Evaluating the effectiveness and cost-effectiveness of free influenza vaccination policy for older adults in Yinzhou, China: Study protocol of a real-world analyses.

Background: Influenza causes excessive morbidity and mortality among older adults. While influenza vaccine provides protection against its infection, the vaccination coverage in China among older adults has been very low. Previous evidence on the cost-effectiveness of government-sponsored free influenza vaccination programs in China was primarily based on literature data, which might not always reflect real-world patient populations.

Mediation analysis of leisure activities on the association between cognitive function and mortality: a longitudinal study of 42,942 Chinese adults 65 years and older.

Objectives: Previous studies have established associations of cognitive function and leisure activities with mortality. This study aimed to evaluate whether leisure activities causally mediate these associations.

Methods: This longitudinal study included 42,246 participants aged over 65 years from the Chinese Longitudinal Healthy Longevity Survey.

Conformational-specific self-assembled peptides as dual-mode, multi-target inhibitors and detectors for different amyloid proteins.

Prevention and detection of misfolded amyloid proteins and their β-structure-rich aggregates are the two promising but different (pre)clinical strategies to treat and diagnose neurodegenerative diseases including Alzheimer's diseases (AD) and type II diabetes (T2D). Conventional strategies prevent the design of new pharmaceutical molecules with both amyloid inhibition and detection functions. Here, we propose a "like-interacts-like" design principle to design a series of new self-assembling peptides (SAPs), enabling them to specifically and strongly interact with conformationally similar β-sheet motifs of Aβ (association with AD) and hIAPP (association with T2D).

Experimental and Computational Protocols for Studies of Cross-Seeding Amyloid Assemblies.

Alzheimer's disease (AD) and type 2 diabetes (T2D) are two common protein aggregation diseases. Compelling evidence has shown a link between AD and T2D, which may derive from interspecies cross-sequence interactions between amyloid-β peptide (Aβ), associated with AD, and human islet amyloid polypeptide (hIAPP), associated with T2D. Herein, we present experimental and computational protocols and tools to study the aggregate structures and kinetics, conformational conversion, and molecular interactions of Aβ-hIAPP mixtures.

Role of Protein Charge Density on Hepatitis B Virus Capsid Formation.

The role of electrostatic interactions in the viral capsid assembly process was studied by comparing the assembly process of a truncated hepatitis B virus capsid protein Cp149 with its mutant protein D2N/D4N, which has the same conformational structure but four fewer charges per dimer. The capsid protein self-assembly was investigated under a wide range of protein surface charge densities by changing the protein concentration, buffer pH, and solution ionic strength. Lowering the protein charge density favored the capsid formation.

Seed-Induced Heterogeneous Cross-Seeding Self-Assembly of Human and Rat Islet Polypeptides.

Amyloid peptides can misfold and aggregate into amyloid oligomers and fibrils containing conformationally similar β-sheet structures, which are linked to the pathological hallmark of many neurodegenerative diseases. These β-sheet-rich amyloid aggregates provide common structural motifs to accelerate amyloid formation by acting as seeds. However, little is known about how one amyloid peptide aggregation will affect another one (namely, cross-seeding).

Identification of a New Function of Cardiovascular Disease Drug 3-Morpholinosydnonimine Hydrochloride as an Amyloid-β Aggregation Inhibitor.

Cardiovascular disease (CVD) and Alzheimer's disease (AD) have a mutual cause-and-effect relationship, and they share some common risk factors. Although numerous Food and Drug Administration (FDA)-approved drugs have been developed for CVD treatment, no drugs are clinically available for AD treatment. Given the common disease-causing factors and links between the two diseases and the well-demonstrated drugs for CVD, we propose to re-examine the new potential of the existing CVD drugs as amyloid-β (Aβ) inhibitors.

Molecular Understanding of Aβ-hIAPP Cross-Seeding Assemblies on Lipid Membranes.

Amyloid-β (Aβ) and human islet polypeptide (hIAPP) are the causative agents responsible for Alzheimer's disease (AD) and type II diabetes (T2D), respectively. While numerous studies have reported the cross-seeding behavior of Aβ and hIAPP in solution, little effort has been made to examine the cross-seeding of Aβ and hIAPP in the presence of cell membranes, which is more biologically relevant to the pathological link between AD and T2D. In this work, we computationally study the cross-seeding and adsorption behaviors of Aβ and hIAPP on zwitterionic POPC and anionic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylglycerol (POPG) mixed bilayers using all-atom molecular dynamics (MD) simulations, particularly aiming to the effects of the initial orientation of the Aβ-hIAPP assembly and the lipid composition of cell membranes on mutual structural and interaction changes in both Aβ-hIAPP assembly and lipid bilayers at the atomic level.

A comparative study of the mechanical properties of hybrid double-network hydrogels in swollen and as-prepared states.

Significant efforts have been made to develop highly tough hydrogels towards many scientific and industrial applications. However, most of the as-prepared tough hydrogels lose their mechanical strength and toughness when they swell in aqueous solution. Current knowledge about the swelling-induced mechanical property changes mainly stems from single-network (SN) hydrogels and chemically linked double-network (DN) hydrogels, but little is known about the swelling mechanical properties of hybrid physically-chemically linked DN gels.

HP-β-cyclodextrin as an inhibitor of amyloid-β aggregation and toxicity.

Amyloid deposits of misfolded amyloid-β protein (Aβ) on neuronal cells are a pathological hallmark of Alzheimer's disease (AD). Prevention of the abnormal Aβ aggregation has been considered as a promising therapeutic strategy for AD treatment. To prevent reinventing the wheel, we proposed to search the existing drug database for other diseases to identify potential Aβ inhibitors.

Salt-responsive polyzwitterionic materials for surface regeneration between switchable fouling and antifouling properties.

Unlabelled: Development of smart regenerative surface is a highly challenging but important task for many scientific and industrial applications. Specifically, very limited research efforts were made for surface regeneration between bio-adhesion and antifouling properties, because bioadhesion and antifouling are the two highly desirable but completely opposite properties of materials. Herein, we developed salt-responsive polymer brushes of poly(3-(1-(4-vinylbenzyl)-1H-imidazol-3-ium-3-yl) propane-1-sulfonate) (polyVBIPS), which can be switched reversibly and repeatedly between protein capture/release and surface wettability in a controllable manner.

Polymorphic cross-seeding amyloid assemblies of amyloid-β and human islet amyloid polypeptide.

Epidemiological studies have shown that the development of Alzheimer's disease (AD) is associated with type 2 diabetes (T2D), but it still remains unclear how AD and T2D are connected. Heterologous cross-seeding between the causative peptides of Aβ and hIAPP may represent a molecular link between AD and T2D. Here, we computationally modeled and simulated a series of cross-seeding double-layer assemblies formed by Aβ and hIAPP peptides using all-atom and coarse-gained molecular dynamics (MD) simulations.

Cross-Seeding Interaction between β-Amyloid and Human Islet Amyloid Polypeptide.

Alzheimer's disease (AD) and type 2 diabetes (T2D) are two common protein misfolding diseases. Increasing evidence suggests that these two diseases may be correlated with each other via cross-sequence interactions between β-amyloid peptide (Aβ) associated with AD and human islet amyloid polypeptide (hIAPP) associated with T2D. However, little is known about how these two peptides work and how they interact with each other to induce amyloidogenesis.

Mechanically strong hybrid double network hydrogels with antifouling properties.

The development of mechanically tough and biocompatible polymer hydrogels has great potential and promise for many applications. Herein, we synthesized a new type of hybrid physically-chemically crosslinked Agar/PAM double network (DN) hydrogel using a simple, one-pot method. Agar/PAM gels are designed with desirable/balanced mechanical properties by varying the network-forming parameters.

Polymorphic Associations and Structures of the Cross-Seeding of Aβ1-42 and hIAPP1-37 Polypeptides.

Emerging evidence have shown that the patients with Alzheimer's disease (AD) often have a higher risk of later developing type II diabetes (T2D), and vice versa, suggesting a potential pathological link between AD and T2D. Amyloid-β (Aβ) and human islet amyloid polypeptide (hIAPP) are the principle causative components responsible for the pathologies of AD and T2D, respectively. The cross-sequence interactions between Aβ and hIAPP may provide a molecular basis for better understanding the potential link between AD and T2D.

Enhanced Thermoelectric Properties of Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) by Binary Secondary Dopants.

Unlabelled: To simultaneously increase the electrical conductivity and Seebeck coefficient of poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (

Pedot: PSS) was a challenge for realizing efficient organic thermoelectrics. In this study, for the first time, we report both increased electrical conductivities and Seebeck coefficients, hence, enhanced thermoelectric properties of

Pedot: PSS thin films by doped with binary secondary dopants, dimethyl sulfoxide (DMSO) and poly(ethylene oxide) (PEO). Without modifying film morphology, the molar ratios of PEDOT to PSS are tuned by PEO, resulting in increased proportions of PEDOT in the bipolaron states.

Interfacial interaction and lateral association of cross-seeding assemblies between hIAPP and rIAPP oligomers.

Cross-sequence interactions between different amyloid peptides are important not only for the fundamental understanding of amyloid aggregation and polymorphism mechanisms, but also for probing a potential molecular link between different amyloid diseases. Here, we computationally modeled and simulated a series of hybrid hIAPP (human islet amyloid polypeptide)-rIAPP (rat islet amyloid polypeptide) assemblies and probed their structural stability, lateral association, and interfacial interactions using combined peptide-packing search, molecular dynamics (MD) simulations, and the Monte Carlo sampling method. We then identified a number of stable and highly populated hIAPP-rIAPP assemblies at the lowest energy states, in which hIAPP and rIAPP oligomers were stacked laterally on top of each other to form supramolecular β-sheet double layers in an antiparallel fashion.

Synthesis and characterization of antifouling poly(N-acryloylaminoethoxyethanol) with ultralow protein adsorption and cell attachment.

Rational design of effective antifouling polymers is challenging but important for many fundamental and applied applications. Herein we synthesize and characterize an N-acryloylaminoethoxyethanol (AAEE) monomer, which integrates three hydrophilic groups of hydroxyl, amide, and ethylene glycol in the same material. AAEE monomers were further grafted and polymerized on gold substrates to form polyAAEE brushes with well-controlled thickness via surface-initiated atomic transfer radical polymerization (SI-ATRP), with particular attention to a better understanding of the molecular structure-antifouling property relationship of hydroxyl-acrylic-based polymers.

Structural and energetic insight into the cross-seeding amyloid assemblies of human IAPP and rat IAPP.

The misfolding and aggregation of human islet amyloid polypeptide (hIAPP or amylin) into small oligomers and large amyloid fibrils is believed to be responsible for the dysfunction and death of pancreatic β-cells in diabetes type II. However, rat IAPP (rIAPP), which differs from the hIAPP by only 6 of 37 residues, lacks the ability to form amyloid fibrils and to induce cell death. Little is known about the cross-sequence interactions and cross-seeding structures between hIAPP and rIAPP peptides.

Binding characteristics between polyethylene glycol (PEG) and proteins in aqueous solution.

Polymer-protein interactions are crucial for determining the activity of both polymer and protein for many bio-related applications. Poly(ethylene glycol) (PEG) as a well-known antifouling material is often coated on surfaces to form highly solvated brushes, which exhibit excellent protein-repellent properties. However, unlike surface-induced antifouling effects, little is known about the intrinsic PEG-protein interactions in aqueous solution, which is an important yet neglected problem.

Cross-sequence interactions between human and rat islet amyloid polypeptides.

Human islet amyloid polypeptide (hIAPP) can assemble into toxic oligomers and fibrils, which are associated with cell degeneration and the pathogenesis of type 2 diabetes. Cross-interaction of hIAPP with rat IAPP (rIAPP)--a non-amyloidogenic peptide with high sequence similarity to hIAPP--might influence the aggregation and toxicity of hIAPP. However, the exact role of rIAPP in hIAPP aggregation and toxicity still remains unclear.

Non-selective ion channel activity of polymorphic human islet amyloid polypeptide (amylin) double channels.

Fundamental understanding of ion channel formation by amyloid peptides, which is strongly linked to cell toxicity, is very critical for (pre)clinical treatment of neurodegenerative diseases. Here, we combine atomistic simulations and experiments to demonstrate a broad range of conformational states of hIAPP double channels in lipid membranes. All individual channels display high selectivity for Cl(-) ions over cations, but the co-existence of polymorphic double channels of different conformations and orientations with different populations determines the non-ionic selectivity nature of the channels, which is different from the typical amyloid-β channels that exhibit Ca(2+) selective ion-permeable characteristics.

Probing the weak interaction of proteins with neutral and zwitterionic antifouling polymers.

Protein-polymer interactions are of great interest in a wide range of scientific and technological applications. Neutral poly(ethylene glycol) (PEG) and zwitterionic poly(sulfobetaine methacrylate) (pSBMA) are two well-known nonfouling materials that exhibit strong surface resistance to proteins. However, it still remains unclear or unexplored how PEG and pSBMA interact with proteins in solution.

Tanshinones inhibit amyloid aggregation by amyloid-β peptide, disaggregate amyloid fibrils, and protect cultured cells.

The misfolding and aggregation of amyloid-β (Aβ) peptides into amyloid fibrils is regarded as one of the causative events in the pathogenesis of Alzheimer's disease (AD). Tanshinones extracted from Chinese herb Danshen (Salvia Miltiorrhiza Bunge) were traditionally used as anti-inflammation and cerebrovascular drugs due to their antioxidation and antiacetylcholinesterase effects. A number of studies have suggested that tanshinones could protect neuronal cells.