The misfolding and abnormal amyloid fibrillation of proteins/peptides are associated with more than 20 human diseases. Although dozens of nanoparticles have been investigated the inhibition effect on the misfolding and...
Chemical and physical properties of nanobio interface substantially affect the conformational transitions of adjacent biomolecules. Previous studies have reported the chiral effect and charge effect of nanobio interface on the misfolding, aggregation, and fibrillation of amyloid protein. However, the isomeric effect of nanobio interface on protein/peptides amyloidosis is still unclear. Here, three isomeric nanobio interfaces were designed and fabricated based on the same sized gold nanoclusters (AuNCs) modified with 4-mercaptobenzoic acid (p-MBA), 3-mercaptobenzoic acid (m-MBA), and 2-mercaptobenzoic acid (o-MBA). Then three isomeric AuNCs were employed as models to explore the isomeric effect on the misfolding, aggregation, and fibrillation of Aβ40 at nanobio interfaces. Site-specific replacement experiments on the basis of theoretical analysis revealed the possible mechanism of Aβ40 interacting with isomeric ligands of AuNCs at the nanobio interfaces. The distance and orientation of −COOH group from the surface of AuNCs can affect the electrostatic interaction between isomeric ligands and the positively charged residues (R5, K16, and K28) of Aβ40, which may affect the inhibition efficiency of isomeric AuNCs on protein amyloidosis. Actually, the amyloid fibrillation kinetics results together with atomic force microscope (AFM) images, dynamic light scattering (DLS) results and circular dichroism (CD) spectra indeed proved that all the three isomeric AuNCs could inhibit the misfolding, aggregation and fibrillation of Aβ40 in a dose-dependent manner, and the inhibition efficiency was definitely different from each other. The inhibition efficiency of o-MBA-AuNCs was higher than that of m-MBA-AuNCs and p-MBA-AuNCs at the same dosage. These results provide an insight for isomeric effect at nanobio interfaces, and open an avenue for structure-based nanodrug design target Alzheimer’s disease (AD) and even other protein conformational diseases.
The continuous basalt fiber-reinforced polymer column filled with concrete (BFRPC composite column) can well resist the erosion of the external environment, improve the durability of the structure, and reduce the life-cycle cost of the project. To evaluate the mechanical behaviors of the BFRPC composite column under cyclic lateral loading, laboratory low-cycle reverse loading tests were implemented on a BFRPC composite column specimen, a prestressed reinforced concrete (PRC) tube column specimen, and a prestressed high-strength concrete (PHC) tube column specimen. The failure features, hysteretic curve, and skeleton curve for these three types of column specimens were compared and analyzed through the load–displacement hysteretic curve. The results indicated that the BFRPC composite column possesses the better bearing capacity and deformation performance. The horizontal bearing capacity of the BFRPC composite column is at least three times better than that of PHC and PRC tube columns. Finally, the functional expression of the skeleton curves for the BFRPC composite column is fitted by the rational function fitting method.
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