一种.NET框架下基于XPO的VOD节目发布系统的设计

随着"三网合一"向纵深发展,电视节目的数字化工程越来越重要。但是,大部分有线电视用户由于使用单向机顶盒而无法享受数字节目和视屏点播带来的好处。为了解决上述问题,急需开发一种VOD节目发布系统,以便广大的数字电视用户都能加入到VOD的阵营中。为此提出一种.NET框架下基于XPO的VOD节目发布系统的设计和实现方法,研究了基于该方法下的模块划分和功能集成,该系统在重庆有线电视网络有限公司已经投入运营,效果良好。     

Chemoproteomic Profiling of Covalent XPO1 Inhibitors to Assess Target Engagement and Selectivity

Selinexor, a covalent XPO1 inhibitor, is approved in the USA in combination with dexamethasone for penta-refractory multiple myeloma. Additional XPO1 covalent inhibitors are currently in clinical trials for multiple diseases including hematologic malignancies, solid tumor malignancies, glioblastoma multiforme (GBM), and amyotrophic lateral sclerosis (ALS). It is important to measure the target engagement and selectivity of covalent inhibitors to understand the degree of engagement needed for efficacy, while avoiding both mechanism-based and off-target toxicity. Herein, we report clickable probes based on the XPO1 inhibitors selinexor and eltanexor for the labeling of XPO1 in live cells to assess target engagement and selectivity. We used mass spectrometry-based chemoproteomic workflows to profile the proteome-wide selectivity of selinexor and eltanexor and show that they are highly selective for XPO1. Thermal profiling analysis of selinexor further offers an orthogonal approach to measure XPO1 engagement in live cells. We believe these probes and assays will serve as useful tools to further interrogate the biology of XPO1 and its inhibition in cellular and in vivo systems.