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A large-scale coaxial line filled with the plasma of RF discharge has been developed for laboratory modeling of the effects of the interaction of ultrashort electromagnetic pulses (EMPs) with the atmosphere and the ionosphere in the KROT facility. The oversized coaxial line ensures pulse transmission through an ionized medium in the TEM mode, which corresponds to the polarization of the transverse electromagnetic wave in free space, and in uniform isotropic plasma. The coaxial line has a length of 10 m and a diameter of 140 cm. The processes of propagation of the nanosecond and subnanosecond pulses in this line, in vacuum and with plasma, have been simulated numerically.

Detection of biologically active components in mixtures of complex composition which include biological fluids (blood, urine, etc.) is the most difficult problem of the analytical chemistry and requires the use of modern highly informative research methods. One of the most effective and universal ways to study the structure of unknown substances is the method of liquid chromatography- high resolution mass spectrometry that combines the possibility of highly selective separation of the mixtures under study, the reliable detection of unknown substances and high sensitivity of the procedure. We propose a method for the simultaneous extraction of highly polar biomarkers of nitrogen mustard — N-triethanolamine (TEA), N-ethyl diethanolamine (EDEA) and N-methyldiethanolamine (MDEA) — from urine with subsequent determination by HPLC and detection by high resolution tandem mass spectrometry. The mass spectra of fragmentation of protonated molecular ions of TEA, EDEA, and MDEA have been studied and possible structural formulas of the fragment ions are given. The sample preparation of urine and mass spectrometric detection in the multiple reaction monitoring mode were optimized. The five-fold dilution with deionized water was chosen as a method of urine sample preparation for analysis. Separation of the components was performed in the reversed-phase chromatography mode with retention times for TEA, EDEA, and MDEA of 2.00, 2.05, and 1.92 min, respectively. The time required to complete all steps of the urine sample analysis did not exceed 25 min. The detection limits in urine were 1 ng/ml for TEA and 2 ng/ml for EDEA and MDEA. The developed approach provides determination of the fact of application of specific nitrogen mustard in enquiry of possible exposure of living organism to the blister agents.

The SHiP experiment is proposed to search for very weakly interacting particles beyond the Standard Model which are produced in a 400 GeV/$c$ proton beam dump at the CERN SPS. About $10^{11}$ muons per spill will be produced in the dump. To design the experiment such that the muon-induced background is minimized, a precise knowledge of the muon spectrum is required. To validate the muon flux generated by our Pythia and GEANT4 based Monte Carlo simulation (FairShip), we have measured the muon flux emanating from a SHiP-like target at the SPS. This target, consisting of 13 interaction lengths of slabs of molybdenum and tungsten, followed by a 2.4 m iron hadron absorber was placed in the H4 400 GeV/$c$ proton beam line. To identify muons and to measure the momentum spectrum, a spectrometer instrumented with drift tubes and a muon tagger were used. During a three-week period a dataset for analysis corresponding to $(3.27\pm0.07)~\times~10^{11}$ protons on target was recorded. This amounts to approximatively 1% of a SHiP spill. The SHiP experiment will search for very weakly interacting particles beyond the Standard Model which are produced in a 400 \GeV/$c$ proton beam dump at the CERN SPS. About $10^{11}$ muons per spill will be produced in the dump. To design the experiment such that the muon-induced background is minimized, a precise knowledge of the muon spectrum is required. To validate the muon flux generated by our Pythia and GEANT4 based Monte Carlo simulation (FairShip), we have measured the muon flux emanating from a SHiP-like target at the SPS. This target, consisting of 13 interaction lengths of slabs of molybdenum and tungsten, followed by a 2.4 m iron hadron absorber was placed in the H4 400~\GeV/$c$ proton beam line. To identify muons and to measure the momentum spectrum, a spectrometer instrumented with drift tubes and a muon tagger were used. During a three-week period a dataset for analysis corresponding to $(3.27\pm0.07)~\times~10^{11}$ protons on target was recorded. This amounts to approximatively 1\% of a SHiP spill. The SHiP experiment is proposed to search for very weakly interacting particles beyond the Standard Model which are produced in a 400 GeV/c proton beam dump at the CERN SPS. About $10^{11}$ muons per spill will be produced in the dump. To design the experiment such that the muon-induced background is minimized, a precise knowledge of the muon spectrum is required. To validate the muon flux generated by our Pythia and GEANT4 based Monte Carlo simulation (FairShip), we have measured the muon flux emanating from a SHiP-like target at the SPS. This target, consisting of 13 interaction lengths of slabs of molybdenum and tungsten, followed by a 2.4 m iron hadron absorber was placed in the H4 400 GeV/c proton beam line. To identify muons and to measure the momentum spectrum, a spectrometer instrumented with drift tubes and a muon tagger were used. During a 3-week period a dataset for analysis corresponding to $(3.27\pm 0.07)~\times ~10^{11}$ protons on target was recorded. This amounts to approximatively 1% of a SHiP spill.

The spectroscopic performance of Er3+ doped glass at 0.55 mm emission contain different nanoparticles NPs have been comparatively evaluated. Glass containing 1.0 mol % of Er3+ doped with different NPs (Ag, Co and Fe ) have been prepared using melt quenching technique. X-ray diffraction analysis reveals the all the prepared samples are amorphous. The UV-Vis absorption spectra of all glasses show several prominent peaks at 525 nm, 660 nm, 801nm, 982 nm and 959 nm due to transition from ground state 4I15/2 to different excited of 2H11/2, 4F9/2, 4I9/2, 4I11/2, and 4I13/2. The emission of Er3+ at 0.55 mm for glass contain Ag NP shows significant enhancement about 3 folds up to 0.6 mol%. On the other hand, the emission of Er3+ at 0.55 mm for glass containing Fe NPs and Co NPs intensely quench probably due to the energy-transfer from Er3+ ion to NPs and magnetic contributions.

Polyurethane hydrogels containing polyethylene glycol as a linear fragment and incomplete β-cyclodextrin nitrate as a cross-linking agent were synthesized. The polyols were cross-linked with 1,6-hexamethylene diisocyanate. The hydrogel swelling ratio was studied as a function of the content of partially nitrated β-cyclodextrin in the hydrogel, molecular mass of polyethylene glycol, and degree of substitution of hydroxy groups by nitrate groups in incomplete β-cyclodextrin nitrates. As the cyclodextrin nitrate content is increased from 13 to 44 wt %, the swelling ratio relative to the dry substance weight decreases from 9.5 to 2.3. An increase in the molecular mass of polyethylene glycol from 0.4 to 20 kDa leads to an increase in the swelling ratio from 1.6 to 5.1 for weakly cross-linked polyurethane hydrogels and from 1.2 to 2.8 for the thickly cross-linked hydrogels. The ability of the synthesized compounds to absorb Methylene Blue, Methyl Orange, and phenol was studied. Polyurethane hydrogels do not absorb Methylene Blue. The absorption of Methyl Orange and phenol depends both on the content of incomplete β-cyclodextrin nitrate and on the hydrogel swelling ratio. The synthesized polyurethane hydrogels are biologically compatible.

Mucosal-associated invariant T (MAIT) cells are unconventional T cells recognizing microbial metabolites, presented by the invariant MR1 protein. Upon activation, MAIT cells rapidly secrete cytokines and exert cytotoxic functions, and may thus be highly relevant also in tumor immunity. MAIT cells accumulate in colon tumors, but in contrast to other cytotoxic T cell subsets, their presence in tumors has been associated with worse patient outcome. Here we investigated if exhaustion may contribute to reduced anti-tumor immunity by MAIT cells. Freshly isolated lymphocytes from colon tumors, unaffected tissue and blood from the same patients were analyzed by flow cytometry to detect MAIT cells with effector functions that are relevant for tumor immunity, and their expression of inhibitory receptors and other exhaustion markers. Our studies show that MAIT cells with a PD-1highTim-3+CD39+ terminally exhausted phenotype and an increased proliferation accumulate in colon tumors. The exhausted MAIT cells have reduced polyfunctionality with regard to production of important anti-tumor effector molecules, and blocking antibodies to PD-1 partly improved activation of tumor-infiltrating MAIT cells in vitro. We conclude that the tumor microenvironment leads to exhaustion not only of conventional T cells, but also MAIT cells, and that checkpoint blockade therapy may be useful also to reinvigorate tumor-infiltrating MAIT cells. Supplementary Information The online version contains supplementary material available at 10.1007/s00262-021-02939-y.

Background Airway hyperresponsiveness (AHR) is a feature of asthma in which airways are hyperreactive to stimuli causing extensive airway narrowing. Methacholine provocations assess AHR in asthma patients mainly by direct stimulation of smooth muscle cells. Using in vivo mouse models, mast cells have been implicated in AHR, but the mechanism behind has remained unknown. Methods Cpa3Cre /+ mice, which lack mast cells, were used to assess the role of mast cells in house dust mite (HDM)-induced experimental asthma. Effects of methacholine in presence or absence of ketanserin were assessed on lung function and in lung mast cells in vitro. Airway inflammation, mast cell accumulation and activation, smooth muscle proliferation, and HDM-induced bronchoconstriction were evaluated. Results Repeated intranasal HDM sensitization induced allergic airway inflammation associated with accumulation and activation of lung mast cells. Lack of mast cells, absence of activating Fc-receptors, or antagonizing serotonin (5-HT)2A receptors abolished HDM-induced trachea contractions. HDM-sensitized mice lacking mast cells had diminished lung-associated 5-HT levels, reduced AHR and methacholine-induced airway contraction, while blocking 5-HT2A receptors in wild types eliminated AHR, implying that mast cells contribute to AHR by releasing 5-HT. Primary mouse and human lung mast cells express muscarinic M3 receptors. Mouse lung mast cells store 5-HT intracellularly, and methacholine induces release of 5-HT from lung-derived mouse mast cells and Ca2+ flux in human LAD-2 mast cells. Conclusions Methacholine activates mast cells to release 5-HT, which by acting on 5-HT2A receptors enhances bronchoconstriction and AHR. Thus, M3-directed asthma treatments like tiotropium may also act by targeting mast cells.

In this work cannabidiol (CBD) was investigated as a possible drug against the cytotoxicity of Aβ(31-35) and Aβ(25-35) peptides with the help of atomistic molecular dynamics (MD) and well-tempered metadynamics simulations. Four interrelated mechanisms of possible actions of CBD are proposed from our computations. This implies that one mechanism can be a cause or/and a consequence of another. CBD is able to decrease the aggregation of peptides at certain concentrations of compounds in water. This particular action is more prominent for Aβ(25-35), since originally Aβ(31-35) did not exhibit aggregation properties in aqueous solutions. Interactions of CBD with the peptides affect secondary structures of the latter ones. Clusters of CBD are seen as possible adsorbents of Aβ(31-35) and Aβ(25-35) since peptides are tending to aggregate around them. And last but not least, CBD exhibits binding to MET35. All four mechanisms of actions can possibly inhibit the Aβ-cytotoxicity as discussed in this paper. Moreover, the amount of water also played a role in peptide clustering: with a growing concentration of peptides in water without a drug, the aggregation of both Aβ(31-35) and Aβ(25-35) increased. The number of hydrogen bonds between peptides and water was significantly higher for simulations with Aβ(25-35) at the higher concentration of peptides, while for Aβ(31-35) that difference was rather insignificant. The presence of CBD did not substantially affect the number of hydrogen bonds in the simulated systems.

This paper considers publications devoted to the development and improvement of methods for the determination of markers and biomarkers of chemical warfare agents (CWAs) using various combinations and modifications of gas and liquid chromatography–mass spectrometry. Attention is focused on the importance of choosing an optimal analysis strategy and optimizing sample preparation procedures and operating modes of analytical instruments. Published data on the selection of characteristic markers of organophosphorus CWAs and sulfur mustard gas and methods for their determination are summarized.

By measuring the hydrodynamic characteristics (viscosity, density of extraction mixture, and interfacial tension) and determining the composition of degradation products by the IR, CMS, and nuclear magnetic resonance methods, the efficiency of using solutions of methylamine and guanidine carbonates at the stage of intracycle regeneration was evaluated. It has been experimentally proven that, when using these solutions, the same efficiency is achieved as when using a sodium bicarbonate solution. The main products of radiation destruction of the 30% Tri-n-butyl-phosphate in Isopar-M extraction mixture irradiated after saturation with nitric acid are determined: dibutyl phosphoric and monobutyl phosphoric acids, carboxylic acids, ketones, carbonyl compounds, and hydrocarbons.

Introduction. Birch bark contains biologically active substances (BAS). In this regard, the search for ways to increase yield of its bioactive agents is relevant. Aim. To study the effect of birch bark grinding methods on the extract of its BAS during extraction. Materials and methods. Samples of birch bark of silver birch (Betula pendula Roth.) and downy birch (Betula pubescens Ehrh.) were ground up on devices with various force effects on plant material — disk (mainly squeezing, shear, tensile and shearing forces), three-roll annular (crushing and abrasive forces) and ball (crushing, abrasive and shock-shear forces) mills. Morphological and microscopic studies were carried out, the content of extractive substances and moisture in the ground up samples was determined. The composition and content of BAS were analyzed. Results. The smallest changes in the morphological and anatomical structure of plant material were observed when using a disk mill (the morphological features of birch bark and its cellular structure are preserved), grinding on three-roll ring and ball mills leads to serious changes in the morphological and anatomical structure of birch bark (the morphological and anatomical structure is lost, cell walls are destroyed). Comparative analysis of the yield of extractive substances from ground up birch bark samples, depending on the grinding method and the extractant used (purified water and ethyl alcohol of different concentrations: 96, 80, 70, 40, 20 and 10%) showed that the best extractant is 80% ethyl alcohol. The highest yield of extractive substances was noted for a sample of birch bark ground up in a ball mill — 36.85%, for ground up in a disc mill — 29.96%, on a three-roll ring mill — 30.88%. When studying the yield of the main groups of BAS (saponins, tannins, coumarins, hydroxycinnamic acids) from ground up birch bark samples, it was found that when using grinding methods that do not lead to the destruction of cell walls, the yield of BAS is limited by the capillary-porous structure of the plant material. Conclusion. When using grinding methods that lead to the destruction of cell walls, the greatest yield of BAS from birch bark is observed in the case of using a more severe impact on it, including not only abrasion, crushing, but also impact (ball mills).

We develop a method on the basis of high-performance liquid phase chromatography–mass spectrometry (HPLC-MS) for determination of triterpene glycosides in ginseng extracts. In contrast to procedures based on HPLC with ultraviolet detection (HPLC-UV), commonly used for extract standardization, superior selectivity afforded by the developed method enables identification and quantitation of 23 major and minor ginsenosides. For this, in addition to using MS for highly selective detection of adduct ions composed of ginsenoside molecules and sodium and fragment sapogenin ions, we identify the conditions for chromatographic separation on a sorbent with grafted pentafluorophenyl groups. The effects that the temperature and mobile phase composition have on the selectivity of glycoside determination receive special attention here. For some pairs of compounds (F4/Rg6 and Rk3/Rh4), complete separation of chromatographic peaks is not achieved; nevertheless, even if present simultaneously, they can be determined owing to their different m/z ratios. The linearity ranges, equations for calibration curves, and analytical parameters (i.e., the limit of detection and reproducibility) are established for all analytes. The developed method is tested for standardization of reference extracts of Asian (P. ginseng) and American (P. quinquefolius) ginseng roots. For some ginsenosides, the content claimed by the manufacturer is at variance with the actual values, while for others the determined concentrations proved to be close to the claimed values. Additionally, we succeed in expanding the range of determinable ginsenosides, which is important for medical application of such extracts.

We proposed a method for determining the presence of trace amounts of adducts of isopropylmethylphosphonic acid (IMPA) and cyclohexylmethylphosphonic acid (CMPA), biomarkers of exposure to sarin and cyclosarin in a body, with a tripeptide (Tyr-Thr-Lys). The method is based on plasma trypsinolysis with the formation of stable adducts IMPA–Tyr-Thr-Lys and СMPA–Tyr-Thr-Lys and their detection by high-performance liquid chromatography (HPLC) with high-resolution tandem mass spectrometry detection. The following conditions for the sample preparation of human blood plasma exposed to sarin and cyclosarin were optimized: aliquot portion volume, enzymatic hydrolysis conditions, mass spectrometric detection (selection of optimal pairs of ion reactions and detection modes), and gradient elution programs in the HPLC separation of the test mixture. The limit of detection for sarin and cyclosarin in human blood plasma was 5 ng mL–1. The proposed approach was tested in the analysis of blood plasma samples submitted to analysis in the framework of the Fourth Official Biomedical Test of the Organization for the Prohibition of Chemical Weapons; the results showed good determination specificity.

A multipurpose reagent, p-methoxyphenacyl bromide, is proposed for the derivatization of polar products of the degradation (markers) of nerve agents, which allows their determination by high-performance liquid chromatography with tandem mass spectrometric detection or by gas chromatography in combination with high-resolution mass spectrometry. The reaction conditions for the derivatization of alkylphosphonic and alkylmethylphosphonic acids with this reagent were optimized, the features and general patterns of the formation of MS1 and MS2 spectra of derivates were found, and the conditions for their chromatographic separation by two independent methods were selected. The limits of detection reached are in the range from 0.02 to 0.2 ng/mL for high-performance liquid chromatography with tandem mass spectrometric detection and from 10 to 50 ng/mL for gas chromatography with tandem mass spectrometric detection.

Eleutherococcus senticosus is a plant with medicinal properties due to the presence of glycosides, called eleutherosides А, В and В1, C, D, E, and F, in its roots and rhizomes. In this paper, a procedure for the simultaneous determination of Eleutheroside B and Eleutheroside E in dry samples of Eleutherococcus senticosus roots from different manufactures by high performance liquid chromatography/tandem mass spectrometry was proposed. The quantification of eleutheroside B and eleutheroside E was performed using electrospray ionization in the negative ion mode with detection by multiple reaction monitoring (MRM), which ensured a better signal-to-noise ratio. To isolate eleutherosides from plant materials, simple and rapid methods of sample preparation were used, including extraction in an ultrasonic bath with various solvents. The calibration curve was linear in the concentration range from 40 to 4000 ng/mL.

The expression of some structural and regulatory muscle protein genes as well as the activity of the main intracellular proteases (calpains, proteasomes) in caged rainbow trout in the periods favorable for growth and under hyperthermia were estimated. Intense growth of fish was accompanied by high transcriptional activity of the myosin heavy chain (MyHC) gene with the constraining influence of myostatin, high protein turnover rate, and stable levels of myogenic factors, MyoG and MyoD1b. Trout growth retardation in response to summer increase in water temperature was associated with a decrease in gene expression of the main protein of myofibrils, myosin. In hyperthermia, proteolytic activity of calpains and proteasomes, which determine the level of protein degradation in muscle and thereby regulate the intensity of protein accumulation and overall growth, also decreased. Thus, changes in the intensity of myofibrillar protein synthesis, myogenesis, and protein degradation in rainbow trout during periods favorable for growth and under hyperthermia occur in a coordinated manner indicating a relationship of these processes.

The hepatoprotective activity of 8,8-dimethyl-5-p-tolyl-3,4,7,8-tetrahydro-2H-pyrido[4,3,2-de]cinnolin-3-one was studied in vivo using a model of CCl4-induced acute toxic hepatitis. It was found that this compound affected indices determining the level of free-radical oxidation, i.e., levels of malondialdehyde (MDA) and diene conjugates (DC), and the activities of the key antioxidant enzymes superoxide dismutase (SOD) and catalase. Hepatoprotective activity was analyzed using the activity levels of the enzymes alanine aminotransferase (AlAT), aspartate aminotransferase (AsAT), and alkaline phosphatase and the bilirubin level. The mechanism of the antioxidant activity was determined from the effect of this compound on the expression levels of the gene katG encoding catalase-hydroperoxidase I and the gene sodA encoding Mn-superoxide dismutase. It was found that 8,8-dimethyl-5-p-tolyl-3,4,7,8-tetrahydro-2H-pyrido[4,3,2-de]-cinnolin-3-one exhibited antioxidant activity by increasing the SOD and catalase levels.

—The results of the density functional theory calculation of the segregation energy of refractory metals at grain boundaries (GBs) in the alloys based on nickel (fcc solid solutions), chromium (bcc), and titanium (hcp) are analyzed. The influence of segregation on the cohesive strength of GBs is estimated using the Rice–Wong model, in which the mechanical strength of GBs is characterized by the boundary splitting energy. Refractory metals are shown to contain “useful” elements, which enrich GBs and increase their cohesive strength in alloys of all types. The calculated data are used to design experimental high-temperature alloys (HTAs), the alloying system of which contains useful elements in the form of a package of low-alloy additives in HTAs, namely, nickel (Zr, Nb, Hf, Ta), chromium-based (Nb, Ta), and titanium (W, Ta, Re) alloys. The results of testing the mechanical properties of these experimental alloys are presented. The low-alloy additives are shown to increase the creep resistance of all alloys at elevated temperatures.

The influence of the segregation energy on the diffusion of second-component atoms in copper is studied by molecular statics and dynamics methods. A number of modified potential is considered. The segregation energy of atoms in a grain boundary is calculated. The number of second-component atoms involved in a diffusion process is found to decrease because of desorption, which leads to a decrease in the grain-boundary diffusion coefficient.

All life on Earth is built of organic molecules, so the primordial sources of reduced carbon remain a major open question in studies of the origin of life. A variant of the alkaline-hydrothermal-vent theory for life's emergence suggests that organics could have been produced by the reduction of CO2 via H2 oxidation, facilitated by geologically sustained pH gradients. The process would be an abiotic analog-and proposed evolutionary predecessor-of the Wood-Ljungdahl acetyl-CoA pathway of modern archaea and bacteria. The first energetic bottleneck of the pathway involves the endergonic reduction of CO2 with H2 to formate (HCOO-), which has proven elusive in mild abiotic settings. Here we show the reduction of CO2 with H2 at room temperature under moderate pressures (1.5 bar), driven by microfluidic pH gradients across inorganic Fe(Ni)S precipitates. Isotopic labeling with 13C confirmed formate production. Separately, deuterium (2H) labeling indicated that electron transfer to CO2 does not occur via direct hydrogenation with H2 but instead, freshly deposited Fe(Ni)S precipitates appear to facilitate electron transfer in an electrochemical-cell mechanism with two distinct half-reactions. Decreasing the pH gradient significantly, removing H2, or eliminating the precipitate yielded no detectable product. Our work demonstrates the feasibility of spatially separated yet electrically coupled geochemical reactions as drivers of otherwise endergonic processes. Beyond corroborating the ability of early-Earth alkaline hydrothermal systems to couple carbon reduction to hydrogen oxidation through biologically relevant mechanisms, these results may also be of significance for industrial and environmental applications, where other redox reactions could be facilitated using similarly mild approaches.

Water-propylene glycol extracts of medicinal plants are widely used as active components in therapeutic and cosmetic products for external use. However, sparse data on the extracting efficiency of water-propylene glycol mixtures and chemical composition of water-propylene glycol extracts of plant raw materials are available in the scientific literature. Usually the manufacturer documentation also provides information about characteristics of the products that are not related to their biological activity. The results of HPLC/MS/MS study of Matricaria chamomilla L. flowers have shown that water-propylene glycol and water-ethanol extracts are similar in the composition of phenolic compounds: the dominant compounds of water-propylene glycol extract of Matricaria chamomilla L. flowers are apigenin and its glycosides (apigenin-7-glucoside, apigenin-7-O-6-O-malonyl-D-glycoside, apigenin-7-acetylglycoside, acetyl-malonyl-apigenin-7-O-glycoside), as well as 5,4’-dioxy-3,6,7,3’-tetramethoxyflavone, cis- and trans-forms of 2-O-glucopyranoside 2-hydroxy-4-methoxycoric acid, 7-methoxycumarin. Spectral and analytical characteristics in the UV-visible range of the spectra of water-propylene glycol extracts of a number of medicinal plants most often used in the cosmetic industry were studied to reveal extracts with the highest protective properties against UV radiation in A and B areas (extracts of Salvia officinalis L. leaves, Matricaria chamomilla L. flowers, Achillea millefolium L. grass), free radicals (extracts of Camellia sinensis L. leaves, Hypericum perforatum L. herb), and the highest content of flavonoids (extracts of Hypericum perforatum L. herb, leaves of Salvia officinalis L.) were revealed. When extracting raw materials from the same batch, the optical density at a wavelength of 270 nm is associated with the content of flavonoids, antioxidants and dry matter by a functional relationship, which is very convenient for rapid control of extraction processes in order to obtain a product with reproducible characteristics. Formulas for calculating the content of antioxidants in extracts using the DPPH method in comparison with standard samples of rutin and gallic acid are derived. Interpretation of data on the antioxidant content in different extracts in comparison with other analytical parameters are also presented. Demonstrated high repeatability of the shape of the spectral curves of Matricaria chamomilla L. flowers extract, observed regardless of the source of raw materials can be used in combination with the individuality of the curve shape of the extracts of raw materials of different types as one of the authenticity criteria. The proposed UV-spectrometric method was used to study the dynamics of Matricaria chamomilla L. flower extraction under different process parameters (temperature, propylene glycol/water ratio in the extractant). It is shown that extraction of raw materials with 50% water-propylene glycol for 4 h at a temperature of 50°C is optimal.

Under laboratory conditions, the decomposition of glyphosate with the formation of aminomethylphosphonic acid (AMPA) and its effect on the total abundance of bacteria and fungi as well as the number of copies of genes encoding the enzymes C–P lyase of α-proteobacteria (phnJ), acid and alkaline phosphatase (phoC and phoD) and Fe protein of nitrogenase (nifH) in agro-sod-podzolic soil (Epialbic Retisol) were determined. It was shown that when applying glyphosate in recommended doses (5–10 mg/kg), only 5–7% of the introduced herbicide were detected after 14 days, but when the dose was increased to 100 mg/kg, this value increased up to 23%. Decreasing the rate of the herbicide degradation was observed only during the first week of incubation and was accompanied by a decrease in the number of copies of the phoC, phoD, and nifH genes and an increase in the abundance of fungi. The obtained results indicate that glyphosate was mainly degraded by means of C–P bond breaking and the formation of phosphates, and also suggest possible inhibition of the nitrogen fixation process. It is shown that at an application dose of glyphosate of 100 mg/kg may lead to the accumulation of AMPA, the first metabolite of the herbicide degradation pathway, formed after the C–N bond break. Bioassay using wheat showed that when applying glyphosate at a dose of 100 mg/kg, an inhibition of plant development was observed: the length of the roots and the biomass of the shoots reduced by 60 and 20% compared to the control, respectively. Based on the data obtained, it was proposed to use the reduction in the content of copies of the phoC gene and the increase in the number of copies of ITS rRNA as indicators of the predominant decomposition of glyphosate through the sarcosine pathway. The decrease in the number of copies of ITS rRNA gene by 40% or more can be used as an indicator of the possibility of AMPA accumulation during glyphosate degradation.

Conditions for the extraction of a phosphonylated nonapeptide, phosphonylated tyrosine, and cyclohexylmethylphosphonic acid from human blood plasma followed by HPLC determination with detection by high-resolution tandem mass spectrometry were optimized. Conditions for human blood plasma sample preparation, mass-spectrometric detection in selected reaction monitoring mode, and gradient elution were chosen to determine the above markers of exposure to cyclohexylmethylfluorophosphonate. The detection limit of the initial substance introduced into blood plasma was 0.05–0.1 ng/mL depending on the test marker.

Irradiation with accelerated electrons of an extraction mixture of 30% TBP in Isopar-M isoparaffin diluent on the lower temperature limit of flame propagation (Тl) has been studied. It was found that, under irradiation up to a dose of 2 MGy, the value of Тl of the extraction mixture may decrease to 45°С, which should be taken into account when organizing the technological process. It was shown that, when an irradiated extraction mixture is bubbled with air, the value of Тl nearly reaches the Тl of the starting solution.

Different NMR methodologies have been considered in studying water as a part of the structure of heterogeneous biosystems. The current work mostly describes NMR techniques to investigate slow translational dynamics of molecules affecting anisotropic properties of polymers and biomaterials. With these approaches, information about organized structures and their stability could be obtained in conditions when external factors affect biomolecules. Such changes might include rearrangement of macromolecular conformations at fabrication of nano-scaffolds for tissue engineering applications. The changes in water-fiber interactions could be mirrored by the magnetic resonance methods in various relaxations, double-quantum filtered (DQF), 1D and 2D translational diffusion experiments. These findings effectively demonstrate the current state of NMR studies in applying these experiments to the various systems with the anisotropic properties. For fibrous materials, it is shown how NMR correlation experiments with two gradients (orthogonal or collinear) encode diffusion coefficients in anisotropic materials and how to estimate the permeability of cell walls. It is considered how the DQF NMR technique discovers anisotropic water in natural polymers with various cross-links. The findings clarify hydration sites, dynamic properties, and binding of macromolecules discovering the role of specific states in improving scaffold characteristics in tissue engineering processes. Showing the results in developing these NMR tools, this review focuses on the ways of extracting information about biophysical properties of biomaterials from the NMR data obtained.

Application of monoammonium phosphate has been demonstrated to re-immobilize glyphosate sorbed by soil under model laboratory experiment conditions. This effect was most pronounced in the gray forest soil (Haplic Phaeozem), where the concentration of herbicide in the presence of fertilizer was 3.6 times higher than in its absence. For soddy-podzolic soil (Albic Retisol) and leached Chernozem (Luvic Chernozem), this ratio was 1.5 and 2.8, respectively. Thus, the introduction of monoammonium phosphate into soils contaminated with glyphosate may result in an increase of the risk of herbicide migration into the neighboring environments. The estimated number of functional genes of bacteria responsible for glyphosate degradation by means of the C–P bond cleavage did not show statistically significant effect of the fertilizer on the number of copies of the phnJ gene, encoding the C–P lyase of α- and γ-proteobacteria. The release of glyphosate was not accompanied by any adverse effects on the length and biomass of wheat plants.

First triplets of mRNA coding region affect the yield of translation. We have applied the flowseq method to analyze >30 000 variants of the codons 2–11 of the fluorescent protein reporter to identify factors affecting the protein synthesis. While the negative influence of mRNA secondary structure on translation has been confirmed, a positive role of rare codons at the beginning of a coding sequence for gene expression has not been observed. The identity of triplets proximal to the start codon contributes more to the protein yield then more distant ones. Additional in-frame start codons enhance translation, while Shine–Dalgarno-like motifs downstream the initiation codon are inhibitory. The metabolic cost of amino acids affects the yield of protein in the poor medium. The most efficient translation was observed for variants with features resembling those of native Escherichia coli genes.

Electron probe microanalysis (EPMA) was used to obtain concentration curves and calculate bulk diffusion coefficients in solid solutions of the copper-tin system in the tin concentration range of less than 13.9 wt.% (7.96 at.%) and temperature range of 500 to 650 ° С . Diffusion couples were made of pure copper (99,995 %) and two-component alloy obtained by direct alloying of metallic copper with chemically pure tin in Ar—H atmosphere at 1100 °C in the quartz reactor during 2 hours. Diffusion coefficients were calculated using the Matano-Boltzmann method and the method proposed by Grube, i.e. in the tin concentration range from 6 to 8 at.% ( D 1 ) on the top of the concentration curve, and from 2 at.% to zero ( D 2 ) on the bottom of the concentration curve. It is shown that tin diffusion coefficients in the concentrated solution were several times greater than in the diluted one. It is shown that diffusion activation energy values virtually coincide with isotope measurement data on tin diffusion in pure copper (187 kJ/mol). A qualitative interpretation is proposed for the tin diffusion acceleration effect in the concentrated solid solution of the copper-tin system.

The presence of activated T cells in colorectal cancer tissues is a strong predictor of patient survival. Our previous studies have shown that regulatory T cells (Treg) are able to reduce T cell transendothelial migration in vitro and accumulation of effector T cells in intestinal tumors in vivo in the murine APCMin/+ model for microsatellite stable intestinal tumors. In this study, we investigated the effect of Treg depletion on the density and effector functions of different TCRαβ+ and TCRγδ+ T cell populations in intestinal tumors. We used the APCMin/+\DEREG mouse model, which harbor a diphtheria toxin receptor under the control of the FOXP3 promoter, to deplete Treg in tumor bearing mice. We found that the density of conventional TCRαβ+CD8αβ+ T cells was significantly increased in Treg-depleted tumors in comparison with Treg-proficient tumors. Furthermore, TCRαβ+CD8αβ+ T cells showed increased proliferation and activation as well as increased Granzyme B and IFN-γ production in Treg-depleted tumors. In sharp contrast, the densities and effector functions of TCRαβ+CD8αα+ T cells and TCRγδ+ T cells remained unchanged by Treg depletion. We also documented a distinct population of IL-17A+TNF+ TCRγδ+CD8− T cells in tumors, which were not affected by Treg depletion. We conclude that Treg depletion affects only conventional TCRαβ+CD8αβ+ T cells in intestinal tumors, while unconventional T cells and T cells in unaffected tissue are not altered. Immunotherapies aimed at depleting Treg from tumors may thus be a viable option for reinvigoration of conventional cytotoxic T cells with a Th1 cytokine profile.

Summary. The disbalanced feeding and the uneven distribution of micro- and macroelements in the environment leads to a trace element, in particular hypomelanosis. To accelerate the growth and preservation of young farm animals include in the diet of various biological additives and drugs, which include selenium. For stimulation of weight gain in the livestock industry, as well as for the prevention and treatment of pathological processes in addition to micro - and macrouse amino acids, primarily methionine. The aim of this work was to study the influence of composition of DAFS-25+Polizon on morpho-biochemical parameters of blood and functional state of the liver in fattening bulls of black-motley breed in the conditions of the Republic of Bashkortostan. Experiments using were conducted on bull-calves of black-motley breed of the properties in the properties age from 6 to 15 months. The first experimental group during the experiment was additionally given the composition of DAFS-25+Polizon at a dose of 2 mg/kg, the animals of the control group received a standard diet. To assess the impact of the composition DAFS-25+Polizon on metabolism cattle studied morphological and biochemical indicators of blood and conducted histological examination of the liver. It is established that the use of the composition of DAFS-25+Polizon at a dose of 2 mg/kg increases the number of erythrocytes and hemoglobin in the experimental group and reduces the amount of white blood cells. The serum content of total protein, phosphorus and calcium increases in the group of experimental animals. Microscopic examination of the liver revealed no changes in the structure of the organ and hepatocytes in the experimental group, whereas in the control group hemodynamic disorders and dystrophic changes in liver cells were observed. Thus, the use of the composition DAFS-25+Polizon at a dose of 2 mg/kg of live weight in fattening bulls black-and-white breed contributes to the increase of redox processes in the body, stimulation of metabolism, prevent the development of liver disorders of cellular mechanisms of metabolism, optimizes the structure of the liver, which generally provides higher productivity.

Possible physical mechanism of enhanced low dose rate sensitivity (ELDRS) and reduced low dose rate sensitivity (RLDRS) in bipolar devices is described. Modification of the low dose rate conversion model is presented. The enhanced or reduced sensitivity can be connected with a specific position of the effective Fermi level relatively acceptor and donor radiation-induced interface traps. The qualitative and quantitative analysis of the low dose rate effects is presented. The effect of the oxide trapped charge on the value of the oxide electric field and the yield of the oxide charge were taken into account. It leads to dependence of the accumulation of radiation induced oxide charge and interface traps on the dose rate. In enhancement version the ELDRS and RLDRS conversion model describes the low dose rate effect in as ?true? dose rate effect.

The influence of the segregation energy on the diffusion of second-component atoms in copper is studied by molecular statics and dynamics methods. A number of modified potential is considered. The segregation energy of atoms in a grain boundary is calculated. The number of second-component atoms involved in a diffusion process is found to decrease because of desorption, which leads to a decrease in the grainboundary diffusion coefficient.

The GaN planar hexagonal microcavities are grown by the selective vapor-phase epitaxy technique. The spectra are measured by the low-temperature cathodoluminescence method using a scanning electron microscope. The obtained spectra show a huge Rabi splitting (~100 meV). Numerical simulation of the spatial distribution of the intensities of modes in a hexagonal cavity is carried out. Certain modes can have a high spatial localization leading to strong coupling with the exciton and huge Rabi splitting. The fraction of excitons in polariton modes, which correlates with the intensity of exciton radiation associated with these modes, is theoretically calculated for hexagonal-shaped microcavities. Thus, the form of the dependence of the radiation probability on the eigenfrequencies of the structure is obtained.

Short-chain fatty acids (SCFAs) are a group of fatty acids predominantly produced during the fermentation of dietary fibers by the gut anaerobic microbiota. SCFAs affect many host processes in health and disease. SCFAs play an important role in the 'gut-brain axis', regulating central nervous system processes, for example, cell-cell interaction, neurotransmitter synthesis and release, microglia activation, mitochondrial function, and gene expression. SCFAs also promote the growth of neurospheres from human neural stem cells and the differentiation of embryonic stem cells into neural cells. It is plausible that maternally derived SCFAs may pass the placenta and expose the fetus at key developmental periods. However, it is unclear how SCFA exposure at physiological levels influence the early-stage neural cells. In this study, we explored the effect of SCFAs on the growth rate of human neural progenitor cells (hNPCs), generated from human embryonic stem cell line (HS980), with IncuCyte live-cell analysis system and immunofluorescence. We found that physiologically relevant levels (µM) of SCFAs (acetate, propionate, butyrate) increased the growth rate of hNPCs significantly and induced more cells to undergo mitosis, while high levels (mM) of SCFAs had toxic effects on hNPCs. Moreover, no effect on apoptosis was observed in physiological-dose SCFA treatments. In support, data from q-RT PCR showed that SCFA treatments influenced the expression of the neurogenesis, proliferation, and apoptosis-related genes ATR, BCL2, BID, CASP8, CDK2, E2F1, FAS, NDN, and VEGFA. To conclude, our results propose that SCFAs regulates early neural system development. This might be relevant for a putative 'maternal gut-fetal brain-axis'. Cover Image for this issue: doi: 10.1111/jnc.14761.

One of central problems of the technical and forensic examination of documents is the determination of the time and sequence of ink depositions by such conventional writing instruments as ballpoint pens. To solve it, it is necessary to obtain information on the composition of the ballpoint pen ink used for recordings, on what qualitative and quantitative changes the ink components underwent in the time after application and under the action of environmental or external sources, such as photo, thermal, UV, IR, or microwave exposure. The purpose of this work was to develop an approach that enables the identification of changes in the composition of inks that occur in the strokes over time and to determine the time dependences ensuring the evaluation of the time of application. The possibilities of liquid chromatography–mass spectrometry in revealing changes in the composition of inks of BIC Original, Corvina 51, and Pilot ballpoint pens were estimated. The dye degradation processes under the effect of UV radiation on strokes was simulated, and the kinetic parameters describing the degree of dye conversion were determined.

Hypoxia is a key characteristic of the tumor microenvironment, too rarely considered during drug development due to the lack of a user-friendly method to culture naturally hypoxic 3D tumor models. In this study, we used soft lithography to engineer a microfluidic platform allowing the culture of up to 240 naturally hypoxic tumor spheroids within an 80 mm by 82.5 mm chip. These jumbo spheroids on a chip are the largest to date (&gt, 750 µm), and express gold-standard hypoxic protein CAIX at their core only, a feature absent from smaller spheroids of the same cell lines. Using histopathology, we investigated response to combined radiotherapy (RT) and hypoxic prodrug Tirapazamine (TPZ) on our jumbo spheroids produced using two sarcoma cell lines (STS117 and SK-LMS-1). Our results demonstrate that TPZ preferentially targets the hypoxic core (STS117: p = 0.0009, SK-LMS-1: p = 0.0038), but the spheroids’ hypoxic core harbored as much DNA damage 24 h after irradiation as normoxic spheroid cells. These results validate our microfluidic device and jumbo spheroids as potent fundamental and pre-clinical tools for the study of hypoxia and its effects on treatment response.