药物相互作用研究在新药研发和审评决策中的应用

药物相互作用改变了剂量效应关系，可能会降低疗效或增加毒性，是临床应用中合并用药治疗时重要的考虑因素。预测具有临床意义的药物相互作用是药物研发过程中获益风险评估的重要环节。本文概述了药物研发过程中药物相互作用研究的目的和意义，体内和体外研究的主要内容；梳理分析了2020年国家药品监督管理局（National Medical Products Administration, NMPA）和美国食品药品监督管理局（Food and Drug Administration, FDA）批准上市的新药药物相互作用研究情况，旨在为我国药物研发过程中药物相互作用研究及其监管审评提供参考。     

Customization of ZrO2 loose/tight bilayer ultrafiltration membranes by reverse micelles-mediated aqueous sol-gel process for wastewater treatment

Two types of spherical zirconyl oxalate aqueous sols were successfully customized by a reverse micelles-mediated aqueous sol-gel process, and the sols were sequentially spin-coated on porous supports to prepare ZrO₂ loose/tight bilayer ultrafiltration membranes. After three times of spin-coating process, a defect-free ZrO₂ loose ultrafiltration membrane with pure water permeability of 110.5 ± 2.25 L m^?2 h^-1 bar^-1, molecular weight cut-off (MWCO) of 16.5 kDa and excellent rejection of up to 97.5 % for bovine serum albumin was fabricated. Then, the loose ultrafiltration membrane was used as a substrate to prepare ZrO₂ tight ultrafiltration membrane. Performances of tight ultrafiltration membrane regarding to permeability, retention of polyethylene glycol and treatment of dyes wastewater were evaluated. The tight ultrafiltration membrane with a thickness of 200 nm exhibited a pure water permeability of 22.5 ± 0.3 L m^-2 h^-1 bar^-1 and MWCO of 1150 Da. Additionally, the rejections of methyl red and methyl orange by the tight ultrafiltration membrane were both <65 %, while of alizarin red, direct red, bromocresol green and methyl blue achieved maximum values of 98.5 %, 99.2 %, 99.5 % and 99.6 %, respectively. The fouled membranes could restore the virgin performance for reuse by cleaning and low-temperature calcination.     

The surface carboxyl group of carbonaceous microspheres effects on the synthesis and structure of SiOC ceramics

In this study, C/SiOC and C/SiO₂ composites were prepared by using carbonaceous microspheres with different surface functional groups. Carbonaceous microspheres based on hydrothermal reaction of glucose contains hydroxyl group, while the surface carboxyl group increases after NaOH etching. The hydroxyl group increases the oxygen-enriched structural units of SiOC ceramics, and the C spheres are closely enwrapped in SiOC matrix after pyrolysis at 900 °C. However, the interfacial reaction of surface carboxyl with Si–OH results in the formation of cristobalite SiO₂, and C spheres are not only encased inside the SiOC matrix, but also dispersed outside of SiOC ceramics. After removal of C via calcination at 500 °C for 5 h, C/SiOC and C/SiO₂ composites are transformed into amorphous SiO₂ and cristobalite SiO₂, respectively. The thermogravimetric analysis indicates the oxidation resistance of SiOC is superior to that of C and SiO₂.     

BS960E高强钢激光-电弧复合焊接头氢脆行为研究

氢脆具有很强的微观组织敏感性,威胁着各类高强结构材料的安全服役.采用激光-电弧复合焊工艺对BS960E型高强钢进行焊接,并对接头在原位电化学充氢的条件下进行慢应变速率(10-5s-1)拉伸试验,结合微观组织和断裂特征进行分析并对接头的氢脆行为进行研究.结果 表明,焊接热循环所形成的富马氏体中的细晶区可以使接头表现出一定的氢脆敏感性,马氏体较大的氢扩散系数和较低的氢溶解度以及氢在晶界上的快速扩散是引起接头对氢脆敏感的主要原因,通过控制焊接工艺参数可抑制焊接热循环所引起的马氏体转变量,能够降低BS960E型高强钢激光-电弧复合焊接头的氢脆敏感性.     

Effects of Different Short-Term UV-B Radiation Intensities on Metabolic Characteristics of Porphyra haitanensis

The effects of ultraviolet (UV) radiation, particularly UV-B on algae, have become an important issue as human-caused depletion of the protecting ozone layer has been reported. In this study, the effects of different short-term UV-B radiation on the growth, physiology, and metabolism of Porphyra haitanensis were examined. The growth of P. haitanensis decreased, and the bleaching phenomenon occurred in the thalli. The contents of total amino acids, soluble sugar, total protein, and mycosporine-like amino acids (MAAs) increased under different UV-B radiation intensities. The metabolic profiles of P. haitanensis differed between the control and UV-B radiation-treated groups. Most of the differential metabolites in P. haitanensis were significantly upregulated under UV-B exposure. Short-term enhanced UV-B irradiation significantly affected amino acid metabolism, carbohydrate metabolism, glutathione metabolism, and phenylpropane biosynthesis. The contents of phenylalanine, tyrosine, threonine, and serine were increased, suggesting that amino acid metabolism can promote the synthesis of UV-absorbing substances (such as phenols and MAAs) by providing precursor substances. The contents of sucrose, D-glucose-6-phosphate, and beta-D-fructose-6-phosphate were increased, suggesting that carbohydrate metabolism contributes to maintain energy supply for metabolic activity in response to UV-B exposure. Meanwhile, dehydroascorbic acid (DHA) was also significantly upregulated, denoting effective activation of the antioxidant system. To some extent, these results provide metabolic insights into the adaptive response mechanism of P. haitanensis to short-term enhanced UV-B radiation.     

Colossal dielectric response and relaxation behavior in novel system of Zr4+ and Nb5+ co-substituted CaCu3Ti4O12 ceramics

In this work, we developed a novel system of isovalent Zr⁴⁺ and donor Nb⁵⁺ co-doped CaCu₃Ti₄O₁₂ (CCTO) ceramics to enhance dielectric response. The influences of Zr⁴⁺ and Nb⁵⁺ co-substituting on the colossal dielectric response and relaxation behavior of the CCTO ceramics fabricated by a conventional solid-phase synthesis method were investigated methodically. Co-doping of Zr⁴⁺ and Nb⁵⁺ ions leads to a significant reduction in grain size for the CCTO ceramics sintered at 1060 °C for 10 h. XRD and Raman results of the CaCu₃Ti_3.8-xZr_xNb_0.2O₁₂ (CCTZNO) ceramics show a cubic perovskite structure with space group Im-3. The first principle calculation result exhibits a better thermodynamic stability of the CCTO structure co-doped with Zr⁴⁺ and Nb⁵⁺ ions than that of single-doped with Zr⁴⁺ or Nb⁵⁺ ion. Interestingly, the CCTZNO ceramics exhibit greatly improved dielectric constant (~10⁵) at a frequency range of 10²–10⁵ Hz and at a temperature range of 20–210 °C, indicating a giant dielectric response within broader frequency and temperature ranges. The dielectric properties of CCTZNO ceramics were analyzed from the viewpoints of defect-dipole effect and internal barrier layer capacitance (IBLC) model. Accordingly, the immensely enhanced dielectric response is primarily ascribed to the complex defect dipoles associated with oxygen vacancies by co-doping Zr⁴⁺ and Nb⁵⁺ ions into CCTO structure. In addition, the obvious dielectric relaxation behavior has been found in CCTZNO ceramics, and the relaxation process in middle frequency regions is attributed to the grain boundary response confirmed by complex impedance spectroscopy and electric modulus.     

Microstructure and electric properties of Pr-doped Pb(Zr0.52Ti0.48)O3 ceramics

Improving the piezoelectric activity of lead zirconate titanate (PZT) ceramics is of great importance for practical applications. In this study, the influence of Pr³⁺ doping on the ferroelectric phase composition, microstructure, and electric properties on the A-site of (Pb_1-1.5xPr_x)(Zr_0.52Ti_0.48)O₃ is extensively investigated. A dense and fine microstructural sample is obtained with the introduction of Pr³⁺. The results show that the morphotropic phase boundary (MPB) moves to the rhombohedral phase region. The rhombohedral and tetragonal phases exhibit an ideal coexistence in the 4 mol.% Pr³⁺ doped (PPZT4) samples. Lead vacancy and the reduction of the potential energy barrier are considered to be the key mechanisms for donor doping, which is upheld by the Pr³⁺ doping. Combining the I-E hysteresis loops with the P-E hysteresis loops, it becomes apparent that both contribution maximums of the domain switching and residual polarisation are in PPZT4. Moreover, the thermal aging resistance of PZT is improved by doping, and the temperature stability is optimised from 83% in PZT to 96% in PPZT4. Hence, an appropriate amount of Pr³⁺ doping can effectively improve the piezoelectric activity of PZT ceramics in the MPB area and optimise the performance stability of the material under application temperatures.     

两台煤立磨无法同时运行原因分析及解决措施

为了实现万吨生产线产能扩大后的用煤量需求，单台煤立磨产量已无法满足，面对同时运转两台煤立磨出现的问题，逐步进行分析，查找原因，通过将入磨热风管一分为二，解决了风量分配不均、工况波动造成的磨机振动跳停等一系列问题，效果显著。     

Electrodeposition of B,Ni co-doped diamond-like carbon films on AZ91D magnesium alloy: Corrosion and wear resistance

Diamond-like carbon (DLC) possesses brilliant and excellent properties, including excellent corrosion resistance as well as outstanding wear resistance. Ni and B co-doped DLC films were deposited on AZ91D magnesium alloy by electrodeposition under mild conditions (300 V and 25°C). Uniform and dense morphology of co-doped DLC films were observed, and Ni and B were uniformly incorporated into the carbon-based films. Among all the electrodeposits, the appearance of D and G peaks near 1330 and 1570 cm⁻¹ revealed that the as-deposited films were typical DLC films. As the addition of Ni was increased to 0.05 g, the highest microindentation hardness, the lowest friction coefficient, and wear loss were achieved to be 164.5 HV, 0.3, and 0.6 × 10⁻⁵ kg/m, respectively. The amorphous carbon films fabricated at 0.05 g Ni had the lowest corrosion current density and the most positive corrosion potential, which was mainly due to the small and dense granular structure effectively hindering the penetration of corrosion media.     

Nacre-Inspired,Liquid Metal-Based Ultrasensitive Electronic Skin by Spatially Regulated Cracking Strategy

The realization of liquid metal-based wearable systems will be a milestone toward high-performance, integrated electronic skin. However, despite the revolutionary progress achieved in many other components of electronic skin, liquid metal-based flexible sensors still suffer from poor sensitivity due to the insufficient resistance change of liquid metal to deformation. Herein, a nacre-inspired architecture composed of a biphasic pattern (liquid metal with Cr/Cu underlayer) as “bricks” and strain-sensitive Ag film as “mortar” is developed, which breaks the long-standing sensitivity bottleneck of liquid metal-based electronic skin. With 2 orders of magnitude of sensitivity amplification while maintaining wide (>85%) working range, for the first time, liquid metal-based strain sensors rival the state-of-art counterparts. This liquid metal composite features spatially regulated cracking behavior. On the one hand, hard Cr cells locally modulate the strain distribution, which avoids premature cut-through cracks and prolongs the defect propagation in the adjacent Ag film. On the other hand, the separated liquid metal cells prevent unfavorable continuous liquid-metal paths and create crack-free regions during strain. Demonstrated in diverse scenarios, the proposed design concept may spark more applications of ultrasensitive liquid metal-based electronic skins, and reveals a pathway for sensor development via crack engineering.