ACE2, the Receptor that Enables Infection by SARS-CoV-2: Biochemistry,Structure, Allostery and Evaluation of the Potential Development of ACE2 Modulators

Angiotensin converting enzyme 2 (ACE2) is the human receptor that interacts with the spike protein of coronaviruses, including the one that produced the 2020 coronavirus pandemic (COVID-19). Thus, ACE2 is a potential target for drugs that disrupt the interaction of human cells with SARS-CoV-2 to abolish infection. There is also interest in drugs that inhibit or activate ACE2, that is, for cardiovascular disorders or colitis. Compounds binding at alternative sites could allosterically affect the interaction with the spike protein. Herein, we review biochemical, chemical biology, and structural information on ACE2, including the recent cryoEM structures of full-length ACE2. We conclude that ACE2 is very dynamic and that allosteric drugs could be developed to target ACE2. At the time of the 2020 pandemic, we suggest that available ACE2 inhibitors or activators in advanced development should be tested for their ability to allosterically displace the interaction between ACE2 and the spike protein.     

Synergistic antimicrobial effect of lactocin AL705 and nisin combined with organic acid salts against Listeria innocua 7 in broth and a hard cheese

The effectiveness of antimicrobial mixtures against Listeria innocua 7, used as a L. monocytogenes surrogate, was investigated in broth and a food system. Synergistic effects were found for nisin (Nis), potassium sorbate (PS), calcium propionate (CP) and sodium lactate (SL), Nis + PS being the most effective binary mixture that exhibited listericidal activity in broth. To assess the effect of adding lactocin AL705 (AL705) to Nis + organic acid salt combinations, tridimensional isobolograms were generated. Sub-MIC combinations of the antimicrobials exerted bactericidal activity against L. innocua 7 after AL705 addition to the binary mixtures. However, when applied on Sardo cheese contaminated with L. innocua 7 (initial inoculum 4.45 ± 0.06 CFU g⁻¹), only Nis + PS + AL705 produced count reductions respect to the control, reaching 3.04 ± 0.35 CFU g⁻¹ counts after 15 days at 15 °C. Ternary combinations containing AL705 showed potential to reduce antimicrobial usages for L. innocua 7 inhibition.     

Influence of Cu<Superscript>2+</Superscript> ions on structural and magnetic properties of NiZn ferrites

The paper is devoted to the preparation of NiZn ferrite with small substitutions of copper by means of ceramic technology. The influence of small Cu substitution on the microstructural and magnetic properties of NiZn ferrites have been analysed by means of various experimental methods and interpreted from the point of view of preparation technology optimisation and possible applications of such materials. A strong correlation between the substituent content and resulting properties has been observed, thus allowing preparation of material with the properties tailored for any particular application.     

Laser Induced Periodic Structures on Polymer Surfaces

Subhalf micron (0.2 nm) space and amplitude linear periodic structures and an array of dot images are obtained with the Nd:YAG laser irradiation on Kapton polyimide films, poly(ethylene terephthalate) films, spin-coated polyimide films and others. Different from the excimer laser irradiation, which requires a polarizer, our solid state Nd:YAG laser source provides polarized beams without a polarizer with advantage over excimer laser irradiation. AFM and SEM studies have been carried out. XPS studies of laser exposed areas indicate no significant chemical reactions took place on exposed areas.     

A NEW APPROACH FOR THE CLASSIFICATION AND ENUMERATION OF UNIQUE REACTION ROUTES AND UNIQUE OVERALL REACTIONS IN MULTIPLE CHEMICAL REACTION SYSTEMS

The methodology of response reactions (RERs) introduced earlier from thermodynamic and kinetic considerations is used in this work to develop a new algorithm for the classification and enumeration of unique/direct reaction routes (RRs) and overall reactions (ORs). According to the RERs approach, a unique set of both RRs and ORs may be generated starting from any conceivable set of linearly independent RRs and ORs. In particular, the direct ORs may be most conveniently enumerated starting from the formula matrix of the terminal species (reactants and products), i.e., without any relation to the elementary reactions comprising the detailed mechanism. Depending on the type of ORs produced by the RRs one can distinguish between two distinct types of direct RRs. Namely, one option is to define a direct RR by specifying the intermediate species that need to be eliminated. This type of RR is referred to as Milner RRs. The other option is to require the direct RRs to produce RERs, thus resulting in RRs referred to as Happel-Sellers RRs.     

Immersive electronic books for surgical training

Immersive electronic books (IEBooks) for surgical training will let surgeons explore previous surgical procedures in 3D. The authors describe the techniques and tools for creating a preliminary IEBook, embodying some of the basic concepts.     

A New Triazole-Thiol Compound Organofunctionalized on the Silica Gel Surface: Chemical Properties and Copper Sorption in Ethanol / Water Media

Silicon - This study describes the preparation and characterization of 3-chloropropyl silica gel with 4-amino-5-(4pyridyl)-4H-1,2,4-triazole-3-thiol (SGA) for copper adsorption in different media....     

Visceral Adipose Tissue Displays Unique Metabolomic Fingerprints in Obesity,Pre-Diabetes and Type 2 Diabetes

Visceral adipose tissue (VAT) metabolic profiling harbors the potential to disentangle molecular changes underlying obesity-related dysglycemia. In this study, the VAT exometabolome of subjects with obesity and different glycemic statuses are analyzed. The subjects (n = 19) are divided into groups according to body mass index and glycemic status: subjects with obesity and euglycemia (Ob+NGT, n = 5), subjects with obesity and pre-diabetes (Ob+Pre-T2D, n = 5), subjects with obesity and type 2 diabetes under metformin treatment (Ob+T2D, n = 5) and subjects without obesity and with euglycemia (Non-Ob, n = 4), used as controls. VATs are incubated in culture media and extracellular metabolite content is determined by proton nuclear magnetic resonance (¹H-NMR). Glucose consumption is not different between the groups. Pyruvate and pyroglutamate consumption are significantly lower in all groups of subjects with obesity compared to Non-Ob, and significantly lower in Ob+Pre-T2D as compared to Ob+NGT. In contrast, isoleucine consumption is significantly higher in all groups of subjects with obesity, particularly in Ob+Pre-T2D, compared to Non-Ob. Acetate production is also significantly lower in Ob+Pre-T2D compared to Non-Ob. In sum, the VAT metabolic fingerprint is associated with pre-diabetes and characterized by higher isoleucine consumption, accompanied by lower acetate production and pyruvate and pyroglutamate consumption. We propose that glucose metabolism follows different fates within the VAT, depending on the individuals’ health status.