OBJECTIVE To investigate the damage effect and mechanisms of cyclophosphamide(CTX)and its active metabolite derivative 4-hydroperoxycyclophosphamide(4-HC)to human neuroblas⁃toma SH-SY5Y cells.METHODS SH-SY5Y cells wer...OBJECTIVE To investigate the damage effect and mechanisms of cyclophosphamide(CTX)and its active metabolite derivative 4-hydroperoxycyclophosphamide(4-HC)to human neuroblas⁃toma SH-SY5Y cells.METHODS SH-SY5Y cells were treated with CTX[0(cell control),0.01,0.1,1,5,10,20,40 and 80 mmol·L^(-1)]and 4-HC[0(cell control),0.01,0.1,1,5,10,20,40 and 80μmol·L^(-1)]for 48 h.Cell confluence and morphology were observed by the IncuCyte ZOOM system.Cell viability was assessed by CCK-8 assay.Lactate dehydrogenase(LDH)release was measured by LDH assay kit.SH-SY5Y cells were treated with CTX(0,1,5,10 and 20 mmol·L^(-1))and 4-HC(0,1,5,10 and 20μmol·L^(-1))for 48 h before cell proliferation was analyzed by 5-ethynyl-2′-deoxyuridine(EdU)staining assay.Immunofluorescence was employed to assess the levels of the DNA double-strand break markerγ-H2AX and to evaluate changes in mitochondrial membrane potential.SH-SY5Y cells were treated with CTX(0,1,5 and 10 mmol·L^(-1))and 4-HC(0,1,5 and 10μmol·L^(-1))for 48 h,and the alterations in glycolysis and oxidative phosphorylation levels were analyzed using the Seahorse XFe96 Analyzer.RESULTS Compared with the cell control group,cell confluence and cell viability were significantly reduced in the CTX and 4-HC groups(P<0.01),and the half-maximal inhibitory concentrations(IC50)for CTX and 4-HC were 4.44 mmol·L^(-1) and 4.78μmol·L^(-1),respectively.The release rate of LDH was signif⁃icantly increased while the percentage of EdU+cells was significantly reduced in the CTX and 4-HC groups(P<0.01).The percentage ofγ-H2AX+cells was significantly increased and mitochondrial membrane potential significantly decreased in the CTX and 4-HC group(P<0.05).Treatment with CTX and 4-HC resulted in reduced levels of maximum glycolytic capacity,glycolytic reserve,maximal respi⁃ration,and ATP production(P<0.05).CONCLUSION CTX and 4-HC exert significant cytotoxic effects on SH-SY5Y cells by disrupting cell membrane structure,impeding cell proliferation,and reducing cell viability.The mechanisms underlying these effects may involve intracellular DNA damage,disturbance of energy metabolism and mitochondrial dysfunction.展开更多
A redox‐neutral avenue to access isoquinolines has been realized by a Co（III）‐catalyzed C–H activa‐tion process. Starting from readily available N‐sulfinyl imine substrates and alkynes, the reaction occurred vi...A redox‐neutral avenue to access isoquinolines has been realized by a Co（III）‐catalyzed C–H activa‐tion process. Starting from readily available N‐sulfinyl imine substrates and alkynes, the reaction occurred via N–S cleavage with broad substrate scope and functional group compatibility in the presence of cost‐effective cobalt catalysts.展开更多
Developing mild and efficient catalytic methods for the selective synthesis of amines is a longstanding research objective.In this respect,catalytic deoxygenative amide reduction has proven to be promising but challen...Developing mild and efficient catalytic methods for the selective synthesis of amines is a longstanding research objective.In this respect,catalytic deoxygenative amide reduction has proven to be promising but challenging,as this approach necessitates selective C-O bond cleavage.Herein,we report the selective hydroboration of primary,secondary,and tertiary amides at room temperature catalyzed by an earth-abundant-metal catalyst,Zr-H,for accessing diverse amines.Various readily reducible functional groups,such as esters,alkynes,and alkenes,were well tolerated.Furthermore,the methodology was extended to the synthesis of bio-and drug-derived amines.Detailed mechanistic studies revealed a reaction pathway entailing aldehyde and amido complex formation via an unusual C-N bond cleavage-reformation process,followed by C-O bond cleavage.展开更多
A simple and efficient sonochemical method was developed for the degradation of organic matter and ammonia nitrogen in azodicarbonamide wastewater.The effects of initial pH,ultrasound format and peripheral water level...A simple and efficient sonochemical method was developed for the degradation of organic matter and ammonia nitrogen in azodicarbonamide wastewater.The effects of initial pH,ultrasound format and peripheral water level on the sonolysis of hydrazine,urea,COD and ammonia nitrogen were investigated.It is found that the initial pH has a significant influence on the degradation of hydrazine and ammonia nitrogen,whereas this impact to urea is relatively small.It also shows that a noticeable enhancement of ammonia nitrogen removal could be achieved in a proper intermittent ultrasound operation mode,i.e.,1/1 min on/off mode.The height difference between the periph-eral water level and the inner water level of the flask affects the efficiency of ultrasonic treatment as well.展开更多
Asymmetric hydrogenation of α-keto Weinreb amides has been realized with [Ru（（S）-Sunphos）（benzene）C1]C1 as the catalyst and CeC13·7H20 as the additive. A series of enantiopure -hydroxy Weinreb amides （up ...Asymmetric hydrogenation of α-keto Weinreb amides has been realized with [Ru（（S）-Sunphos）（benzene）C1]C1 as the catalyst and CeC13·7H20 as the additive. A series of enantiopure -hydroxy Weinreb amides （up to 97% ee） have been obtained. Cata- lytic amount of CeC13·7H20 is essential for the high reactivity and enantioselectivity and the ratio of CeC13·7H20 to [Ru（（S）-Sunphos）（benzene）C1]C1 plays an important role in the hydrogenation reaction.展开更多
文摘OBJECTIVE To investigate the damage effect and mechanisms of cyclophosphamide(CTX)and its active metabolite derivative 4-hydroperoxycyclophosphamide(4-HC)to human neuroblas⁃toma SH-SY5Y cells.METHODS SH-SY5Y cells were treated with CTX[0(cell control),0.01,0.1,1,5,10,20,40 and 80 mmol·L^(-1)]and 4-HC[0(cell control),0.01,0.1,1,5,10,20,40 and 80μmol·L^(-1)]for 48 h.Cell confluence and morphology were observed by the IncuCyte ZOOM system.Cell viability was assessed by CCK-8 assay.Lactate dehydrogenase(LDH)release was measured by LDH assay kit.SH-SY5Y cells were treated with CTX(0,1,5,10 and 20 mmol·L^(-1))and 4-HC(0,1,5,10 and 20μmol·L^(-1))for 48 h before cell proliferation was analyzed by 5-ethynyl-2′-deoxyuridine(EdU)staining assay.Immunofluorescence was employed to assess the levels of the DNA double-strand break markerγ-H2AX and to evaluate changes in mitochondrial membrane potential.SH-SY5Y cells were treated with CTX(0,1,5 and 10 mmol·L^(-1))and 4-HC(0,1,5 and 10μmol·L^(-1))for 48 h,and the alterations in glycolysis and oxidative phosphorylation levels were analyzed using the Seahorse XFe96 Analyzer.RESULTS Compared with the cell control group,cell confluence and cell viability were significantly reduced in the CTX and 4-HC groups(P<0.01),and the half-maximal inhibitory concentrations(IC50)for CTX and 4-HC were 4.44 mmol·L^(-1) and 4.78μmol·L^(-1),respectively.The release rate of LDH was signif⁃icantly increased while the percentage of EdU+cells was significantly reduced in the CTX and 4-HC groups(P<0.01).The percentage ofγ-H2AX+cells was significantly increased and mitochondrial membrane potential significantly decreased in the CTX and 4-HC group(P<0.05).Treatment with CTX and 4-HC resulted in reduced levels of maximum glycolytic capacity,glycolytic reserve,maximal respi⁃ration,and ATP production(P<0.05).CONCLUSION CTX and 4-HC exert significant cytotoxic effects on SH-SY5Y cells by disrupting cell membrane structure,impeding cell proliferation,and reducing cell viability.The mechanisms underlying these effects may involve intracellular DNA damage,disturbance of energy metabolism and mitochondrial dysfunction.
基金supported by the Dalian Institute of Chemical Physics,Chinese Academy of Sciencesthe National Natural Science Foundation of China (21272231)~~
文摘A redox‐neutral avenue to access isoquinolines has been realized by a Co（III）‐catalyzed C–H activa‐tion process. Starting from readily available N‐sulfinyl imine substrates and alkynes, the reaction occurred via N–S cleavage with broad substrate scope and functional group compatibility in the presence of cost‐effective cobalt catalysts.
文摘Developing mild and efficient catalytic methods for the selective synthesis of amines is a longstanding research objective.In this respect,catalytic deoxygenative amide reduction has proven to be promising but challenging,as this approach necessitates selective C-O bond cleavage.Herein,we report the selective hydroboration of primary,secondary,and tertiary amides at room temperature catalyzed by an earth-abundant-metal catalyst,Zr-H,for accessing diverse amines.Various readily reducible functional groups,such as esters,alkynes,and alkenes,were well tolerated.Furthermore,the methodology was extended to the synthesis of bio-and drug-derived amines.Detailed mechanistic studies revealed a reaction pathway entailing aldehyde and amido complex formation via an unusual C-N bond cleavage-reformation process,followed by C-O bond cleavage.
基金Supported by the National Natural Science Foundation of China (21121064,20990224)National Science and Technology Ministry of China (2008BAE64B02)
文摘A simple and efficient sonochemical method was developed for the degradation of organic matter and ammonia nitrogen in azodicarbonamide wastewater.The effects of initial pH,ultrasound format and peripheral water level on the sonolysis of hydrazine,urea,COD and ammonia nitrogen were investigated.It is found that the initial pH has a significant influence on the degradation of hydrazine and ammonia nitrogen,whereas this impact to urea is relatively small.It also shows that a noticeable enhancement of ammonia nitrogen removal could be achieved in a proper intermittent ultrasound operation mode,i.e.,1/1 min on/off mode.The height difference between the periph-eral water level and the inner water level of the flask affects the efficiency of ultrasonic treatment as well.
文摘Asymmetric hydrogenation of α-keto Weinreb amides has been realized with [Ru（（S）-Sunphos）（benzene）C1]C1 as the catalyst and CeC13·7H20 as the additive. A series of enantiopure -hydroxy Weinreb amides （up to 97% ee） have been obtained. Cata- lytic amount of CeC13·7H20 is essential for the high reactivity and enantioselectivity and the ratio of CeC13·7H20 to [Ru（（S）-Sunphos）（benzene）C1]C1 plays an important role in the hydrogenation reaction.
