Background:The prognostic significance of the chemokine receptor CCR7 in diffuse large B-cell lymphoma(DLBCL)has been reported previously.However,the detailed mechanisms of CCR7 in DLBCL,particularly regarding its int...Background:The prognostic significance of the chemokine receptor CCR7 in diffuse large B-cell lymphoma(DLBCL)has been reported previously.However,the detailed mechanisms of CCR7 in DLBCL,particularly regarding its interaction with lenalidomide treatment,are not fully understood.Methods:Our study utilized bioinformatics approaches to identify hub genes in SU-DHL-2 cell lines treated with lenalidomide compared to control groups.Immunohistochemical data and clinical information from 122 patients with DLBCL were analyzed to assess the correlation of CCR7 and p-ERK1/2 expression with the prognosis of DLBCL.Furthermore,in vitro and in vivo experiments were conducted to clarify the role of CCR7 in the response of DLBCL to lenalidomide treatment.Results:Our bioinformatics analysis pinpointed CCR7 as a hub gene in the context of lenalidomide treatment in DLBCL.Notably,31.14%and 36.0%(44/122)of DLBCL cases showed positive expression for CCR7 and ERK1/2 respectively,establishing them as independent prognostic factors for adverse outcomes in DLBCL via multivariate Cox regression analysis.Additionally,our studies demonstrated that the external application of the protein CCL21 promoted proliferation,migration,invasion,and activation of the ERK1/2 pathway in SU-DHL-2 and OCI-LY3 cell lines with high levels of CCR7 expression.This effect was mitigated by CCR7 silencing through siRNA,application of ERK inhibitors,or lenalidomide treatment.In vivo experiments reinforced the efficacy of lenalidomide,significantly reducing tumor growth rate,tumor mass,serum total LDH levels,and expression of CCR7 and p-ERK1/2 in a SUDHL-2 xenograft model in nude mice(p<0.05).Conclusion:Our study clarifies the potential role of the CCL21/CCR7/ERK1/2 axis in the therapeutic effects of lenalidomide in DLBCL treatment.展开更多
Background:Diabetic cardiomyopathy(DCM)is a type of cardiomyopathy caused by long-term diabetes,characterized by abnormal myocardial structure and function,which can lead to heart failure.Berberine(BBR),a quaternary a...Background:Diabetic cardiomyopathy(DCM)is a type of cardiomyopathy caused by long-term diabetes,characterized by abnormal myocardial structure and function,which can lead to heart failure.Berberine(BBR),a quaternary ammonium alkaloid isolated from Coptidis Rhizoma,a traditional Chinese medicine,has superior anti-diabetic and heart-protective properties.The purpose of this study is to assess the impact of BBR on DCM.Methods:This study used a systems pharmacology approach to evaluate the related proteins and signalling pathways between BBR and DCM targets,combined with experimental validation using diabetic mouse heart sections.Microstructural and pathological changes were observed using Hematoxylin-eosin,Masson’s trichrome stain and wheat germ agglutinin staining.Immunofluorescence and western blot were used to determine protein expression.Results:The results indicate that BBR and DCM share 21 core relevant targets,with cross-targets predominantly located in mitochondrial,endoplasmic reticulum,and plasma membrane components.BBR exerts its main effects in improving DCM by maintaining mitochondrial integrity,particularly involving the PI3K-AKT-GSK3βand apoptosis signalling pathways.In addition,post-treatment changes in the key targets of BBR,including cysteine aspartate specific protease(Caspase)-3,phosphoinositide 3-kinase(PI3K)and mitochondria-related proteins,are suggestive of its efficacy.Conclusion:BBR crucially improves DCM by maintaining mitochondrial integrity,inhibiting apoptosis,and modulating PI3K-AKT-GSK3βsignaling.Further studies must address animal model limitations and validate clinical efficacy to understand BBR’s mechanisms fully and its potential clinical use.展开更多
A rapidly deployable dense seismic monitoring system which is capable of transmitting acquired data in real time and analyzing data automatically is crucial in seismic hazard mitigation after a major earthquake.Howeve...A rapidly deployable dense seismic monitoring system which is capable of transmitting acquired data in real time and analyzing data automatically is crucial in seismic hazard mitigation after a major earthquake.However,it is rather difficult for current seismic nodal stations to transmit data in real time for an extended period of time,and it usually takes a great amount of time to process the acquired data manually.To monitor earthquakes in real time flexibly,we develop a mobile integrated seismic monitoring system consisting of newly developed nodal units with 4G telemetry and a real-time AI-assisted automatic data processing workflow.The integrated system is convenient for deployment and has been successfully applied in monitoring the aftershocks of the Yangbi M_(S) 6.4 earthquake occurred on May 21,2021 in Yangbi County,Dali,Yunnan in southwest China.The acquired seismic data are transmitted almost in real time through the 4G cellular network,and then processed automat-ically for event detection,positioning,magnitude calculation and source mechanism inversion.From tens of seconds to a couple of minutes at most,the final seismic attributes can be presented remotely to the end users through the integrated system.From May 27 to June 17,the real-time system has detected and located 7905 aftershocks in the Yangbi area before the internal batteries exhausted,far more than the catalog provided by China Earthquake Networks Center using the regional permanent stations.The initial application of this inte-grated real-time monitoring system is promising,and we anticipate the advent of a new era for Real-time Intelligent Array Seismology(RIAS),for better monitoring and understanding the subsurface dynamic pro-cesses caused by Earth's internal forces as well as anthropogenic activities.展开更多
Based on 60 years of climate data from three national-level stations in Ziyang City,the characteristics of interdecadal variations of temperature,humidity,precipitation and sunshine that were closely related to heat i...Based on 60 years of climate data from three national-level stations in Ziyang City,the characteristics of interdecadal variations of temperature,humidity,precipitation and sunshine that were closely related to heat island effect were analyzed.The data of township regional stations were used for comparison.The results show that the heat island effect value of Ziyang was between 0.3 and 4.3℃.It was the highest in 2015,up to 4.3℃;the minimum 0.3℃ appeared in 2011.The average heat island strength in the past 10 years was 1.2℃,and the average heating rate was 0.12℃/a.Among the four seasons,the highest value of heat island effect was 3.2℃ in summer,while the lowest value was 1.2℃ in winter.The order of heat island value in various seasons is as follows:summer>autumn>spring>winter.展开更多
The M6.2 earthquake in Jishishan,Gansu Province,on December 18,2023,caused extraordinary earthquake disasters.It was located in the northern part of the north−south seismic zone,which is a key area for earthquake moni...The M6.2 earthquake in Jishishan,Gansu Province,on December 18,2023,caused extraordinary earthquake disasters.It was located in the northern part of the north−south seismic zone,which is a key area for earthquake monitoring in China.The newly built dense strong motion stations in this area provide unprecedented conditions for high-precision earthquake relocation,especially the earthquake focal depth.This paper uses the newly built strong motion and traditional broadband seismic networks to relocate the source locations of the M3.0 and above aftershocks and to invert their focal mechanisms.The horizontal error of earthquake location is estimated to be 0.5−1 km,and the vertical error is 1−2 km.The focal depth range of aftershocks is 9.6−14.6 km,distributed in a 12-km-long strip with SSE direction.Aftershocks in the south are more concentrated horizontally and vertically,while aftershocks in the north are more scattered.The focal mechanisms of the main shock and aftershocks are relatively consistent,and the P-axis orientation is consistent with the regional strain direction.There is a seismic blank area of M3.0 and above,about 3−5 km between the main shock and aftershocks.It is suggested that the energy released by the main shock rupture is concentrated in this area.Based on the earthquake location and focal mechanism of the main shock,it is inferred that the Northern Lajishan fault zone is the seismogenic structure of the main shock,and the main shock did not occur on the main fault,but on a secondary fault.The initial rupture depth and centroid depth of the main shock were 12.8 and 14.0 km,respectively.The source rupture depth may not be the main reason for the severe earthquake disaster.展开更多
为了探究单轴受压下石粉-钢渣混凝土的本构关系,根据正交试验方案配制了不同掺量钢渣砂(30%、40%、50%)、钢渣石(30%、40%、50%)、石粉(0%、7.5%、15%)的石粉-钢渣混凝土,对石粉-钢渣混凝土的应力-应变关系进行了实验研究,建立了单轴受...为了探究单轴受压下石粉-钢渣混凝土的本构关系,根据正交试验方案配制了不同掺量钢渣砂(30%、40%、50%)、钢渣石(30%、40%、50%)、石粉(0%、7.5%、15%)的石粉-钢渣混凝土,对石粉-钢渣混凝土的应力-应变关系进行了实验研究,建立了单轴受压下石粉-钢渣混凝土的本构关系模型。实验结果表明:当受到单轴压力时,石粉-钢渣混凝土的破坏模式与普通混凝土相似,表现出斜剪切的特征。石粉-钢渣混凝土峰值应力、峰值应变及弹性模量随着钢渣骨料掺量的增加而提高。为了更好地模拟无量纲应力-应变曲线,本工作采用了Carreira and Chu模型的上升段和过镇海模型的下降段进行了分段拟合。结果表明,实验曲线与分段模型曲线吻合较好。展开更多
基金supported by the Key Research and Development Program of Science and Technology Department of Guizhou Province(No.20204Y147).
文摘Background:The prognostic significance of the chemokine receptor CCR7 in diffuse large B-cell lymphoma(DLBCL)has been reported previously.However,the detailed mechanisms of CCR7 in DLBCL,particularly regarding its interaction with lenalidomide treatment,are not fully understood.Methods:Our study utilized bioinformatics approaches to identify hub genes in SU-DHL-2 cell lines treated with lenalidomide compared to control groups.Immunohistochemical data and clinical information from 122 patients with DLBCL were analyzed to assess the correlation of CCR7 and p-ERK1/2 expression with the prognosis of DLBCL.Furthermore,in vitro and in vivo experiments were conducted to clarify the role of CCR7 in the response of DLBCL to lenalidomide treatment.Results:Our bioinformatics analysis pinpointed CCR7 as a hub gene in the context of lenalidomide treatment in DLBCL.Notably,31.14%and 36.0%(44/122)of DLBCL cases showed positive expression for CCR7 and ERK1/2 respectively,establishing them as independent prognostic factors for adverse outcomes in DLBCL via multivariate Cox regression analysis.Additionally,our studies demonstrated that the external application of the protein CCL21 promoted proliferation,migration,invasion,and activation of the ERK1/2 pathway in SU-DHL-2 and OCI-LY3 cell lines with high levels of CCR7 expression.This effect was mitigated by CCR7 silencing through siRNA,application of ERK inhibitors,or lenalidomide treatment.In vivo experiments reinforced the efficacy of lenalidomide,significantly reducing tumor growth rate,tumor mass,serum total LDH levels,and expression of CCR7 and p-ERK1/2 in a SUDHL-2 xenograft model in nude mice(p<0.05).Conclusion:Our study clarifies the potential role of the CCL21/CCR7/ERK1/2 axis in the therapeutic effects of lenalidomide in DLBCL treatment.
基金supported by the National Natural Science Foundation of China(Grant No.82270892)Natural Science Foundation of Hubei Province(Grant No.2022CFB287)+2 种基金Xianning City Science and Technology Plan Project(Grant No.2022ZRKX052)School projects of Hubei University of Science and Technology(Grant No.2022T01,2021WG05,2021TNB01)Hubei University of Science and Technology School-level Fund(Grant No.BK202122).
文摘Background:Diabetic cardiomyopathy(DCM)is a type of cardiomyopathy caused by long-term diabetes,characterized by abnormal myocardial structure and function,which can lead to heart failure.Berberine(BBR),a quaternary ammonium alkaloid isolated from Coptidis Rhizoma,a traditional Chinese medicine,has superior anti-diabetic and heart-protective properties.The purpose of this study is to assess the impact of BBR on DCM.Methods:This study used a systems pharmacology approach to evaluate the related proteins and signalling pathways between BBR and DCM targets,combined with experimental validation using diabetic mouse heart sections.Microstructural and pathological changes were observed using Hematoxylin-eosin,Masson’s trichrome stain and wheat germ agglutinin staining.Immunofluorescence and western blot were used to determine protein expression.Results:The results indicate that BBR and DCM share 21 core relevant targets,with cross-targets predominantly located in mitochondrial,endoplasmic reticulum,and plasma membrane components.BBR exerts its main effects in improving DCM by maintaining mitochondrial integrity,particularly involving the PI3K-AKT-GSK3βand apoptosis signalling pathways.In addition,post-treatment changes in the key targets of BBR,including cysteine aspartate specific protease(Caspase)-3,phosphoinositide 3-kinase(PI3K)and mitochondria-related proteins,are suggestive of its efficacy.Conclusion:BBR crucially improves DCM by maintaining mitochondrial integrity,inhibiting apoptosis,and modulating PI3K-AKT-GSK3βsignaling.Further studies must address animal model limitations and validate clinical efficacy to understand BBR’s mechanisms fully and its potential clinical use.
基金supported by the National Natural Science Foundation of China (under grants 41874048,41790464,41790462).
文摘A rapidly deployable dense seismic monitoring system which is capable of transmitting acquired data in real time and analyzing data automatically is crucial in seismic hazard mitigation after a major earthquake.However,it is rather difficult for current seismic nodal stations to transmit data in real time for an extended period of time,and it usually takes a great amount of time to process the acquired data manually.To monitor earthquakes in real time flexibly,we develop a mobile integrated seismic monitoring system consisting of newly developed nodal units with 4G telemetry and a real-time AI-assisted automatic data processing workflow.The integrated system is convenient for deployment and has been successfully applied in monitoring the aftershocks of the Yangbi M_(S) 6.4 earthquake occurred on May 21,2021 in Yangbi County,Dali,Yunnan in southwest China.The acquired seismic data are transmitted almost in real time through the 4G cellular network,and then processed automat-ically for event detection,positioning,magnitude calculation and source mechanism inversion.From tens of seconds to a couple of minutes at most,the final seismic attributes can be presented remotely to the end users through the integrated system.From May 27 to June 17,the real-time system has detected and located 7905 aftershocks in the Yangbi area before the internal batteries exhausted,far more than the catalog provided by China Earthquake Networks Center using the regional permanent stations.The initial application of this inte-grated real-time monitoring system is promising,and we anticipate the advent of a new era for Real-time Intelligent Array Seismology(RIAS),for better monitoring and understanding the subsurface dynamic pro-cesses caused by Earth's internal forces as well as anthropogenic activities.
基金Supported by Major Research and Development Project of Sichuan Province(2021YFS0282)Basic Scientific Research Project of Institute of Plateau Meteorology,China Meteorological Administration(BROP202109)。
文摘Based on 60 years of climate data from three national-level stations in Ziyang City,the characteristics of interdecadal variations of temperature,humidity,precipitation and sunshine that were closely related to heat island effect were analyzed.The data of township regional stations were used for comparison.The results show that the heat island effect value of Ziyang was between 0.3 and 4.3℃.It was the highest in 2015,up to 4.3℃;the minimum 0.3℃ appeared in 2011.The average heat island strength in the past 10 years was 1.2℃,and the average heating rate was 0.12℃/a.Among the four seasons,the highest value of heat island effect was 3.2℃ in summer,while the lowest value was 1.2℃ in winter.The order of heat island value in various seasons is as follows:summer>autumn>spring>winter.
文摘The M6.2 earthquake in Jishishan,Gansu Province,on December 18,2023,caused extraordinary earthquake disasters.It was located in the northern part of the north−south seismic zone,which is a key area for earthquake monitoring in China.The newly built dense strong motion stations in this area provide unprecedented conditions for high-precision earthquake relocation,especially the earthquake focal depth.This paper uses the newly built strong motion and traditional broadband seismic networks to relocate the source locations of the M3.0 and above aftershocks and to invert their focal mechanisms.The horizontal error of earthquake location is estimated to be 0.5−1 km,and the vertical error is 1−2 km.The focal depth range of aftershocks is 9.6−14.6 km,distributed in a 12-km-long strip with SSE direction.Aftershocks in the south are more concentrated horizontally and vertically,while aftershocks in the north are more scattered.The focal mechanisms of the main shock and aftershocks are relatively consistent,and the P-axis orientation is consistent with the regional strain direction.There is a seismic blank area of M3.0 and above,about 3−5 km between the main shock and aftershocks.It is suggested that the energy released by the main shock rupture is concentrated in this area.Based on the earthquake location and focal mechanism of the main shock,it is inferred that the Northern Lajishan fault zone is the seismogenic structure of the main shock,and the main shock did not occur on the main fault,but on a secondary fault.The initial rupture depth and centroid depth of the main shock were 12.8 and 14.0 km,respectively.The source rupture depth may not be the main reason for the severe earthquake disaster.
文摘为了探究单轴受压下石粉-钢渣混凝土的本构关系,根据正交试验方案配制了不同掺量钢渣砂(30%、40%、50%)、钢渣石(30%、40%、50%)、石粉(0%、7.5%、15%)的石粉-钢渣混凝土,对石粉-钢渣混凝土的应力-应变关系进行了实验研究,建立了单轴受压下石粉-钢渣混凝土的本构关系模型。实验结果表明:当受到单轴压力时,石粉-钢渣混凝土的破坏模式与普通混凝土相似,表现出斜剪切的特征。石粉-钢渣混凝土峰值应力、峰值应变及弹性模量随着钢渣骨料掺量的增加而提高。为了更好地模拟无量纲应力-应变曲线,本工作采用了Carreira and Chu模型的上升段和过镇海模型的下降段进行了分段拟合。结果表明,实验曲线与分段模型曲线吻合较好。
