Repurposing of antitumor drug candidate Quisinostat lead to novel spirocyclic antimalarial agents

Antimalarial chemotherapies endowed with effectiveness against drug-resistant parasites and good safety are urgently required in clinical.Our previous research revealed that clinical phase II antitumor drug Quisinostat was a promising antimalarial prototype by inhibiting the activity of Plasmodium falciparum(P.falciparum) histone deacetylase(PfHDAC).Herein,30 novel spirocyclic linker derivatives were designed and synthesized based on Quisinostat as lead compound,and then their antimalarial activities and cytotoxicity were systematically evaluated.Among them,compounds 8 and 27 could effectively eliminate wild-type and multi-drug resistant P.falciparum parasites,and display weakened cytotoxicity and good metabolic stability.Western blot assay demonstrated that they could inhibit PfHDAC activity like Quisinostat.In addition,both 8 and 27 showed certain antimalarial efficacy in rodent malaria model,and the animal toxicity of 8 was significantly improved compared with Quisinostat.Overall,8 and 27 were structurally novel PfHDAC inhibitors and provided prospective prototype for further antimalarial drug research.     

基于多层结构设计的高储能密度氧化石墨烯/聚酰亚胺复合材料

采用逐层涂布、 分层控制固化程度的方法, 利用聚酰胺酸(PAA, 聚酰亚胺前体)溶液和含有氧化石墨烯（GO）的PAA溶液制备了一系列由高绝缘性PI层与GO@PI介电层交替组合而成的界面清晰且紧密衔接的多层复合薄膜. 通过调控介电层中GO含量及分层结构, 使多层复合薄膜兼具高介电常数和高击穿强度特征. 结果表明, 三层复合薄膜PI/1.0GO@PI/PI的击穿强度为261.5 kV/mm, 储能密度达到1.27 J/cm³, 与相同介电层厚度的单层薄膜相比, 击穿强度和储能密度分别提高了97%和144%, 同时, 其介电损耗也保持在较低水平(tanδ=0.0079). 绝缘层和高介电常数层的协同作用提升了氧化石墨烯/聚酰亚胺复合薄膜的储能密度. 这种简单的多层结构设计有利于氧化石墨烯/聚合物复合材料在介质储能领域的应用.     

一次化学实验操作竞赛的设计、组织和体会

最近,我校进行了自建校以来首次高中化学实验操作竞赛。中学化学教学大纲要求加强演示实验和学生实验,以使学生能更好地理解知识、发展智力和培养能力。     

非饱和土壤水流问题的广义差分法及其数值模拟

本文利用广义差分法建立了一维非饱和水流问题的守恒形式的数值模型,讨论了半离散广义差分解和全离散广义差分解的存在唯一性,并给出了其误差估计．数值结果表明,该格式具有计算量小和稳定性等特点,且对求解非饱和水流问题有较好的适应性．     

稳定高质量光参量啁啾脉冲放大系统优化设计

要实现光参量啁啾脉冲放大（OPCPA）系统稳定、高质量输出,需要同时对光参量放大和泵浦光倍频这两个非线性过程进行优化设计。在光参量放大系统优化设计中,建立了描述光参量放大过程的多种简化物理模型;通过模拟泵浦光和信号光口径匹配关系,分析了放大信号光空间两维对称性并提出了优化方法;建立了非线性晶体最佳长度确定及调谐方法,以实现信号光输出高稳定性。在泵浦光倍频系统优化设计过程中,提出应用位相失配法实现稳定倍频输出,研究表明这种方法不仅能实现倍频光能量起伏抖动远远小于基频光能量的起伏抖动,而且能减小泵浦光近场调制度和时间波形调制,极大地改善输出倍频光光束质量,进而提高OPCPA系统输出信号光质量。     

A reduced finite element formulation based on POD method for two-dimensional solute transport problems

A proper orthogonal decomposition (POD) method is applied to a usual finite element (FE) formulation for two-dimensional solute transport problems with real practical applied background such that it is reduced into a reduced FE formulation with lower dimensions and high enough accuracy. The error estimates between the reduced POD FE solutions and the usual FE solutions are provided. It is shown by numerical examples that the results of numerical computation are consistent with theoretical conclusions. Moreover, it is also shown that this validates the feasibility and efficiency of POD FE method.     

A REDUCED FE FORMULATION BASED ON POD METHOD FOR HYPERBOLIC EQUATIONS

A proper orthogonal decomposition(POD) method was successfully used in the reduced-order modeling of complex systems.In this paper,we extend the applications of POD method,namely,apply POD method to a classical finite element(FE) formulation for second-order hyperbolic equations with real practical applied background,establish a reduced FE formulation with lower dimensions and high enough accuracy,and provide the error estimates between the reduced FE solutions and the classical FE solutions and the implementation of algorithm for solving reduced FE formulation so as to provide scientific theoretic basis for service applications.Some numerical examples illustrate the fact that the results of numerical computation are consistent with theoretical conclusions.Moreover,it is shown that the reduced FE formulation based on POD method is feasible and efficient for solving FE formulation for second-order hyperbolic equations.     

Construction of a hierarchical architecture in a wormhole-like mesostructure for enhanced mass transport

A unique hierarchical architecture is successfully constructed in a wormhole-like mesopore structure via a multiple nanocasting route. This novel type of hierarchical porous carbon (HPC) consists of three-dimensional ordered macropores (ca. 150 nm) with interconnecting pore windows, and the walls of these macropores are rich in wormhole-like mesopores (ca. 2.7 nm) and large spherical mesopores (ca. 10 nm), as well as a significant microporosity, presenting a macro-meso-microporous structure with a three-dimensional interconnectivity. Such a hierarchically porous structure may provide fine diffusion pathways for reaction species, which is demonstrated by the experimental result of an enhanced performance in a supercapacitor. For example, with the introduction of a hierarchical porous structure for fast transport and effective access of ions, the as-prepared HPC exhibits a specific capacitance as high as 247 F g(-1), whereas traditional wormhole-like mesoporous carbon has only a specific capacitance of 176 F g(-1).     

Altering alkyl-chains branching positions for boosting the performance of small-molecule acceptors for highly efficient nonfullerene organic solar cells

The emergence of the latest generation of small-molecule acceptor(SMA) materials,with Y6 as a typical example,accounts for the surge in device performance for organic solar cells(OSCs).This study proposes two new acceptors named Y6-C2 and Y6-C3,from judicious alteration of alkyl-chains branching positions away from the Y6 backbone.Compared to the Y6,the Y6-C2 exhibits similar optical and electrochemical properties,but better molecular packing and enhanced crystallinity.In contrast,the Y6-C3 shows a significant blue-shift absorption in the solid state relative to the Y6 and Y6-C2.The as-cast PM6:Y6-C2-based OSC yields a higher power conversion efficiency(PCE) of 15.89% than those based on the Y6(15.24%) and Y6-C3(13.76%),representing the highest known value for as-cast nonfullerene OSCs.Prominently,the Y6-C2 displays a good compatibility with the PC_(71)BM.Therefore,a ternary OSC device based on PM6:Y6-C2:PC_(71)BM(1.0:1.0:0.2) was produced,and it exhibits an outstanding PCE of 17.06% and an impressive fill factor(FF) of 0.772.Our results improve understanding of the structureproperty relationship for state-of-the-art SMAs and demonstrate that modulating the structure of SMAs via fine-tuning of alkylchains branching positions is an effective method to enhance their performance.     

二维水滑石纳米片对氧化铝/聚酰亚胺复合薄膜耐电晕性能的影响

将二维层状材料水滑石剥离为二维纳米片分散液,向其中加入纳米氧化铝,并进行聚酰亚胺(PI)的原位聚合,构筑PI/水滑石纳米片/氧化铝纳米粒子三元复合薄膜。 结果表明,在PI薄膜中同时加入质量分数为10%氧化铝和2%水滑石纳米片,比仅加入质量分数为10%氧化铝时的耐电晕时间(180 min)提高了12倍,拉伸强度提高了37.8%。 聚合物中同时加入纳米片、纳米粒子两种不同形貌填料,能够同时提升复合材料的耐电晕性能和机械性能。