Objective To evaluate the relationship of expressions of nucleoside diphosphate kinase （nm23） and proliferating cell nuclear antigen （PCNA）, as well as apoptosis, with the prognosis of HCC patients by analyzing th...Objective To evaluate the relationship of expressions of nucleoside diphosphate kinase （nm23） and proliferating cell nuclear antigen （PCNA）, as well as apoptosis, with the prognosis of HCC patients by analyzing their pathological and clinical data. Methods The expressions of nm23 and PCNA were analyzed by immunohistochemistry and the apoptotic phenomena were detected by TUNEL technique in the liver samples from 43 HCC tissues, 39 para-neoplastic tissues, and 10 normal tissues. The mean apoptosis index （AI） and proliferative index （PI） in individual sample were calculated. Results As shown by the detection, 32.6% of carcinomas had negative nm23 signal in tumor tissues, whereas all para-neoplastic and normal tissues had positive nm23. The AI in nm23 positive HCC was significantly higher than that in nm23 negative one, with statistical difference （P0.05）. Furthermore, the expressions of nm23, and the values of AI and PI were contrastively analyzed with some main pathological and clinical data of HCC. It revealed that HCC with extrahepatic metastasis showed remarkable correlation with the negative nm23 （P=0.013） and higher PI values of HCC （P=0.015）. The disease-free survival in HCC patients with negative nm23 expression was significantly poorer than that in patients with positive nm23 expression. Conclusion These data suggest that expressions of nm23 protein in tumor tissues are correlated with occurrences of metastasis and length of survival of the HCC patients, which may be an indicator for their prognosis.展开更多
Objective To establish a sandwich ELISA method for detecting vascular endothelial growth factor （VEGF） in sera of population and the patients with hepatocellular carcinoma （HCC）. Methods Full length and two trunca...Objective To establish a sandwich ELISA method for detecting vascular endothelial growth factor （VEGF） in sera of population and the patients with hepatocellular carcinoma （HCC）. Methods Full length and two truncated human VEGF cDNA sequences were amplified from a commercial plasmid pBLAST49-hVEGF by PCR and inserted into the prokaryotic-expression plasmid pET-32a or pGEX-2T. Various VEGF proteins were expressed and purified from E. coli in His-Trx or GST fusion forms. The specific VEGF antibodies were elicited in experimental rabbits and mice by immunization of the full length VEGF fusion protein His-Trx-VEGF1-165. After purification of antibodies with chromatograph of Protein G, a sandwich ELISA technique was established. Serum VEGF levels were evaluated in 229 adults and 291 HCC patients. Results SDS-PAGE displayed that the molecular weights of the expressed full length （His-Trx-VEGF1-165）, N-terminal （His-Trx-VEGF1-100） and C-terminal （GST-VEGF100-165） human VEGF fusion proteins were about 38KD, 31KD, and 33KD, respectively. Western blots confirmed that the prepared antisera were able to recognize both prokaryoticly and eukaryoticly expressed recombinant VEGF proteins. Assays of serially diluted His-Trx-VEGF1-100 by the established sandwich ELISA method showed that the linear range of the standard curve was 0.625-320 ng/mL, with the squared correlation coefficient R^2=0.991. Screening of a serum panel containing 291 serum samples of HCC patients and 229 health adults revealed that the average VEGF level in HCC patients was higher than that in healthy controls, with a statically significant difference. Conclusion The established sandwich ELISA reflects the level of serum VEGF and provide scientific basis for screening metastasis and recurrence of HCC using serum VEGF as an index.展开更多
Electrochemical reduction of CO_(2) to value-added chemicals holds promise for carbon utilization and renewable electricity storage.However,selective CO_(2) reduction to multi-carbon fuels remains a significant challe...Electrochemical reduction of CO_(2) to value-added chemicals holds promise for carbon utilization and renewable electricity storage.However,selective CO_(2) reduction to multi-carbon fuels remains a significant challenge.Here,we report that B/N-doped sp^(3)/sp^(2) hybridized nanocarbon(BNHC),consisting of ultra-small nanoparticles with a sp^(3) carbon core covered by a sp^(2) carbon shell,is an efficient electrocatalyst for electrochemical reduction of CO_(2) to ethanol at relatively low overpotentials.CO_(2) reduction occurs with a Faradaic efficiency of 58.8%-69.1% for ethanol and acetate production at -0.5∼-0.6 V(vs.RHE),among which 51.6%-56.0% is for ethanol.The high selectivity for ethanol is due to the integrated effect of sp^(3)/sp^(2) carbon and B/N doping.Both sp^(3) carbon and B/N doping contribute to enhanced ethanol production with sp^(2) carbon reducing the overpotential for CO_(2) reduction to ethanol.展开更多
Chaperone-mediated autophagy(CMA)is a lysosome-dependent selective degradation pathway implicated in the pathogenesis of cancer and neurodegenerative diseases.However,the mechanisms that regulate CMA are not fully und...Chaperone-mediated autophagy(CMA)is a lysosome-dependent selective degradation pathway implicated in the pathogenesis of cancer and neurodegenerative diseases.However,the mechanisms that regulate CMA are not fully understood.Here,using unbiased drug screening approaches,we discover Metformin,a drug that is commonly the first medication prescribed for type 2 diabetes,can induce CMA.We delineate the mechanism of CMA induction by Metformin to be via activation of TAK1-IKKα/β signaling that leads to phosphorylation of Ser85 of the key mediator of CMA,Hsc70,and its activation.Notably,we find that amyloid-beta precursor protein(APP)is a CMA substrate and that it binds to Hsc70 in an IKKα/β-dependent manner.The inhibition of CMA-mediated degradation of APP enhances its cytotoxicity.Importantly,we find that in the APP/PS1 mouse model of Alzheimer's disease(AD),activation of CMA by Hsc70 overexpression or Metformin potently reduces the accumulated brain Aβplaque levels and reverses the molecular and behavioral AD phenotypes.Our study elucidates a novel mechanism of CMA regulation via Metformin-TAK1-IKKα/β-Hsc70 signaling and suggests Metformin as a new activator of CMA for diseases,such as AD,where such therapeutic intervention could be beneficial.展开更多
Intrinsic partial occupation of Cu induces strong phonon scattering for an extremely low lattice thermal conductivity in TmCuTe_(2),which leads this material to be a promising candidate for thermoelectric applications...Intrinsic partial occupation of Cu induces strong phonon scattering for an extremely low lattice thermal conductivity in TmCuTe_(2),which leads this material to be a promising candidate for thermoelectric applications.This work focus on the electronic and phononic transport properties of TmCuTe_(2) with Agalloying on the Cu site.Such a Ag/Cu substitution is found to enable a decrease in Hall carrier concentration from 141019 to 81019 cm^(3) for an evaluation of the charge transport based on a single parabolic band(SPB)model with acoustic scattering.In addition,Ag-substitution simultaneously introduces Cu/Ag point defects for extra phonon scattering,leading the lattice thermal conductivity to be as low as~0.25 W/m-K in a broad temperature.The optimization in carrier concentration and the reduction in lattice thermal conductivity contribute to a~40%improvement in average thermoelectric figure of merit(zT).The determination of band parameters enables a guidance for further advancements in this promising thermoelectric material.展开更多
CORRECTION TO:PROTEIN CELL HTTPS://DOI.ORG/10.1007/S13238-021-00858-3 In legend of figure 1,this sentence“(C)293THK cells were treated as in a”should be corrected as“(C)293THK cells were treated as in(A)”.In legen...CORRECTION TO:PROTEIN CELL HTTPS://DOI.ORG/10.1007/S13238-021-00858-3 In legend of figure 1,this sentence“(C)293THK cells were treated as in a”should be corrected as“(C)293THK cells were treated as in(A)”.In legend of figure 2,“E-64D(10μmol/L)”in description of panel(B)should be removed.In section“Metformin activates chaperone-mediated autophagy”of RESULTS,E-64D in sentence“Metformininduced degradation of HK2 and PKM2 was blocked by lysosomal inhibitors(E-64D,Bafilomycin A1 and Leupeptin+NH4Cl)”should be removed.展开更多
基金supported by National Basic Research Program of China (973 Program) (2007CB310505)China Mega-Project for Infectious Disease (2009ZX10004-101)the SKLID development Grant (2008SKLID102 and 2008SKLID202)
文摘Objective To evaluate the relationship of expressions of nucleoside diphosphate kinase （nm23） and proliferating cell nuclear antigen （PCNA）, as well as apoptosis, with the prognosis of HCC patients by analyzing their pathological and clinical data. Methods The expressions of nm23 and PCNA were analyzed by immunohistochemistry and the apoptotic phenomena were detected by TUNEL technique in the liver samples from 43 HCC tissues, 39 para-neoplastic tissues, and 10 normal tissues. The mean apoptosis index （AI） and proliferative index （PI） in individual sample were calculated. Results As shown by the detection, 32.6% of carcinomas had negative nm23 signal in tumor tissues, whereas all para-neoplastic and normal tissues had positive nm23. The AI in nm23 positive HCC was significantly higher than that in nm23 negative one, with statistical difference （P0.05）. Furthermore, the expressions of nm23, and the values of AI and PI were contrastively analyzed with some main pathological and clinical data of HCC. It revealed that HCC with extrahepatic metastasis showed remarkable correlation with the negative nm23 （P=0.013） and higher PI values of HCC （P=0.015）. The disease-free survival in HCC patients with negative nm23 expression was significantly poorer than that in patients with positive nm23 expression. Conclusion These data suggest that expressions of nm23 protein in tumor tissues are correlated with occurrences of metastasis and length of survival of the HCC patients, which may be an indicator for their prognosis.
基金National High-tech Development Project (863 Project) (No. 2002AA215021)
文摘Objective To establish a sandwich ELISA method for detecting vascular endothelial growth factor （VEGF） in sera of population and the patients with hepatocellular carcinoma （HCC）. Methods Full length and two truncated human VEGF cDNA sequences were amplified from a commercial plasmid pBLAST49-hVEGF by PCR and inserted into the prokaryotic-expression plasmid pET-32a or pGEX-2T. Various VEGF proteins were expressed and purified from E. coli in His-Trx or GST fusion forms. The specific VEGF antibodies were elicited in experimental rabbits and mice by immunization of the full length VEGF fusion protein His-Trx-VEGF1-165. After purification of antibodies with chromatograph of Protein G, a sandwich ELISA technique was established. Serum VEGF levels were evaluated in 229 adults and 291 HCC patients. Results SDS-PAGE displayed that the molecular weights of the expressed full length （His-Trx-VEGF1-165）, N-terminal （His-Trx-VEGF1-100） and C-terminal （GST-VEGF100-165） human VEGF fusion proteins were about 38KD, 31KD, and 33KD, respectively. Western blots confirmed that the prepared antisera were able to recognize both prokaryoticly and eukaryoticly expressed recombinant VEGF proteins. Assays of serially diluted His-Trx-VEGF1-100 by the established sandwich ELISA method showed that the linear range of the standard curve was 0.625-320 ng/mL, with the squared correlation coefficient R^2=0.991. Screening of a serum panel containing 291 serum samples of HCC patients and 229 health adults revealed that the average VEGF level in HCC patients was higher than that in healthy controls, with a statically significant difference. Conclusion The established sandwich ELISA reflects the level of serum VEGF and provide scientific basis for screening metastasis and recurrence of HCC using serum VEGF as an index.
基金supported by National Natural Science Foundation of China(Nos.22076019 and 21707016)The Youth Talent Support Program of Liaoning Province(No.XLYC2007069)U.S.Department of Energy(DOE),Office of Basic Energy Sciences under Award(No.DE-SCO015739).
文摘Electrochemical reduction of CO_(2) to value-added chemicals holds promise for carbon utilization and renewable electricity storage.However,selective CO_(2) reduction to multi-carbon fuels remains a significant challenge.Here,we report that B/N-doped sp^(3)/sp^(2) hybridized nanocarbon(BNHC),consisting of ultra-small nanoparticles with a sp^(3) carbon core covered by a sp^(2) carbon shell,is an efficient electrocatalyst for electrochemical reduction of CO_(2) to ethanol at relatively low overpotentials.CO_(2) reduction occurs with a Faradaic efficiency of 58.8%-69.1% for ethanol and acetate production at -0.5∼-0.6 V(vs.RHE),among which 51.6%-56.0% is for ethanol.The high selectivity for ethanol is due to the integrated effect of sp^(3)/sp^(2) carbon and B/N doping.Both sp^(3) carbon and B/N doping contribute to enhanced ethanol production with sp^(2) carbon reducing the overpotential for CO_(2) reduction to ethanol.
基金Financial support was received from the National Key R&D Program of China(2017YFA0104200)the National Natural Science Foundation of China(No.91854108,81773182 and 31601121).
文摘Chaperone-mediated autophagy(CMA)is a lysosome-dependent selective degradation pathway implicated in the pathogenesis of cancer and neurodegenerative diseases.However,the mechanisms that regulate CMA are not fully understood.Here,using unbiased drug screening approaches,we discover Metformin,a drug that is commonly the first medication prescribed for type 2 diabetes,can induce CMA.We delineate the mechanism of CMA induction by Metformin to be via activation of TAK1-IKKα/β signaling that leads to phosphorylation of Ser85 of the key mediator of CMA,Hsc70,and its activation.Notably,we find that amyloid-beta precursor protein(APP)is a CMA substrate and that it binds to Hsc70 in an IKKα/β-dependent manner.The inhibition of CMA-mediated degradation of APP enhances its cytotoxicity.Importantly,we find that in the APP/PS1 mouse model of Alzheimer's disease(AD),activation of CMA by Hsc70 overexpression or Metformin potently reduces the accumulated brain Aβplaque levels and reverses the molecular and behavioral AD phenotypes.Our study elucidates a novel mechanism of CMA regulation via Metformin-TAK1-IKKα/β-Hsc70 signaling and suggests Metformin as a new activator of CMA for diseases,such as AD,where such therapeutic intervention could be beneficial.
基金supported by the National Natural Science Foundation of China(Grant No.52022068,51861145305 and 51772215)the National Key Research and Development Program of China(2018YFB0703600)the Innovation Program of Shanghai Municipal Education Commission and Shanghai Natural Science Foundation(19ZR1459900).
文摘Intrinsic partial occupation of Cu induces strong phonon scattering for an extremely low lattice thermal conductivity in TmCuTe_(2),which leads this material to be a promising candidate for thermoelectric applications.This work focus on the electronic and phononic transport properties of TmCuTe_(2) with Agalloying on the Cu site.Such a Ag/Cu substitution is found to enable a decrease in Hall carrier concentration from 141019 to 81019 cm^(3) for an evaluation of the charge transport based on a single parabolic band(SPB)model with acoustic scattering.In addition,Ag-substitution simultaneously introduces Cu/Ag point defects for extra phonon scattering,leading the lattice thermal conductivity to be as low as~0.25 W/m-K in a broad temperature.The optimization in carrier concentration and the reduction in lattice thermal conductivity contribute to a~40%improvement in average thermoelectric figure of merit(zT).The determination of band parameters enables a guidance for further advancements in this promising thermoelectric material.
文摘CORRECTION TO:PROTEIN CELL HTTPS://DOI.ORG/10.1007/S13238-021-00858-3 In legend of figure 1,this sentence“(C)293THK cells were treated as in a”should be corrected as“(C)293THK cells were treated as in(A)”.In legend of figure 2,“E-64D(10μmol/L)”in description of panel(B)should be removed.In section“Metformin activates chaperone-mediated autophagy”of RESULTS,E-64D in sentence“Metformininduced degradation of HK2 and PKM2 was blocked by lysosomal inhibitors(E-64D,Bafilomycin A1 and Leupeptin+NH4Cl)”should be removed.
