A snapshot of enzyme catalysis using electrospray ionization mass spectrometry

Insights into the early molecular events involving protein-ligand/substrate interactions such as protein signaling and enzyme catalysis can be obtained by examining these processes on a very short, millisecond time scale. We have used time-resolved electrospray mass spectrometry to delineate the catalytic mechanism of a key enzyme in bacterial lipopolysaccharide biosynthesis, 3-deoxy-d-manno-2-octulosonate-8-phosphate synthase (KDO8PS). Direct real-time monitoring of the catalytic reaction under single enzyme turnover conditions reveals a novel hemiketal phosphate intermediate bound to the enzyme in a noncovalent complex that establishes the reaction pathway. This study illustrates the successful application of mass spectrometry to reveal transient biochemical processes and opens a new time domain that can provide detailed structural information of short-lived protein-ligand complexes.     

Growth of Aligned Carbon Nanotubes on Large Scale by Methane Decomposition with Deactivation Inhibitor

The effects of additives containing iron or nickel during chemical vapor deposition(CVD)on the growth of carbon nanotubes(CNTs)by methane decomposition on Mo/MgO catalyst were investigated. Ferrocene and nickel nitrate were introduced as deactivation inhibitors by in-situ evaporation during CVD. The precisely controlled in-situ introduction of these inhibitors increased the surface renewal of catalyst, and therefore prevented the catalyst from deactivation.Using this method,aligned multi-walled CNTs with parallel mesopores can be produced on a large scale.     

新型N-甲氧基-N-苯基氨基甲酸酯类化合物的合成及生物活性研究

为了寻找高效、低毒的新农药,采用活性结构拼接法合成了含1H-1,2,4-三氮唑基的N-甲氧基-N-{2-[1-取代苯基-2-(1H-1,2,4-三氮唑-1-基)-1-丙酮]}苯基氨基甲酸甲酯化合物10个。所有的化合物都经^1H NMR、红外、LC／MS进行了表征。生测活性表明,部分化合物对小麦赤霉病、稻瘟病、黄瓜灰霉病、小麦白粉病有较好的抑菌活性。     

Metabonomic study of biochemical changes in urinary of type 2 diabetes mellitus patients after the treatment of sulfonylurea antidiabetic drugs based on ultra‐performance liquid chromatography/mass spectrometry

A metabonomic study on biochemical changes in the urine of type 2 diabetes mellitus (T2DM) patients after the treatment of sulfonylurea (SU) antidiabetic drugs was performed. An ultra‐performance liquid chromatography/mass spectrometry (UPLC/MS) method was used to generate metabolic fingerprints for the metabonomic analysis of urinary samples obtained from 20 T2DM patients without any drug treatment and 20 T2DM patients treated with SU antidiabetic drugs and 20 normal glucose tolerance subjects. The resulting data were subjected to chemometric analysis (principal component analysis and partial least squares discriminant analysis) to investigate the effect of SU antidiabetic drugs on urinary metabolite profiles of T2DM patients. Biomarkers such as xanthine, phenylalanine, tryptophan, hippurate, phenylacetylglutamine, carnitine C8:1, carnitine C10:3, uric acid and citrate were found to be responsible for the separation of T2DM and SU‐treated groups, which indicates a potential effect of SU on energy metabolism, Tricarboxylic acid (TCA) cycle, gut microflora metabolism and oxidative stress. The study may be helpful to the understanding of the action of mechanism of SU antidiabetic drugs. Copyright © 2014 John Wiley & Sons, Ltd.     

Efficient Preparation of Photolabile Agent MNI-glu by Regioselective Nitration of 4-Methoxyindoline Derivative

The present work investigates the nitration of 4-methoxy indoline derivative with different reagents and optimized conditions. We now report a simple methodology for nitration employing claycop in the presence of amine, which offers significant improvement with regard to the yield and regioselectivity, and a much more favorable isomeric ratio of products was obtained under mild conditions. Therefore, a useful method for preparation of a photolabile L-glutamate derivative was concurrently established.     

Unravelling the Correlation between the Aspect Ratio of Nanotubular Structures and Their Electrochemical Performance To Achieve High‐Rate and Long‐Life Lithium‐Ion Batteries

The fundamental understanding of the relationship between the nanostructure of an electrode and its electrochemical performance is crucial for achieving high‐performance lithium‐ion batteries (LIBs). In this work, the relationship between the nanotubular aspect ratio and electrochemical performance of LIBs is elucidated for the first time. The stirring hydrothermal method was used to control the aspect ratio of viscous titanate nanotubes, which were used to fabricate additive‐free TiO₂‐based electrode materials. We found that the battery performance at high charging/discharging rates is dramatically boosted when the aspect ratio is increased, due to the optimization of electronic/ionic transport properties within the electrode materials. The proof‐of‐concept LIBs comprising nanotubes with an aspect ratio of 265 can retain more than 86 % of their initial capacity over 6000 cycles at a high rate of 30 C. Such devices with supercapacitor‐like rate performance and battery‐like capacity herald a new paradigm for energy storage systems.     

HF离子交换膜在电渗析器上的性能研究

研究了ＨＦ高性能阴阳离子交换膜在电渗析器上的性能。采用比较苛刻的介质对离子交换膜的性能进行了考验。结果表明在连续运转十五个月后，离子交换膜本身的电化学性能没有明显变化，并且电渗析器的操作性能与初装时相近。     

A pharmaco-metabonomic study on the therapeutic basis and metabolic effects of Epimedium brevicornum Maxim. on hydrocortisone-induced rat using UPLC-MS

This paper describes the pharmaco-metabonomic study on Epimedium brevicornum Maxim. treated rats with a pathologic condition similar to the 'kidney deficiency syndromes' in traditional Chinese medicine and its therapeutic basis. UPLC-MS technique was used for the development of chemical profile of Epimedium brevicornum Maxim. and endogenous metabolite profiles of rats pre- and post-hydrocortisone interfered and treated with this herbal medicine. The comparison among profiles was performed with a statistical technique, principle component analysis (PCA). Significant difference in endogenous metabolite profiles was observed in the intervention rats and the abnormality of metabolism recovered towards the normal level after administration with Epimedium brevicornum Maxim. extract. Four active constituents of Epimedium brevicornum Maxim. were found into the blood circulation of kidney-deficient rats and two of their metabolites in the urine. This work suggests that the metabonomic approach is a potentially powerful tool to explore the therapeutic basis and to clarify the possible action mechanism of traditional Chinese medicine.     

Why does β-secretase zymogen possess catalytic activity? Molecular modeling and molecular dynamics simulation studies

Beta-secretase is a potential target for inhibitory drugs against Alzheimer's disease as it cleaves amyloid precursor protein (APP) to form insoluble amyloid plaques and vascular deposits in the brain. Beta-secretase is matured from its precursor protein, called beta-secretase zymogen, which, different from most of other zymogens, is also partially active in cleaving APP. Hence, it is important to study on the mechanism of the zymogen's activation process. This study was to model the 3-D structure of the zymogen, followed by intensive molecular dynamics (MD) simulations to identify the most probable 3-D model and to study the dynamic structural behavior of the zymogen for understanding the effects of pro-segment on the function of the enzyme. The results revealed that the dropping in catalytic activity of the beta-secretase zymogen could be attributed to the occupation of the entrance of the catalytic site of the zymogen by its pro-segment. On the other hand, the partial catalytic activity of the zymogen could be explained by high fluctuation of the pro-segment in comparison with that of other zymogens, resulting in the occasionally exposure of the catalytic site for access its substrate APP. Indeed, steered MD (SMD) simulation revealed a weak pulling force at quasi-equilibrium state for the pro-segment of the zymogen leaving from the entrance, indicating that this swinging process could take place spontaneously. Furthermore, MM-PBSA calculation revealed a small change of free energy of 10.56 kal/mol between the initial and final states of the process of pro-segment swung outside the binding pocket of beta-secretase zymogen. These results not only account for the partial catalytic activity of beta-secretase zymogen, but also provide useful clues for discovering new potent ligands, as new type of drug leads for curing Alzheimer's disease, to prevent the pro-segment of the zymogen from leaving its catalytic site.     

Coherent microwave rayleigh scattering from resonance-enhanced multiphoton ionization in argon

Multiphoton ionization and electron recombination processes are studied in argon using coherent microwave Rayleigh scattering from a localized, resonance-enhanced multiphoton ionization produced plasma. A time dependent one-dimensional plasma dynamic model is developed to predict the time evolution of the microwave scattering from the plasma. Experimental results of the argon ionization spectrum and electron recombination rates are in good agreement with the model predictions.