Programmable and Reversible Integrin-Mediated Cell Adhesion Reveals Hysteresis in Actin Kinetics that Alters Subsequent Mechanotransduction.

Dynamically evolving adhesions between cells and extracellular matrix (ECM) transmit time-varying signals that control cytoskeletal dynamics and cell fate. Dynamic cell adhesion and ECM stiffness regulate cellular mechanosensing cooperatively, but it has not previously been possible to characterize their individual effects because of challenges with controlling these factors independently. Therefore, a DNA-driven molecular system is developed wherein the integrin-binding ligand RGD can be reversibly presented and removed to achieve cyclic cell attachment/detachment on substrates of defined stiffness. Using this culture system, it is discovered that cyclic adhesion accelerates F-actin kinetics and nuclear mechanosensing in human mesenchymal stem cells (hMSCs), with the result that hysteresis can completely change how hMSCs transduce ECM stiffness. Results are dramatically different from well-known results for mechanotransduction on static substrates, but are consistent with a mathematical model of F-actin fragments retaining structure following loss of integrin ligation and participating in subsequent repolymerization. These findings suggest that cyclic integrin-mediated adhesion alters the mechanosensing of ECM stiffness by hMSCs through transient, hysteretic memory that is stored in F-actin.

[Hormone replacement therapy in perimenopausal women with chronic tinnitus].

Objective:To explore and analyze the effect and indication of hormone replacement therapy（HRT） in perimenopausal women with chronic tinnitus. Methods:The perimenopausal women with chronic tinnitus were divided into mild group and moderate to severe group according to Kupperman score of menopause, and then were divided into treatment group and untreated group according to whether they received MHT treatment or not. The serum 5-HT level, tinnitus handicap inventory （THI） and Pittsburgh sleep quality index （PSQI） were compared before and after treatment. Results:In moderate to severe perimenopausal tinnitus, the serum 5-HT level, THI and PSQI in the treatment group were statistically different before and after treatment（P<0.05）, and no significant difference was found in the untreated group. In mild perimenopausal tinnitus, there was no significant difference in 5-HT levels, THI and PSQI between the treated group and the untreated group before and after treatment. The 5-HT levels were correlated with THI. The lower the 5-HT level was, the more severe tinnitus was. Conclusion:HRT is helpful in the treatment of perimenopausal chronic tinnitus, especially in moderate to severe perimenopausal patients, and is recommended for clinical use.