There are several cofactors which affect body iron metabolism and accelerate iron overload. Alcohol and hepatic viral infections are the most typical examples for clarifying the role of cofactors in iron overload. In ...There are several cofactors which affect body iron metabolism and accelerate iron overload. Alcohol and hepatic viral infections are the most typical examples for clarifying the role of cofactors in iron overload. In these conditions, iron is deposited in hepatocytes and Kupffer cells and reactive oxygen species （ROS） produced through Fenton reaction have key role to facilitate cellular uptake of transferrin-bound iron. Furthermore, hepcidin, antimicrobial peptide produced mainly in the liver is also responsible for intestinal iron absorption and reticuloendothelial iron release. In patients with ceruloplasmin deficiency, anemia and secondary iron overload in liver and neurodegeneration are reported. Furthermore, there is accumulating evidence that fatty acid accumulation without alcohol and obesity itself modifies iron overload states. Ineffective erythropoiesis is also an important factor to accelerate iron overload, which is associated with diseases such as thalassemia and myelodysplastic syndrome. When this condition persists, the dietary iron absorption is increased due to the increment of bone marrow erythropoiesis and tissue iron overload will thereafter occurs. In porphyria cutanea tarda, iron is secondarily accumulated in the liver.展开更多
Cytochrome P450 enzymes catalyze diverse oxidative transformations at the expense of reduced nicotinamide adenine dinucleotide phosphate(NADPH),however,their applications remain limited largely because NADPH is cost-p...Cytochrome P450 enzymes catalyze diverse oxidative transformations at the expense of reduced nicotinamide adenine dinucleotide phosphate(NADPH),however,their applications remain limited largely because NADPH is cost-prohibitive for biocatalysis at scale yet tightly regulated in host cells.A highly challenging task for P450 catalysis has been to develop an alternative and biocompatible electrondonating system.Here we engineered P450 BM3 to favor reduced nicotinamide cytosine dinucleotide(NCDH)and created non-natural cofactor-dependent P450 catalysis.Two outstanding mutants were identified with over 640-fold NCDH preference improvement and good catalytic efficiencies of over15,000 M^(-1)s^(-1)for the oxidation of the fatty acid probe 12-(para-nitrophenoxy)-dodecanoate.Molecular docking analysis indicated that these mutants bear a compacted cofactor entrance.Upon fusing with an NCD-dependent formate dehydrogenase,fused proteins functioned as NCDH-specific P450catalysts by using formate as the electron donor.Importantly,these mutants and fusions catalyzed NCDH-dependent hydroxylation of fatty acids with similar chain length preference to those by natural P450 BM3 in the presence of NADPH and also similar regioselectivity for subterminal hydroxylation of lauric acid.As P450 BM3 and its variants are catalytically powerful to take diverse substrates and convey different reaction paths,our results offer an exciting opportunity to devise advanced cell factories that convey oxidative biocatalysis with an orthogonal reducing power supply system.展开更多
The iron molybdenum cofactor(FeMoco) of nitrogenase MoFe protein from Azotobacter vinelandii OP was extracted by N methylformamide(NMF). The effects of FeMoco(in NMF) on electronic spectrum and fluorescence...The iron molybdenum cofactor(FeMoco) of nitrogenase MoFe protein from Azotobacter vinelandii OP was extracted by N methylformamide(NMF). The effects of FeMoco(in NMF) on electronic spectrum and fluorescence intensity of fluorescein dimercury acetate(FDMA)(in 1 mol/L NaOH) were investigated by fluorophotometric titrations and compared with those of (NH 4) 2MoS 4 and complexes of (NH 4) 2MoS 4 with Na 2S or Na 2S 2 or (NH 4) 2S x on the relative properties of FDMA. It was found that the electronic spectrum of FDMA displayed hypsochromic shift(17 nm) in the presence of FeMoco just like that in the presence of other inorganic sulfides and that the titration curve for the quench of FDMA with FeMoco is very similar to that for the quench of FDMA with complex of (NH 4) 2MoS 4 with Na 2S 2(mole ratio is 1∶3). The results showed that FeMoco(N) probably contained S—S bonds and its structure was found to be changed compared with Kim Rees structural model. This change should profit the formation of the polymer.展开更多
Two k-hyperconnection expressions of a general k-order cofactor Y<sub>（i,j）</sub> are presentedfor the indefinite parameter matrix Y of a linear system by applying directed hypergraph theory,and based on...Two k-hyperconnection expressions of a general k-order cofactor Y<sub>（i,j）</sub> are presentedfor the indefinite parameter matrix Y of a linear system by applying directed hypergraph theory,and based on it a decomposition theorem of Y<sub>（i,j）</sub> is derived.By this theorem,the multi-leveltearing and analysis can be carried out easily for any linear large system.This is a new mul-tilevel topological analysis method.Using proposed method the scale of systems which can betopologically analysed by a computer will be enlarged.展开更多
Microtubules play important roles in neuronal morphogenesis, including cellular polarization, neurite growth, and branching. A microtubule is a polymer of a- and β-tubulin heterodimers that are formed by a multistep ...Microtubules play important roles in neuronal morphogenesis, including cellular polarization, neurite growth, and branching. A microtubule is a polymer of a- and β-tubulin heterodimers that are formed by a multistep process assisted by at least five tubulin-fold- ing cofactors （TBCA-E） （Lopez-Fanarraga et al., 2001）. Newly syn- thesized α- and β-tubulins associate with the cytosolic chaperonin complex （CCT）, and then the quasi-native tubulins interact with five tubulin-folding cofactors. The α- and β-tubulins first interact with TBCB and TBCA, which are further transferred to TBCE and TBCD, respectively. The α- and β-tubulins, TBCC, TBCD, and TBCE form a supercomplex, and guanosine triphosphate （GTP） hydrolysis occurs within the supercomplex, releasing a tubulin heterodimer. In addition to their functions in tubulin folding and tubulin heterodimer formation, excess amounts of TBCD or TBCE may interact with tubulin heterodimers, leading to their degrada- tion. Thus, tubulin-folding cofactors may play a role in both the synthesis and degradation of tubulin heterodimers.展开更多
Introduction: High grade dysplasia of the cervix has a high incidence and can progress to cervical cancer. The aim was to study cofactors associated with high-grade cervical dysplasia. Methodology: This was a retrospe...Introduction: High grade dysplasia of the cervix has a high incidence and can progress to cervical cancer. The aim was to study cofactors associated with high-grade cervical dysplasia. Methodology: This was a retrospective case-control study without matching. Women with high grade dysplasia were the cases while those with a normal screening test represented the controls. The study took place at the Gabriel Touré University Hospital Center in Bamako. We included 351 cases and 420 controls. The capture and analysis were performed using the SPSS 20 software. A univariate and multivariate logistic regression analysis was performed for the analysis of risk cofactors. The statistical tests used were the odds ratio and its confidence interval and the statistical significance threshold was set at p Results: In univariate analysis, the co-factors statistically significantly associated with the occurrence of high-grade dysplasia were parity 0.6 (0.5 - 0.9), gestational 0.7 (0.5 - 0.9), smoking of the spouse 3.4 (1.1 - 11.3), the non-schooling 1.4 (1.2 - 2.1). In multivariate analysis after adjusting for confounding factors, two co-factors have significantly increased the risk of high-grade dysplasia: lack of schooling 1.4 (1.2 - 2.0) and polygamy 1.5 (1.4 - 2.5). Conclusion: At the end of this study, polygamy and lack of schooling were the main risk factors. The prevention of cervical cancer will go through the education of girls and women as well as communication for behavioral change and social change.展开更多
In literature, neutral polyethylene oxide (PEO) flocculated fines at low shear rates, while with cofactor (CF) addition, the formed CF-PEO complex showed larger ability to bridge fines, producing flocs. In this work, ...In literature, neutral polyethylene oxide (PEO) flocculated fines at low shear rates, while with cofactor (CF) addition, the formed CF-PEO complex showed larger ability to bridge fines, producing flocs. In this work, some process factors were found having significant effects on fines flocculation. Increases in CF to PEO ratio at constant PEO enhanced the bridging bonds, causing increases in flocculation initial rate (efficiency), amplitude (floc size), and fastness (a decrease in characteristic time). On the other hand, an increase in stirring rate (shear rate) in flocculation vessel caused decreases in initial rate and amplitude, and an increase in the fastness. All runs showed transient flocculation;the amplitude increased with time, reached maximum at equilibrium, and then started to decrease showing deflocculation. In brief, the CF to PEO ratio and the shear rate were found important parameters in mill operation, having significant effects on flocculation efficiency, fastness, and floc size.展开更多
Chemoenzymatic catalysis can give full play to the advantages of versatile reactivity of chemocatalysis and excellent chemo-,regio-,and stereoselectivities of biocatalysis.These chemoenzymatic methods can not only sav...Chemoenzymatic catalysis can give full play to the advantages of versatile reactivity of chemocatalysis and excellent chemo-,regio-,and stereoselectivities of biocatalysis.These chemoenzymatic methods can not only save resource,cost,and operating time but also reduce the number of reaction steps,and avoid separating unstable intermediates,leading to the generation of more products under greener circumstances and thereby playing an indispensable role in the fields of medicine,materials and fine chemicals.Although incompatible challenges between chemocatalyst and biocatalyst remain,strategies such as biphasic system,artificial metalloenzymes,immobilization or supramolecular host,and protein engineering have been designed to overcome these issues.In this review,chemoenzymatic catalysis according to different chemocatalysis types was classifiably described,and in particular,the classic dynamic kinetic resolutions(DKR)and cofactor regeneration were summarized.Finally,the bottlenecks and development of chemoenzymatic catalysis were summarized,and future development was prospected.展开更多
The mechanical background of the bivariate spline space of degree 2 and smoothness 1 on rectangular partition is presented constructively. Making use of mechanical analysis method, by acting couples along the interior...The mechanical background of the bivariate spline space of degree 2 and smoothness 1 on rectangular partition is presented constructively. Making use of mechanical analysis method, by acting couples along the interior edges with suitable evaluations, the deflection surface is divided into piecewise form, therefore, the relation between a class of bivariate splines on rectangular partition and the pure bending of thin plate is established. In addition, the interpretation of smoothing cofactor and conformality condition from the mechanical point of view is given. Furthermore, by introducing twisting moments, the mechanical background of any spline belong to the above space is set up.展开更多
A contiguous derivation of radius and center of the insphere of a general tetrahedron is given. Therefore a linear system is derived. After a transformation of it the calculation of radius and center can be separated ...A contiguous derivation of radius and center of the insphere of a general tetrahedron is given. Therefore a linear system is derived. After a transformation of it the calculation of radius and center can be separated from each other. The remaining linear system for the center of the insphere can be solved after discovering the inverse of the corresponding coefficient matrix. This procedure can also be applied in the planar case to determine radius and center of the incircle of a triangle.展开更多
The ONIOM quantum mechanics method is used to study the reaction of one-carbon unit transfer from an imidazolidine to 6- aminouracil model with the participation of water molecules.The computation results show that in...The ONIOM quantum mechanics method is used to study the reaction of one-carbon unit transfer from an imidazolidine to 6- aminouracil model with the participation of water molecules.The computation results show that in this reaction the participation of H_2O molecule makes the energy barrier lower because of the H-bond interaction.展开更多
Density Functional Theory (DFT) method was used in this paper to study one-carbon transfer from 1,10-tetrahydroquinoxaline, an analogue of tetrahydrofolic acid, to methylamine. This reaction can be completed via two ...Density Functional Theory (DFT) method was used in this paper to study one-carbon transfer from 1,10-tetrahydroquinoxaline, an analogue of tetrahydrofolic acid, to methylamine. This reaction can be completed via two paths. From the computation result we can conclude that a general-acid catalysis exists in this reaction. By computation we find DFT has its limitation in describing a newly incorporated structure with a unit charge.展开更多
i) Instead of x￣n+ y￣n = z￣n ,we use as the general equation of Fermat's Last Theorem (FLT),where a and b are two arbitrary natural numbers .By means of binomial expansion ,(0.1) an be written as Because a￣...i) Instead of x￣n+ y￣n = z￣n ,we use as the general equation of Fermat's Last Theorem (FLT),where a and b are two arbitrary natural numbers .By means of binomial expansion ,(0.1) an be written as Because a￣r-(-b)￣r always contains a +b as its factor ,(0.2) can be written as where φ_r =[a￣r-(-b)￣r]/ (a+b ) are integers for r=1 . 2, 3. ...n (ii) Lets be a factor of a+b and let (a +b) = se. We can use x= sy to transform (0.3 ) to the following (0.4)(iii ) Dividing (0.4) by s￣2 we have On the left side of (0.5) there is a polynomial of y with integer coefficient and on the right side there is a constant cφ/s .If cφ/s is not an integer ,then we cannot find an integer y to satisfy (0.5), and then FLT is true for this case. If cφ_n/s is an integer ,we may change a and c such the cφ_n/s≠an integer .展开更多
文摘There are several cofactors which affect body iron metabolism and accelerate iron overload. Alcohol and hepatic viral infections are the most typical examples for clarifying the role of cofactors in iron overload. In these conditions, iron is deposited in hepatocytes and Kupffer cells and reactive oxygen species （ROS） produced through Fenton reaction have key role to facilitate cellular uptake of transferrin-bound iron. Furthermore, hepcidin, antimicrobial peptide produced mainly in the liver is also responsible for intestinal iron absorption and reticuloendothelial iron release. In patients with ceruloplasmin deficiency, anemia and secondary iron overload in liver and neurodegeneration are reported. Furthermore, there is accumulating evidence that fatty acid accumulation without alcohol and obesity itself modifies iron overload states. Ineffective erythropoiesis is also an important factor to accelerate iron overload, which is associated with diseases such as thalassemia and myelodysplastic syndrome. When this condition persists, the dietary iron absorption is increased due to the increment of bone marrow erythropoiesis and tissue iron overload will thereafter occurs. In porphyria cutanea tarda, iron is secondarily accumulated in the liver.
基金supported by the National Key R&D Program of China(2019YFA0904900)the National Natural Science Foundation of China(21877112,21837002,21721004)。
文摘Cytochrome P450 enzymes catalyze diverse oxidative transformations at the expense of reduced nicotinamide adenine dinucleotide phosphate(NADPH),however,their applications remain limited largely because NADPH is cost-prohibitive for biocatalysis at scale yet tightly regulated in host cells.A highly challenging task for P450 catalysis has been to develop an alternative and biocompatible electrondonating system.Here we engineered P450 BM3 to favor reduced nicotinamide cytosine dinucleotide(NCDH)and created non-natural cofactor-dependent P450 catalysis.Two outstanding mutants were identified with over 640-fold NCDH preference improvement and good catalytic efficiencies of over15,000 M^(-1)s^(-1)for the oxidation of the fatty acid probe 12-(para-nitrophenoxy)-dodecanoate.Molecular docking analysis indicated that these mutants bear a compacted cofactor entrance.Upon fusing with an NCD-dependent formate dehydrogenase,fused proteins functioned as NCDH-specific P450catalysts by using formate as the electron donor.Importantly,these mutants and fusions catalyzed NCDH-dependent hydroxylation of fatty acids with similar chain length preference to those by natural P450 BM3 in the presence of NADPH and also similar regioselectivity for subterminal hydroxylation of lauric acid.As P450 BM3 and its variants are catalytically powerful to take diverse substrates and convey different reaction paths,our results offer an exciting opportunity to devise advanced cell factories that convey oxidative biocatalysis with an orthogonal reducing power supply system.
文摘The iron molybdenum cofactor(FeMoco) of nitrogenase MoFe protein from Azotobacter vinelandii OP was extracted by N methylformamide(NMF). The effects of FeMoco(in NMF) on electronic spectrum and fluorescence intensity of fluorescein dimercury acetate(FDMA)(in 1 mol/L NaOH) were investigated by fluorophotometric titrations and compared with those of (NH 4) 2MoS 4 and complexes of (NH 4) 2MoS 4 with Na 2S or Na 2S 2 or (NH 4) 2S x on the relative properties of FDMA. It was found that the electronic spectrum of FDMA displayed hypsochromic shift(17 nm) in the presence of FeMoco just like that in the presence of other inorganic sulfides and that the titration curve for the quench of FDMA with FeMoco is very similar to that for the quench of FDMA with complex of (NH 4) 2MoS 4 with Na 2S 2(mole ratio is 1∶3). The results showed that FeMoco(N) probably contained S—S bonds and its structure was found to be changed compared with Kim Rees structural model. This change should profit the formation of the polymer.
文摘Two k-hyperconnection expressions of a general k-order cofactor Y<sub>（i,j）</sub> are presentedfor the indefinite parameter matrix Y of a linear system by applying directed hypergraph theory,and based on it a decomposition theorem of Y<sub>（i,j）</sub> is derived.By this theorem,the multi-leveltearing and analysis can be carried out easily for any linear large system.This is a new mul-tilevel topological analysis method.Using proposed method the scale of systems which can betopologically analysed by a computer will be enlarged.
基金supported by grants from the Ministry of Education,Culture,Sports,Science and Technology in Japan to MM and TCthe Japan Society for the Promotion of Science to MO,MM,and TCthe Japan Science and Technology Agency to M.M.and TC
文摘Microtubules play important roles in neuronal morphogenesis, including cellular polarization, neurite growth, and branching. A microtubule is a polymer of a- and β-tubulin heterodimers that are formed by a multistep process assisted by at least five tubulin-fold- ing cofactors （TBCA-E） （Lopez-Fanarraga et al., 2001）. Newly syn- thesized α- and β-tubulins associate with the cytosolic chaperonin complex （CCT）, and then the quasi-native tubulins interact with five tubulin-folding cofactors. The α- and β-tubulins first interact with TBCB and TBCA, which are further transferred to TBCE and TBCD, respectively. The α- and β-tubulins, TBCC, TBCD, and TBCE form a supercomplex, and guanosine triphosphate （GTP） hydrolysis occurs within the supercomplex, releasing a tubulin heterodimer. In addition to their functions in tubulin folding and tubulin heterodimer formation, excess amounts of TBCD or TBCE may interact with tubulin heterodimers, leading to their degrada- tion. Thus, tubulin-folding cofactors may play a role in both the synthesis and degradation of tubulin heterodimers.
文摘Introduction: High grade dysplasia of the cervix has a high incidence and can progress to cervical cancer. The aim was to study cofactors associated with high-grade cervical dysplasia. Methodology: This was a retrospective case-control study without matching. Women with high grade dysplasia were the cases while those with a normal screening test represented the controls. The study took place at the Gabriel Touré University Hospital Center in Bamako. We included 351 cases and 420 controls. The capture and analysis were performed using the SPSS 20 software. A univariate and multivariate logistic regression analysis was performed for the analysis of risk cofactors. The statistical tests used were the odds ratio and its confidence interval and the statistical significance threshold was set at p Results: In univariate analysis, the co-factors statistically significantly associated with the occurrence of high-grade dysplasia were parity 0.6 (0.5 - 0.9), gestational 0.7 (0.5 - 0.9), smoking of the spouse 3.4 (1.1 - 11.3), the non-schooling 1.4 (1.2 - 2.1). In multivariate analysis after adjusting for confounding factors, two co-factors have significantly increased the risk of high-grade dysplasia: lack of schooling 1.4 (1.2 - 2.0) and polygamy 1.5 (1.4 - 2.5). Conclusion: At the end of this study, polygamy and lack of schooling were the main risk factors. The prevention of cervical cancer will go through the education of girls and women as well as communication for behavioral change and social change.
文摘In literature, neutral polyethylene oxide (PEO) flocculated fines at low shear rates, while with cofactor (CF) addition, the formed CF-PEO complex showed larger ability to bridge fines, producing flocs. In this work, some process factors were found having significant effects on fines flocculation. Increases in CF to PEO ratio at constant PEO enhanced the bridging bonds, causing increases in flocculation initial rate (efficiency), amplitude (floc size), and fastness (a decrease in characteristic time). On the other hand, an increase in stirring rate (shear rate) in flocculation vessel caused decreases in initial rate and amplitude, and an increase in the fastness. All runs showed transient flocculation;the amplitude increased with time, reached maximum at equilibrium, and then started to decrease showing deflocculation. In brief, the CF to PEO ratio and the shear rate were found important parameters in mill operation, having significant effects on flocculation efficiency, fastness, and floc size.
基金The authors thank the financial support by National Natural Science Foundation of China(21776132,21878142)Jiangsu Province Natural Science Foundation for Distinguished Young Scholars(BK20190035)+2 种基金National Key Research and Development Program of China(2019YFD1101202)Jiangsu Province Natural Science Foundation for Youths(BK20200685)China Postdoctoral Science Foundation(2019M660113).
文摘Chemoenzymatic catalysis can give full play to the advantages of versatile reactivity of chemocatalysis and excellent chemo-,regio-,and stereoselectivities of biocatalysis.These chemoenzymatic methods can not only save resource,cost,and operating time but also reduce the number of reaction steps,and avoid separating unstable intermediates,leading to the generation of more products under greener circumstances and thereby playing an indispensable role in the fields of medicine,materials and fine chemicals.Although incompatible challenges between chemocatalyst and biocatalyst remain,strategies such as biphasic system,artificial metalloenzymes,immobilization or supramolecular host,and protein engineering have been designed to overcome these issues.In this review,chemoenzymatic catalysis according to different chemocatalysis types was classifiably described,and in particular,the classic dynamic kinetic resolutions(DKR)and cofactor regeneration were summarized.Finally,the bottlenecks and development of chemoenzymatic catalysis were summarized,and future development was prospected.
基金Project supported by the National Natural Science Foundation of China(Nos.60533060,69973010 and 10271022)
文摘The mechanical background of the bivariate spline space of degree 2 and smoothness 1 on rectangular partition is presented constructively. Making use of mechanical analysis method, by acting couples along the interior edges with suitable evaluations, the deflection surface is divided into piecewise form, therefore, the relation between a class of bivariate splines on rectangular partition and the pure bending of thin plate is established. In addition, the interpretation of smoothing cofactor and conformality condition from the mechanical point of view is given. Furthermore, by introducing twisting moments, the mechanical background of any spline belong to the above space is set up.
文摘A contiguous derivation of radius and center of the insphere of a general tetrahedron is given. Therefore a linear system is derived. After a transformation of it the calculation of radius and center can be separated from each other. The remaining linear system for the center of the insphere can be solved after discovering the inverse of the corresponding coefficient matrix. This procedure can also be applied in the planar case to determine radius and center of the incircle of a triangle.
文摘The ONIOM quantum mechanics method is used to study the reaction of one-carbon unit transfer from an imidazolidine to 6- aminouracil model with the participation of water molecules.The computation results show that in this reaction the participation of H_2O molecule makes the energy barrier lower because of the H-bond interaction.
基金This work was supported by the grant from the National Natural Science Foundation of China (No. 29973021)
文摘Density Functional Theory (DFT) method was used in this paper to study one-carbon transfer from 1,10-tetrahydroquinoxaline, an analogue of tetrahydrofolic acid, to methylamine. This reaction can be completed via two paths. From the computation result we can conclude that a general-acid catalysis exists in this reaction. By computation we find DFT has its limitation in describing a newly incorporated structure with a unit charge.
文摘i) Instead of x￣n+ y￣n = z￣n ,we use as the general equation of Fermat's Last Theorem (FLT),where a and b are two arbitrary natural numbers .By means of binomial expansion ,(0.1) an be written as Because a￣r-(-b)￣r always contains a +b as its factor ,(0.2) can be written as where φ_r =[a￣r-(-b)￣r]/ (a+b ) are integers for r=1 . 2, 3. ...n (ii) Lets be a factor of a+b and let (a +b) = se. We can use x= sy to transform (0.3 ) to the following (0.4)(iii ) Dividing (0.4) by s￣2 we have On the left side of (0.5) there is a polynomial of y with integer coefficient and on the right side there is a constant cφ/s .If cφ/s is not an integer ,then we cannot find an integer y to satisfy (0.5), and then FLT is true for this case. If cφ_n/s is an integer ,we may change a and c such the cφ_n/s≠an integer .
