Metabonomic Profiles Delineate the Effect of Traditional Chinese Medicine Sini Decoction on Myocardial Infarction in Rats

Background: In spite of great advances in target-oriented Western medicine for treating myocardial infarction (MI), it is still a leading cause of death in a worldwide epidemic. In contrast to Western medicine, Traditional Chinese medicine (TCM) uses a holistic and synergistic approach to restore the balance of Yin-Yang of body energy so the body’s normal function can be restored. Sini decoction (SND) is a well-known formula of TCM which has been used to treat MI for many years. However, its holistic activity evaluation and mechanistic understanding are still lacking due to its complex components. Methodology/Principal Findings: A urinary metabonomic method based on nuclear magnetic resonance and ultra highperformance liquid chromatography coupled to mass spectrometry was developed to characterize MI-related metabolic profiles and delineate the effect of SND on MI. With Elastic Net for classification and selection of biomarkers, nineteen potential biomarkers in rat urine were screened out, primarily related to myocardial energy metabolism, including the glycolysis, citrate cycle, amino acid metabolism, purine metabolism and pyrimidine metabolism. With the altered metabolism pathways as possible drug targets, we systematically analyze the therapeutic effect of SND, which demonstrated that SND administration could provide satisfactory effect on MI through partially regulating the perturbed myocardial energy metabolism. Conclusions/Significance: Our results showed that metabonomic approach offers a useful tool to identify MI-relate

Analyzing the Effectiveness of Policy Instruments on New Energy Vehicle Industry using Consistent Fuzzy Preference Relations A case study in China

New energy vehicles (NEVs) have important implications for traffic pollution management and energy consumption. A series of industrial incentive policies have been introduced to promote the development of the NEV industry. However, the actual effects of the policies do not come up to expectations. Aiming to analyze the relationship between the policy instruments and the market acceptance of NEVs, a consistent fuzzy preference relations model is proposed to evaluate the efficiency of policies on the NEV industry. The model introduces an assessment criteria system with three criterions (industry development, technology research and development (R&D), and NEV popularization). The quantitative weights of evaluation criteria are calculated by the fuzzy preference relation. The weights indicate the significance of the factors in the development of NEVs, especially when NEVs have not been widely accepted. With the proposed model, a case study in China shows that the policy of technology R&D is the most crucial for the NEV industry in China. The policy of NEV industry development, on the other hand, is equally important. The results are hoped to give a better understanding of the relationship between government policy instruments and NEV development, the measures for enhancing the policy efficiency of NEV development

Mixture Augmented Lagrange Multiplier Method for Tensor Recovery and Its Applications

The problem of data recovery in multiway arrays (i.e., tensors) arises in many fields such as computer vision, image processing, and traffic data analysis. In this paper, we propose a scalable and fast algorithm for recovering a low-n-rank tensor with an unknown fraction of its entries being arbitrarily corrupted. In the new algorithm, the tensor recovery problem is formulated as a mixture convex multilinear Robust Principal Component Analysis (RPCA) optimization problem by minimizing a sum of the nuclear norm and the ℓ1-norm. The problem is well structured in both the objective function and constraints. We apply augmented Lagrange multiplier method which can make use of the good structure for efficiently solving this problem. In the experiments, the algorithm is compared with the state-of-art algorithm both on synthetic data and real data including traffic data, image data, and video data

Potential Biomarkers in Mouse Myocardium of Doxorubicin-Induced Cardiomyopathy: A Metabonomic Method and Its Application

BACKGROUND: Doxorubicin (DOX) is one of the most potent antitumor agents available; however, its clinical use is limited because of the risk of severe cardiotoxicity. Though numerous studies have ascribed DOX cardiomyopathy to specific cellular pathways, the precise mechanism remains obscure. Sini decoction (SND) is a well-known formula of Traditional Chinese Medicine (TCM) and is considered as efficient agents against DOX-induced cardiomyopathy. However, its action mechanisms are not well known due to its complex components. METHODOLOGY/PRINCIPAL FINDINGS: A tissue-targeted metabonomic method using gas chromatography-mass spectrometry was developed to characterize the metabolic profile of DOX-induced cardiomyopathy in mice. With Elastic Net for classification and selection of biomarkers, twenty-four metabolites corresponding to DOX-induced cardiomyopathy were screened out, primarily involving glycolysis, lipid metabolism, citrate cycle, and some amino acids metabolism. With these altered metabolic pathways as possible drug targets, we systematically analyzed the protective effect of TCM SND, which showed that SND administration could provide satisfactory effect on DOX-induced cardiomyopathy through partially regulating the perturbed metabolic pathways. CONCLUSIONS/SIGNIFICANCE: The results of the present study not only gave rise to a systematic view of the development of DOX-induced cardiomyopathy but also provided the theoretical basis to prevent or modify expected damage

Особенности вазомоторной функции эндотелия у больных стабильной стенокардией с факторами риска (артериальной гипертензией, гиперхолестеринемией, курением)

ВАЗОМОТОРНАЯ СИСТЕМАЭНДОТЕЛИЙ /ФИЗИОЛЭПИТЕЛИЙСТЕНОКАРДИЯКОРОНАРНАЯ БОЛЕЗНЬГРУДНАЯ КЛЕТКА, БОЛИФАКТОРЫ РИСКАГИПЕРТЕНЗИЯКРОВЕНОСНЫХ СОСУДОВ БОЛЕЗНИГИПЕРХОЛЕСТЕРИНЕМИЯГИПЕРЛИПИДЕМИЯКУРЕНИЕ /ВРЕД ВОЗДТАБАКА УПОТРЕБЛЕНИЕ, РАССТРОЙСТВА ЗДОРОВЬ

Molecular Modeling Study of Chiral Separation and Recognition Mechanism of β-Adrenergic Antagonists by Capillary Electrophoresis

Chiral separations of five β-adrenergic antagonists (propranolol, esmolol, atenolol, metoprolol, and bisoprolol) were studied by capillary electrophoresis using six cyclodextrins (CDs) as the chiral selectors. Carboxymethylated-β-cyclodextrin (CM-β-CD) exhibited a higher enantioselectivity power compared to the other tested CDs. The influences of the concentration of CM-β-CD, buffer pH, buffer concentration, temperature, and applied voltage were investigated. The good chiral separation of five β-adrenergic antagonists was achieved using 50 mM Tris buffer at pH 4.0 containing 8 mM CM-β-CD with an applied voltage of 24 kV at 20 °C. In order to understand possible chiral recognition mechanisms of these racemates with CM-β-CD, host-guest binding procedures of CM-β-CD and these racemates were studied using the molecular docking software Autodock. The binding free energy was calculated using the Autodock semi-empirical binding free energy function. The results showed that the phenyl or naphthyl ring inserted in the hydrophobic cavity of CM-β-CD and the side chain was found to point out of the cyclodextrin rim. Hydrogen bonding between CM-β-CD and these racemates played an important role in the process of enantionseparation and a model of the hydrogen bonding interaction positions was constructed. The difference in hydrogen bonding formed with the –OH next to the chiral center of the analytes may help to increase chiral discrimination and gave rise to a bigger separation factor. In addition, the longer side chain in the hydrophobic phenyl ring of the enantiomer was not beneficial for enantioseparation and the chiral selectivity factor was found to correspond to the difference in binding free energy

A Large-Scale Zebrafish Gene Knockout Resource for the Genome-Wide Study of Gene Function

With the completion of the zebrafish genome sequencing project, it becomes possible to analyze the function of zebrafish genes in a systematic way. The first step in such an analysis is to inactivate each protein-coding gene by targeted or random mutation. Here we describe a streamlined pipeline using proviral insertions coupled with high-throughput sequencing and mapping technologies to widely mutagenize genes in the zebrafish genome. We also report the first 6144 mutagenized and archived F1’s predicted to carry up to 3776 mutations in annotated genes. Using in vitro fertilization, we have rescued and characterized ~0.5% of the predicted mutations, showing mutation efficacy and a variety of phenotypes relevant to both developmental processes and human genetic diseases. Mutagenized fish lines are being made freely available to the public through the Zebrafish International Resource Center. These fish lines establish an important milestone for zebrafish genetics research and should greatly facilitate systematic functional studies of the vertebrate genome

A numerical approach for understanding the temporal and spatial correlation scales of sound velocity in long term: a case study for the source and surrounding region of the Kuroshio Current

261-268To accurately understand the temporal and spatial distributions of sound velocity fields and their relevant characteristics, numerically investigated the sound velocity auto-correlation index at the source and adjacent region of the Kuroshio Current using 1911-2001 observation data. Auto-correlation index was fitted using a Gaussian function for the temporal and spatial scales of the investigated regions. The correlation scales in time and spatial domain in spring, summer, fall, and winter were 14.2/145.3, 14.2/135.9, 13.5/133.8, and 13.7/143.3 days/km, respectively. These scales are applied to the reconstructed sound velocity model in terms of empirical orthogonal functions. The error of the sound velocity constructed was minimal (3 m/s) compared with those constructed using other methods (up to 4.3 m/s). This method improves the precision of the sound velocity reconstruction compared with that based on monthly data. The use of temporal and spatial scales enhances the accuracy of sound velocity reconstruction