Pre-Senescence Induction in Hepatoma Cells Favors Hepatitis C Virus Replication and Can Be Used in Exploring Antiviral Potential of Histone Deacetylase Inhibitors

Recent evidence suggests that fibrotic liver injury in patients with chronic hepatitis C correlates with cellular senescence in damaged liver tissue. However, it is still unclear how senescence can affect replication of the hepatitis C virus (HCV). In this work, we report that an inhibitor of cyclin-dependent kinases 4/6, palbociclib, not only induced in hepatoma cells a pre-senescent cellular phenotype, including G1 arrest in the cell cycle, but also accelerated viral replicon multiplication. Importantly, suppression of HCV replication by direct acting antivirals (DAAs) was barely affected by pre-senescence induction, and vice versa, the antiviral activities of host-targeting agents (HTAs), such as inhibitors of human histone deacetylases (HDACi), produced a wide range of reactions—from a dramatic reduction to a noticeable increase. It is very likely that under conditions of the G1 arrest in the cell cycle, HDACi exhibit their actual antiviral potency, since their inherent anticancer activity that complicates the interpretation of test results is minimized.     

The “Angiogenic Switch” and Functional Resources in Cyclic Sports Athletes

Regular physical activity in cyclic sports can influence the so-called “angiogenic switch”, which is considered as an imbalance between proangiogenic and anti-angiogenic molecules. Disruption of the synthesis of angiogenic molecules can be caused by local changes in tissues under the influence of excessive physical exertion and its consequences, such as chronic oxidative stress and associated hypoxia, metabolic acidosis, sports injuries, etc. A review of publications on signaling pathways that activate and inhibit angiogenesis in skeletal muscles, myocardium, lung, and nervous tissue under the influence of intense physical activity in cyclic sports. Materials: We searched PubMed, SCOPUS, Web of Science, Google Scholar, Clinical keys, and e-LIBRARY databases for full-text articles published from 2000 to 2020, using keywords and their combinations. Results: An important aspect of adaptation to training loads in cyclic sports is an increase in the number of capillaries in muscle fibers, which improves the metabolism of skeletal muscles and myocardium, as well as nervous and lung tissue. Recent studies have shown that myocardial endothelial cells not only respond to hemodynamic forces and paracrine signals from neighboring cells, but also take an active part in heart remodeling processes, stimulating the growth and contractility of cardiomyocytes or the production of extracellular matrix proteins in myofibroblasts. As myocardial vascularization plays a central role in the transition from adaptive heart hypertrophy to heart failure, further study of the signaling mechanisms involved in the regulation of angiogenesis in the myocardium is important in sports practice. The study of the “angiogenic switch” problem in the cerebrovascular and cardiovascular systems allows us to claim that the formation of new vessels is mediated by a complex interaction of all growth factors. Although the lungs are one of the limiting systems of the body in cyclic sports, their response to high-intensity loads and other environmental stresses is often overlooked. Airway epithelial cells are the predominant source of several growth factors throughout lung organogenesis and appear to be critical for normal alveolarization, rapid alveolar proliferation, and normal vascular development. There are many controversial questions about the role of growth factors in the physiology and pathology of the lungs. The presented review has demonstrated that when doing sports, it is necessary to give a careful consideration to the possible positive and negative effects of growth factors on muscles, myocardium, lung tissue, and brain. Primarily, the “angiogenic switch” is important in aerobic sports (long distance running). Conclusions: Angiogenesis is a physiological process of the formation of new blood capillaries, which play an important role in the functioning of skeletal muscles, myocardium, lung, and nervous tissue in athletes. Violation of the “angiogenic switch” as a balance between proangiogenic and anti-angiogenic molecules can lead to a decrease in the functional resources of the nervous, musculoskeletal, cardiovascular, and respiratory systems in athletes and, as a consequence, to a decrease in sports performance.     

Molecular Mechanisms of the Deregulation of Muscle Contraction Induced by the R90P Mutation in Tpm3.12 and the Weakening of This Effect by BDM and W7

Point mutations in the genes encoding the skeletal muscle isoforms of tropomyosin can cause a range of muscle diseases. The amino acid substitution of Arg for Pro residue in the 90th position (R90P) in γ-tropomyosin (Tpm3.12) is associated with congenital fiber type disproportion and muscle weakness. The molecular mechanisms underlying muscle dysfunction in this disease remain unclear. Here, we observed that this mutation causes an abnormally high Ca²⁺-sensitivity of myofilaments in vitro and in muscle fibers. To determine the critical conformational changes that myosin, actin, and tropomyosin undergo during the ATPase cycle and the alterations in these changes caused by R90P replacement in Tpm3.12, we used polarized fluorimetry. It was shown that the R90P mutation inhibits the ability of tropomyosin to shift towards the outer domains of actin, which is accompanied by the almost complete depression of troponin’s ability to switch actin monomers off and to reduce the amount of the myosin heads weakly bound to F-actin at a low Ca²⁺. These changes in the behavior of tropomyosin and the troponin–tropomyosin complex, as well as in the balance of strongly and weakly bound myosin heads in the ATPase cycle may underlie the occurrence of both abnormally high Ca²⁺-sensitivity and muscle weakness. BDM, an inhibitor of myosin ATPase activity, and W7, a troponin C antagonist, restore the ability of tropomyosin for Ca²⁺-dependent movement and the ability of the troponin–tropomyosin complex to switch actin monomers off, demonstrating a weakening of the damaging effect of the R90P mutation on muscle contractility.     

Phase equilibria in the cobalt oxide-copper oxide system

Thermodynamic properties were determined for the system cobalt oxide-copper oxide by means of an electromotive force (EMF) measurement techniques using galvanic cells with calciastabilized zirconia (CSZ) as the solid electrolyte and with air as the reference electrode according to the following schemes: CuO, Cu₂O | CSZ | air and CoO-CuO, Cu₂O CSZ | air for composition variables y=X_Cu/(X_Co+X_cu equal to 0.05, 0.15, 0.25, 0.35, 0.45, 0.667, and 0.8; and within the temperature interval 1200–1350 K. Thermodynamic properties calculated directly from EMF values were combined with the available literature data on phase equilibria, and thermodynamic properties of solid phases in the Co-Cu-O system were assessed. Both terminal solid solutions, (Co,Cu)O and (Cu,Co)O, were described by a sublattice model with Redlich-Kister excess term. The interaction parameters for both (Co,Cu)O and (Cu,Co)O solid solutions and the Gibbs energy of formation for the intermediate phase Cu₂CoO₃ were obtained. The Gibbs energies of fictive end-members: monoclinic “CoO” and “CuO” with rock salt structure were derived as well. The phase diagrams were calculated using the assessed thermodynamic parameters. The (T, y) phase diagram was calculated for existence under ambient air. The property diagrams log₁₀P(O₂) versus composition and activity of CuO versus composition were calculated at 1273 K. The results of our calculations were in a good agreement with available experimental data.     

Structure–property relationship of modified polypropylene–polycaproamide fiber

The effect of the addition of polyamide on the structure and properties of polypropylene fiber has been studied. Although a good fiber is obtained with a composition containing only a very low concentration of polycaproamide in polypropylene, the increase in polyamide content decreases the drawing strength of the mixed polymer melt due to sudden lowering of melt viscosity and strength. The poor melt strength of the studied polymer mixture is attributed to increased heterogeneity induced in the system with increased concentration of polyamide. Use of an effective interphase modifier, maleic anhydride-grafted polypropylene, however, was found to improve fiber properties of the studied polymer mixtures even with a very high concentration of polyamide as the dispersed phase. Thus, addition of a 1–4 wt % interphase modifier facilitates the formation of good fiber even with 30 wt % polycaproamide in the blend. This improvement is attributed to the improved dispersity of polyamide in the polypropylene matrix as well as improved phase compatibility due to the formation of a chemically modified polyamide during melt extrusion in the presence of maleic anhydride-grafted polypropylene.     

Designing N‐PolyVector Fields with Complex Polynomials

We introduce N‐PolyVector fields, a generalization of N‐RoSy fields for which the vectors are neither necessarily orthogonal nor rotationally symmetric. We formally define a novel representation for N‐PolyVectors as the root sets of complex polynomials and analyze their topological and geometric properties. A smooth N‐PolyVector field can be efficiently generated by solving a sparse linear system without integer variables. We exploit the flexibility of N‐PolyVector fields to design conjugate vector fields, offering an intuitive tool to generate planar quadrilateral meshes.     

Polymer matrices on the basis of polyacrylamide and β-cyclodextrin-containing pseudorotaxane for prolonged drug release: Synthesis and properties

Polymer cross-linked matrices based on polyacrylamide (PAA) and β-cyclodextrin-pseudorotaxane have been designed. The structure and properties of the objects synthesized were confirmed and studied by a series of methods, involving ultraviolet-, Fourier transform infrared-spectroscopy, thermal mass spectrometry, DSC, X-ray diffraction analysis (WAXS and SAXS). Desorption kinetics (especially significant slowing of desorption process) of some drugs, like metoprolol succinate and loratadine from obtained polymer matrices is shown to be optimal with 10 wt% β-CD-pseudorotaxane in their structure.     

Monitoring the curing processes of epoxy oligomers with partially substituted polyethoxymetallosiloxanes by IR spectroscopy and thermomechanical analysis

In this work, the curing of «ED-20» epoxy resin with partially siloxy-substituted aluminum, iron, and zirconium siloxanes that we obtained previously was studied. The initial content of a metallosiloxane in the compositions was 5–50 wt% with respect to the resin. In all the cases, thermal curing was used to obtain a series of samples in the form of solid homogeneous materials. The fact of the epoxy ring opening in the resin was confirmed by IR spectroscopy. The catalytic properties of the metal atom in a metallosiloxane were found to affect the curing process. The samples demonstrate rather a high resistance to thermooxidative destruction, and in most cases, their glass transition temperatures are lower than those obtained upon standard curing of «ED-20» resin with triethylenetetramine. Partially siloxy-substituted metalloalkoxysiloxanes can be efficient agents for curing and formation of a hybrid material based on epoxy resins.     

Texture Mapping Real‐World Objects with Hydrographics

In the digital world, assigning arbitrary colors to an object is a simple operation thanks to texture mapping. However, in the real world, the same basic function of applying colors onto an object is far from trivial. One can specify colors during the fabrication process using a color 3D printer, but this does not apply to already existing objects. Paint and decals can be used during post‐fabrication, but they are challenging to apply on complex shapes. In this paper, we develop a method to enable texture mapping of physical objects, that is, we allow one to map an arbitrary color image onto a three‐dimensional object. Our approach builds upon hydrographics, a technique to transfer pigments printed on a sheet of polymer onto curved surfaces. We first describe a setup that makes the traditional water transfer printing process more accurate and consistent across prints. We then simulate the transfer process using a specialized parameterization to estimate the mapping between the planar color map and the object surface. We demonstrate that our approach enables the application of detailed color maps onto complex shapes such as 3D models of faces and anatomical casts.