Objective To investigate prognostic predictors of long-term survival of patients with cardiac amyloidosis （CA）, and to determine predictive value of high-sensitivity cardiac troponin T （hs-cTnT） in CA patients. Me...Objective To investigate prognostic predictors of long-term survival of patients with cardiac amyloidosis （CA）, and to determine predictive value of high-sensitivity cardiac troponin T （hs-cTnT） in CA patients. Methods We recruited 102 consecutive CA cases and followed these patients for 5 years. We described their clinical characteristics at presentation and used a new, high-sensitivity assay to determine the concentration of cTnT in plasma samples from these patients. Results The patients with poor prognosis showed older age （56 ±12 years vs. 50 ±15 years, P=0.022）, higher incidences of heart failure （36.92%vs. 16.22%, P=0.041）, pericardial effusion （60.00%vs. 35.14%, P=0.023）, greater thickness of interventricular septum （IVS） （15 ±4 mm vs. 13 ±4 mm, P=0.034）, higher level of hs-cTnT （0.186 ±0.249 ng/mL vs. 0.044 ±0.055 ng/mL, P=0.001） and higher NT-proBNP （N-terminal pro-B-type natriuretic pep-tide） levels （11,742 ± 10,464 pg/mL vs. 6,031 ± 7,458 pg/mL, P=0.006）. At multivariate Cox regression analysis, heart failure （HR：1.78, 95%CI：1.09-2.92, P=0.021）, greater wall thickness of IVS （HR：1.44, 95%CI：1.04-3.01, P=0.0375） and higher hs-cTnT level （HR：6.16, 95%CI：2.20-17.24, P=0.001） at enrollment emerged as independent predictors of all-cause mortality. Conclusions We showed that hs-cTnT is associated with a very ominous prognosis, and it is also the strongest predictor of all-cause mortality in multivariate analysis. Examination of hs-cTnT concentrations provides valuable prognostic information concerning long-term outcomes.展开更多
Using blind dock method,we find that thioflavin-T(ThT) can bind to both monomers and fibrils of the full-length β-amyloid peptide(Aβ1-42) and has a higher binding affinity to the fibrils.It is shown that the hydroph...Using blind dock method,we find that thioflavin-T(ThT) can bind to both monomers and fibrils of the full-length β-amyloid peptide(Aβ1-42) and has a higher binding affinity to the fibrils.It is shown that the hydrophobic interaction between the ligand(ThT) and substrate(Aβ1-42) are stronger than hydrogen bonds.Furthermore,ThT tends to be located near the C-terminus of Aβ monomer through hydrophobic and electrostatic interactions,while it tends to contact the residues Met35 and Gly27 of the fibril surface mainly through hydrophobic interaction.Finally,according to the docking results and ThT fluorescence assay,a kinetic equation is proposed to deduce the aggregation rate coefficient of Aβ1-42.展开更多
Compression elasticity of glucagon amyloid fibrils in the transverse direction was investigated by a nanoindentation approach based on atomic force microscopy (AFM).With force-volume mapping, we obtained the correlati...Compression elasticity of glucagon amyloid fibrils in the transverse direction was investigated by a nanoindentation approach based on atomic force microscopy (AFM).With force-volume mapping, we obtained the correlations between radially applied force and compression of amyloid fibrils, from which the radial compressive elasticity can be deduced.The estimated elastic modulus at three typical locations of fibrils varied from (0.72±0.80) GPa to (1.26±0.62) GPa under small external forces, imply-ing the structural heterogeneity of different fibrils.展开更多
Using blind dock method,we find that thioflavin-T(ThT) can bind to both monomers and fibrils of the full-length β-amyloid peptide(Aβ1-42) and has a higher binding affinity to the fibrils.It is shown that the hydroph...Using blind dock method,we find that thioflavin-T(ThT) can bind to both monomers and fibrils of the full-length β-amyloid peptide(Aβ1-42) and has a higher binding affinity to the fibrils.It is shown that the hydrophobic interaction between the ligand(ThT) and substrate(Aβ1-42) are stronger than hydrogen bonds.Furthermore,ThT tends to be located near the C-terminus of Aβ monomer through hydrophobic and electrostatic interactions,while it tends to contact the residues Met35 and Gly27 of the fibril surface mainly through hydrophobic interaction.Finally,according to the docking results and ThT fluorescence assay,a kinetic equation is proposed to deduce the aggregation rate coefficient of Aβ1-42.展开更多
Palladium nanoparticles(Pd NPs) were fabricated by using insulin amyloid fibrils(INSAFs) as biotemplates.Atomic force microscopy measurements showed that ultrasmall Pd NPs were well adsorbed and dispersed on surfaces ...Palladium nanoparticles(Pd NPs) were fabricated by using insulin amyloid fibrils(INSAFs) as biotemplates.Atomic force microscopy measurements showed that ultrasmall Pd NPs were well adsorbed and dispersed on surfaces of INSAFs. X-ray photoelectron spectroscopy confirmed the partial reduction of Pd ion into metallic Pd(0) probably due to the presence of Cys groups on surface of the insulin fibrils. The electrochemical performance of Pd/INSAFs to reduction of H_2O_2 was further evaluated by cyclic voltammetry. The remarkably high electrocatalytic activity, low detection limitation and excellent stability make the Pd/INSAFs a promising bio-nanoelectrocatalyst.展开更多
文摘Objective To investigate prognostic predictors of long-term survival of patients with cardiac amyloidosis （CA）, and to determine predictive value of high-sensitivity cardiac troponin T （hs-cTnT） in CA patients. Methods We recruited 102 consecutive CA cases and followed these patients for 5 years. We described their clinical characteristics at presentation and used a new, high-sensitivity assay to determine the concentration of cTnT in plasma samples from these patients. Results The patients with poor prognosis showed older age （56 ±12 years vs. 50 ±15 years, P=0.022）, higher incidences of heart failure （36.92%vs. 16.22%, P=0.041）, pericardial effusion （60.00%vs. 35.14%, P=0.023）, greater thickness of interventricular septum （IVS） （15 ±4 mm vs. 13 ±4 mm, P=0.034）, higher level of hs-cTnT （0.186 ±0.249 ng/mL vs. 0.044 ±0.055 ng/mL, P=0.001） and higher NT-proBNP （N-terminal pro-B-type natriuretic pep-tide） levels （11,742 ± 10,464 pg/mL vs. 6,031 ± 7,458 pg/mL, P=0.006）. At multivariate Cox regression analysis, heart failure （HR：1.78, 95%CI：1.09-2.92, P=0.021）, greater wall thickness of IVS （HR：1.44, 95%CI：1.04-3.01, P=0.0375） and higher hs-cTnT level （HR：6.16, 95%CI：2.20-17.24, P=0.001） at enrollment emerged as independent predictors of all-cause mortality. Conclusions We showed that hs-cTnT is associated with a very ominous prognosis, and it is also the strongest predictor of all-cause mortality in multivariate analysis. Examination of hs-cTnT concentrations provides valuable prognostic information concerning long-term outcomes.
基金supported by the National Natural Science Foundation of China(20825206,20091350914 & 90913003)the Specialized Research Fund for the Doctoral Program of Higher Education (20100002110069)
文摘Using blind dock method,we find that thioflavin-T(ThT) can bind to both monomers and fibrils of the full-length β-amyloid peptide(Aβ1-42) and has a higher binding affinity to the fibrils.It is shown that the hydrophobic interaction between the ligand(ThT) and substrate(Aβ1-42) are stronger than hydrogen bonds.Furthermore,ThT tends to be located near the C-terminus of Aβ monomer through hydrophobic and electrostatic interactions,while it tends to contact the residues Met35 and Gly27 of the fibril surface mainly through hydrophobic interaction.Finally,according to the docking results and ThT fluorescence assay,a kinetic equation is proposed to deduce the aggregation rate coefficient of Aβ1-42.
基金supported by the National Natural Science Foundation of China (10604034)Natural Science Foundation of Zhejiang Province (Y606309)K. C. Wong Magna Fund in Ningbo University
文摘Compression elasticity of glucagon amyloid fibrils in the transverse direction was investigated by a nanoindentation approach based on atomic force microscopy (AFM).With force-volume mapping, we obtained the correlations between radially applied force and compression of amyloid fibrils, from which the radial compressive elasticity can be deduced.The estimated elastic modulus at three typical locations of fibrils varied from (0.72±0.80) GPa to (1.26±0.62) GPa under small external forces, imply-ing the structural heterogeneity of different fibrils.
文摘Using blind dock method,we find that thioflavin-T(ThT) can bind to both monomers and fibrils of the full-length β-amyloid peptide(Aβ1-42) and has a higher binding affinity to the fibrils.It is shown that the hydrophobic interaction between the ligand(ThT) and substrate(Aβ1-42) are stronger than hydrogen bonds.Furthermore,ThT tends to be located near the C-terminus of Aβ monomer through hydrophobic and electrostatic interactions,while it tends to contact the residues Met35 and Gly27 of the fibril surface mainly through hydrophobic interaction.Finally,according to the docking results and ThT fluorescence assay,a kinetic equation is proposed to deduce the aggregation rate coefficient of Aβ1-42.
基金supported by the Natural Nature Science Foundation of China(No.11474173)the Natural Science Foundation of Zhejiang province(Nos.Y14A040006 and LQ14F040002)+1 种基金Ningbo Natural Science Foundation(Nos.2014A610202 and 2014A610149)the K.C.Wong Magna Fund of Ningbo University
文摘Palladium nanoparticles(Pd NPs) were fabricated by using insulin amyloid fibrils(INSAFs) as biotemplates.Atomic force microscopy measurements showed that ultrasmall Pd NPs were well adsorbed and dispersed on surfaces of INSAFs. X-ray photoelectron spectroscopy confirmed the partial reduction of Pd ion into metallic Pd(0) probably due to the presence of Cys groups on surface of the insulin fibrils. The electrochemical performance of Pd/INSAFs to reduction of H_2O_2 was further evaluated by cyclic voltammetry. The remarkably high electrocatalytic activity, low detection limitation and excellent stability make the Pd/INSAFs a promising bio-nanoelectrocatalyst.
