Cyclin-dependent kinase 9 (CDK9) is a member of the transcription CDK subfamily and plays a role in transcriptional regulation. Selective CDK9 degraders possess potent clinical advantages over reversible CDK9 inhibitors. Herein, we report the first ATG101-recruiting selective CDK9 degrader, AZ-9, based on the hydrophobic tag kinesin degradation technology. AZ-9 showed significant degradation effects and selectivity toward other homologous cell cycle CDKs in vitro and in vivo, which could also affect downstream related phenotypes. Mechanism research revealed that AZ-9 recruits ATG101 to initiate the autophagy-lysosome pathway, and forms autophagosomes through the recruitment of LC3, which then fuses with lysosomes to degrade CDK9 and the partner protein Cyclin T1. These dates validated the existence of non-proteasomal degradation pathway of hydrophobic driven protein degradation strategy for the first time, which might provide research ideas for chemical induction intervention on other types of pathogenic proteins.

Objective To find out the health status and community health care requirement of the elderly in urban Fuzhou and to provide suggestions on how to develop and consummate the community health care for elderly. Methods With the method of stratified random sampling, 3285 elderly people aged 60 years and over were surveyed by a questionnaire. Results The average quality of life of elderly people in urban Fuzhou was above the moderate level. But education level of the elderly was low. And the prevalence rate of chronic diseases was high. There were 2134 elderly people (65.0%) who had more than one chronic disease. The older the people, the higher proportion the coincidence of multiple diseases (P＜0.01). The first five chronic diseases in the elderly were hypertension, diabetes, coronary heart disease, arthropathy and stroke. The incidence rate of depression was high up to 60%. The requirement rate of community health care was 75.2%, and the older the people, the more items they needed(P＜0.05). The requirement of community health care at the first 5 rank position were regular physical examination, health education, regular home visiting, health direction and diet direction. Conclusions Elderly people have many health problems and requirements of community health care.We should provide more and more community health care, in order to improve the quality of life of elderly people.