Accumulation and aggregation of β-amyloid(Aβ) peptides result in neuronal death, leading to cognitive dysfunction in Alzheimer's disease. The self-assembled Aβ molecules form various intermediate aggregates incl...Accumulation and aggregation of β-amyloid(Aβ) peptides result in neuronal death, leading to cognitive dysfunction in Alzheimer's disease. The self-assembled Aβ molecules form various intermediate aggregates including oligomers that are more toxic to neurons than the mature aggregates, including fibrils. Thus, one strategy to alleviate Aβ toxicity is to facilitate the conversion of Aβ intermediates to larger aggregates such as fibrils. In this study, we designed a peptide named A3 that significantly enhanced the formation of amorphous aggregates of Aβ by accelerating the aggregation kinetics. Thioflavin T fluorescence experiments revealed an accelerated aggregation of Aβ monomers, accompanying reduced Aβ cytotoxicity. Transgenic Caenorhabditis elegans over-expressing amyloid precursor protein exhibited paralysis due to the accumulation of Aβ oligomers, and this phenotype was attenuated by feeding the animals with A3 peptide. These findings suggest that the Aβ aggregation-promotion effect can potentially be useful for developing strategies to reduce Aβ toxicity.展开更多
Co-secretion with insulin,highly amyloidogenic human amylin is considered to contribute to the initiation and progression of diabetic heart complications,despite other situations such as hypertension and atheroscleros...Co-secretion with insulin,highly amyloidogenic human amylin is considered to contribute to the initiation and progression of diabetic heart complications,despite other situations such as hypertension and atherosclerosis.In response to insulin resistance,hyperinsulinemia,and consequently hyperamylinemia,is common in prediabetic patients,where highly concentrated amylin is prone to form amylin oligomers,which further assemble into fibrils and amyloids with high b-sheet content.The infusion and deposition of oligomeric amylin in myocytes cause a series of consequences,including cytosolic Ca^(2+)dysregulation,calmodulin activation,myocyte hypertrophy,and ventricular stiffness,eventually leading to heart failure.In this review,we present the latest reports of amylin-related heart complications,provide new insights,and state the underlying pathogenesis,diagnosis,possible treatment,and prevention of diabetic cardiomyopathy.展开更多
Biodegradable magnesium-based alloys are very promising materials for temporary implants. Laser welding is an important joining method in such application. In this study, the as-rolled AZ31B magnesium alloy sheets of ...Biodegradable magnesium-based alloys are very promising materials for temporary implants. Laser welding is an important joining method in such application. In this study, the as-rolled AZ31B magnesium alloy sheets of 1 mm in thickness were successfully joined by Nd : YAG laser welding. The microstructure and properties of the welded joint were investigated. The result shows that the welded joint is characterized by a narrow heat-affected zone, finer grains and a large number of precipitates distribute in the matrix in the weld. Microhardness of the weld is significantly improved to 72 HV 0. 05 as compared to 55 HV 0. 05 of the base metal. Tensile strength of butt-welded joint is 180. 24 MPa, which is 76. 8% that of the base metal. The electrochemical corrosion experiment shows that the corrosion resistance of laser welded joint is significantly improved in a 3.5 wt. % NaCl solution.展开更多
The purpose of this research is to explore the feasibility of roller hemming of AZ31 B magnesium alloy sheet. During the test, a special experimental setup considering the current flow and insulation was designed and ...The purpose of this research is to explore the feasibility of roller hemming of AZ31 B magnesium alloy sheet. During the test, a special experimental setup considering the current flow and insulation was designed and employed. For the sake of simplicity, the flat surface-straight edge hemming style was selected. Electrical pulses were introduced in the pre-hemming and final hemming processes. The results show that when hemming at 448 K with hemming speed of 30 mm/min, AZ31 B magnesium alloy sheet was successfully hemmed with excellent perceived quality. No recoil/warp defect, cracking or springback was observed. Electrical pulses induced dynamic recrystallized grains were observed along the grain boundaries in the severely deformed area, which is of great importance to the improvement of the ductility of the material. The hardness was slightly increased after hemming with electrical pulses, and this fact could improve the friction resistance performance of the hemmed part.展开更多
基金supported by the National Natural Science Foundation of China(91127043,31600803,and 21273051)
文摘Accumulation and aggregation of β-amyloid(Aβ) peptides result in neuronal death, leading to cognitive dysfunction in Alzheimer's disease. The self-assembled Aβ molecules form various intermediate aggregates including oligomers that are more toxic to neurons than the mature aggregates, including fibrils. Thus, one strategy to alleviate Aβ toxicity is to facilitate the conversion of Aβ intermediates to larger aggregates such as fibrils. In this study, we designed a peptide named A3 that significantly enhanced the formation of amorphous aggregates of Aβ by accelerating the aggregation kinetics. Thioflavin T fluorescence experiments revealed an accelerated aggregation of Aβ monomers, accompanying reduced Aβ cytotoxicity. Transgenic Caenorhabditis elegans over-expressing amyloid precursor protein exhibited paralysis due to the accumulation of Aβ oligomers, and this phenotype was attenuated by feeding the animals with A3 peptide. These findings suggest that the Aβ aggregation-promotion effect can potentially be useful for developing strategies to reduce Aβ toxicity.
基金This work was supported by research grants from the National Natural Science Foundation of China(82070392 and 81900332).
文摘Co-secretion with insulin,highly amyloidogenic human amylin is considered to contribute to the initiation and progression of diabetic heart complications,despite other situations such as hypertension and atherosclerosis.In response to insulin resistance,hyperinsulinemia,and consequently hyperamylinemia,is common in prediabetic patients,where highly concentrated amylin is prone to form amylin oligomers,which further assemble into fibrils and amyloids with high b-sheet content.The infusion and deposition of oligomeric amylin in myocytes cause a series of consequences,including cytosolic Ca^(2+)dysregulation,calmodulin activation,myocyte hypertrophy,and ventricular stiffness,eventually leading to heart failure.In this review,we present the latest reports of amylin-related heart complications,provide new insights,and state the underlying pathogenesis,diagnosis,possible treatment,and prevention of diabetic cardiomyopathy.
基金The work was supported by the National Natural Science Foundation of China ( Grant No. 51305292 ) and the Aviation Science Foundation ( Grant No. 20105429001 ).
文摘Biodegradable magnesium-based alloys are very promising materials for temporary implants. Laser welding is an important joining method in such application. In this study, the as-rolled AZ31B magnesium alloy sheets of 1 mm in thickness were successfully joined by Nd : YAG laser welding. The microstructure and properties of the welded joint were investigated. The result shows that the welded joint is characterized by a narrow heat-affected zone, finer grains and a large number of precipitates distribute in the matrix in the weld. Microhardness of the weld is significantly improved to 72 HV 0. 05 as compared to 55 HV 0. 05 of the base metal. Tensile strength of butt-welded joint is 180. 24 MPa, which is 76. 8% that of the base metal. The electrochemical corrosion experiment shows that the corrosion resistance of laser welded joint is significantly improved in a 3.5 wt. % NaCl solution.
基金the National Natural Science Foundation of China(Nos.50975174 and 51275297)
文摘The purpose of this research is to explore the feasibility of roller hemming of AZ31 B magnesium alloy sheet. During the test, a special experimental setup considering the current flow and insulation was designed and employed. For the sake of simplicity, the flat surface-straight edge hemming style was selected. Electrical pulses were introduced in the pre-hemming and final hemming processes. The results show that when hemming at 448 K with hemming speed of 30 mm/min, AZ31 B magnesium alloy sheet was successfully hemmed with excellent perceived quality. No recoil/warp defect, cracking or springback was observed. Electrical pulses induced dynamic recrystallized grains were observed along the grain boundaries in the severely deformed area, which is of great importance to the improvement of the ductility of the material. The hardness was slightly increased after hemming with electrical pulses, and this fact could improve the friction resistance performance of the hemmed part.