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The original etiology of Alzheimer's disease (AD) is the deposition of amyloid-beta (Aβ) proteins, which starts from the aggregation of the Aβ oligomers. The optimal therapeutic strategy targeting Aβ oligomer aggregation is the development of AD vaccines. Despite the fact that positive progress has been made for experimental attempts at AD vaccines, the physicochemical and even structural properties of these AD vaccines remain unclear. In this study, through immunoinformatic and molecular dynamics (MD) simulations, we first designed and simulated an alternative of vaccine TAPAS and found that the structure of the alternative can reproduce the 3D conformation of TAPAS determined experimentally. Meanwhile, immunoinformatic methods were used to analyze the physicochemical properties of TAPAS, including immunogenicity, antigenicity, thermal stability, and solubility, which confirm well the efficacy and safety of the vaccine, and validate the scheme reliability of immunoinformatic and MD simulations in designing and simulating the TAPAS vaccine. Using the same scheme, we predicted the 3D conformation of the optimized ACI-24 peptide vaccine, an Aβ peptide with the first 15 residues of Aβ42 (Aβ1–15). The vaccine was verified once to be effective against both full-length Aβ1–42 and truncated Aβ4–42 aggregates, but an experimental 3D structure was absent. We have also explored the immune mechanism of the vaccine at the molecular level and found that the optimized ACI-24 and its analogues can block the growth of either full-length Aβ1–42 or truncated Aβ4–42 pentamer by contacting the hydrophobic residues within the N-terminus and β1 region on the contact surface of either pentamer. Additionally, residues (D1, D7, S8, H13, and Q15) were identified as the key residues of the vaccine to contact either of the two Aβ oligomers. This work provides a feasible implementation scheme of immunoinformatic and MD simulations for the development of AD small peptide vaccines, validating the power of the scheme as a parallel tool to the experimental approaches and injecting molecular-level information into the understanding and design of anti-AD vaccines. [ABSTRACT FROM AUTHOR]

Customers' self‐congruity has been verified to be an important antecedent of their satisfaction or loyalty in terms of brand consumption. In the era of the experience economy, effects of customers' self‐congruity as well as subject norm on their attitude and behavioral intention concerning the special form of accommodation, that is, B&Bs have been seldomly studied. Therefore, this study applied self‐congruity theory with subjective norm to explain the phenomenon of increasing interests of B&Bs. As a result, first, self‐image congruity was insignificantly associated with B&B customer attitude. Second, B&B customers' functional congruity positively impacts customers' attitude and subsequential their behavioral intention. Third, customers' behavioral intention was influenced by subjective norm, that is, others' recommendation or suggestion could affect customers' behavioral intention. Collectively, the business operators and investors could develop and establish relative marketing strategies from the angles of subjective norm and functional congruity between customers and B&Bs. [ABSTRACT FROM AUTHOR]

Context: Existing researches confirmed that β amyloid (Aβ) has a high affinity for the α7 nicotinic acetylcholine receptor (α7nAChR), associating closely to Alzheimer's disease. The majority of related studies focused on the experimental reports on the neuroprotective role of Aβ fragment (Aβx), however, with a lack of investigation into the most suitable binding region and mechanism of action between Aβ fragment and α7nAChR. In the study, we employed four Aβ1–42 fragments Aβx, Aβ1–16, Aβ10–16, Aβ12–28, and Aβ30–42, of which the first three were confirmed to play neuroprotective roles upon directly binding, to interact with α7nAChR. Methods: The protein–ligand docking server of CABS-DOCK was employed to obtain the α7nAChR-Aβx complexes. Only the top α7nAChR-Aβx complexes were used to perform all-atom GROMACS dynamics simulation in combination with Charmm36 force field, by which α7nAChR-Aβx interactions' dynamic behavior and specific locations of these different Aβx fragments were identified. MM-PBSA calculations were also done to estimate the binding free energies and the different contributions from the residues in the Aβx. Two distinct results for the first three and fourth Aβx fragments in binding site, strength, key residue, and orientation, account for why the fourth fails to play a neuroprotective role at the molecular level. [ABSTRACT FROM AUTHOR]

The pollution characteristics of multi-size atmospheric particulates in Xinxiang, which was one of the most polluted cities across China, are still unclear even through air quality in Xinxiang has been improved in recent years. PM10, PM2.5, and PM1 samples were synchronously collected from 21 December 2019 to 17 January 2020 to explore pollution levels and reveal sources of PM in Xinxiang. The average mass concentrations of PM10, PM2.5, and PM1 were as high as 155.53 μg m−3, 120.07 μg m−3, and 85.64 μg m−3 during the observation period, respectively. Almost all of the chemical compositions in PM10, PM2.5 and PM1 increased continuously and obviously with the aggravation of the pollution level. Compared with the clean period, the enhancement of sulfate (23–27%) in PM was obvious higher than nitrate (19–22%) during the pollution period, which demonstrated that sulfate was the main contributor to the high concentration of PM in this study. Similar source distributions for PM10, PM2.5, and PM1 were also found, including traffic source, combustion source, secondary aerosols, industrial source, and fugitive dust, by using the positive matrix factorization (PMF) model. Furthermore, the contributions of the combustion source and secondary aerosol were found to be higher in smaller particles (PM2.5 and PM1), while the contribution of fugitive dust was higher in PM10. Moreover, dust and sand were entrained by air masses from the northwest that increased the contribution of dust in PM at the observation site. The potential source contribution function (PSCF) analysis illustrated that regional emission sources in northern and eastern Xinxiang might be important potential contributors to PM pollution in Xinxiang. [ABSTRACT FROM AUTHOR]