AIM To observe gene polymorphisms of TPMT and NUDT15, and compare their predictive value for azathioprine(AZA)-induced leukopenia in inflammatory bowel disease(IBD).METHODS This study enrolled 219 patients diagnosed w...AIM To observe gene polymorphisms of TPMT and NUDT15, and compare their predictive value for azathioprine(AZA)-induced leukopenia in inflammatory bowel disease(IBD).METHODS This study enrolled 219 patients diagnosed with IBD in Xiangya Hospital, Central South University, Changsha, China from February 2016 to November 2017. Peripheral blood of all patients was collected to detect their genotypes of TPMT and NUDT15 by pyrosequencing at the Department of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya Hospital. Eighty patients were treated with AZA according to the disease condition. During the first month, patients who received AZA underwent routine blood tests and liver function tests once a week. The endpoint of the study was leukopenia induced by AZA. By analyzing patient characteristics, genotypes and leukopenia induced by drug use, we found the risk factors associated with AZA-induced leukopenia.RESULTS There were 219 patients with IBD(160 men and 59 women), including 39 who were confirmed with ulcerative colitis(UC), 176 with Crohn's disease(CD) and 4 with undetermined IBD(UIBD). There were 44 patients(20.1%) with mutant genotype of NUDT15(C/T); among them, 16 received AZA, and 8(50%) developed leukopenia. There were 175 patients(79.7%) with wild genotype of NUDT15(C/C); among them, 64 received AZA, and 11(17.2%) developed leukopenia. A significant difference was found between NUDT15 C/T and its wild-type C/C(P = 0.004). There were only 3 patients with TPMT mutant genotype of A/G(1.4%) who participated in the research, and 1 of them was treated with AZA and developed leukopenia. The remaining 216 patients(98.6%) were found to bear the wild genotype of TPMT(A/A); among them, 79 patients received AZA, and 18(22.8%) developed leukopenia, and there was no significant difference from those with A/G(P = 0.071). The frequency of TPMT mutation was 1.4%, and NUDT15 mutation rate was significantly higher and reached 20.1%(P = 0.000). Therefore, NUDT15 gene polymorphism was obviously a better biomarker than TPMT gene polymorphism in the prediction of AZA-induced leukopenia.CONCLUSION Mutation rate of NUDT15 in Chinese IBD patients is higher than that of TPMT. NUDT15 polymorphism is a better predictor for AZA-induced leukopenia than TPMT polymorphism.展开更多
The rational design of highly active and stable atomically dispersed M-X4(M=Fe,Co,Ni,etc.,X=C,N)-based catalysts holds promises for wide application in almost all realms of catalysis.Despite great effort in the constr...The rational design of highly active and stable atomically dispersed M-X4(M=Fe,Co,Ni,etc.,X=C,N)-based catalysts holds promises for wide application in almost all realms of catalysis.Despite great effort in the construction of specific M-X4 centers,the possible effect of non-coordinated heteroatoms on the catalytic activity of metal centers has been rarely explored.Herein,we develop a new type of M-X4 catalyst composed of Fe-N4 centers and non-coordinated B heteroatoms(FeNC+B)and find the key role of non-coordinated B adjacent to Fe-N4 centers in tailoring their electron density and final catalytic selectivity.The experimental and theoretical results demonstrated that non-coordinated boron atoms could decrease the electron density of Fe-N4 centers to a suitable level and thus boost the selective production of nitriles from amine oxidation by depressing the formation of imines due to the flattened energy barrier of the reversible conversion of imines back to amines.As a reusable heterocatalyst,the state-of-the-art FeNC+B catalyst provides a turn-over frequency(TOF)value of 21.6 molbenzonitrile·molFe^−1·h^−1(100℃),outpacing that of bench-marked nonnoble-metal-based homogeneous catalyst by a factor of 3.4.展开更多
The greenhouse effect and global warming are serious problems because the increasing global demand for fossil fuels has led to a rapid rise in greenhouse gas exhaust emissions in the atmosphere and disruptive changes ...The greenhouse effect and global warming are serious problems because the increasing global demand for fossil fuels has led to a rapid rise in greenhouse gas exhaust emissions in the atmosphere and disruptive changes in climate. As a major contributor, CO2 has attracted much attention from scientists, who have attempted to convert it into useful products by electrochemical or photoelectrochemical reduction methods. Facile design of efficient but inexpensive and abundant catalysts to convert CO2 into fuels or valuable chemical products is essential for materials chemistry and catalysis in addressing global climate change as well as the energy crisis. Herein, we show that two-dimensional fewlayer graphitic carbon nitride （g-C3N4） can function as an efficient metal-free electrocatalyst for selective reduction of CO2 to CO at low overpotentials with a high Faradaic efficiency of - 80%. The polarized surface of ultrathin g-C3N4 layers （thickness： -1 nm）, with a more reductive conduction band, yields excellent electrochemical activity for CO2 reduction.展开更多
Primary immune thrombocytopenia(ITP),a common hemorrhagic disease causing a tremendous burden to the social economy,is characterized by the bleeding of mucosa,skin,brain,and/or other important organs/11 Serious hemorr...Primary immune thrombocytopenia(ITP),a common hemorrhagic disease causing a tremendous burden to the social economy,is characterized by the bleeding of mucosa,skin,brain,and/or other important organs/11 Serious hemorrhage can even lead to death.Despite its seriousness,the golden criteria for ITP diagnosis and treatment are lacking.Consequently,much hinges upon physician experience as well as the willingness of patients and their families.In fact,standards for diagnosis and treatment of patients with ITP only appeared when the American Society of Hematology published a landmark guideline in 1996.It is important to find out hematologists5 routine strategies for managing ITP and the extent they have complied with or deviated from ITP guidelines.However,such research is few and far between.We published such a study in 2009.121 After that,the context for China-based hematologists diagnosing and treating ITP has undergone fundamental changes,including the publication of the Chinese Society of Hematology(CSH)guideline in 2011 and its update in 2016.展开更多
基金Supported by National Natural Science Foundation of China,No.81370547 and No.81400642
文摘AIM To observe gene polymorphisms of TPMT and NUDT15, and compare their predictive value for azathioprine(AZA)-induced leukopenia in inflammatory bowel disease(IBD).METHODS This study enrolled 219 patients diagnosed with IBD in Xiangya Hospital, Central South University, Changsha, China from February 2016 to November 2017. Peripheral blood of all patients was collected to detect their genotypes of TPMT and NUDT15 by pyrosequencing at the Department of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya Hospital. Eighty patients were treated with AZA according to the disease condition. During the first month, patients who received AZA underwent routine blood tests and liver function tests once a week. The endpoint of the study was leukopenia induced by AZA. By analyzing patient characteristics, genotypes and leukopenia induced by drug use, we found the risk factors associated with AZA-induced leukopenia.RESULTS There were 219 patients with IBD(160 men and 59 women), including 39 who were confirmed with ulcerative colitis(UC), 176 with Crohn's disease(CD) and 4 with undetermined IBD(UIBD). There were 44 patients(20.1%) with mutant genotype of NUDT15(C/T); among them, 16 received AZA, and 8(50%) developed leukopenia. There were 175 patients(79.7%) with wild genotype of NUDT15(C/C); among them, 64 received AZA, and 11(17.2%) developed leukopenia. A significant difference was found between NUDT15 C/T and its wild-type C/C(P = 0.004). There were only 3 patients with TPMT mutant genotype of A/G(1.4%) who participated in the research, and 1 of them was treated with AZA and developed leukopenia. The remaining 216 patients(98.6%) were found to bear the wild genotype of TPMT(A/A); among them, 79 patients received AZA, and 18(22.8%) developed leukopenia, and there was no significant difference from those with A/G(P = 0.071). The frequency of TPMT mutation was 1.4%, and NUDT15 mutation rate was significantly higher and reached 20.1%(P = 0.000). Therefore, NUDT15 gene polymorphism was obviously a better biomarker than TPMT gene polymorphism in the prediction of AZA-induced leukopenia.CONCLUSION Mutation rate of NUDT15 in Chinese IBD patients is higher than that of TPMT. NUDT15 polymorphism is a better predictor for AZA-induced leukopenia than TPMT polymorphism.
基金supported by the National Natural Science Foundation of China(21722103,21720102002,21673140,21673273 and 21872163)the Shanghai Basic Research Program(16JC1401600)+1 种基金the SJTU-MPI partner group and the Open Research Fund of the State Key Laboratory of Inorganic Synthesis and Preparative Chemistry(Jilin University,China,Grant No.201809)Shanghai Synchrotron Radiation Facility for providing beam time(BL14W1)。
基金This work was supported by the National Natural Science Foundation of China(Nos.21722103,21931005,21720102002,and 21673140)Shanghai Science and Technology Committee(No.19JC1412600)the SJTU-MPI partner group.The authors thank Shanghai Synchrotron Radiation Facility for providing beam time(No.BL14W1).
文摘The rational design of highly active and stable atomically dispersed M-X4(M=Fe,Co,Ni,etc.,X=C,N)-based catalysts holds promises for wide application in almost all realms of catalysis.Despite great effort in the construction of specific M-X4 centers,the possible effect of non-coordinated heteroatoms on the catalytic activity of metal centers has been rarely explored.Herein,we develop a new type of M-X4 catalyst composed of Fe-N4 centers and non-coordinated B heteroatoms(FeNC+B)and find the key role of non-coordinated B adjacent to Fe-N4 centers in tailoring their electron density and final catalytic selectivity.The experimental and theoretical results demonstrated that non-coordinated boron atoms could decrease the electron density of Fe-N4 centers to a suitable level and thus boost the selective production of nitriles from amine oxidation by depressing the formation of imines due to the flattened energy barrier of the reversible conversion of imines back to amines.As a reusable heterocatalyst,the state-of-the-art FeNC+B catalyst provides a turn-over frequency(TOF)value of 21.6 molbenzonitrile·molFe^−1·h^−1(100℃),outpacing that of bench-marked nonnoble-metal-based homogeneous catalyst by a factor of 3.4.
基金This work was supported by National Natural Science Foundation of China （Nos. 21331004, 21673140, and 21671134）, Innovation Program of Shanghai Science and Technology Committee （No. 16JC1401600）, Shanghai Eastern Scholar Program, Shanghai Rising-Star Program （No. 16QA1402100） and SJTU-MPI partner group.
文摘The greenhouse effect and global warming are serious problems because the increasing global demand for fossil fuels has led to a rapid rise in greenhouse gas exhaust emissions in the atmosphere and disruptive changes in climate. As a major contributor, CO2 has attracted much attention from scientists, who have attempted to convert it into useful products by electrochemical or photoelectrochemical reduction methods. Facile design of efficient but inexpensive and abundant catalysts to convert CO2 into fuels or valuable chemical products is essential for materials chemistry and catalysis in addressing global climate change as well as the energy crisis. Herein, we show that two-dimensional fewlayer graphitic carbon nitride （g-C3N4） can function as an efficient metal-free electrocatalyst for selective reduction of CO2 to CO at low overpotentials with a high Faradaic efficiency of - 80%. The polarized surface of ultrathin g-C3N4 layers （thickness： -1 nm）, with a more reductive conduction band, yields excellent electrochemical activity for CO2 reduction.
文摘Primary immune thrombocytopenia(ITP),a common hemorrhagic disease causing a tremendous burden to the social economy,is characterized by the bleeding of mucosa,skin,brain,and/or other important organs/11 Serious hemorrhage can even lead to death.Despite its seriousness,the golden criteria for ITP diagnosis and treatment are lacking.Consequently,much hinges upon physician experience as well as the willingness of patients and their families.In fact,standards for diagnosis and treatment of patients with ITP only appeared when the American Society of Hematology published a landmark guideline in 1996.It is important to find out hematologists5 routine strategies for managing ITP and the extent they have complied with or deviated from ITP guidelines.However,such research is few and far between.We published such a study in 2009.121 After that,the context for China-based hematologists diagnosing and treating ITP has undergone fundamental changes,including the publication of the Chinese Society of Hematology(CSH)guideline in 2011 and its update in 2016.
基金This work was financially supported by National Basic Research Program of China (No.2013CB934102),the National Natural Science Foundation of China (Nos.21331004 and 21301116),SJTU-UM joint grant and Shanghai Eastern Scholar Program.
