The Pathophysiology of Long COVID throughout the Renin-Angiotensin System

COVID-19 has expanded across the world since its discovery in Wuhan (China) and has had a significant impact on people’s lives and health. Long COVID is a term coined by the World Health Organization (WHO) to describe a variety of persistent symptoms after acute SARS-CoV-2 infection. Long COVID has been demonstrated to affect various SARS-CoV-2-infected persons, independently of the acute disease severity. The symptoms of long COVID, like acute COVID-19, consist in the set of damage to various organs and systems such as the respiratory, cardiovascular, neurological, endocrine, urinary, and immune systems. Fatigue, dyspnea, cardiac abnormalities, cognitive and attention impairments, sleep disturbances, post-traumatic stress disorder, muscle pain, concentration problems, and headache were all reported as symptoms of long COVID. At the molecular level, the renin-angiotensin system (RAS) is heavily involved in the pathogenesis of this illness, much as it is in the acute phase of the viral infection. In this review, we summarize the impact of long COVID on several organs and tissues, with a special focus on the significance of the RAS in the disease pathogenesis. Long COVID risk factors and potential therapy approaches are also explored.     

Preparation of nano-hydroxyapatite/poly(<Emphasis Type="SmallCaps">l</Emphasis>-lactide) biocomposite microspheres

Nano-hydroxyapatite (HA)/poly(l-lactide) (PLLA) composite microspheres with relatively uniform size distribution were prepared by a solid-in-oil-in-water (s/o/w) emusion solvent evaporation method. The encapsulation of the HA nanopaticles in microshperes was significantly improved by grafting PLLA on the surface of the HA nanoparticles (p-HA) during emulsion process. This procedure gave a possibility to obtain p-HA/PLLA composite microspheres with uniform morphology and the encapsulated p-HA nanoparticle loading reached up to 40 wt% (33 wt% of pure HA) in the p-HA/PLLA composite microspheres. The microstructure of composite microspheres from core-shell to single phase changed with the variation of p-HA to PLLA ratios. p-HA/PLLA composite microspheres with the diameter range of 2–3 μm were obtained. The entrapment efficiency of p-HA in microspheres could high up to 90 wt% and that of HA was only 13 wt%. Surface and bulk characterizations of the composite microspheres were performed by measurements such as wide angle X-ray diffraction (WAXD), thermal gravimetric analysis (TGA), environmental scanning electron microscope (ESEM) and transmission electron microscopy (TEM).     

Effects of Two Natural Bisbenzylisoquinolines,Curine and Guattegaumerine,Extracted from Isolona hexaloba on Rhodamine Efflux by Abcb1b from Rat Glycocholic-Acid-Resistant Hepatocarcinoma Cells

To develop new therapeutic molecules, it is essential to understand the biological effects and targets of clinically relevant compounds. In this article, we describe the extraction and characterization of two alkaloids from the roots of Isolona hexaloba—curine and guattegaumerine. The effect of these alkaloids on the multidrug efflux pump ABCB1 (MDR1/P-Glycoprotein) and their antiproliferative properties were studied. Compared to verapamil, a widely used inhibitor of P-gp, curine and guattegaumerine were found to be weak inhibitors of MDR1/P-Glycoprotein. The highest inhibition of efflux produced by verapamil disappeared in the presence of curine or guattegaumerine as competitors, and the most pronounced effect was achieved with curine. Altogether, this work has provided new insights into the biological effects of these alkaloids on the rat Mdr1b P-gp efflux mechanism and would be beneficial in the design of potent P-gp inhibitors.     

Molecular Dynamics Study of the Structural and Mechanical Properties of Skutterudite CoSb<Subscript>3</Subscript>: Surface Effect

Molecular dynamics simulations of the structural and mechanical properties of single-crystalline CoSb₃ have been carried out at room temperature. Special emphasis was given to the surface effect. Four different boundary conditions were applied to represent a wide range of surface-atom fractions. The LAMMPS program in conjunction with a multibody potential was employed. First, free relaxation was performed to obtain the corresponding stable configurations. The atomic rearrangements and energy distributions were observed. Then, uniaxial tensile deformation was simulated at a constant strain rate. The stress–strain responses and structural evolutions were examined during the process. Comparison of simulation results between different boundary conditions was carefully made. It was found that, when the scale of the single-crystalline CoSb₃ model becomes nanometric and the fraction of the surface atoms increases, the mechanical performance becomes substantially worse. Nonetheless, the deformation mechanism and intrinsic mechanical nature are very similar.     

Organic–Inorganic Nanohybrids as Novel Thermoelectric Materials: Hybrids of Polyaniline and Bismuth(III) Telluride Nanoparticles

Thermoelectric materials have received much attention recently from the viewpoint of global environmental issues and effective utilization of energy resources. Especially those effective at relatively low temperature, such as below 100°C, which are usually abandoned without use, have become noteworthy recently. From this point of view, organic thermoelectric materials are most attractive, because they could be prepared at low cost and applied in various locations due to their flexibility. We have investigated the thermoelectric properties of organic conducting polymers such as polyaniline, polypyrrole, and polyphenylenevinylene, and succeeded in increasing the thermoelectric performance by selecting dopants, stretching conducting films, etc. Recently we have focused on new systems of organic–inorganic hybrid thermoelectric materials. Herein we present the preparation of a novel system of hybrids of polyaniline and bismuth(III) telluride nanoparticles, starting from bismuth(III) chloride and tetrachlorotellurium by using polyvinylpyrrolidone as a protecting reagent, as well as their thermoelectric properties. The hybrids prepared by this particular method showed much higher thermoelectric performance than the starting organic conducting polymer.     

Microstructure and Thermoelectric Properties of Dense YB<Subscript>22</Subscript>C<Subscript>2</Subscript>N Samples Fabricated Through Spark Plasma Sintering

Dense samples of the higher boride YB₂₂C₂N have been fabricated through the spark plasma sintering (SPS) method with different sintering aids. YB₂₂C₂N is a representative of a series of newly discovered rare-earth borocarbonitrides, which may be the long-awaited n-type counterpart of boron carbide, “B₄C.” The effect of Si, SiC, Al, and TiC additions on the sintering process of YB₂₂C₂N has been studied. The best sintered bodies with densities higher than 90% of theoretical density were obtained by means of SPS at 1700°C. We show that the additive choice and pressure have an effect on grain size and density. An investigation of the effect of atmosphere on the sintering behavior has also been carried out. It was found that sinterability is enhanced under nitrogen atmosphere. Thermoelectric properties of the materials sintered with additives have been evaluated, and we discuss their dependences on the fabrication process route.     

Aqueous-Develop,Photosensitive Polynorbornene Dielectric: Optimization of Mechanical and Electrical Properties

The impact of thermal cure conditions on the mechanical and electrical properties of an epoxy cross-linked network incorporating a polynorbornene (PNB) dielectric polymer was studied. The cross-linking of the dielectric composition was achieved by an acid-catalyzed cationic cure reaction initiated by either thermal or photolytic activation of a photoacid generator. It is proposed that the observed mechanical and electrical properties of the fully cured polymer composition are the result of the development of a three-dimensional cross-linked network tying together the PNB polymer and multifunctional epoxy additives. The epoxy ring-opening reaction was measured using Fourier-transform infrared spectroscopy. The reduced modulus, internal film stress, dielectric constant, and swelling behavior of cross-linked films were studied as a function of curing temperature. Trends in the observed properties are explained by formation of a three-dimensional cross-linked network and degradation of the cross-links between the multifunctional epoxy additives at high temperature. It was also found that exposure of the film to aqueous base plays a role in the cure process and has a positive effect on the final properties. The optimum values of modulus, dielectric constant, residual stress, and moisture content were found for films cured at 160°C for 1 h. This relatively low cure temperature is potentially advantageous in device assembly and processing.