Objective To study the adverse effects of PM2.5 from Beijing urban areas on human lung adenocarcinoma cells(A549) and the expression of NF-?B in the cells. Methods A549 cells were treated with PM2.5 at 25,50,100 and 200 ?g/ml for 24 h. Cytotoxicity of PM2.5 was measured by MTT assay. The activity of NF-?B was measured by ELISA assay. Western blot method was used to detect the expression of NF-?B and NO levels was determined by using the nitrate reductase method. Results PM2.5 could induce A549 cell proliferation at low doses,but inhibit cell proliferation at high doses. The activity of NF-?B increased in the cell nucleus,but decreased in the cytoplasm after exposure to PM2.5 with a significant dose-dependent manner(P

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.