Atherosclerosis (AS) is the main cause of death and disability all over the world. A lot of efforts have been devoted to treat AS, among which tissue engineering blood vessel materials, including artificial blood vess...Atherosclerosis (AS) is the main cause of death and disability all over the world. A lot of efforts have been devoted to treat AS, among which tissue engineering blood vessel materials, including artificial blood vessels, stents and vascular patches, have brought hope to ameliorate the symptoms in AS patients. However, there remains a large percentage of implantation failure due to the incompatibility of the material with the body. AS is a multi-factor related disease, and chronic inflammation is a major event that involves with its pathogenesis and development. Since previous studies suggested that the stiffness of the blood vessel might affect the inflammatory conditions, in this paper, we investigate the mechanism of how substrate stiffness could affect the inflammation response of the endothelial cells (ECs). Polyacrylamide (PA) based hydrogels at different concentrations were used as the culture substrate for ECs. The mRNA expression level of VCAM-1 and ICAM-1 was determined by qRT-PCR. EC chemotactic effect was evaluated by the number of THP-1 adhered to EC monolayer. The protein levels of IκBα and NF-κB were determined by western blotting analysis. The expression and localization of the major adherens junctions (AJs) proteins, VE-cadherin and β-catenin, were evaluated by western blotting and immunofluorescence staining. Our results showed that ECs cultured on soft substrate (1 kPa) demonstrated more chemotactic effect and the amount of the monocytes adhered to them was higher than that on harder substrate (20 kPa, p < 0.05). Moreover, NF-κB signaling pathway in ECs on 1 kPa substrate was more activated compared to those on 20 kPa substrate, with the IκBα protein expression level in the cytoplasm decreasing and NF-κB translocating more into the nuclear. In addition, the AJs of the endothelial monolayer changed with the substrate stiffness. Compared with ECs on normal substrate (20 kPa), the protein expression level of β-catenin decreased (p < 0.05), and immunofluorescence staining of VE-cadherin and β-catenin showed the AJs between the ECs on soft substrate (1 kPa) were punctuated. Taken together, our results suggested the stiffness of the substrate was important in regulating inflammation of the ECs and the integrity of the cell-cell junction. Therefore, the stiffness of the tissue engineering blood vessel material should be considered as an important criterium to avoid EC inflammation.展开更多
The pathogenesis of atherosclerosis is accompanied by chronic inflammation with changes in the stiffness of the coronary artery wall. Being the main component of the vascular media, the smooth muscle cells (SMCs) are ...The pathogenesis of atherosclerosis is accompanied by chronic inflammation with changes in the stiffness of the coronary artery wall. Being the main component of the vascular media, the smooth muscle cells (SMCs) are crucial to maintain blood vessel function. SMCs are mechano-sensitive, which can rapidly adapt to the fluctuations in the microenvironment of the blood vessel, including the subtle changes of the vascular stiffness. However, how substrate stiffness influences the phenotype and inflammatory response of SMCs is not well understood. In this study, we investigated the effects of substrate stiffness on SMCs phenotype, inflammatory gene expression and the nuclear factorkappa B (NFκB) signaling pathway of vascular SMCs. From 1 kPa to 100 kPa, the SMCs cytoskeleton became more and more organized with the increase of the substrate stiffness, representing by the uniformed distribution of the stress fibers. SMCs cultured on both soft (1 kPa) and hard (100 kPa) substrate increased the expression of macrophage marker CD68 molecule (CD68) and Galectin 3 (LGALS3) and the inflammatory gene Interleukin-6 (IL-6) and Interleukin-1β (IL-1β) than those on 40 kPa substrate. Moreover, the protein expression level of phosphorylated nuclear factor kappa B inhibitor (p-IκB) was higher on either soft (1 kPa) or hard (100 kPa) substrate. In consistent, the dephosphorylated IκB showed a higher expression level on the substrate stiffness of 40 kPa. These results suggested that substrate stiffness played an important role in SMCs cell morphology, phenotype and inflammatory response by affecting NFκB signaling pathway.展开更多
The aerodynamic performance of high-speed trains passing each other was investigated on a simply supported box girder bridge,with a span of 32 m,under crosswinds.The bridge and train models,modeled at a geometric scal...The aerodynamic performance of high-speed trains passing each other was investigated on a simply supported box girder bridge,with a span of 32 m,under crosswinds.The bridge and train models,modeled at a geometric scale ratio of 1:30,were used to test the aerodynamic forces of the train,with the help of a designed moving test rig in the XNJD-3 wind tunnel.The effects of wind speed,train speed,and yaw angle on the aerodynamic coefficients of the train were analyzed.The static and moving model tests were compared to demonstrate how the movement of the train influences its aerodynamic characteristics.The results show that the sheltering effect introduced by trains passing each other can cause a sudden change in force on the leeward train,which is further influenced by the wind and running speeds.Detailed analyses related to the effect of wind and train speeds on the aerodynamic coefficients were conducted.The relationship between the change in aerodynamic coefficients and yaw angle was finally described by a series of proposed fitting formulas.展开更多
文摘Atherosclerosis (AS) is the main cause of death and disability all over the world. A lot of efforts have been devoted to treat AS, among which tissue engineering blood vessel materials, including artificial blood vessels, stents and vascular patches, have brought hope to ameliorate the symptoms in AS patients. However, there remains a large percentage of implantation failure due to the incompatibility of the material with the body. AS is a multi-factor related disease, and chronic inflammation is a major event that involves with its pathogenesis and development. Since previous studies suggested that the stiffness of the blood vessel might affect the inflammatory conditions, in this paper, we investigate the mechanism of how substrate stiffness could affect the inflammation response of the endothelial cells (ECs). Polyacrylamide (PA) based hydrogels at different concentrations were used as the culture substrate for ECs. The mRNA expression level of VCAM-1 and ICAM-1 was determined by qRT-PCR. EC chemotactic effect was evaluated by the number of THP-1 adhered to EC monolayer. The protein levels of IκBα and NF-κB were determined by western blotting analysis. The expression and localization of the major adherens junctions (AJs) proteins, VE-cadherin and β-catenin, were evaluated by western blotting and immunofluorescence staining. Our results showed that ECs cultured on soft substrate (1 kPa) demonstrated more chemotactic effect and the amount of the monocytes adhered to them was higher than that on harder substrate (20 kPa, p < 0.05). Moreover, NF-κB signaling pathway in ECs on 1 kPa substrate was more activated compared to those on 20 kPa substrate, with the IκBα protein expression level in the cytoplasm decreasing and NF-κB translocating more into the nuclear. In addition, the AJs of the endothelial monolayer changed with the substrate stiffness. Compared with ECs on normal substrate (20 kPa), the protein expression level of β-catenin decreased (p < 0.05), and immunofluorescence staining of VE-cadherin and β-catenin showed the AJs between the ECs on soft substrate (1 kPa) were punctuated. Taken together, our results suggested the stiffness of the substrate was important in regulating inflammation of the ECs and the integrity of the cell-cell junction. Therefore, the stiffness of the tissue engineering blood vessel material should be considered as an important criterium to avoid EC inflammation.
文摘The pathogenesis of atherosclerosis is accompanied by chronic inflammation with changes in the stiffness of the coronary artery wall. Being the main component of the vascular media, the smooth muscle cells (SMCs) are crucial to maintain blood vessel function. SMCs are mechano-sensitive, which can rapidly adapt to the fluctuations in the microenvironment of the blood vessel, including the subtle changes of the vascular stiffness. However, how substrate stiffness influences the phenotype and inflammatory response of SMCs is not well understood. In this study, we investigated the effects of substrate stiffness on SMCs phenotype, inflammatory gene expression and the nuclear factorkappa B (NFκB) signaling pathway of vascular SMCs. From 1 kPa to 100 kPa, the SMCs cytoskeleton became more and more organized with the increase of the substrate stiffness, representing by the uniformed distribution of the stress fibers. SMCs cultured on both soft (1 kPa) and hard (100 kPa) substrate increased the expression of macrophage marker CD68 molecule (CD68) and Galectin 3 (LGALS3) and the inflammatory gene Interleukin-6 (IL-6) and Interleukin-1β (IL-1β) than those on 40 kPa substrate. Moreover, the protein expression level of phosphorylated nuclear factor kappa B inhibitor (p-IκB) was higher on either soft (1 kPa) or hard (100 kPa) substrate. In consistent, the dephosphorylated IκB showed a higher expression level on the substrate stiffness of 40 kPa. These results suggested that substrate stiffness played an important role in SMCs cell morphology, phenotype and inflammatory response by affecting NFκB signaling pathway.
基金This work was financially supported by the National Natural Science Foundation of China (U1434205, 51708645).
文摘The aerodynamic performance of high-speed trains passing each other was investigated on a simply supported box girder bridge,with a span of 32 m,under crosswinds.The bridge and train models,modeled at a geometric scale ratio of 1:30,were used to test the aerodynamic forces of the train,with the help of a designed moving test rig in the XNJD-3 wind tunnel.The effects of wind speed,train speed,and yaw angle on the aerodynamic coefficients of the train were analyzed.The static and moving model tests were compared to demonstrate how the movement of the train influences its aerodynamic characteristics.The results show that the sheltering effect introduced by trains passing each other can cause a sudden change in force on the leeward train,which is further influenced by the wind and running speeds.Detailed analyses related to the effect of wind and train speeds on the aerodynamic coefficients were conducted.The relationship between the change in aerodynamic coefficients and yaw angle was finally described by a series of proposed fitting formulas.
