Unconditional Positivity-Preserving and Energy Stable Schemes for a Reduced Poisson-Nernst-Planck System

The Poisson-Nernst-Planck (PNP) system is a widely accepted model for simulation of ionic channels. In this paper, we design, analyze, and numerically validate a second order unconditional positivity-preserving scheme for solving a reduced PNP system, which can well approximate the three dimensional ion channel problem. Positivity of numerical solutions is proven to hold true independent of the size of time steps and the choice of the Poisson solver. The scheme is easy to implement without resorting to any iteration method. Several numerical examples further confirm the positivity-preserving property, and demonstrate the accuracy, efficiency, and robustness of the proposed scheme, as well as the fast approach to steady states.     

预防性静滴钾离子、镁离子对急性心梗后并发室性心律失常的预防作用

目的 探究预防性静滴钾离子、镁离子对急性心梗后并发室性心律失常的预防作用。方法 选择2015年1月-2018年1月于西宁市第一人民医院进行治疗的78例急性心肌梗死患者为研究对象，按照随机数字表法将其均分为观察组与对照组，每组各39例患者。对照组患者进行常规急性心梗治疗，观察组患者在对照组基础上加用门冬氨酸钾镁进行治疗，对比两组治疗有效率，对比两组治疗前后血液流变学指标纤维蛋白原（Fib）、凝血酶原时间（PT）、血小板计数（Plt），对比两组治疗期间不良反应发生率及心律失常发生率。结果 治疗后，观察组患者治疗有效率为87.18%，对照组为76.92%，两组对比差异具有统计学意义（P<0.05）。治疗前两组患者Fib、PT以及Plt水平对比差异不具有统计学意义；治疗后，两组患者Plt及Fib水平低于治疗前，PT水平高于治疗前，差异有统计学意义（P<0.05）；治疗后观察组患者Plt及Fib水平低于对照组，PT水平高于对照组（P<0.05）。观察组患者不良反应发生率稍高于对照组，但对比差异不具有统计学意义。观察组心律失常发生率为7.69%，对照组为15.38%，两组对比差异具有统计学意义（P<0.05）。结论 预防性静滴钾离子与镁离子能够显著降低急性心梗患者心律失常发生率，同时有利于提高治疗有效率，改善其血流变指标，且安全性较高。     

基于UPLC-LTQ-Orbitrap-MS分析刺果番荔枝叶的化学成分

目的利用UPLC-LTQ-Orbitrap-MS技术对刺果番荔枝叶的化学成分进行定性分析。方法采用Waters Acquity UPLC HSS T 3色谱柱(2.1 mm×100 mm,1.8μm),流动相为0.1%甲酸水(A)和乙腈(B)梯度洗脱,流速为0.3 mL/min,进样量2μL,在电喷雾正负离子模式下采集数据。经Reaxys数据库检索番荔枝属类化合物信息,通过质谱信息比对各化合物的m/z值、保留时间、质谱特征碎片等,并结合文献数据对鉴定的化合物进行验证。结果根据各化合物的特征裂解规律,从刺果番荔枝叶中共鉴定出45个化合物,包括16个生物碱类,14个番荔枝内酯类,7个黄酮类和8个其他类化合物,其中以番荔枝内酯类和生物碱类成分居多,与文献报道番荔枝内酯与生物碱类化合物是发挥抗癌的主要活性成分一致。结论利用UPLC-LTQ-Orbitrap-MS技术对刺果番荔枝叶中的化学成分进行了快速、准确的定性分析,为刺果番荔枝叶的提取分离与药效物质基础的研究提供依据。     

Carboxylesterase catalyzed 18O-labeling of carboxylic acid and its potential application in LC-MS/MS based quantification of drug metabolites

LC-MS quantification of drug metabolites is sometimes impeded by the availability of internal standards that often requires customized synthesis and/or extensive purification. Although isotopically labeled internal standards are considered ideal for LC-MS/MS based quantification, de novo synthesis using costly isotope-enriched starting materials makes it impractical for early stage of drug discovery. Therefore, quick access to these isotope-enriched compounds without chemical derivatization and purification will greatly facilitate LC-MS/MS based quantification. Herein, we report a novel ¹⁸O-labeling technique using metabolizing enzyme carboxylesterase (CES) and its potential application in metabolites quantification study. Substrates of CES typically undergo a two-step oxygen exchange with H₂¹⁸O in the presence of the enzyme, generating singly- and doubly-¹⁸O-labeled carboxylic acids; however, unexpected hydrolytic behavior was observed for three of the test compounds – indomethacin, piperacillin and clopidogrel. These unusual observations led to the discovery of several novel hydrolytic mechanisms. Finally, when used as internal standard for LC-MS/MS based quantification, these in situ labeled compounds generated accurate quantitation comparable to the conventional standard curve method. The preliminary results suggest that this method has potential to eliminate laborious chemical synthesis of isotope-labeled internal standards for carboxylic acid-containing compounds, and can be developed to facilitate quantitative analysis in early-stage drug discovery.     

硫化氢及一氧化氦气体信号分子在高原高血压发病中的作用

目的 探讨气体信号分子硫化氢（H2S）及一氧化氮（NO）在高原高血压的病理生理意义。方法 平原体检正常者进入海拔5000m高原（1～3）月期间，在高原暴露时间、劳动强度及生活条件相同的施工群体中随机抽样127人。依血压变化将其分为高原高血压（Ⅰ～Ⅲ级）组78人（进一步分为收缩期高原高血压组与舒张期高原高血压组），高原正常血压组49人，采取肘静脉血，采用敏感硫电极法测定其H2S浓度，Griess法测定血清NO含量。结果 高原高血压组、收缩期高原高血压组、舒张期高原高血压组的血清H2S与NO平均含量均显著增加，分别比正常血压组高34．5％，36．9％，31.7％（均P〈0．001）与28．4％，33．1％，39．7％，（均P〈0．05），尤以H2S更为突出；随着血压分级程度的升高H2S与NO血清含量相应增高，也以H2S更显著（R^2=0．918）；H2S与NO、舒张压间均有密切正相关关系及良好的拟和优度、与氧饱和度呈显著的负相关与拟和优度（R^2=0．374，P=0．001）。结论 H2S与NO的代谢失常可能参与了高原高血压发病过程。     

Heterodetic bicyclic decapeptide cyclo (Glu1 -Leu2 -Pro3-Gly4-Ser5-Ile6-Pro7-Ala8) cyclo-(1γ-5β) Phe9-Gly10

Bycyclic peptides are useful model molecules that can mimic the constrained local folding of a great number of natural peptides and proteins, such as ionophoric peptides, enzyme active site, and ligand-receptor active site. The synthesis of the bicyclic title compound with the liquid phase method is described with experimental details. Of particular interest is the heterodetic closure of the second ring. The peptide showed a complexing activity with metal cations like Ba²⁺, Ca²⁺, and Mg²⁺ . The free bicyclic peptide conformation in solution has been studied by means of NMR spectroscopy and a plausible structure model worked out with model building on NMR constraints is proposed.     

A reaction route graph analysis of the electrochemical hydrogen oxidation and evolution reactions

The reaction route (RR) graph approach recently developed by us for complex, non-linear kinetic mechanisms is applied to the hydrogen oxidation and evolution reactions. A corresponding RR graph is constructed and translated into an equivalent electrical circuit network by associating each elementary step with a characteristic resistance for the steady-state case and considering the overall reaction as a power source. It is further shown that the steady-state kinetics of the reaction can be investigated employing the conventional methods of the electrical network theory. Using a set of rate constants for the hydrogen evolution reaction (her) in alkaline solutions from the literature, the dominant RRs are identified and simplified mechanisms and kinetics derived.     

瘦蛋白的分子生物学特性研究进展

瘦蛋白 (leptin)是由肥胖基因编码、脂肪细胞分泌的一种分子量为 16kDa的蛋白质 ,是一种重要的代谢调节信号 ,对人和动物的采食量、能量代谢、繁殖性能等具有重要调节功能 ,对人肥胖病的治疗和改善动物的生产性能、胴体组成等有良好的潜在应用前景 .主要概述了瘦蛋白基因的克隆、转录、表达调控以及瘦蛋白受体与信号转导等分子生物学特性     

脂肪族聚酯与高氯酸锂络合物的结构与导电性

本文通过酯交换反应合成了一系列脂肪族聚丁二酸酯,对他们的结构和性能作了表征。发现聚酯存在多晶现象,其熔点有奇偶性变化规律。探索了由此系列聚酯与高氯酸锂形成的固体电解质的结构和离子导电性。无机盐的加入提高了电解质的玻璃化温度但降低了聚酯的熔点及结晶度。聚酯电解质的晶体类似于聚酯,其无机盐主要溶解于聚酯的无定形区域。聚酯系列电解质的导电率也有偶奇效应,与熔点变化相反;熔点高的电解质导电率低,熔点低的电解质导电率高。电解质的导电率随温度改变而变化,在室温下电解质的导电率可达10~(-6)s/cm。高分子链上侧基的引入将大大降低电解质的导电性。