Allergic rhinitis (AR), a globally prevalent immune-mediated inflammatory condition, is still an incurable disease. In the present study, we have validated the impact of the Kelch-like ECH associated protein 1 (Keap1)-related oxidative stress and inflammatory response in clinical AR patient peripheral blood and nasal swab samples, emphasizing the biological relevance of Keap1 and AR. Targeting Keap1 -nuclear factor erythroid 2-related factor 2 (Nrf2) related anti-oxidative stress may be effective for AR intervention. Drawing inspiration from the Keap1 homodimerization and the E3 ligase characteristics, we herein present a design of novel bivalent molecules for chemical knockdown of Keap1. For the first time, we characterized ternary complexes of Keap1 dimer and one molecule of bivalent compounds. The best bivalent molecule 8 encompasses robust capacity to degrade Keap1 as a homoPROTAC^KEAP1. It efficaciously suppresses inflammatory cytokines in extensively different cells, including human nasal epithelial cells. Moreover, in an AR mouse model, we confirmed that the chemical degradation induced by homoPROTAC^KEAP1 led to therapeutic benefits in managing AR symptoms, oxidative stress and inflammation. In summary, our findings underscore the efficacy of targeting the Keap1 system through the homoPROTAC-ing technology as an innovative and promising treatment strategy for the incurable allergic disorders.

Objective:The establish a standardized training assessment indicator system for young teachers in medical colleges and universities, and to improve the quality of training.Methods:A preliminary assessment indicator system was established through literature analysis and small-sample expert interviews, and then the Delphi method was used to conduct consultation with 40 experts familiar with the standardized training of young teachers in medical colleges and universities. The assessment indicator system was modified based on the opinions of the experts, and consultation was conducted again until basically consistent opinions were obtained from the experts. The analytic hierarchy process was used to assign weights to each indicator, and SPSS 17.0 was used for data analysis and processing.Results:After two rounds of expert consultation, 35 experts agreed with each indicator at a rate of more than 90%, and their opinions were basically consistent. The weight variation coefficient (W value) of each indicator ranged from 0.00 to 0.15, indicating a high degree of concentration. Finally, a standardized training assessment indicator system was established for young teachers, which consisted of 4 first-level indicators, 11 second-level indicators, and 35 third-level indicators.Conclusions:This assessment indicator system provides a basis for scientific evaluation of the quality of standardized training for young teachers in medical colleges and universities and improves the quality and efficiency of standardized training for young teachers by "promoting construction through evaluation and promoting supervision through evaluation".

The blood flow in the aortic arch and branch vessels in vitro is simulated,and the blood model is optimized with a non-Newtonian model.A numerical simulation analysis is conducted based on bidirectional fluid-solid coupling to analyze the hemodynamic characteristics(blood flow velocity,vascular wall pressure and vascular wall stress)in a cardiac cycle,and discuss their relationships with the formation of aortic dissection.It is concluded that the long-term existence of"chaotic"blood flow distribution in the blood vessel and the sudden changes of wall pressure and wall stress are liable to cause changes in the structure and function of the cells of the arterial wall,and ultimately induce the formation of aortic dissection.The study provides a more reliable basis for medical diagnosis,and further protects the life,health and safety of patients.