Background:Ultrasound-triggered microbubble destruction(UTMD) is a widely used noninvasive technology in both military and civilian medicine,which could enhance radiosensitivity of various tumors.However,little inform...Background:Ultrasound-triggered microbubble destruction(UTMD) is a widely used noninvasive technology in both military and civilian medicine,which could enhance radiosensitivity of various tumors.However,little information is available regarding the effects of UTMD on radiotherapy for glioblastoma or the underlying mechanism.This study aimed to delineate the effect of UTMD on the radiosensitivity of glioblastoma and the potential involvement of autophagy.Methods:GL261,U251 cells and orthotopic glioblastoma-bearing mice were treated with ionizing radiation(IR) or IR plus UTMD.Autophagy was observed by confocal microscopy and transmission electron microscopy.Western blotting and immunofluorescence analysis were used to detect progesterone receptor membrane component 1(PGRMC1),light chain 3 beta 2(LC3B2) and sequestosome 1(SQSTM1/p62) levels.Lentiviral vectors or siRNAs transfection,and fluorescent probes staining were used to explore the underlying mechanism.Results:UTMD enhanced the radiosensitivity of glioblastoma in vitro and in vivo(P<0.01).UTMD inhibited autophagic flux by disrupting autophagosome-lysosome fusion without impairing lysosomal function or autophagosome synthesis in IR-treated glioblastoma cells.Suppression of autophagy by 3-methyladenine,bafilomycin A1 or ATG5 siRNA had no significant effect on UTMD-induced radiosensitization in glioblastoma cells(P<0.05).Similar results were found when autophagy was induced by rapamycin or ATG5 overexpression(P>0.05).Furthermore,UTMD inhibited PGRMC1expression and binding with LC3B2 in IR-exposed glioblastoma cells(P<0.01).PGRMC1 inhibitor AG-205 or PGRMC1siRNA pretreatment enhanced UTMD-induced LC3B2 and p62 accumulation in IR-exposed glioblastoma cells,thereby promoting UTMD-mediated radiosensitization(P<0.05).Moreover,PGRMC1 overexpression abolished UTMD-caused blockade of autophagic degradation,subsequently inhibiting UTMD-induced radiosensitization of glioblastoma cells.Finally,compared with IR plus UTMD group,PGRMC1 overexpression significantly increased tumor size [(3.8±1.1) mm^(2)vs.(8.0±1.9) mm^(2),P<0.05] and decreased survival time [(67.2±2.6) d vs.(40.0±1.2) d,P=0.0026] in glioblastoma-bearing mice.Conclusions:UTMD enhanced the radiosensitivity of glioblastoma partially by disrupting PGRMC1-mediated autophagy.展开更多
Many forecasting models based on the concepts of Fuzzy time series have been proposed in the past decades. These models have been widely applied to various problem domains, especially in dealing with forecasting probl...Many forecasting models based on the concepts of Fuzzy time series have been proposed in the past decades. These models have been widely applied to various problem domains, especially in dealing with forecasting problems in which historical data are linguistic values. In this paper, we present a new fuzzy time series forecasting model, which uses the historical data as the universe of discourse and uses the K-means clustering algorithm to cluster the universe of discourse, then adjust the clusters into intervals. The proposed method is applied for forecasting University enrollment of Alabama. It is shown that the proposed model achieves a significant improvement in forecasting accuracy as compared to other fuzzy time series forecasting models.展开更多
Bone homeostasis is maintained by the balance between osteoblastic bone formation and osteoclastic bone resorption.Dysregulation of this process leads to multiple diseases,including osteoporosis.However,the underlying...Bone homeostasis is maintained by the balance between osteoblastic bone formation and osteoclastic bone resorption.Dysregulation of this process leads to multiple diseases,including osteoporosis.However,the underlying molecular mechanisms are not fully understood.Here,we show that the global and conditional osteoblast knockout of a deubiquitinase Otub1 result in low bone mass and poor bone strength due to defects in osteogenic differentiation and mineralization.Mechanistically,the stability of FGFR2,a crucial regulator of osteogenesis,is maintained by OTUB1.OTUB1 attenuates the E3 ligase SMURF1-mediated FGFR2 ubiquitination by inhibiting SMURF1’s E2 binding.In the absence of OTUB1,FGFR2 is ubiquitinated excessively by SMURF1,followed by lysosomal degradation.Consistently,adeno-associated virus serotype 9(AAV9)-delivered FGFR2 in knee joints rescued the bone mass loss in osteoblast-specific Otub1-deleted mice.Moreover,Otub1 mRNA level was significantly downregulated in bones from osteoporotic mice,and restoring OTUB1 levels through an AAV9-delivered system in ovariectomy-induced osteoporotic mice attenuated osteopenia.Taken together,our results suggest that OTUB1 positively regulates osteogenic differentiation and mineralization in bone homeostasis by controlling FGFR2 stability,which provides an optical therapeutic strategy to alleviate osteoporosis.展开更多
To the Editor:Osteoporosis is becoming a common,serious,and costly health problem,which causes over nine million fractures annually worldwide.[1] Currently,osteoporotic fractures are a considerable burden to public he...To the Editor:Osteoporosis is becoming a common,serious,and costly health problem,which causes over nine million fractures annually worldwide.[1] Currently,osteoporotic fractures are a considerable burden to public health services and have fairly high morbidity and mortality.[2] Vertebral fractures are the most common osteoporotic fracture and may lead to a high risk of further fracture and could be prevalent in both females and males.[3] Ling et al[4] and Ms.OS studies[5] evaluated the prevalence of vertebral fractures in Beijing and Hong Kong,respectively.However,our knowledge of the descriptive epidemiology and risk factors for vertebral fracture in China still remains poor.展开更多
The interaction mechanism of B and Ti in liquid Gd metal was theoretically analyzed,and the occurrence state transformation and removal of Ti impurity were experimentally analyzed in this study.The research results in...The interaction mechanism of B and Ti in liquid Gd metal was theoretically analyzed,and the occurrence state transformation and removal of Ti impurity were experimentally analyzed in this study.The research results indicated that the B additive reacted with the Ti impurity in liquid Gd metal to form the high-melting-point TiB_(2)at 1673 K.Owing to the low density of TiB_(2)that is far lower than that of Gd,TiB_(2)floated up to the liquid surface,and then,the Ti impurity could be effectively removed from Gd metal.Prolonging melting time and increasing B additive amount could increase Ti removal rate,but the increase in the rate slows beyond a certain duration and B content.The recommended operating parameter,melting time of 60 min and B additive content of 0.1394 wt%could reduce Ti content from 0.1534 wt%to 0.0433 wt%,and the removal rate was 71.9%.展开更多
Dear Editor,Ectromelia virus(ECTV)is a large double-stranded DNA virus belonging to the genus Orthopoxviruses in the family Poxviridae.It is the causative agent of mousepox,which is a lethal,acute toxic disease with h...Dear Editor,Ectromelia virus(ECTV)is a large double-stranded DNA virus belonging to the genus Orthopoxviruses in the family Poxviridae.It is the causative agent of mousepox,which is a lethal,acute toxic disease with high mortality rate in most strains of laboratory mice.It was first discovered in 1930 when mice were first used as animal models(Marchal 1930).展开更多
Objective To study the pharmacokinetic properties of Fufang Baijiezi Gel（FBG） after different acupoints administration. Methods Sinapine thiocyanate, tetrahydropalmatine, 6-gingerol, and asarinin, which were four su...Objective To study the pharmacokinetic properties of Fufang Baijiezi Gel（FBG） after different acupoints administration. Methods Sinapine thiocyanate, tetrahydropalmatine, 6-gingerol, and asarinin, which were four substances of FBG, were determined by a sensitive liquid chromatography tandem mass spectrometry method（LC-MS） both in plasma and dermal microdialysates of guinea pig simultaneously. Microdialysates were separated on an Ultimate？ XB-Phenyl analytical column（150 mm ×2.1 mm, 5μm） and detected by electrospray ionization（ESI） in selected ion monitoring（SIM） mode. The method was validated in terms of selectivity, linearity, sensitivity, and recovery. Result A significant difference was observed in main pharmacokinetic parameters of C max, t max, and AUC between acupoints administration and nonacupoints administration. Conclusion Acupoints administration resulted in a more obvious increase in bioavailability of sinapine thiocyanate, tetrahydropalmatine, 6-gingerol, and asarinin than nonacupoints administration.展开更多
基金Project(51504036) supported by the National Natural Science Foundation of ChinaProject(2012CBA01207) supported by the National Basic Research Program of ChinaProject(2011AA03A409) supported by the National High-Tech Research and Development Program of China
基金supported by the National Natural Science Foundation of China (82073544 and 81971774)the Chongqing Talent Project (CQYC2019)the Chongqing Chief Expert Program in Medicine (CQYC2018)。
文摘Background:Ultrasound-triggered microbubble destruction(UTMD) is a widely used noninvasive technology in both military and civilian medicine,which could enhance radiosensitivity of various tumors.However,little information is available regarding the effects of UTMD on radiotherapy for glioblastoma or the underlying mechanism.This study aimed to delineate the effect of UTMD on the radiosensitivity of glioblastoma and the potential involvement of autophagy.Methods:GL261,U251 cells and orthotopic glioblastoma-bearing mice were treated with ionizing radiation(IR) or IR plus UTMD.Autophagy was observed by confocal microscopy and transmission electron microscopy.Western blotting and immunofluorescence analysis were used to detect progesterone receptor membrane component 1(PGRMC1),light chain 3 beta 2(LC3B2) and sequestosome 1(SQSTM1/p62) levels.Lentiviral vectors or siRNAs transfection,and fluorescent probes staining were used to explore the underlying mechanism.Results:UTMD enhanced the radiosensitivity of glioblastoma in vitro and in vivo(P<0.01).UTMD inhibited autophagic flux by disrupting autophagosome-lysosome fusion without impairing lysosomal function or autophagosome synthesis in IR-treated glioblastoma cells.Suppression of autophagy by 3-methyladenine,bafilomycin A1 or ATG5 siRNA had no significant effect on UTMD-induced radiosensitization in glioblastoma cells(P<0.05).Similar results were found when autophagy was induced by rapamycin or ATG5 overexpression(P>0.05).Furthermore,UTMD inhibited PGRMC1expression and binding with LC3B2 in IR-exposed glioblastoma cells(P<0.01).PGRMC1 inhibitor AG-205 or PGRMC1siRNA pretreatment enhanced UTMD-induced LC3B2 and p62 accumulation in IR-exposed glioblastoma cells,thereby promoting UTMD-mediated radiosensitization(P<0.05).Moreover,PGRMC1 overexpression abolished UTMD-caused blockade of autophagic degradation,subsequently inhibiting UTMD-induced radiosensitization of glioblastoma cells.Finally,compared with IR plus UTMD group,PGRMC1 overexpression significantly increased tumor size [(3.8±1.1) mm^(2)vs.(8.0±1.9) mm^(2),P<0.05] and decreased survival time [(67.2±2.6) d vs.(40.0±1.2) d,P=0.0026] in glioblastoma-bearing mice.Conclusions:UTMD enhanced the radiosensitivity of glioblastoma partially by disrupting PGRMC1-mediated autophagy.
文摘Many forecasting models based on the concepts of Fuzzy time series have been proposed in the past decades. These models have been widely applied to various problem domains, especially in dealing with forecasting problems in which historical data are linguistic values. In this paper, we present a new fuzzy time series forecasting model, which uses the historical data as the universe of discourse and uses the K-means clustering algorithm to cluster the universe of discourse, then adjust the clusters into intervals. The proposed method is applied for forecasting University enrollment of Alabama. It is shown that the proposed model achieves a significant improvement in forecasting accuracy as compared to other fuzzy time series forecasting models.
基金supported by the National Key Research and Development Project of China (2021YFA1300200)China Postdoctoral Science Foundation (2021T140797)+2 种基金the National Natural Science Foundation of China (82192881,81825014,31830003,32201023,81900765)the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB29020000)the State Key Laboratory of Proteomics (SKLP-K202001).
文摘Bone homeostasis is maintained by the balance between osteoblastic bone formation and osteoclastic bone resorption.Dysregulation of this process leads to multiple diseases,including osteoporosis.However,the underlying molecular mechanisms are not fully understood.Here,we show that the global and conditional osteoblast knockout of a deubiquitinase Otub1 result in low bone mass and poor bone strength due to defects in osteogenic differentiation and mineralization.Mechanistically,the stability of FGFR2,a crucial regulator of osteogenesis,is maintained by OTUB1.OTUB1 attenuates the E3 ligase SMURF1-mediated FGFR2 ubiquitination by inhibiting SMURF1’s E2 binding.In the absence of OTUB1,FGFR2 is ubiquitinated excessively by SMURF1,followed by lysosomal degradation.Consistently,adeno-associated virus serotype 9(AAV9)-delivered FGFR2 in knee joints rescued the bone mass loss in osteoblast-specific Otub1-deleted mice.Moreover,Otub1 mRNA level was significantly downregulated in bones from osteoporotic mice,and restoring OTUB1 levels through an AAV9-delivered system in ovariectomy-induced osteoporotic mice attenuated osteopenia.Taken together,our results suggest that OTUB1 positively regulates osteogenic differentiation and mineralization in bone homeostasis by controlling FGFR2 stability,which provides an optical therapeutic strategy to alleviate osteoporosis.
文摘To the Editor:Osteoporosis is becoming a common,serious,and costly health problem,which causes over nine million fractures annually worldwide.[1] Currently,osteoporotic fractures are a considerable burden to public health services and have fairly high morbidity and mortality.[2] Vertebral fractures are the most common osteoporotic fracture and may lead to a high risk of further fracture and could be prevalent in both females and males.[3] Ling et al[4] and Ms.OS studies[5] evaluated the prevalence of vertebral fractures in Beijing and Hong Kong,respectively.However,our knowledge of the descriptive epidemiology and risk factors for vertebral fracture in China still remains poor.
基金financially supported by the National key research and development program of China(No.2017YFB0405901)the National Natural Science Foundation of China(No.51504036 and 51604033)。
文摘The interaction mechanism of B and Ti in liquid Gd metal was theoretically analyzed,and the occurrence state transformation and removal of Ti impurity were experimentally analyzed in this study.The research results indicated that the B additive reacted with the Ti impurity in liquid Gd metal to form the high-melting-point TiB_(2)at 1673 K.Owing to the low density of TiB_(2)that is far lower than that of Gd,TiB_(2)floated up to the liquid surface,and then,the Ti impurity could be effectively removed from Gd metal.Prolonging melting time and increasing B additive amount could increase Ti removal rate,but the increase in the rate slows beyond a certain duration and B content.The recommended operating parameter,melting time of 60 min and B additive content of 0.1394 wt%could reduce Ti content from 0.1534 wt%to 0.0433 wt%,and the removal rate was 71.9%.
基金supported by the National Natural Science Foundation of China(31900154)Special Project of Science,Technology,and Condition(2060503)+4 种基金EVA-GLOBAL(871029)Special Project of Strategic Biological Resources and Science and Technology Supporting and Operating System,Chinese Academy of Sciences(CZBZX-1)National Platform of Basic Scientific Data Sharing Service(Y706061YZ1)Biological Resources Program,Chinese Academy of Sciences(KFJ-BRP-017-06)Scientific Technology,Condition,and Platform Construction Project of Hubei Province(2017BEC003)
文摘Dear Editor,Ectromelia virus(ECTV)is a large double-stranded DNA virus belonging to the genus Orthopoxviruses in the family Poxviridae.It is the causative agent of mousepox,which is a lethal,acute toxic disease with high mortality rate in most strains of laboratory mice.It was first discovered in 1930 when mice were first used as animal models(Marchal 1930).
基金National Natural Science Foundation of China(No.81001649)
文摘Objective To study the pharmacokinetic properties of Fufang Baijiezi Gel（FBG） after different acupoints administration. Methods Sinapine thiocyanate, tetrahydropalmatine, 6-gingerol, and asarinin, which were four substances of FBG, were determined by a sensitive liquid chromatography tandem mass spectrometry method（LC-MS） both in plasma and dermal microdialysates of guinea pig simultaneously. Microdialysates were separated on an Ultimate？ XB-Phenyl analytical column（150 mm ×2.1 mm, 5μm） and detected by electrospray ionization（ESI） in selected ion monitoring（SIM） mode. The method was validated in terms of selectivity, linearity, sensitivity, and recovery. Result A significant difference was observed in main pharmacokinetic parameters of C max, t max, and AUC between acupoints administration and nonacupoints administration. Conclusion Acupoints administration resulted in a more obvious increase in bioavailability of sinapine thiocyanate, tetrahydropalmatine, 6-gingerol, and asarinin than nonacupoints administration.
