Therapeutic drugs for Alzheimer’s disease have been extensively studied due to its recurrence and abundance among neurodegenerative diseases. It is thought that the accumulation of amyloid precursor protein (APP) products, a consequence of an up-regulation of the β-site APP-cleaving enzyme 1 (BACE1), is the main triggering mechanism during the early stages of the disease. This study aims to explore the ability of a multifunctional conjugate based on magnetite nanoparticles for the cellular delivery of siRNA against the expression of the BACE1 gene. We immobilized the siRNA strand on PEGylated magnetite nanoparticles and investigated the effects on biocompatibility and efficacy of the conjugation. Similarly, we co-immobilized the translocating protein OmpA on PEGylated nanoparticles to enhance cellular uptake and endosomal escape. BACE1 suppression was statistically significant in HFF-1 cells, without any presence of a cytotoxic effect. The delivery of the nanoconjugate was achieved through endocytosis pathways, where endosome formation was likely escaped due to the proton-sponge effect characteristic of PEGylated nanoparticles or mainly by direct translocation in the case of OmpA/PEGylated nanoparticles.

Glycoengineered bacteria have emerged as a cost-effective platform for rapid and controllable biosynthesis of designer conjugate vaccines. However, little is known about the engagement of such conjugates with naı̈ve B cells to induce the formation of germinal centers (GC), a subanatomical microenvironment that converts naı̈ve B cells into antibody-secreting plasma cells. Using a three-dimensional biomaterials-based B-cell follicular organoid system, we demonstrate that conjugates triggered robust expression of hallmark GC markers, B cell receptor clustering, intracellular signaling, and somatic hypermutation. These responses depended on the relative immunogenicity of the conjugate and correlated with the humoral response in vivo. The occurrence of these mechanisms was exploited for the discovery of high-affinity antibodies against components of the conjugate on a time scale that was significantly shorter than for typical animal immunization-based workflows. Collectively, these findings highlight the potential of synthetic organoids for rapidly predicting conjugate vaccine efficacy as well as expediting antigen-specific antibody discovery.

Removal of azo and diazo dye content from textile industry wastewaters is crucial due to their environmental impact. Here, we report on the use of the fungal laccase from Pycnoporus sanguineus CS43 immobilized on silica nanoparticles and entrapped in textile-based filters for the degradation of Congo Red. Laccase immobilization and synthesis of the nanocomposites were carried out by two different methods, one in the presence of acetone and the second using water as solvent. This led to a change in the hydrophobicity of the obtained biofilters. Successful preparation of the nanocomposites was confirmed via FTIR spectroscopy. Changes in the secondary structure of the enzyme were inspected through the second derivative of the FTIR spectra. Six different types of filter were fabricated and tested in a continuous flow bioreactor in terms of their decolorization capabilities of Congo Red. The results indicate removal efficiencies that approached 40% for enzymes immobilized on the more hydrophobic supports. Backscattered electron (BSE) images of the different filters were obtained before and after the decolorization process. Percentage of decolorization and activity loss were determined as a function of time until a plateau in decolorization activity was reached. Experimental data was used to recreate the decolorization process in COMSOL Multiphysics^® (Stockholm, Sweden). These simulations were used to determine the proper combination of parameters to maximize decolorization. Our findings suggest that the treatment of textile-based filters with immobilized laccase in conjunction with hydrophobic nanocomposites provides a suitable avenue to achieve more efficient laccase dye decolorization (39%) than that obtained with similar filters treated only with free laccase (8%). Filters treated with silica-based nanocomposites and immobilized laccases showed an increase in their decolorization capability, probably due to changes in their wetting phenomena.

Determining vaccination coverage amongst children (<5 years old) having multiple socio-economic risk factors and their relationship to insurance status. This was a cross-sectional study of 514 families from urban settlements receiving people displaced by the armed conflict in 4 municipalities in the Santander department ( Colombia ). The households were selected by probabilistic sampling, using proportional modelling by municipality. Immunisation data was collected from vaccination cards; interviews provided socio-demographic data. The dependent variable consisted of having the complete vaccination scheme by age according to the official Ministry of Social Protection's programme. The probability of being vaccinated was modelled by a logistical regression, adjusted for sociodemographic variables. 369 children were studied, of whom 48,8 % belonged to families displaced by the armed conflict. 46,1 % of the people being interviewed presented their vaccination cards. Contrary to what had been expected, only 21,2 % of those having a vaccination card were insured and 22,9 % of them had a complete vaccination scheme for their age. The probability of having a complete vaccination scheme for those individuals who were covered by the subsidised health system was 2,4 times higher when compared to those who were not insured (p=0.042). Low vaccination coverage indicated barriers for people living in conditions of poverty and displacement obtaining health services and low insurance coverage suggested faults in health insurance policies addressing similar populations.