Inhibition of bacterial adhesion to live human cells: Activity and cytotoxicity of synthetic mannosides

AbstractBacterial adhesion to glycosylated surfaces is a key issue in human health and disease. Inhibition of bacterial adhesion by suitable carbohydrates could lead to an anti-adhesion therapy as a novel approach against bacterial infections. A selection of five α-mannosides has been evaluated as inhibitors of bacterial adhesion to the polysaccharide mannan, as well as to the surface of live human HT-29 cells. Cell toxicity studies were performed to identify the therapeutic window for a potential in vivo-application of the tested carbohydrates. A previously published mannosidic squaric acid diamide was shown to be exceptionally effective as inhibitor of the bacterial lectin FimH

MixMesh Zones – Changing Pseudonyms Using Device-to-Device Communication in Mix Zones

Mobile device tracking has become ever so pervasive in our world of location-based services and prying eyes. While users can somewhat restrict the flow of information towards the services they consciously use, this is not as easily possible for the mobile network they are connected to. Here, they can be tracked with relative ease by whoever controls the access points they connect to, or even by anyone that is able to monitor the air interface. Trends towards smaller cells and dynamic access point ownership within the scope of 5G only exacerbate this issue. In this paper, we present a new mix zone approach, called MixMesh, based on device-to-device communication, intended to hinder mobile network tracking through enabling secure and privacy-friendly pseudonym changes, aligned with the requirements resulting from the aforementioned trends. Our evaluation shows that our MixMesh approach is able to deliver better anonymity at an unchanged level of service quality compared to existing mix zone techniques, all the while being configurable to a desired level of anonymity in order to adapt to different scenarios

Clinical evaluation of a web-based personalized recommendation system with electronic health record interface to optimize healthcare resources during SARS-CoV-2 surges

Abstract During the SARS-CoV-2 pandemic, the German healthcare system faced challenges of efficiently allocating testing resources. To address this, we developed an open-source personalized recommendation system (PRS) called “CovApp”. The PRS utilized a questionnaire to estimate the risk of infection, provided personalized recommendations such as testing, self-isolation, or quarantine, and featured QR code data transmission to electronic health records. The PRS served up to 2.5 million monthly users and received 67,000 backlinks from 1800 domains. We clinically evaluated the PRS at the SARS-CoV-2 testing facility at Charité and observed a 21.7% increase in patient throughput per hour and a 22.5% increase in patients per day. Patients using the PRS were twice as likely to belong to the High Risk group eligible for testing (18.6% vs. 8.9%, p < 0.0001), indicating successful compliance with CovApp’s recommendations. CovApp served as a digital bridge between the population and medical staff and significantly improved testing efficiency. As an open-source platform, CovApp can be readily customized to address emerging public health crises. Further, given the EHR interface, the app is of great utility for other applications in clinical settings

A versatile route to edge-specific modifications to pristine graphene by electrophilic aromatic substitution

This work presents a general method for producing edge-modified graphene using electrophilic aromatic substitution. Five types of edge-modified graphene were created from graphene/graphite nanoplatelets sourced commercially and produced by ultrasonic exfoliation of graphite in N-methyl-2-pyrrolidone. In contrast to published methods based on Friedel–Crafts acylation, this method does not introduce a carbonyl group that may retard electron transfer between the graphene sheet and its pendant groups. Graphene sulphonate (G–SO3−) was prepared by chlorosulphonation and then reduced to form graphene thiol (G–SH). The modifications tuned the graphene nanoparticles’ solubility: G–SO3− was readily dispersible in water, and G–SH was dispersible in toluene. The synthetic utility of the directly attached reactive moieties was demonstrated by creating a “glycographene” through radical addition of allyl mannoside to G–SH. Chemical modifications were confirmed by FT-IR and XPS. Based on XPS analysis of edge-modified GNPs, G–SO3− and G–SH had a S:C atomic ratio of 0.3:100. XPS showed that a significant amount of carbon sp2 character remained after functionalisation, indicating little modification to the conductive basal plane. The edge specificity of the modifications was visualised on edge-modified samples of graphene produced by chemical vapour deposition (CVD): scanning electron microscopy of gold nanoparticles attached to G–SH samples, epifluorescence microscopy of a glycographene bioconjugate with a fluorescently tagged lectin, and quenched stochastic optical reconstruction microscopy (qSTORM) of thiol-reactive fluorophores on CVD G–SH samples. Microelectrochemistry of unmodified CVD graphene and dye-modified CVD G–SH showed no statistically significant difference in interfacial electron transfer rate (k0). This platform synthesis technology can allow pristine graphene, rather than graphene oxide or its derivatives, to be used in applications that require the superior mechanical or electronic properties of pristine graphene, including theranostics and tissue engineering

Label-Free Discovery Array Platform for the Characterization of Gly-can Binding Proteins and Glycoproteins

The identification of carbohydrate–protein interactions is central to our understanding of the roles of cell–surface carbohydrates (the glycocalyx), fundamental for cell-recognition events. Therefore, there is a need for fast high-throughput biochemical tools to capture the complexity of these biological interactions. Here, we describe a rapid method for qualitative label-free detection of carbohydrate–protein interactions on arrays of simple synthetic glycans, more complex natural glycosaminoglycans (GAG), and lectins/carbohydrate binding proteins using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. The platform can unequivocally identify proteins that are captured from either purified or complex sample mixtures, including biofluids. Identification of proteins bound to the functionalized array is achieved by analyzing either the intact protein mass or, after on-chip proteolytic digestion, the peptide mass fingerprint and/or tandem mass spectrometry of selected peptides, which can yield highly diagnostic sequence information. The platform described here should be a valuable addition to the limited analytical toolbox that is currently available for glycomics

A versatile route to edge-specific modification of graphene nanoplatelets by electrophilic aromatic substitution

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