAlpine, James B.,Napolitano, José,G.,Franzblau, Sc American Chemical Society 2014 ORGANIC LETTERS Vol.16 No.23

<P>The new tuberculosis (TB) lead ecumicin (<B>1</B>), a cyclic tridecapeptide, was isolated from <I>Nonomuraea sp.</I> MJM5123, following a high-throughput campaign for anti-TB activity. The large molecular weight of 1599 amu detected by LC-HR-MS precluded the initial inference of its molecular formula. The individual building blocks were identified by extensive NMR experiments. The resulting two possible planar structures were distinguished by LC-MS<SUP>2</SUP>. Determination of absolute configuration and unambiguous structural confirmation were carried out by X-ray crystallography and Marfey’s analysis.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/orlef7/2014/orlef7.2014.16.issue-23/ol5026603/production/images/medium/ol-2014-026603_0003.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ol5026603'>ACS Electronic Supporting Info</A></P>

Burden of Total and Cause-Specific Mortality Related to Tobacco Smoking among Adults Aged ≥45 Years in Asia: A Pooled Analysis of 21 Cohorts

Zheng, Wei,McLerran, Dale F.,Rolland, Betsy A.,Fu, Zhenming,Boffetta, Paolo,He, Jiang,Gupta, Prakash Chandra,Ramadas, Kunnambath,Tsugane, Shoichiro,Irie, Fujiko,Tamakoshi, Akiko,Gao, Yu-Tang,Koh, Woon Public Library of Science 2014 PLoS medicine Vol.11 No.4

<▼1><P>Wei Zheng and colleagues quantify the burden of tobacco-smoking-related deaths for adults in Asia.</P><P><I>Please see later in the article for the Editors' Summary</I></P></▼1><▼2><P><B>Background</B></P><P>Tobacco smoking is a major risk factor for many diseases. We sought to quantify the burden of tobacco-smoking-related deaths in Asia, in parts of which men's smoking prevalence is among the world's highest.</P><P><B>Methods and Findings</B></P><P>We performed pooled analyses of data from 1,049,929 participants in 21 cohorts in Asia to quantify the risks of total and cause-specific mortality associated with tobacco smoking using adjusted hazard ratios and their 95% confidence intervals. We then estimated smoking-related deaths among adults aged ≥45 y in 2004 in Bangladesh, India, mainland China, Japan, Republic of Korea, Singapore, and Taiwan—accounting for ∼71% of Asia's total population. An approximately 1.44-fold (95% CI = 1.37–1.51) and 1.48-fold (1.38–1.58) elevated risk of death from any cause was found in male and female ever-smokers, respectively. In 2004, active tobacco smoking accounted for approximately 15.8% (95% CI = 14.3%–17.2%) and 3.3% (2.6%–4.0%) of deaths, respectively, in men and women aged ≥45 y in the seven countries/regions combined, with a total number of estimated deaths of ∼1,575,500 (95% CI = 1,398,000–1,744,700). Among men, approximately 11.4%, 30.5%, and 19.8% of deaths due to cardiovascular diseases, cancer, and respiratory diseases, respectively, were attributable to tobacco smoking. Corresponding proportions for East Asian women were 3.7%, 4.6%, and 1.7%, respectively. The strongest association with tobacco smoking was found for lung cancer: a 3- to 4-fold elevated risk, accounting for 60.5% and 16.7% of lung cancer deaths, respectively, in Asian men and East Asian women aged ≥45 y.</P><P><B>Conclusions</B></P><P>Tobacco smoking is associated with a substantially elevated risk of mortality, accounting for approximately 2 million deaths in adults aged ≥45 y throughout Asia in 2004. It is likely that smoking-related deaths in Asia will continue to rise over the next few decades if no effective smoking control programs are implemented.</P><P><I>Please see later in the article for the Editors' Summary</I></P></▼2><▼3><P><B>Editors' Summary</B></P><P><B>Background</B></P><P>Every year, more than 5 million smokers die from tobacco-related diseases. Tobacco smoking is a major risk factor for cardiovascular disease (conditions that affect the heart and the circulation), respiratory disease (conditions that affect breathing), lung cancer, and several other types of cancer. All told, tobacco smoking kills up to half its users. The ongoing global “epidemic” of tobacco smoking and tobacco-related diseases initially affected people living in the US and other Western countries, where the prevalence of smoking (the proportion of the population that smokes) in men began to rise in the early 1900s, peaking in the 1960s. A similar epidemic occurred in women about 40 years later. Smoking-related deaths began to increase in the second half of the 20th century, and by the 1990s, tobacco smoking accounted for a third of all deaths and about half of cancer deaths among men in the US and other Western countries. More recently, increased awareness of the risks of smoking and the introduction of various tobacco control measures has led to a steady decline in tobacco use and in smoking-related diseases in many developed countries.</P><P><B>Why Was This Study Done?</B></P><P>Unfortunately, less well-developed tobacco control programs, inadequate public awareness of smoking risks, and tobacco company marketing have recently led to sharp increases in the prevalence of smoking in many low- and middle-income countries, particularly in Asia. More than 50% of men in many Asian countries are now smokers, about tw

The Cyclic Peptide Ecumicin Targeting ClpC1 Is Active against <i>Mycobacterium tuberculosis In Vivo</i>

Gao, Wei,Kim, Jin-Yong,Anderson, Jeffrey R.,Akopian, Tatos,Hong, Seungpyo,Jin, Ying-Yu,Kandror, Olga,Kim, Jong-Woo,Lee, In-Ae,Lee, Sun-Young,McAlpine, James B.,Mulugeta, Surafel,Sunoqrot, Suhair,Wang, American Society for Microbiology 2015 Antimicrobial Agents and Chemotherapy Vol.59 No.2

<P>Drug-resistant tuberculosis (TB) has lent urgency to finding new drug leads with novel modes of action. A high-throughput screening campaign of >65,000 actinomycete extracts for inhibition of <I>Mycobacterium tuberculosis</I> viability identified ecumicin, a macrocyclic tridecapeptide that exerts potent, selective bactericidal activity against <I>M. tuberculosis</I> <I>in vitro</I>, including nonreplicating cells. Ecumicin retains activity against isolated multiple-drug-resistant (MDR) and extensively drug-resistant (XDR) strains of <I>M. tuberculosis</I>. The subcutaneous administration to mice of ecumicin in a micellar formulation at 20 mg/kg body weight resulted in plasma and lung exposures exceeding the MIC. Complete inhibition of <I>M. tuberculosis</I> growth in the lungs of mice was achieved following 12 doses at 20 or 32 mg/kg. Genome mining of lab-generated, spontaneous ecumicin-resistant <I>M. tuberculosis</I> strains identified the ClpC1 ATPase complex as the putative target, and this was confirmed by a drug affinity response test. ClpC1 functions in protein breakdown with the ClpP1P2 protease complex. Ecumicin markedly enhanced the ATPase activity of wild-type (WT) ClpC1 but prevented activation of proteolysis by ClpC1. Less stimulation was observed with ClpC1 from ecumicin-resistant mutants. Thus, ClpC1 is a valid drug target against <I>M. tuberculosis</I>, and ecumicin may serve as a lead compound for anti-TB drug development.</P>

Identification of S-Nitrosylation of Proteins of Helicobacter pylori in Response to Nitric Oxide Stress

Wei Qu,Yabin Zhou,Yundong Sun,Ming Fang,Han Yu,Wenjuan Li,Zhifang Liu,Jiping Zeng,Chunyan Chen,Chengjiang Gao,Jihui Jia 한국미생물학회 2011 The journal of microbiology Vol.49 No.2

Innate and adaptive immune responses are activated in humans when Helicobacter pylori invades the gastric mucosa. Nitric oxide (NO) and reactive nitrogen species are important immune effectors, which can exert their functions through oxidation and S-nitrosylation of proteins. S-nitrosoglutathione and sodium nitroprusside were used as NO donors and H. pylori cells were incubated with these compounds to analyze the inhibitory effect of NO. The suppressing effect of NO on H. pylori has been shown in vitro. Furthermore,the proteins modified by S-nitrosylation in H. pylori were identified through the biotin switch method in association with matrix-assisted laser desorption ionization/time-of-flight tandem mass spectrometry (MALDITOF-MS/MS). Five S-nitrosylated proteins identified were a chaperone and heat-shock protein (GroEL),alkyl hydroperoxide reductase (TsaA), urease alpha subunit (UreA), HP0721, and HP0129. Importantly,S-nitrosylation of TsaA and UreA were confirmed using purified recombinant proteins. Considering the importance of these enzymes in antioxidant defenses, adherence, and colonization, NO may exert its antibacterial actions by targeting enzymes through S-nitrosylation. Identification of protein S-nitrosylation may contribute to an understanding of the antibacterial actions of NO. Our findings provide an insight into potential targets for the development of novel therapeutic agents against H. pylori infection.

Influence of Different Inlet Conditions on Micromixer

Wei Xu,Xiuhua He,Lingfeng Gao,Tian Xia,Zhengying Yu 한국유체기계학회 2018 International journal of fluid machinery and syste Vol.11 No.2

This paper presents the influence of different inlet conditions on the performance of micromixer. On the purpose of obtaining the internal flow fields and mixing characteristics, there are 28 micromixers with different structural parameters have been studied by numerical simulations. The influence of different inlet conditions on the mixing performance of micromixers with periodic triangle baffles and rectangle baffles was examined by experiments. The results of experiment and numerical simulation were completely discussed and analyzed. The consistency between results of experiment and numerical simulation proves the reliability of research method and the accuracy of numerical simulation. It also indicates that different numbers of inlets have significant effects on the mixing performance of micromixers. The optimum inclination angles of inlets for each kind of micromixer were obtained under different conditions. For optimizing or designing passive micromixers, it is an effective way to improve the performance of micromixers by increasing the number of inlets or changing the angle of the inlets.

A new integrative evaluation method for candidate reservoirs of hydrocarbon gas drive

Wei Hu,Zhe Wang,Jingchen Ding,Zhilin Wang,Quanzheng Ma,Yu Gao 한국자원공학회 2015 Geosystem engineering Vol.18 No.1

Before implementing hydrocarbon gas drive, an applicable evaluation of reservoirs for hydrocarbon gas drive can improve the success rate and economic benefit. On the basis of a large amount of literature research, 11 factors affecting the hydrocarbon gas injection development have been screened out. These 11 factors constitute the suitability evaluation indexes of candidate reservoirs for hydrocarbon gas drive. Meantime, the classification of 11 evaluation indexes has also been set up, and fuzzy statistical method, analytic hierarchy process, and expert assessment method have been adopted to obtain the weight value of each evaluation index. Three candidate reservoirs have been taken for example; using multi-level fuzzy comprehensive evaluation to optimize the most suitable candidate reservoir, the potential size of three candidate reservoirs for hydrocarbon gas drive is provided. By comparing the evaluation results with the numerical reservoir simulation results, the evaluation method not only gives a correct evaluation for candidate reservoirs but also has a high practicability and reliability.

Structural evaluation of an existing steel natatorium by FEM and dynamic measurement

Wei Liu,Wei-Cheng Gao,Yi Sun,Yan-Lei Yu 국제구조공학회 2009 Structural Engineering and Mechanics, An Int'l Jou Vol.31 No.5

Based on numerical and experimental methods, a systematic structural evaluation of a steel natatorium in service was carried out in detail in this paper. Planning of inspection tasks was proposed firstly according to some national codes in China in order to obtain the economic and reliable results. The field visual inspections and static computation were conducted in turn under in-service environmental conditions. Further a three-dimensional finite element model was developed according to its factual geometry properties obtained from the field inspection. An analytical modal analysis was performed to provide the analytical modal properties. The field vibration tests on the natatorium were conducted and then two different system identification methods were used to obtain the dynamic characteristics of the natatorium. A good correlation was achieved in results obtained from the two system identification methods and the finite element method (FEM). The numerical and experimental results demonstrated that the main structure of the natatorium in its present status is safe and it still satisfies the demand of the national codes in China. But the roof system such as purlines and skeletons must be removed and rebuilt completely. Moreover the system identification results showed that field vibration test is sufficient to identify the reliable dynamic properties of the natatorium. The constructive suggestion on structural evaluation of the natatorium is that periodic assessment work must be maintained to ensure the natatorium’s safety in the future.

Wind velocity simulation of spatial three-dimensional fields based on autoregressive model

Wei-cheng Gao,Yan-lei Yu 한국풍공학회 2008 Wind and Structures, An International Journal (WAS Vol.11 No.3

This paper adopts autoregressive (AR) model to simulate the wind velocity of spatial threedimensional fields in accordance with the time and space dependent characteristics of the 3-D fields. Based on the built MATLAB programming, this paper discusses in detail the issues of the AR model deduced by matrix form in the simulation and proposes the corresponding solving methods: the overrelaxation iteration to solve the large sparse matrix equations produced by large number of degrees of freedom of structures; the improved Gauss formula to calculate the numerical integral equations which integral functions contain oscillating functions; the mixed congruence and central limit theorem of Lindberg-Levy to generate random numbers. This paper also develops a method of ascertaining the rank of the AR model. The numerical examples show that all those methods are stable and reliable, which can be used to simulate the wind velocity of all large span structures in civil engineering.