Poly(A)-binding proteins are functionally distinct and have essential roles during vertebrate development

Translational control of many mRNAs in developing metazoan embryos is achieved by alterations in their poly(A) tail length. A family of cytoplasmic poly(A)-binding proteins (PABPs) bind the poly(A) tail and can regulate mRNA translation and stability. However, despite the extensive biochemical characterization of one family member (PABP1), surprisingly little is known about their in vivo roles or functional relatedness. Because no information is available in vertebrates, we address their biological roles, establishing that each of the cytoplasmic PABPs conserved in Xenopus laevis [PABP1, embryonic PABP (ePABP), and PABP4] is essential for normal development. Morpholino-mediated knockdown of PABP1 or ePABP causes both anterior and posterior phenotypes and embryonic lethality. In contrast, depletion of PABP4 results mainly in anterior defects and lethality at later stages. Unexpectedly, cross-rescue experiments reveal that neither ePABP nor PABP4 can fully rescue PABP1 depletion, establishing that PABPs have distinct functions. Comparative analysis of the uncharacterized PABP4 with PABP1 and ePABP shows that it shares a mechanistically conserved core role in promoting global translation. Consistent with this analysis, each morphant displays protein synthesis defects, suggesting that their roles in mRNA-specific translational regulation and/or mRNA decay, rather than global translation, underlie the functional differences between PABPs. Domain-swap experiments reveal that the basis of the functional specificity is complex, involving multiple domains of PABPs, and is conferred, at least in part, by protein-protein interactions.     

胆管端端吻合治疗腹腔镜胆囊切除术中胆总管横断伤的诊治体会

目的探讨胆管端端吻合治疗腹腔镜胆囊切除术(LC)中胆总管横断伤的可行性。方法回顾性分析9例LC术中胆总管横断后及时中转开腹行胆管端端吻合术的患者的资料,其中2例为大部横断,7例完全横断,8例术中发现随即中转开腹手术,1例术后次日发现再次开腹治疗。结果 9例患者均顺利完成手术,术后常规留置T管6个月,2例出现术后胆管狭窄,经内窥镜胆道球囊扩张解除狭窄,无胆瘘、出血等严重并发症的发生。结论 LC术中横断胆管后及时中转开腹行胆管端端吻合是有效的治疗方法。     

食管胃端端吻合在食管胃交界部癌切除术中的应用

目的:探讨食管胃端端吻合在食管胃交界部癌切除术中的临床应用价值。方法:48例食管胃交界部癌行常规近半胃切除及区域淋巴结清扫后,采用食管胃端端吻合重建消化道,并重点观察术后切缘癌残留率、吻合口瘘以及术后3个月胃肠功能,包括吻合口狭窄、胃食管反流、进食量、进食频率、胃排空情况及体重恢复情况。结果:本组48例患者手术均顺利完成,术后无切缘癌残留、吻合口瘘、胃排空障碍以及胸胃综合征等并发症的发生。术后3个月吻合口狭窄3例(6.3%),胃食管反流症状者13例(27.0%),进餐量与术前进餐量之比为(0.83±0.14)kg,每天进餐频率为(4.1±1.2)次,体重恢复到术前的患者占41.5%。结论:食管胃端端吻合在食管胃交界部癌切除手术中安全可行,能降低食管胃切缘癌残留的发生率和全胃切除的可能性,预防术后胃排空障碍,减小术后饭量损失,利于患者树立生活信心,改善术后生活质量,值得临床推广应用,特别适用于贲门肿瘤较大(胃体侵犯较多)和胃体较小者。     

人工智能在药物靶点的筛选及验证方面的应用进展

近年来人工智能发展迅速，随着算力的提升、算法的迭代，人工智能极大方便了生物信息、化学信息和临床数据的收集及处理，为新药研发注入了新的活力。本综述对人工智能在制药领域的发展历程及其主要算法进行了简要介绍，随后结合具体实例对人工智能在药物靶点筛选及验证方面的不同阶段进行了详细描述，包括药物靶点发现、蛋白结构预测以及苗头化合物生成与优化等。最后对人工智能平台“端到端”的一次高效应用过程进行了具体讨论。