Ballastless tracks have been widely applied in high-speed railway (HSR). The adaptability research between continuous welded rails (CWR) and long-span bridges of HSR is of great practical engineering significance. Bas...Ballastless tracks have been widely applied in high-speed railway (HSR). The adaptability research between continuous welded rails (CWR) and long-span bridges of HSR is of great practical engineering significance. Based on the HSR long-span continuous bridges, the integrative spatial finite element model of track-bridge-pier-foundation system was established with the nonlinear spring element simulating the longitudinal resistance between track and bridge. Comparative study on the various additional longitudinal forces of CWR using the common fasteners and small resistance fasteners was carried out. Analysis results indicate that the additional expansion forces and additional rail-breaking forces in long-span ballastless continuous girders can be reduced evidently by 40% 50% after adopting small resistance fasteners, but lead to greater rail broken gap. The small resistance fasteners have little influence on the additional force only caused by vertical load, but can reduce the additional force caused by vertical load combined with braking load by over 10%. Besides, transient analysis method is proved to be more accurate and safe in calculating additional longitudinal forces when the train running or braking on the bridge, compared with the traditional static method.展开更多
Cancerous inhibitor of protein phosphatase 2A(CIP2A) is a human oncoprotein that is overexpressed in multiple kinds of cancers including non-small cell lung cancer(NSCLC). CIP2A plays an ’oncogenic nexus’ to partici...Cancerous inhibitor of protein phosphatase 2A(CIP2A) is a human oncoprotein that is overexpressed in multiple kinds of cancers including non-small cell lung cancer(NSCLC). CIP2A plays an ’oncogenic nexus’ to participate in the tumorigenesis and chemoresistance in several cancer types. AKT and m TORC1 overactivation are detected in NSCLC and many other cancers. Previous studies found that the CIP2A/AKT/m TOR pathway controls cell growth, apoptosis, autophagy process. Polyphyllin I(PPI) and polyphyllin VII(PPVII) are natural components extracted from Paris polyphylla that display anti-cancer properties. In the present study, we investigated whether PPI and PPVII can be used in the cisplatin(DDP)-resistant human NSCLC cell line A549/DDP. Results demonstrated that PPI and PPVII treatment significantly suppressed A549/DDP cell proliferation, migration, invasion and EMT, induced apoptosis and autophagy. Further examination of the mechanism revealed that the PPI and PPVII significantly upregulated the p53, induced caspase-dependent apoptosis and suppressed the CIP2A/AKT/m TOR pathway. The activation of autophagy was mediated through PPI and PPVII induced inhibition of m TOR. We propose that PPI and PPVII might be developed as candidate drugs for DDP-resistant NSCLC.展开更多
Recent evidence suggests that the condition of the gut and its microbiota greatly influence the course of liver disease,especially cirrhosis.This introduces the concept of the gut-liver axis,which can be imagined as a...Recent evidence suggests that the condition of the gut and its microbiota greatly influence the course of liver disease,especially cirrhosis.This introduces the concept of the gut-liver axis,which can be imagined as a chain connected by several links.Gut dysbiosis,small intestinal bacterial overgrowth,and intestinal barrier alteration lead to bacterial translocation,resulting in systemic inflammation.Systemic inflammation further causes vasodilation,arterial hypotension,and hyperdynamic circulation,leading to the aggravation of portal hypertension,which contributes to the development of complications of cirrhosis,resulting in a poorer prognosis.The majority of the data underlying this model were obtained initially from animal experiments,and most of these correlations were further reproduced in studies including patients with cirrhosis.However,despite the published data on the relationship of the disorders of the gut microbiota with the complications of cirrhosis and the proposed pathogenetic role of hemodynamic disorders in their development,the direct relations between gut dysbiosis and hemodynamic changes in this disease are poorly studied.They remain a missing link in the gut-liver axis and a challenge for future research.展开更多
Nowadays, the mitigation of damage to a ship caused by the underwater explosion attracts more and more attention from the modern ship designers. In this study, two kinds of scale tests were conducted to investigate th...Nowadays, the mitigation of damage to a ship caused by the underwater explosion attracts more and more attention from the modern ship designers. In this study, two kinds of scale tests were conducted to investigate the effects of polyurea coatings on the blast resistance of hulls subjected to underwater explosion. Firstly, small-scale model tests with different polyurea coatings were carried out. Results indicate that polyurea has a better blast resistance performance when coated on the front face, which can effectively reduce the maximum deflection of the steel plate by more than 20% and reduce the deformation energy by 35.7%-45.4%. Next, a full-scale ship(approximately 50 m × 9 m) under loadings produced by the detonation of 33 kg of spherical TNT charges was tested, where a part of the ship was coated with polyurea on the front face(8 mm + 24 mm) and not on the contrast area. Damage characteristics on the bottom were statistically analyzed based on a 3D scanning technology, indicating that polyurea contributes to enhancing the blast protection of the ship. However, damage results of this test were different from those of the small-scale tests. Moreover, the deformation area of the bottom with polyurea was greatly increased by 40.1% to disperse explosion energy, a conclusion that cannot be drown from the small-scale tests.展开更多
Small cell lung cancer(SCLC)is a highly malignant tumor with a very poor prognosis;therefore,more effective treatments are urgently needed for patients afflicted with the disease.In recent years,emerging molecular cla...Small cell lung cancer(SCLC)is a highly malignant tumor with a very poor prognosis;therefore,more effective treatments are urgently needed for patients afflicted with the disease.In recent years,emerging molecular classifications based on key transcription factors of SCLC have provided more information on the tumor pathophysiology,metastasis,immune microenvironment,and acquired therapeutic resistance and reflected the intertumoral heterogeneity of the various SCLC phenotypes.Additionally,advances in genomics and single-cell sequencing analysis have further revealed the high intratumoral heterogeneity and plasticity of the disease.Herein,we review and summarize these recent lines of evidence and discuss the possible pathogenesis of SCLC.展开更多
基金Projects(50908232, 51108460) supported by the National Natural Science Foundation of China
文摘Ballastless tracks have been widely applied in high-speed railway (HSR). The adaptability research between continuous welded rails (CWR) and long-span bridges of HSR is of great practical engineering significance. Based on the HSR long-span continuous bridges, the integrative spatial finite element model of track-bridge-pier-foundation system was established with the nonlinear spring element simulating the longitudinal resistance between track and bridge. Comparative study on the various additional longitudinal forces of CWR using the common fasteners and small resistance fasteners was carried out. Analysis results indicate that the additional expansion forces and additional rail-breaking forces in long-span ballastless continuous girders can be reduced evidently by 40% 50% after adopting small resistance fasteners, but lead to greater rail broken gap. The small resistance fasteners have little influence on the additional force only caused by vertical load, but can reduce the additional force caused by vertical load combined with braking load by over 10%. Besides, transient analysis method is proved to be more accurate and safe in calculating additional longitudinal forces when the train running or braking on the bridge, compared with the traditional static method.
基金supported by the National Natural Science Foundation of China(No.81473485)the Natural Science Foundation of Shandong Province(No.2014ZRE27321)
文摘Cancerous inhibitor of protein phosphatase 2A(CIP2A) is a human oncoprotein that is overexpressed in multiple kinds of cancers including non-small cell lung cancer(NSCLC). CIP2A plays an ’oncogenic nexus’ to participate in the tumorigenesis and chemoresistance in several cancer types. AKT and m TORC1 overactivation are detected in NSCLC and many other cancers. Previous studies found that the CIP2A/AKT/m TOR pathway controls cell growth, apoptosis, autophagy process. Polyphyllin I(PPI) and polyphyllin VII(PPVII) are natural components extracted from Paris polyphylla that display anti-cancer properties. In the present study, we investigated whether PPI and PPVII can be used in the cisplatin(DDP)-resistant human NSCLC cell line A549/DDP. Results demonstrated that PPI and PPVII treatment significantly suppressed A549/DDP cell proliferation, migration, invasion and EMT, induced apoptosis and autophagy. Further examination of the mechanism revealed that the PPI and PPVII significantly upregulated the p53, induced caspase-dependent apoptosis and suppressed the CIP2A/AKT/m TOR pathway. The activation of autophagy was mediated through PPI and PPVII induced inhibition of m TOR. We propose that PPI and PPVII might be developed as candidate drugs for DDP-resistant NSCLC.
文摘Recent evidence suggests that the condition of the gut and its microbiota greatly influence the course of liver disease,especially cirrhosis.This introduces the concept of the gut-liver axis,which can be imagined as a chain connected by several links.Gut dysbiosis,small intestinal bacterial overgrowth,and intestinal barrier alteration lead to bacterial translocation,resulting in systemic inflammation.Systemic inflammation further causes vasodilation,arterial hypotension,and hyperdynamic circulation,leading to the aggravation of portal hypertension,which contributes to the development of complications of cirrhosis,resulting in a poorer prognosis.The majority of the data underlying this model were obtained initially from animal experiments,and most of these correlations were further reproduced in studies including patients with cirrhosis.However,despite the published data on the relationship of the disorders of the gut microbiota with the complications of cirrhosis and the proposed pathogenetic role of hemodynamic disorders in their development,the direct relations between gut dysbiosis and hemodynamic changes in this disease are poorly studied.They remain a missing link in the gut-liver axis and a challenge for future research.
基金the project of State Key Laboratory of Explosion Science and Technology(Beijing Institute of Technology).The project number is NO.QNKT19-04.
文摘Nowadays, the mitigation of damage to a ship caused by the underwater explosion attracts more and more attention from the modern ship designers. In this study, two kinds of scale tests were conducted to investigate the effects of polyurea coatings on the blast resistance of hulls subjected to underwater explosion. Firstly, small-scale model tests with different polyurea coatings were carried out. Results indicate that polyurea has a better blast resistance performance when coated on the front face, which can effectively reduce the maximum deflection of the steel plate by more than 20% and reduce the deformation energy by 35.7%-45.4%. Next, a full-scale ship(approximately 50 m × 9 m) under loadings produced by the detonation of 33 kg of spherical TNT charges was tested, where a part of the ship was coated with polyurea on the front face(8 mm + 24 mm) and not on the contrast area. Damage characteristics on the bottom were statistically analyzed based on a 3D scanning technology, indicating that polyurea contributes to enhancing the blast protection of the ship. However, damage results of this test were different from those of the small-scale tests. Moreover, the deformation area of the bottom with polyurea was greatly increased by 40.1% to disperse explosion energy, a conclusion that cannot be drown from the small-scale tests.
基金supported by grants from the Jilin Scientific and Technological Development Program(CN)(No.20190303146SF)General Program of National Natural Science Foundation of China(No.81874052)
文摘Small cell lung cancer(SCLC)is a highly malignant tumor with a very poor prognosis;therefore,more effective treatments are urgently needed for patients afflicted with the disease.In recent years,emerging molecular classifications based on key transcription factors of SCLC have provided more information on the tumor pathophysiology,metastasis,immune microenvironment,and acquired therapeutic resistance and reflected the intertumoral heterogeneity of the various SCLC phenotypes.Additionally,advances in genomics and single-cell sequencing analysis have further revealed the high intratumoral heterogeneity and plasticity of the disease.Herein,we review and summarize these recent lines of evidence and discuss the possible pathogenesis of SCLC.
