The Discovery of Potential MDM2 Inhibitors: A Combination of Pharmacophore Modeling,Virtual Screening,Molecular Docking Studies,and in vitro/in vivo Biological Evaluation

Small-molecule inhibitors of MDM2 that block the MDM2-p53 protein-protein interaction have been considered as potential therapeutic agents for the treatment of cancer. Here, we identify five highly potent inhibitors of MDM2 (termed as WY 1–5) that display significant inhibitory effects on MDM2-p53 interaction by using a combined strategy of pharmacophore modeling, virtual screening, and molecular docking studies. Among them, WY-5 is the most active MDM2 inhibitor with an IC₅₀ value of 14.1±2.8 nM. Moreover, WY-5 significantly up-regulate the protein level of p53 in SK-Hep-1 cells harboring wild-type p53. In vitro anticancer study reveals that WY-5 markedly inhibits the survival of SK-Hep-1 cells. In vivo anticancer study suggests that WY-5 significantly inhibits the growth of SK-Hep-1 cells-derived xenograft in nude mice, with no observable toxicity. Our results demonstrate that WY-5 may be a promising candidate for the treatment of cancer harboring wild-type p53.     

Effect of binder system on the thermophysical properties of 3D-printed zirconia ceramics

Fabrication of 3D-printed ceramic parts with high complexity and high spatial resolution often demands low wall thickness as well as high stiffness at the green state, whereas printing simpler geometries may tolerate thicker, more compliant walls with the advantage of a rapid binder-burn-out and sintering process. In this work, the influence of the binder system on the thermophysical properties of 3D-printed stabilized zirconia ceramics was investigated. Samples were fabricated with the lithography-based ceramic manufacturing (LCM) technology using two different photosensitive ceramic suspensions (LithaCon 3Y230 and LithaCon 3Y210), with the same ZrO₂ powder. A significant difference in stiffness in the green state (~3 MPa vs. ~32 MPa for LithaCon 3Y230 and LithaCon 3Y210, respectively) was measured, associated with a rather loose or a linked network formed in the binder due to photopolymerization. Both materials reached high relative densities, that is, >99%, exhibiting a homogeneous fine-grained microstructure. No significant differences on the coefficient of thermal expansion (11.18 ppm/K vs. 11.17 ppm/K) or Young's modulus (207 GPa vs. 205 GPa) were measured, thus demonstrating the potential of tailoring binder systems to achieve the required accuracy in 3D-printed parts, without detrimental effects on material's microstructure and thermophysical properties at the sintered state.     

Characterization of 3D elastic porous polydimethylsiloxane (PDMS) cell scaffolds fabricated by VARTM and particle leaching

In this study, elastic porous polydimethylsiloxane (PDMS) cell scaffolds were fabricated by vacuum‐assisted resin transfer moulding (VARTM) and particle leaching technologies. To control the porous morphology and porosity, different processing parameters, such as compression load, compression time, and NaCl particle size for preparing NaCl preform, were studied. The porous structures of PDMS cell scaffolds were characterized by scanning electron microscopy (SEM). The properties of PDMS cell scaffolds, including porosity, water absorption, interconnectivity, compression modulus, and compression strength were also investigated. The results showed that after the porogen–NaCl particles had been leached, the remaining pores had the sizes of 150–300, 300–450, and 450–600 μm, which matched the sizes of the NaCl particles. The interconnectivity of PDMS cell scaffolds increases with an increase in the size of NaCl particles. It was also found that the smaller the size of the NaCl particles, the higher the porosity and water absorption of PDMS cell scaffolds. The content of residual NaCl in PDMS/NaCl scaffolds reduces under ultrasonic treatment. In addition, PDMS scaffolds with a pore size of 300–450 μm have better mechanical properties compared to those with pore sizes of 150–300 and 450–600 μm. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 42909.     

Printability of elastomer latex for additive manufacturing or 3D printing

Additive manufacturing, sometimes referred to as 3D printing is a new, rapidly developing technology which has the potential to revolutionize fabrication of certain high value, complex products. Until now conventional elastomers have not been widely used in the additive manufacturing process. The goal of our work was to determine the feasibility of additive manufacturing using ink jet printing of elastomeric latex materials. Particle size, viscosity, and surface tension were measured for five different latex materials—poly(2‐chloro‐1,3‐butadiene), carboxylated styrene‐butadiene rubber, carboxylated butadiene‐acrylonitrile copolymer, natural rubber, and prevulcanized natural rubber. The XSBR latex was predicted as the one most likely to be printable. Printing trials carried out with the XSBR as the ink proved it to be printable, although technical problems of agglomeration and print head clogging need to be addressed and both the material and process need to be optimized for consistent printing to be achieved. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 42931.     

污水管网远程数字化管理系统设计

结合重庆市污水管理处对排水管网进行数字化管理的工程实例,介绍了基于虚拟专用网的污水管网数字化管理系统的设计方案和组成结构。由于管辖的污水管网覆盖面积大、流通里程长,因此采用逐级分区、区域分片和终端远传的分级分区监控布局设计。使用非对称数字用户线路挂载虚拟专用网的网络拓扑方案,实现对远程分散泵站的自动化控制和管理,同时实现对污水各项参数指标数据和图像的实时监控存储。测试结果表明,该污水管网数字化管理系统的数据传输实时性、可靠性较好,具备远程访问功能,达到了项目设计要求。     

Inkjet printing of polyvinyl alcohol multilayers for additive manufacturing applications

Here we demonstrate that inkjet printing technology is capable of producing polyvinyl alcohol (PVOH) multilayer structures. PVOH water‐based inks were formulated with the addition of additives such as humectant and pigments. The intrinsic properties of the inks, such as surface tension, rheological behavior, pH, wetting, and time stability were investigated. The ink's surface tension was in the range 30–40 mN/m. All formulated inks displayed a pseudoplastic (non‐Newtonian shear thinning and thixotropic) behavior at low‐shear rates and a Newtonian behavior at high‐shear rates; were neutral solutions (pH7) and demonstrated a good time stability. A proprietary 3D inkjet printing system was utilized to print polymer multilayer structures. The morphology, surface profile, and the thickness uniformity of inkjet printed multilayers were evaluated by optical microscopy and FT‐IR microscopy. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43572.     

Identification and Structure–Activity Relationship Studies of Small‐Molecule Inhibitors of the Methyllysine Reader Protein Spindlin1

The methyllysine reader protein Spindlin1 has been implicated in the tumorigenesis of several types of cancer and may be an attractive novel therapeutic target. Small‐molecule inhibitors of Spindlin1 should be valuable as chemical probes as well as potential new therapeutics. We applied an iterative virtual screening campaign, encompassing structure‐ and ligand‐based approaches, to identify potential Spindlin1 inhibitors from databases of commercially available compounds. Our in silico studies coupled with in vitro testing were successful in identifying novel Spindlin1 inhibitors. Several 4‐aminoquinazoline and quinazolinethione derivatives were among the active hit compounds, which indicated that these scaffolds represent promising lead structures for the development of Spindlin1 inhibitors. Subsequent lead optimization studies were hence carried out, and numerous derivatives of both lead scaffolds were synthesized. This resulted in the discovery of novel inhibitors of Spindlin1 and helped explore the structure–activity relationships of these inhibitor series.     

复合材料在地面机动武器装备上的应用

介绍了先进树脂基复合材料的基本特性,讨论了其在不同地面武器机动装备上的应用情况与发展现状,剖析了其在低成本制造技术、结构一体化集成技术等方面亟待解决的问题。同时,提出了树脂基复合材料在地面武器机动装备上研究应用的发展趋势。     

虚拟计算环境下基于聚类的资源匹配优化模型

虚拟计算环境中任务具有数量庞大、需求模糊、种类多样等特征,使得资源匹配面临巨大挑战.依据虚拟计算实验床平台公布数据,提出了一种融合虚拟资源与任务聚类的资源匹配优化模型.该模型通过分析任务需求、消耗等特征,基于改进二分K均值进行任务聚类,并结合虚拟资源类型生成优化的资源匹配列表.经实验分析验证,该模型有效缩小资源匹配范围,提高任务运行成功率,为精准匹配提供基础.     

聚乙烯醇薄膜的生产及应用现状与展望

聚乙烯醇(PVA)薄膜在水溶性、可降解性等方面的独特优点使其成为当前研究的热点。开发新的生产工艺、制备性能广泛的PVA薄膜是目前国内外共同的目标。详细阐述了PVA薄膜的优点、特性、种类及主要用途;分析了近年来PVA薄膜的生产工艺发展及市场前景;并对PVA薄膜的开发现状与应用动向进行了概述。