Rational Design of Polymeric Hybrid Micelles with Highly Tunable Properties to Co‐Deliver MicroRNA‐34a and Vismodegib for Melanoma Therapy

A polymeric hybrid micelle (PHM) system with highly tunable properties is reported to co‐deliver small molecule and nucleic acid drugs for cancer therapy; this system is structurally simple and easy‐to‐fabricate. The PHM consists of two amphiphilic diblock copolymers, polycaprolactone‐polyethylenimine (PCL‐PEI) and polycaprolactone‐polyethyleneglycol (PCL‐PEG). PHMs are rationally designed with different physicochemical properties by simply adjusting the ratio of the two diblock copolymers and the near neutral PHM‐2 containing a low ratio of PCL‐PEI achieves the optimal balance between high tumor distribution and subsequent cellular uptake after intravenous injection. Encapsulating Hedgehog (Hh) pathway inhibitor vismodegib (VIS) and microRNA‐34a (miR‐34a) into PHM‐2 generates the VIS/PHM‐2/34a co‐delivery system. VIS/PHM‐2/34a shows synergistic anticancer efficacy in murine B16F10‐CD44⁺ cells, a highly metastatic tumor model of melanoma. VIS/PHM‐2/34a synergistically attenuates the expression of CD44, a vital receptor indicating the metastasis of melanoma. Intriguingly, inhibiting Hh pathway by VIS is accompanied by downregulation of CD44 expression, revealing that Hh signaling might be an upstream regulator of CD44 expression in melanoma. Thus, co‐delivery of miR‐34a and VIS demonstrates great potential in cancer therapy, and PHM offers a structurally simple and highly tunable platform for the co‐delivery of small molecule and nucleic acid drugs in tumor combination therapy.     

旋挖钻机设备油液智能分析与健康监测

为了对直升机盒段件入水载荷进行分析，开展了模型垂直入水冲击试验，同时采用有限元-光滑粒子流体动力学（finite element method-smooth particle hydrodynamics，简称FEM-SPH）耦合数值方法进行仿真分析，计算了不同材料构型和速度下的过载、压力及应变结果。与试验结果进行对比表明，仿真结果与试验值吻合较好，预测的结构失效破坏模式与试验结果基本一致，可为真实直升机入水冲击的结构设计提供参考。     

Study of residual stress variation with depth of friction stir welded aluminium plates with different thicknesses

ABSTRACT

The residual stress may greatly vary through thickness due to the large temperature gradients and severe plastic deformation in depth for thick section friction stir welded plates. AA 2024-T351 plates with 6.5, 12 and 20?mm thicknesses were joined by friction stir welding to investigate the differences of residual stress variations with depth between thin and thick plates. The surface residual stresses were compared between the X-ray diffraction and contour measurements. Significant variations of stress peaks, root central residual stresses and widths of ‘M’ profiles were observed along the thickness for thick plates. The origins of the aggravated variations with depth were investigated from the temperature gradients and material flow variations through thickness.     

采用泡沫铜电极的热再生氨电池性能数值模拟

以采用泡沫铜电极的热再生氨电池（thermally regenerative ammonia-based battery，TRAB）为研究对象，建立了多孔介质内物质传输与电化学反应耦合的稳态模型，计算获得了电池性能及多孔电极内物质传输特性，并研究了电解质浓度和电极孔隙率对电池性能的影响。研究结果表明，从主流区界面到多孔电极内部，阳极氨和阴极铜离子浓度逐渐降低，存在一定的浓度梯度，而且随着反应电流的增大，浓度梯度明显增大。在一定的范围内分别增大阳极氨浓度和阴极铜离子浓度，从主流区向多孔电极内物质传输增强，电池性能均能不断提升；随着硫酸铵浓度的增大，电解质电导率增大，电池性能逐渐提升，但增幅逐渐减小。此外，多孔电极孔隙率也会影响电池性能，本研究中TRAB在电极孔隙率为0.6时获得最高的最大功率(15.3 mW)。     

输电线路架线施工计算软件开发与应用

青海送变电工程公司在以往工程计算数据的基础上,利用计算机软件编程技术发展快、操作简单、运算快、精度高的优点,开发了涵盖牵张力和牵引力计算、弧垂计算、连续爬坡弧垂修正计算、布线计算等10项计算模块的张力放线计算软件,通过在张力放线计算软件中设置各计算参数计算公式,设计人性化的操作界面,按设定计算功能快速准确得出计算结果,在架线施工中得到了广泛应用,有效减少技术人员复杂繁琐的计算过程,提高了计算效率。     

MicroRNA-181a is elevated by 10-hydroxycamptothecin and represses lung carcinoma progression by downregulating FOXP1

Tumor progression is usually characterized by proliferation, migration, and angiogenesis, which is essential for supplying both nutrients and oxygen to the tumor cells. Therefore, targeting angiogenesis has been considered a promising therapeutic strategy for cancer prevention and treatment. In the present study, we demonstrated that in addition to suppressing lung cancer cell proliferation and migration in vitro, 10-hydroxycamptothecin (10-HCPT) is also capable of inhibiting angiogenesis in vivo with a miR-181a-dependent manner. Mechanistically, by upregulating miR-181a, which in turn downregulating FOXP1, 10-HCPT can inhibit the PI3K/Akt/ERK signaling pathwaymediated angiogenesis. Furthermore, reduced levels of miR-181a have been found in both lung cancer cell lines and xenograft with concurrently elevated levels of FOXP1, VEGF, bFGF, and HDGF. Consistent with the findings from the in vitro experiments, miR-181a impairs neovascularization in our xenograft model. In summary, our findings have not only established the anti-oncogenic role of miR-181a in lung cancer angiogenesis but also suggest that 10-HCPT could be a potential therapeutic reagent for lung cancer treatment.