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。     

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。     

Structural dependence of microwave dielectric properties in ilmenite-type Mg(Ti1-xNbx)O3 solid solutions by Rietveld refinement and Raman spectra

Mg(Ti_1-xNb_x)O₃ (x = 0–0.09) ceramics were prepared by the conventional solid-state reaction method. The phase composition, sintering characteristics, microstructure and dielectric properties of Ti⁴⁺ replacement by Nb⁵⁺ in the formed solid solution Mg(Ti_1-xNb_x)O₃ (x = 0–0.09) ceramics were systematically studied. The structural variations and influence of Nb⁵⁺ doping in Mg(Ti_1-xNb_x)O₃ were also systematically investigated by X-ray diffraction and Raman spectroscopy, respectively. X-ray diffraction and its Rietveld refinement results confirmed that Mg(Ti_1-xNb_x)O₃ (x = 0–0.09) ceramics crystallised into an ilmenite-type with R-3 (148) space group. The replacement of the low valence Ti⁴⁺ by the high valence Nb⁵⁺ can improve the dielectric properties of Mg(Ti_1-xNb_x)O₃ (x = 0–0.09). This paper also studied the different sintering temperatures for Mg(Ti_1-xNb_x)O₃ (x = 0–0.09) ceramics. The obtained results proved that 1350 °C is the best sintering temperature. The permittivity and Q × f initially increased and then decreased mainly due to the effects of porosity caused by the sintering temperature and the doping amount of Nb₂O₅, respectively. Furthermore, the increased Q × f is correlated to the increase in Ti–O bond strength as confirmed by Raman spectroscopy, and the electrons generated by the oxygen vacancies will be compensated by Nb⁵⁺ to a certain extent to suppress Ti⁴⁺ to Ti³⁺, which was confirmed by XPS. The increase in τ_f from ?47 ppm/°C to ?40.1 ppm/°C is due to the increment in cell polarisability. Another reason for the increased τ_f is the reduction in the distortion degree of the [TiO₆] octahedral, which was also confirmed by Raman spectroscopy. Mg(Ti_0.95Nb_0.05)O₃ ceramics sintered at 1350 °C for 2 h possessed excellent microwave dielectric properties of ε_r = 18.12, Q × f = 163618 GHz and τ_f = ?40.1 ppm/°C.     

ZIF衍生氧还原反应催化剂的研究进展

从沸石咪唑酯骨架材料(ZIF)衍生的含过渡金属催化剂出发,介绍ZIF衍生催化剂前驱体的制备和热解温度、气氛对催化剂的影响,总结ZIF衍生的铂和非贵金属催化剂材料用于氧还原反应(ORR)的研究进展.提出有关ZIF衍生ORR催化剂发展面临的实际应用挑战和活性位点探究问题.     

Dual-phase rare-earth-zirconate high-entropy ceramics with glass-like thermal conductivity

A series of rare earth zirconates (RE₂Zr₂O₇) high-entropy ceramics with single- and dual-phase structure were prepared. Compared with La₂Zr₂O₇ and Yb₂Zr₂O₇, the smaller “rattling” ions (Yb³⁺, Er³⁺, Y³⁺) have been incorporated into pyrochlore lattice in (La_0.2Nd_0.2Y_0.2Er_0.2Yb_0.2)₂Zr₂O₇ (LNYEY) while larger ions (La³⁺, Nd³⁺, Sm³⁺, Eu³⁺) incorporated into fluorite lattice in (La_0.2Nd_0.2Sm_0.2Gd_0.2Yb_0.2)₂Zr₂O₇ (LNSGY). Due to high-entropy lattice distortion and resonant scattering derived from smaller ions Yb³⁺, Er³⁺, and Y³⁺, LNYEY shows a lower glass-like thermal conductivity (1.62-1.59 W m^-1 K^-1, 100-600℃) than LNSGY (1.74-1.75 W m^-1 K^-1, 100-600℃). Moreover, LNYEY and LNSGY exhibit enhanced Vickers’ hardness (LNYEY, H_v = 11.47 ± 0.41 GPa; LNSGY, H_v = 10.96 ± 0.26 GPa) and thermal expansion coefficients (LNYEY, 10.45 × 10^-6 K^-1, 1000℃; LNSGY, 11.02 × 10^-6 K^-1, 1000℃). These results indicate that dual-phase rare-earth-zirconate high-entropy ceramics could be desirable for thermal barrier coatings.     

Nanovaccine-Mediated Cell Selective Delivery of Neoantigens Potentiating Adoptive Dendritic Cell Transfer for Personalized Immunization

Neoantigen vaccines and adoptive dendritic cell (DC) transfer are major clinical approaches to initiate personalized immunity in cancer patients. However, the immunization efficacy is largely limited by the in vivo trajectory including neoantigens’ access to resident DCs and DCs’ access to lymph nodes (LNs). Herein, an innovative strategy is proposed to improve personalized immunization through neoantigen-loaded nanovaccines synergized with adoptive DC transfer. It is found that it enables selective delivery of neoantigens to resident DCs and macrophages by coating cancer cell membranes onto neoantigen-loaded nanoparticles. In addition, the nanovaccines promote the secretion of chemokine C-C motif ligand 2 (CCL2), CCL3, and C-X-C motif ligand 10 from macrophages, thus potentiating the access of transferred DCs to LNs. This immunization strategy enables coordinated delivery of identified neoantigens and autologous tumor lysate-derived undefined antigens, leading to initiation of antitumor T cell immunity in a personalized manner. It significantly inhibits tumor growth in prophylactic and established mouse tumor models. The findings provide a new vision for potentiating adoptive cell transfer by nanovaccines, which may open the door to a transformative possibility for improving personalized immunization.     

Preparation and antifouling performance of thin inorganic ultrafiltration membrane via assisted sol-gel method with different composition of dual additives

A novel TiO₂ thin film was prepared on the ceramic hollow fiber by the sol-gel method using poly(vinylpyrrolidone) (PVP) and polyvinyl alcohol (PVA) as additives. SEM images verified the formation of TiO₂ layer with various thickness using different composition of titania sols. The effect of the PVP and PVA contents on the TiO₂ sol properties, the separation and the antifouling performance of the ultrafiltration membranes were investigated thoroughly. When the contents of PVP and PVA were 1.0 wt% and 0.8 wt%, respectively, the resultant membrane showed a thickness of 0.55 μm with a pure water flux of 255 L m^?2 h^?1. In addition, the adherent foulant bovine serum albumin was applied to evaluate the antifouling performance. During the three fouling-recovery cycles, the flux recovery ratio and the flux decay ratio maintained about 99% and 30%. The BSA flux and rejection were still 169 L m^?2 h^?1 and 96.9% after the cycles, indicating a superior antifouling property.     

多孔SiO2分子巢制备多功能涤纶纤维试验研究

针对传统PET材料不具备抗菌、不耐洗等问题,以煎煮法为基础,以草珊瑚、艾叶和薄荷为原料,制备含植物活性成分的溶液,其具有抗菌、杀菌的作用;以溶胶-凝胶法为多孔材料制备方法,用十六烷基三甲基溴化铵、十二烷基苯磺酸钠表面活性剂为模板剂,正硅酸乙酯为有机硅源,氨水为催化剂,乙醇和乙醚为助溶剂,在水-乙醇-乙醚体系中合成多孔二氧化硅微球;然后,多孔二氧化硅微球与提取液混合制备含植物活性成分的多孔二氧化硅分子巢;最后以制备的多孔二氧化硅分子巢与普通的聚酯切片用熔融纺丝工艺进行造粒、纺丝,得到具有抗菌、杀菌和耐洗的多功能涤纶纤维.通过SEM微观观察和力学性能测试、抗菌试验、耐洗性测试,对上述制备的多功能涤纶纤维性能进行验证.结果表明:在模板剂总浓度为0.029 mol·L-1、V醇:V醚=20:20、两种表面活性剂比为4:1时,得到的多孔SiO2微球排列规整;当多孔二氧化硅分子巢掺量(质量分数)在0.5％～1％时,通过熔融共混纺丝得到的新型多功能涤纶纤维力学性能表现最优;当多孔二氧化硅分子巢掺量(质量分数)在1％时,得到的新型多功能涤纶纤维的抗菌性能达到87.9％.而二氧化硅分子巢掺量越高,纤维材料越耐洗.以上结果说明本试验制备涤纶纤维的方案可行.     

基于双时间点检测的毫米波雷达人流量监测方法

针对现有基于视频监控的人流量统计方案成本高、算法复杂且不利于个人隐私保护的局限性，利用毫米波雷达体积小、成本低、分辨率高的特点，提出了一种基于双时间点检测的人流量监测方法。该方法先获取人体目标散射点位置和多普勒频移信息来构成点云数据，然后根据多普勒频移正负来判断人体的运动方向，并筛选具有高多普勒频移值的点云数据以降低干扰点对聚类结果的影响；在双时间点对特定区域内人员数量进行统计，并根据双时间点之间所获取的点云数据聚类结果对所统计人员数据进行修正。实验结果表明，该方法能够用匿名的方式以较高的正确率统计人员进出。     

Mechanism in chlorine-enhanced Pd catalyst for H2O2 in situ synthesis in electro-Fenton system

Palladium-based catalysts have been widely employed in the electro-Fenton process for in situ generation of H₂O₂. However, the process is still far from being practical on a large scale. In this work, a series of Cl_xFePd/γ-Al₂O₃/Al catalysts were prepared by a three-step-impregnation method. They exhibited excellent activity in H₂O₂ in situ synthesis and high efficiency in phenol degradation. The characterization results showed that Cl could assist in increasing the content of Pd⁰ and reducing the isoelectric point of catalysts, which led to the drastic promotion in the synthesis of H₂O₂. Theoretical calculations further demonstrated that Cl doping could facilitate the main reaction in H₂O₂ synthesis, as well as inhibit side reactions such as dissociation of the O O bond. Furthermore, kinetic models were proposed and fitted. A plausible reaction mechanism as well as degradation pathways were elaborated based on electron spin resonance and gas chromatography–mass spectrometry results. These findings illustrate the value of palladium-based Cl_xFePd/γ-Al₂O₃/Al catalysts for their application in the electro-Fenton process.