Ultrasensitive and rapid detection of organophosphates using a dual-signal naked-eye hydrogel sensor based on acetylcholinesterase inhibition.

Accurate determination of pesticide residues is crucial for food safety. A self-calibration method was developed for dual-signal "naked-eye" detection of organophosphorus pesticides (OPs) using bifunctional gold nanozymes (AuNEs). OPs inhibit the cascade reaction of acetylcholinesterase/choline oxidase (AChE/CHO) to reduce hydrogen peroxide (HO) production, which affects the AuNE-catalyzed color reaction and quenches the fluorescence of AuNEs with the assistance of Fe.

Enzyme-mediated multifunctional self-healing lysozyme hydrogel for synergistic treatment of chronic diabetic wounds.

Self-healing hydrogels have attracted significant attention in chronic diabetic wound healing due to their potential to minimize the risk of secondary infections caused by joint movement or dressing rupture. Herein, a multifunctional self-healing hydrogel mediated utilizing an enzyme-triggered cascade reaction based on dynamic imine bonds was designed. The hydrogel employs three enzymes: lysozyme (LYZ), glucose oxidase (GOx), and catalase (CAT), as building blocks.

Using near-infrared enhanced thermozyme and dual-conjugated Au nanorods for detection and targeted photothermal treatment of Alzheimer's disease.

Investigation of targeting inhibitors of Aβ aggregation, heme-Aβ peroxidase-like activity and efficient detectors of Aβ aggregation, are of therapeutic value and diagnostics significance for the treatment of Alzheimer's disease (AD). Due to the complex pathogenesis of AD, theranostics treatment with multiple functions are necessary. Herein we constructed the NIR absorption property of gold nanorods (GNRs) loaded with single chain variable fragment () 12B4 and thermophilic acylpeptide hydrolase (APH) ST0779 as a smart theranostic complex (GNRs-APH-, GAS), which possesses both rapid detection of Aβ aggregates and NIR photothermal treatment that effectively disassembles Aβ aggregates and inhibits Aβ-mediated toxicity.

Multiple Antigenic Peptide System Coupled with Amyloid Beta Protein Epitopes As An Immunization Approach to Treat Alzheimer's Disease.

Latest studies suggest that Alzheimer's disease (AD) is one of the "four big killers" that threaten the health of the elderly. AD affects about 46 million people across the world, and there is a critical need for research on new therapies for treating AD. The purpose of the present study was to develop and evaluate immunogens to elicit antibodies against the formation of amyloid beta protein (Aβ), a pathological hallmark of AD, as a therapeutic strategy in AD.

Humanization and directed evolution of the selenium-containing phage abzyme.

According to the binding site structure and the catalytic mechanism of the native glutathione peroxidase (GPX), three glutathione derivatives, GSH-S-DNP butyl ester (hapten Be), GSH-S-DNP hexyl ester (hapten He) and GSH-S-DNP hexamethylene ester (hapten Hme) were synthesized. By a four-round panning with a human synthetic phage library against three haptens, the enrichment of the phage particles with specific binding activity could be determined. Three phage particles were selected binding to each glutathione derivative, respectively.

Effects of insulin on transcriptional response and permeability in an in vitro model of human blood-brain barrier.

Alzheimer's disease (AD) is the most prevalent form of dementia worldwide and is an emerging global epidemic. Active and passive immune therapies targeting beta amyloid (Aβ) have shown very limited evidence in human studies of clinical benefits from these approaches. Epidemiological studies have shown that subjects with type 2 diabetes (T2D) are at higher risk of developing AD.

A novel small molecule displays two different binding modes during inhibiting H1N1 influenza A virus neuraminidases.

Neuraminidase (NA) inhibitors can suppress NA activity to block the release of progeny virions and are effective against influenza viruses. As potential anti-flu drugs with unique functions, NA inhibitors are greatly concerned by the worldwide scientists. It has been reported recently that one of the novel quindoline derivatives named 7a, could inhibit both A/Puerto Rico/8/34 (H1N1) NA (NA) and A/California/04/09 (H1N1) NA (NA).

Effects of poly(I:C) and MF59 co-adjuvants on immunogenicity and efficacy of survivin polypeptide immunogen against melanoma.

Malignant tumors pose a public health problem that jeopardizes human life and quality of living. At present, tumor vaccines in clinical research typically are aimed at stimulating the cellular immune response, while more effective vaccines should take into account the synergy between broad spectrum antibodies and high levels of cellular immunity. In this study, epitope peptides (68-81, 95-104, 80-88) of the tumor antigen survivin were chosen as immunogens and supplemented with poly(I:C) and/or MF59 adjuvant to evaluate the immune effects and anti-melanoma activities.

Screening HCV genotype-specific epitope peptides based on conserved sequence analysis and B cell epitope prediction in HCV E2 region.

The high mutation rate of the hepatitis C virus (HCV) genome increases the genotype diversity and renders the detection of the virus more difficult. Therefore, prediction and assessment of highly conserved and strongly antigenic epitope polypeptide sequences have become a focus of current research. The E2 region is the target binding region of neutralizing antibodies.

Exploration of binding and inhibition mechanism of a small molecule inhibitor of influenza virus H1N1 hemagglutinin by molecular dynamics simulation.

Influenza viruses are a major public health threat worldwide. The influenza hemagglutinin (HA) plays an essential role in the virus life cycle. Due to the high conservation of the HA stem region, it has become an especially attractive target for inhibitors for therapeutics.

A novel "turn-on" thiooxofluorescein-based colorimetric and fluorescent sensor for Hg and its application in living cells.

A novel water-soluble fluorescent probe FLS2 based on the thiooxofluorescein derivative has been firstly designed and synthesized. UV-vis absorption and fluorescence spectra studies showed that the FLS2 as a colorimetric and ratiometric fluorescent probe exhibited high selectivity and sensitivity towards Hg, which was mainly attributed to the special binding with the receptor unit accompanied with the spirolactam ring-opening progress. In addition, the probe FLS2 could be used as a naked-eye indicator for Hg with reversible response.

Eliciting 10E8-like antibodies by the membrane proximal external region peptide of HIV-1 in guinea pigs.

Objective: To develop an immunotherapy for HIV that can elicit 10E8-like broadly-neutralizing antibodies in guinea pigs, using a multiple antigen peptide (MAP) system as the platform and 10E8 peptide as the epitope.

Results: The immunogen, 10E8-MAP, was synthetized using the MAP system. The synthetic 10E8-MAP was stable, and the epitopes could be exposed for recognition.

Expression of HIV-1 broadly neutralizing antibodies mediated by recombinant adeno-associated virus 8 in vitro and in vivo.

Despite unremitting efforts since the discovery of human immunodeficiency virus type 1 (HIV-1), an effective vaccine has not been generated. Viral vector-mediated transfer for expression of HIV-1 broadly neutralizing antibodies (BnAbs) is an attractive strategy. In this study, a recombinant adeno-associated virus 8 (rAAV8) vector was used to encode full-length antibodies against HIV-1 in 293T cells and Balb/c mice after gene transfer.

Evaluation of the immunogenicity and protective effects of a trivalent chimeric norovirus P particle immunogen displaying influenza HA2 from subtypes H1, H3 and B.

The ectodomain of the influenza A virus (IAV) hemagglutinin (HA) stem is highly conserved across strains and has shown promise as a universal influenza vaccine in a mouse model. In this study, potential B-cell epitopes were found through sequence alignment and epitope prediction in a stem fragment, HA2:90-105, which is highly conserved among virus subtypes H1, H3 and B. A norovirus (NoV) P particle platform was used to express the HA2:90-105 sequences from subtypes H1, H3 and B in loops 1, 2 and 3 of the protrusion (P) domain, respectively.

Conserved stem fragment from H3 influenza hemagglutinin elicits cross-clade neutralizing antibodies through stalk-targeted blocking of conformational change during membrane fusion.

Currently available influenza vaccines typically fail to elicit/boost broadly neutralizing antibodies due to the mutability of virus sequences and conformational changes during protective immunity, thereby limiting their efficacy. This problem needs to be addressed by further understanding the mechanisms of neutralization and finding the desired neutralizing site during membrane fusion. This study specifically focused on viruses of the H3N2 subtype, which have persisted as a principal source of influenza-related morbidity and mortality in humans since the 1968 influenza pandemic.

A novel antimicrobial peptide derived from membrane-proximal external region of human immunodeficiency virus type 1.

With increasing microbial drug resistance worldwide, antimicrobial peptides (AMPs) are considered promising alternatives to addressing this problem. In this study, a series of synthetic peptides were designed based on the membrane-disrupting properties of the membrane-proximal external region (MPER) of human immunodeficiency virus type 1 (HIV-1) envelope protein. The peptide AP16-A was found to exhibit the most effective antimicrobial activities against both Gram-negative and Gram-positive bacteria.

Elicitation of HIV-1 neutralizing antibodies by presentation of 4E10 and 10E8 epitopes on Norovirus P particles.

Eliciting efficient broadly neutralizing antibodies (BnAbs) is a major goal in vaccine development against human immunodeficiency virus type 1 (HIV-1). Conserved epitopes in the membrane-proximal external region (MPER) of HIV-1 are a significant target. In this study, Norovirus P particles (NoV PPs) were used as carriers to display conformational 4E10 and 10E8 epitopes in different patterns with an appropriate linker.