The effects of Zn addition on the microstructure and mechanical properties of Mg.10Gd.3Y.0.6Zr(wt.%)alloys in the as-cast,solution-treated,and peak-aged conditions were investigated.Experimental results reveal that th...The effects of Zn addition on the microstructure and mechanical properties of Mg.10Gd.3Y.0.6Zr(wt.%)alloys in the as-cast,solution-treated,and peak-aged conditions were investigated.Experimental results reveal that the microstructure of the as-cast alloy without Zn consists ofα-Mg and Mg24(Gd,Y)5 phases,and the alloy with 0.5 wt.%Zn consists ofα-Mg,(Mg,Zn)3(Gd,Y)and Mg24(Gd,Y,Zn)5 phases.With the addition of Zn increasing to 1 wt.%,the Mg24(Gd,Y,Zn)5 phase disappears and some needle-like stacking faults distribute along the grain boundaries.Moreover,the 18R long-period stacking ordered(LPSO)phase is observed in the as-cast alloy with 2 wt.%Zn.After solution treatment,the Mg24(Gd,Y)5 and Mg24(Gd,Y,Zn)5 eutectic phases are completely dissolved,and the(Mg,Zn)3(Gd,Y)phase,needle-like stacking faults and 18R LPSO phase all transform into 14H LPSO phase.Both the suitable volume fraction of 14H LPSO phases and the fine ellipsoidal-shapedβ′phases make the peak-aged alloy with 0.5 wt.%Zn exhibit excellent comprehensive mechanical properties and the UTS,YS and elongation are 338 MPa,201 MPa and 6.8%,respectively.展开更多
Objective： To examine modulations caused by cyclooxygenase-2 （COX-2） inhibitors on altered microenvironments and overbalanced neurotransmitters in pilocarpine-induced epileptic status rats and to investigate possib...Objective： To examine modulations caused by cyclooxygenase-2 （COX-2） inhibitors on altered microenvironments and overbalanced neurotransmitters in pilocarpine-induced epileptic status rats and to investigate possible mechanisms. Methods： Celecoxib （a COX-2 inhibitor） was administered 45 min prior to pilocarpine administration. The effects of COX-2 inhibitors on mlPSCs （miniature GABAergic inhibitory postsynaptic currents） of CA3 pyramidal cells in the hippocampus were recorded. Expressions of COX-2, c-Fos, newly generated neurons, and activated microgliosis were analyzed by immunohistochemistry, and expressions of c^-subunit of y-amino butyric acid （GABAA） receptors and mitogen-activated protein kinase/extracellular signal-regulated protein kinase （MAPK/ERK） activity were detected by Western blotting. Results： Pretreatment with celecoxib showed protection against pilocarpine-induced seizures. Celecoxib prevented microglia activation in the hilus and inhibited the abnormal neurogenesis and astrogliosis in the hippocampus by inhibiting MAPK/ERK activity and c-Fos transcription. Celecoxib also up-regulated the expression of GABAA receptors. NS-398 （N-2-cyclohexyloxy-4-nitrophenyl-methanesulfonamide）, another COX-2 inhibitor, enhanced the frequency and decay time of mIPSCs. Conclusion： The COX-2 inhibitor celecoxib decreased neuronal excitability and prevented epileptogenesis in pilocarpine-induced status epilepticus rats. Celecoxib regulates synaptic reorganization by inhibiting astrogliosis and ectopic neurogenesis by attenuating MAPK/ERK signal activity, mediated by a GABAergic mechanism.展开更多
The microstructure and mechanical properties of the as-cast and heat-treated Mg-4.6 Y-2.5 Zn-0.6 Zr-x Sn(x = 0, 0.2 and0.5 wt%) alloys were investigated in this work. The results showed that the eutectics have been re...The microstructure and mechanical properties of the as-cast and heat-treated Mg-4.6 Y-2.5 Zn-0.6 Zr-x Sn(x = 0, 0.2 and0.5 wt%) alloys were investigated in this work. The results showed that the eutectics have been refined with 0.2% Sn addition and it has no effect on the phase category of the alloys. However, Sn3 Y5 phase was found in 0.5% Sn-added alloy.After heat treatment at 520 °C, the transformation of the long-period stacking ordered(LPSO) phase takes place in the Mg-Y-Zn-Zr alloy, but the transition is not completed in the alloys containing Sn. In addition, during the heat treatment, the mechanical properties of Sn-free alloys are significantly improved, and the strength of alloys containing Sn does not change much. Through observation and analysis of the microstructure and mechanical properties, it is found that Sn addition hinders the process of a0-Mg ? a-Mg ? 14 H and the process is the key to the transition of 18 H-LPSO to 14 H-LPSO.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)exhibits high invasiveness and mortality rates,and the molecular mechanisms of HCC have gained increasing research interest.The abnormal DNA damage response has long been recogn...BACKGROUND Hepatocellular carcinoma(HCC)exhibits high invasiveness and mortality rates,and the molecular mechanisms of HCC have gained increasing research interest.The abnormal DNA damage response has long been recognized as one of the important factors for tumor occurrence and development.Recent studies have shown the potential of the protein RING finger and WD repeat domain 3(RFWD3)that positively regulates p53 stability in response to DNA damage as a therapeutic target in cancers.AIM To investigate the relationship between HCC and RFWD3 in vitro and in vivo and explored the underlying molecular signalling transduction pathways.METHODS RFWD3 gene expression was analyzed in HCC tissues and adjacent normal tissues.Lentivirus was used to stably knockdown RFWD3 expression in HCC cell lines.After verifying the silencing efficiency,Celigo/cell cycle/apoptosis and MTT assays were used to evaluate cell proliferation and apoptosis.Subsequently,cell migration and invasion were assessed by wound healing and transwell assays.In addition,transduced cells were implanted subcutaneously and injected into the tail vein of nude mice to observe tumor growth and metastasis.Next,we used lentiviral-mediated rescue of RFWD3 shRNA to verify the phenotype.Finally,the microarray,ingenuity pathway analysis,and western blot analysis were used to analyze the regulatory network underlying HCC.RESULTS Compared with adjacent tissues,RFWD3 expression levels were significantly higher in clinical HCC tissues and correlated with tumor size and TNM stage(P<0.05),which indicated a poor prognosis state.RFWD3 silencing in BEL-7404 and HCC-LM3 cells increased apoptosis,decreased growth,and inhibited the migration in shRNAi cells compared with those in shCtrl cells(P<0.05).Furthermore,the in vitro results were supported by the findings of the in vivo experiments with the reduction of tumor cell invasion and migration.Moreover,the rescue of RFWD3 shRNAi resulted in the resumption of invasion and metastasis in HCC cell lines.Finally,gene expression profi展开更多
基金Projects(51774254,51774253,51701187,U1610123,51674226,51574207,51574206)supported by the National Natural Science Foundation of ChinaProject(MC2016-06)supported by the Science and Technology Major Project of Shanxi Province,ChinaProject(201601D021062)supported by Shanxi Province Science Foundation for Youths,China
文摘The effects of Zn addition on the microstructure and mechanical properties of Mg.10Gd.3Y.0.6Zr(wt.%)alloys in the as-cast,solution-treated,and peak-aged conditions were investigated.Experimental results reveal that the microstructure of the as-cast alloy without Zn consists ofα-Mg and Mg24(Gd,Y)5 phases,and the alloy with 0.5 wt.%Zn consists ofα-Mg,(Mg,Zn)3(Gd,Y)and Mg24(Gd,Y,Zn)5 phases.With the addition of Zn increasing to 1 wt.%,the Mg24(Gd,Y,Zn)5 phase disappears and some needle-like stacking faults distribute along the grain boundaries.Moreover,the 18R long-period stacking ordered(LPSO)phase is observed in the as-cast alloy with 2 wt.%Zn.After solution treatment,the Mg24(Gd,Y)5 and Mg24(Gd,Y,Zn)5 eutectic phases are completely dissolved,and the(Mg,Zn)3(Gd,Y)phase,needle-like stacking faults and 18R LPSO phase all transform into 14H LPSO phase.Both the suitable volume fraction of 14H LPSO phases and the fine ellipsoidal-shapedβ′phases make the peak-aged alloy with 0.5 wt.%Zn exhibit excellent comprehensive mechanical properties and the UTS,YS and elongation are 338 MPa,201 MPa and 6.8%,respectively.
文摘Objective： To examine modulations caused by cyclooxygenase-2 （COX-2） inhibitors on altered microenvironments and overbalanced neurotransmitters in pilocarpine-induced epileptic status rats and to investigate possible mechanisms. Methods： Celecoxib （a COX-2 inhibitor） was administered 45 min prior to pilocarpine administration. The effects of COX-2 inhibitors on mlPSCs （miniature GABAergic inhibitory postsynaptic currents） of CA3 pyramidal cells in the hippocampus were recorded. Expressions of COX-2, c-Fos, newly generated neurons, and activated microgliosis were analyzed by immunohistochemistry, and expressions of c^-subunit of y-amino butyric acid （GABAA） receptors and mitogen-activated protein kinase/extracellular signal-regulated protein kinase （MAPK/ERK） activity were detected by Western blotting. Results： Pretreatment with celecoxib showed protection against pilocarpine-induced seizures. Celecoxib prevented microglia activation in the hilus and inhibited the abnormal neurogenesis and astrogliosis in the hippocampus by inhibiting MAPK/ERK activity and c-Fos transcription. Celecoxib also up-regulated the expression of GABAA receptors. NS-398 （N-2-cyclohexyloxy-4-nitrophenyl-methanesulfonamide）, another COX-2 inhibitor, enhanced the frequency and decay time of mIPSCs. Conclusion： The COX-2 inhibitor celecoxib decreased neuronal excitability and prevented epileptogenesis in pilocarpine-induced status epilepticus rats. Celecoxib regulates synaptic reorganization by inhibiting astrogliosis and ectopic neurogenesis by attenuating MAPK/ERK signal activity, mediated by a GABAergic mechanism.
基金supported financially by the National Natural Science Foundation of China (Nos. 51774254, 51774253, 51701187, U1610123, 51674226, 51574207, and 51574206)the Science and Technology Major Project of Shanxi Province (No. MC2016-06)the Shanxi Province Science Foundation for Youths (No. 201601D021062)
文摘The microstructure and mechanical properties of the as-cast and heat-treated Mg-4.6 Y-2.5 Zn-0.6 Zr-x Sn(x = 0, 0.2 and0.5 wt%) alloys were investigated in this work. The results showed that the eutectics have been refined with 0.2% Sn addition and it has no effect on the phase category of the alloys. However, Sn3 Y5 phase was found in 0.5% Sn-added alloy.After heat treatment at 520 °C, the transformation of the long-period stacking ordered(LPSO) phase takes place in the Mg-Y-Zn-Zr alloy, but the transition is not completed in the alloys containing Sn. In addition, during the heat treatment, the mechanical properties of Sn-free alloys are significantly improved, and the strength of alloys containing Sn does not change much. Through observation and analysis of the microstructure and mechanical properties, it is found that Sn addition hinders the process of a0-Mg ? a-Mg ? 14 H and the process is the key to the transition of 18 H-LPSO to 14 H-LPSO.
基金Supported by National Natural Science Foundation of China,No.82172944 and No.81900558Co-operation Research Plan of Medical Science and Technology of Henan Province,No.LHGJ20190149the Key Scientific Research Projects of Universities of Henan Province,No.21A320052。
文摘BACKGROUND Hepatocellular carcinoma(HCC)exhibits high invasiveness and mortality rates,and the molecular mechanisms of HCC have gained increasing research interest.The abnormal DNA damage response has long been recognized as one of the important factors for tumor occurrence and development.Recent studies have shown the potential of the protein RING finger and WD repeat domain 3(RFWD3)that positively regulates p53 stability in response to DNA damage as a therapeutic target in cancers.AIM To investigate the relationship between HCC and RFWD3 in vitro and in vivo and explored the underlying molecular signalling transduction pathways.METHODS RFWD3 gene expression was analyzed in HCC tissues and adjacent normal tissues.Lentivirus was used to stably knockdown RFWD3 expression in HCC cell lines.After verifying the silencing efficiency,Celigo/cell cycle/apoptosis and MTT assays were used to evaluate cell proliferation and apoptosis.Subsequently,cell migration and invasion were assessed by wound healing and transwell assays.In addition,transduced cells were implanted subcutaneously and injected into the tail vein of nude mice to observe tumor growth and metastasis.Next,we used lentiviral-mediated rescue of RFWD3 shRNA to verify the phenotype.Finally,the microarray,ingenuity pathway analysis,and western blot analysis were used to analyze the regulatory network underlying HCC.RESULTS Compared with adjacent tissues,RFWD3 expression levels were significantly higher in clinical HCC tissues and correlated with tumor size and TNM stage(P<0.05),which indicated a poor prognosis state.RFWD3 silencing in BEL-7404 and HCC-LM3 cells increased apoptosis,decreased growth,and inhibited the migration in shRNAi cells compared with those in shCtrl cells(P<0.05).Furthermore,the in vitro results were supported by the findings of the in vivo experiments with the reduction of tumor cell invasion and migration.Moreover,the rescue of RFWD3 shRNAi resulted in the resumption of invasion and metastasis in HCC cell lines.Finally,gene expression profi
