Amyloid β-peptide （Aβ） aggregation is a critical step in the pathogenesis of Alzheimer＇s disease （AD）. Inhibition of A[3 production, dissolution of existing aggregates and clearance of Aβ represent valid thera...Amyloid β-peptide （Aβ） aggregation is a critical step in the pathogenesis of Alzheimer＇s disease （AD）. Inhibition of A[3 production, dissolution of existing aggregates and clearance of Aβ represent valid therapeutic strategies against AD. Herein, a novel platinum（II）-coordinated graphitic carbon nitride （g-C3N4） nanosheet （g-C3N4@Pt） has been designed to covalently bind to Aβ and modulate the peptide＇s aggregation and toxicity. Furthermore, g-CBN4@Pt nanosheets possess high photocatalytic activity and can oxygenate Aβ upon visible light irradiation, remarkably attenuating both the aggregation potency and neurotoxicity of Aβ Due to its ability to cross the blood-brain barrier （BBB） and its good biocompatibility, g-C3N4@Pt nanosheet is a promising inhibitor of Aβ aggregation. This study may serve as a model for the engineering of novel multifunctional nanomaterials used for the treatment of AD.展开更多
Recent clinical and epidemiological research has shown that insulin is associated with the pathological mechanisms of Alzheimer＇s disease （AD） and can protect against the oxidative stress triggered by amyloidq3 pep...Recent clinical and epidemiological research has shown that insulin is associated with the pathological mechanisms of Alzheimer＇s disease （AD） and can protect against the oxidative stress triggered by amyloidq3 peptide （Aβ3）. Herein, we present a systematic study on how the cross-fibrillation of insulin and Aβ is influenced by the surface chirality of an interface designed to mimic their aggregation on the cytomembrane. Intriguingly, the surface chirality strongly affected the aggregation kinetics, structure, morphologβ and cellular responses of the cross-aggregates of insulin and Aβ. On a D-phenylalanine- modified surface, Aβ induced insulin to co-aggregate into β-sheet-rich fibrils and cross-fibrils that showed a pronounced cellular toxicity. However, on an L-phenylalanine-modified surface, insulin and Aβ3 formed non-toxic amorphous aggregates. Our work indicates that surface chirality can influence the cross- fibrillation of Aβ and insulin as well as the cytotoxicity of their aggregates.展开更多
The aggregation of amyloid-β peptide （Aβ） is implicated in the pathology of Alzheimer＇s disease （AD）, and Aβ oligomers are considered the most toxic species. Therefore, the detection and clearance of Aβ oligo...The aggregation of amyloid-β peptide （Aβ） is implicated in the pathology of Alzheimer＇s disease （AD）, and Aβ oligomers are considered the most toxic species. Therefore, the detection and clearance of Aβ oligomers are crucial for the theranostic strategies for AD. However, effective methods for the detection of Aβ oligomers are rare, and only few of the oligomer-specific sensors have therapeutic functions as well. Recent studies have demonstrated that the toxicity of Aβ oligomers is related to the number of exposed hydrophobic residues. In this study, an oligomer-specific fluorescent probe, which was based on the hydrophobic regions that are exposed on Aβ oligomer surfaces was designed and synthesized. For improving the ability to recognize Aβ oligomers, the in situ treatment of AD symptoms and the ability to penetrate the blood-brain barrier, the probe and KLVFF peptide （an Aβ-target peptide） were modified on the surfaces of magnetic nanoparticles （MNP@NFP-pep）. This complex could detect Aβ oligomers specifically, and achieve the wireless deep magnetothermally mediated disaggregation of Aβ aggregates with an alternating magnetic field. This work provides new insights into the development of a ＂sense and treat＂ system for AD therapy.展开更多
In the span of thousands of years of history,especially during the confrontation with western powers in the past centuries,the Chinese nation has transformed itself from a"self-being"to a"self-conscious...In the span of thousands of years of history,especially during the confrontation with western powers in the past centuries,the Chinese nation has transformed itself from a"self-being"to a"self-conscious"national entity,forming a multi-level and multi-dimensional community structure.As"the marginal"in the"Chinese cultural circle",visible and intangible,overseas O Chinese communities have always maintained a dynamic relationship with the"core",and overseas Chinese have constantly expanded the scope of the Chinese national space through alternative channels of culture and society.By analyzing the progression of three phases,namely the period before the 1850s,1850s-1950s and the period after the 1950s,this paper examines the role of overseas Chinese in the multidimensional space expansion of the Chinese nation.We deem that overseas Chinese maintained varied degrees of spatial connection and participated in the construction of the national homeland in multiple scales such as ethnic identity,cultural identity,economic ties and social networks;The sense of ethnic community of overseas Chinese is embodied in the inclinations toward the ancestral country,multi-dimensional identification and the concept of righteousness,showing the characteristics of pluralism and consensus;Due to the variance of affecting factors,such as migration time and intergenerational relations,geographical distance and cyberspace accessibility,policies of the country of origin and transnational interaction,there are distinguishable traits between different groups of overseas Chinese and the"core"of the multidimensional space of the Chinese nation.Overseas Chinese not only expand out,but also bridge and tie up the multidimensional and three-dimensional space of the Chinese nation.展开更多
基金This work was supported by the National Basic Research Program of China （Nos. 2012CB720602 and 2011CB936004）, and the National Natural Science Foundation of China （Nos. 21210002, 21431007, and 21533008）.
文摘Amyloid β-peptide （Aβ） aggregation is a critical step in the pathogenesis of Alzheimer＇s disease （AD）. Inhibition of A[3 production, dissolution of existing aggregates and clearance of Aβ represent valid therapeutic strategies against AD. Herein, a novel platinum（II）-coordinated graphitic carbon nitride （g-C3N4） nanosheet （g-C3N4@Pt） has been designed to covalently bind to Aβ and modulate the peptide＇s aggregation and toxicity. Furthermore, g-CBN4@Pt nanosheets possess high photocatalytic activity and can oxygenate Aβ upon visible light irradiation, remarkably attenuating both the aggregation potency and neurotoxicity of Aβ Due to its ability to cross the blood-brain barrier （BBB） and its good biocompatibility, g-C3N4@Pt nanosheet is a promising inhibitor of Aβ aggregation. This study may serve as a model for the engineering of novel multifunctional nanomaterials used for the treatment of AD.
文摘Recent clinical and epidemiological research has shown that insulin is associated with the pathological mechanisms of Alzheimer＇s disease （AD） and can protect against the oxidative stress triggered by amyloidq3 peptide （Aβ3）. Herein, we present a systematic study on how the cross-fibrillation of insulin and Aβ is influenced by the surface chirality of an interface designed to mimic their aggregation on the cytomembrane. Intriguingly, the surface chirality strongly affected the aggregation kinetics, structure, morphologβ and cellular responses of the cross-aggregates of insulin and Aβ. On a D-phenylalanine- modified surface, Aβ induced insulin to co-aggregate into β-sheet-rich fibrils and cross-fibrils that showed a pronounced cellular toxicity. However, on an L-phenylalanine-modified surface, insulin and Aβ3 formed non-toxic amorphous aggregates. Our work indicates that surface chirality can influence the cross- fibrillation of Aβ and insulin as well as the cytotoxicity of their aggregates.
基金Financial support was provided by the National Basic Research Program of China （973 Program） （No. 2012CB720602）, the Project of Science and Technology Development Plan for Jilin Province （No. 20150520004JH） and the National Natural Science Foundation of China （NSFC） （Nos. 21210002, 21431007, 21402183 and 21533008）.
文摘The aggregation of amyloid-β peptide （Aβ） is implicated in the pathology of Alzheimer＇s disease （AD）, and Aβ oligomers are considered the most toxic species. Therefore, the detection and clearance of Aβ oligomers are crucial for the theranostic strategies for AD. However, effective methods for the detection of Aβ oligomers are rare, and only few of the oligomer-specific sensors have therapeutic functions as well. Recent studies have demonstrated that the toxicity of Aβ oligomers is related to the number of exposed hydrophobic residues. In this study, an oligomer-specific fluorescent probe, which was based on the hydrophobic regions that are exposed on Aβ oligomer surfaces was designed and synthesized. For improving the ability to recognize Aβ oligomers, the in situ treatment of AD symptoms and the ability to penetrate the blood-brain barrier, the probe and KLVFF peptide （an Aβ-target peptide） were modified on the surfaces of magnetic nanoparticles （MNP@NFP-pep）. This complex could detect Aβ oligomers specifically, and achieve the wireless deep magnetothermally mediated disaggregation of Aβ aggregates with an alternating magnetic field. This work provides new insights into the development of a ＂sense and treat＂ system for AD therapy.
文摘In the span of thousands of years of history,especially during the confrontation with western powers in the past centuries,the Chinese nation has transformed itself from a"self-being"to a"self-conscious"national entity,forming a multi-level and multi-dimensional community structure.As"the marginal"in the"Chinese cultural circle",visible and intangible,overseas O Chinese communities have always maintained a dynamic relationship with the"core",and overseas Chinese have constantly expanded the scope of the Chinese national space through alternative channels of culture and society.By analyzing the progression of three phases,namely the period before the 1850s,1850s-1950s and the period after the 1950s,this paper examines the role of overseas Chinese in the multidimensional space expansion of the Chinese nation.We deem that overseas Chinese maintained varied degrees of spatial connection and participated in the construction of the national homeland in multiple scales such as ethnic identity,cultural identity,economic ties and social networks;The sense of ethnic community of overseas Chinese is embodied in the inclinations toward the ancestral country,multi-dimensional identification and the concept of righteousness,showing the characteristics of pluralism and consensus;Due to the variance of affecting factors,such as migration time and intergenerational relations,geographical distance and cyberspace accessibility,policies of the country of origin and transnational interaction,there are distinguishable traits between different groups of overseas Chinese and the"core"of the multidimensional space of the Chinese nation.Overseas Chinese not only expand out,but also bridge and tie up the multidimensional and three-dimensional space of the Chinese nation.
