Background: Ankyrin repeat and SOCS box protein 3(ASB3) is a member of ASB family and contains ankyrin repeat sequence and SOCS box domain. Previous studies indicated that it mediates the ubiquitination and degradatio...Background: Ankyrin repeat and SOCS box protein 3(ASB3) is a member of ASB family and contains ankyrin repeat sequence and SOCS box domain. Previous studies indicated that it mediates the ubiquitination and degradation of tumor necrosis factor receptor 2 and is likely involved in inflammatory responses. However, its effects on oncogenesis are unclear. This study aimed to investigate the effects of ASB3 on the growth and metastasis of colorectal cancer(CRC).Methods: We used next?generation sequencing or Sanger sequencing to detect ASB3 mutations in CRC specimens or cell lines, and used real?time quantitative polymerase chain reaction, Western blotting, and immunohistochemical or immunofluorescence assay to determine gene expression. We evaluated cell proliferation by MTT and colony for?mation assays, tested cell cycle distribution by flow cytometry, and assessed cell migration and invasion by transwell and wound healing assays. We also performed nude mouse experiments to evaluate tumorigenicity and hepatic metastasis potential of tumor cells.Results: We found that ASB3 gene was frequently mutated(5.3%) and down?regulated(70.4%) in CRC cases. Knock?down of endogenous ASB3 expression promoted CRC cell proliferation, migration, and invasion in vitro and facilitated tumorigenicity and hepatic metastasis in vivo. Conversely, the ectopic overexpression of wild?type ASB3, but not that of ASB3 mutants that occurred in clinical CRC tissues, inhibited tumor growth and metastasis. Further analysis showed that ASB3 inhibited CRC metastasis likely by retarding epithelial?mesenchymal transition, which was characterized by the up?regulation of β?catenin and E?cadherin and the down?regulation of transcription factor 8, N?cadherin, and vimentin.Conclusion: ASB3 dysfunction resulted from gene mutations or down?regulated expression frequently exists in CRC and likely plays a key role in the pathogenesis and progression of CRC.展开更多
Coal and gas outburst is a complex dynamic disaster during coal underground mining.Revealing the disaster mechanism is of great signifcance for accurate prediction and prevention of coal and gas outburst.The geo-dynam...Coal and gas outburst is a complex dynamic disaster during coal underground mining.Revealing the disaster mechanism is of great signifcance for accurate prediction and prevention of coal and gas outburst.The geo-dynamic system of coal and gas outburst is proposed.The framework of geo-dynamic system is composed of gassy coal mass,geological dynamic environment and mining disturbance.Equations of stress–damage–seepage interaction for gassy coal mass is constructed to resolve the outburst elimination process by gas extraction with boreholes through layer in foor roadway.The results show the occurrence of outburst is divided into the evolution process of gestation,formation,development and termination of geo-dynamic system.The scale range of outburst occurrence is determined,which provides a spatial basis for the prevention and control of outburst.The formation criterion and instability criterion of coal and gas outburst are established.The formation criterion F1 is defned as the scale of the geo-dynamic system,and the instability criterion F2 is defned as the scale of the outburst geo-body.According to the geo-dynamic system,the elimination mechanism of coal and gas outburst—‘unloading+depressurization’is established,and the gas extraction by boreholes through layer in foor roadway for outburst elimination is given.For the research case,when the gas extraction is 120 days,the gas pressure of the coal seam is reduced to below 0.4 MPa,and the outburst danger is eliminated efectively.展开更多
In deep underground engineering,understanding of time-related stress memory properties is critical to evaluate the in situ stress conditions of a rock mass.In this study,the time-sensitivity mechanism of the rock stre...In deep underground engineering,understanding of time-related stress memory properties is critical to evaluate the in situ stress conditions of a rock mass.In this study,the time-sensitivity mechanism of the rock stress memory properties under tensile stress was investigated.It was found that the material property(Poisson’s ratio)and crack angle were the controlling factors of the Kaiser effect(KE)under tensile stress.In particular,the time-sensitivity of the stress memory properties was closely related to the crack growth path.When the failure of the rock specimen was dominated by tensile microcracks and the crack development direction was deflected by up to 30°in the successive loading process,the stress memory capacity was likely to be time-independent for a sandstone specimen.The distribution of the Felicity ratio in a Brazilian test was more discrete than that in a three-point bending test It also showed that the changes in the crack path,rather than the time interval between successive loading cycles,led to inaccuracy of the detected KE.This study provides insights into stress memory-related issues under uniaxial or more complex stress conditions and thus facilitates development of methods for testing in situ mechanical behaviors of rocks with acoustic emission(AE)technology.展开更多
基金supported by the National Natural Science Foundation of China (No. 81472256, 81272638)the Guangdong Provincial Science and Technology Project (No. 2016A020215081, 2016A020217007)the National High Technology Research and Development Program of China (863 Program, No. 2012AA02A204)
文摘Background: Ankyrin repeat and SOCS box protein 3(ASB3) is a member of ASB family and contains ankyrin repeat sequence and SOCS box domain. Previous studies indicated that it mediates the ubiquitination and degradation of tumor necrosis factor receptor 2 and is likely involved in inflammatory responses. However, its effects on oncogenesis are unclear. This study aimed to investigate the effects of ASB3 on the growth and metastasis of colorectal cancer(CRC).Methods: We used next?generation sequencing or Sanger sequencing to detect ASB3 mutations in CRC specimens or cell lines, and used real?time quantitative polymerase chain reaction, Western blotting, and immunohistochemical or immunofluorescence assay to determine gene expression. We evaluated cell proliferation by MTT and colony for?mation assays, tested cell cycle distribution by flow cytometry, and assessed cell migration and invasion by transwell and wound healing assays. We also performed nude mouse experiments to evaluate tumorigenicity and hepatic metastasis potential of tumor cells.Results: We found that ASB3 gene was frequently mutated(5.3%) and down?regulated(70.4%) in CRC cases. Knock?down of endogenous ASB3 expression promoted CRC cell proliferation, migration, and invasion in vitro and facilitated tumorigenicity and hepatic metastasis in vivo. Conversely, the ectopic overexpression of wild?type ASB3, but not that of ASB3 mutants that occurred in clinical CRC tissues, inhibited tumor growth and metastasis. Further analysis showed that ASB3 inhibited CRC metastasis likely by retarding epithelial?mesenchymal transition, which was characterized by the up?regulation of β?catenin and E?cadherin and the down?regulation of transcription factor 8, N?cadherin, and vimentin.Conclusion: ASB3 dysfunction resulted from gene mutations or down?regulated expression frequently exists in CRC and likely plays a key role in the pathogenesis and progression of CRC.
基金supported by the National Natural Science Foundation of China(52004117,52174117 and 51674132)the Postdoctoral Science Foundation of China(2021T140290 and 2020M680975)the Discipline Innovation Team of Liaoning Technical University(LNTU20TD-03 and LNTU20TD-30).
文摘Coal and gas outburst is a complex dynamic disaster during coal underground mining.Revealing the disaster mechanism is of great signifcance for accurate prediction and prevention of coal and gas outburst.The geo-dynamic system of coal and gas outburst is proposed.The framework of geo-dynamic system is composed of gassy coal mass,geological dynamic environment and mining disturbance.Equations of stress–damage–seepage interaction for gassy coal mass is constructed to resolve the outburst elimination process by gas extraction with boreholes through layer in foor roadway.The results show the occurrence of outburst is divided into the evolution process of gestation,formation,development and termination of geo-dynamic system.The scale range of outburst occurrence is determined,which provides a spatial basis for the prevention and control of outburst.The formation criterion and instability criterion of coal and gas outburst are established.The formation criterion F1 is defned as the scale of the geo-dynamic system,and the instability criterion F2 is defned as the scale of the outburst geo-body.According to the geo-dynamic system,the elimination mechanism of coal and gas outburst—‘unloading+depressurization’is established,and the gas extraction by boreholes through layer in foor roadway for outburst elimination is given.For the research case,when the gas extraction is 120 days,the gas pressure of the coal seam is reduced to below 0.4 MPa,and the outburst danger is eliminated efectively.
基金funded by the National Natural Science Foundation of China(Grant No.51779021)Chongqing Natural Science Foundation(Grant No.cstc2019jcyj-msxm2176)Scientific and Technological Research Program of Chongqing Municipal Education Commission(Grant No.KJQN201800745).
文摘In deep underground engineering,understanding of time-related stress memory properties is critical to evaluate the in situ stress conditions of a rock mass.In this study,the time-sensitivity mechanism of the rock stress memory properties under tensile stress was investigated.It was found that the material property(Poisson’s ratio)and crack angle were the controlling factors of the Kaiser effect(KE)under tensile stress.In particular,the time-sensitivity of the stress memory properties was closely related to the crack growth path.When the failure of the rock specimen was dominated by tensile microcracks and the crack development direction was deflected by up to 30°in the successive loading process,the stress memory capacity was likely to be time-independent for a sandstone specimen.The distribution of the Felicity ratio in a Brazilian test was more discrete than that in a three-point bending test It also showed that the changes in the crack path,rather than the time interval between successive loading cycles,led to inaccuracy of the detected KE.This study provides insights into stress memory-related issues under uniaxial or more complex stress conditions and thus facilitates development of methods for testing in situ mechanical behaviors of rocks with acoustic emission(AE)technology.
