摘要：Focal adhesion kinase(FAK)is an intracellular tyrosine kinase that plays a critical role in the occurrence,development,and metastasis of cancer through both its kinase-dependent catalytic functions and kinase-independent scaffolding *** kinase inhibitors target only its catalytic activity,leaving the scaffolding functions ***,proteolysis targeting chimeras(PROTACs)offers a promising approach by degrading the entire FAK protein,thereby inhibiting both functions *** this study,we designed and synthesized novel PROTAC degraders,utilizing a defactinib derivative(compound 12)as the FAK ligand and a lenalidomide analog as the E3 ligase *** structures of these compounds were confirmed through^(1)H NMR,^(13)C NMR,and high-resolution mass spectrometry(HRMS).Among the synthesized compounds,the optimized compound 16b exhibited potent degradation activity against FAK protein in A549 cells,with a DC_(50)of 6.16±1.13 n M,significantly inhibiting the proliferation and colony formation of these *** to defactinib,16b showed enhanced inhibition of A549 cell migration and ***,our research demonstrated that the rapid and effective FAK degradation induced by 16b was mediated by a CRBN-dependent proteasome mechanism.

摘要：为解决大面积钛/钢爆炸焊接窗口窄,在结合区易出现"过熔"和"射流堆积"等微观缺陷的问题,开展了双立爆炸+轧制综合制造技术,进行了低爆速爆炸焊接用炸药试验优化,发明了一种最低临界爆速爆炸焊接用炸药,设计确定了刚性防护板和柔性防护墙构成的双立综合防护结构及参数,研究了钛/钢爆炸焊接装药厚度窗口.结果表明,双立钛/钢复合板结合界面成波状结合,几乎不存在金属熔化、漩涡等微观缺陷.

摘要：目的合成14-N-(3-乙酰基苯)-氨基粉防己碱,并考察其体外抗肿瘤活性。方法本研究以粉防己碱为原料,依次经硝化、还原和Chan-Lam-Evans偶联共计三步反应,合成了一种双苄基异喹啉衍生物,新合成的化合物的结构经核磁共振氢谱(^(1)H-nuclear magnetic resonance,^(1)H-NMR)、核磁共振碳谱(^(13)C-nuclear magnetic resonance,^(13)C-NMR)和高分辨质谱(high resolution mass spectrometer,HRMS)确证。采用MTT法将所得衍生物14-N-(3-乙酰基苯)粉防己碱对人肝癌细胞HepG2和人正常肝细胞HL7702的体外抑制活性进行了初步评价;通过设计细胞划痕、侵袭实验探究化合物对HepG2细胞迁移和侵袭能力影响。结果MTT实验结果表明,该化合物可以剂量依赖性地抑制HepG2细胞增殖,其IC_(50)值为4.61μmol/L。细胞划痕、侵袭实验表明该化合物明显抑制HepG2细胞迁移和侵袭能力,且呈剂量依赖性,差异具有统计学意义(P<0.005)。结论结果表明,14-N-(3-乙酰基苯)-氨基粉防己碱可作为一种潜在的抗肝癌药物。

摘要：为了寻找更高效、更经济的抗肿瘤药物,以L-苯丙氨酸为起始原料,经氨基保护、酰胺缩合、脱保护、再缩合、再脱保护、再缩合等多步反应,设计并合成了8种新型苯丙氨酸衍生物的小分子肽,并采用FTIR、1H NMR、I3C NMR、HRMS和元素分析等测试方法对其结构进行确认.采用溴化噻唑蓝四氮唑法(MTT)比色法对所有目标化合物进行了抗肿瘤活性测试,测试结果表明,所有化合物对肝癌细胞SMC7721均有一定的抑制作用,其中化合物5e和8b对肝癌细胞的抑制作用最强.

摘要：以一款两相步进电机控制芯片TC1002,实现了一种结构简单的高性能、多细分、微型化两相混合式步进电动机驱动器。该系统采用恒流斩波控制方式,可调的电流衰减模式可以进一步改善步进电机绕组的电流波形。驱动器最高细分数为256,提供正反向控制、使能控制、自动半流锁定功能以及过流、过热等电动机驱动器的保护功能。这种控制器成本低、容易实现、性能稳定,是步进电机控制器的一种较好选择。