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Background: Depression and low mood are leading contributors to disability worldwide. Research indicates that clinical depression may be associated with low creatine concentrations in the brain and low prefrontal grey matter volume. Because subclinical depression also contributes to difficulties in day-to-day life, understanding the neural mechanisms of depressive symptoms in all individuals, even at a subclinical level, may aid public health. Methods: Eighty-four young adult participants completed the Depression, Anxiety and Stress Scale (DASS) to quantify severity of depression, anxiety and stress, and underwent 1H-Magnetic Resonance Spectroscopy of the medial prefrontal cortex and structural magnetic resonance imaging (MRI) to determine whole-brain grey matter volume. Results/outcomes: DASS depression scores were negatively associated (a) with concentrations of creatine (but not other metabolites) in the prefrontal cortex and (b) with grey matter volume in the right superior medial frontal gyrus. Medial prefrontal creatine concentrations and right superior medial frontal grey matter volume were positively correlated. DASS anxiety and DASS stress scores were not related to prefrontal metabolite concentrations or whole-brain grey matter volume. Conclusions/interpretations: This study provides preliminary evidence from a representative group of individuals who exhibit a range of depression levels that prefrontal creatine and grey matter volume are negatively associated with depression. While future research is needed to fully understand this relationship, these results provide support for previous findings, which indicate that increasing creatine concentrations in the prefrontal cortex may improve mood and well-being.

The Sr1-xSmxTiO3 (х = 0.025, 0.05, 0.075, 0.1, 0.2) strontium titanate solid solutions were prepared from oxides and carbonates using a conventional ceramic technology based on the mechanochemical activation. The electrical conductivity and Seebeck coefficient of the synthesized compounds were measured in the temperature range from 300 to 800 K. We found that the properties of the samples significantly depend on the preliminary mechanochemical activation. The thermoelectric power factor attains maximum value in the hydrogen reduced samples with concentration of х = 0.05 and 0.075 obtained from nanoparticles: 5.5 μW/(cm · K2) for Sr0.95Sm0.05TiO3 (580 K) and 4.10 μW/(cm · K2) for Sr0.925Sm0.075TiO3 (650 K). An increase in the annealing temperature of mechanically activated samples leads to an even greater increase in electrical conductivity and power factor: 9.2 μW/(cm · K2) for Sr0.925Sm0.075TiO3 (650 K).

Antimicrobial resistance is a global threat. The use of biologically active natural products alone or in combination with the clinically proven antimicrobial agents might be a useful strategy to fight the resistance. The scientific hypotheses of this study were twofold: (1) the natural humic substances rich in dicarboxyl, phenolic, heteroaryl, and other fragments might possess inhibitory activity against β-lactamases, and (2) this inhibitory activity might be linked to the molecular composition of the humic ensemble. To test these hypotheses, we used humic substances (HS) from different sources (coal, peat, and soil) and of different fractional compositions (humic acids, hymatomelanic acids, and narrow fractions from solid-phase extraction) for inhibiting serine β-lactamase TEM-1. Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) was used to characterize the molecular composition of all humic materials used in this study. The kinetic assay with chromogenic substrate CENTA was used for assessment of inhibitory activity. The inhibition data have shown that among all humic materials tested, a distinct activity was observed within apolar fractions of hymatomelanic acid isolated from lignite. The decrease in the hydrolysis rate in the presence of most active fractions was 42% (with sulbactam-87%). Of particular importance is that these very fractions caused a synergistic effect (2-fold) for the combinations with sulbactam. Linking the observed inhibition effects to molecular composition revealed the preferential contribution of low-oxidized aromatic and acyclic components such as flavonoid-, lignin, and terpenoid-like molecules. The binding of single low-molecular-weight components to the cryptic allosteric site along with supramolecular interactions of humic aggregates with the protein surface could be considered as a major contributor to the observed inhibition. We believe that fine fractionation of hydrophobic humic materials along with molecular modeling studies on the interaction between humic molecules and β-lactamases might contribute to the development of novel β-lactamase inhibitors of humic nature.

Variants for the synthesis of aluminum acrylates, including substituted hydroxoacrylates, as well as an adduct of aluminum isopropylate with allylamine, were tested to develop a mixture that can be formed by photopolymerization, followed by annealing while maintaining the shape of the ceramic, for further use in molding using stereolithographic 3D printing. By photopolymerization of a polymer precursor based on an acrylate suspension of in situ synthesized alumoxane Al(OH)2(ООСН2СН=СН2), corundum ceramics of a given shape were prepared. The inhomogeneity of the polymer precursor does not prevent its use in technology. A significant percentage of weight loss during heat treatment of the polymer precursor suggests its possible use as a binder when filled with dispersed aluminum oxide powder. The highest shrinkage of a ceramic product occurs in the range of 200–400°C; it is necessary to develop a special program for heating up the product to the sintering temperature to minimize the consequences of severe shrinkage. When a molded product is heat treated in an inert atmosphere, the shrinkage is less than when annealed in air, since pyrolysis leaves behind a large amount of amorphous carbon. Annealing such ceramics with amorphous carbon in a nitrogen atmosphere is promising for carrying out the carbonitridization process in the preparation of aluminum nitride and oxynitride.

Reaction of Pd(acac)2 with BF3·OEt2 in the presence of tri(2-furyl)phosphine in toluene yields complex [Pd(acac)(TFP)2]BF4 (I) (TFP is tri(2-furyl)phosphine) whose structure is determined by XRD. The crystal structure of I contains short H⋯F contacts. The energies of these contacts are studied using DFT quantum chemical methods. Coordination complex I in combination with BF3·OEt2 in appropriate concentrations and solvents demonstrates catalytic activity in the reaction of morpholine allylic alkylation characterized by the catalyst turnover number from 198 mol to 268 mol of 4-allylmorpholine per mole of palladium and an integral selectivity to the main product of 88-99%.

New potentially biologically active sulfonamide derivatives of pentacyclic lupane-type triterpenoids, the sulfonamide group of which was bonded to C-17 of the triterpene skeleton through an amidoethane spacer, were synthesized via conjugation of 2-aminoethanesulfonamides to betulinic and betulonic acids in the presence of Mukaiyama reagent (2-bromo-1-methylpyridinium iodide).

We modify and optimize a cheap, simple and effective synthesis of zinc oxide nanosized particles by electrodeposition. The core method encompasses the synthesis of ZnO product on the soluble zinc anode of the two-zinc-electrode cell emerged in aqueous NaCl. Resulting particles have the shape of cocoa fruit, thick in the middle and sharp at the edges. They have uniform shape, but broad size distributions with most of the ZnO product 1-2 µm long and 0,5-0,7 µm thick. Thus, auxiliary stabilizers are added to aqueous phase to reduce the size and narrow its distribution in the target product. Here we present the size stabilizing action of four successful stabilizers: urea, polyvinyl alcohol, Triton x-100 and Atlas G3300. All of them reduce particle size and polydispersity. An anionactive surfactant atlas is the most effective, giving an order of magnitude nanorod size reduction.

Quantum-mechanical methods are used to assess the energy barriers to dissociation and recombination reactions of UF6 ↔ UF5 + F and UF6 ↔ UF4 + F2. The energy characteristics of these reactions are found to be strongly asymmetric: the dissociation reaction barriers exceed the recombination reactions barriers by more than 4 eV. The equilibrium atomic configurations of F2, UF4, UF5 and UF6 have been determined using precision quantum mechanical calculations. The U-F bond lengths obtained as a result of the calculations are in good agreement with experimental data. It was found that the decay reaction UF6 → UF5 + F is either barrier-free, or the energy barrier for such a reaction is less than the resolving power of the method (~ 0.1 eV). For the decay of UF6 → UF4 + F2, there is an energy barrier with a height of about 0.3 eV. An initial approximation was proposed for the arrangement of UF6 atoms in order to find the saddle points of the UF6 dissociation reactions. In this initial configuration, all 7 atoms of the UF6 molecule are located in the same plane. The F atoms are located at the vertices of a regular hexagon, and the U atom is at the center of such a hexagon. The results of this work can be used to determine the constants of thermal reactions of dissociation and recombination UF6 ↔ UF5 + F и UF6 ↔ UF4 + F2. These constants are necessary for modeling the physicochemical processes occurring during the enrichment of spent nuclear fuel (SNF).

In this paper, methods for removing corrosion product deposits from the primary circuit of light-water reactors with pressurized coolant under transient operating conditions are considered. The analysis of these methods, which are successfully used in the main types of light-water reactors, such as PWRs, VVERs, and nuclear marine propulsion reactors, has shown that the promising lines for their development are the selection of chemical reagents that do not violate the water chemistry of the coolant and provide the effective removal (disintegration or dissolution) of corrosion product deposits and experimental validation of their use. To disintegrate the deposits in the VVER-type reactors, hydrazine can be used; hydrazine and ammonia can be used for this purpose in marine nuclear propulsion reactors. The formation on the surface of fuel assemblies of bonaccordite (Ni2FeBO5) as a result of coolant boiling is a serious problem that may arise during the purification of the primary circuit from corrosion product deposits under transient conditions in the PWRs. To prevent the formation of this compound, it is proposed to adjust the water chemistry of the primary coolant so that the pH value of the medium is at 7.4 throughout the entire reactor’s operational period. The mutual influence of the methods for removing corrosion product deposits under transient operating conditions of nuclear reactors and the technology of injecting zinc into the primary circuit coolant has been analyzed. It has been shown that the technological solutions proposed can complement each other and, despite widespread applications of the zinc-injection technology, the purification methods still remain topical under transient operating conditions of the reactor. The purification methods under investigation have proven their applicability to the basic light-water reactors, such as PWRs and VVERs, as well as nuclear marine propulsion reactors.

With an exception of few reports, the plasma concentration of ouabain and marinobufagenin, mostly studied cardiotonic steroids (CTS) assessed by immunoassay techniques, is less than 1 nM. During the last 3 decades, the implication of these endogenous CTS in the pathogenesis of hypertension and other volume-expanded disorders is widely disputed. The threshold for inhibition by CTS of human and rodent α1-Na,K-ATPase is ∼1 and 1000 nM, respectively, that rules out the functioning of endogenous CTS (ECTS) as natriuretic hormones and regulators of cell adhesion, cell-to-cell communication, gene transcription and translation, which are mediated by dissipation of the transmembrane gradients of monovalent cations. In several types of cells ouabain and marinobufagenin at concentrations corresponding to its plasma level activate Na,K-ATPase, decrease the [Na+]i/[K+]i-ratio and increase cell proliferation. Possible physiological significance and mechanism of non-canonical Na+i/K+i-dependent and Na+i/K+i-independent cell responses to CTS are discussed.

Cystic fibrosis (CF) is a systemic hereditary disease caused by a mutation of the CFTR gene and characterized by damage to the glands of external secretion and severe dysfunctions of the respiratory system. The “severe” genotypes are associated with more pronounced and early clinical manifestations. The “mild” genotypes are associated with a delayed onset of clinical manifestations.Methods. An analysis of the medical history of patients with asymptomatic CF from the Russian CF centers was carried out. Rectal biopsy specimens were used for intestinal current measurement (ICM) and forskolin-induced swelling assay in intestinal organoids. DNA for sequencing was isolated from the venous blood leukocytes.Results. 2 CF patients with genotypes F508del/c.1584+18672A>G (patient 1, 12 years old) and F508del/G509D-E217G (patient 2, 3 years old) were examined. The diagnosis was based on neonatal screening. The ICM assay showed a reduced function of the CFTR channel: ΔISC for forskolin was 12.33 ± 2.35 μA/cm2 in patient 1 and 25 ± 3.37 μA/cm2 in patient 2. The negative response to carbachol and histamine reflects the entry of potassium ions into the cells, which is typical for CF. The assay in intestinal organoids showed that the amount of functional protein on the apical membrane of the intestinal epithelium increases both under the action of the potentiator and the corrector in both patients. The greatest effect is observed when the VX-770 and VX-809 are used together.Conclusion. The ICM functional assay and the forskolin-induced swelling assay in intestinal organoids are sensitive enough to determine the residual functional activity of the CFTR channel and clarify the diagnosis in difficult cases. The studied genetic variants c.1584+18672A>G and G509D-E217G belong to class IV – VI mutations. The clinical picture corresponds to the manifestations of “mild” mutations. The studied patients still attend the Russian cystic fibrosis centers.

The article presents testing of polymer protective coating based on polyurethane developed in Bauman Moscow State Technical University. It is shown that the developed coating has an increased resistance to erosive wear, an increased level of adhesion and temperature resistance, compared with the existing coatings, certified by aviation.

―A new anion-deficient Sr2.4Dy0.6Co2O7‒δ (δ = 0.33–1.1) perovskite phase with a structure of the A3B2O7 Raddlesden‒Popper homologous series has been obtained by the solid-state synthesis in the reducing/oxidizing atmosphere and its structural characterization has been performed by the Rietveld refinement of the X-ray powder diffraction data. It has been stablished that the Sr2.4Dy0.6Co2O7‒δ compound (sp. gr. I4/mmm) has parameters of a = b = 3.8526(1) and c = 19.9431(7) A in the reduced form (δ = 1.1) and a = b = 3.8086(1) and c = 19.9190(6) A in the oxidized form (δ ≈ 0.33) and oxygen vacancies occupy mainly the sites linking CoO5 polyhedra inside two perovskite layers. It has been established using differential scanning calorimetry and thermogravimetry that, at T

This paper studies the influence of lattice and shell type architecture on the mechanical properties of biodegradable polymer scaffolds (cellular matrices) designed to create structures for bone tissue engineering. Varying the topology of nodal connections makes it possible to control the relative rigidity of the metamaterial in the range from 0.004 to 0.123. It is shown to be possible to create permeable scaffolds using thermally extruded 3D printing based on polymers of different elasticities—polylactide and polyurethane. The use of “unit cells” of various types allows fabricating structures such as shells based on polylactide with a compressive strength of 1.5 to 19.7 MPa. Shells with a cubic type architecture based on polyurethane can be almost reversibly deformed at values of deformation of more than 50%. The developed approaches for obtaining polymer metamaterials and modifying their surface with calcium phosphate layer using an artificial interstitial fluid can increase the hydrophilicity of materials.

The effect of nitrating mixture and 2-ethylhexanol temperatures on the yield and purity of 2-ethylhexyl nitrate produced in a continuously operating unit having a centrifugal mass transfer apparatus (nitrator) is studied. It is demonstrated that elevation of temperature of the reagents from 12 to 20°C enhances the yield and purity of the desired product. The degree of completeness of the chemical reaction in the nitrator and the coil heat exchanger was determined using materials balance equations.

BACKGROUND: Patients with metastatic colorectal cancer with the BRAF V600E mutation have a poor prognosis, with a median overall survival of 4 to 6 months after failure of initial therapy. Inhibition of BRAF alone has limited activity because of pathway reactivation through epidermal growth factor receptor signaling. METHODS: In this open-label, phase 3 trial, we enrolled 665 patients with BRAF V600E-mutated metastatic colorectal cancer who had had disease progression after one or two previous regimens. Patients were randomly assigned in a 1:1:1 ratio to receive encorafenib, binimetinib, and cetuximab (triplet-therapy group); encorafenib and cetuximab (doublet-therapy group); or the investigators' choice of either cetuximab and irinotecan or cetuximab and FOLFIRI (folinic acid, fluorouracil, and irinotecan) (control group). The primary end points were overall survival and objective response rate in the triplet-therapy group as compared with the control group. A secondary end point was overall survival in the doublet-therapy group as compared with the control group. We report here the results of a prespecified interim analysis. RESULTS: The median overall survival was 9.0 months in the triplet-therapy group and 5.4 months in the control group (hazard ratio for death, 0.52; 95% confidence interval [CI], 0.39 to 0.70; P

The reduction of TiO2 and CaTiO3 in a mixture with calcium has been studied in an argon atmosphere and vacuum at temperatures in the range 1023–1123 K. The adiabatic temperature of the reduction reactions involved has been calculated as a function of the excess of calcium in the starting mixture and its initial temperature. The presence of a thin CaCl2 film on calcium particles and the use of calcium titanate as a precursor have been shown to increase the reduction rate. The use of a CaTiO3 precursor and CaCl2-activated calcium has made it possible to obtain titanium powders containing 0.5 wt % oxygen and having a specific surface area of 1.2 m2/g via reduction at a temperature of 1073 K for 6 h.

The conditions for the synthesis of silicon carbide nanoparticles in a SiH4/C2H2/Ar/He gas mixture under the action of CO2 laser radiation with a wavelength of 10.6 μm are determined. It was found that laser synthesis of SiC particles is observed when the ratio of gas flows SiH4/C2H2 is in the range of 1.6-3.2. The temperature in the region of the reaction zone was ~1400-1500°C. Silicon carbide nanoparticles ~6 nm in diameter were obtained and their composition was investigated.

The kinetics of cesium and strontium sorption by natural clinoptilolite and its ferrocyanide-modified analogs, NPF-Cl and NPF-Cl (Ca-form), from solutions of various compositions containing 100 mg L–1 sorbate was studied, and the texture and porosity of the sorbent samples before and after the sorption of cesium and strontium were determined. The sorption process occurs in three-stages and is limited by a heterogeneous ion exchange reaction (HIOR) on the ferrocyanide phase located on the outer surface of clinoptilolite and in its macropores, internal diffusion of cesium and strontium into sorbent granule, and precipitation of ferrocyanide phases of complex composition in small mesopores and micropores of sorbents. The HIOR and precipitation occur with involvement of solution components (sodium, calcium, and iron). Sorption of cesium and strontium is accompanied by a significant change in the texture and porosity of the sorbents.

Nonstoichiometric silicon nitride SiNx is a promising material for developing a new generation of high-speed, reliable flash memory device based on the resistive effect. The advantage of silicon nitride over other dielectrics is its compatibility with the silicon technology. In the present work, a silicon nitride-based memristor deposited by the plasma-enhanced chemical vapor deposition method was studied. To develop a memristor based on silicon nitride, it is necessary to understand the charge transport mechanisms in all states. In the present work, it was established that the charge transport in high-resistance states is not described by the Frenkel effect model of Coulomb isolated trap ionization, Hill–Adachi model of overlapping Coulomb potentials, Makram–Ebeid and Lannoo model of multiphonon isolated trap ionization, Nasyrov–Gritsenko model of phonon-assisted tunneling between traps, Shklovskii–Efros percolation model, Schottky model and the thermally assisted tunneling mechanisms. It is established that, in the initial state, low-resistance state, intermediate-resistance state and high-resistance state, the charge transport in the forming-free SiNx-based memristor is described by the space charge limited current model. The trap parameters responsible for the charge transport in various memristor states are determined.

We report here the first evidence for the interaction of poly(ethylene glycol) (PEG) with hyaluronan (HA) in aqueous solutions. PEG-HA complexes (Kapp = 45,000 ± 8000 M-1) contained about 3.3 ± 0.1 of ethylene glycol units per disaccharide of HA. The carboxyl of the D-glucuronic acid and the amide of the N-acetyl-D-glucosamine did not participate in PEG binding. Similar experiments performed with dextran and monosaccharides showed that multiple free primary hydroxyls regularly distributed along the polysaccharide chain are necessary for PEG binding. Another novelty of our study is contraction of HA upon PEG binding. The effect was observed with HA in solution or adsorbed on positively charged liposomes. The thickness of the HA layer on the liposomes decreased 2-fold upon PEG addition. HA compaction induced by PEG may underlie the changes in the plasma membrane properties and resealing of mechanical injuries induced by Pluronics.

Background Modern guidelines recommend sodium-glucose cotransporter-2 (SGLT2) inhibitors as the preferred antihyperglycemic agents for patients with type 2 diabetes and chronic kidney disease. However, the mechanisms underlying the renal protective effect of SGLT2 inhibitors are not fully understood. Aim To estimate the effect of the SGLT2 inhibitor, empagliflozin (EMPA), on the structure of podocytes and nephrin expression in glomeruli in db/db diabetic mice. Methods We treated 8-wk-old male db/db mice with EMPA (10 mg/kg/d) or vehicle for 8 wk. Age-matched male db/+ mice were included as non-diabetic controls. Parameters of body composition, glycemic and lipid control, and plasma concentrations of leptin, insulin and glucagon were assessed. We evaluated renal hypertrophy as kidney weight adjusted to lean mass, renal function as plasma levels of creatinine, and albuminuria as the urinary albumin-to-creatinine ratio (UACR). Renal structures were studied by light and transmission electron microscopy with a focus on mesangial volume and podocyte structure, respectively. Glomerular nephrin and transforming growth factor beta (TGF-β) were assessed by immunohistochemistry. Results Severe obesity and hyperglycemia developed in db/db mice prior to the start of the experiment; increased plasma concentrations of fructosamine, glycated albumin, cholesterol, leptin, and insulin, and elevated UACR were detected. Mesangial expansion, glomerular basement membrane thickening, and increased area of TGF-β staining in glomeruli were revealed in vehicle-treated mice. Podocytopathy was manifested by effacement of foot processes; nephrin-positive areas in glomeruli were reduced. EMPA decreased the levels of glucose, fructosamine and glycated albumin, UACR, kidney hypertrophy, mesangial expansion, glomerular basement membrane thickening, and glomerular TGF-β staining, alleviated podocytopathy and restored glomerular staining of nephrin. Conclusion These data indicate that EMPA attenuates podocytopathy in experimental diabetic kidney disease. The anti-albuminuric effect of EMPA could be attributed to mitigation of podocyte injury and enhancement of nephrin expression.

The work juxtaposes electron density distributions in N,N-dimethylaniline, its three parasubstituted derivatives, two orthosubstituted derivatives of benzoic acid, 2-[4-[(dimethylamino)-phenyl]diazenil]benzoic acid (methyl red), and benzene. Intramolecular weak interactions C⋯H, H⋯H, and O⋯N and the rings they form are considered within the “quantum theory of atoms in molecules” (QTAIM). The characteristics of QTAIM bonds at critical points are found. The stability of rings is estimated; relative stability of C⋯H and O⋯N bonds stabilizing spatial molecular configuration in methyl red is demonstrated.

Calcium alkali metal (potassium and sodium) double and triple phosphates have been synthesized in different ways. Was for the first time used reaction sintering to produce ceramics based on calcium alkali metal mixed phosphates and investigated the densification behavior of mixed phosphate-based multiphase materials during sintering by this method. Was presented the microstructure of polished surfaces of sintered samples differing in phase composition and determined the density of ceramics prepared using reaction mixtures differing in composition. The effect of reaction sintering on the porosity of the ceramics has been assessed. Using stereolithographic printing and reaction sintering, was produced macroporous mixed calcium phosphate-based ceramic implants. Their compressive strength has been determined to be 0.78 ± 0.21 MPa for two-phase samples and 1.02 ± 0.13 MPa for three-phase samples.

Ekaterina A Skomorokhova,1,2 Tatiana P Sankova,3 Iurii A Orlov,1 Andrew N Savelev,3 Daria N Magazenkova,3 Mikhail G Pliss,4,5 Alexey N Skvortsov,3 Ilya M Sosnin,1 Demid A Kirilenko,1,6 Ivan V Grishchuk,3 Elena I Sakhenberg,7 Elena V Polishchuk,1,8 Pavel N Brunkov,1,6 Alexey E Romanov,1,6 Ludmila V Puchkova,1– 3 Ekaterina Yu Ilyechova1,2 1International Research Center of Functional Materials and Devices of Optoelectronics, ITMO University, St. Petersburg, Russia; 2Department of Molecular Genetics, Research Institute of Experimental Medicine, St. Petersburg, Russia; 3Higher Engineering Physics School of the Institute of Physics, Nanotechnology and Telecommunications, Peter the Great St. Petersburg Polytechnic University, St. Petersburg, Russia; 4Department of Experimental Physiology and Pharmacology, Almazov National Medical Research Centre, St. Petersburg, Russia; 5Laboratory of Blood Circulation Biophysics, Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russia; 6Center of Nanoheterostructures Physics, Ioffe Institute, Russian Academy of Sciences, St. Petersburg, Russia; 7Laboratory of Cell Protection Mechanisms, Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russia; 8Telethon Institute of Genetics and Medicine, Pozzuoli, Naples, ItalyCorrespondence: Ekaterina Yu Ilyechova Department of Molecular GeneticsResearch Institute of Experimental Medicine, Acad. Pavlov Street, 12, St. Petersburg 197376, RussiaTel +79217605274Fax +78122322307Email ilichevaey@itmo.ruPurpose: The ability of silver nanoparticles (AgNPs) of different sizes to influence copper metabolism in mice is assessed.Materials and Methods: AgNPs with diameters of 10, 20, and 75 nm were fabricated through a chemical reduction of silver nitrate and characterized by UV/Vis spectrometry, transmission and scanning electronic microscopy, and laser diffractometry. To test their bioactivity, Escherichia coli cells, cultured A549 cells, and C57Bl/6 mice were used. The antibacterial activity of AgNPs was determined by inhibition of colony-forming ability, and cytotoxicity was tested using the MTT test (viability, %). Ceruloplasmin (Cp, the major mammalian extracellular copper-containing protein) concentration and enzymatic activity were measured using gel-assay analyses and WB, respectively. In vitro binding of AgNPs with serum proteins was monitored with UV/Vis spectroscopy. Metal concentrations were measured using atomic absorption spectrometry.Results: The smallest AgNPs displayed the largest dose- and time-dependent antibacterial activity. All nanoparticles inhibited the metabolic activity of A549 cells in accordance with dose and time, but no correlation between cytotoxicity and nanoparticle size was found. Nanosilver was not uniformly distributed through the body of mice intraperitoneally treated with low AgNP concentrations. It was predominantly accumulated in liver. There, nanosilver was included in ceruloplasmin, and Ag-ceruloplasmin with low oxidase activity level was formed. Larger nanoparticles more effectively interfered with the copper metabolism of mice. Large AgNPs quickly induced a drop of blood serum oxidase activity to practically zero, but after cancellation of AgNP treatment, the activity was rapidly restored. A major fraction of the nanosilver was excreted in the bile with Cp. Nanosilver was bound by alpha-2-macroglobulin in vitro and in vivo, but silver did not substitute for the copper atoms of Cp in vitro.Conclusion: The data showed that even at low concentrations, AgNPs influence murine copper metabolism in size-dependent manner. This property negatively correlated with the antibacterial activity of AgNPs.Keywords: silver nanoparticles, copper status, ceruloplasmin, alpha-2-macroglobulin, bile, urine

We have studied the effect of precursors on the synthesis conditions and characteristics of molybdenum nitrides. Mo, MoO3, and MgMoO4 powders were nitrided in flowing ammonia at temperatures in the range 500–800°C. The use of molybdenum nanopowder as a precursor has made it possible to reduce the synthesis temperature and time. We have demonstrated the possibility of direct ammonolysis of the double oxide MgMoO4. Using this molybdate, we have obtained a material with a specific surface area up to 29 m2/g, which is a factor of 2 to 3 larger than that reached by nitriding MoO3. In all cases, the synthesis products consisted of the γ- and β-phases of Mo2N, with cubic and tetragonal lattices, respectively.

Anisotropic periodic relief in form of ripples was formed on surface of amorphous hydrogenated silicon (a-Si:H) films by femtosecond laser pulses with the wavelength of 1.25 μm. The orientation of the surface structures relative to laser radiation polarization vector depended on the number of laser pulses N acting on the film surface. When N = 30, the structures with 0.88 μm period were formed orthogonal to the laser radiation polarization; at N = 750 the surface structures had period of 1.12 μm and direction parallel to the polarization. The conductivity of the laser-modified a-Si:H films increased by 3 to 4 orders of magnitude, up to 3.8·10–5 (Ω∙cm)–1, due to formation of nanocrystalline Si phase with a volume fraction from 17 to 30%. Anisotropy of the dark conductivity, as well as anisotropy of the photoconductivity spectral dependences was observed in the modified films due to depolarizing influence of periodic microscale relief and uneven distribution of nanocrystalline Si phase within such laser-induced structure.

Objective:to assess the presence and degree of bronchial hyperreactivity in convalescents of whooping cough based on the results of bronchial provocation tests.Materials and methods. Using bronchial provocative samples with a 0,02/0,33% histamine solution and 0,33% methacholine solution on a PROVOTEST-2 apparatus from PARI, bronchial hyperreactivity was studied in 12 pertussis convalescents aged 7 to 17 years. The level of endogenous nitrogen monoxide in exhaled air (FeNO) was measured using a portable NObreath electrochemical analyzer (from Bedfont Scientific Ltd.).The results.According to the results of BPP, 6 of 12 convalescents of whooping cough were found to have bronchial hyperreactivity of varying degrees. When conducting a breath test with a histamine solution, bronchial hyperreactivity was recorded in three children, in a sample with methacholine, in five. In 3 out of 6 children with revealed signs of bronchial hyperreactivity, the history of atopy was not burdened, which suggests a connection between the pertussis and the development of bronchial hyperreactivity. A significant increase in the level of endogenous nitric monoxide (above 16 ppb) was observed in 2 out of 10 patients. Follow-up observation showed that the duration of cough with whooping cough ranged from 3 to 6 months, and in patients with positive results of several tests it was maximum. Two out of three children with bronchial asthma showed elevated levels of FeNO and samples with methacholine. Follow-up observation showed that whooping cough aggravated bronchial asthma and demanded correction therapy.Conclusion. A pilot study on the evaluation of bronchial provocative tests suggests that the formation of bronchial hyperreactivity in convalescents of whooping cough is probable, including without a history of atopy, which increases the risk of developing bronchial asthma, however, additional studies are required for a final conclusion.

Pluripotential cephalosporin antibiotics of different generations active against Gram-negative bacteria are used when treating urinary tract infections, mild and moderate pyelonephritis, acute otitis in children, etc. Rapid determination of cephalosporin antibiotics in the biological fluids is important to evaluate physiological and biochemical processes resulting from their metabolism in a human organism. Planar potentiometric sensors of different types — unmodified and modified with polyaniline (0.3 – 1%), NiZnFeO nanoparticles, and their binary mixes — are developed on the basis of associates of tetradecylammonium (TDA) with complex compounds silver (I) — β -lactam [Ag (I) – ( β -lac) 2 ] which are sensitive to some cephalosporin antibiotics, i.e., cefazoline (Cef), cefuroksime (Cefur) and ceftriaksone (Ceftr). In the sensors of type I, electrode-active components (EAC) and modifiers were added to carbon-containing ink, whereas in type II sensors the polyvinylchloride plasticized unmodified and modified membranes based on [Ag 2 (Ceftr) 2 ] 2 · 2TDA were used. Electroanalytic and operational characteristics of unmodified and modified planar sensors in aqueous solutions of cefazoline, cefuroxime, ceftriaxone and against the background of oral fluid were estimated. It is shown that introduction of the modifiers into sensor membranes leads to stabilization of their potential, increases angular coefficients of electrode functions, decreases the antibiotic detection limit to 1.7 Ч 10 –5 M, reduces the response time and potential drift. Nanoparticles of NiZnFeO appeared to be the most effective modifier. For the sensors of type II linearity of electrode functions is observed in the range of ceftriaxone concentrations of 3.1 Ч 10 –5 – 0.1 Ч 10 –1 M. Depending on the content of the electrode active components in the membrane phase of the unmodified planar sensors, the values of the angular coefficients of the electrode functions vary within 25 – 27 mV/p C and correspond to the values of the non-static value for doubly-charged ions. The linearity intervals of sensor electrode functions are identical at all EAC concentrations under study; as Ceas increases, potential drift and response time decreases. The developed planar sensors were used for determination of cephalosporin antibiotics in model aqueous solutions, medicinal preparations and oral fluid.

Thiazole derivatives represent an important class of azole heterocycles with a broad spectrum of biological activity and, therefore, the synthesis of these compounds is of remarkable concern. We present here practical and reliable protocol for synthesis of some 5-acylthiazoles and demonstrate their utility in the preparation of several new series of thiazole-containing building blocks through transformation of 5-acyl function. Specifically, thiazole-based alcohols, oximes, primary, and secondary amines were successively synthesized in good to excellent yields. The chemical structures of obtained compounds were confirmed by 1H and 13C NMR-spectroscopy, elemental analysis, and mass-spectrometry.

Silicon oxide and silicon nitride are two key dielectrics in silicon devices. The advantage of silicon nitride over other dielectrics is that silicon nitride is compatible with silicon technology. Despite numerous studies, the mechanism of charge transfer in the storage elements of resistive memory based on silicon nitride is still not clear. It is required to study in detail the mechanism of charge transfer in a memristor based on silicon nitride in order to further improve the cell information storage element and create a matrix of these elements. Metal–nitride–oxide–silicon (MNOS) structures that exhibit memristor properties are obtained using chemical vapor deposition at low pressure at 700°C. The fabricated structure of the resistive memory storage element based on metal–nitride–oxide–silicon does not require a molding procedure. In addition, such a memristor has a memory window of about five orders of magnitude. We establish that the main mechanism of charge transfer in the MNOS memristor in the high-resistance state is the current model with a limited spatial charge of the traps. In a low resistance state, the charge transfer mechanism is described by the current model with a limited spatial charge with filled traps. The trap’s parameters are determined in a memristor based on silicon nitride in a high-resistance state.

We have studied characteristic features of the reduction of single-crystal lithium tantalate and lithium niobate powders with magnesium vapor in the temperature range 1023–1123 K. The results demonstrate that the reduction of single-crystal particles is accompanied by their spontaneous mechanical disintegration. The presence of Li2O in the double oxides has not led to an increase in the specific surface area of the metallic powders obtained. Li2O has been completely reduced in the final stage of the process, without contributing to an increase in the number of pores in the structure of the powder particles.

We have studied tungsten powders prepared by reducing the MgWO4 and Ca3WO6 tungstates containing 0.05–1.5 wt % phosphorus at temperatures from 700 to 800°C. The reduction of MgWO4 containing less than 0.3 wt % phosphorus was accompanied by separation of reaction products. Most of the magnesium oxide formed was located beyond the reaction zone. The tungsten powders prepared by reducing MgWO4 consisted of α-W. The powders prepared by reducing Ca3WO6 at a temperature below 740°C consisted of a mixture of the α- and β-phases. Raising the percentage of phosphorus in the starting tungstate led to an increase in the percentage of the β-phase. The highest β-W content of the powder was 60 wt %.

Activating RAS mutations occur in more than a half of colorectal cancers (CRCs). RAS-mutated CRCs are notoriously difficult to treat given that they are characterized by the aggressive disease course and the lack of appropriate targeted therapies. Recent preclinical studies demonstrated that RAS-mutated cells escape from therapeutic MEK inhibition by the development of autophagy, and this escape may be prevented by the administration of an antimalarial drug, hydroxychloroquine. The available clinical data are limited to a single case observation involving a patient with KRAS-mutated pancreatic cancer. Here, we report a woman with KRAS G12D-mutated CRC, whose tumor did not respond to conventional therapy. The combination of binimetinib, hydroxychloroquine, and bevacizumab was administered as a last-hope option. The patient experienced rapid improvement of the performance status. The tumor lumps demonstrated 17% reduction in the size within the first 6 weeks of the therapy. This report calls for evaluation of the efficacy of a combination of MEK inhibitors and hydroxychloroquine, possibly with the addition of bevacizumab, in chemotherapy-resistant patients with RAS-mutated cancers.

The thermoelectric properties of the NdCoO3 and SmCoO3 rare-earth cobalt oxides with a perovskite structure have been investigated in a wide temperature range. It is shown that, in the low-temperature region, the thermal conductivity of the compounds has a sharp maximum and the electrical conductivity of the samples increases with temperature, whereas the Seebeck coefficient behaves nonmonotonically with increasing temperature. The SmCoO3 oxide is characterized by the positive thermopower over the entire investigated range with a sharp growth in the low-temperature region, attaining the maximum value (S ≈ 1000 μV/K) near room temperature, and a further decrease. It has been established that, in the NdCoO3 oxide, the Seebeck coefficient changes its sign, which was rarely observed in the La-based compounds and is atypical of the undoped rare-earth cobalt oxides. The thermopower maximum obtained at a temperature of 450 K is 400 μV/K. The regions of the fastest growth of the thermoelectric power factor correspond to the anomalies caused by the spin transition of Со3+ ions and the dielectric–metal transition.

Relevance. Impairment of apoptosis regulation in P19 cells is correlated with generation of oxidative stress. Under hypoxia, changes in mitochondrial functions occur, which may exacerbate oxidative stress in the tumor cell. The aim of the study was to evaluate the effects of N-ethylmaleimide and 1,4-dithioerythritol on implementation and regulation of apoptosis in P19 cells under hypoxia in vitro.Materials and methods. P19 cells (mouse teratocarcinoma) cultured under hypoxia served as the material for the study. For redox status modulation, 5mM N-ethylmaleimide and 1,4-dithioerythritol in the final concentrations of 5 mM were used. The intracellular concentration of calcium ions, the transmembrane potential and the number of Annexin V, CD95 and CD120 positive cells were determined by flow cytometry. The levels of reduced, oxidized and protein-bound glutathione, protein SH groups, hydroxyl radical and protein carbonyl derivatives were measured by spectrophotometry.Results. The alteration in the redox status of the glutathione system under hypoxia, accompanied by oxidative modification of proteins (glutathionylation and carbonylation), influences the metabolism in the tumor cell on the whole. Under the effects of 1,4-dithioerythritol, an SH group protector, this alteration promotes formation of additional mechanisms to escape apoptosis, whereas under the effects of N-ethylmaleimide, an SH group blocker, it, on the contrary, promotes apoptosis activation.Conclusions. The changes in the redox homeostasis of the tumor cell and modulation of oxidative modification of proteins (glutathionylation and carbonylation) under hypoxia are one of the promising approaches to targeted regulation of cell death.

Introduction. Hypoxia in tumor growth contributes to mitochondrial dysfunction and exacerbates oxidative stress in the immortalized cell. The objective of the study was to investigate the molecular mechanisms of the effects of N-acetylcysteine on redox regulation of tumor cell apoptosis under hypoxia.Material and Methods. P19 cells (mouse teratocarcinoma) cultured under hypoxia served as the material for the study. The redox status was modulated with N-acetylcysteine in the final concentration of 5 mM. The level of reactive oxygen species, concentration of calcium ions, transmembrane potential and the number of CD95-, CD120- and Annexin V-positive cells were determined by flow cytometry. The concentration of glutathione system components as well as the levels of protein SH groups and protein carbonyl derivatives were measured by spectrophotometry.Results. The use of N-acetylcysteine under hypoxic conditions was accompanied by the increased total glutathione concentration and protein SH groups levels, decreased levels of Са2+ ions, proteinbound glutathione and protein carbonyl derivatives, as well as the production of reactive oxygen species and more appropriate functioning of P19 cells mitochondria. N-acetylcysteine contributed to the development of additional resistance of P19 cells to apoptosis under hypoxia.Conclusion. The alteration in the state of the glutathione system under hypoxia influences the changes in tumor cell metabolism on the whole and promotes formation of additional mechanisms to escape apoptosis.

Objective:to assess the potentials of using indocyanine green fluorescence angiography in evaluating revascularization of tissue-engineered construct that was obtained from the decellularized biological matrix of primate trachea, including using mesenchymal stem cells, after heterotopic tracheal allotransplantation.Material and methods.Tracheas were obtained from two male hamadryas baboons. After decellularization, 4 cm segments of tracheas were implanted under the lateral part of the latissimus dorsi in two healthy primates, one after recellularization with mesenchymal stem cells (animal 1), and the second without recellularization (animal 2). Immunosuppressive therapy was not performed. Blood flow in the transplanted segment of the trachea was evaluated 60 days after transplantation by surgical isolation of the flap of the latissimus dorsi with the transplanted segment of the trachea, while maintaining blood flow through the thoracodorsal artery. Indocyanine green near-infrared fluorescence angiography was visualized using a FLUM-808 multispectral fluorescence organoscope.Results.Sixty days after implantation, the tracheal cartilaginous framework macroscopically appeared to be intact in both animals, tightly integrated into the muscle tissue. The framework retained its natural color. After intravenous injection of indocyanine green, the tracheal vessels were visualized in both animals. Intercartilaginous vessels and portions of the cartilaginous semi-rings devoid of vessels were clearly distinguished. The entire implanted segment was almost uniformly vascularized. No local disruptions in blood supply were observed. The fluorescence brightness of the tracheal vessels was 193 ± 17 cu and 198 ± 10 cu in animals 1 and 2, respectively. The average muscle brightness in the implantation zone was 159 ± 9 cu and 116 ± 8 cu in animals 1 and 2, respectively.Conclusion. Indocyanine green fluorescence angiography is characterized by high-contrast images and high sensitivity. This facilitates vascular patency visualization and allows to assess the degree of neoangiogenesis after experimental transplantation of the tracheal segment, at different stages of experiment, without euthanizing the animal.

Vinylation by acetylene of lupane-type pentacyclic triterpene C-28- and C-3β-alcohols and C-20-oximes in superbase solutions synthesized the corresponding C-28- and C-3β-O-vinyl ethers and C-20-O-vinyloximes. The reaction of 3β,28-dimethoxy-29-norlupan-20-one with acetylene in superbase KOH–DMSO produced a derivative with an N-vinylpyrrole ring in the C-19 side chain.

Long-term study on the identification of Na,K-ATPase endogenous inhibitors in mammalian tissues has resulted in the discovery of ouabain, marinobufagenin (MBG), and other cardiotonic steroids (CTS) in the blood plasma. Production of ouabain and MBG is increased in essential hypertension and other diseases associated with hypervolemia. Here, we compared the effects of ouabain and MBG on the Na,K-ATPase activity (measured as the transport of Na+, K+, and Rb+ ions) and proliferation and death of human renal epithelial cells (HRECs) and human umbilical vein endothelial cells (HUVEC) expressing α1-Na,K-ATPase. Ouabain concentration that provided the half-maximal inhibition of the Rb+ influx (IC50) into HRECs and HUVECs was 0.07 μM. In both types of cells, the IC50 values for MBG were 10 times higher than for ouabain. Incubation of HREC and HUVEC with 0.001-0.01 μM ouabain for 30 h resulted in 40% increase in the [3H]thymidine incorporation into DNA; further elevation of ouabain concentration to 0.1 μM completely suppressed DNA synthesis. MBG at the concentration of 0.1 μM activated DNA synthesis by 25% in HRECs, but not in HUVECs; 1 μM MBG completely inhibited DNA synthesis in HRECs and by 50% in HUVECs. In contrast to HRECs, incubation of HUVECs in the serum-free medium induced apoptosis, which was almost completely suppressed by ouabain and MBG at the concentrations of 0.1 and 3 μM, respectively. Based on these data, we can conclude that (i) the effect of MBG at the concentrations detected in the blood plasma (

Methods were presented to synthesize tricalcium phosphate Ca3(PO4)2 (TCP), calcium pyrophosphate Ca2P2O7 (CPP), and TCP/CPP composites in nonaqueous media in the temperature range 25–300°C. It was shown that solvo- and ionothermal synthesis methods can give phosphates of complex composition. The phase composition, micromorphology, and particle size distribution of the obtained powders and their evolution during synthesis were described. The synthesis at 110°C while slowly adding ammonium hydrophosphate to a solution of calcium ethylene glycolate in ethylene glycol gives a nanocrystalline β-TCP powder with an average size of aggregates of platy crystals of 150 nm and a distribution width of 50 nm. The morphological characteristics and sinterability of the powders synthesized in solutions in ethylene glycol make them suitable for producing macroporous ceramics by stereolithography 3D printing methods.

The process of 2-ethylhexyl nitrate (a diesel additive) production in a laboratory unit with a centrifugal mass transfer apparatus is studied. The 2-ethylhexyl nitrate yield is influenced primarily by the length of coil heat exchanger channel, nitrator rotor speed, and nitromixture (HNO3 + H2SO4 + H2O) temperature. A regression equation is proposed for determining 2-ethylhexyl nitrate yield as a function of treatment parameters. The optimum process conditions for getting maximum primary product yield are determined by reduced gradient method.

—Using Raman spectroscopy (RS) approach in a spectral range of 1000–3000 cm–1 were used to study the conformational and structural changes that arise in the heme group and globin moiety of hemoglobin in human red blood cells at various temperatures and oxygen contents. In hypoxia, the hemoglobin conformation was shown to change as a result of the increasing contribution of hematoporphyrin pyrrole rings and vibrational motions of vinyl groups. Modifications were additionally detected in the contributions of symmetric and asymmetric vibrations of the CH2 and CH3 radicals of histidine (2850, 2860, and 2900 cm–1) and lysine (2880 and 2860 cm–1) residues. The mechanisms of oxygen binding are discussed for hemoglobin located in the submembrane region and cytoplasm of the cell.

The purpose of this work was to reveal the intra- and inter-individual variability of the urine proteomic composition and of biochemical blood parameters in cosmonauts with different preflight autonomic status when they are back to Earth (on the 1st and 7th day after space flight). The objects of the study were 5-min samples of electrocardiogram (ECG) at rest and urine and venous blood samples, obtained in the same timeline from twelve male cosmonauts (age 46.5 ± 3.4 years), who performed space flights (SF) with duration 169–199 days onboard the Russian segment of the International Space Station (ISS). Two groups with different sympathetic-parasympathetic balance were identified (each consists of 6 cosmonauts) by the results of preflight heart rate variability (HRV) analysis. We have revealed in groups of cosmonauts with preflight predominance of sympathetic or parasympathetic tone the significant differences in the directionality of changes on days 1 and 7 after the SF as compared to the preflight values in three proteins (from total amount around 200): alpha-1 subunit of collagen type VI, Mucin 1, Cadherin-13. A set of biochemical parameters, unidirectionally changing with these proteins, was different in classified groups. Direct bilirubin, potassium and total calcium move unidirectionally with collagen, direct bilirubin, potassium – with mucin, and uric acid, ferrum, alpha-1, KFK, potassium - with cadherin in group with a sympathetic tone. Potassium, ferrum, alpha-1 move unidirectionally with collagen, amylase, KFK, AST, urea, inorganic phosphate, glucose, alkaline phosphatase, ionized calcium – with mucin, and total ferrum biding capacity, transferrin, glucose gamma globulin transferase - with cadherin in group with parasympathetic predominance. Probably, differences between groups in the concentration of these proteins and their different relationship with some biochemical parameters reflect different ways to achieve the same goal - adaptation to a complex of SF factors and re-adaptation after returning to Earth.

A new peptidomimetic conjugate of natural methionine and pyridine-2,6-dicarboxylate was synthesized and evaluated as a potential ligand for 97Ru radiopharmaceuticals. The distribution of this radiopharmaceutical in mice was investigated. A fundamental difference was found in the distribution and excretion of ruthenium complex and free ruthenium ion in the body, which suggests a difference in their transport pathways due to the stability of the complex in the body.

This work is devoted to the influence of phosphazene modifiers with different substituents on the curing process, thermal properties and flammability of benzoxazine resin. Novel catalysts with m-toluidine substituents were introduced. The catalytic activity of studied phosphazene compounds decreased in the row: hexachlorocyclotriphosphazene (HCP) &gt, tetra m-toluidine substituted phosphazene PN-mt (4) &gt, hexa m-toluidine substituted phosphazene PN-mt (6) &gt, hexaphenoxycyclotriphosphazene (HPP), where HPP is totally inactive. Two types of catalysis: basic and acid were proposed. A brief study of resulting properties of polybenzoxazines was presented. The addition of any studied modifier caused the decrease of glass transition temperature and thermal stability of polymers. The morphology of cured compositions was characterized by matrix-dispersion phase structure. All phosphazene containing polybenzoxazines demonstrated the improved flame resistance.

The article presents an analysis of the composition of green silicon carbide by structure. Microscopic analysis showed that green silicon carbide consists of single crystals, their debris, dense compact aggregates consisting of several crystals. We recommend that you presort the lumped carbide to improve the resistance of the abrasive tool.