Osteocytes are mechanosensitive bone cells, but little is known about their effects on tumor cells in response to mechanical stimulation. We treated breast cancer cells with osteocyte-derived conditioned medium(CM) an...Osteocytes are mechanosensitive bone cells, but little is known about their effects on tumor cells in response to mechanical stimulation. We treated breast cancer cells with osteocyte-derived conditioned medium(CM) and fluid flow-treated conditioned medium(FFCM) with 0.25 Pa and 1 Pa shear stress. Notably, CM and FFCM at 0.25 Pa induced the mesenchymal-to-epithelial transition(MET), but FFCM at 1 Pa induced the epithelial-to-mesenchymal transition(EMT). This suggested that the effects of fluid flow on conditioned media depend on flow intensity. Fluorescence resonance energy transfer(FRET)-based evaluation of Src activity and vinculin molecular force showed that osteopontin was involved in EMT and MET switching. A mouse model of tumorinduced osteolysis was tested using dynamic tibia loadings of 1, 2, and 5 N. The low 1 N loading suppressed tumor-induced osteolysis, but this beneficial effect was lost and reversed with loads at 2 and 5 N, respectively. Changing the loading intensities in vivo also led to changes in serum TGFβ levels and the composition of tumor-associated volatile organic compounds in the urine.Collectively, this study demonstrated the critical role of intensity-dependent mechanotransduction and osteopontin in tumorosteocyte communication, indicating that a biophysical factor can tangibly alter the behaviors of tumor cells in the bone microenvironment.展开更多
Typhoons are one of the most serious natural disasters that occur annually on China’s southeast coast.A technique for analyzing the typhoon wind hazard was developed based on the empirical track model,and used to gen...Typhoons are one of the most serious natural disasters that occur annually on China’s southeast coast.A technique for analyzing the typhoon wind hazard was developed based on the empirical track model,and used to generate 1000-year virtual typhoons for Northwest Pacific basin.The influences of typhoon decay model,track model,and the extreme value distribution on the predicted extreme wind speed were investigated.We found that different typhoon decay models have least influence on the predicted extreme wind speed.Over most of the southeast coast of China,the predicted wind speed by the non-simplified empirical track model is larger than that from the simplified tracking model.The extreme wind speed predicted by different extreme value distribution is quite different.Four super typhoons Meranti(2016),Hato(2017),Mangkhut(2018)and Lekima(2019)were selected and the return periods of typhoon wind speeds along the China southeast coast were estimated in order to assess the typhoon wind hazard.展开更多
基金supported in part by funds from the breast cancer advocacy group 100 Voices of Hope, as well as by NIHR01 AR52144, R03 CA238555 (HY) and R01 AR053237 (AGR).NIHR01 AR52144,R03 CA238555 (HY) and R01 AR053237 (AGR)100 Voices of Hope (HY)。
文摘Osteocytes are mechanosensitive bone cells, but little is known about their effects on tumor cells in response to mechanical stimulation. We treated breast cancer cells with osteocyte-derived conditioned medium(CM) and fluid flow-treated conditioned medium(FFCM) with 0.25 Pa and 1 Pa shear stress. Notably, CM and FFCM at 0.25 Pa induced the mesenchymal-to-epithelial transition(MET), but FFCM at 1 Pa induced the epithelial-to-mesenchymal transition(EMT). This suggested that the effects of fluid flow on conditioned media depend on flow intensity. Fluorescence resonance energy transfer(FRET)-based evaluation of Src activity and vinculin molecular force showed that osteopontin was involved in EMT and MET switching. A mouse model of tumorinduced osteolysis was tested using dynamic tibia loadings of 1, 2, and 5 N. The low 1 N loading suppressed tumor-induced osteolysis, but this beneficial effect was lost and reversed with loads at 2 and 5 N, respectively. Changing the loading intensities in vivo also led to changes in serum TGFβ levels and the composition of tumor-associated volatile organic compounds in the urine.Collectively, this study demonstrated the critical role of intensity-dependent mechanotransduction and osteopontin in tumorosteocyte communication, indicating that a biophysical factor can tangibly alter the behaviors of tumor cells in the bone microenvironment.
基金Supported by the National Key Research and Development Program of China(Nos.2016YFC1402000,2018YFC1407003,2016YFC1402004)the National Natural Science Foundation of China(Nos.U1606402,41421005)the Strategic Priority Research Program of the Chinese Academy of Sciences(Nos.XDA19060202,XDA19060502)。
文摘Typhoons are one of the most serious natural disasters that occur annually on China’s southeast coast.A technique for analyzing the typhoon wind hazard was developed based on the empirical track model,and used to generate 1000-year virtual typhoons for Northwest Pacific basin.The influences of typhoon decay model,track model,and the extreme value distribution on the predicted extreme wind speed were investigated.We found that different typhoon decay models have least influence on the predicted extreme wind speed.Over most of the southeast coast of China,the predicted wind speed by the non-simplified empirical track model is larger than that from the simplified tracking model.The extreme wind speed predicted by different extreme value distribution is quite different.Four super typhoons Meranti(2016),Hato(2017),Mangkhut(2018)and Lekima(2019)were selected and the return periods of typhoon wind speeds along the China southeast coast were estimated in order to assess the typhoon wind hazard.
