Primary toppling usually occurs in layered rock slopes with large anti-dip angles.In this paper,the block toppling evolution was explored using a large-scale centrifuge system.Each block column in the layered model sl...Primary toppling usually occurs in layered rock slopes with large anti-dip angles.In this paper,the block toppling evolution was explored using a large-scale centrifuge system.Each block column in the layered model slope was made of cement mortar.Some artificial cracks perpendicular to the block column were prefabricated.Strain gages,displacement gages,and high-speed camera measurements were employed to monitor the deformation and failure processes of the model slope.The centrifuge test results show that the block toppling evolution can be divided into seven stages,i.e.layer compression,formation of major tensile crack,reverse bending of the block column,closure of major tensile crack,strong bending of the block column,formation of failure zone,and complete failure.Block toppling is characterized by sudden large deformation and occurs in stages.The wedge-shaped cracks in the model incline towards the slope.Experimental observations show that block toppling is mainly caused by bending failure rather than by shear failure.The tensile strength also plays a key factor in the evolution of block toppling.The simulation results from discrete element method(DEM)is in line with the testing results.Tensile stress exists at the backside of rock column during toppling deformation.Stress concentration results in the fragmented rock column and its degree is the most significant at the slope toe.展开更多
全球变暖背景下,新疆极端天气气候事件频发,深入研究气温极值的均一化,将有助于准确分析气候变化特征,为制定有效的气候变化应对策略提供参考。利用RHtestsV5软件中惩罚最大T检验方法(Penalized Maximal T Test,PMT),选用均一化的月平...全球变暖背景下,新疆极端天气气候事件频发,深入研究气温极值的均一化,将有助于准确分析气候变化特征,为制定有效的气候变化应对策略提供参考。利用RHtestsV5软件中惩罚最大T检验方法(Penalized Maximal T Test,PMT),选用均一化的月平均最高气温和月平均最低气温作为参考序列,对新疆105个国家级地面气象站1951—2022年月极端最高、极端最低气温序列进行均一性检验,分析造成新疆月极端最高、最低气温序列非均一的主要原因,采用分位数匹配(Quantile-Matching,QM)方法对非均一序列进行订正。结果表明:1)105个国家级地面气象站中26站月极端最低气温、8站月极端最高气温序列存在断点,极端最低气温比极端最高气温更易受非自然因素影响;2)台站迁移是极端最高、最低气温序列产生断点的主要原因,极端最高气温产生断点的次要原因是环境变化,而极端最低气温产生断点的原因还包括仪器换型、环境变化和观测时次改变;3)订正前、后全疆年极端最高气温和极端最低气温趋势变化差异不大,但墨玉站等月极端最高、最低气温订正后由降温趋势变为增温趋势,订正后新疆极端最高、最低气温更符合西北地区气候变暖特征,气候变化的空间一致性得到明显改善;4)墨玉极端最高气温和库尔勒极端最低气温订正后的数据序列变化趋势与旧址数据保持一致,且与新疆气候变暖特征的研究结果吻合度更好,说明订正方法具有可靠性和科学性。展开更多
A custom micro-arc oxidation(MAO)apparatus is employed to produce coatings under optimized constant voltage–current two-step power supply mode.Various analytical techniques,including scanning electron microscopy,conf...A custom micro-arc oxidation(MAO)apparatus is employed to produce coatings under optimized constant voltage–current two-step power supply mode.Various analytical techniques,including scanning electron microscopy,confocal laser microscopy,X-ray diffraction,X-ray photoelectron spectroscopy,transmission electron microscopy,and electrochemical analysis,are employed to characterize MAO coatings at different stages of preparation.MAO has MgO,hydroxyapatite,Ca_(3)(PO_(4))_(2),and Mg2SiO4 phases.Its microstructure of the coating is characterized by"multiple breakdowns,pores within pores",and"repaired blind pores".The porosity and the uniformity of MAO coating first declines in the constant voltage mode,then augments while the discharge phenomenon takes place,and finally decreases in the repair stage.These analyses reveal a four-stage growth pattern for MAO coatings:anodic oxidation stage,micro-arc oxidation stage,breakdown stage,and repairing stage.During anodic oxidation and MAO stages,inward growth prevails,while the breakdown stage sees outward and accelerated growth.Simultaneous inward and outward growth in the repair stage results in a denser,more uniform coating with increased thickness and improved corrosion resistance.展开更多
Objective Patients with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection frequently develop central nervous system damage,yet the mechanisms driving this pathology remain unclear.This study investi...Objective Patients with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection frequently develop central nervous system damage,yet the mechanisms driving this pathology remain unclear.This study investigated the primary pathways and key factors underlying brain tissue damage induced by the SARS-CoV-2 beta variant(lineage B.1.351).Methods K18-hACE2 and C57BL/6 mice were intranasally infected with the SARS-CoV-2 beta variant.Viral replication,pathological phenotypes,and brain transcriptomes were analyzed.Gene Ontology(GO)analysis was performed to identify altered pathways.Expression changes of host genes were verified using reverse transcription-quantitative polymerase chain reaction and Western blot.Results Pathological alterations were observed in the lungs of both mouse strains.However,only K18-hACE2 mice exhibited elevated viral RNA loads and infectious titers in the brain at 3 days post-infection,accompanied by neuropathological injury and weight loss.GO analysis of infected K18-hACE2 brain tissue revealed significant dysregulation of genes associated with innate immunity and antiviral defense responses,including type I interferons,pro-inflammatory cytokines,Toll-like receptor signaling components,and interferon-stimulated genes.Neuroinflammation was evident,alongside activation of apoptotic and pyroptotic pathways.Furthermore,altered neural cell marker expression suggested viral-induced neuroglial activation,resulting in caspase 4 and lipocalin 2 release and disruption of neuronal molecular networks.Conclusion These findings elucidate mechanisms of neuropathogenicity associated with the SARS-CoV-2 beta variant and highlight therapeutic targets to mitigate COVID-19-related neurological dysfunction.展开更多
Efficient selective adsorption and separation using porous frameworks are critical in many industrial processes,where adsorption energy and dynamic diffusion rate are predominant factors governing selectivity.They are...Efficient selective adsorption and separation using porous frameworks are critical in many industrial processes,where adsorption energy and dynamic diffusion rate are predominant factors governing selectivity.They are highly susceptible to framework charge,which plays a significant role in selective adsorption.Currently,ionic porous frameworks can be divided into two types.One of them is composed of a charged backbone and counter ions.The framework with zwitterionic channels is another type.It is composed of regular and alternating arrangements of cationic and anionic building units.Herein,we report a hydrogen-bonded ionic framework(HIF)of{(CN_(3)H_(6))_(2)[Ti(μ_(2)-O)(SO_(4))_(2)]}_nwith 1D channel exhibits unique adsorption selectivity for Ar against N_(2)and CO_(2).Density functional theory(DFT)results suggest that CO_(2)cannot be adsorbed by HIF at the experimental temperature due to a positive adsorption free energy.In addition,due to a relatively large diffusion barrier at 77 K,N_(2)molecules hardly diffuse in HIF channels,while Ar has a negligible diffusion barrier.The unique net positively-charged space in the channel is the key to the unusual phenomena,based on DFT simulations and structural analysis.The findings in this work proposes the new adsorption mechanism and provides unique perspective for special separation applications,such as isotope and noble gasses separations.展开更多
BACKGROUND Liver fibrosis is a global health issue that lacks effective treatments.Tibetan medicine,with a long history,has accumulated rich experience in the treatment of chronic liver diseases.The saffron(Saf)and Ca...BACKGROUND Liver fibrosis is a global health issue that lacks effective treatments.Tibetan medicine,with a long history,has accumulated rich experience in the treatment of chronic liver diseases.The saffron(Saf)and Calculus bovis(Cal b)combination is among the most commonly used medicines in clinical practice in Tibetan medicine for hepatic disease.Its characteristic therapies and drug compatibility provide unique ideas for the treatment of liver fibrosis and have research value and application potential.AIM To investigate the efficacy of the Saf-Cal b therapy in treating liver fibrosis and explored its underlying mechanism.METHODS We initially established a carbon tetrachloride-induced rat liver fibrosis model to assess Saf-Cal b’s anti-fibrotic effects.Subsequently,we conducted network pharmacology analysis to identify the potential therapeutic targets and pathways of Saf-Cal b in liver fibrosis intervention.Finally,we performed in vivo validation of key regulatory targets.RESULTS Saf-Cal b combination therapy exerted superior effects in ameliorating liver fibrosis in model rats compared with Saf or Cal b monotherapy.Through network pharmacology prediction,key targets of the combination were identified.Mechanistic validation revealed that Saf-Cal b inhibited the p38 mitogen-activated protein kinases pathway,which in turn suppressed the transforming growth factor-β/small mother against decapentaplegic pathway.This sequential inhibition led to reduced activation of hepatic stellate cells,a central event in liver fibrosis progression.CONCLUSION These findings demonstrate that Saf-Cal b combination therapy is more effective than either monotherapy in alleviating liver fibrosis,with its therapeutic effect mediated through the p38 mitogen-activated protein kinases/transforming growth factor-β/small mother against decapentaplegic signaling axis,providing a potential therapeutic strategy for liver fibrosis.展开更多
Two racemic pairs of new stilbenoid dimers,(±)-heterosmilaxones A(1)and B(2),with unique 6/6/6and 6/5/7 tricyclic core systems,respectively,were isolated from the rhizomes of Heterosmilax yunnanensis.Their struct...Two racemic pairs of new stilbenoid dimers,(±)-heterosmilaxones A(1)and B(2),with unique 6/6/6and 6/5/7 tricyclic core systems,respectively,were isolated from the rhizomes of Heterosmilax yunnanensis.Their structures were elucidated through comprehensive spectroscopic analyses,quantum chemical calculations and X-ray diffraction crystallography.Compound(+)-1,initially reported as syagrusin A with a 1,4,4a,9a-tetrahydrofluoren-9-one skeleton,is now revised to a new structure characteristic with a benzo bicyclo[3.3.1]nonene scaffold.And compound 2 bears an unprecedented carbon skeleton with four continuous chiral centers in the central benzo bicyclo[4.2.1]nonene motif.Biogenetically,both 1 and2 were proposed to derive from 3,3',4,5,5'-pentahydroxy stilbene and could be generated through key inverse-electron-demand[4+2]and[5+2]cycloadditions,respectively.Interestingly,both(±)-1 and(±)-2 showed significant inhibition againstα-glucosidase.(±)-1 and its pure enantiomers could modulate protein tyrosine phosphatase-1B(PTP1B)enzyme activities and increased glucose consumption in HepG2 cells in a dose-dependent manner.展开更多
Objective:To investigate the effect of the spinal cord extracts(SCE)after spinal cord injuries(SCIs)on the proliferation of rat embryonic neural stem cells(NSCs)and the expressions of mRNA of Notch1 as well as of Hes1...Objective:To investigate the effect of the spinal cord extracts(SCE)after spinal cord injuries(SCIs)on the proliferation of rat embryonic neural stem cells(NSCs)and the expressions of mRNA of Notch1 as well as of Hes1 in this process in vitro.Methods:The experiment was conducted in 4 different mediums:NSCs+PBS(Group A-blank control group),NSCs+SCE with healthy SD rats(Croup B-normal control group),NSCs+SCE with SD rats receiving sham-operation treatment(Croup C-sham-operation group)and NSCs+SCE with SCIs rats(Group D-paraplegic group).Proliferative abilities of 4 different groups were analyzed by MTT chromatometry after co-culture for 1,2,3,4 and 5 d,respectively.The expressions of Notch 1 and Hes1 mRNA were also detected with RT-PCR after co-culture for 24 and 48 h,respectively.Results:After co-culture for 1,2,3,4 and 5 d respectively,the MTT values of group D were significantly higher than those of group A,group B and group C(P<0.05).However,there were no significantly differences regarding MTT values between group A,group B and group C after co-culture for 1,2,3,4 and 5 d,respectively(P>0.05).Both the expressions of Notch1 and Hes1 mRNA of group D were significantly higher than those of other 3 groups after co-culture for 24 h and 48 h as well(P<0.05).But there was no difference oin expressions of Notch1 and Hes1 mRNA among group A,group B and group C after co-culture for 24 h and 48 h(P>0.05).There was no difference in expressions of Notch1and Hes1 mRNA between 24 h and 48 h treatment in group D.Conclusions:SCE could promote the proliferation of NSCs.It is demonstrated that the microenvironment of SCI may promote the proliferation of NSCs.Besides,SCE could increase the expression of Notch1 and Hes1 mRNA of NSC.It can be concluded that the Notch signaling pathway activation is one of the mechanisms that locally injured microenvironment contributes to the proliferation of ENSC after SCIs.This process may be performed by up-regulating the expressions of Notch1 and Hes1 gene.展开更多
AIM:To determine the effects of curcumin,(-)-epigallocatechin-3-gallate (EGCG),lovastatin,and their combinations on inhibition of esophageal cancer.METHODS:Esophageal cancer TE-8 and SKGT-4 cell lines were subjected t...AIM:To determine the effects of curcumin,(-)-epigallocatechin-3-gallate (EGCG),lovastatin,and their combinations on inhibition of esophageal cancer.METHODS:Esophageal cancer TE-8 and SKGT-4 cell lines were subjected to cell viability methyl thiazolyl tetrazolium and tumor cell invasion assays in vitro and tumor formation and growth in nude mouse xenografts with or without curcumin,EGCG and lovastatin treatment.Gene expression was detected using immunohistochemistry and Western blotting in tumor cell lines,tumor xenografts and human esophageal cancer tissues,respectively.RESULTS:These drugs individually or in combinations significantly reduced the viability and invasion capacity of esophageal cancer cells in vitro.Molecularly,these three agents reduced the expression of phosphorylated extracellular-signal-regulated kinases (Erk1/2),c-Jun and cyclooxygenase-2 (COX-2),but activated caspase 3 in esophageal cancer cells.The nude mouse xenograft assay showed that EGCG and the combinations of curcumin,EGCG and lovastatin suppressed esophageal cancer cell growth and reduced the expression of Ki67,phosphorylated Erk1/2 and COX-2.The expression of phosphorylated Erk1/2 and COX-2 in esophageal cancer tissue specimens was also analyzed using immunohistochemistry.The data demonstrated that 77 of 156 (49.4%) tumors expressed phosphorylated Erk1/2 and that 121 of 156 (77.6%) esophageal cancers expressed COX-2 protein.In particular,phosphorylated Erk1/2 was expressed in 23 of 50 (46%) cases of esophageal squamous cell carcinoma (SCC) and in 54 of 106 (50.9%) cases of adenocarcinoma,while COX-2 was expressed in 39 of 50 (78%) esophageal SCC and in 82 of 106 (77.4%) esophageal adenocarcinoma.CONCLUSION:The combinations of curcumin,EGCG and lovastatin were able to suppress esophageal cancer cell growth in vitro and in nude mouse xenografts,these drugs also inhibited phosphorylated Erk1/2,c-Jun and COX-2 expression.展开更多
基金The authors wish to thank National Key R&D Program of China(Grant No.2022YFC308100)the National Nature Science Foundation of China(Grant Nos.42107172 and 42072303)for financial support.
文摘Primary toppling usually occurs in layered rock slopes with large anti-dip angles.In this paper,the block toppling evolution was explored using a large-scale centrifuge system.Each block column in the layered model slope was made of cement mortar.Some artificial cracks perpendicular to the block column were prefabricated.Strain gages,displacement gages,and high-speed camera measurements were employed to monitor the deformation and failure processes of the model slope.The centrifuge test results show that the block toppling evolution can be divided into seven stages,i.e.layer compression,formation of major tensile crack,reverse bending of the block column,closure of major tensile crack,strong bending of the block column,formation of failure zone,and complete failure.Block toppling is characterized by sudden large deformation and occurs in stages.The wedge-shaped cracks in the model incline towards the slope.Experimental observations show that block toppling is mainly caused by bending failure rather than by shear failure.The tensile strength also plays a key factor in the evolution of block toppling.The simulation results from discrete element method(DEM)is in line with the testing results.Tensile stress exists at the backside of rock column during toppling deformation.Stress concentration results in the fragmented rock column and its degree is the most significant at the slope toe.
文摘全球变暖背景下,新疆极端天气气候事件频发,深入研究气温极值的均一化,将有助于准确分析气候变化特征,为制定有效的气候变化应对策略提供参考。利用RHtestsV5软件中惩罚最大T检验方法(Penalized Maximal T Test,PMT),选用均一化的月平均最高气温和月平均最低气温作为参考序列,对新疆105个国家级地面气象站1951—2022年月极端最高、极端最低气温序列进行均一性检验,分析造成新疆月极端最高、最低气温序列非均一的主要原因,采用分位数匹配(Quantile-Matching,QM)方法对非均一序列进行订正。结果表明:1)105个国家级地面气象站中26站月极端最低气温、8站月极端最高气温序列存在断点,极端最低气温比极端最高气温更易受非自然因素影响;2)台站迁移是极端最高、最低气温序列产生断点的主要原因,极端最高气温产生断点的次要原因是环境变化,而极端最低气温产生断点的原因还包括仪器换型、环境变化和观测时次改变;3)订正前、后全疆年极端最高气温和极端最低气温趋势变化差异不大,但墨玉站等月极端最高、最低气温订正后由降温趋势变为增温趋势,订正后新疆极端最高、最低气温更符合西北地区气候变暖特征,气候变化的空间一致性得到明显改善;4)墨玉极端最高气温和库尔勒极端最低气温订正后的数据序列变化趋势与旧址数据保持一致,且与新疆气候变暖特征的研究结果吻合度更好,说明订正方法具有可靠性和科学性。
文摘A custom micro-arc oxidation(MAO)apparatus is employed to produce coatings under optimized constant voltage–current two-step power supply mode.Various analytical techniques,including scanning electron microscopy,confocal laser microscopy,X-ray diffraction,X-ray photoelectron spectroscopy,transmission electron microscopy,and electrochemical analysis,are employed to characterize MAO coatings at different stages of preparation.MAO has MgO,hydroxyapatite,Ca_(3)(PO_(4))_(2),and Mg2SiO4 phases.Its microstructure of the coating is characterized by"multiple breakdowns,pores within pores",and"repaired blind pores".The porosity and the uniformity of MAO coating first declines in the constant voltage mode,then augments while the discharge phenomenon takes place,and finally decreases in the repair stage.These analyses reveal a four-stage growth pattern for MAO coatings:anodic oxidation stage,micro-arc oxidation stage,breakdown stage,and repairing stage.During anodic oxidation and MAO stages,inward growth prevails,while the breakdown stage sees outward and accelerated growth.Simultaneous inward and outward growth in the repair stage results in a denser,more uniform coating with increased thickness and improved corrosion resistance.
基金supported by the National Key Research and Development Program of China(2023YFC3041500).
文摘Objective Patients with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection frequently develop central nervous system damage,yet the mechanisms driving this pathology remain unclear.This study investigated the primary pathways and key factors underlying brain tissue damage induced by the SARS-CoV-2 beta variant(lineage B.1.351).Methods K18-hACE2 and C57BL/6 mice were intranasally infected with the SARS-CoV-2 beta variant.Viral replication,pathological phenotypes,and brain transcriptomes were analyzed.Gene Ontology(GO)analysis was performed to identify altered pathways.Expression changes of host genes were verified using reverse transcription-quantitative polymerase chain reaction and Western blot.Results Pathological alterations were observed in the lungs of both mouse strains.However,only K18-hACE2 mice exhibited elevated viral RNA loads and infectious titers in the brain at 3 days post-infection,accompanied by neuropathological injury and weight loss.GO analysis of infected K18-hACE2 brain tissue revealed significant dysregulation of genes associated with innate immunity and antiviral defense responses,including type I interferons,pro-inflammatory cytokines,Toll-like receptor signaling components,and interferon-stimulated genes.Neuroinflammation was evident,alongside activation of apoptotic and pyroptotic pathways.Furthermore,altered neural cell marker expression suggested viral-induced neuroglial activation,resulting in caspase 4 and lipocalin 2 release and disruption of neuronal molecular networks.Conclusion These findings elucidate mechanisms of neuropathogenicity associated with the SARS-CoV-2 beta variant and highlight therapeutic targets to mitigate COVID-19-related neurological dysfunction.
基金support from the Chinese Academy of Sciences and University of Science and Technology of China,National Key Research and Development Program of China(No.2021YFA1500402)National Natural Science Foundation of China(Nos.21571167,51502282 and 22075266)Fundamental Research Funds for the Central Universities(Nos.WK2060190053 and WK2060190100)。
文摘Efficient selective adsorption and separation using porous frameworks are critical in many industrial processes,where adsorption energy and dynamic diffusion rate are predominant factors governing selectivity.They are highly susceptible to framework charge,which plays a significant role in selective adsorption.Currently,ionic porous frameworks can be divided into two types.One of them is composed of a charged backbone and counter ions.The framework with zwitterionic channels is another type.It is composed of regular and alternating arrangements of cationic and anionic building units.Herein,we report a hydrogen-bonded ionic framework(HIF)of{(CN_(3)H_(6))_(2)[Ti(μ_(2)-O)(SO_(4))_(2)]}_nwith 1D channel exhibits unique adsorption selectivity for Ar against N_(2)and CO_(2).Density functional theory(DFT)results suggest that CO_(2)cannot be adsorbed by HIF at the experimental temperature due to a positive adsorption free energy.In addition,due to a relatively large diffusion barrier at 77 K,N_(2)molecules hardly diffuse in HIF channels,while Ar has a negligible diffusion barrier.The unique net positively-charged space in the channel is the key to the unusual phenomena,based on DFT simulations and structural analysis.The findings in this work proposes the new adsorption mechanism and provides unique perspective for special separation applications,such as isotope and noble gasses separations.
基金Supported by Tibetan Medicine Administration of Tibet Autonomous Region,No.JJKT2020006Key Research and Development Project of Tibet Autonomous Region,No.XZ202201ZY0019GNational Administration of Traditional Chinese Medicine High-level Key Discipline Construction Project,No.zyyzdxk-2023262.
文摘BACKGROUND Liver fibrosis is a global health issue that lacks effective treatments.Tibetan medicine,with a long history,has accumulated rich experience in the treatment of chronic liver diseases.The saffron(Saf)and Calculus bovis(Cal b)combination is among the most commonly used medicines in clinical practice in Tibetan medicine for hepatic disease.Its characteristic therapies and drug compatibility provide unique ideas for the treatment of liver fibrosis and have research value and application potential.AIM To investigate the efficacy of the Saf-Cal b therapy in treating liver fibrosis and explored its underlying mechanism.METHODS We initially established a carbon tetrachloride-induced rat liver fibrosis model to assess Saf-Cal b’s anti-fibrotic effects.Subsequently,we conducted network pharmacology analysis to identify the potential therapeutic targets and pathways of Saf-Cal b in liver fibrosis intervention.Finally,we performed in vivo validation of key regulatory targets.RESULTS Saf-Cal b combination therapy exerted superior effects in ameliorating liver fibrosis in model rats compared with Saf or Cal b monotherapy.Through network pharmacology prediction,key targets of the combination were identified.Mechanistic validation revealed that Saf-Cal b inhibited the p38 mitogen-activated protein kinases pathway,which in turn suppressed the transforming growth factor-β/small mother against decapentaplegic pathway.This sequential inhibition led to reduced activation of hepatic stellate cells,a central event in liver fibrosis progression.CONCLUSION These findings demonstrate that Saf-Cal b combination therapy is more effective than either monotherapy in alleviating liver fibrosis,with its therapeutic effect mediated through the p38 mitogen-activated protein kinases/transforming growth factor-β/small mother against decapentaplegic signaling axis,providing a potential therapeutic strategy for liver fibrosis.
基金financially supported by the CAMS Innovation Fund for Medical Sciences(CIFMS,No.2021-I2M-1-028)。
文摘Two racemic pairs of new stilbenoid dimers,(±)-heterosmilaxones A(1)and B(2),with unique 6/6/6and 6/5/7 tricyclic core systems,respectively,were isolated from the rhizomes of Heterosmilax yunnanensis.Their structures were elucidated through comprehensive spectroscopic analyses,quantum chemical calculations and X-ray diffraction crystallography.Compound(+)-1,initially reported as syagrusin A with a 1,4,4a,9a-tetrahydrofluoren-9-one skeleton,is now revised to a new structure characteristic with a benzo bicyclo[3.3.1]nonene scaffold.And compound 2 bears an unprecedented carbon skeleton with four continuous chiral centers in the central benzo bicyclo[4.2.1]nonene motif.Biogenetically,both 1 and2 were proposed to derive from 3,3',4,5,5'-pentahydroxy stilbene and could be generated through key inverse-electron-demand[4+2]and[5+2]cycloadditions,respectively.Interestingly,both(±)-1 and(±)-2 showed significant inhibition againstα-glucosidase.(±)-1 and its pure enantiomers could modulate protein tyrosine phosphatase-1B(PTP1B)enzyme activities and increased glucose consumption in HepG2 cells in a dose-dependent manner.
基金supported by Health Bureau of Luzhou No:2012-S-40(1/5)Health Department of Sichuan(120389)
文摘Objective:To investigate the effect of the spinal cord extracts(SCE)after spinal cord injuries(SCIs)on the proliferation of rat embryonic neural stem cells(NSCs)and the expressions of mRNA of Notch1 as well as of Hes1 in this process in vitro.Methods:The experiment was conducted in 4 different mediums:NSCs+PBS(Group A-blank control group),NSCs+SCE with healthy SD rats(Croup B-normal control group),NSCs+SCE with SD rats receiving sham-operation treatment(Croup C-sham-operation group)and NSCs+SCE with SCIs rats(Group D-paraplegic group).Proliferative abilities of 4 different groups were analyzed by MTT chromatometry after co-culture for 1,2,3,4 and 5 d,respectively.The expressions of Notch 1 and Hes1 mRNA were also detected with RT-PCR after co-culture for 24 and 48 h,respectively.Results:After co-culture for 1,2,3,4 and 5 d respectively,the MTT values of group D were significantly higher than those of group A,group B and group C(P<0.05).However,there were no significantly differences regarding MTT values between group A,group B and group C after co-culture for 1,2,3,4 and 5 d,respectively(P>0.05).Both the expressions of Notch1 and Hes1 mRNA of group D were significantly higher than those of other 3 groups after co-culture for 24 h and 48 h as well(P<0.05).But there was no difference oin expressions of Notch1 and Hes1 mRNA among group A,group B and group C after co-culture for 24 h and 48 h(P>0.05).There was no difference in expressions of Notch1and Hes1 mRNA between 24 h and 48 h treatment in group D.Conclusions:SCE could promote the proliferation of NSCs.It is demonstrated that the microenvironment of SCI may promote the proliferation of NSCs.Besides,SCE could increase the expression of Notch1 and Hes1 mRNA of NSC.It can be concluded that the Notch signaling pathway activation is one of the mechanisms that locally injured microenvironment contributes to the proliferation of ENSC after SCIs.This process may be performed by up-regulating the expressions of Notch1 and Hes1 gene.
基金Supported by A United States National Cancer Institute Grant,No.R01CA117895a grant from the Duncan Family Institute for Cancer Prevention and Risk Assessment,UT MDAnderson Cancer Center
文摘AIM:To determine the effects of curcumin,(-)-epigallocatechin-3-gallate (EGCG),lovastatin,and their combinations on inhibition of esophageal cancer.METHODS:Esophageal cancer TE-8 and SKGT-4 cell lines were subjected to cell viability methyl thiazolyl tetrazolium and tumor cell invasion assays in vitro and tumor formation and growth in nude mouse xenografts with or without curcumin,EGCG and lovastatin treatment.Gene expression was detected using immunohistochemistry and Western blotting in tumor cell lines,tumor xenografts and human esophageal cancer tissues,respectively.RESULTS:These drugs individually or in combinations significantly reduced the viability and invasion capacity of esophageal cancer cells in vitro.Molecularly,these three agents reduced the expression of phosphorylated extracellular-signal-regulated kinases (Erk1/2),c-Jun and cyclooxygenase-2 (COX-2),but activated caspase 3 in esophageal cancer cells.The nude mouse xenograft assay showed that EGCG and the combinations of curcumin,EGCG and lovastatin suppressed esophageal cancer cell growth and reduced the expression of Ki67,phosphorylated Erk1/2 and COX-2.The expression of phosphorylated Erk1/2 and COX-2 in esophageal cancer tissue specimens was also analyzed using immunohistochemistry.The data demonstrated that 77 of 156 (49.4%) tumors expressed phosphorylated Erk1/2 and that 121 of 156 (77.6%) esophageal cancers expressed COX-2 protein.In particular,phosphorylated Erk1/2 was expressed in 23 of 50 (46%) cases of esophageal squamous cell carcinoma (SCC) and in 54 of 106 (50.9%) cases of adenocarcinoma,while COX-2 was expressed in 39 of 50 (78%) esophageal SCC and in 82 of 106 (77.4%) esophageal adenocarcinoma.CONCLUSION:The combinations of curcumin,EGCG and lovastatin were able to suppress esophageal cancer cell growth in vitro and in nude mouse xenografts,these drugs also inhibited phosphorylated Erk1/2,c-Jun and COX-2 expression.
