摘要：Angiokinases, such as vascular endothelial-, fibroblast-and platelet-derived growth factor receptors(VEGFRs, FGFRs and PDGFRs) play crucial roles in tumor angiogenesis. Anti-angiogenesis therapy using multi-angiokinase inhibitor has achieved great success in recent years. In this study, we presented the design, synthesis, target identification, molecular mechanism, pharmacodynamics(PD)and pharmacokinetics(PK) research of a novel triple-angiokinase inhibitor WXFL-152. WXFL-152,identified from a series of 4-oxyquinoline derivatives based on a structureeactivity relationship study,inhibited the proliferation of vascular endothelial cells(ECs) and pericytes by blocking the angiokinase signals VEGF/VEGFR2, FGF/FGFRs and PDGF/PDGFRβ simultaneously in vitro. Significant anticancer effects of WXFL-152 were confirmed in multiple preclinical tumor xenograft models, including a patientderived tumor xenograft(PDX) model. Pharmacokinetic studies of WXFL-152 demonstrated high favourable bioavailability with single-dose and continuous multi-dose by oral administration in rats and *** conclusion, WXFL-152, which is currently in phase Ib clinical trials, is a novel and effective tripleangiokinase inhibitor with clear PD and PK in tumor therapy.

摘要：In the processes of product innovation and design, it is important for the designers to find and capture customer＇s focus through customer requirement weight calculation and ranking. Based on the fuzzy set theory and Euclidean space distance, this paper puts forward a method for customer requirement weight calculation called Euclidean space distances weighting ranking method. This method is used in the fuzzy analytic hierarchy process that satisfies the additive consistent fuzzy matrix. A model for the weight calculation steps is constructed; meanwhile, a product innovation design module on the basis of the customer requirement weight calculation model is developed. Finally, combined with the instance of titanium sponge production, the customer requirement weight calculation model is validated. By the innovation design module, the structure of the titanium sponge reactor has been improved and made innovative.

摘要：目的:先导式截止阀可通过一个先导阀,利用流体在阀门前后自身的压差控制主阀的启闭,是一种新型节能型截止阀。本文探讨该阀在开启和关闭状态下、不同入口速度情况下和不同阀芯位置下的流动和汽蚀特性,为后期结构优化提供设计建议。创新点:1.分析先导式截止阀的阀芯上下表面压差的变化情况,验证其可行性和模型准确性;2.建立数值模型,对先导式截止阀在不同启闭状态和不同阀芯位移情况下进行流动和汽蚀分析。方法:1.通过数值模拟,分析阀芯上下表面的压差,并与现有文献进行比较,验证模型的准确性(图3);2.建立开启和关闭条件下的阀门模型,比较两种状态下该阀的流动和汽蚀特性(图4和5);3.建立不同入口速度条件下的阀门模型,比较分析速度对该阀的汽蚀情况的影响(图6);4.建立不同阀芯位置的阀门模型,比较分析不同阀芯位置下的速度和压力情况,进一步验证该阀的可行性,并分析阀芯位置对阀门汽蚀的影响(图7)。结论:1.在开启和关闭状态下,流速和汽含率在阀座底部靠近出口处达到峰值;2.入口速度更高的情况下,阀的开启速度更快,但汽含率并不一定同步上升;3.当阀芯处于低位置时,虽然对阀门出口处影响位置较小,但其压力梯度较大、汽含率较高,选取合适的弹簧刚度非常重要。

摘要：研究温度对新型体心立方(BCC)基Fe_(3.5)Cr_(1.5)NiAl_(0.8)多组元合金(MCA)中有序椭圆状B2-NiAl纳米析出相的显微组织稳定性和力学性能的影响。采用XRD、EBSD、EPMA和TEM等检测方法对该多组元合金的显微组织和物相组成进行表征。结果表明,所设计的高含量椭圆状B2纳米析出相与BCC基体完全共格且能在1073 K高温下保持稳定,平均粒径为245.509~251.328 nm。铸态和热处理态(873 K≤T≤1073 K)合金具有独特的共格结构,这是由于低错配度的共格析出强化机制可使合金具有较高的屈服强度(809.2~1164.1 MPa)。随着热处理温度的进一步提高(1173 K≤T≤1273 K),B2纳米析出相的平均粒径逐渐粗化,载荷传递强化机制对其屈服强度提高起主要作用。