Btk/JAK3双靶点共价抑制剂的设计、合成及其活性研究

布鲁顿式酪氨酸激酶(Btk)和两面神激酶3(JAK3)均是自身免疫性疾病和血液系统恶性肿瘤的潜力靶标。以4-氯吡咯并嘧啶为原料,经7步反应合成了一系列7H-吡咯并[2,3-d]嘧啶-4-胺衍生物,其结构经¹HNMR、¹³CNMR和MS(ESI)分析证实。体外依次考察了所得化合物分别对Btk和JAK3激酶的活性、以及对部分B淋巴细胞瘤细胞系的抗增殖活性。结果表明,四氢吡咯烷基取代的衍生物NB1~4对Btk(IC₅₀<3 nmol/L)和JAK3(IC₅₀<165 nmol/L)均能有效抑制,其余化合物只对Btk显示抑制效果;而且NB2和NB4对所测试的多种B细胞淋巴瘤细胞系的抗增殖活性均优于阳性对照泛激酶抑制剂依鲁替尼及Btk单靶点抑制剂。其中,对Jeko-1细胞的抑制能力最佳(IC₅₀<3μmol/L),其次是OCI-LYI(IC₅₀<4μmol/L)、SUDHL-6(IC₅₀<6μmol/L)和HBL-1^*(IC₅₀<6.5μmol/L),最差为SUDHL-4细胞(IC₅₀<11μmol/L)。这些发现可为开发B细胞淋巴瘤的多靶点药物提供新的思路。     

斑衣蜡蝉在葡萄上的危害及防治措施

斑衣蜡蝉是一种危害多种林木和果树的重要刺吸性害虫,主要分布于中国、日本、越南、韩国、印度和美国等地。该虫在经济林木中最喜危害葡萄,目前在宁夏地区随着转换寄主,现已扩散到了部分葡萄园,成为贺兰山东麓酿酒葡萄的重要虫害之一。为全面了解其研究进展,本文概述了国内外关于斑衣蜡蝉的寄主植物、形态特征、危害状况、发生规律、生活习性、诱发因素及防治措施等研究现状,以期为防治该虫,寻求进一步研究方向及探讨新的防治途径提供帮助。     

非全日制研究生线上线下混合式教学模式研究 ——以《现代电气控制技术》为例

随着教育信息化技术的发展，线上线下混合式教学模式已成为一种趋势。为了解决非全日制研究生课堂教学召集困难、效果不佳等问题，提出了基于“互联网＋虚拟仿真技术”的线上线下混合式教学模式。本文以控制工程专业学位研究生为例，结合《现代电气控制技术》课程，探讨了线上线下混合式教学实现途径、师生互动方法、项目驱动案例教学法以及电气控制系统虚拟仿真实验平台的构建方法，切实提升非全日制研究生的培养质量。     

Ferroptosis-Related Flavoproteins: Their Function and Stability

Ferroptosis has been described recently as an iron-dependent cell death driven by peroxidation of membrane lipids. It is involved in the pathogenesis of a number of diverse diseases. From the other side, the induction of ferroptosis can be used to kill tumor cells as a novel therapeutic approach. Because of the broad clinical relevance, a comprehensive understanding of the ferroptosis-controlling protein network is necessary. Noteworthy, several proteins from this network are flavoenzymes. This review is an attempt to present the ferroptosis-related flavoproteins in light of their involvement in anti-ferroptotic and pro-ferroptotic roles. When available, the data on the structural stability of mutants and cofactor-free apoenzymes are discussed. The stability of the flavoproteins could be an important component of the cellular death processes.     

Engineering Nanorobots for Tumor-Targeting Drug Delivery: From Dynamic Control to Stimuli-Responsive Strategy

Nanotechnology has been widely applied to the fabrication of drug delivery systems in the past decades. Recently, with the progress made in microfabrication approaches, nanorobots are steadily becoming a promising means for tumor-targeting drug delivery. In general, nanorobots can be divided into two categories: nanomotors and stimuli-responsive nanorobots. Nanomotors are nanoscale systems with the ability to convert surrounding energies into mechanical motion, whereas stimuli-responsive nanorobots are featured with activatable capacity in response to various endogenous and exogenous stimulations. In this minireview, the dynamic control of nanomotors and the rational design of stimuli-responsive nanorobots are overviewed, with particular emphasis on their contribution to tumor-targeting therapy. Moreover, challenges and perspectives associated with the future development of nanorobots are presented.     

In Vivo Simultaneous Analysis of Gene Expression by Dual-Color Luciferases in Caenorhabditis elegans

Both fluorescent and luminescent observation are widely used to examine real-time gene expression patterns in living organisms. Several fluuorescent and luminescent proteins with specific optical properties have been developed and applied for simultaneous, multi-color observation of more than two gene expression profiles. Compared to fluorescent proteins, however, the application of multi-color luminescent imaging in living organisms is still limited. In this study, we introduced two-color luciferases into the soil nematode C. elegans and performed simultaneous analysis of two gene expression profiles. Using a green-emitting luciferase Eluc (emerald luciferase) and red-emitting luciferase SLR (stable luciferase red), the expression patterns of two genes were simultaneously observed in single animals from embryonic to adult stages over its whole life span. In addition, dual gene activities were observed at the single embryo level, with the simultaneous observation of morphological changes. These are the first application of a two-color luciferase system into a whole animal and suggest that precise relationship of expression patterns of multiple genes of interest can be analyzed over the whole life of the animal, dependent on the changes in genetic and/or environmental conditions.     

Form selection of concomitant polymorphs: A case study informed by crystallization kinetics modeling

Molecular mechanisms and process kinetics of crystallizing concomitant polymorphs remain poorly understood. Solvent-mediated phase transformation and concomitant crystallization are difficult to be distinguished in practice, as multiple forms can be detected at the same time. Herein, we developed a population balance model to simulate a concomitant crystallization process of two polymorphs of tolfenamic acid. Our kinetic modeling aims to understand concomitant crystallization and help guide form selection of such a molecular system. Crystallization kinetics of ethanolic solutions were uncovered from induction time measurements, as well as seeded and unseeded crystallization experiments. Experimental and simulation results demonstrate that the stable form I crystallizes concomitantly with the metastable form II. The faster growing form II results in an intermediate decline in the composition of form I in crystallized samples, a characteristic feature of the concomitantly crystallized system. A four-quadrant scheme of attainable polymorph outcome was simulated under various crystallization conditions.     

Warpage control method during surface forming process of plastic film-reinforced flexible decorative veneer

The plastic film of the new plastic film reinforced pliable decorative veneer (PRPDSV) is used as a flexible reinforcement material and an adhesive material. It has good water resistance, impermeability, simple preparation and finishing processes, and no formaldehyde release. However, warpage phenomenon during hot pressing has been a bottleneck problem restricting its industrial development. In order to solve this problem solve, the study proposed a concave, and convex molds method, established an elastic–plastic FEA model of hot pressing processes of the PRPDSV using concave and convex molds with static/general static solution module in the nonlinear ABAQUS, and researched the effect on the performances of the PRPDSV from the parameters of temperature, pressure, and mold curvature radius theoretically and verified experimentally. Analysis results showed that the surface forming temperature had a great effect on warpage control for PRPDSV. The higher the temperature is, the smaller the curvature radius of the corresponding mold will be and the better the warpage will be. The curvature radius of the molds had a significant effect on the warpage control. Under the conditions with the same hot pressing parameters, the smaller the curvature radius is, and the better control on the warpage for the PRPDSV will be.     

AP2M1 Supports TGF-β Signals to Promote Collagen Expression by Inhibiting Caveolin Expression

The extracellular matrix (ECM) is important for normal development and disease states, including inflammation and fibrosis. To understand the complex regulation of ECM, we performed a suppressor screening using Caenorhabditis elegans expressing the mutant ROL-6 collagen protein. One cuticle mutant has a mutation in dpy-23 that encodes the μ2 adaptin (AP2M1) of clathrin-associated protein complex II (AP-2). The subsequent suppressor screening for dpy-23 revealed the lon-2 mutation. LON-2 functions to regulate body size through negative regulation of the tumor growth factor-beta (TGF-β) signaling pathway responsible for ECM production. RNA-seq analysis showed a dominant change in the expression of collagen genes and cuticle components. We noted an increase in the cav-1 gene encoding caveolin-1, which functions in clathrin-independent endocytosis. By knockdown of cav-1, the reduced TGF-β signal was significantly restored in the dpy-23 mutant. In conclusion, the dpy-23 mutation upregulated cav-1 expression in the hypodermis, and increased CAV-1 resulted in a decrease of TβRI. Finally, the reduction of collagen expression including rol-6 by the reduced TGF-β signal influenced the cuticle formation of the dpy-23 mutant. These findings could help us to understand the complex process of ECM regulation in organism development and disease conditions.     

基于Matlab的量子激光雷达稳频通信模拟系统设计

传统通信模拟系统设计较为复杂,导致模拟过程消耗能量较大,不能准确模拟稳频通信质量。因此,提出基于Matlab的量子激光雷达稳频通信模拟系统。由于振荡器是雷达形成初始信号源的基础,通过分析振荡电路与相位噪声,获得相位噪声函数与通信频率存在的关系;为确保通信过程的稳定,将准确性与稳定性作为信号质量的评价指标,并采用锁频环稳频技术计算频率偏移程度,根据PID控制算法控制频率,量子激光雷达稳频通信;利用Matlab确定激光器、探测器等硬件组成结构,通过时序与数字阵列的设置完成模拟系统设计。仿真结果表明所提系统结构简便、性能稳定,能够真实模拟出稳频通信的信号质量。