Exploring Internal Structure of Nanoporous Glasses Obtained by Leaching of Phase‐Separated Alkali Borosilicate Glasses

Mesoporous glasses – the leaching products of phase‐separated alkali borosilicate glasses – are widely used in fundamental research and practical applications. In this work, the option to control their internal mesopore structure by varying the conditions of microphase separation has been studied. Structure and transport characterization of a family of nanoporous glasses obtained under different conditions has been performed using a combination of several experimental techniques, including gas adsorption, nuclear magnetic resonance cryoporometry and diffusometry.     

Microwave-Assisted Synthesis of the Flexible Iron-based MIL-88B Metal–Organic Framework for Advanced Energetic Systems

The 3D metal–organic framework (MOF), MIL-88B, built from the trivalent metal ions and the ditopic 1,4-Benzene dicarboxylic acid linker (H₂BDC), distinguishes itself from the other MOFs for its flexibility and high thermal stability. MIL-88B was synthesized by a rapid microwave-assisted solvothermal method at high power (850 W). The iron-based MIL-88B [Fe₃.O.Cl.(O₂C–C₆H₄–CO₂)₃] exposed oxygen and iron content of 29% and 24%, respectively, which offers unique properties as an oxygen-rich catalyst for energetic systems. Upon dispersion in an organic solvent and integration into ammonium perchlorate (AP) (the universal oxidizer for energetic systems), the dispersion of the MOF particles into the AP energetic matrix was uniform (investigated via elemental mapping using an EDX detector). Therefore, MIL-88B(Fe) could probe AP decomposition with the exclusive formation of mono-dispersed Fe₂O₃ nanocatalyst during the AP decomposition. The evolved nanocatalyst can offer superior combustion characteristics. XRD pattern for the MIL-88B(Fe) framework TGA residuals confirmed the formation of α-Fe₂O₃ nanocatalyst as a final product. The catalytic efficiency of MIL-88B(Fe) on AP thermal behavior was assessed via DSC and TGA. AP solely demonstrated a decomposition enthalpy of 733 J g^?1, while AP/MIL-88B(Fe) showed a 66% higher decomposition enthalpy of 1218 J g^?1; the main exothermic decomposition temperature was decreased by 71 °C. Besides, MIL-88B(Fe) resulted in a decrease in AP decomposition activation energy by 23% and 25% using Kissinger and Kissinger–Akahira–Sunose (KAS) models, respectively.

     

Sterically Hindered Quaternary Phosphonium Salts (QPSs): Antimicrobial Activity and Hemolytic and Cytotoxic Properties

Structure–activity relationships are important for the design of biocides and sanitizers. During the spread of resistant strains of pathogenic microbes, insights into the correlation between structure and activity become especially significant. The most commonly used biocides are nitrogen-containing compounds; the phosphorus-containing ones have been studied to a lesser extent. In the present study, a broad range of sterically hindered quaternary phosphonium salts (QPSs) based on tri-tert-butylphosphine was tested for their activity against Gram-positive (Staphylococcus aureus, Bacillus cereus, Enterococcus faecalis) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria and fungi (Candida albicans, Trichophyton mentagrophytes var. gypseum). The cation structure was confirmed to determine their biological activity. A number of QPSs not only exhibit high activity against both Gram-positive and -negative bacteria but also possess antifungal properties. Additionally, the hemolytic and cytotoxic properties of QPSs were determined using blood and a normal liver cell line, respectively. The results show that tri-tert-butyl(n-dodecyl)phosphonium and tri-tert-butyl(n-tridecyl)phosphonium bromides exhibit both low cytotoxicity against normal human cells and high antimicrobial activity against bacteria, including methicillin-resistant strains S. aureus (MRSA). The mechanism of QPS action on microbes is discussed. Due to their high selectivity for pathogens, sterically hindered QPSs could serve as effective tunable biocides.     

CHID1 Is a Novel Prognostic Marker of Non-Small Cell Lung Cancer

There is an urgent need for identification of new prognostic markers and therapeutic targets for non-small cell lung cancer (NSCLC). In this study, we evaluated immune cells markers in 100 NSCLC specimens. Immunohistochemical analysis revealed no prognostic value for the markers studied, except CD163 and CD206. At the same time, macrophage markers iNOS and CHID1 were found to be expressed in tumor cells and associated with prognosis. We showed that high iNOS expression is a marker of favorable prognosis for squamous cell lung carcinoma (SCC), and NSCLC in general. Similarly, high CHID1 expression is a marker of good prognosis in adenocarcinoma and in NSCLC in general. Analysis of prognostic significance of a high CHID1/iNOS expression combination showed favorable prognosis with 20 months overall survival of patients from the low CHID1/iNOS expression group. For the first time, we demonstrated that CHID1 can be expressed by NSCLC cells and its high expression is a marker of good prognosis for adenocarcinoma and NSCLC in general. At the same time, high expression of iNOS in tumor cells is a marker of good prognosis in SCC. When used in combination, CHID1 and iNOS show a very good prognostic capacity for NSCLC. We suggest that in the case of lung cancer, tumor-associated macrophages are likely ineffective as a therapeutic target. At the same time, macrophage markers expressed by tumor cells may be considered as targets for anti-tumor therapy or, as in the case of CHID1, as potential anti-tumor agents.     

Therapeutic Effects of hiPSC-Derived Glial and Neuronal Progenitor Cells-Conditioned Medium in Experimental Ischemic Stroke in Rats

Transplantation of various types of stem cells as a possible therapy for stroke has been tested for years, and the results are promising. Recent investigations have shown that the administration of the conditioned media obtained after stem cell cultivation can also be effective in the therapy of the central nervous system pathology (hypothesis of their paracrine action). The aim of this study was to evaluate the therapeutic effects of the conditioned medium of hiPSC-derived glial and neuronal progenitor cells in the rat middle cerebral artery occlusion model of the ischemic stroke. Secretory activity of the cultured neuronal and glial progenitor cells was evaluated by proteomic and immunosorbent-based approaches. Therapeutic effects were assessed by overall survival, neurologic deficit and infarct volume dynamics, as well as by the end-point values of the apoptosis- and inflammation-related gene expression levels, the extent of microglia/macrophage infiltration and the numbers of formed blood vessels in the affected area of the brain. As a result, 31% of the protein species discovered in glial progenitor cells-conditioned medium and 45% in neuronal progenitor cells-conditioned medium were cell type specific. The glial progenitor cell-conditioned media showed a higher content of neurotrophins (BDNF, GDNF, CNTF and NGF). We showed that intra-arterial administration of glial progenitor cells-conditioned medium promoted a faster decrease in neurological deficit compared to the control group, reduced microglia/macrophage infiltration, reduced expression of pro-apoptotic gene Bax and pro-inflammatory cytokine gene Tnf, increased expression of anti-inflammatory cytokine genes (Il4, Il10, Il13) and promoted the formation of blood vessels within the damaged area. None of these effects were exerted by the neuronal progenitor cell-conditioned media. The results indicate pronounced cytoprotective, anti-inflammatory and angiogenic properties of soluble factors secreted by glial progenitor cells.     

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.     

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.     

Nanocrystalline Metal Oxides from the Injection of Metal Oxide Sols in Coordinating Solutions: Synthesis,Characterization, Thermal Stabilization,Device Processing,and Gas‐Sensing Properties

Metal oxide (SnO₂, TiO₂, In₂O₃, ZnO) sols are prepared by various sol–gel processes in such a way as to hinder the condensation reactions. The obtained sols are injected at 160 °C into a solution of tetradecene and dodecylamine, and kept under heating for different periods of time. Depending on the starting sol, variously crystallized oxide nanoparticles are obtained, whose phase compositions and chemical structure have been studied by X‐ray diffraction (XRD) and Fourier transform IR spectroscopy. The elimination of the organic residuals has been carried out by thermal treatment, and the thermal evolution of the nanoparticles has been studied by thermal analyses and Raman spectroscopy. High‐resolution transmission electron microscopy studies coupled with XRD measurements show that the thermal treatment does not markedly affect the particle size, which remains in the nanometer‐sized regime (from 3.5 to 8.5 nm, depending on the system), except in the case of ZnO. The thermally purified and stabilized powders, drop‐coated onto alumina substrates with pre‐deposited electrical contacts, have been tested as gas‐sensing devices, displaying outstanding sensing properties even at room temperature.