Fluorescence Detection and Inhibition Mechanisms of DNTPH on Aβ42 Oligomers Characterized as Products in the Four Stages of Aggregation.

Aβ42 aggregation was implicated in the pathogenesis of Alzheimer's disease (AD) without effective treatment available currently. Future efforts in clinical trials should instead focus on applying those antiamyloid treatment strategies to the preclinical stage and "the earlier, the better". How to identify and inhibit Aβ42 oligomers in the different stages of aggregation is therefore becoming the key to controlling primary aggregation and consequent AD development.

Uncovering the action mechanism of Shenqi Tiaoshen formula in the treatment of chronic obstructive pulmonary disease through network pharmacology, molecular docking, and experimental verification.

Objective: To reveal the potential underlying mechanism of the Shenqi Tiaoshen formula (, SQTS) in the treatment of chronic obstructive pulmonary disease (COPD) by utilizing network pharmacology, molecular docking, and experimental verification.

Methods: Multiple open-source databases and research related to Traditional Chinese Medicine or compounds were employed to screen active ingredients and corresponding potential targets of the SQTS. The protein-protein interaction network screened hub genes, the relevant molecular mechanism and gene regulation were initially identified through the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis, and molecular docking was used to confirm further the interaction of the main components bound to the core targets.

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.

Specific interaction from different Aβ peptide fragments to α7nAChR-A study of molecular dynamics simulation.

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 (Aβ), 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 Aβ fragments Aβ, Aβ, Aβ, Aβ, and Aβ, of which the first three were confirmed to play neuroprotective roles upon directly binding, to interact with α7nAChR.

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.

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.

[The expression of interferon-stimulating gene (STING/TMEM173) in liver tissue and its correlation with liver inflammation in patients with chronic hepatitis B].

Objective To investigate the relationship between the expression and distribution of interferon-stimulating gene/transmembrane protein 173(STING/TMEM173) in liver tissue and the grade of liver inflammation in patients with chronic hepatitis B, and to explore the underlying mechanisms in vitro. Methods The expression of STING/TMEM173 protein in liver tissue of 62 naive patients with chronic hepatitis B was detected by immunohistochemistry. Rank sum test and spearman correlation coefficient were used to analyze the correlation between hepatic STING/TMEM173 expression and liver inflammation grades as well as serum ALT levels.

Image-Based Artificial Intelligence in Wound Assessment: A Systematic Review.

Accurately predicting wound healing trajectories is difficult for wound care clinicians due to the complex and dynamic processes involved in wound healing. Wound care teams capture images of wounds during clinical visits generating big datasets over time. Developing novel artificial intelligence (AI) systems can help clinicians diagnose, assess the effectiveness of therapy, and predict healing outcomes.

Multiclass wound image classification using an ensemble deep CNN-based classifier.

Acute and chronic wounds are a challenge to healthcare systems around the world and affect many people's lives annually. Wound classification is a key step in wound diagnosis that would help clinicians to identify an optimal treatment procedure. Hence, having a high-performance classifier assists wound specialists to classify wound types with less financial and time costs.

Fully automatic wound segmentation with deep convolutional neural networks.

Acute and chronic wounds have varying etiologies and are an economic burden to healthcare systems around the world. The advanced wound care market is expected to exceed $22 billion by 2024. Wound care professionals rely heavily on images and image documentation for proper diagnosis and treatment.

Processing Induced Nonequilibrium Behavior of Polyvinylpyrrolidone Nanofilms Revealed by Dewetting.

Polyvinylpyrrolidone (PVP) nanofilms prepared by spin-coating have vast applications in biological and microdevice fields. However, detailed knowledge of processing induced nonequilibrium behavior of PVP nanofilms and solutions for minimizing residual stresses toward high-quality films has still been lacking. In the present study, we first explored the rapid film formation process via statistics on nascent holes.

[Antiviral effects of IL-27 on HBV in HepG2.2.15 cells via inducing MxA by STAT1 signal transduction pathway].

Objective To investigate the effect of interleukin 27 (IL-27) on hepatitis B virus (HBV) replication and antigen secretion in HepG2.2.15 cells and related mechanisms.

Effect of Liuweibuqi capsule, a Chinese patent medicine, on the JAK1/STAT3 pathway and MMP9/TIMP1 in a chronic obstructive pulmonary disease rat model.

Objective: To observe effect of Liuweibuqi Capsule, a Traditional Chinese Medicine (TCM), on the janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway and matrix metalloproteinases (MMPs) in a chronic obstructive pulmonary disease (COPD) rat model with lung deficiency in terms of TCM's pattern differentiation.

Methods: Rats were randomly divided into a normal group, model group, Liuweibuqi group, Jinshuibao group, and spleen aminopeptidase group (n=10). Aside from the normal group, all rats were exposed to smoke plus lipopolysaccharide tracheal instillation to establish the COPD model with lung deficiency.

[Regulation of Thl/Th2 cells by T cell-mediated transcription factor in rats with chronic obstructive pulmonary disease].

Objective: To determine T box expressed in T cells (T bet), GATA binding protein-3 (GATA 3), and retinoid-related orphan nuclear receptor gammat (RORgammat) in rats with chronic obstructive pulmonary disease (COPD).

Methods: Thirty rats were randomly divided into a control and a COPD group. The COPD model was established through smoking and lipopolysaccharide (LPS) tracheal instillation.

[Role of Foxp3/Treg and RORγt/Th17 cell imbalance in rat model of chronic obstructive pulmonary disease].

Objective: To observe the changes in forkhead/winged helix transcription factor p3(Foxp3), regulatory T cells (Treg), retinoid-related orphan receptor gamma (RORγt) in rat model of chronic obstructive pulmonary disease (COPD).

Methods: Twenty Sprague-Dawley (SD) rats were randomly divided into normal control group and COPD model group, with 10 rats in each group. The COPD model was reproduced by smoke inhalation and tracheal instillation of lipopolysaccharide (LPS), and no such treatment was conducted in normal control group.

[Imbalance in the expression of Foxp3, T-bet and GATA-3 is correlated with inflammation of chronic obstructive pulmonary disease].

Objective: To observe the change of regulatory T cells(Tregs), fork head-like transcription factor 3 (Foxp3), T box expressed in T cells (T-bet) and GATA binding protein 3 (GATA3) in rat models of chronic obstructive pulmonary disease (COPD).

Methods: Thirty rats were randomly divided into control group and model group (n=15 each). The rats of model group were developed by lipopolysaccharide (LPS) and smoking.