Dose‐dependent exposure profile and metabolic characterization of notoginsenoside R1 in rat plasma by ultra‐fast liquid chromatography–electrospray ionization–tandem mass spectrometry

Notoginsenoside R₁ (NGR₁), a diagnostic protopanaxatriol‐type (ppt‐type) saponin in Panax notoginseng, possesses potent biological activities including antithrombotic, anti‐inflammatory, neuron protection and improvement of microcirculation, yet its pharmacokinetics and metabolic characterization as an individual compound remain unclear. The aim of this study was to investigate the exposure profile of NGR₁ in rats after oral and intravenous administration and to explore the metabolic characterization of NGR₁. A simple and sensitive ultra‐fast liquid chromatographic–tandem mass spectrometric method was developed and validated for the quantitative determination of NGR₁ and its major metabolites, and for characterization of its metabolic profile in rat plasma. The blood samples were precipitated with methanol, quantified in a negative multiple reaction monitoring mode and analyzed within 6.0 min. Validation parameters (linearity, precision and accuracy, recovery and matrix effect, stability) were within acceptable ranges. After oral administration, NGR₁ exhibited dose‐independent exposure behaviors with t_1/2 over 8.0 h and oral bioavailability of 0.25–0.29%. A total of seven metabolites were characterized, including two pairs of epimers, 20(R)‐notoginsenoside R₂/20(S)‐notoginsenoside R₂ and 20(R)‐ginsenoside Rh₁/20(S)‐ginsenoside Rh₁, with the 20(R) form of saponins identified for the first time in rat plasma. Five deglycometabolites were quantitatively determined, among which 20(S)‐notoginsenoside R₂, ginsenoside Rg₁, ginsenoside F₁ and protopanaxatriol displayed relatively high exploration, which may partly explain the pharmacodynamic diversity of ginsenosides after oral dose.     

Electrical Impedance Spectroscopic Study of CNT/Ethylene-alt-CO/Propylene-alt-CO Polyketones Nanocomposite

Impedance spectroscopy was utilized to investigate the dielectric properties, ac conductivity and charge transport mechanisms in propylene-alt-CO/ethylene-alt-CO (EPEC) random terpolymer filled with multi-walled carbon nanotubes (MWCNT) as a function of nanofiller content, frequency, and temperature. Equivalent resistor-capacitor (RC) circuit models were proposed to describe the impedance characteristics of the unfilled terpolymer and the nanocomposite at different temperatures. For the nanocomposites, the ac conductivity tended to be frequency independent at low frequencies. At high frequencies, the ac conductivity increased with frequency. The dc conductivity (i.e., plateau of the ac conductivity at low frequencies) at room temperature increased from 10^?9 (Ω·m)^?1 for the unfilled polymer to l0^?3 (Ω·m)^?1 for the 6 wt% MWCNT/EPEC nanocomposite. At low temperatures, the equivalent RC model for EPEC-0 and EPEC-2 was found to consist of a parallel RC circuit. However, for 6 wt% MWCNT/EPEC nanocomposite, an RC model consisting of an R/constant phase element (CPE) circuit and a resistor in series was required to describe the impedance behavior of the nanocomposite.     

Modeling and character analyzing of multiple fractional-order memcapacitors in parallel connection

Recently,the memory elements-based circuits have been addressed frequently in the nonlinear circuit theory due to their unique behaviors.Thus,the modeling and characterizing of the mem-elements become essential.In this paper,the analysis of the multiple fractional-order voltage-controlled memcapacitors model in parallel connection is studied.Firstly,two fractional-order memcapacitors are connected in parallel,the equivalent model is derived,and the characteristic of the equivalent memcapacitor is analyzed in positive or negative connection.Then a new understanding manner according to different rate factor K and fractional orderαis derived to explain the equivalent modeling structure conveniently.Additionally,the negative order appears,which is a consequence of the combination of memcapacitors in different directions.Meanwhile,the equivalent parallel memcapacitance has been drawn to determine that multiple fractional-order memcapacitors could be calculated as one composite memcapacitor.Thus,an arbitrary fractional-order equivalent memcapacitor could be constructed by multiple fractional-order memcapacitors.     

Simultaneous quantitation of rosuvastatin and ezetimibe in human plasma by LC–MS/MS: Pharmacokinetic study of fixed‐dose formulation and separate tablets

A simple, high‐throughput and highly sensitive liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) method has been developed for the simultaneous estimation of rosuvastatin and free ezetimibe. Liquid–liquid extraction was carried out using methyl‐tert butyl ether after prior acidification from 300 μL human plasma. The recovery for both the analytes and their deuterated internal standards (ISs) ranged from 95.7 to 99.8%. Rosuvastatin and ezetimibe were separated on Symmetry C₁₈ column using acetonitrile and ammonium formate buffer, pH 3.5 (30:70, v/v) as the mobile phase. The analytes were well resolved with a resolution factor of 3.8. Detection and quantitation were performed under multiple reaction monitoring using ESI(+) for rosuvastatin (m/z 482.0 → 258.1) and ESI(−) for ezetimibe (m/z 407.9 → 271.1). A linear response function was established in the concentration ranges of 0.05–50.0 ng/mL and 0.01–10.0 ng/mL for rosuvastatin and ezetimibe, respectively, with correlation coefficient, r² ≥ 0.9991. The IS‐normalized matrix factors for the analytes ranged from 0.963 to 1.023. The developed method was successfully used to compare the pharmacokinetics of a fixed‐dose combination tablet of rosuvastatin‐ezetimibe and co‐administered rosuvastatin and ezetimibe as separate tablets to 24 healthy subjects. The reliability of the assay was also assessed by reanalysis of 115 subject samples.     

210Pb in magnesium dietary supplements

The idea behind this study was to investigate the most popular magnesium dietary supplements as a potential additional source of ²¹⁰Pb in the human diet. The paper presents the results of ²¹⁰Pb activities determined in different magnesium supplements, as well as an estimation of the annual effective radiation doses from ²¹⁰Pb decay. The results showed that the highest value of ²¹⁰Pb activity was found in a magnesium supplement of natural origin (dolomite) with a value of 2.97?±?0.18 mBq g^–1. The highest annual radiation dose from ²¹⁰Pb obtained from the magnesium daily recommended value (0.4 g of pure Mg) was calculated for dolomite tablets as 3.71?±?0.02 µSv·year^–1.     

Radiation shielding effectiveness with correlated uncertainties

The space radiation environment is composed of energetic particles which can deliver harmful doses of radiation that may lead to acute radiation sickness, cancer, and even death for insufficiently shielded crew members. Spacecraft shielding must provide structural integrity and minimize the risk associated with radiation exposure. The risk of radiation exposure induced death (REID) is a measure of the risk of dying from cancer induced by radiation exposure. Uncertainties in the risk projection model, quality factor, and spectral fluence are folded into the calculation of the REID by sampling from probability distribution functions. Consequently, determining optimal shielding materials that reduce the REID in a statistically significant manner has been found to be difficult. In this work, the difference of the REID distributions for different materials is used to study the effect of composition on shielding effectiveness. It is shown that the use of correlated uncertainties allows for the determination of statistically significant differences between materials despite the large uncertainties in the quality factor. This is in contrast to previous methods where uncertainties have been generally treated as uncorrelated. It is concluded that the use of correlated quality factor uncertainties greatly reduces the uncertainty in the assessment of shielding effectiveness for the mitigation of radiation exposure.     

带凹性生产成本运输问题的新随机规划模型及其求解

提出了一种新的能反映决策者满意度的随机变量序关系,并据此研究了随机不等式的确定性等价类,方法被称为满意度方法.最后将其应用于带凹性生产成本运输问题的求解中,并将方法与常用的机会约束方法进行比较,说明满意度法不仅合理可行,而且当决策者对约束条件的要求越高时,它所得最优值越优于机会约束法所得最优值.     

重度子痫前期产妇剖宫产布比卡因蛛网膜下腔阻滞麻醉适合剂量的临床研究

目的 探讨重度子痫前期产妇剖宫产重比重布比卡因蛛网膜下腔阻滞麻醉（腰麻）的适合剂量。方法 选取200例重度子痫前期产妇,ASAⅠ级或Ⅱ级,按随机数字表法分为4组,每组各50 例,相应各组鞘内注入布比卡因剂量分别为10、8、6 及4mg,并混合2.5μg 舒芬太尼。选择L3~4行腰硬联合穿刺,注药10min 后记录麻醉平面。根据结果进行Probit 回归分析,计算布比卡因腰麻的ED50和ED95。观察各组利多卡因及去氧肾上腺素的用量、肌松效果及患者麻醉满意度,观察各组术中并发症以及新生儿的Apgar 评分和脐动脉pH。结果 重度子痫前期患者腰麻剖宫产布比卡因ED50 和ED95分别为：6.51（95%CI：5.81～7.01）和8.68（95%CI：7.96～10.26）。4 组患者10min 后麻醉平面的差异均有统计学意义（均P＜0.05）。4mg 组利多卡因用量高于其他3组,差异有统计学意义（P＜0.05）。8mg 组、10mg 组去氧肾上腺素的用量高于其他两组,差异均有统计学意义（均P＜0.05）。低血压的发生率8mg 组、10mg 组高于其他两组,差异均有统计学意义（均P＜0.05）。４ 组间其他不良反应恶心、呕吐、寒战以及心动过缓发生率的差异无统计学意义（P＞0.05）。4 组胎儿娩出后1、5min Apgar 评分及脐动脉血气分析的结果差异均无统计学意义（均P＞0.05）。结论 重度子痫前期产妇剖宫产鞘内注入6mg 布比卡因混合2.5μg舒芬太尼,必要时辅以硬膜外麻醉,麻醉效果确切,血流动力学稳定,适合该类患者手术麻醉。     

An Efficient One-Pot Synthesis of Nitriles from Carboxylic Acids Without Solvent Under Microwave Irradiation

Nitriles were prepared from alkyl and aryl carboxylic acids in dry media conditions, under microwave irradiation. Heating of the carboxylic acid, urea and amidosulfonic acid adsorbed on alumina support in a microwave oven affords nitriles in 20–93% yields.     

Resonant equations with the Neumann p-Laplacian plus an indefinite potential

We consider a nonlinear Neumann problem driven by the p  -Laplacian plus an indefinite potential and a Carathéodory reaction which at ±∞ is resonant with respect to any nonprincipal variational eigenvalue of the differential operator. Using critical point theory and Morse theory (critical groups), we show that the problem has at least three nontrivial smooth solutions, two of which have constant sign. In the process we prove some results of independent interest concerning the unique continuation property of eigenfunctions and the critical groups at infinity of a C¹$C^1$-functionals.