Prediction of the 3D conformation of a small peptide vaccine targeting Aβ42 oligomers.

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.

Inverted loading strategy regulates the Mn-O-Ce sites for efficient fenton-like catalysis.

Regulating interfacial active sites to improve peroxymonosulfate (PMS) activation efficiency is a hot topic in the heterogeneous catalysis field. In this study, we develop an inverted loading strategy to engineer asymmetric Mn-O-Ce sites for PMS activation. MnO@CeO prepared by loading CeO nanoparticles onto MnO nanorods exhibits the highest catalytic activity and stability, which is due to the formation of more oxygen vacancies (O) at the Mn-O-Ce sites, and the surface CeO layer effectively inhibits corrosion by preventing the loss of manganese ion active species into the solution.

Aggregation Dynamics Characteristics of Seven Different Aβ Oligomeric Isoforms-Dependence on the Interfacial Interaction.

The aggregation of β-amyloid (Aβ) peptides has been confirmed to be associated with the onset of Alzheimer's disease (AD). Among the three phases of Aβ aggregation, the lag phase has been considered to be the best time for early Aβ pathological deposition clinical intervention and prevention for potential patients with normal cognition. Aβ peptide exists in various lengths in vivo, and Aβ oligomer in the early lag phase is neurotoxic but polymorphous and metastable, depending on Aβ length (isoform), molecular weight, and specific phase, and therefore hardly characterized experimentally.

Identification and characterization of the conformation and size of amyloid-β (42) oligomers targeting the receptor LilrB2.

Experimental observations revealed that the amyloid-β 42 oligomer (AβO) can directly bind to the LilrB2 D1D2(LDD) receptor with nanomolar-affinity, leading to changes in synaptic plasticity and cognitive deficits. However, the dependence of neurotoxicity on the morphology, size, and aggregation stage (SP1, SP2) of AβO, as well as the specific molecular mechanism of AβO-LDD interaction, remain uncertain. To address these uncertainties, we investigated the interaction between the LDD neuroreceptor and AβO with different Aβ42 species (nontoxic species, toxic species, and protofibril) and sizes.

Origin of stronger binding of ionic pair (IP) inhibitor to Aβ42 than the equimolar neutral counterparts: synergy mechanism of IP in disrupting Aβ42 protofibril and inhibiting Aβ42 aggregation under two pH conditions.

Fibrous aggregates of beta-amyloid (Aβ) is a hallmark of Alzheimer's disease (AD). Several major strategies of drugs or inhibitors, including neutral molecules, positive or negative ions, and dual-inhibitor, are used to inhibit the misfolding or aggregation of Aβ42, among which a kind of dual-inhibitor composed of a pair of positive and negative ions is emerging as the most powerful candidate. This knowledge lacks the origin of the strong inhibitory effect and synergy mechanisms blocking the development and application of such inhibitors.

Two novel phosphorus/potassium-degradation bacteria: Bacillus aerophilus SD-1/Bacillus altitudinis SD-3 and their application in two-stage composting of corncob residue.

For effective utilization of corncob residue to realize green circular production, using composting to obtain a high-quality and low-cost biomass fertilizer has become a very important transformation avenue. In this paper, two novel phosphorus/potassium-degradation bacterial strains were isolated from tobacco straw and identified as Bacillus aerophilus SD-1/Bacillus altitudinis SD-3 (abbreviated as SD-1/SD-3). These identified two novel bacteria SD-1/SD-3 show that the soluble phosphorus content of SD-1/SD-3 reached 360.

Recognition of Aβ oligomer by LilrB2 acceptor: a tetracoordinated zipper mechanism.

Leukocyte immunoglobulin-like receptor B2 (LilrB2) is one of discovered cell surface β-amyloid (Aβ) receptors and taken as a promising therapeutic target for the treatment of Alzheimer's disease (AD). Aβ42 oligomer rather than monomer is toxic to neuronal cells and can directly bind to LilrB2, resulting in synaptic loss and cognitive impairment in the development of AD. Therefore, uncovering the mechanism of interaction between Aβ42 oligomer and LilrB2 becomes the first step to obtain a clear drug target and specific binding sites.

Toxicity Mechanism of Aβ42 Oligomer in the Binding between the GABAR1a sushi1 Domain and Amyloid Precursor Protein 9mer: A Mechanism like Substitution Reaction.

Amyloid-β peptide (Aβ), characterized by its abnormal folding into neurotoxic aggregates, impairs synaptic plasticity and causes synaptic loss associated with Alzheimer's disease (AD). The neurotoxicity of Aβ oligomers via the binding to various cell-surface receptors was frequently observed experimentally; however, the toxic mechanism still remains unknown. In this paper, we study the intervention of Aβ oligomers to the receptor-peptide binding in the GABAR1a sushi1-APP 9mer complex, a key node in increasing short-term synaptic facilitation in the mouse hippocampus and decreasing neuronal activity by inhibiting neurotransmitter release by molecular dynamics simulations.

Identification of the probable structure of the sAPPα-GABAR1a complex and theoretical solutions for such cases.

Amyloid precursor protein (APP) is the core of the pathogenesis of Alzheimer's disease (AD). Existing studies have shown that the soluble secreted APP (sAPPα) fragment obtained from the hydrolysis of APP by α-secretase has a synaptic function. Thereinto, a nine-residue fragment (APP9mer) of the extension domain region of sAPPα can bind directly and selectively to the N-terminal sushi1 domain (SD1) of the γ-aminobutyric acid type B receptor subunit 1a (GABAR1a) protein, which can influence synaptic transmission and plasticity by changing the GABAR1a conformation.

Small-Molecule Targeted Aβ Aggregate Degradation: Negatively Charged Small Molecules Are More Promising than the Neutral Ones.

Heavy evidence has confirmed that Aβ42 oligomers are the most neurotoxic aggregates and play a critical role in the occurrence and development of Alzheimer's disease by causing functional neuron death, cognitive damage, and dementia. Disordered Aβ42 oligomers are challenging therapeutic targets, and no drug is currently in clinical use that modifies the properties of their monomeric states. Here, a negatively charged molecule (ER), rather than the neutral TS1 one, is identified by a molecular dynamics simulation method to be more capable of binding and sequestering the intrinsically disordered amyloid-β peptide Aβ42 in its soluble pentameric state as well as its monomeric components.

A novel lignin degradation bacteria-Bacillus amyloliquefaciens SL-7 used to degrade straw lignin efficiently.

Using tobacco straw (Ts) and lignin as the sole carbon source, a strain was isolated from Ts and identified as Bacillus amyloliquefaciens SL-7 by 16S rDNA gene-sequencing technology.7-day incubation of Bacillus amyloliquefaciens SL-7 can reduce the chemical oxygen demand (COD) by 69.35% in lignin mineral salt medium.