背景:纳米技术与医学的结合在选择性靶向及治疗肿瘤领域开辟了一条全新的道路,通过应用纳米载体确保了装载药物的靶向递送与稳定性,增强了细胞摄取和生物相容性。目的:制备一种谷胱甘肽和pH值双响应性CD24适配体修饰的载铁死亡激动剂Era...背景:纳米技术与医学的结合在选择性靶向及治疗肿瘤领域开辟了一条全新的道路,通过应用纳米载体确保了装载药物的靶向递送与稳定性,增强了细胞摄取和生物相容性。目的:制备一种谷胱甘肽和pH值双响应性CD24适配体修饰的载铁死亡激动剂Erastin和双质粒的纳米药物递送系统PC(coBP)Ca,探讨其在体外对三阴性乳腺癌中CD24高表达细胞的精准靶向性和可行性。方法:PEG-CAPDB经过多次聚合反应生成纳米微球骨架COOH-PEG-CPADB-[co BMA co PDSMA],再通过自组装合成内载铁死亡激动剂Erastin、1-2M2ge化合物、NF2敲除质粒和YAP过表达质粒形成PC(coBP),利用SELEX技术筛选CD24适配体,进一步修饰PC(coBP),最终形成载药纳米微球PC(coBP)Ca。检测PC(coBP)Ca表面CD24适配体修饰、对谷胱甘肽和pH值的敏感性、逃逸免疫细胞吞噬的性能及靶向性能、逃逸溶酶体吞噬和药物突释性能及对吞噬细胞吞噬作用的影响。结果与结论:PC(coBP)Ca的平均粒径为(141.11±13.43)nm,平均多分散性指数为0.353±0.074,平均Zeta电位显示良好分散性;PC(coBP)Ca中铁死亡激动剂Erastin的平均载药量为(23.34±2.45)%、包封率为(90.24±3.11)%;PC(coBP)Ca在谷胱甘肽和pH值双重响应作用下的4 h释放量约为90%,可有效逃避免疫细胞吞噬精准靶向CD24高表达三阴乳腺癌细胞,逃逸溶酶体,达到药物突释,激活铁死亡途径和促进吞噬细胞吞噬。实验成功合成载药纳米微球PC(coBP)Ca具备精准、有效、安全和低毒性的特点,有望成为三阴乳腺癌中CD24高表达细胞靶向纳米药物递送系统。展开更多
目的探讨泛素蛋白连接酶E3A(ubiquitin protein ligase E3A,UBE3A)与泛素特异性蛋白酶25(ubiquitin specific protease 25,USP25)在乳腺癌组织中的表达及与临床病理特征的相关性,并分析UBE3A与USP25在乳腺癌泛素蛋白酶体系统中的关系。...目的探讨泛素蛋白连接酶E3A(ubiquitin protein ligase E3A,UBE3A)与泛素特异性蛋白酶25(ubiquitin specific protease 25,USP25)在乳腺癌组织中的表达及与临床病理特征的相关性,并分析UBE3A与USP25在乳腺癌泛素蛋白酶体系统中的关系。方法采用免疫组织化学染色检测50例乳腺癌组织及癌旁相对正常组织石蜡标本中UBE3A与USP25的表达情况,并分析它们与乳腺癌患者临床病理特征的关系;shRNA-UBE3A慢病毒转染乳腺癌MCF-7细胞,通过荧光定量PCR与Western Blot检测UBE3A基因及蛋白的敲减水平,然后观察敲减UBE3A后USP25的表达水平。结果UBE3A与USP25在乳腺癌组织中的阳性表达率分别为64%、72%,而在邻近相对正常组织中的表达均为阴性,两者在乳腺癌组织与相对正常组织中的表达差异具有统计学意义(P<0.001);UBE3A的表达与淋巴结转移(P=0.001)、Ki-67的表达(P<0.001)相关,USP25的表达与组织学分级(P=0.046)、淋巴结转移(P=0.041)、Ki-67的表达(P=0.029)相关;shRNA-UBE3A慢病毒转染乳腺癌MCF-7细胞后,UBE3A蛋白及mRNA的表达均明显降低(P<0.001),且敲减UBE3A后USP25的蛋白及mRNA的表达明显降低(P<0.001)。结论UBE3A与USP25和乳腺癌细胞的增殖、转移等生物学行为相关,在乳腺癌泛素蛋白酶体系统中UBE3A与USP25功能作用明显增强且保持动态平衡,它们可能共同作用促进乳腺癌的的发生发展。展开更多
Experimental evidence showed that declination exists in most sentences in Chinese Putonghua. However, the specific pitch variation of prosodic words （PWs） within sentences has not been fully understood. The dialogue...Experimental evidence showed that declination exists in most sentences in Chinese Putonghua. However, the specific pitch variation of prosodic words （PWs） within sentences has not been fully understood. The dialogue material used in this study was taken from the 973 telephone conversation corpus, which includes 69 dialogues, with 79 speakers involved. The read speech material was recordings of news announcement by two announcers from radio, totally 221 sentences. Top and bottom points of pitch contour and the range of prosodic words with the sentences were studied. It was found that, for both dialogue and read speech, pitch declination exists for most sentences, with minor exceptions in the first part of longer sentences for dialogue. Compared to read speech, the pitch range of prosodic words for dialogue is smaller. For dialogue, the pitch range of the last prosodic words of the sentences are relatively larger, while there is no significant difference for pitch ranges of prosodic words in most sentences of read speech. This study will be helpful for the modeling of the pitch range and register of prosodic words in sentences in speech synthesis.展开更多
文摘背景:纳米技术与医学的结合在选择性靶向及治疗肿瘤领域开辟了一条全新的道路,通过应用纳米载体确保了装载药物的靶向递送与稳定性,增强了细胞摄取和生物相容性。目的:制备一种谷胱甘肽和pH值双响应性CD24适配体修饰的载铁死亡激动剂Erastin和双质粒的纳米药物递送系统PC(coBP)Ca,探讨其在体外对三阴性乳腺癌中CD24高表达细胞的精准靶向性和可行性。方法:PEG-CAPDB经过多次聚合反应生成纳米微球骨架COOH-PEG-CPADB-[co BMA co PDSMA],再通过自组装合成内载铁死亡激动剂Erastin、1-2M2ge化合物、NF2敲除质粒和YAP过表达质粒形成PC(coBP),利用SELEX技术筛选CD24适配体,进一步修饰PC(coBP),最终形成载药纳米微球PC(coBP)Ca。检测PC(coBP)Ca表面CD24适配体修饰、对谷胱甘肽和pH值的敏感性、逃逸免疫细胞吞噬的性能及靶向性能、逃逸溶酶体吞噬和药物突释性能及对吞噬细胞吞噬作用的影响。结果与结论:PC(coBP)Ca的平均粒径为(141.11±13.43)nm,平均多分散性指数为0.353±0.074,平均Zeta电位显示良好分散性;PC(coBP)Ca中铁死亡激动剂Erastin的平均载药量为(23.34±2.45)%、包封率为(90.24±3.11)%;PC(coBP)Ca在谷胱甘肽和pH值双重响应作用下的4 h释放量约为90%,可有效逃避免疫细胞吞噬精准靶向CD24高表达三阴乳腺癌细胞,逃逸溶酶体,达到药物突释,激活铁死亡途径和促进吞噬细胞吞噬。实验成功合成载药纳米微球PC(coBP)Ca具备精准、有效、安全和低毒性的特点,有望成为三阴乳腺癌中CD24高表达细胞靶向纳米药物递送系统。
文摘目的探讨泛素蛋白连接酶E3A(ubiquitin protein ligase E3A,UBE3A)与泛素特异性蛋白酶25(ubiquitin specific protease 25,USP25)在乳腺癌组织中的表达及与临床病理特征的相关性,并分析UBE3A与USP25在乳腺癌泛素蛋白酶体系统中的关系。方法采用免疫组织化学染色检测50例乳腺癌组织及癌旁相对正常组织石蜡标本中UBE3A与USP25的表达情况,并分析它们与乳腺癌患者临床病理特征的关系;shRNA-UBE3A慢病毒转染乳腺癌MCF-7细胞,通过荧光定量PCR与Western Blot检测UBE3A基因及蛋白的敲减水平,然后观察敲减UBE3A后USP25的表达水平。结果UBE3A与USP25在乳腺癌组织中的阳性表达率分别为64%、72%,而在邻近相对正常组织中的表达均为阴性,两者在乳腺癌组织与相对正常组织中的表达差异具有统计学意义(P<0.001);UBE3A的表达与淋巴结转移(P=0.001)、Ki-67的表达(P<0.001)相关,USP25的表达与组织学分级(P=0.046)、淋巴结转移(P=0.041)、Ki-67的表达(P=0.029)相关;shRNA-UBE3A慢病毒转染乳腺癌MCF-7细胞后,UBE3A蛋白及mRNA的表达均明显降低(P<0.001),且敲减UBE3A后USP25的蛋白及mRNA的表达明显降低(P<0.001)。结论UBE3A与USP25和乳腺癌细胞的增殖、转移等生物学行为相关,在乳腺癌泛素蛋白酶体系统中UBE3A与USP25功能作用明显增强且保持动态平衡,它们可能共同作用促进乳腺癌的的发生发展。
文摘Experimental evidence showed that declination exists in most sentences in Chinese Putonghua. However, the specific pitch variation of prosodic words （PWs） within sentences has not been fully understood. The dialogue material used in this study was taken from the 973 telephone conversation corpus, which includes 69 dialogues, with 79 speakers involved. The read speech material was recordings of news announcement by two announcers from radio, totally 221 sentences. Top and bottom points of pitch contour and the range of prosodic words with the sentences were studied. It was found that, for both dialogue and read speech, pitch declination exists for most sentences, with minor exceptions in the first part of longer sentences for dialogue. Compared to read speech, the pitch range of prosodic words for dialogue is smaller. For dialogue, the pitch range of the last prosodic words of the sentences are relatively larger, while there is no significant difference for pitch ranges of prosodic words in most sentences of read speech. This study will be helpful for the modeling of the pitch range and register of prosodic words in sentences in speech synthesis.
