Background:Osteosarcoma is the most common bone malignancy in children and adolescents,and 20%-30%of the patients suffer from poor prognosis because of individual chemoresistance.The Hippo/yes-associated protein(YAP) ...Background:Osteosarcoma is the most common bone malignancy in children and adolescents,and 20%-30%of the patients suffer from poor prognosis because of individual chemoresistance.The Hippo/yes-associated protein(YAP) signaling pathway has been shown to play a role in tumor chemoresistance,but no previous report has focused on its involvement in osteosarcoma chemoresistance.This study aimed to investigate the role of the Hippo/YAP signaling pathway in osteosarcoma chemoresistance and to determine potential treatment targets.Methods:Using the Cell Titer-Glo Luminescent cell viability assay and flow cytometry analysis,we determined the proliferation and chemosensitivity of YAP-overexpressing and YAP-knockdown osteosarcoma cells.In addition,using western blotting and the real-time polymerase chain reaction technique,we investigated the alteration of the Hippo/YAP signaling pathway in osteosarcoma cells treated with chemotherapeutic agents.Results:Mammalian sterile 20-like kinase 1(MST1) degradation was increased,and large tumor suppressor kinase1/2(LAT51/2) total protein levels were decreased by methotrexate and doxorubicin,which increased activation and nuclear translocation of YAP.Moreover,YAP increased the proliferation and chemoresistance of MG63 cells.Conclusions:The Hippo/YAP signaling pathway plays a role in osteosarcoma chemoresistance,and YAP is a potential target for reducing chemoresistance.展开更多
A small focused library which comprised of L-AA lactone derivatives was built with a facile method.This reported method was optimized by modifying the acidity of the solvent.As a result,12 L-AA lactones were synthesiz...A small focused library which comprised of L-AA lactone derivatives was built with a facile method.This reported method was optimized by modifying the acidity of the solvent.As a result,12 L-AA lactones were synthesized.Among these lactones,lactones 8–12 were new compounds.The cytotoxicity of these synthetic compounds were investigated.展开更多
A simplified approach is proposed to reduce computational cost in conventional parametric optimization of open or in-filled trenches isolating rail-induced structural vibrations. In particular, it stands on an FEM-bas...A simplified approach is proposed to reduce computational cost in conventional parametric optimization of open or in-filled trenches isolating rail-induced structural vibrations. In particular, it stands on an FEM-based hybrid optimization scheme consisting of multiple two-dimensional models and one global three-dimensional model. First, representative planar FE （finite element） models orthogonal to the rail-direction are identified. For each section, the sensitivity of the trench＇s design parameters, such as geometry and backfill materials, to its vibration screening effect is respectively evaluated. Second, a full trench along the rail-direction is determined according to the two-dimensional optimization result. The global performance of the optimal trench is simulated in the three-dimensional model and finally becomes a reference for practical design. By optimizing the design parameters of a case study project, the proposed approach has shown the capability of solving complex engineering problems at a minimum computational cost, therefore is applicable in determining design parameters of rail-induced vibration isolation trenches.展开更多
基金supported by the National Natural Science Foundation of China(No.81172553 and 81472513 to WB)
文摘Background:Osteosarcoma is the most common bone malignancy in children and adolescents,and 20%-30%of the patients suffer from poor prognosis because of individual chemoresistance.The Hippo/yes-associated protein(YAP) signaling pathway has been shown to play a role in tumor chemoresistance,but no previous report has focused on its involvement in osteosarcoma chemoresistance.This study aimed to investigate the role of the Hippo/YAP signaling pathway in osteosarcoma chemoresistance and to determine potential treatment targets.Methods:Using the Cell Titer-Glo Luminescent cell viability assay and flow cytometry analysis,we determined the proliferation and chemosensitivity of YAP-overexpressing and YAP-knockdown osteosarcoma cells.In addition,using western blotting and the real-time polymerase chain reaction technique,we investigated the alteration of the Hippo/YAP signaling pathway in osteosarcoma cells treated with chemotherapeutic agents.Results:Mammalian sterile 20-like kinase 1(MST1) degradation was increased,and large tumor suppressor kinase1/2(LAT51/2) total protein levels were decreased by methotrexate and doxorubicin,which increased activation and nuclear translocation of YAP.Moreover,YAP increased the proliferation and chemoresistance of MG63 cells.Conclusions:The Hippo/YAP signaling pathway plays a role in osteosarcoma chemoresistance,and YAP is a potential target for reducing chemoresistance.
基金This work was financially supported by the National Natural Science Foundation of China(No.U0932602)the National Basic Research Program of China(973 Program No.2011CB915503).
文摘A small focused library which comprised of L-AA lactone derivatives was built with a facile method.This reported method was optimized by modifying the acidity of the solvent.As a result,12 L-AA lactones were synthesized.Among these lactones,lactones 8–12 were new compounds.The cytotoxicity of these synthetic compounds were investigated.
文摘A simplified approach is proposed to reduce computational cost in conventional parametric optimization of open or in-filled trenches isolating rail-induced structural vibrations. In particular, it stands on an FEM-based hybrid optimization scheme consisting of multiple two-dimensional models and one global three-dimensional model. First, representative planar FE （finite element） models orthogonal to the rail-direction are identified. For each section, the sensitivity of the trench＇s design parameters, such as geometry and backfill materials, to its vibration screening effect is respectively evaluated. Second, a full trench along the rail-direction is determined according to the two-dimensional optimization result. The global performance of the optimal trench is simulated in the three-dimensional model and finally becomes a reference for practical design. By optimizing the design parameters of a case study project, the proposed approach has shown the capability of solving complex engineering problems at a minimum computational cost, therefore is applicable in determining design parameters of rail-induced vibration isolation trenches.
