The plant hormone ethylene regulates ripening in climacteric fruits.The phytohormone abscisic acid(ABA)affects ethylene biosynthesis,but whether ethylene influences ABA biosynthesis is unknown.To explore this possibil...The plant hormone ethylene regulates ripening in climacteric fruits.The phytohormone abscisic acid(ABA)affects ethylene biosynthesis,but whether ethylene influences ABA biosynthesis is unknown.To explore this possibility,we investigated the interactions between the ABA biosynthesis genes PpNCED2/3 and the ethylene response transcription factor PpERF3 in peach fruit.The ABA content increased during fruit maturation and reached a peak at stage S4 III.The increase was greatly inhibited by the ethylene inhibitor 1-MCP,which also suppressed PpERF3 expression.PpERF3 shared a similar expression profile with PpNCED2/3,encoding a rate-limiting enzyme involved in ABA biosynthesis,during fruit ripening.A yeast one-hybrid assay suggested that the nuclear-localized PpERF3 might bind to the promoters of PpNCED2/3.PpERF3 increased the expression of PpNCED2/3 as shown by dual-luciferase reporters,promoter-GUS assays and transient expression analyses in peach fruit.Collectively,these results suggest that ethylene promotes ABA biosynthesis through PpERF3’s regulation of the expression of ABA biosynthesis genes PpNCED2/3.展开更多
Peach(Prunus persica)is a typical climacteric fruit that produces ethylene rapidly during ripening,and its fruit softens quickly.Stony hard peach cultivars,however,do not produce large amounts of ethylene,and the frui...Peach(Prunus persica)is a typical climacteric fruit that produces ethylene rapidly during ripening,and its fruit softens quickly.Stony hard peach cultivars,however,do not produce large amounts of ethylene,and the fruit remains firm until fully ripe,thus differing from melting flesh peach cultivars.To identify the key proteins involved in peach fruit ripening,an antibody-based proteomic analysis was conducted.A mega-monoclonal antibody(mAb)library was generated and arrayed on a chip(mAbArray)at a high density,covering~4950 different proteins of peach.Through the screening of peach fruit proteins with the mAbArray chip,differentially expressed proteins recognized by 1587 mAbs were identified,and 33 corresponding antigens were ultimately identified by immunoprecipitation and mass spectrometry.These proteins included not only important enzymes involved in ethylene biosynthesis,such as ACO1,SAHH,SAMS,and MetE,but also novel factors such as NUDT2.Furthermore,protein–protein interaction analysis identified a metabolon containing SAHH and MetE.By combining the antibody-based proteomic data with the transcriptomic and metabolic data,a mathematical model of ethylene biosynthesis in peach was constructed.Simulation results showed that MetE is an important regulator during peach ripening,partially through interaction with SAHH.展开更多
BACKGROUND Dandy-Walker malformation(DWM)was first reported in 1914.In this case report,a pediatric case was complicated with giant and isolated arachnoid cysts in the right cerebellar hemisphere along with the typica...BACKGROUND Dandy-Walker malformation(DWM)was first reported in 1914.In this case report,a pediatric case was complicated with giant and isolated arachnoid cysts in the right cerebellar hemisphere along with the typical DWM.CASE SUMMARY The patient was at 20 mo old boy,with the complaint of staggering for more than 2 mo.He was admitted to the hospital due to high intracranial pressure and staggering.At admission,the patient had typical manifestations of high intracranial pressure,including vomiting,poor appetite and feeding difficulty.Physical examination revealed increased head circumference,closed anterior fontanelle,unstable standing,staggering,leaning right while walking and ataxia.After admission,he was diagnosed with DWM accompanied by giant isolated arachnoid cysts in the posterior fossa.He underwent Y-shaped three-way valve repair for treating differential pressure between the supratentorial hydrocephalus and the subtentorial arachnoid cysts at once.The child recovered well after the surgery.CONCLUSION In this case,supratentorial and subtentorial shunts were placed,which solved the problem of differential pressure between the supratentorial and subtentorial parts simultaneously.This provides useful information regarding treatment exploration in this rare disease.展开更多
BACKGROUND BIR repeat-containing ubiquitin conjugating enzyme(BRUCE)is a liver tumor suppressor,which is downregulated in a large number of patients with liver diseases.BRUCE facilitates DNA damage repair to protect t...BACKGROUND BIR repeat-containing ubiquitin conjugating enzyme(BRUCE)is a liver tumor suppressor,which is downregulated in a large number of patients with liver diseases.BRUCE facilitates DNA damage repair to protect the mouse liver against the hepatocarcinogen diethylnitrosamine(DEN)-dependent acute liver injury and carcinogenesis.While there exists an established pathologic connection between fibrosis and hepatocellular carcinoma(HCC),DEN exposure alone does not induce robust hepatic fibrosis.Further studies are warranted to identify new suppressive mechanisms contributing to DEN-induced fibrosis and HCC.AIM To investigate the suppressive mechanisms of BRUCE in hepatic fibrosis and HCC development.METHODS Male C57/BL6/J control mice[loxp/Loxp;albumin-cre(Alb-cre)-]and BRUCE Alb-Cre KO mice(loxp/Loxp;Alb-Cre+)were injected with a single dose of DEN at postnatal day 15 and sacrificed at different time points to examine liver disease progression.RESULTS By using a liver-specific BRUCE knockout(LKO)mouse model,we found that BRUCE deficiency,in conjunction with DEN exposure,induced hepatic fibrosis in both premalignant as well as malignant stages,thus recapitulating the chronic fibrosis background often observed in HCC patients.Activated in fibrosis and HCC,β-catenin activity depends on its stabilization and subsequent translocation to the nucleus.Interestingly,we observed that livers from BRUCE KO mice demonstrated an increased nuclear accumulation and elevated activity ofβ-catenin in the three stages of carcinogenesis:Pre-malignancy,tumor initiation,and HCC.This suggests that BRUCE negatively regulatesβ-catenin activity during liver disease progression.β-catenin can be activated by phosphorylation by protein kinases,such as protein kinase A(PKA),which phosphorylates it at Ser-675(pSer-675-β-catenin).Mechanistically,BRUCE and PKA were colocalized in the cytoplasm of hepatocytes where PKA activity is maintained at the basal level.However,in BRUCE deficient mouse livers or a human liver cancer cell line,both PKA activity and pSer-675-β-catenin levels were observed to be elevated.CONCLUSION Our data support a“BRUCE-PKA-β-catenin”signaling axis in the mouse liver.The BRUCE interaction with PKA in hepatocytes suppresses PKA-dependent phosphorylation and activation ofβ-catenin.This study implicates BRUCE as a novel negative regulator of both PKA andβ-catenin in chronic liver disease progression.Furthermore,BRUCE-liver specific KO mice serve as a promising model for understanding hepatic fibrosis and HCC in patients with aberrant activation of PKA andβ-catenin.展开更多
A three-dimensional mathematical model coupling electromagnetic,flow,heat transfer,and solidification has been developed to investigate the effect of eccentric mold electromagnetic stirring(EM-EMS)on the flow and heat...A three-dimensional mathematical model coupling electromagnetic,flow,heat transfer,and solidification has been developed to investigate the effect of eccentric mold electromagnetic stirring(EM-EMS)on the flow and heat transfer of molten steel in round blooms with different cross sections.The uneven distribution of the flow field caused by EM-EMS was improved by changing the straight submerged entry nozzle(SEN)to a four-port SEN.The symmetry index was determined by the velocity distributions on the left and right sides of the center cross section of mold electromagnetic stirring(M-EMS),which quantitatively evaluated the symmetry of EM-EMS on the flow field.In the presence of EM-EMS,the maximum temperature difference ofϕ500 mm andϕ650 mm round blooms between the inner and outer curves amounted to 63 and 26 K,respectively.The maximum distinction between the solidified shells in the inner and outer curves was 11.5 and 5.3 mm,respectively.After using the four-port SEN,the temperature and the shell distribution on the inner and outer curves for theϕ500 mm round bloom were almost the same.The symmetry indices ofϕ500 mm andϕ650 mm round blooms were increased from 0.55 and 0.70 to 0.77 and 0.87,respectively.The four-port SEN can be used to mitigate the negative impact of EM-EMS on the steel flow field.展开更多
Using forward and reverse genetics and global gene expression analyses, we explored the crosstalk between the IKB kinase β (IKKβ) and the transforming growth factor β (TGFβ) signaling pathways. We show that in...Using forward and reverse genetics and global gene expression analyses, we explored the crosstalk between the IKB kinase β (IKKβ) and the transforming growth factor β (TGFβ) signaling pathways. We show that in vitro ablation of Ikkβ in fibroblasts led to progressive ROS accumulation and TGFβ activation, and ultimately accelerated cell migration, fibroblast-myofibroblast transformation and senescence. Mechanistically, the basal IKKβ activity was required for anti-oxidant gene expression and redox homeostasis. Lacking this activity, IKKβ-null cells showed ROS accumulation and activation of stress-sensitive transcription factor AP-1/c- Jun. AP-1/c-Jun activation led to up-regulation of the Tgfβ2 promoter, which in turn further potentiated intracellular ROS through the induction of NADPH oxidase (NOX). These data suggest that by blocking the autocrine amplification of a ROS-TGFβ loop IKKβ plays a crucial role in the prevention of fibroblast-myofibroblast transformation and senescence.展开更多
Supercapacitors are highly valued energy storage devices with high power density,fast charging ability,and exceptional cycling stability.A profound understanding of their charging mechanisms is crucial for continuous ...Supercapacitors are highly valued energy storage devices with high power density,fast charging ability,and exceptional cycling stability.A profound understanding of their charging mechanisms is crucial for continuous performance enhancement.Electrochemical quartz crystal microbalance(EQCM),a detection means that provides in situ mass change information during charging–discharging processes at the nanogram level,has received greatly significant attention during the past decade due to its high sensitivity,non-destructiveness and low cost.Since being used to track ionic fluxes in porous carbons in 2009,EQCM has played a pivotal role in understanding the charging mechanisms of supercapacitors.Herein,we review the critical progress of EQCM hitherto,including theory fundamentals and applications in supercapacitors.Finally,we discuss the fundamental effects of ion desolvation and transport on the performance of supercapacitors.The advantages and defects of applying EQCM in supercapacitors are thoroughly examined,and future directions are proposed.展开更多
基金support of the National Natural Science Foundation of China[No.31501732]the Agricultural Science and Technology Innovation Program(ASTIP)[CAAS-ASTIP-2018-ZFRI].
文摘The plant hormone ethylene regulates ripening in climacteric fruits.The phytohormone abscisic acid(ABA)affects ethylene biosynthesis,but whether ethylene influences ABA biosynthesis is unknown.To explore this possibility,we investigated the interactions between the ABA biosynthesis genes PpNCED2/3 and the ethylene response transcription factor PpERF3 in peach fruit.The ABA content increased during fruit maturation and reached a peak at stage S4 III.The increase was greatly inhibited by the ethylene inhibitor 1-MCP,which also suppressed PpERF3 expression.PpERF3 shared a similar expression profile with PpNCED2/3,encoding a rate-limiting enzyme involved in ABA biosynthesis,during fruit ripening.A yeast one-hybrid assay suggested that the nuclear-localized PpERF3 might bind to the promoters of PpNCED2/3.PpERF3 increased the expression of PpNCED2/3 as shown by dual-luciferase reporters,promoter-GUS assays and transient expression analyses in peach fruit.Collectively,these results suggest that ethylene promotes ABA biosynthesis through PpERF3’s regulation of the expression of ABA biosynthesis genes PpNCED2/3.
基金supported by the National Key Research and Development Program[2018YFD1000200]the National Natural Science Foundation of China[31872085]the Agricultural Science and Technology Innovation Program(ASTIP)[CAAS-ASTIP-2020-ZFRI].
文摘Peach(Prunus persica)is a typical climacteric fruit that produces ethylene rapidly during ripening,and its fruit softens quickly.Stony hard peach cultivars,however,do not produce large amounts of ethylene,and the fruit remains firm until fully ripe,thus differing from melting flesh peach cultivars.To identify the key proteins involved in peach fruit ripening,an antibody-based proteomic analysis was conducted.A mega-monoclonal antibody(mAb)library was generated and arrayed on a chip(mAbArray)at a high density,covering~4950 different proteins of peach.Through the screening of peach fruit proteins with the mAbArray chip,differentially expressed proteins recognized by 1587 mAbs were identified,and 33 corresponding antigens were ultimately identified by immunoprecipitation and mass spectrometry.These proteins included not only important enzymes involved in ethylene biosynthesis,such as ACO1,SAHH,SAMS,and MetE,but also novel factors such as NUDT2.Furthermore,protein–protein interaction analysis identified a metabolon containing SAHH and MetE.By combining the antibody-based proteomic data with the transcriptomic and metabolic data,a mathematical model of ethylene biosynthesis in peach was constructed.Simulation results showed that MetE is an important regulator during peach ripening,partially through interaction with SAHH.
文摘BACKGROUND Dandy-Walker malformation(DWM)was first reported in 1914.In this case report,a pediatric case was complicated with giant and isolated arachnoid cysts in the right cerebellar hemisphere along with the typical DWM.CASE SUMMARY The patient was at 20 mo old boy,with the complaint of staggering for more than 2 mo.He was admitted to the hospital due to high intracranial pressure and staggering.At admission,the patient had typical manifestations of high intracranial pressure,including vomiting,poor appetite and feeding difficulty.Physical examination revealed increased head circumference,closed anterior fontanelle,unstable standing,staggering,leaning right while walking and ataxia.After admission,he was diagnosed with DWM accompanied by giant isolated arachnoid cysts in the posterior fossa.He underwent Y-shaped three-way valve repair for treating differential pressure between the supratentorial hydrocephalus and the subtentorial arachnoid cysts at once.The child recovered well after the surgery.CONCLUSION In this case,supratentorial and subtentorial shunts were placed,which solved the problem of differential pressure between the supratentorial and subtentorial parts simultaneously.This provides useful information regarding treatment exploration in this rare disease.
基金Supported by NIH(Du CY),No.R21CA241025-01NIH(Du CY),No.RO1CA158323+3 种基金NCI RO1 Diversity Supplement(Du CY),No.R01CA158323-05SNational Center for Advancing Translational Sciences of the National Institutes of Health(Du CY),No.2UL1TR001425-05A1University of Cincinnati Center for Environmental Genetics-NIH/NIEHS Award(Du CY),No.P30 ES006096Pathways to Cancer Therapeutics T32(Du CY and Vilfranc CL),No.CA117846-12.
文摘BACKGROUND BIR repeat-containing ubiquitin conjugating enzyme(BRUCE)is a liver tumor suppressor,which is downregulated in a large number of patients with liver diseases.BRUCE facilitates DNA damage repair to protect the mouse liver against the hepatocarcinogen diethylnitrosamine(DEN)-dependent acute liver injury and carcinogenesis.While there exists an established pathologic connection between fibrosis and hepatocellular carcinoma(HCC),DEN exposure alone does not induce robust hepatic fibrosis.Further studies are warranted to identify new suppressive mechanisms contributing to DEN-induced fibrosis and HCC.AIM To investigate the suppressive mechanisms of BRUCE in hepatic fibrosis and HCC development.METHODS Male C57/BL6/J control mice[loxp/Loxp;albumin-cre(Alb-cre)-]and BRUCE Alb-Cre KO mice(loxp/Loxp;Alb-Cre+)were injected with a single dose of DEN at postnatal day 15 and sacrificed at different time points to examine liver disease progression.RESULTS By using a liver-specific BRUCE knockout(LKO)mouse model,we found that BRUCE deficiency,in conjunction with DEN exposure,induced hepatic fibrosis in both premalignant as well as malignant stages,thus recapitulating the chronic fibrosis background often observed in HCC patients.Activated in fibrosis and HCC,β-catenin activity depends on its stabilization and subsequent translocation to the nucleus.Interestingly,we observed that livers from BRUCE KO mice demonstrated an increased nuclear accumulation and elevated activity ofβ-catenin in the three stages of carcinogenesis:Pre-malignancy,tumor initiation,and HCC.This suggests that BRUCE negatively regulatesβ-catenin activity during liver disease progression.β-catenin can be activated by phosphorylation by protein kinases,such as protein kinase A(PKA),which phosphorylates it at Ser-675(pSer-675-β-catenin).Mechanistically,BRUCE and PKA were colocalized in the cytoplasm of hepatocytes where PKA activity is maintained at the basal level.However,in BRUCE deficient mouse livers or a human liver cancer cell line,both PKA activity and pSer-675-β-catenin levels were observed to be elevated.CONCLUSION Our data support a“BRUCE-PKA-β-catenin”signaling axis in the mouse liver.The BRUCE interaction with PKA in hepatocytes suppresses PKA-dependent phosphorylation and activation ofβ-catenin.This study implicates BRUCE as a novel negative regulator of both PKA andβ-catenin in chronic liver disease progression.Furthermore,BRUCE-liver specific KO mice serve as a promising model for understanding hepatic fibrosis and HCC in patients with aberrant activation of PKA andβ-catenin.
基金supported by the National Natural Science Foundation of China(No.52074207).
文摘A three-dimensional mathematical model coupling electromagnetic,flow,heat transfer,and solidification has been developed to investigate the effect of eccentric mold electromagnetic stirring(EM-EMS)on the flow and heat transfer of molten steel in round blooms with different cross sections.The uneven distribution of the flow field caused by EM-EMS was improved by changing the straight submerged entry nozzle(SEN)to a four-port SEN.The symmetry index was determined by the velocity distributions on the left and right sides of the center cross section of mold electromagnetic stirring(M-EMS),which quantitatively evaluated the symmetry of EM-EMS on the flow field.In the presence of EM-EMS,the maximum temperature difference ofϕ500 mm andϕ650 mm round blooms between the inner and outer curves amounted to 63 and 26 K,respectively.The maximum distinction between the solidified shells in the inner and outer curves was 11.5 and 5.3 mm,respectively.After using the four-port SEN,the temperature and the shell distribution on the inner and outer curves for theϕ500 mm round bloom were almost the same.The symmetry indices ofϕ500 mm andϕ650 mm round blooms were increased from 0.55 and 0.70 to 0.77 and 0.87,respectively.The four-port SEN can be used to mitigate the negative impact of EM-EMS on the steel flow field.
文摘Using forward and reverse genetics and global gene expression analyses, we explored the crosstalk between the IKB kinase β (IKKβ) and the transforming growth factor β (TGFβ) signaling pathways. We show that in vitro ablation of Ikkβ in fibroblasts led to progressive ROS accumulation and TGFβ activation, and ultimately accelerated cell migration, fibroblast-myofibroblast transformation and senescence. Mechanistically, the basal IKKβ activity was required for anti-oxidant gene expression and redox homeostasis. Lacking this activity, IKKβ-null cells showed ROS accumulation and activation of stress-sensitive transcription factor AP-1/c- Jun. AP-1/c-Jun activation led to up-regulation of the Tgfβ2 promoter, which in turn further potentiated intracellular ROS through the induction of NADPH oxidase (NOX). These data suggest that by blocking the autocrine amplification of a ROS-TGFβ loop IKKβ plays a crucial role in the prevention of fibroblast-myofibroblast transformation and senescence.
基金the funding support from the National Natural Science Foundation of China(52161135104 and 52106090)Hubei Provincial Natural Science Foundation of China(2020CFA093)as well as the Program for HUST Academic Frontier Youth TeamM.C.also thanks to the Postdoctoral Creative Research Funding of Hubei Province.The INM authors thank Eduard Arzt(INM)for his continued support.
文摘Supercapacitors are highly valued energy storage devices with high power density,fast charging ability,and exceptional cycling stability.A profound understanding of their charging mechanisms is crucial for continuous performance enhancement.Electrochemical quartz crystal microbalance(EQCM),a detection means that provides in situ mass change information during charging–discharging processes at the nanogram level,has received greatly significant attention during the past decade due to its high sensitivity,non-destructiveness and low cost.Since being used to track ionic fluxes in porous carbons in 2009,EQCM has played a pivotal role in understanding the charging mechanisms of supercapacitors.Herein,we review the critical progress of EQCM hitherto,including theory fundamentals and applications in supercapacitors.Finally,we discuss the fundamental effects of ion desolvation and transport on the performance of supercapacitors.The advantages and defects of applying EQCM in supercapacitors are thoroughly examined,and future directions are proposed.