Structure-Based Development of SARS-CoV-2 Spike Interactors

Coronaviruses, including SARS-CoV-2 (the etiological agent of the current COVID-19 pandemic), rely on the surface spike glycoprotein to access the host cells, mainly through the interaction of their receptor-binding domain (RBD) with the human angiotensin-converting enzyme 2 (ACE2). Therefore, molecular entities able to interfere with the binding of the SARS-CoV-2 spike protein to ACE2 have great potential to inhibit viral entry. Starting from the available structural data on the interaction between SARS-CoV-2 spike protein and the host ACE2 receptor, we engineered a set of soluble and stable spike interactors, here denoted as S-plugs. Starting from the prototype S-plug, we adopted a computational approach by combining stability prediction, associated to single-point mutations, with molecular dynamics to enhance both S-plug thermostability and binding affinity to the spike protein. The best developed molecule, S-plug3, possesses a highly stable α-helical con-formation (with melting temperature Tm of 54 °C) and can interact with the spike RBD and S1 domains with similar low nanomolar affinities. Importantly, S-plug3 exposes the spike RBD to almost the same interface as the human ACE2 receptor, aimed at the recognition of all ACE2-accessing coronaviruses. Consistently, S-plug3 preserves a low nanomolar dissociation constant with the delta B.1.617.2 variant of SARS-CoV-2 spike protein (K_D = 29.2 ± 0.6 nM). Taken together, we provide valid starting data for the development of therapeutical and diagnostic tools against coronaviruses accessing through ACE2.     

Light emitting devices based on Si nanoclusters： the integration with a photonic-crystal and electroluminescence properties

We present the properties and potentialities of light emitting devices based on amorphous Si nanoclusters. Amorphousnanostructures may constitute an interesting alternative to Si nanocrystals for the monolithic integration of optical andelectrical functions in Si technology. In fact, they exhibit an intense room temperature electroluminescence (EL). The ELproperties of these devices have been studied as a function of current and of temperature. Moreover, to improve theextraction efficiency of the light, we have integrated the emitting system with a 2D photonic crystal structure opportunelyfabricated by using conventional optical lithography to reduce the total internal reflection of the emitted light. The extractionefficiency in such devices increases by a factor of 4 at a resonance wavelength.     

SPR-Based Detection of ASF Virus in Cells

African swine fever (ASF) is one of the most dangerous hemorrhagic infectious diseases that affect domestic and wild pigs. Currently, neither a vaccine nor effective treatments are available for this disease. As regards the degree of virulence, ASFV strains can be divided into high, moderate, or low virulence. The main detection methods are based on the use of the polymerase chain reaction (PCR). In order to prevent an uncontrolled spread of ASF, new on-site techniques that can enable the identification of an early-stage disease are needed. We have developed a specific immunological SPR-based assay for ASFV antigen detection directly in liquid samples. The developed assay allows us to detect the presence of ASFV at the dose of 10³ HAD₅₀/_mL.     

Cannabidiol Antiproliferative Effect in Triple-Negative Breast Cancer MDA-MB-231 Cells Is Modulated by Its Physical State and by IGF-1

Cannabidiol (CBD) is a non-psychoactive phytocannabinoid that has been discussed for its safety and efficacy in cancer treatments. For this reason, we have inquired into its use on triple-negative human breast cancer. Analyzing the biological effects of CBD on MDA-MB-231, we have demonstrated that both CBD dosage and serum concentrations in the culture medium influence its outcomes; furthermore, light scattering studies demonstrated that serum impacts the CBD aggregation state by acting as a surfactant agent. Pharmacological studies on CBD in combination with chemotherapeutic agents reveal that CBD possesses a protective action against the cytotoxic effect exerted by cisplatin on MDA-MB-231 grown in standard conditions. Furthermore, in a low serum condition (0.5%), starting from a threshold concentration (5 µM), CBD forms aggregates, exerts cytostatic antiproliferative outcomes, and promotes cell cycle arrest activating autophagy. At doses above the threshold, CBD exerts a highly cytotoxic effect inducing bubbling cell death. Finally, IGF-1 and EGF antagonize the antiproliferative effect of CBD protecting cells from harmful consequences of CBD aggregates. In conclusion, CBD effect is strongly associated with the physical state and concentration that reaches the treated cells, parameters not taken into account in most of the research papers.     

Therapeutic Potential of Allicin and Aged Garlic Extract in Alzheimer’s Disease

Garlic, Allium sativum, has long been utilized for a number of medicinal purposes around the world, and its medical benefits have been well documented. The health benefits of garlic likely arise from a wide variety of components, possibly working synergistically. Garlic and garlic extracts, especially aged garlic extracts (AGEs), are rich in bioactive compounds, with potent anti-inflammatory, antioxidant and neuroprotective activities. In light of these effects, garlic and its components have been examined in experimental models of Alzheimer’s disease (AD), the most common form of dementia without therapy, and a growing health concern in aging societies. With the aim of offering an updated overview, this paper reviews the chemical composition, metabolism and bioavailability of garlic bioactive compounds. In addition, it provides an overview of signaling mechanisms triggered by garlic derivatives, with a focus on allicin and AGE, to improve learning and memory.     

Genesis of “Solitary Cations” Induced by Atomic Hydrogen

Substitution of constituent atoms and/or changes of crystal structure are routinely used to tailor the fundamental properties of a semiconductor. Here, it is shown that such a tailoring can also be realized thanks to a novel hydrogen effect. Four hydrogen atoms can screen the effect the crystal potential has on a constituent cation, thus generating a solitary cation: an effectively isolated impurity, so chemically different from the unscreened constituent cations that it strongly perturbs the electronic properties of the material by increasing its fundamental band‐gap energy. Such a hydrogen‐induced screening effect is removed by thermal treatments, thus permitting reversible modifications of both the “crystal chemistry” and material's properties. This phenomenon, observed in InN and other topical nitrides, should permit the development of a new class of materials as well as the fabrication of photonic devices and optical integrated circuits with distinct, tailor‐made regions emitting or absorbing light, all integrated onto a monolithic semiconductor structure.     

In-plane behavior of perforated brick masonry walls

This paper reports the results of experimental and theoretical research conducted on perforated brick masonry walls under in-plane loading. The walls?? structural behavior depends strongly on their specific features, e.g. geometry, mechanical properties of the masonry material, brick arrangement and loading conditions. The experimental program was designed to study the incidence of brick arrangement in the spandrels and piers, and of the acting vertical load on the failure mode and load-bearing capacity of the walls. Six specimens of brick masonry wall with a central opening were submitted to a constant vertical load and a monotonic horizontal force that was gradually increased until the kinematic mechanism condition was reached. The object of the theoretical research was to develop a simplified analytical model for describing the kinematic mechanism of the walls. The results of the experiments indicate that brick arrangement strongly influences the failure mode and load-bearing capacity of the walls. Proper a priori assessment of the failure mode of walls becomes fundamental to an accurate evaluation of their load-bearing capacity using the proposed model.