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The influence of combined treatment with the additional including of systemic enzyme therapy on the clinical manifestations of postinfarction syndrome, cardiohemodynamic parameters and free radical lipid peroxidation indexes has been studied in 42 patients with myocardial infarction and type 2 diabetes mellitus or without it. It was found that additional systemic enzyme therapy enables to achieve positive clinical, hemodynamic and persistent antioxidant effect in patients with postinfarction syndrome and type 2 diabetes mellitus.

Non-catalytic partial oxidation of methane in matrix reformers offers the possibility of producing hydrogen directly at sites of its consumption, in particular from local bioresources and non-traditional fossil hydrocarbons. The kinetics simulation of the process shows that it proceeds in two stages. In the flame zone, in the presence of oxygen, along with CO, H2, CO2 and H2O, methane pyrolysis products are formed. Then, in the post-flame zone, in the absence of oxygen, at 1400–1600 K the slow pyrolysis and steam conversion of the products occur. Kinetic analysis shows that the pyrolysis of methane into acetylene and the subsequent steam reforming of the latter proceeds much faster than the direct interaction of methane with H2O, which leads to decreasing methane and acetylene concertation and increasing H2 and CO concentration. It is necessary to optimize conditions in the prost-flame zone to increase hydrogen yield and decrease acetylene yield.

Abstract A detailed kinetic modeling of the noncatalytic processes of thermal pyrolysis and steam and carbon dioxide reforming of methane revealed almost completely identical kinetics of the methane conversion in these processes. This suggests that, in the temperature range 1400–1800 K, the initial stage of conversion of methane in all these processes is its thermal pyrolysis. The modeling results agree well with the experimental data on methane pyrolysis. For the temperature range examined, the Arrhenius expressions (pre-exponential factors and activation energy) were obtained in the first-order kinetics approximation for the rate of methane conversion in the processes studied. The expressions derived may be useful for making preliminary estimates and carrying out engineering calculations.

Recent studies suggest that brain cell type specific intracellular environments may play important roles in the generation of structurally different protein aggregates that define neurodegenerative diseases. Using human induced pluripotent stem cells (hiPSC) and biochemical and vibrational spectroscopy techniques, we studied whether Parkinson’s disease (PD) patient genomes could modulate alpha-synuclein (aSYN) protein aggregates formation. We found increased β-sheets and aggregated aSYN in PD patient hiPSC-derived midbrain cells, compared to controls. Importantly, we discovered that aSYN protein aggregation is modulated by patient brain cells’ intracellular milieus at the primary nucleation phase. Additionally, we found changes in the formation of aSYN fibrils when employing cellular extracts from familial PD compared to idiopathic PD, in a Thioflavin T-based fluorescence assay. The data suggest that changes in cellular milieu induced by patient genomes trigger structural changes of aSYN potentially leading to the formation of strains having different structures, properties and seeding propensities.

The effect of technological conditions of the process and zirconia (ZrO(2)) nanoparticles on the properties of fine-fibrous filter materials (FMs) obtained by matrix polymer extraction from a microfibrillar composite formed using the material extrusion-based additive manufacturing method from a polypropylene (PP)/copolyamide blend is studied. Different processing schemes were used for obtaining filaments for material extrusion: scheme I—the use of a single-screw extruder at the stage of compounding; scheme II—the use of a single-screw extruder at the stage of compounding and orientational stretching in the course of strand formation; scheme III—the use of a twin-screw extruder at the stage of compounding, scheme IV—the addition of ZrO(2) nanoparticles and use of a twin-screw extruder. It has been shown the possibility of reducing the diameters of the formed in situ PP microfibrils by using the twin-screw extruder, as well as additional orientation drawing. The introduction into the melt of ZrO(2) nanoparticles provides further improvement of the microstructure—the average diameter of the microfibrils is reduced by 1.4 times compared with the initial blend. Developed FMs are characterized by high efficiency of air purification from solid particles with a size of 0.3 μm. At the same time, the use of nanoadditives is the most effective—a two-layer FM with nanoparticles provides cleaning efficiency at the level of four- to six-layer materials without filler.

The paper considers the growing importance of gas chemistry for the world economy and the related necessity of developing new, particularly noncatalytic technologies for the conversion of natural gas and other hydrocarbon gases into chemical products. The available and promising noncatalytic processes of their conversion into syngas as well as the direct methods for the synthesis of chemical products from methane, which is the main component of natural gas, are discussed.

Белые ночи - 2021 Сателлитные симпозиумы в рамках XXVII Международного офтальмологического конгресса Грибковые поражения глаз Всероссийская научно-практическая конференция Грибковые поражения глаз Всероссийская научно-практическая конференция Sochi Cornea 2021 Всероссийская научно-практическая конференция с международным участием Конференция Sochi Cornea 2021 Всероссийская научно-практическая конференция с международным участием Пироговская офтальмологическая академия Пироговская офтальмологическая академия Актуальные вопросы офтальмологии. Круглый стол компании «Бауш Хелс» Актуальные вопросы офтальмологии. Круглый стол компании «Бауш Хелс» Лечение глаукомы: инновационный вектор. II Всероссийская научно-практическая конференция с международным участием Конференция Лечение глаукомы: инновационный вектор. II Всероссийская научно-практическая конференция с международным участием Роговица V Новые достижения и перспективы Конференция Роговица V Новые достижения и перспективы Научно-образовательные вебинары Научно-образовательные вебинары Сателлитные симпозиумы в рамках РООФ-2020 Сателлитные симпозиумы в рамках РООФ-2020 Расширенное заседание Экспертного Совета по проблемам глаукомы и группы «Научный авангард» Конгресс Расширенное заседание Экспертного Совета по проблемам глаукомы и группы «Научный авангард» Сателлитные симпозиумы в рамках XII Съезда Общества офтальмологов России Сателлитные симпозиумы в рамках XII Съезда Общества офтальмологов России Все видео... Red eye СИНДРОМ КРАСНОГО ГЛАЗА Источник Современные технологии в офтальмологии №3 2021 Раздел 1. Эндовитреальная хирургия Реферат RUS Реферат ENG Литература Полный текст УДК: DOI: https://doi.org/10.25276/2312-4911-2021-3-61-67 N.V. Ivanova, A.V. Savchenko, O.A. Litvinenko Surgical treatment of silicone glaucoma after successful rhegmatogenous retinal detachment surgery Медицинская академия имени С. И. Георгиевского Федерального государственного автономного образовательного учреждения высшего образования «Крымский федеральный университет имени В. И. Вернадского» "Компания "Этель" Abstract Surgical treatment of silicone glaucoma after successful rhegmatogenous retinal detachment surgery N.V. Ivanova, A.V. Savchenko, O.A. Litvinenko V.I. Vernadsky Crimean Federal University, Simferopol Etel Co ltd, Simferopol

The paper reports the results of a kinetic modeling and thermodynamic analysis of non-catalytic steam reforming (NCSR) of methane and C2–C4 hydrocarbons at 1400–1800 K. The hydrocarbon-to-syngas conversion sequence and the time periods of the major process steps were identified. The initial step consists of hydrocarbon pyrolysis to acetylene and H2 with essentially no involvement of H2O. Noticeable H2O conversion starts at a significantly later point than thermal hydrocarbon conversion, under the effects of radicals formed from the pyrolysis. The H2O conversion results in the generation of OH● radicals, which subsequently react with acetylene to form CO and H2. The key step in the NCSR of C1–C4 hydrocarbons, as well as in their high-temperature interaction with CO2 (carbon-dioxide conversion) is conversion of the acetylene formed from the hydrocarbon pyrolysis. The study findings are important for the optimization of high-temperature syngas production via partial oxidation of hydrocarbons.

Adsorption of Cu(II), Co(II), Cd(II), Ni(II), Pb(II), Zn(II) and Fe(III) ions from aqueous solutions of their salts on the surface of pine sawdust in situ immobilized by polyaniline has been studied under static mode at various pH values. The adsorption of all the ions has been found to increase as the pH value grows. The sawdust in situ immobilized by polyaniline has been shown to adsorb as much as 56 mg/g of Fe(III) ions from slightly alkaline solutions (pH 8) within just the first several minutes of the experiment which could be used for the purification of industrial waste solutions from these ions. Such composites based on the sawdust in situ modified by polyaniline could also be potential adsorbents for purification of national water resourced contaminated by Pb(II) and Cd(II) in slightly alkaline solutions (pH 8) to reach their limit concentrations.

To ensure required complex of steel strength properties, pipes heat treatment is widely used as a quenching for martensite followed by tempering. It is accepted, that metal microstructure formed at that, has a little effect on a steel corrosion resistance in carbon dioxide mediums. Studies were accomplished of steel microstructure effect of the carbon dioxide corrosion speed. In particular, a low-alloyed structural steel, used for production of oil field pipes was selected. As the object of the study, seamless pumpcompressor pipes (PCP), made of medium-carbon steels of several grades with chrome content about 1% (mass.), subjected to two methods of heat treatment: quenching with tempering or normalization with tempering. Corrosion resistance of the steels were accomplished under laboratory conditions of JSC “RusNITI” by application of autoclave facility imitating operation conditions parameters of a working medium at oil extraction. The speed of general metal corrosion was measured as samples mass loss during tests (from 360 to 70 hours) by gravimetric method. By the results of laboratory tests the steel 35ХГФА was recommended to the industrial production of PCP of K72 and N80 strength groups due to GOST 31446 with normalization and tempering. It was established that pipes of steel 35ХГФА with ferrite-pearlite microstructure have higher corrosion resistance in mineralized water mediums at carbon dioxide partial pressure up to 0.20 atm, comparing with regular pipes, manufactured with quenching and tempering. A complex of field tests of PCP was carried out, the pipes made of experimental steel 35ХГФА at an oil deposit. The result of operation of CPC of 88.9×6.45 mm made of steel 35ХГФА having K72 group of strength (after normalization with tempering) during 550 days under conditions of high-mineralized water phase at СО2 partial pressure up to 0.27 atm was found positive. After an intermediate inspection (550 days) the column of PCP was assembled and is in operation at present, the current running time exceeding 1000 days. Based on the results of the complex comparative tests carried out in the corrosion laboratory and under field oil extraction conditions it was established that usage of experimental steel 35ХГФА containing 1% of Cr, after application of normalization technology with tempering resulted in increasing of operating reliability of CPC.

This article examines the development of water-swellable rubbers for oil and gas production packer equipment. The object of the investigation is to document the effect of rubber's acrylonitrile content on the swelling of the elastomers modified with sodium-carboxymethyl cellulose and a copolymer of acrylamide and potassium acrylate. After testing the samples at room temperature, the most influential factor in a material's swelling was discovered to be the mineral content in the liquids imitating well fluids. NBR polarity stemming from the inherent acrylonitrile (CN-group) level was not explicitly detected to affect the swelling rate and maximum ratio under the described conditions of the experiment. It was determined that in sodium chloride aqueous solutions with concentrations from 3 to 22%, swelling of nitrile rubber mostly depends on its cross-linking degree.

By mean of heterophase polymerization on the silica gel surface has been made in situ immobilization of poly [8-methacroyloxy-quinoline], has been received new organic-mineral composite material. I...

Various options for designing the direct oxidation of natural gas to methanol are considered: flow-through, with a distributed supply of the oxidizer along the length of the reactor, and circulation. For each of the considered options for designing the process, the methanol yield was calculated, as well as the parameters at which the resulting blow-off gas can be used as a fuel. The optimal recycling rate in the circulation process has been determined.

Telomere length can be measured by polymerase chain reaction (PCR), allowing to obtain the absolute length of telomeres (ALT) in base pair, and by flow cytometry, which can only estimate the relative telomere length. The aim of the study was to compare the results of the two methods and to develop an accurate and reliable way of converting the relative telomere length to absolute. The peripheral blood from 21 donors was analyzed. Measurement of leukocyte telomere length by flow cytometry was carried out using a commercial Telomere PNA Kit / FITC (Dako, Denmark) with two CytoFLEX flow cytometers (Beckman Coulter, China) and BD FACSCanto II (Becton Dickinson, USA), obtaining the molecular equivalent of fluorescence (MEF). To measure telomere length by real-time PCR, calibrators with a known number of telomeric repeats were prepared. Two quantitative PCRs were carried out: one for telomeric repeats, the other for determining the number of genome-equivalents of DNA, three times for each sample, which made it possible to calculate ALT. A strong direct relationship was found between the MEF obtained with BD FACSCanto II and CytoFLEX (r = 0.97). Analysis of PCR and flow cytometry results showed a significant correlation between ALT and MEF. We calculated the regression equations of ALT and MEF for CytoFLEX - y = 0.0043x (r = 0.84) and for BD FACSCanto II - y = 0.0051x (r = 0.82). Correlation analysis showed a high comparability of telomere lengths measured by two methods. The obtained regression equations allow converting the results of flow cytometry into absolute values, allowing the comparison of the results of different research groups and the use of this method in clinical trials.

Aim. To study the relationship between the levels of synthesis of reactive oxygen species (ROS) by platelets and neutrophils in patients with coronary heart disease (CHD) before and after coronary artery bypass grafting (CABG), depending on sensitivity to acetylsalicylic acid (ASA).Material and methods. The study included 95 patients with coronary artery disease who are indicated for CABG surgery. The control group consisted of 30 healthy donors. The antiplatelet therapy was stopped for at least 5 days before CABG. In the postoperative period, from the first day, all patients were received 100 mg of an enteric form of acetylsalicylic acid (ASA). Resistance to ASA was determined at the level of platelet aggregation with arachidonic acid ≥20% by optical agregometry at least at one observation point: before CABG, on 1-3 day and on 8-10 day after surgery. We evaluated the spontaneous and induced lucigenin-dependent chemiluminescence (CL) of platelets (ADP induction) and neutrophils (zymosan induction) by the exit time to maximum intensity (Tmax), maximum intensity (Imax) and area (S) under the CL curve.Results. 70.5% sensitive (sASA) and 29.5% resistant (rASA) to ASA patients were revealed. Prior to CABG, in sASA patients, the Imax of spontaneous and zymosan-induced neutrophil CL and CL platelet activity was increased relative to control values. Tmax of spontaneous platelet CL, Imax and S under the ADP-induced platelet CL curve were lower in sASA patients, if to compare with rASA patients. On the 1st and 8-10th day after CABG in sASA patients, the CL indicators of neutrophil and platelet activity also remained elevated compared to control values. On the 1st day after CABG decreased levels of S under the spontaneous CL curve of neutrophils in rASA patients was established compared with sASA patients, and increased levels of Imax and S under the curve of induced neutrophil CL were detected in comparison with the control range. In rASA patients, the values of Tmax of spontaneous platelet CL decreased in relation to the values detected in the control group and sASA patients. On the 8–10th day after CABG, most indicators of spontaneous and zymosan-induced CL neutrophils in rASA patients were also increased compared to control values. In rASA patients a positive correlation of Imax-induced CL was found (r=0.83) on the 1st day after CABG and negative correlations of Tmax of spontaneous CL (r=- 0.75) and S under the curve induced CL (r=-0.70) on the 8-10th day were detected between platelets and neutrophils.Conclusion. In sASA patients with coronary heart disease before and after CABG, a high level of synthesis of superoxide radical by neutrophils and platelets was detected. The relationship between the levels of the synthesis of superoxide radical by neutrophils and platelets was found only after CABG in rASA patients. Increased synthesis of superoxide radical due to metabolic and regulatory relationships in neutrophils and platelets stimulates pro-inflammatory processes in coronary artery disease and determines the sensitivity of platelets to ASA.

The article presents the results of studying the chemical composition of ore-bearing rocks, as well as the mineralogy of base metal sulfides and platinum group elements (PGE), of the Nyud-II sulfide PGE–Cu–Ni deposit in the southwestern part of the Nyud massif of the Monchegorsk Pluton (Monchepluton). The ores of the deposit are represented by vein-disseminated and nest-schlieren types. They are characterized by significant predominance of Pd over Pt, fractionation of low-melting PGE (PPGE subgroup) with respect to high-melting ones (IPGE subgroup), and close correlations of Ni and Cu with S in the presence of increased As, Se, Te, and Bi contents. The S/Se ratios in ore (3470−3530) correspond to the mantle values. Among the platinum group minerals (PGM), the most widespread are Pt and Pd bismuth–tellurides and tellurides (merenskyite, michenerite, and moncheite), subordinate amounts of Pt–Fe alloys and sperrylite, and native osmium and Ir, Rh, and Pt sulfoarsenides (irarsite, hollingworthite, and platarsite). The formation of ore sulfide concentrations resulted from separation of an immiscible sulfide liquid upon cooling of a sulfur-saturated silicate magma with a mafic composition. Subsequent fractional crystallization of the sulfide liquid contributed to the uneven distribution of Ni, Cu, and PGE. PGE–sulfide ore formation took place in a fairly wide temperature range, starting at 1100−1000°C and ending at 600−400°C. At an early stage, IPGE minerals (native osmium and erlichmanite) separated. Upon cooling to a temperature of 1000−900°C, the sulfide liquid fractionated with the formation of monosulfide solid solution (mss), in which compatible IPGE were concentrated, and a residual sulfide liquid enriched in Ni, Cu, PtPGE, and chalcophile elements. With a further decrease in temperature (to 600°C), Pt–Fe alloys, sperrylite, and IPGE + Pt sulfoarsenides crystallized, with separation of the residual sulfide melt enriched in Cu, PPGE and chalcophile elements. At 600−400°C, ore formation ended with the complete crystallization of base metal sulfides and the formation of Pt and Pd bismuth–tellurides and tellurides.

The ion mobility and conduction in the (NH4)6LiHf2Zr2F23 compound are studied by 1H, 19F NMR and impedance spectroscopy methods. The types of ion motion in fluoride and ammonium sublattices are determined in the temperature interval from 150 to 450 K. As a result of the order‑disorder phase transition at the temperature above 400 K, the metastable high-temperature β-modification of this compound with ionic diffusion in both sublattices is formed. The conductivity in this compound at 450 K is found to be 4.5 × 10–3 S/cm.

The long-standing perception of Protein Kinase C (PKC) as a family of oncoproteins has increasingly been challenged by evidence that some PKC isoforms may act as tumor suppressors. To explore the hypothesis that activation, rather than inhibition, of these isoforms is critical for anticancer activity, we isolated and characterized a family of 16 novel phorboids closely-related to tigilanol tiglate (EBC-46), a PKC-activating epoxytigliane showing promising clinical safety and efficacy for intratumoral treatment of cancers. While alkyl branching features of the C12-ester influenced potency, the 6,7-epoxide structural motif and position was critical to PKC activation in vitro. A subset of the 6,7-epoxytiglianes were efficacious against established tumors in mice; which generally correlated with in vitro activation of PKC. Importantly, epoxytiglianes without evidence of PKC activation showed limited antitumor efficacy. Taken together, these findings provide a strong rationale to reassess the role of PKC isoforms in cancer, and suggest in some situations their activation can be a promising strategy for anticancer drug discovery.

Cultivation of Azotobacter vinelandii D-08 in media with molasses and distillery waste was shown to increase levansaccharase activity and levan biosynthesis. Levansaccharase also exhibited maximal activity when grown in a molasses medium, which correlated with the highest level of the polysaccharide synthesis. An additional fraction of high molecular weight levan (more than 1000 kDa) with a modified molecular structure (reduced contribution of double bond oscillations and decreased molecule hydration) was synthesized by bacteria, which resulted in a higher capacity for the binding of Na, Mg, S, Ca, and Fe in the cultivation medium. Cryogels based on polyvinyl alcohol and levan were capable of efficient maximal absorption of different ions at different times: copper (1 h), zinc (24 h), and cadmium (10 min), radioactive plutonium (4 h), and uranium (168 h). This suggests that they can be used as sorbents for wastewater treatment to eliminate heavy metals and radionuclides.

It is possible to increase crop yields and product quality through the use of electrophysical methods of pre-sowing seed treatment, among which pre-sowing seed treatment in a magnetic field is promising. For successful introduction of magnetic seed treatment in production it is necessary to establish mode parameters of treatment and their optimum values. To do this, it is necessary to establish the effect of the magnetic field on the change in activation energy during pre-sowing seed treatment. The aim of the study was to determine the change in activation energy during pre-sowing treatment of crop seeds in a magnetic field. To determine the change in the activation energy, the change in the biopotential of the seed during its treatment in a magnetic field was experimentally investigated by the experimental planning method. It was found that the change in seed biopotential depends on the square of the magnetic induction and the velocity of the seed in a magnetic field. An analytical expression was obtained that relates the change in activation energy to the change in seed biopotential, which made it possible to establish the dependence of the change in activation energy on the treatment parameters. It was found that the greatest seed biopotential and activation energy change at a magnetic induction of 0.065 T, a magnetic field gradient of 0.57 T/m and a velocity of 0.4 m/s. Under this mode of pre-sowing seed treatment of agricultural crops, the activation energy changes by 3.1 - 5.7 kJ/g-eq.

Antipsychotics are a first-line treatment for psychotic disorders. The cytochrome P450 isoenzymes CYP3A4/5 and CYP2D6 metabolize most antipsychotics. The activity of these isoenzymes in children changes with maturation, so it is different from that in adults. Objective: to study the associations of CYP3A and CYP2D6 isoenzyme activity parameters with the efficacy and safety of antipsychotics in adolescents with an acute psychotic episode. Patients and methods. The investigation enrolled 53 adolescents with an acute psychotic episode who took antipsychotics. The observation period lasted 14 days. The CGAS, PANSS, UKU SERS, SAS, and BARS scales were used to evaluate the efficiency and safety of the therapy on day 14. The activity of CYP3A and CYP2D6 isoenzymes was measured by determining the metabolic ratios of the concentrations of endogenous substrates of the isoenzymes and their metabolites in a morning urine sample on days 1 and 14 of the study. The activity of CYP3A was assessed by the 6-beta hydroxycortisol/cortisol ratio; that of CYP2D6 was measured by the 6-hydroxy-1,2,3,4-tetrahydro-beta-carboline/pinoline ratio. The influence of carriage of polymorphic variants CYP2D6*4,*9,*10, CYP3A4*22, CYP3A5*3 on the activity of isoenzymes was excluded by removing their carriers from the analysis. Results and discussion. The investigators revealed an association of certain antipsychotic-induced undesirable symptoms with CYP3A and CYP2D6 activity parameters. On day 1, a lower CYP2D6 activity was initially observed in patients with tremor (0.54 [0.34; 1.34] vs 1.25 [0.91; 1.75]; p=0.023). Also, patients with any documented adverse reaction (ARs) to therapy had initially a decreased CYP3A activity (1.2 [0.85; 2.29] vs 2.55 [1.44; 4.83]; p=0.047) and an enhanced CYP3A activity during therapy (the activity difference between day 14 and day 1 was 0.28 [-0.28; 2.32] vs -1.3 [-3.47; 0.66]; p=0.042). Conclusion. The initially reduced activity of CYP2D6 and CYP3A isoenzymes is a significant predictor of antipsychotic-induced ARs in adolescents with an acute psychotic episode. The predictive role of CYP2D6 and CYP3A activity levels in the efficacy of antipsychotics has not been confirmed.

The influence of selenium derivatives selenoline, cysteine selenate, and methionine selenate on the main indicators of HSP70-dependent mechanisms of endogenous neuroprotection under conditions of acute cerebrovascular accident (CVA) modeling has been investigated, and pathogenetic substantiation of prospects for their further study as potential neuroprotectors has been given. The experiments have been performed on white Wistar rats by bilateral irreversible ligation of the common carotid artery. Cysteine selenite and methionine selenite at a dose of 30 μg/kg, and selenoline at a dose of 50 μg/kg were introduced intraperitoneally to the experimental animals once-daily for 4 days. Every day for 4 days, the severity of neurological reactions was assessed in points on a stroke-index scale, and the mortality rate in animals was recorded. In the process of biochemical studies of brain tissue, the state of mRNA expression, HSP70 level, hypoxia-induced factors (HIF) – HIF1α and HIF-3α were evaluated using the method of polymerase chain reaction (PCR) with real-time reverse transcription. While false-operated animals developed mild neurological disorders, the control group developed bilateral ptosis, circling movements, paresis and paralysis of the limbs. On the 4th day the mean score on Stroke-index P. McGraw neurological deficit assessment scale was 16.7 ± 0.52, and 40 % of animals survived. In the cytosol and mitochondria of brain tissues, a decrease in HSP70 was detected by 47% and 59%, respectively. The administration of selenite cysteine, selenite methionine and selenoline contributed to the normalization of this indicator, to a greater extent under the action of selenite cysteine. In the control group there was a decrease in HSP70 mRNA expression. After administration of all the studied compounds, a tendency to increase the expression of HSP70 mRNA was observed compared to the controls. Under conditions of cerebral circulation insufficiency ACCI, in brain tissue, a decrease in the synthesis of HIF-1α at the stage of translation with ATP deficiency was noted. The course administration of selenium-containing drugs to rats with ACCI induced an increase in HIF1α levels: cysteine selenite – by 11.2 times, selenite methionine – by 3.13 times, and selenoline – by 1.1 times (p ˃0.05). A significant difference in relation to the expression of HIF-3α was shown only after administration of cysteine selenite (by 4.3 times higher than the control). The study of antioxidant modulation of HSP70-dependent mechanisms of endogenous neuroprotection of the brain have demonstrated that administration of selenium-containing medications cysteine selenite, methionine selenite, and selenoline lead to a decrease in neurological signs and the mortality rate in animals with ACCI. The action of selenium-containing drugs is realized due to their positive influence on the glutathione system, the preservation of energy-producing function of organs and mitoprotective effect. The obtained results indicate the relevance of further study of selenium-containing drugs on other models of pathological processes accompanied by ischemia.

This paper reports a study into the impact of cadmium telluride layer thickness on the effectiveness of the CdS/CdTe/Cu/Au film solar cells. The physical mechanisms have been investigated of charge transfer in the CdS/CdTe/Cu/Au solar cells, which are intended for use as a backup power source for the systems of safety and control of objects. This is important because, despite the growing popularity of solar cell application, the effectiveness of laboratory samples differs greatly from the theoretical maximum. Thus, it has been established that the optimum thickness of the base layer of film CdS/CdTe/Cu/Au SCs is 4µm. When the thickness of the cadmium telluride layer is reduced, the effectiveness of such an assembly decreases. The decrease in efficiency occurs as a result of reducing the shunting electric resistance, increasing the density of a diode saturation current, as well as consistent electric resistance. With the increase in the thickness of the telluride layer exceeding 4µm, there is also a decrease in the efficiency of a solar cell due to the reduced shunting resistance and the increased serial electric resistance. The deterioration of the specified light diode characteristics of CdS/CdTe/Cu/Au SCs, which occurs when the thickness of the base layer is reduced by more than 4µm, is due to the diffusion of copper from the contact to the area of the separating barrier. The deterioration of light diode characteristics when increasing the thickness of the base layer of cadmium telluride is associated with a decrease in the positive effects of "chloride" treatment. The examined physical charge transfer mechanisms in the CdS/CdTe/Cu/Au solar cells have made it possible to establish the height of the rear potential barrier. In the samples studied, the height of the rear potential barrier is 0.3eV. The existence of such a barrier gives rise to the thermal-emission mechanism of charge transfer in such solar cells when applying a direct offset exceeding 1V

The formation of self-oscillations of temperature and concentration of radicals in an electron-irradiated methane film at low temperatures has been investigated experimentally and theoretically. Self-oscillations arise due to the activation nature of diffusion and radical recombination processes. Self-oscillations were studied experimentally by measuring the desorption of particles from an irradiated sample and theoretically by solving the kinetic equations for defects in a methane sample. Concentration self-oscillations of two types of particles have been found and investigated; namely, hydrogen atoms and CH3 radicals formed during the irradiation of methane by electrons. It is shown that with an increase in the irradiation intensity, the oscillation periods decrease, and the calculation value are of the order of magnitude observed in the experiment. A model of a manifestation of the self-oscillation of hydrogen molecule concentration during desorption is presented.

The secretome of human mesenchymal stem cells (MSCs) after osteogenic differentiation of FetMSC cells in vitro was obtained to develop tissue engineering technologies for bone tissue. For standard secretome samples a large number of FetMSC cells (7 × 108 cells) were cultured in serum-free conditioned medium (SFCM). All steps of cell processing were performed in the CompacT SelecT automatic system (Sartorius, United Kingdom). The SFCM was concentrated by ultrafiltration, then subjected to dialysis and dried in a vacuum rotary evaporator. The osteoinductive properties of SFCM concentrate (SFCMC) were tested on FetMSC cells by means of adding it to the growth medium at different concentrations. There were no changes in cell morphology during cultivation in the presence of SFCMC. Analysis of the transcription factors Runx2 and YAP1 (markers of osteogenic differentiation) expression using immunofluorescence staining and real-time polymerase chain reaction (RT-PCR) showed an increase in their level of expression in the presence of SFCMC. These findings demonstrate that it is possible to use SFCMC obtained from osteogenic MSCs to induce differentiation of other (undifferentiated) MSCs. The results are useful for the development of cell therapy products for bone restoration based on MSCs secretome.

The reaction of 2-chloro-N-(3-oxoalkenyl)acetamides with 1,3-benzothiazole-2(3H)-thione, 1,3-benzoxazole-2(3H)-thione, and 1-methyl-1,3-dihydro-2H-benzimidazole-2-thione led to the formation of 2-(heteroarylsulfanyl)-N-(3-oxoalkenyl)acetamides. By the action of a base, these compounds were converted into pyridin-2(1H)-ones containing a divalent sulfur atom in position C-3 bonded to a heterocyclic ring. Bromination, nitration, alkylation of 3-(1,3-benzothiazol-2-ylsulfanyl)pyridin-2(1H)-ones have been studied. The action of zinc in acetic acid transformed these compounds into 3-sulfanylpyridin-2(1H)-ones.

We studied changes in the bone tissue in patients with diffuse large B-cell lymphoma at the onset of the disease (N=41; before chemotherapy) and 5-16 years after the end of treatment (N=47). Osteodensitometry, biochemical markers of osteoporosis in the blood and urine, and gene expression in multipotent mesenchymal stromal cells were analyzed. In multipotent mesenchymal stromal cells of all patients, the expression of genes associated with bone and cartilage differentiation (FGF2, FGFR1, FGFR2, BGLAP, SPP1, TGFB1, and SOX9) was changed. In primary patients, the ratio of deoxypyridinoline/creatinine in the urine and blood level of β-cross-laps were increased, while plasma concentration of vitamin D was reduced, which indicates activation of bone resorption. No differences between the groups were revealed by osteodensitometry. No direct relationship between changes in gene expression in multipotent mesenchymal stromal cells and osteoporosis markers was found. The presence of a tumor in the body affects the bone marrow stroma, but achievement of remission and compensatory mechanisms provide age-appropriate condition of the bone tissue.

The authors analyze gas control readings obtained in Butovskaya Mine, Kemerovo Region, in step-down phase of seismicity and after blasting operations. It is estimated how seismic waves induced by blasting influences methane drainage in coal seams. It is found that methane release from coal seam to roadways increases after seismic impact.

A novel chemiluminescent method was developed to evaluate ROS generation by platelets. This method allows measuring activities of NADPH oxidase (NOX2) and enzymes synthesizing secondary ROS (superoxide dismutase, catalase, etc.) in resting and ADP-activated platelets (inductor of platelet aggregation and ROS generation) using a small number of cells. The method was tested in the examination of patients with coronary heart disease. It was found that platelets from patients with coronary heart disease were characterized by NOX2 activation, while cell metabolism is tuned for a long-term intensive production of superoxide anion radical. The enzymes synthesizing secondary ROS were also activated, but cell metabolism could not maintain their enhanced activity for a long time.

In this article the image processing of workflow from raw camera frames is detailed. The results of the visualization and quantitative analysis of the images from the rhodamine 6 G solution obtained using total internal reflection fluorescence microscopy are presented. The main stages for image processing of fluorescent molecules are considered. The following actions are described: acquisition of raw data, noise reduction, segmentation of areas of interest by characteristic features, localization of potential fluorophores, postprocessing (assessment of area parameters). Spatial information (time dependence of relative movement of the molecule positions, the concentration distribution depending on the wavelength) is obtained. These results confirm the possibility of applying computer analysis to study the nature of the movement of molecules in a system, their interactions, and dynamic properties of various molecular systems.

An experimental study and detailed kinetic modeling of characteristics of the matrix conversion of a methane–oxygen mixture with the addition of hydrogen, carbon monoxide, synthesis gas, and steam have been carried out. It has been shown that the most significant effect on the product composition is provided by the admixture of steam, which reduces the yield of acetylene and at the same time increases the H2/CO ratio. The kinetic simulation results appear to agree well with the experimental data obtained.

The efficiency of diamomd grinding of the sapphire and polycrystalline zirconium dioxide spherical surfaces with a diamond tool based on a metal binder with a reduced spread of porous inclusions in size is experimentally investigated. The tool composite is compacted using polyethylene glycol modified with adamantane derivatives, which increases the nonlinearity of the humidifier flow at the stage of briquetting. It is shown that the amplitude of the coefficient of friction decreases by a factor of 3 when such a composite is in friction with zirconium dioxide compared to sapphire friction. In addition, scratches are observed on the polished surface of sapphire in contrast to the case of grinding of zirconium dioxide, to exclude which it is advisable to make sure that the structure of the porous space of the composite has not only a certain size distribution of porous inclusions, but also a reduced value of their most probable size. The parameters of the relative productivity and wear of the diamond tool when grinding sapphire and zirconium dioxide differ by a factor of 2 to 3 depending on the grit size of the abrasive material. The surface roughness of polycrystalline zirconium dioxide upon its fine grinding is generally four to five times lower than that of sapphire.

Interaction of vinyl trichlorosilane with sodium salt of ricinoleic acid is investigated. It is established that the composition and structure of silicon-containing ethers depends on the content of crystallization water in sodium ricinoleate, and the concentration and nature of solvent. Thus, in the case of a mixture of absolute alcohol with ether and low content of crystallization water, the reaction proceeds by hydroxyl of alcohol to form salt-like compounds containing silicon. In the case of a salt with a high content of crystallization water, the reaction proceeds along two reaction centers with the formation of ether and ester simultaneously. The composition and structure of the obtained compounds were established using elemental analysis, IR, 1H, 13C NMR spectroscopy, and gel chromatography. It is proposed to use prepared organosilicon ethers of ricinoleic acid as additives to motor oils instead of castor oil.

An investigation is performed of the effect the high-energy ball milling (mechanical alloying, MA) of a mixture of iron and hexagonal boron nitride (h-BN) powders at a component weight ratio of Fe : BN = 1 has on the phase composition and magnetic properties of the synthesized material. High-energy ball milling with subsequent annealing of the MA powder at 600°C is shown to alter its phase composition, structure, and magnetic characteristics substantially.

Reversible UbiD-like (de)carboxylases represent a large family of mostly uncharacterized enzymes, which require the recently discovered prenylated FMN (prFMN) cofactor for activity. Functional characterization of novel UbiDs is hampered by a lack of robust protocols for prFMN generation and UbiD activation. Here, we report two systems for in vitro and in vivo FMN prenylation and UbiD activation under aerobic conditions. The in vitro one-pot prFMN cascade includes five enzymes: FMN prenyltransferase (UbiX), prenol kinase, polyphosphate kinase, formate dehydrogenase, and FMN reductase, which use prenol, polyphosphate, formate, ATP, NAD+, and FMN as substrates and cofactors. Under aerobic conditions, this cascade produced prFMN from FMN with over 98% conversion and activated purified ferulic acid decarboxylase Fdc1 from Aspergillus niger and protocatechuic acid decarboxylase ENC0058 from Enterobacter cloaceae. The in vivo system for FMN prenylation and UbiD activation is based on the coexpression of Fdc1 and UbiX in Escherichia coli cells under aerobic conditions in the presence of prenol. The in vitro and in vivo FMN prenylation cascades will facilitate functional characterization of novel UbiDs and their applications.

Phenazepam® is prescribed to relieve anxiety and sleep disorders during alcohol withdrawal, although it is associated with undesirable side effects. Aim: To demonstrate changes in the safety and efficacy profiles of Phenazepam in patients with anxiety disorders and comorbid alcohol use disorder. Materials & methods: A total of 94 Russian patients with alcohol use disorder received 4.0 mg of Phenazepam per day in tablets. We used a urinary 6-beta-hydroxycortisol/cortisol ratio to evaluate CYP3A activity. Results: A statistically significant inverse correlation between Phenazepam plasma concentration and CYP3A activity was found (r = -0.340 and p = 0.017). Correlation between the concentration/dose ratio and phenotyping results was also statistically significant (r = 0.301 and p = 0.026). Conclusion: The safety and efficacy of Phenazepam depend on CYP3A genetic polymorphisms.

The use of pre-sowing treatment of seeds in a magnetic field makes it possible to increase crop yields, reduce plant morbidity, improve plant biochemical parameters and product quality. During seed treatment in a magnetic field, the rate of chemical reactions, ion transport, membrane permeability, seed water absorption and oxygen concentration in the cells increase, which contributes to the improvement of seed sowing qualities. It is established that the change of sowing qualities of seeds during their treatment in a magnetic field depends on the square of magnetic induction, the gradient of the magnetic field and the velocity of movement of seeds. With a change in magnetic induction from 0 to 0.065 T germination energy and seed germination increase, and with a further increase in magnetic induction begin to decrease. The change in sowing qualities of seeds is influenced by the velocity of their movement in the magnetic field and the gradient of the magnetic field, although they are less significant factors than magnetic induction. The best results were at lower velocity values and a larger magnetic field gradient. The most effective mode of pre-sowing seed treatment in a magnetic field is a magnetic induction of 0.065 T with four re-magnetization, a magnetic field gradient of 0.57 T m and a velocity of 0.4 m/s. With this mode of pre-sowing treatment of seeds in a magnetic field, the germination energy of cereals compared to the control increased by 16 – 50 %, and germination - by 10 – 38 %. Key words: seeds, magnetic induction, seed velocity, magnetic field gradient, germination energy, germination

The aim of this work was to reveal the interrelations between the number of T regulatory cells (Tregs) in patients with kidney cancer (KC) and phenotype of peripheral blood monocytes and their capacities to produce ROS. Patients with KC (T3N0M0, clear cell type) were examined prior to surgical treatment. Tregs phenotype and blood monocytes were identified by flow cytometry. ROS production of purified monocytes was carried out through the determination of lucigenin- and luminol-dependent spontaneous and zymosan-induced chemiluminescence activity. It has been found that the relative number of Tregs within total lymphocyte subset in KC patients was increased if compared to control values (in KC patients — Me = 6.3%). Then the patients were divided into two groups according to the median of Tregs number (less and more than 6.3%). The most pronounced changes in the phenotype of monocytes and their chemiluminescent activity were found in KC patients with the Tregs count of less than 6.3%. Our findings suggest that low frequency of Tregs in the periphery was associated with increased relative numbers of “intermediate” and “non-classical” (“pro-inflammatory”) monocytes as it was shown on the samples from patients with KC with a low level of Tregs. According to our data, both groups of KC patients had low levels of HLA-DR expression when comparing to control group. Furthermore, both groups of patients had decreased rates of HLA-DR and CD64 co-expressing cells. Changes in the phenotype of monocytes in patients with KC were closely linked with imbalance in ROS production. Thus, the monocytes spontaneous superoxide radical (primary ROS) synthesis in KC patients with a low Treg numbers were characterized by redused NADPH-oxidase activation time and increased level of its activity if compared to patients with a high Treg rates in peripheral blood. Next, the activation index for lucigenin-dependent chemiluminescence in KC patients was reduced, as well as it was independent of circulating Tregs rates and was determined apparently by the insufficiency of metabolic reserves. Similarly, spontaneous secondary ROS production by the monocytes in KC patients was lower then in healthy controls and was also independent of circulating Tregs rates. Finally, the induced secondary ROS synthesis and activation index for their synthesis in monocytes were reduced only in patients with KC with a low number of Tregs in the blood. In general, the characteristics of the chemiluminescent reaction of monocytes in patients with KC determined the imbalance in peripheral blood monocytes primary and secondary ROS production. Monocytes in patients with KC with a low number of Tregs in the blood were characterized by more pro-inflammatory activity due to the rapid activation and intensity of the synthesis of primary ROS.

Metallopolymers based on the Yb(III) complexes with 2-methyl-5-phenyl-1-pentendione-3,5 (mphpd) and allyl-3-oxobutanoate (alacac) were obtained by radical polymerization. The copolymers with methylmethacrylate and styrene in a ratio of 5:95 are obtained. The kinetics of radical polymerization of synthesized metal polymers has been studied. The complexes were characterized by infrared, absorption, diffuse reflectance and fluorescence emission spectra. The spectroscopic studies of the synthesized compounds showed that the configuration of the chelate unit is unchanged during the polymerization. By the luminescent spectroscopy is shown that all studied compounds exhibit effective luminescence. It is established that the luminescence intensity of metalopolymers and copolymers is highest for copolymers and depends on the nature of the ligands.

The Australian rainforest plant, Croton insularis, has provided a further casbane diterpene family member in the form of EBC-342, which contains a novel tetrahydrofuran ring. A combination of DP4 and TD-DFT CD methods were required to confirm both structure and absolute stereochemistry.

Here, we characterized in public health organizations prevalence of carbapenemase-producing Klebsiella pneumoniae , sensitivity to antimicrobial agents (AMAs), combined antimicrobial agents, and decontaminants. For this, there were selected 58 clinical isolates of K. pneumoniae resistant to carbapenems and/or polymyxins and examined within the microbiological monitoring program. Genes encoding KPC, OXA-48, VIM, IMP, NDM carbapenemases were detected by real-time multiplex PCR. Sensitivity to antimicrobial agents was determined by an automated method on a microbiological VITEK-2 Compact analyzer (bioMerieux, France) and by serial broth microdilution method. Sensitivity to 11 dual antimicrobial agent combinations was determined by a modified method of multiple combination bactericidal antibiotic testing. As a part of combinations, AMAs at pharmacokinetic/pharmacodynamics (PK/PD) threshold concentrations (meropenem — 8 μg/ml, amikacin — 16 μg/ml, levofloxacin — 1 μg/ml, tigecycline — 0.5 μg/ml, phosphomycin — 32 μg/ml, colistin — 2 μg/ml) were tested. Susceptibility to 7 combined decontaminants of different composition was determined by the suspension method. Carbapenemase genes were detected in 22 K. pneumoniae clinical isolates, of which 19 isolates contained a bla OXA-48 gene and 3 isolates — gene bla NDM . Carbapenemase producing K. pneumoniae were identified in 10 Gomel public health organizations and five regional centers of the Gomel region. The majority of such strains were isolated from patients in ICU (63.6%) and surgical departments (27.3%). Tigecycline (100% of the sensitive isolates, МIC 50 — 1 μg/ml, MIC 90 — 1 μg/ml) and colistin (86.4% of the sensitive isolates, МIC 50 — 0.5 μg/ml, MIC 90 — 4 μg/ml) exhibited the highest activity against carbapenemase-producing K. pneumoniae , whereas aminopenicillins, cephalosporins, aztreonam, aminoglycosides, fluoroquinolones, chloramphenicol (no sensitive isolates) had exhibited the lowest efficacy. Bactericidal activity of all antibiotic combinations containing colistin was shown against 86.4–95.5% of K. pneumoniae isolates. At least 3 distinct combinations of antimicrobial agents with bactericidal activity were efficient against 21 K. pneumoniae isolates (95.5%). Only 1 bactericidal combination (meropenem–amikacin) was unveiled for one isolate (producer of NDM MBL with MIC of colistin 32 μg/ml). Geksadekon, duacid, oksidez, hlorocid and diajsid exerted a bactericidal effect at 1/4 work dose against all isolates. Duacid, oksidez, hlorocid and diajsid showed bactericidal effect at 1/16 work dose against 95.5–100% isolates. Thus, several decontaminant groups (oxidizing agents, chlorine-containing preparations) were characterized by bactericidal activity against multidrug-resistant and extremely drug-resistant of K. pneumoniae even at 4–16 times lower than recommended concentration.

Vancomycin and related glycopeptides are drugs of last resort for the treatment of severe infections caused by Gram‐positive bacteria such as Enterococcus species, Staphylococcus aureus, and Clostridium difficile. Vancomycin was long considered immune to resistance due to its bactericidal activity based on binding to the bacterial cell envelope rather than to a protein target as is the case for most antibiotics. However, two types of complex resistance mechanisms, each comprised of a multi‐enzyme pathway, emerged and are now widely disseminated in pathogenic species, thus threatening the clinical efficiency of vancomycin. Vancomycin forms an intricate network of hydrogen bonds with the d‐Ala‐d‐Ala region of Lipid II, interfering with the peptidoglycan layer maturation process. Resistance to vancomycin involves degradation of this natural precursor and its replacement with d‐Ala‐d‐lac or d‐Ala‐d‐Ser alternatives to which vancomycin has low affinity. Through extensive research over 30 years after the initial discovery of vancomycin resistance, remarkable progress has been made in molecular understanding of the enzymatic cascades responsible. Progress has been driven by structural studies of the key components of the resistance mechanisms which provided important molecular understanding such as, for example, the ability of this cascade to discriminate between vancomycin sensitive and resistant peptidoglycan precursors. Important structural insights have been also made into the molecular evolution of vancomycin resistance enzymes. Altogether this molecular data can accelerate inhibitor discovery and optimization efforts to reverse vancomycin resistance. Here, we overview our current understanding of this complex resistance mechanism with a focus on the structural and molecular aspects.

Dysphania is an abundant genus of plants, many of which are endemic to the Australian continent, occurring primarily in arid and temperate zones. Despite their prevalence, very few investigations into the phytochemistry of native Dysphania have been undertaken. Described herein, is the isolation and elucidation of two enantiomeric diastereomers of humulene diepoxide C from D. kalpari and D. rhadinostachya, of which unassigned diastereomers of humulene diepoxide C have been previously reported as components in beer brewed from aged hops. In addition, two (+)-humulene diepoxiols (humulene diepoxiol C-I and C-II) were isolated from D. rhadinostachya. Analysis of Chinook hops oil confirmed the presence of both humulene diepoxide C-I and C-II as trace components, and in turn enabled GC-MS peak assignment to the relative stereochemistry. Anticancer assays did not reveal any significant activity for the (+)-humulene diepoxides. Antifungal assays showed good activity against a drug-resistant strain of C. auris, with MIC50 values of 8.53 and 4.91 μm obtained for (+)-humulene diepoxide C-I and C-II, respectively.

The chemical synthesis of nanoparticles with a preassigned size and shape is important for an optimized performance in any application. Therefore, systematic monitoring of the synthesis is required for the control and detailed understanding of the nucleation and growth of the nanoparticles. Here, we study Fe3O4-Au hybrid nanoparticles in detail using probes of the reaction mixture during synthesis and their thorough characterization. The proposed approach eliminates the problem of repeatability and reproducibility of the chemical synthesis and was carried out using laboratory equipment (standard transmission electron microscopy, X-ray diffraction, and magnetometry) for typically 10 μL samples instead of, for example, a dedicated synthesis and inspection at a synchrotron radiation facility. From the three independent experimental techniques we extract the nanoparticle size at 12 stages of the synthesis. These diameters show identical trends and good quantitative agreement. Two consecutive processes occur during the synthesis of Fe3O4-Au nanoparticles, the nucleation and the growth of spherical Fe3O4 nanoparticles on the surface of Au seeds during the heating stage and their faceting towards octahedral shape during reflux. The final nanoparticles with sizes of 15 nm Fe3O4 and 4 nm Au exhibit superparamagnetic behavior at ambient temperature. These are high-quality, close to stoichiometric Fe3O4 nanocrystals with nearly volumetric magnetic behavior as confirmed by the presence of the Verwey transition. Understanding the processes occurring during the synthesis allows the nanoparticle size and shape to be adjusted, improving their capabilities in biomedical applications.

OBJECTIVE The aim: To study the pathomorphological characteristics and immunohistochemical features of placentae from human immunodeficiency virus-positive (HIV-positive) pregnant women with FGR. PATIENTS AND METHODS Materials and methods: The study material was 32 placentae, including 12 placentae from HIV-positive pregnant women with FGR (study group), 10 placentae from HIVpositivepregnant women without FGR (comparison group) and 10 placentae from HIV-negative women with physiological pregnancy (control group). An immunohistochemical study was performed using monoclonal antibodies (MCA) against CD31+ and vascular endothelial growth factor (VEGF). RESULTS Results: Pathomorphologic changes of the placentae from HIV-positive pregnant women with FGR were characterized by edema in the umbilical cord tissue, partial dissection of the vascular wall fibers, dysmucoidosis; intracellular edema and hemorrhage in the fetal membrane tissues. In the placentae tissue it was found marked manifestations of degenerative changes in the form of the areas of fibrinoid necrosis, pronounced manifestations of dysmucoidosis, vacuolation of the villi stroma, an increase in the number of avascular villi and immature villi of small caliber with the phenomena of syncytiotrophoblast focal hyperplasia. An immunohistochemical study with MCA against CD31+ revealed the expression (optical density) of the vascular endothelial cells up to 2 points, and the expression level up to 3 points in the isolated areas with the appearance of the expression on the villi surface and in their thickness. During immunohistochemical studies with VEGF the expression level and its optical density increased up to 2-3 points, in some areas the expression of deposits were detected on the villi surface, in their thickness and in the intervillous space. CONCLUSION Conclusions: The comparative pathomorphological and immunohistochemical study of the placentae demonstrated more significant changes in the group of HIV-positive pregnant women with FGR. In the placentae of HIV-positive pregnant women with FGR immunohistochemical examinations revealed a high level of CD31+ and VEGF expression.

Carbon–carbon bond formation is one of the most important reactions in biocatalysis and organic chemistry. In nature, aldolases catalyze the reversible stereoselective aldol addition between two carbonyl compounds, making them attractive catalysts for the synthesis of various chemicals. In this work, we identified several 2-deoxyribose-5-phosphate aldolases (DERAs) having acetaldehyde condensation activity, which can be used for the biosynthesis of (R)-1,3-butanediol (1,3BDO) in combination with aldo-keto reductases (AKRs). Enzymatic screening of 20 purified DERAs revealed the presence of significant acetaldehyde condensation activity in 12 of the enzymes, with the highest activities in BH1352 from Bacillus halodurans, TM1559 from Thermotoga maritima, and DeoC from Escherichia coli. The crystal structures of BH1352 and TM1559 at 1.40–2.50 Å resolution are the first full-length DERA structures revealing the presence of the C-terminal Tyr (Tyr224 in BH1352). The results from structure-based site-directed mutagenesis of BH1352 indicated a key role for the catalytic Lys155 and other active-site residues in the 2-deoxyribose-5-phosphate cleavage and acetaldehyde condensation reactions. These experiments also revealed a 2.5-fold increase in acetaldehyde transformation to 1,3BDO (in combination with AKR) in the BH1352 F160Y and F160Y/M173I variants. The replacement of the WT BH1352 by the F160Y or F160Y/M173I variants in E. coli cells expressing the DERA + AKR pathway increased the production of 1,3BDO from glucose five and six times, respectively. Thus, our work provides detailed insights into the molecular mechanisms of substrate selectivity and activity of DERAs and identifies two DERA variants with enhanced activity for in vitro and in vivo 1,3BDO biosynthesis.