Background:U2AF homology motif kinase 1(UHMK1)has been associated with RNA processing and protein phosphorylation,thereby influencing tumor progression.The study aimed to explore its regulatory mechanisms and biologic...Background:U2AF homology motif kinase 1(UHMK1)has been associated with RNA processing and protein phosphorylation,thereby influencing tumor progression.The study aimed to explore its regulatory mechanisms and biological functions in human prostate cancer(PCa).Methods:In this study,we systematically evaluated the expression and prognostic significance of UHMK1 in public databases,followed by validation through immunohis-tochemistry(IHC)in PCa specimens.Both gain-of-function and loss-of-function experiments were conducted to elucidate the role of UHMK1 in vitro and in vivo.Additionally,a series of molecular and biochemical assays were performed to investigate the regulatory mechanisms underlying UHMK1 activity.Results:Our findings revealed that UHMK1 expression was significantly upregulated in PCa tissues and correlated with poor patient prognosis,as demonstrated by analysis of public datasets and confirmed by immunohistochemical staining.Functional studies showed that UHMK1 depletion suppressed tumor cell proliferation and metastasis,while its overexpression promoted these processes.Mechanistically,we identified that UHMK1 phosphorylates nuclear receptor coactivator 3(NCOA3),which subsequently activates activating transcription factor 4(ATF4)to upregulate methylenetetrahydrofolate dehy-drogenase 2(MTHFD2)transcription.Interestingly,MTHFD2 was found to reciprocally enhance UHMK1 expression,establishing a positive feedback loop.Conclusions:In conclusion,our data suggest that the UHMK1-MTHFD2 axis forms a positive feedback loop that drives PCa progression.Targeting this loop represents a promising therapeutic strategy for restraining prostate cancer development and progression.展开更多
Hepatocellular carcinoma(HCC)is a highly heterogenous dis-ease in histology,genetic aberrations,and protein expression.Over the past decade,the development of new omics techniques has fa-cilitated significant advances...Hepatocellular carcinoma(HCC)is a highly heterogenous dis-ease in histology,genetic aberrations,and protein expression.Over the past decade,the development of new omics techniques has fa-cilitated significant advances in the field of molecular typing stud-ies of HCC.In the era of precision medicine,it is of great signif-icance to improve the efficacy of HCC treatment based on tumor molecular subtyping.Cytokeratin(CK)19-positive HCC has gained increasing atten-tion.Although CK19 is a marker of biliary epithelial cells,10%−30%of HCCs are observed to be CK19 positive[1].Differing from com-bined hepatocellular and cholangiocarcinoma,CK19-positive HCC displays typical HCC morphological features,exhibiting strong co-express of both hepatocyte and cholangiocyte markers within the same tumor cells.Consequently,CK19-positive HCC is also referred to as dual-phenotype HCC,with displaying cholangiolar differenti-ation.展开更多
In order to support the physical research on the EAST tokamak,a new positive ion source with designed beam energy of 120 keV was proposed to be developed.Accelerator structure is one of the key components of the ion s...In order to support the physical research on the EAST tokamak,a new positive ion source with designed beam energy of 120 keV was proposed to be developed.Accelerator structure is one of the key components of the ion source.Through the finite element analysis method,the electrostatic analyses of insulators and grid plates were carried out,the material and structure parameters of insulators were determined.The maximum electric field around each insulator is about 4 kV/mm,and the maximum electric field between grids is about 14 kV/mm,which can meet the 120 keV withstand voltage holding.The insulation system for the positive ion source accelerator with 120 keV is designed,and the connection and basic parameters of insulators and support flanges are analyzed and determined.展开更多
Dear Editor,General anesthetics play a pivotal role in inducing a safe and reversible loss of consciousness in patients,the importance of which cannot be overstated[1].Among the intravenous anesthetics,propofol stands...Dear Editor,General anesthetics play a pivotal role in inducing a safe and reversible loss of consciousness in patients,the importance of which cannot be overstated[1].Among the intravenous anesthetics,propofol stands out for its rapid onset and swift systemic clearance,effectively eliminating the prolonged sedation associated with earlier agents[2].展开更多
Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,...Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,and necroptosis.Oligomerization of mitochondrial voltage-dependent anion channel 1 is an important pathological event in regulating cell death in retinal ischemia–reperfusion injury.However,its role in PANoptosis remains largely unknown.In this study,we demonstrated that voltage-dependent anion channel 1 oligomerization-mediated mitochondrial dysfunction was associated with PANoptosis in retinal ischemia–reperfusion injury.Inhibition of voltage-dependent anion channel 1 oligomerization suppressed mitochondrial dysfunction and PANoptosis in retinal cells subjected to ischemia–reperfusion injury.Mechanistically,mitochondria-derived reactive oxygen species played a central role in the voltagedependent anion channel 1-mediated regulation of PANoptosis by promoting PANoptosome assembly.Moreover,inhibiting voltage-dependent anion channel 1 oligomerization protected against PANoptosis in the retinas of rats subjected to ischemia–reperfusion injury.Overall,our findings reveal the critical role of voltage-dependent anion channel 1 oligomerization in regulating PANoptosis in retinal ischemia–reperfusion injury,highlighting voltage-dependent anion channel 1 as a promising therapeutic target.展开更多
The TSJT1 protein belongs to the class-II glutamine amidotransferase(GATase)superfamily.Research on the functions and underlying mechanisms of TSJT1 in plants is limited.In this study,the abscisic acid(ABA)-inducible ...The TSJT1 protein belongs to the class-II glutamine amidotransferase(GATase)superfamily.Research on the functions and underlying mechanisms of TSJT1 in plants is limited.In this study,the abscisic acid(ABA)-inducible gene IbTSJT1 was isolated from drought-tolerant sweetpotato line Xushu 55-2.Its expression was strongly induced by PEG6000 and ABA.The IbTSJT1 protein was localized in the nucleus and cell membrane.IbTSJT1-overexpressing sweetpotato plants exhibited significantly enhanced drought tolerance.Their ABA and proline contents and superoxide dismutase(SOD)and peroxidase(POD)activities were increased,and their reactive oxygen species(ROS)scavenging-related genes were upregulated under drought stress.The stomatal aperture assay confirmed that the IbTSJT1-overexpressing plants had greater sensitivity to ABA.The results of yeast onehybrid(Y1H)assay,electrophoretic mobility shift assay(EMSA),luciferase reporter assay and ChIP-qPCR assay indicated that IbABF2 can directly bind to the cis-acting ABA-responsive element(ABRE)in the IbTSJT1 promoter to activate the expression of IbTSJT1.These findings suggest that IbTSJT1 mediates ABA-dependent drought stress responses and enhances drought tolerance by inducing stomatal closure and activating the ROS scavenging system in transgenic sweetpotato.Our study provides a novel gene for improving drought tolerance in sweetpotato and other plants.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.81902617 and 82100816)Guangdong Natural Science Foundation(Grant No.2021A1515012322)Guangzhou Basic and Applied Basic Research Subject-Young Doctor’s“Sailing”Project(Grant No.2024A04J4702).
文摘Background:U2AF homology motif kinase 1(UHMK1)has been associated with RNA processing and protein phosphorylation,thereby influencing tumor progression.The study aimed to explore its regulatory mechanisms and biological functions in human prostate cancer(PCa).Methods:In this study,we systematically evaluated the expression and prognostic significance of UHMK1 in public databases,followed by validation through immunohis-tochemistry(IHC)in PCa specimens.Both gain-of-function and loss-of-function experiments were conducted to elucidate the role of UHMK1 in vitro and in vivo.Additionally,a series of molecular and biochemical assays were performed to investigate the regulatory mechanisms underlying UHMK1 activity.Results:Our findings revealed that UHMK1 expression was significantly upregulated in PCa tissues and correlated with poor patient prognosis,as demonstrated by analysis of public datasets and confirmed by immunohistochemical staining.Functional studies showed that UHMK1 depletion suppressed tumor cell proliferation and metastasis,while its overexpression promoted these processes.Mechanistically,we identified that UHMK1 phosphorylates nuclear receptor coactivator 3(NCOA3),which subsequently activates activating transcription factor 4(ATF4)to upregulate methylenetetrahydrofolate dehy-drogenase 2(MTHFD2)transcription.Interestingly,MTHFD2 was found to reciprocally enhance UHMK1 expression,establishing a positive feedback loop.Conclusions:In conclusion,our data suggest that the UHMK1-MTHFD2 axis forms a positive feedback loop that drives PCa progression.Targeting this loop represents a promising therapeutic strategy for restraining prostate cancer development and progression.
基金supported by grants from the Major Re-search Plan of the National Natural Science Foundation of China(92159202)the National Key Research and Development Pro-gram of China(2021YFA1100500)+5 种基金the Key Research&Develop-ment Plan of Zhejiang Province(2024C03051)the Innovation Team of Hangzhou Medical College(CXLJ202401)Joint TCM Science&Technology Projects of National Demonstration Zones for Compre-hensive TCM Reform(GZY-KJS-ZJ-2025-002)the National Natural Science Foundation of China(82303387)the Natural Science Foun-dation of Zhejiang Province(LQ23H160048)the Construction Fund of Key Medical Disciplines of Hangzhou(2025HZGF05).
文摘Hepatocellular carcinoma(HCC)is a highly heterogenous dis-ease in histology,genetic aberrations,and protein expression.Over the past decade,the development of new omics techniques has fa-cilitated significant advances in the field of molecular typing stud-ies of HCC.In the era of precision medicine,it is of great signif-icance to improve the efficacy of HCC treatment based on tumor molecular subtyping.Cytokeratin(CK)19-positive HCC has gained increasing atten-tion.Although CK19 is a marker of biliary epithelial cells,10%−30%of HCCs are observed to be CK19 positive[1].Differing from com-bined hepatocellular and cholangiocarcinoma,CK19-positive HCC displays typical HCC morphological features,exhibiting strong co-express of both hepatocyte and cholangiocyte markers within the same tumor cells.Consequently,CK19-positive HCC is also referred to as dual-phenotype HCC,with displaying cholangiolar differenti-ation.
基金supported by National Natural Science Foundation of China(No.11975261)。
文摘In order to support the physical research on the EAST tokamak,a new positive ion source with designed beam energy of 120 keV was proposed to be developed.Accelerator structure is one of the key components of the ion source.Through the finite element analysis method,the electrostatic analyses of insulators and grid plates were carried out,the material and structure parameters of insulators were determined.The maximum electric field around each insulator is about 4 kV/mm,and the maximum electric field between grids is about 14 kV/mm,which can meet the 120 keV withstand voltage holding.The insulation system for the positive ion source accelerator with 120 keV is designed,and the connection and basic parameters of insulators and support flanges are analyzed and determined.
基金supported by grants from the National Natural Science Foundation of China(82101273)the Second Affiliated Hospital of the Army Medical University Incubation Program for Young Doctoral Talents(2023YQB007).
文摘Dear Editor,General anesthetics play a pivotal role in inducing a safe and reversible loss of consciousness in patients,the importance of which cannot be overstated[1].Among the intravenous anesthetics,propofol stands out for its rapid onset and swift systemic clearance,effectively eliminating the prolonged sedation associated with earlier agents[2].
基金supported by the National Natural Science Foundation of China,Nos.82172196(to KX),82372507(to KX)the Natural Science Foundation of Hunan Province,China,No.2023JJ40804(to QZ)the Key Laboratory of Emergency and Trauma(Hainan Medical University)of the Ministry of Education,China,No.KLET-202210(to QZ)。
文摘Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,and necroptosis.Oligomerization of mitochondrial voltage-dependent anion channel 1 is an important pathological event in regulating cell death in retinal ischemia–reperfusion injury.However,its role in PANoptosis remains largely unknown.In this study,we demonstrated that voltage-dependent anion channel 1 oligomerization-mediated mitochondrial dysfunction was associated with PANoptosis in retinal ischemia–reperfusion injury.Inhibition of voltage-dependent anion channel 1 oligomerization suppressed mitochondrial dysfunction and PANoptosis in retinal cells subjected to ischemia–reperfusion injury.Mechanistically,mitochondria-derived reactive oxygen species played a central role in the voltagedependent anion channel 1-mediated regulation of PANoptosis by promoting PANoptosome assembly.Moreover,inhibiting voltage-dependent anion channel 1 oligomerization protected against PANoptosis in the retinas of rats subjected to ischemia–reperfusion injury.Overall,our findings reveal the critical role of voltage-dependent anion channel 1 oligomerization in regulating PANoptosis in retinal ischemia–reperfusion injury,highlighting voltage-dependent anion channel 1 as a promising therapeutic target.
基金supported by the earmarked fund for CARS-10-Sweetpotato and the Beijing Food Crops Innovation Consortium Program,China(BJLSTD03)。
文摘The TSJT1 protein belongs to the class-II glutamine amidotransferase(GATase)superfamily.Research on the functions and underlying mechanisms of TSJT1 in plants is limited.In this study,the abscisic acid(ABA)-inducible gene IbTSJT1 was isolated from drought-tolerant sweetpotato line Xushu 55-2.Its expression was strongly induced by PEG6000 and ABA.The IbTSJT1 protein was localized in the nucleus and cell membrane.IbTSJT1-overexpressing sweetpotato plants exhibited significantly enhanced drought tolerance.Their ABA and proline contents and superoxide dismutase(SOD)and peroxidase(POD)activities were increased,and their reactive oxygen species(ROS)scavenging-related genes were upregulated under drought stress.The stomatal aperture assay confirmed that the IbTSJT1-overexpressing plants had greater sensitivity to ABA.The results of yeast onehybrid(Y1H)assay,electrophoretic mobility shift assay(EMSA),luciferase reporter assay and ChIP-qPCR assay indicated that IbABF2 can directly bind to the cis-acting ABA-responsive element(ABRE)in the IbTSJT1 promoter to activate the expression of IbTSJT1.These findings suggest that IbTSJT1 mediates ABA-dependent drought stress responses and enhances drought tolerance by inducing stomatal closure and activating the ROS scavenging system in transgenic sweetpotato.Our study provides a novel gene for improving drought tolerance in sweetpotato and other plants.
