摘要：In order to enhance the targeted delivery of anticancer drugs by polymeric micelles, folic acid(FA), the ligand of folate receptor(FR) over-expressed in the most cancer cells, modified p H-sensitive polymeric micelles were designed and fabricated to encapsulate doxorubicin(DOX) by combination of p H-sensitive amphiphilic polymer poly(2-ethyl-2-oxazoline)-poly(D,L-lactide) with FA-conjugated poly(2-ethyl-2-oxazoline)-poly(D,L-lactide). The prepared micelles were characterized to have about 36 nm in diameter with narrow distribution, well-defined spherical shape observed under TEM and p H-responsive drug release behavior. Moreover, the tumor targeting ability of the FA-modified p H-sensitive polymeric micelles was demonstrated by the cellular uptake, in vitro cytotoxicity to FR-positive KB cells and in vivo real time near-infrared fluorescence imaging in KB tumor-bearing nude mice. The efficient drug delivery by the micelles was ascribed to the synergistic effects of FR-mediated targeting and p H-triggered drug release. In conclusion, the designed FR-targeted p H-sensitive polymeric micelles might be of great potential in tumor targeted delivery of water-insoluble anticancer drugs.

摘要：To overcome the main barrier of intestinal epithelium for the oral absorption of poorly water-soluble drugs and further improve their oral absorption, Gly-Sar, the substrate of the oligopeptide transporter PepT1 widely distributed in the small intestine,conjugated poly(ethylene glycol)-block-poly(D,L-lactide)(Gly-Sar-PEG-b-PLA) was designed and synthesized, and Pep T1-targeted polymeric micelles were prepared and characterized. The structure of the synthesized Gly-Sar-PEG-b-PLA was confirmed by use of TLC and 1 H-NMR. The average molecular weight measured by GPC was 5954 g/mol with PDI of 1.34. The DiI-loaded polymeric micelles from Gly-Sar-PEG-b-PLA with drug loading content of 0.076% were characterized to exhibit 40.36 nm in diameter with PDI of 0.294, and well-defined spherical shape observed by TEM. Furthermore, the PepT1-targeted polymeric micelles profoundly enhanced intestinal absorption of poorly water-soluble drug. Therefore, the designed PepT1-targeted polymeric micelles might have a promising potential for oral delivery of water-insoluble drugs.

摘要：In the present study, we designed and fabricated pH-sensitive polymeric micelles based on the conjugate of poly（2-ethyl-2-oxazoline）-poly（D,L-lactide）（PEOz-PLA） with doxorubicin（PEOz-PLA-imi-DOX） to efficiently inhibit tumor cell growth. Hence, PEOz-PLA-imi-DOX was successfully synthesized by connecting DOX to the hydrophobic end of pH-sensitive PEOz-PLA via acid cleavable benzoic imine linker and characterized by 1 H NMR spectrum and thin layer chromatography. The critical micelle concentration of PEOz-PLA-imi-DOX was determined to be（14.84±3.85） mg/L. The conjugate micelles（denoted as PP-DOX-PM） formed by PEOz-PLA-imi-DOX using film-hydration method were characterized to have a nano-scaled size of about 21 nm in diameter, and the drug loading content was 1.67%. PP-DOX-PM showed pH-dependent drug release behavior with gradually accelerated release of DOX with decrease of pH value, illustrating the micelles＇ distinguishing feature of endo/lysosomal pH from physiological pH by accelerating drug release. As anticipated, PP-DOX-PM maintained the cytotoxicity of DOX against MDA-MB-231 cells. Collectively, PP-DOX-PM might have great potential for effective suppression of tumor growth.

摘要：The intestinal epithelium is the main barrier to the oral delivery of poorly water-soluble drugs. Based on the specific transporters expressed on the apical membrane of the intestinal epithelium, novel polymer micelles targeting to the organic cation transporter 2（OCTN2） were constructed by combining carnitine conjugated poly（2-ethyl-2-oxazoline）-poly（D,L-lactide）（Car-PEOz-PLA） with monomethoxy poly（ethylene glycol）-poly（D,L-lactide）（mP EG-PLA）. The structure of the synthesized Car-PEOz-PLA was confirmed by -1H NMR, TLC and ammonium reineckate precipitation reaction, and the number-average molecular weight determined by GPC was 7260 g/mol with a low PDI of 1.44. Coumarin 6-loaded carnitine modified polymeric micelles prepared by film hydration method were characterized to have a nano-scaled size of about 31 nm in diameter, uniform spherical morphology, high drug loading content of 0.098%±0.03% and encapsulation efficiency of 92.67%±2.80%. Moreover, the carnitine-modified micelles exhibited the similar in vitro release behavior in SGF and SIF, and evidently enhanced intestinal absorption of poorly water-soluble agent. Therefore, the designed OCTN2-targeted micelles might have a promising potential for oral delivery of poorly water-soluble drugs.

摘要：To ensure the delivery of antitumor drugs to tumor site and quick release in tumor cells, we designed and prepared pH-sensitive polymeric micelles by combining cationic ring-opening polymerization of 2-ethyl-2-oxazoline （EOz） with vitamin E succinate （VES）, and then encapsulating paclitaxel （PTX） into the micelles self-assembled by poly（2-ethyl-2-oxazoline）-vitamin E succinate （PEOz-VES）. The structure of the synthesized PEOz-VES was confirmed by ^1H NMR spectrum, and the molecular weight measured by GPC was 1212 g/mol. The pKa of PEOz-VES with a low critical micelle concentration of （5.84±0.02） mg/L was determined to be 6.01. The PTX-loaded PEOz-VES polymeric micelles prepared by film hydration method were characterized to have a nanoscaled size of about 30 nm in diameter, a positive Zeta potential of 4.86 mV and uniform spherical morphology by TEM observation. The drug loading content and encapsulation efficiency were （2.63±0.16）% and （84.1±3.38）%, respectively. The in vitro release behavior of PTX from PEOz-VES micelles in PBS displayed pH-dependent pattern and was gradually accelerated with decrease of pH value, implying that the micelles could distinguish endo/lysosomal pH and tumor extracellular pH from physiological pH by accelerating drug release. Therefore, the designed PEOz-VES micelles might have significant promise for anti-cancer drug delivery.

摘要：为解决目前双三角钻臂液压系统参数设计采用相关经验值加安全系数的方法存在的系统压力设计偏高、液压部件选配耐压等级大、系统发热严重、制造维保成本高、系统功耗大等问题,对双三角钻臂结构进行理论分析,采用运动轨迹投影和静力学分析的方法,建立钻臂运动过程中双三角负载与运动位置之间的关系,根据臂架设计参数获取其极值及其极值位置的油缸负载参数。根据双三角结构工作原理并结合臂架工作环境,设计一种负载敏感液压控制系统,经理论分析和计算,确定系统的原理和液压元件的主要参数并试验。试验结果表明,运动极值位置的液压系统负载参数与理论分析参数基本一致,系统运行整体平稳可靠,随动油缸调节功能正常,隧道内试验3 h液压系统温升65.5℃,证明该液压系统设计的合理性和可应用性。

摘要：目的通过结合人工神经网络和激光冲击有限元仿真,以减少激光冲击强化最佳参数设计的迭代次数,提高参数优化效率。方法构建基于冲击波压力幅值的激光冲击强化Abaqus有限元模型。采用Vdload子程序与对应二次开发脚本形成光斑重叠区域残余应力的初始数据集。建立人工神经网络(ANN)算法模型,采用测试集对ANN模型进行测试,对超参数进行优化,对比分析不同机器学习算法的R2得分、MAE和RMSE。设计并优化镍铝青铜模型表面的残余应力大小与分布,对比分析经机器学习预测后的模型表面残余应力分布情况。结果经ANN预测整个面LSCP处理的模型表面形成了高达‒413 MPa的残余压应力,并且预测了均匀与非均匀的残余压应力分布;RMSE均方根误差仅为1.1891,既显示出较好的预测精度,又避免了模型的过拟合,保证了一定的泛化能力,模型综合性能远优于其他经典的ML算法回归模型。所预测的残余压应力分布模型均达到了较深的影响层深,且在1 Hz的脉冲重复频率下,最大效率达到了1.87 mm^(2)/s。结论激光冲击强化与机器学习的结合实现了易产生残余应力孔洞的镍铝青铜光斑重叠区域的最大残余压应力分布,且该方法优化出了整个表面的均匀与相对非均匀的残余压应力分布,为非均匀塑性应变引起镍铝青铜材料异质结构的形成开辟了新的设计途径。

摘要：针对预应力连续刚构桥的病害和传统加固方法存在的不足,提出一种在原结构上增设钢上弦杆和腹杆,并以原预应力混凝土结构作为下弦杆,形成桁式结构共同抵抗部分荷载的加固方法.通过增设钢结构,将部分原本由混凝土结构独自承担的荷载,转由桁式结构承担,从而达到以较少代价提高结构的抗弯能力、抗剪能力和承载力的目的.以香江圩郁江特大桥加固为例,详细阐述所提方法及其力学原理,并进行详细的加固设计.结果表明:所提方法在增加较少用钢量的前提下,能有效提高结构的刚度、强度和动力特性等,且施工方便,因此,适用于既有连续刚构桥的提载和加固改造.

摘要：在恒载作用下,上承式拱桥可通过设置合理拱轴线达到拱肋成为小偏心受压构件的目的。然而,在活载作用下,拱肋不再是单向受力状态,伴随明显的弯剪变形,导致力学性能下降,在一定程度上限制了大跨拱桥在活载占比重较大的铁路桥中的应用。据此,基于拱式、桁式结构的受力特点,考虑合理的体系转换方式,提出一种上承式加V拱桥结构,研究其力学特性和体系转换机理,并分别采用试验和有限元方法对其进行验证。试验研究表明,体系转换前后,上承式加V拱桥分别体现拱式结构和桁式结构受力特点;与同等用钢量的上承式拱桥相比,在结构强度和稳定性不降低的情况下,上承式加V拱桥竖向刚度和面内自振频率分别提高54.75%和104.28%。

摘要：为解决隧道锚杆安装过程中效率低、阻力大、不易完全装入等问题,采用D-H法建立锚杆安装机械手坐标系。通过对机械手结构的齐次坐标变换建立机械手运动学方程,并结合工程施工参数,得出推进机构运动与机械手爪运动之间的关系,理论计算出锚杆安装机械手相关设计参数,从而设计一种新型的隧道锚杆安装机械手。该机械手安装速度为38.9 mm/s,与传统钻杆推进安装方式相比,单循环节约工时约2 h,经济优势突出。