This paper expounds the needs analysis and system design of traditional Chinese medical science and technology of sci-tech novelty search management system,discusses the architecture of the system and each functional module,and summarizes and discusses the meaning of this system when applied in sci-tech novelty search.

The hematopoietic microenvironment provides an important place for hematopoietic stem cell (HSC) to self-renew, directional differentiation and maintain relative homeostasis, and it can regulate hematopoietic activity through various cellular components and factors. HSC is a primitive pluripotent stem cell in the blood system featured by the potential ability to self-renew for a long time and to differentiate into various mature blood cells, which exists in the bone marrow (BM). HSC plays an important role in regulating and maintaining the physiological balance of various cellular components of the blood system in the body, to ensure the continuous regeneration of the blood system. The hematopoietic microenvironment affects the development of HSC all the time, but the related cellular molecules and signals in the microenvironment still need to be studied in depth. This paper reviews the main components of the hematopoietic microenvironment, signaling pathways and the effects of abnormal changes on the diseases.

Bromodomain containing protein 4 (BRD4), as an epigenetic reader, can specifically bind to the acetyl lysine residues of histones and has emerged as an attractive therapeutic target for various diseases, including cancer, cardiac remodeling and heart failure. Herein, we described the discovery of hit 5 bearing 4-phenylquinazoline skeleton through a high-throughput virtual screen using 2,003,400 compound library (enamine). Then, structure-activity relationship (SAR) study was performed and 47 new 4-phenylquinazoline derivatives toward BRD4 were further designed, synthesized and evaluated, using HTRF assay set up in our lab. Eventually, we identified compound C-34, which possessed better pharmacokinetic and physicochemical properties as well as lower cytotoxicity against NRCF and NRCM cells, compared to the positive control JQ1. Using computer-based molecular docking and cellular thermal shift assay, we further verified that C-34 could target BRD4 at molecular and cellular levels. Furthermore, treatment with C-34 effectively alleviated fibroblast activation in vitro and cardiac fibrosis in vivo, which was correlated with the decreased expression of BRD4 downstream target c-MYC as well as the depressed TGF-β1/Smad2/3 signaling pathway. Taken together, our findings indicate that novel BRD4 inhibitor C-34 tethering a 4-phenylquinazoline scaffold can serve as a lead compound for further development to treat fibrotic cardiovascular disease.