On the regularity of domains satisfying a uniform hour–glass condition and a sharp version of the Hopf–Oleinik boundary point principle

We prove that an open, proper, nonempty subset of _boxclose^n{\mathbb{R}}^n is a locally Lyapunov domain if and only if it satisfies a uniform hour-glass condition. The limiting cases are as follows: Lipschitz domains may be characterized by a uniform double cone condition, and domains of class may be characterized by a uniform two-sided ball condition. We discuss a sharp generalization of the Hopf–Oleinik boundary point principle for domains satisfying an interior pseudoball condition, for semi-elliptic operators with singular drift and obtain a sharp version of the Hopf strong maximum principle for second order, nondivergence form differential operators with singular drift. Bibliography: 66 titles. Illustrations: 7 figures.     

Naphthyl methacrylate-phenylene diacrylate-based monolithic column for reversed-phase capillary electrochromatography via hydrophobic and π interactions

A neutral naphthyl methacrylate-phenylene diacrylate-based monolith (NPM) was introduced for RP-CEC of various neutral and charged solute probes via hydrophobic and π interactions. The NPM column was prepared by the in situ polymerization of naphthyl methacrylate as the functional monomer and 1,4-phenylene diacrylate (PDA) as the crosslinker in a ternary porogenic solvent containing cyclohexanol, dodecanol and water. The NPM column exhibited cathodal EOF despite the fact that it was devoid of any fixed charges. NPM exhibited stronger EOF than its counterpart naphthyl methacrylate monolith (NMM) made from the in situ polymerization of naphthyl methacrylate and trimethylolpropane trimethacrylate (TRIM). As for NMM, it is believed that the EOF arises from the adsorption of mobile phase ions onto the monolith surface. The higher EOF exhibited by NPM may be attributed to the acrylate nature of PDA as compared to the methacrylate nature of TRIM, and therefore PDA has a higher binding capacity for mobile phase ions due to its higher polarity than TRIM. The adsorption of mobile phase ions together with the additional π interactions offered by the aromatic rings of the NPM matrix modulated solute retention and separation selectivity. The applications of NPM were demonstrated by the separation of a wide range of small and large solutes including peptides, tryptic peptide maps and proteins.     

An Optical Chemical Sensor Based on Swellable Dicarboxylate Functionalized Polymer Microspheres for pH Copper and Calcium Determination

An optical chemical sensor based on polymer swelling and shrinking has been studied by way of optical transmission. Polyvinylbenzyl chloride cross-linked with divinylbenzene and derivatized as the dicarboxylate was dispersed as microspheres in a hydrogel membrane. The absorbance was measured vs. the wavelength upon exposing the modified membrane to solutions of varying pH (3.0–9.0). At low pH (3.0), the absorbance had the highest value (1.34), while the absorbance decreased significantly (1.10) when the pH was increased to 9.0, indicating polymer swelling.The modified membrane was also used for sensing metal ions, in particular calcium and copper. Complex formation with the dicarboxylate functionality caused the polymer to shrink. This resulted in an increase in absorbance for a concentration ranging from 1.0×10^–3 to 4.0×10^–3M.     

Optical beam instabilities in nonlinear nanosuspensions

We investigate the modulation instability of plane waves and the transverse instabilities of soliton stripe beams propagating in nonlinear nanosuspensions. We show that in these systems the process of modulational instability depends on the input beam conditions. On the other hand, the transverse instability of soliton stripes can exhibit new features as a result of 1D collapse caused by the exponential nonlinearity.     

Deprotometalation-Iodolysis and Direct Iodination of 1-Arylated 7-Azaindoles: Reactivity Studies and Molecule Properties

Five protocols were first compared for the copper-catalyzed C-N bond formation between 7-azaindole and aryl/heteroaryl iodides/bromides. The 1-arylated 7-azaindoles thus obtained were subjected to deprotometalation-iodolysis sequences using lithium 2,2,6,6-tetramethylpiperidide as the base and the corresponding zinc diamide as an in situ trap. The reactivity of the substrate was discussed in light of the calculated atomic charges and the pK_a values. The behavior of the 1-arylated 7-azaindoles in direct iodination was then studied, and the results explained by considering the HOMO orbital coefficients and the atomic charges. Finally, some of the iodides generated, generally original, were involved in the N-arylation of indole. While crystallographic data were collected for fifteen of the synthesized compounds, biological properties (antimicrobial, antifungal and antioxidant activity) were evaluated for others.     

Angiotensin II Type I Receptor (AT1R): The Gate towards COVID-19-Associated Diseases

The binding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein to its cellular receptor, the angiotensin-converting enzyme 2 (ACE2), causes its downregulation, which subsequently leads to the dysregulation of the renin–angiotensin system (RAS) in favor of the ACE–angiotensin II (Ang II)–angiotensin II type I receptor (AT1R) axis. AT1R has a major role in RAS by being involved in several physiological events including blood pressure control and electrolyte balance. Following SARS-CoV-2 infection, pathogenic episodes generated by the vasoconstriction, proinflammatory, profibrotic, and prooxidative consequences of the Ang II–AT1R axis activation are accompanied by a hyperinflammatory state (cytokine storm) and an acute respiratory distress syndrome (ARDS). AT1R, a member of the G protein-coupled receptor (GPCR) family, modulates Ang II deleterious effects through the activation of multiple downstream signaling pathways, among which are MAP kinases (ERK 1/2, JNK, p38MAPK), receptor tyrosine kinases (PDGF, EGFR, insulin receptor), and nonreceptor tyrosine kinases (Src, JAK/STAT, focal adhesion kinase (FAK)), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. COVID-19 is well known for generating respiratory symptoms, but because ACE2 is expressed in various body tissues, several extrapulmonary pathologies are also manifested, including neurologic disorders, vasculature and myocardial complications, kidney injury, gastrointestinal symptoms, hepatic injury, hyperglycemia, and dermatologic complications. Therefore, the development of drugs based on RAS blockers, such as angiotensin II receptor blockers (ARBs), that inhibit the damaging axis of the RAS cascade may become one of the most promising approaches for the treatment of COVID-19 in the near future. We herein review the general features of AT1R, with a special focus on the receptor-mediated activation of the different downstream signaling pathways leading to specific cellular responses. In addition, we provide the latest insights into the roles of AT1R in COVID-19 outcomes in different systems of the human body, as well as the role of ARBs as tentative pharmacological agents to treat COVID-19.     

The Renin-Angiotensin System: A Key Role in SARS-CoV-2-Induced COVID-19

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), was first identified in Eastern Asia (Wuhan, China) in December 2019. The virus then spread to Europe and across all continents where it has led to higher mortality and morbidity, and was declared as a pandemic by the World Health Organization (WHO) in March 2020. Recently, different vaccines have been produced and seem to be more or less effective in protecting from COVID-19. The renin–angiotensin system (RAS), an essential enzymatic cascade involved in maintaining blood pressure and electrolyte balance, is involved in the pathogenicity of COVID-19, since the angiotensin-converting enzyme II (ACE2) acts as the cellular receptor for SARS-CoV-2 in many human tissues and organs. In fact, the viral entrance promotes a downregulation of ACE2 followed by RAS balance dysregulation and an overactivation of the angiotensin II (Ang II)–angiotensin II type I receptor (AT1R) axis, which is characterized by a strong vasoconstriction and the induction of the profibrotic, proapoptotic and proinflammatory signalizations in the lungs and other organs. This mechanism features a massive cytokine storm, hypercoagulation, an acute respiratory distress syndrome (ARDS) and subsequent multiple organ damage. While all individuals are vulnerable to SARS-CoV-2, the disease outcome and severity differ among people and countries and depend on a dual interaction between the virus and the affected host. Many studies have already pointed out the importance of host genetic polymorphisms (especially in the RAS) as well as other related factors such age, gender, lifestyle and habits and underlying pathologies or comorbidities (diabetes and cardiovascular diseases) that could render individuals at higher risk of infection and pathogenicity. In this review, we explore the correlation between all these risk factors as well as how and why they could account for severe post-COVID-19 complications.