Functional Nanogels as Platforms for Imparting Antibacterial,Antibiofilm, and Antiadhesion Activities to Stainless Steel

In this work, long‐term antibacterial, antiadhesion, and antibiofilm activities are afforded to industrial stainless steel surfaces following a green and bio‐inspired strategy. Starting from catechol bearing synthetic polymers, the film cross‐linking and the grafting of active (bio)molecules are possible under environmentally friendly conditions (in aqueous media and at room temperature). A bio‐inspired polyelectrolyte, a polycation‐bearing catechol, is used as the film‐anchoring polymer while a poly(methacrylamide)‐bearing quinone groups serves as the cross‐linking agent in combination with a polymer bearing primary amine groups. The amine/quinone reaction is exploited to prepare stable solutions of nanogels in water at room temperature that can be easily deposited to stainless steel. This coating provides quinone‐functionalized surfaces that are then used to covalently anchor active (bio)molecules (antibiofilm enzyme and antiadhesion polymer) through thiol/quinone reactions.     

From the web of data to a world of action

This paper takes as its premise that the web is a place of action, not just information, and that the purpose of global data is to serve human needs. The paper presents several component technologies, which together work towards a vision where many small micro-applications can be threaded together using automated assistance to enable a unified and rich interaction. These technologies include data detector technology to enable any text to become a start point of semantic interaction; annotations for web-based services so that they can link data to potential actions; spreading activation over personal ontologies, to allow modelling of context; algorithms for automatically inferring ‘typing’ of web-form input data based on previous user inputs; and early work on inferring task structures from action traces. Some of these have already been integrated within an experimental web-based (extended) bookmarking tool, Snip!t, and a prototype desktop application On Time, and the paper discusses how the components could be more fully, yet more openly, linked in terms of both architecture and interaction. As well as contributing to the goal of an action and activity-focused web, the work also exposes a number of broader issues, theoretical, practical, social and economic, for the Semantic Web.     

Cardiomyopathies: An Overview

Background: Cardiomyopathies are a heterogeneous group of pathologies characterized by structural and functional alterations of the heart. Aims: The purpose of this narrative review is to focus on the most important cardiomyopathies and their epidemiology, diagnosis, and management. Methods: Clinical trials were identified by Pubmed until 30 March 2021. The search keywords were “cardiomyopathies, sudden cardiac arrest, dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy, arrhythmogenic cardiomyopathy (ARCV), takotsubo syndrome”. Results: Hypertrophic cardiomyopathy (HCM) is the most common primary cardiomyopathy, with a prevalence of 1:500 persons. Dilated cardiomyopathy (DCM) has a prevalence of 1:2500 and is the leading indication for heart transplantation. Restrictive cardiomyopathy (RCM) is the least common of the major cardiomyopathies, representing 2% to 5% of cases. Arrhythmogenic cardiomyopathy (ARCV) is a pathology characterized by the substitution of the myocardium by fibrofatty tissue. Takotsubo cardiomyopathy is defined as an abrupt onset of left ventricular dysfunction in response to severe emotional or physiologic stress. Conclusion: In particular, it has been reported that HCM is the most important cause of sudden death on the athletic field in the United States. It is needless to say how important it is to know which changes in the heart due to physical activity are normal, and when they are pathological.     

Spiro[chromane-2,4'-piperidine]-based histone deacetylase inhibitors with improved in vivo activity

A series of spiro[chromane-2,4'-piperidine] derivatives based on a previously published lead benzyl spirocycle 1 and bearing various N-aryl and N-alkylaryl substituents on the piperidine ring were prepared as novel histone deacetylase (HDAC) inhibitors. The compounds were evaluated for their abilities to inhibit nuclear HDACs, their in vitro antiproliferative activities, and in vitro ADME profiles. Based on these activities, 4-fluorobenzyl and 2-phenylethyl spirocycles were selected for further characterization. In vivo pharmacokinetic (PK) studies showed that both compounds exhibit an overall lower clearance rate, an increased half-life, and higher AUCs after intravenous and oral administration than spiropiperidine 1 under the conditions used. The improved PK behavior of these two compounds also correlated with superior in vivo antitumor activity in an HCT-116 xenograft model.     

Validation and Data-Integration of Yeast-Based Assays for Functional Classification of BRCA1 Missense Variants

Germline mutations in the BRCA1 gene have been reported to increase the lifetime risk of developing breast and/or ovarian cancer (BOC). By new sequencing technologies, numerous variants of uncertain significance (VUS) are identified. It is mandatory to develop new tools to evaluate their functional impact and pathogenicity. As the expression of pathogenic BRCA1 variants in Saccharomyces cerevisiae increases the frequency of intra- and inter-chromosomal homologous recombination (HR), and gene reversion (GR), we validated the two HR and the GR assays by testing 23 benign and 23 pathogenic variants and compared the results with those that were obtained in the small colony phenotype (SCP) assay, an additional yeast-based assay, that was validated previously. We demonstrated that they scored high accuracy, sensitivity, and sensibility. By using a classifier that was based on majority of voting, we have integrated data from HR, GR, and SCP assays and developed a reliable method, named yBRCA1, with high sensitivity to obtain an accurate VUS functional classification (benign or pathogenic). The classification of BRCA1 variants, important for assessing the risk of developing BOC, is often difficult to establish with genetic methods because they occur rarely in the population. This study provides a new tool to get insights on the functional impact of the BRCA1 variants.     

Novel Chiral Biheteroaromatic Diphosphine Oxides for Lewis Base Activation of Lewis Acids in Enantioselective Allylation and Epoxide Opening

Enantiomerically pure biheteroaromatic diphosphine oxides were synthesised and tested as organocatalysts in two different reactions involving trichlorosilyl compounds. The allylation of aldehydes with allyl(trichloro)silane afforded homoallylic alcohols in fair to good yields and up to 95% ee. Preliminary experiments showed that this new class of metal‐free catalysts was able also to promote the stilbene oxide opening by addition of tetrachlorosilane with enantioselectivity higher than 80%. The interesting results in terms of chemical and stereochemical efficiency open the way to further studies towards the development of new chiral heteroaromatic Lewis bases as efficient metal‐free catalysts.