通过基于infomaxnet的网络毒理学和分子模拟,揭示1,3-二烯的凝血毒性
Yan Pan1, Hongxia Cai1, Yufeng Ran2
1Department of Neurology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China; Institute for Toxicology, Beijing Center for Disease Prevention and Control, Beijing 100013, China; Laboratory of Aging Research, School of Medicine, University of Electronic Science and Technology of China, Chengdu 611731, China.
塑料中的1,3-二烯 (SD-1) 通过向F9 (FIXa) 和AKT2.2来破坏血液凝固. 本研究引入InfomaxNet,揭示了环境污染物的有毒机制.
科学领域:
- 环境毒理学环境毒理学
- 计算生物学 计算生物学
- 分子毒理学 分子毒理学
背景情况:
- 塑料产品释放出1,3-二烯 (SD-1),一种聚乙烯二聚体,对健康构成风险.
- 众所周知,SD-1会诱导凝血障碍,但其毒性机制尚不清楚.
研究的目的:
- 引入InfomaxNet,一个新的网络毒理学分析框架.
- 使用Infomax.Net阐明SD-1在凝血系统上的毒性机制.
主要方法:
- 使用InfomaxNet框架和深度学习 (MolTrans) 的网络毒理学分析.
- 分子动力学模拟来分析SD-1与F9 (FIXa) 的结合.
- 在体外实验和Caenorhabditis elegans毒性测定.
主要成果:
- InfomaxNet确定AKT2和F9是受SD-1影响的关键蛋白质.
- SD-1与F9 (FIXa) 结合会导致活性部位异常,破坏凝血.
- SD-1影响AKT2信号通路,在C. elegans中得到了验证.
结论:
- 在没有先前的生物知识的情况下,InfomaxNet有效地分析了毒理学机制.
- SD-1通过准F9的化酶域来破坏凝血.
- 这项研究为塑料衍生污染物的毒理学影响提供了新的见解.
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