l-Arginine Improves Solubility and ANTI SARS-CoV-2 Mpro Activity of Rutin but Not the Antiviral Activity in Cells

The COVID-19 pandemic outbreak prompts an urgent need for efficient therapeutics, and repurposing of known drugs has been extensively used in an attempt to get to anti-SARS-CoV-2 agents in the shortest possible time. The glycoside rutin shows manifold pharmacological activities and, despite its use being limited by its poor solubility in water, it is the active principle of many pharmaceutical preparations. We herein report our in silico and experimental investigations of rutin as a SARS-CoV-2 Mpro inhibitor and of its water solubility improvement obtained by mixing it with l-arginine. Tests of the rutin/l-arginine mixture in a cellular model of SARS-CoV-2 infection highlighted that the mixture still suffers from unfavorable pharmacokinetic properties, but nonetheless, the results of this study suggest that rutin might be a good starting point for hit optimization.     

A preconditioning approach to the pagerank computation problem

Some spectral properties of the transition matrix of an oriented graph indicate the preconditioning of Euler-Richardson (ER) iterative scheme as a good way to compute efficiently the vertexrank vector associated with such graph. We choose the preconditioner from an algebra U of matrices, thereby obtaining an ER_U method, and we observe that ER_U can outperform ER in terms of rate of convergence. The proposed preconditioner can be updated at a very low cost whenever the graph changes, as is the case when it represents a generic set of information. The particular U utilized requires a surplus of operations per step and memory allocations, which make ER_U superior to ER for not too wide graphs. However, the observed high improvement in convergence rate obtained by preconditioning and the general theory developed, are a reason for investigating different choices of U, more efficient for huge graphs.     

Oxygenation of calixarene phenol rings

[structure: see text] The first examples of epoxy-p-quinol and diepoxy-p-quinol calixarene derivatives have been obtained by base-promoted direct addition of O(2)(oxygenation) to calixarene phenol rings. The regio- and stereochemistry of these derivatives was determined by 2D NMR studies, in conjunction with MM3 calculations, and X-ray crystallography. Both the oxygenation and the subsequent carbonyl reduction occur with a preferential attack to the less hindered exo face of the calixarene rings.     

Ancillary ligand effect on single-site styrene polymerization: isospecificity of group 4 metal bis(phenolate) catalysts

Styrene is polymerized isospecifically by group 4 metal complexes that contain a C2-symmetrically coordinated 1,4-dithiabutane-linked bis(phenolato) ligand activated by methylaluminoxane.     

Dynamic-mechanical properties and melting points of some aliphatic and partially aromatic polyamides

Some aliphatic and partially aromatic polyamides have been prepared from hexamethylene diamine and the following dicarboxylic acids: deca-, octa-, hexa-methylenedicarboxylic, p-carboxymethylphenoxyacetic, p-carboxyethylphenoxyacetic, p-phenylenedipropionic, p-phenylenediacetic, p-carboxymethoxyphenoxyacetic, β(p-carboxymethyl)phenylpropionic.The dynamic-mechanical properties at 110 Hz have been measured between ?140° and about 200. Three relaxation processes α β and γ have been found: only the main transition α appreciably depends on chemical structure.The influences of the length of repeating unit and of in-chain substitution on melting points, crystallinity and the dynamic-mechanical α transition have been investigated. The results have been discussed in terms of chain flexibility, chain packing and intermolecular forces.     

Novel topological insulators from crystalline symmetries

We discuss recent advances in the study of topological insulators protected by spatial symmetries by reviewing three representative, theoretical examples. In three dimensions (3D), these states of matter are generally characterized by the presence of gapless boundary states at surfaces that respect the protecting spatial symmetry. We discuss the appearance of these topological states in both crystals with negligible spin–orbit coupling and a fourfold rotational symmetry, as well as in mirror-symmetric crystals with sizable spin–orbit interaction characterized by the so-called mirror Chern number. Finally, we also discuss similar topological crystalline states in one-dimensional (1D) insulators, such as nanowires or atomic chains, with mirror symmetry. There, the prime physical consequence of the non-trivial topology is the presence of quantized end charges.     

From a Medicinal Mushroom Blend a Direct Anticancer Effect on Triple-Negative Breast Cancer: A Preclinical Study on Lung Metastases

Bioactive metabolites isolated from medicinal mushrooms (MM) used as supportive treatment in conventional oncology have recently gained interest. Acting as anticancer agents, they interfere with tumor cells and microenvironment (TME), disturbing cancer development/progression. Nonetheless, their action mechanisms still need to be elucidated. Recently, using a 4T1 triple-negative mouse BC model, we demonstrated that supplementation with Micotherapy U-Care, a MM blend, produced a striking reduction of lung metastases density/number, paralleled by decreased inflammation and oxidative stress both in TME and metastases, together with QoL amelioration. We hypothesized that these effects could be due to either a direct anticancer effect and/or to a secondary/indirect impact of Micotherapy U-Care on systemic inflammation/immunomodulation. To address this question, we presently focused on apoptosis/proliferation, investigating specific molecules, i.e., PARP1, p53, BAX, Bcl2, and PCNA, whose critical role in BC is well recognized. We revealed that Micotherapy U-Care is effective to influence balance between cell death and proliferation, which appeared strictly interconnected and inversely related (p53/Bax vs. Bcl2/PARP1/PCNA expression trends). MM blend displayed a direct effect, with different efficacy extent on cancer cells and TME, forcing tumor cells to apoptosis. Yet again, this study supports the potential of MM extracts, as adjuvant supplement in the TNBC management.     

Interpretation of NMR Relaxation as a Tool for Characterising the Adsorption Strength of Liquids inside Porous Materials

Nuclear magnetic resonance (NMR) relaxation times are shown to provide a unique probe of adsorbate–adsorbent interactions in liquid‐saturated porous materials. A short theoretical analysis is presented, which shows that the ratio of the longitudinal to transverse relaxation times (T₁/T₂) is related to an adsorbate–adsorbent interaction energy, and we introduce a quantitative metric e_surf (based on the relaxation time ratio) characterising the strength of this surface interaction. We then consider the interaction of water with a range of oxide surfaces (TiO₂ anatase, TiO₂ rutile, γ‐Al₂O₃, SiO₂, θ‐Al₂O₃ and ZrO₂) and show that e_surf correlates with the strongest adsorption sites present, as determined by temperature programmed desorption (TPD). Thus we demonstrate that NMR relaxation measurements have a direct physical interpretation in terms of the characterisation of activation energy of desorption from the surface. Further, for a series of chemically similar solid materials, in this case a range of oxide materials, for which at least two calibration values are obtainable by TPD, the e_surf parameter yields a direct estimate of the maximum activation energy of desorption from the surface. The results suggest that T₁/T₂ measurements may become a useful addition to the methods available to characterise liquid‐phase adsorption in porous materials. The particular motivation for this work is to characterise adsorbate–surface interactions in liquid‐phase catalysis.     

Path integral synthesis of lyapunov functionals for partial differential equations

A method is given for constructing Lyapunov Functionals for dynamical systems governed by partial differential equations. The functionals are obtained as path integrals in a suitably chosen state space of a generalized gradient operator, and the method may be viewed as an extension to infinite dimensional systems of the variable gradient technique. Some of the fundamental concepts underlying the formalism are reviewed, and examples of applications to some linear, non-linear and hybrid systems are given.     

Material electromagnetic fields and material forces

Electromagnetic fields address configurational forces in a natural way through an energy–stress tensor, which reduces to the Maxwell tensor in the simplest case. This tensor is related to physical forces and to the Cauchy traction in a continuum. Material forces, as opposed to physical forces, are of a different nature as they act upon a site of a continuum where the possible material inhomogeneity is located. A material energy–stress tensor, which is reminiscent of the Maxwell stress, is associated with these forces. Through appropriate balance laws, a material momentum is also associated with material forces. The material momentum is of particular interest in electromagnetic materials as it is intimately related to the pseudomomentum of light [Peierls in Highlights of Condensed Matter Physics, pp. 237–255 (1985) and in Surprises in Theoretical Physics, pp. 91–99 (1979); Thellung in Ann. Phys. 127, 289–301 (1980)]. The balance law for the material momentum can be derived either from the classical physical laws or independently of them. This derivation, which is based on the material electromagnetic potentials and the related gauge transformations, is discussed and commented on for an electromagnetic body.