OBJECTIVE To investigate effects of Wudang cherry on urate excretion and renal function and examined whether renal organic ion transporters were involved in potassium oxonateinduced hyperuricemic mice.METHODS The mode...OBJECTIVE To investigate effects of Wudang cherry on urate excretion and renal function and examined whether renal organic ion transporters were involved in potassium oxonateinduced hyperuricemic mice.METHODS The model of hyperuricemic mice was induced by intraperitoneal injection of potassium oxonate(250 mg·kg^(-1))for 7 d.Water extracts of Wudang cherry at 500 mg·kg^(-1)were orally administered to hyperuricemic mice for 7 d,benzbromarone(20 mg·kg^(-1))and allopurinol(20 mg·kg^(-1))were given as positive controls,vehicle control group was given equal normal saline.Serum and urine levels of uric acid were measured in hyperuricemic and normal mice.Simultaneously,the m RNA and protein levels of mouse urate transporter 1(m URAT1),glucose transporter 9(mGLUT9),organic anion transporters(mOAT1 and mOAT3),ATP-binding cassette,subfamily G,membrane 2(mABCG2)and organic cation/carnitine transporters(m OCT1,m OCT2,m OCTN1 and m OCTN2)in the kidney were analyzed by Western blot,RT-PCR,immunohistochemical and immunofluorescent assay,respectively.RESULTS Wudang cherry significantly reduced serum uric acid levels and increased urine uric acid levels in hyperuricemic mice.And it effectively reversed potassium oxonate-induced alterations in renal m URAT1,mGLUT9,mOAT1,mOAT3 and mABCG2 m RNA and protein levels,resulting in the enhancement of renal urate excretion in mice.Moreover,Wudang Cherry increased renal m OCT1,m OCT2,m OCTN1 and m OCTN2 m RNA and protein levels,and improved renal impairment in this model.CONCLUSION Wudang cherry processes uricosuric and nephroprotective actions by regulating renal organic ion transporters in hyperuricemic mice.展开更多
The pyrolysis of cyclohexane,methylcyclohexane,and ethylcyclohexane have been studied behind reflected shock waves at pressures of 5 and10 bar and at temperatures of 930-1550 K for 0.05%fuel diluted by Argon.A single-...The pyrolysis of cyclohexane,methylcyclohexane,and ethylcyclohexane have been studied behind reflected shock waves at pressures of 5 and10 bar and at temperatures of 930-1550 K for 0.05%fuel diluted by Argon.A single-pulse shock tube(SPST)is used to perform the pyrolysis experiments at reaction times varying from 1.65 to 1.74 ms.Major products are obtained and quantified using gas chromatography analysis.A flame ionization detector and a thermal conductivity detector are used for species identification and quantification.Kinetic modeling has been performed using several detailed and lumped chemical kinetic mechanisms.Differences in modeling results among the kinetic models are described.Reaction path analysis and sensitivity analysis are performed to determine the important reactions controlling fuel pyrolysis and their influence on the predicted concentrations of reactant and product species profiles.The present work provides new fundamental knowledge in understating pyrolysis characteristics of cyclohexane compounds and additional data set for detailed kinetic mechanism development.展开更多
目的探讨无创头架结合改良穿刺探针在高血压性基底节区脑出血手术中的应用价值。方法选取2017年1月至2020年12月复旦大学附属金山医院符合纳入标准和排除标准的高血压性基底节区脑出血患者76例,随机分成无创头架组和有创头架组,进行神...目的探讨无创头架结合改良穿刺探针在高血压性基底节区脑出血手术中的应用价值。方法选取2017年1月至2020年12月复旦大学附属金山医院符合纳入标准和排除标准的高血压性基底节区脑出血患者76例,随机分成无创头架组和有创头架组,进行神经导航辅助脑内血肿微创穿刺置管引流。其中,无创头架组使用改良穿刺探针。比较两组患者手术时间、导航注册误差、住院周期、肺部感染率及术后6个月神经功能恢复情况。结果两组患者在年龄、性别、入院收缩压、入院时血肿量和入院格拉斯哥昏迷评分(Glasgow Coma Scale,GCS)等基线数据差异无统计学意义,术后6个月神经功能恢复亦无统计学差异。然而,在手术时长、导航注册误差、住院时长、肺部感染率等方面无创头架组均优于有创头架组,差异有显著统计学意义(P<0.01)。结论无创头架结合改良穿刺探针在神经导航辅助脑内血肿微创穿刺置管治疗高血压性基底节区脑出血手术中具有注册误差小、手术时间短、操作简单精准、住院周期短、并发症少等优势。展开更多
The migration mode transition of cancer cell enhances its invasive capability and the drug resistance,where physical confinement of cell microenvironment has been revealed to induce the mesenchymal-amoeboid transition...The migration mode transition of cancer cell enhances its invasive capability and the drug resistance,where physical confinement of cell microenvironment has been revealed to induce the mesenchymal-amoeboid transition(MAT).However,most existing studies are performed in PDMS microchannels,of which the stiffness is much higher than that of most mammalian tissues.Therefore,the amoeboid migration transition observed in these studies is actually induced by the synergistic effect of matrix stiffness and confinement.Since the stiffness of cell microenvironment has been reported to influence the cell migration in 2D substrate,the decoupling of stiffness and confinement effects is thus in need for elucidating the underlying mechanism of MAT.However,it is technically challenging to construct microchannels with physiologically relevant stiffness and channel size,where existing microchannel platforms with physiological relevance stiffness are all with>10μm channel width.Such size is too wide to mimic the physical confinement that migrating cancer cells confront in vivo,and also larger than the width of PDMS channel,in which the MAT of cancer cell was observed.Therefore,an in vitro cell migration platform,which could mimic both stiffness and confinement of the native physical microenvironment during cancer metastasis,could profoundly contribute to researches on cancer cell migration and cellular mechanotransduction.In this paper,we overcome the limitations of engineering soft materials in microscale by combining the collagen-alginate hydrogel with photolithography.This enables us to improve the accuracy of molded microchannel,and thus successfully construct a 3D microchannel platform,which matches the stiffness and width ranges of native environmental confinement that migrating cancer cells confront in vivo.The stiffness(0.3~20 kPa),confinement(channel width:3.5~14μm)and the adhesion ligand density of the microchannel can be tuned independently.Interestingly,using this platform,we observed that the migration speed of cancer cell is influenced by the synergistic effect of channel stiffness and width,and the increasing stiffness reverses the effect of channel width on the migration speed of cancer cells.In addition,MAT has a strong correlation with the channel stiffness.These findings make us reconsider the widely accepted hypothesis:physical confinement can induce MAT.Actually,this transition can only occur in stiff confined microenvironment not in soft one.For soft microchannels,the compliance of the channel walls could cause little cell/nucleus deformation,and the MAT could not be induced.To further investigate the mechanism of MAT,we developed a computational model to simulate the effect of nucleus deformation on MAT.With the model,we found that deforming the cell nuclear by decreasing the nucleus stiffness will reduce the cellmigration speed.This implies that nuclear stiffness plays an important role in the regulation of cancer migration speed and thus MAT in microchannels.The effect of channel stiffness on MAT and migration speed as observed in our experiment could partially explain previous findings reported in the literature,where the increasing matrix stiffness of tumor microenvironment promotes cancer metastasis.Our observations thus highlight the critical role of cell nuclear deformation not only in MAT,but also in regulating cellular mechanotransduction and cell-ECM interactions.This developed platform is capable of mimicking the native physical microenvironment during metastasis,providing a powerful tool for high-throughput screening applications and investigating the interaction between cancer migration and biophysical microenvironment.展开更多
基金supported by National Natural Science Foundation of China(81402994)Natural Science Foundation of Hubei Province(2014CFB652)"2011 Plan" Open Fund Innovation Team Project of Hubei Province(2011JH-2014CXTT08)
文摘OBJECTIVE To investigate effects of Wudang cherry on urate excretion and renal function and examined whether renal organic ion transporters were involved in potassium oxonateinduced hyperuricemic mice.METHODS The model of hyperuricemic mice was induced by intraperitoneal injection of potassium oxonate(250 mg·kg^(-1))for 7 d.Water extracts of Wudang cherry at 500 mg·kg^(-1)were orally administered to hyperuricemic mice for 7 d,benzbromarone(20 mg·kg^(-1))and allopurinol(20 mg·kg^(-1))were given as positive controls,vehicle control group was given equal normal saline.Serum and urine levels of uric acid were measured in hyperuricemic and normal mice.Simultaneously,the m RNA and protein levels of mouse urate transporter 1(m URAT1),glucose transporter 9(mGLUT9),organic anion transporters(mOAT1 and mOAT3),ATP-binding cassette,subfamily G,membrane 2(mABCG2)and organic cation/carnitine transporters(m OCT1,m OCT2,m OCTN1 and m OCTN2)in the kidney were analyzed by Western blot,RT-PCR,immunohistochemical and immunofluorescent assay,respectively.RESULTS Wudang cherry significantly reduced serum uric acid levels and increased urine uric acid levels in hyperuricemic mice.And it effectively reversed potassium oxonate-induced alterations in renal m URAT1,mGLUT9,mOAT1,mOAT3 and mABCG2 m RNA and protein levels,resulting in the enhancement of renal urate excretion in mice.Moreover,Wudang Cherry increased renal m OCT1,m OCT2,m OCTN1 and m OCTN2 m RNA and protein levels,and improved renal impairment in this model.CONCLUSION Wudang cherry processes uricosuric and nephroprotective actions by regulating renal organic ion transporters in hyperuricemic mice.
文摘The pyrolysis of cyclohexane,methylcyclohexane,and ethylcyclohexane have been studied behind reflected shock waves at pressures of 5 and10 bar and at temperatures of 930-1550 K for 0.05%fuel diluted by Argon.A single-pulse shock tube(SPST)is used to perform the pyrolysis experiments at reaction times varying from 1.65 to 1.74 ms.Major products are obtained and quantified using gas chromatography analysis.A flame ionization detector and a thermal conductivity detector are used for species identification and quantification.Kinetic modeling has been performed using several detailed and lumped chemical kinetic mechanisms.Differences in modeling results among the kinetic models are described.Reaction path analysis and sensitivity analysis are performed to determine the important reactions controlling fuel pyrolysis and their influence on the predicted concentrations of reactant and product species profiles.The present work provides new fundamental knowledge in understating pyrolysis characteristics of cyclohexane compounds and additional data set for detailed kinetic mechanism development.
文摘目的探讨无创头架结合改良穿刺探针在高血压性基底节区脑出血手术中的应用价值。方法选取2017年1月至2020年12月复旦大学附属金山医院符合纳入标准和排除标准的高血压性基底节区脑出血患者76例,随机分成无创头架组和有创头架组,进行神经导航辅助脑内血肿微创穿刺置管引流。其中,无创头架组使用改良穿刺探针。比较两组患者手术时间、导航注册误差、住院周期、肺部感染率及术后6个月神经功能恢复情况。结果两组患者在年龄、性别、入院收缩压、入院时血肿量和入院格拉斯哥昏迷评分(Glasgow Coma Scale,GCS)等基线数据差异无统计学意义,术后6个月神经功能恢复亦无统计学差异。然而,在手术时长、导航注册误差、住院时长、肺部感染率等方面无创头架组均优于有创头架组,差异有显著统计学意义(P<0.01)。结论无创头架结合改良穿刺探针在神经导航辅助脑内血肿微创穿刺置管治疗高血压性基底节区脑出血手术中具有注册误差小、手术时间短、操作简单精准、住院周期短、并发症少等优势。
基金financially supported by the National Natural Science Foundation of China ( 11532009, 11602191,21775117)the General Financial Grant from the China Postdoctoral Science Foundation ( 2016M592773)the High Level Returned Overseas Students Foundation ( [2018]642)
文摘The migration mode transition of cancer cell enhances its invasive capability and the drug resistance,where physical confinement of cell microenvironment has been revealed to induce the mesenchymal-amoeboid transition(MAT).However,most existing studies are performed in PDMS microchannels,of which the stiffness is much higher than that of most mammalian tissues.Therefore,the amoeboid migration transition observed in these studies is actually induced by the synergistic effect of matrix stiffness and confinement.Since the stiffness of cell microenvironment has been reported to influence the cell migration in 2D substrate,the decoupling of stiffness and confinement effects is thus in need for elucidating the underlying mechanism of MAT.However,it is technically challenging to construct microchannels with physiologically relevant stiffness and channel size,where existing microchannel platforms with physiological relevance stiffness are all with>10μm channel width.Such size is too wide to mimic the physical confinement that migrating cancer cells confront in vivo,and also larger than the width of PDMS channel,in which the MAT of cancer cell was observed.Therefore,an in vitro cell migration platform,which could mimic both stiffness and confinement of the native physical microenvironment during cancer metastasis,could profoundly contribute to researches on cancer cell migration and cellular mechanotransduction.In this paper,we overcome the limitations of engineering soft materials in microscale by combining the collagen-alginate hydrogel with photolithography.This enables us to improve the accuracy of molded microchannel,and thus successfully construct a 3D microchannel platform,which matches the stiffness and width ranges of native environmental confinement that migrating cancer cells confront in vivo.The stiffness(0.3~20 kPa),confinement(channel width:3.5~14μm)and the adhesion ligand density of the microchannel can be tuned independently.Interestingly,using this platform,we observed that the migration speed of cancer cell is influenced by the synergistic effect of channel stiffness and width,and the increasing stiffness reverses the effect of channel width on the migration speed of cancer cells.In addition,MAT has a strong correlation with the channel stiffness.These findings make us reconsider the widely accepted hypothesis:physical confinement can induce MAT.Actually,this transition can only occur in stiff confined microenvironment not in soft one.For soft microchannels,the compliance of the channel walls could cause little cell/nucleus deformation,and the MAT could not be induced.To further investigate the mechanism of MAT,we developed a computational model to simulate the effect of nucleus deformation on MAT.With the model,we found that deforming the cell nuclear by decreasing the nucleus stiffness will reduce the cellmigration speed.This implies that nuclear stiffness plays an important role in the regulation of cancer migration speed and thus MAT in microchannels.The effect of channel stiffness on MAT and migration speed as observed in our experiment could partially explain previous findings reported in the literature,where the increasing matrix stiffness of tumor microenvironment promotes cancer metastasis.Our observations thus highlight the critical role of cell nuclear deformation not only in MAT,but also in regulating cellular mechanotransduction and cell-ECM interactions.This developed platform is capable of mimicking the native physical microenvironment during metastasis,providing a powerful tool for high-throughput screening applications and investigating the interaction between cancer migration and biophysical microenvironment.
