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Belactosins and hormaomycins are peptide natural products containing 3-(2-aminocyclopropyl)alanine and 3-(2-nitrocyclopropyl)alanine residues, respectively, with opposite stereoconfigurations of the cyclopropane ring. Herein we demonstrate that the heme oxygenase-like enzymes BelK and HrmI catalyze the N-oxygenation of l-lysine to generate 6-nitronorleucine. The nonheme iron enzymes BelL and HrmJ then cyclize the nitroalkane moiety to the nitrocyclopropane ring with the desired stereochemistry found in the corresponding natural products. We also show that both cyclopropanases remove the 4-proS-H of 6-nitronorleucine during the cyclization, establishing the inversion and retention of the configuration at C4 during the BelL and HrmJ reactions, respectively. This study reveals the unique strategy for stereocontrolled cyclopropane synthesis in nature.

The isothermal process of chemical vapor deposition for the densification with a SiC-matrix of organomorphic carbon-fiber preforms obtained by carbonization of compressed fibers of oxidized polyacrylonitrile is investigated. Such preforms are characterized by a high (up to 70%) porosity and uniform pore size (the reduced pore diameter ranges from several micrometers to tens of micrometers). Technological parameters of the process of obtaining ceramic-matrix composites (CMC) were optimized by a combination of experimental studies and numerical simulations. Experimental samples of CMC were obtained using a non-halogen precursor, methylsilane CH3SiH3, and their residual porosity was determined. For the numerical study of the gas-phase process of densification of preforms, a 1D model was used. The simulation results were compared with experimental observations.

SNF1-Related protein kinases Type 2 (SnRK2) are plant-specific enzymes widely distributed across the plant kingdom. They are key players controlling abscisic acid (ABA)-dependent and ABA-independent signaling pathways in the plant response to osmotic stress. Here we established that SnRK2.4 and SnRK2.10, ABA-nonactivated kinases, are activated in Arabidopsis thaliana rosettes during the early response to salt stress and contribute to leaf growth retardation under prolonged salinity but act by maintaining different salt-triggered mechanisms. Under salinity, snrk2.10 insertion mutants were impaired in the reconstruction and rearrangement of damaged core and antenna protein complexes in photosystem II (PSII), which led to stronger non-photochemical quenching, lower maximal quantum yield of PSII, and lower adaptation of the photosynthetic apparatus to high light intensity. The observed effects were likely caused by disturbed accumulation and phosphorylation status of the main PSII core and antenna proteins. Finally, we found a higher accumulation of reactive oxygen species (ROS) in the snrk2.10 mutant leaves under a few-day-long exposure to salinity which also could contribute to the stronger damage of the photosynthetic apparatus and cause other deleterious effects affecting plant growth. We found that the snrk2.4 mutant plants did not display substantial changes in photosynthesis. Overall, our results indicate that SnRK2.10 is activated in leaves shortly after plant exposure to salinity and contributes to salt stress tolerance by maintaining efficient photosynthesis and preventing oxidative damage.

Barth syndrome is an X-linked disorder characterized by cardiomyopathy, skeletal myopathy and neutropenia, caused by deleterious variants in TAFAZZIN. This gene encodes a phospholipid-lysophospholipid transacylase that is required for the remodeling of the mitochondrial phospholipid cardiolipin (CL). Biochemically, individuals with Barth syndrome have a deficiency of mature CL and accumulation of the remodeling intermediate monolysocardiolipin (MLCL). Diagnosis typically relies on mass spectrometric measurement of CL and MLCL in cells or tissues, and we previously described a method in blood spot that uses a specific MLCL/CL ratio as diagnostic biomarker. Here, we describe the evolution of our blood spot assay that is based on the implementation of reversed phase-UHPLC separation followed by full scan high resolution mass spectrometry. In addition to the MLCL/CL ratio, our improved method also generates a complete CL spectrum allowing the interrogation of the CL fatty acid composition, which considerably enhances the diagnostic reliability. This addition negates the need for a confirmatory test in lymphocytes thereby providing a shorter turn-around-time while achieving a more certain test result. As one of the few laboratories that offer this assay we also evaluated the diagnostic yield and performance from 2006-2021 encompassing the use of both the original and improved assay. In this period we performed 796 diagnostic analyses of which 117 (15%) were characteristic of Barth syndrome. In total we diagnosed 93 unique individuals with Barth syndrome, including three females, which together amounts to about 40% of all reported individuals with Barth syndrome in the world. This article is protected by copyright. All rights reserved.

The oxidation behavior of five different high-entropy alloys from the Al–Co–Cr–Fe–Ni metallic system, namely Alx(CoCrFeNi)100-x (x = 0; 3; 6; 9; 12), was studied under thermal-cycling conditions, at 1273 K in air atmosphere. The choice of selected compositions allowed for covering the chromia-to-alumina former transition, as well as the transition from the FCC single-phase solid solution structure to multiphase alloys with Al-enriched B2-structured constituent. The measurements were taken for 500 cycles (1 cycle - 1 h of heating, 20 min of cooling). The results indicate a profound influence of the thermal-cycling conditions on the oxidation products, with extremely complex scale structures and extensive internal oxidation and nitridation zones, as well as severe spallation of the oxide scale in most cases, showing the limited usefulness of these alloys for high-temperature applications at the current stage of their development.

Use of soldering methods for preparing high-temperature permanent joints of silicon carbide ceramic matrix composites (CMC) with metals is analyzed. The main problems in joining CMC with metals are considered associated with poor wettability of CMC with molten metals, a significant difference in the LTEC of CMC and metals, and formation of substances with high hardness and brittleness within a connecting layer. Analysis of practical experience of using traditional and diffusion soldering methods for joining CMC of the Cf/SiC type with metal alloys based on Ni, Nb, Ti, Mo, and stainless steel is provided. The most typical solder compositions and soldering process production methods are considered. It is shown that these technologies make it possible to create reliable and strong joints for CMC components and various metals.

OBJECTIVE Our objective was to determine the incidence and risk factors for intravenous acetazolamide-associated acute kidney injury (AKI).METHODS We utilized a retrospective cohort study including patients RESULTS A total of 868 patients met study criteria (male 55.8%, median age 0.66 years [IQR 0.19, 3.0 years]). Intravenous acetazolamide was administered at 5.1 ± 2.8 mg/kg/dose for a median of 4 doses (IQR 2, 6). Median baseline SCr was 0.28 mg/dL (IQR 0.22, 0.37), corresponding to a creatinine clearance of 115 ± 55 mL/min/1.73 m2. Acute kidney injury occurred in 26.8% (n = 233) of patients (stage I = 20.1%, stage II = 3.7%, stage III 3.1%), and no patients received renal replacement therapy. An ordinal logistic regression model identified an increased odds of AKI with cyclosporine, ethacrynic acid, and piperacillin-tazobactam administration.CONCLUSIONS Acute kidney injury occurs frequently in critically ill pediatric patients receiving intravenous acetazolamide.

High-efficiency harmonic generation is observed in a semiconducting polymer RR-P3HT [regioregular poly(3-hexylthiophene)], which exhibits a high nonlinear susceptibility [χ (2) > 10−6 m V−1] under pumping by a pulsed fibre laser. The harmonic generation efficiency in RR-P3HT is comparable or higher than that observed for liquid crystals, which are used in reference experiments to estimate the susceptibility [the quadratic susceptibility of a nematic liquid crystal NLC 1289 is χ (2) ≈ 2 × 10−6 m V−1]. No generation is observed in polythiophene with a random structure, RRa-P3HT [regiorandom poly(3-hexylthiophene)], at the same pump power. It is experimentally demonstrated that a necessary condition for generating the second and third harmonics in a polymer, along with a high pump power density, is the presence of a large power density gradient (exceeding 1013 W m−3). Based on a preliminary theoretical analysis, we can suggest that the quadrupole mechanism, which is a consequence of the regularity of RR-P3HT structure in the thin near-wall layer, may contribute significantly to the nonlinear radiation conversion in semiconducting polymers.

Titanium alloys attract wide attention of researchers due to the unique combination of low density, high strength, corrosion resistance, biocompatibility, etc. Therefore, the study of new methods for processing titanium and the creation of protective coatings seems relevant. Metal-ceramic coatings were obtained by electrospark treatment of a titanium alloy Ti6Al4V in a mixture of titanium granules with tantalum carbide powder. Three mixtures of granules were prepared with a TaC content of 2.4; 4.6 and 6.7 vol.%. Coatings were deposited by rectangular pulses with an energy of 0.33 J and a frequency of 1 kHz for 8 minutes in an argon stream. The increase of the volume fraction of tantalum carbide powder in the mixture of granules from 2.4 to 6.7 vol.% does not lead to a significant increase in cathode gain. The average coating thickness ranged from 29 to 36 microns. Using scanning microscopy and energy dispersive analysis methods, it was found that the coating structure is represented by a metal Ti – Ta – C matrix with large ceramic grains. According to x-ray phase analysis, it was found that tantalum carbide TaC prevails in the coating composition. It content increases with increasing powder concentration in the mixture of granules. In addition to it, there are phases of titanium carbide and tantalum subcarbibide TaC0.6, which are the products of TaC decarburization during its interaction with the titanium melt. With an increase of the tantalum carbide concentration in the mixture of granules, the hardness of TaC/Ti coatings increased from 6.1 to 8.9 GPa, which is 2–3 times higher than that of the Ti6Al4V alloy. Coefficient of friction of coatings was in the range of 0.5–0.9. Dry sliding wear tests showed that TaC/Ti coatings had a wear rate ranging from 0.1·10–5 mm3/Nm to 1.7·10–5 mm3/Nm. Thus, the use of these coatings makes it possible to increase the wear resistance of the Ti6Al4V alloy up to 128 times.

The new therapeutic solutions for breast cancer treatment are needed, for example, combined therapy consisted of several drugs that characterize different mechanisms of action and modern drug delivery systems. Therefore, we used combination of epothilone B (EpoB) and rapamycin (Rap) to analyze the cytotoxic effect against breast cancer cells (MCF-7; MDA-MB-231). Also, the effect of drugs co-delivered in bioresorbable micelles functionalized with biotin (PLA-PEG-BIO; poly(lactide)-co-poly(ethylene glycol)-biotin) was studied. The comparison of effects of the mixture of free drugs and the micelles co-loaded with EpoB and Rap revealed a significant decrease in the cell metabolic activity and survival. Moreover, the dual drug-loaded PLA-PEG-BIO micelles enhanced the cytotoxicity of EpoB and Rap against the tested cells as compared with the free drugs. The blank PLA-PEG-BIO micelles did not affect the tested cells. We expect that mixture of EpoB and Rap may be promising in breast cancer treatment and PLA-PEG-BIO micelles as carrier of these two drugs can be applicable for successful targeted delivery.

In the presence work, mycelial growth, sclerotia formation, polygalacturonase, a-amylase and cellulase activities of a Belarusian fungal isolate Sclerotinia sclerotiorum KK-1 collected from infected сarrot (Daucus carota subsp. sativus) were analyzed. It was established that polygalacturonase was induced by pectin and subject to catabolite repression by glucose. The ability of the isolate to produce oxalic acid, an important factor of pathogenesis, was observed throughout fungus incubation on PDA medium amended with bromophenol blue. Glyphosate (commercial counterpart «Tornado») starting from its level in the medium of 200 mg/L caused a significant inhibition of mycelial growth and sclerotia formation. It was observed that a-amylase and cellulase activities were inhibited by glyphosate unlike polygalacturonase activity.

We obtained a Raman spectrum for a surface layer of porous carbon ceramic (porosity ≈5%) of ≈80 nm thick. The analysis of the spectrum showed that the ceramics contain crystals of silicon carbide 6H‑SiC and silicon. The destruction of ceramics by diamond microcrystals resulted in fractoluminescence (FL). Its spectrum contained two bands at 1.6 and 1.9 eV. The first is emerged at the destruction of silicon crystals, and the second is emerged at 6H-SiC crystals. We obtained the time dependence of the intensity of the fractoluminescence signals with a time resolution of 2 ns. Three types of signals were observed: one is formed when the 6H-SiC crystals are destroyed; the second is formed when silicon crystals are destroyed; the third is formed when these crystals are simultaneously destroyed. The appearance of signals is associated with the formation of cracks arising from the breakthrough of barriers formed at the intersection of slip planes of dislocations in silicon carbide and silicon crystals. The size of cracks in 6H-SiC has been estimated: the smallest is 5.5 nm, and the largest is ≈18 nm.

Annotation. Among gynecological diseases, external genital endometriosis leads to disorders of reproductive function and promotes the development of infertility. Currently, the search for less traumatic and more effective treatments for endometriosis continues. The aim of our study was to analyze the diameter of endometrioid cysts in women with infertility on the background of endometriosis before and after sclerotherapy using pre-pregnancy preparation of a complex vitamin preparation with inositol and vitamin D3. The study included 105 women aged 22 to 40 years with endometriosis-associated infertility. The presence of cysts was confirmed by ultrasound and bimanual examination. The drug FT 500 plus was prescribed in a dosage of 1 sachet – once a day from the 2nd or 3rd day of the cycle for 2 menstrual cycles (the cycle in which sclerotherapy was performed and the next cycle). Vitamin D3 “EuTilia D3” was prescribed in prophylactic doses of 2000 IU to women, or therapeutic (depending on the diagnosed or refuted diagnosis of vitamin D hypovitaminosis). The sclerotherapy procedure was performed by transvaginal puncture of the cyst and aspiration of its contents under the control of transvaginal ultrasound, introduction into the capsule of the cyst (without violating its integrity) 76% ethanol solution. It was found that women with endometriosis-associated infertility, who underwent pre-pregnancy preparation with a complex vitamin preparation with inositol and vitamin D3 after sclerotherapy, probably decreased the diameter of cysts in the right (5.85 times) and left (5.57 times) ovaries relative to data before sclerotherapy. When comparing the diameter of cysts in women who underwent pre-pregnancy preparation with a complex vitamin preparation with inositol and vitamin D3, depending on the type of surgery (sclerotherapy or cystectomy) found a probable decrease in the diameter of cysts after sclerotherapy in the right (82.89%) and left (82.05%) ovaries for such data after cystectomy. Therefore, sclerotherapy with pregravidar preparation with a complex vitamin preparation with inositol and vitamin D3 in women with endometriosis-associated infertility probably reduces the diameter of cysts relative to the experimental group without pregravidar preparation, as well as to the group with a history of cystectomy.

BACKGROUND High-dose atorvastatin did not improve 1-year vein graft patency in the recent Aggressive Cholesterol Therapy to Inhibit Vein Graft Events trial. However, it remains unknown whether high-intensity statins may impact graft disease in the years that follow. METHODS In the trial, patients (N = 173) were randomized to receive atorvastatin 10 or 80 mg for 1 year after coronary bypass surgery (CABG). Beyond 1 year, the choice of statin was left to the patient's physician. In this study of participants who agreed to follow-up (N = 76), low-density lipoprotein (LDL) levels were measured and graft patency was assessed 3 years after surgery. RESULTS The rate of vein graft disease 3 years after surgery was not significantly reduced with atorvastatin 80 mg during the first postoperative year or the use of open-label high-intensity statin thereafter (p = NS). However, a trend was observed between higher LDL levels during the first postoperative year and a greater incidence of vein graft disease at 3 years (p = .12). Among patients who had LDL levels more than 90 mg/dl in the first year after CABG, 38.5% had vein graft disease at 3 years, compared to 19.0% for those with LDL levels less than 90 mg/dl (p = .15). Higher mean LDL levels during the first postoperative year were associated with a higher rate of vein disease 3 years after surgery both at the graft level (p = .03) and at the patient level (p = .03) in multivariate analysis. CONCLUSIONS Higher LDL levels during the first postoperative year were associated with significantly greater vein graft disease 3 years after CABG.

The reaction of 1-acylisatins with Girard’s reagent T proceeds with elimination of the acyl substituent and the formation of isatin-3-hydrazone with a quaternary nitrogen atom in the side chain. Depending on the structure of the substituent in position 1, 1-(aminomethyl)isatins reacted with the Girard’s reagent T to form hydrazones either with the elimination of the aminomethyl substituent or with its retention. Isatin derivatives containing no substituents in the aromatic fragment exhibit moderate activity against gram-positive bacteria S. aureus 209p and B. cereus 8035. Low hemotoxicity of the obtained compounds was revealed.

Compounds based on two (11-oxoanthra[1,2-b]thiophene-6-ylidene)dipropanedinitrile moieties joined by a fluorene or phenyl π-linker are investigated as potential substitutes for fullerene acceptors in active layers of organic photovoltaics. The effect a linker has on the optical and morphological properties of conjugated polymeric composites and synthesized compounds, and on the photovoltaic parameters of a cell, is revealed. The values obtained for the coefficient of power conversion efficiency (PCE) are 0.047 and 0.028%, respectively, for compounds with fluorene and phenyl linkers, respectively.

L-phenylglycine (L-Phg) is a rare non-proteinogenic amino acid, which only occurs in some natural compounds, such as the streptogramin antibiotics pristinamycin I and virginiamycin S or the bicyclic peptide antibiotic dityromycin. Industrially, more interesting than L-Phg is the enantiomeric D-Phg as it plays an important role in the fine chemical industry, where it is used as a precursor for the production of semisynthetic β-lactam antibiotics. Based on the natural L-Phg operon from Streptomyces pristinaespiralis and the stereo-inverting aminotransferase gene hpgAT from Pseudomonas putida, an artificial D-Phg operon was constructed. The natural L-Phg operon, as well as the artificial D-Phg operon, was heterologously expressed in different actinomycetal host strains, which led to the successful production of Phg. By rational genetic engineering of the optimal producer strains S. pristinaespiralis and Streptomyces lividans, Phg production could be improved significantly. Here, we report on the development of a synthetic biology-derived D-Phg pathway and the optimization of fermentative Phg production in actinomycetes by genetic engineering approaches. Our data illustrate a promising alternative for the production of Phgs., Deutsche Forschungsgemeinschaft, Baden-Württemberg-Stiftung, Deutsches Zentrum für Infektionsforschung, Projekt DEAL

Various types of biodegradable polymers containing lactide, glycolide, caprolactone, and trimethylene carbonate units have been used to obtain ciprofloxacin (CFX)-enriched coatings developed on the Ti6Al7Nb alloy, intended for short-term therapy. In the first step, the surface of the Ti6Al7Nb alloy was modified, mostly according to sandblasting and anodic oxidation to obtain the TiO2 layer. Anodizing can be an effective method for preparing TiO2 coatings with osteoconductive properties. The polymer containing CFX molecules was deposited on the modified alloy, and Polymer + CFX/TiO 2 /Ti6Al7Nb systems were developed. CFX-enriched coatings adhered well to the surface of the previously modified alloy. Polymer layers maintain the topography of the alloy due to the development of the surface during the sandblasting method. As polymers intended for the study possess degradation ability, they are capable of releasing the incorporated drug. Antibacterial activity of CFX-enriched coatings was examined to verify the functionality of designed Polymer + CFX/TiO 2 /Ti6Al7Nb systems, and the bactericidal effect was confirmed for all cases. The presented study is an extension of previous, initial research and creates an overview of polyester or polyestercarbonate CFX-eluting coatings.

Cell viability is an important indicator while screening drugs. An inaccurate evaluation of cell viability can cause large errors in anti-tumor dose experiments, and this becomes very unfavorable for cancer treatment. Generally, cell viability refers to the ratio of the number of live cells to the total number of cells. However, this evaluation method does not consider the effects of differences in metabolic abilities between different living cells. In this paper, there is a new cell viability evaluation method based on respiratory thermodynamic feature that includes the respiratory intensity, proliferation rate, and heat released by cells. These three parameters can be directly measured by a microscopic infrared thermal imaging sensor, which is fast and non-invasive and does not require consumables. The three parameters were simultaneously measured based on a micro-infrared thermal imaging sensor and fitted to the mathematical model. Finally, the method was verified by comparing it with traditional c ounting method and comparing the amount of omethoate with traditional counting method. The results indicated that omethoate is 12.36% lower than in the traditional counting method with the same level of complete cell inactivation. Therefore, this method is more accurate than the conventional cell viability assessment method, and the dosage is more precise when the uniform effect is achieved, which provides a basis for precise doses in tumor treatment and can reduce side effects in the human body. This method has a significant effect on the manufacture of cell activity detecting sensors.

Despite being attractive targets for functional materials, the discovery of transition metal complexes with high-throughput computational screening is challenged by the amount of feasible coordination numbers, spin states, or oxidation states and the potentially large sizes of ligands. To overcome these limitations, we take inspiration from organic chemistry where full enumeration of neutral, closed-shell molecules under the constraint of size has enriched discovery efforts. We design monodentate and bidentate ligands from scratch for the construction of mononuclear, octahedral transition metal complexes with up to 13 heavy atoms (i.e., metal, C, N, O, P, or S). From >11 000 theoretical ligands, we develop a heuristic score for ranking a chemically feasible 2500 ligand subset, only 71 of which were previously included in common organic molecule databases. We characterize the top 20% of scored ligands with density functional theory (DFT) in an octahedral homoleptic ligand database (OHLDB). The OHLDB contains i) the geometry optimized structures of 1250 homoleptic octahedral complexes obtained from the enumerated pool of ligands and an open-shell transition metal (M(II)/M(III), M = Cr, Mn, Fe, or Co) and ii) the resulting high-spin/low-spin adiabatic electronic energy differences (ΔEH–L) obtained with hybrid DFT. Over the OHLDB, we observe structure–property (i.e., ΔEH–L) relationships different from those expected on the basis of ligand field arguments or from our prior data sets. Finally, we demonstrate how incorporating OHLDB data into artificial neural network (ANN) training improves ANN out-of-sample performance on much larger transition metal complexes.

Background Loss of asthma control and asthma exacerbations are associated with increased sputum eosinophil counts. However, whether eosinophils, or the also present neutrophils, actively contribute to the accompanying inflammation has not been extensively investigated. Methods Twenty-three patients with mild to moderate asthma were included in a standardized prospective inhaled corticosteroid (ICS) withdrawal study; 22 of the patients experienced loss of asthma control. The study assessed various immune, inflammatory, and oxidative stress parameters, as well as markers of eosinophil and neutrophil activity, in exhaled breath condensate, plasma, and sputum collected at three phases (baseline, during loss of control, and following recovery). Results Loss of asthma control was characterized by increased sputum eosinophils, whereas no differences were detected between the three phases for most inflammatory and oxidative stress responses. There were also no differences detected for markers of activated eosinophils (eosinophil cationic protein and bromotyrosine) and neutrophils (myeloperoxidase and chlorotyrosine). However, free eosinophilic granules and citrullinated histone H3, suggestive of eosinophil cytolysis and potentially eosinophil extracellular trap formation, were enhanced. Baseline blood eosinophils and changes in asymmetric dimethylarginine (an inhibitor of nitric oxide synthase) in plasma were found to correlate with the decrease in FEV1 percent predicted upon ICS withdrawal (both, rs = 0.46; P = .03). Conclusions The clinical effect in mild to moderate asthma upon interruption of ICS therapy is not related to the classic inflammatory activation of eosinophils and neutrophils. It may, however, reflect another pathway underlying the onset of loss of disease control and asthma exacerbations. Trial Registry The Netherlands Trial Register; No.: NTR3316; URL: trialregister.nl/trial/3172.

The review of existing technologies of production and processing of ultra-high molecular weight polyethylene, as well as areas of its application, is presented. Ultra high modulus polyethylene has high performance characteristics – wear resistance, low friction coefficient, high corrosion and chemical resistance and high fracture toughness. These unique properties of ultra high modulus polyethylene distinguish it from other varieties of polyethylene.

Nucleic acids are key biomolecules in all life forms. These biomolecules can encode and transfer information via Watson-Crick base-pairing interactions and can form double-stranded structures between complementary sequences with high precision. These properties make nucleic acids extremely successful in applications in materials science as nanoconstruction materials. Herein, we describe a method for the automated synthesis of "oligopeds", which are building blocks based on the boron cluster structure equipped with short DNA adapters; these building blocks assemble into functional nanoparticles. The obtained, well defined, torus-like structures are the first DNA nanoconstructs based on a boron cluster scaffold. The results indicate the potential of boron clusters in DNA nanoconstruction and open the way for the design of entirely new types of buildings blocks based on polyhedral heteroborane geometry and its unique properties. The use of antisense oligonucleotides as DNA adapters illustrates one of the possible applications of the obtained nanoconstructs as vectors for therapeutic nucleic acids.

—The choice of a blocking protein agent for a rapid and sensitive immunochemical assay with surface-enhanced Raman spectroscopy (SERS) was the aim of this study. An optimized metal-dielectric SERS-based nanostructure was used for enhancement of the Raman scattering by proteins; a Raman spectrometer with a wide output laser beam with a wavelength of 532 nm was used to measure the amplified optical response spectra. As a result of this study, SERS substrates were optimized to obtain high-intensity surface-enhanced Raman scattering from tetramethylrodamine isocyanate (TRITC), the label used in the study; the parameters of adsorption of proteins traditionally used in solid-phase immunochemical analysis were also studied; bovine serum albumin and casein were chosen as the optimal proteins. It was shown that the laws described in the classical adsorption theory operate in the adsorption interaction of proteins and the SERS surface.

Temperature-programmed desorption mass spectrometry (TPD MS) was used to study the pyrolysis of p-coumaric acid (pCmA) on the nanoceria surface. The interaction of pCmA with the CeO2 surface was investigated by FT-IR spectroscopy. The obtained data indicated the formation on the nanoceria surface of bidentate carboxylate complexes with chelate (Δν = 62 cm−1) and bridge structure (Δν = 146 cm−1). The thermal decomposition of pCmA over nanoceria occurred in several stages, mainly by decarboxylation. The main decomposition product is 4-vinylphenol (m/z 120). The obtained data can be useful for studying the mechanisms of catalytic thermal transformations of lignin-containing raw materials using catalysts containing cerium oxide and the development of effective technologies for the isolation of pCmA from lignin.

Low spot urinary creatinine concentration (SUCR) is a marker of muscle wasting and clinical outcome. The risk factors for low SUCR in heart failure (HF) remain poorly understood. We explored the risk factors for low SUCR related to poor outcomes. In 721 HF patients (age: 52.3 ± 11 years, female: 14%, NYHA: 2.7 ± 0.7) SUCR and Dexa body composition scans were performed. BMI prior HF-onset, weight loss, and appendicular muscle mass were obtained. Each patient was classified as malnutrition or normal by GLIM criteria and three other biochemical indices (CONUT, PNI, and GRNI). Sarcopenia index (SI) as creatinine to cystatin C ratio was also calculated. Within 1 year, 80 (11.1%) patients died. In ROC curve we identified a SUCR value of 0.628 g/L as optimally discriminating surviving from dead. In low SUCR group more advanced HF, higher weight loss and catabolic components of weight trajectory (CCWT), more frequent under-nutrition by GLIM, and lower SI were observed. In multivariate analysis the independent predictors of low SUCR were SI, CCWT, and GNRI score. In conclusion: the risk of low SUCR was associated with a worse outcome. Low SUCR was associated with greater catabolism and sarcopenia but not with biochemical indices of malnutrition.

In this work, we, for the first time, manufactured a plasma-chemical reactor operating at a frequency of 0.11 MHz. The reactor allows for the activation of large volumes of liquids in a short time. The physicochemical properties of activated liquids (concentration of hydrogen peroxide, nitrate anions, redox potential, electrical conductivity, pH, concentration of dissolved gases) are characterized in detail. Antifungal activity of aqueous solutions activated by a glow discharge has been investigated. It was shown that aqueous solutions activated by a glow discharge significantly reduce the degree of presence of phytopathogens and their effect on the germination of such seeds. Seeds of cereals (sorghum and barley) and fruit (strawberries) crops were studied. The greatest positive effect was found in the treatment of sorghum seeds. Moreover, laboratory tests have shown a significant increase in sorghum drought tolerance. The effectiveness of the use of glow-discharge-activated aqueous solutions was shown during a field experiment, which was set up in the saline semi-desert of the Northern Caspian region. Thus, the technology developed by us makes it possible to carry out the activation of aqueous solutions on an industrial scale. Water activated by a glow discharge exhibits antifungicidal activity and significantly accelerates the development of the grain and fruit crops we studied. In the case of sorghum culture, glow-discharge-activated water significantly increases drought resistance.

The design of bioinspired synthetic inorganic molecular complexes is challenging, due to a lack of understanding of enzyme action and the degree to which that action can be translated into mimics. Exemplary of this challenge is the reversible conversion of formate into CO2 by formate dehydrogenase (FDH) enzymes with Mo/W centers in large molybdopterin cofactors. Despite numerous efforts to synthesize Mo/W-containing molecular complexes, none have been demonstrated to reproduce the full reactivity of FDH. Here, we carry out a large-scale, high-throughput screening study on all mononuclear Mo/W complexes currently deposited in Cambridge Structural Database (CSD). Using density functional theory, we systematically investigate the individual effects of metal identity, ligand identity, oxidation state, and coordination number on structural, electronic and catalytic properties. We compare our results on molecular complexes with quantum mechanics/molecular mechanics simulations on a representative FDH enzyme to further elucidate the influence of the enzyme environment. These comparisons reveal that the enzyme environment primarily influences the metal-local geometry, and these metal-local structural variations can improve catalysis. Through a series of computational mutations on molecular complexes, we extend beyond the CSD structures to further identify the limits of varied chalcogen and metal identity. This broad set and comparison reveal relatively little variation of electronic properties of the metal center due to the presence of the enzyme environment or changes in metal-distant ligand chemistry. Instead, these properties are found to be much more sensitive to the identity of the metal and the nature of the bound terminal chalcogen.

Cleavage of C3 to C3a and C3b plays a central role in the generation of complement-mediated defences. Although the thioester-mediated surface deposition of C3b has been well-studied, fluid phase dimers of C3 fragments remain largely unexplored. Here we show C3 cleavage results in the spontaneous formation of C3b dimers and present the first X-ray crystal structure of a disulphide-linked human C3d dimer. Binding studies reveal these dimers are capable of crosslinking complement receptor 2 and preliminary cell-based analyses suggest they could modulate B cell activation to influence tolerogenic pathways. Altogether, insights into the physiologically-relevant functions of C3d(g) dimers gained from our findings will pave the way to enhancing our understanding surrounding the importance of complement in the fluid phase and could inform the design of novel therapies for immune system disorders in the future.

GM3 Synthase Deficiency (GM3SD) is a neurodevelopmental disorder resulting from pathogenic variants in the ST3GAL5 gene, which encodes GM3 synthase, a glycosphingolipid (GSL)-specific sialyltransferase. This enzyme adds a single α3-linked sialic acid to the terminal galactose of lactosylceramide (LacCer) to produce the monosialylated ganglioside GM3. In turn, GM3 is extended by other glycosyltransferases to generate nearly all the complex gangliosides enriched in neural tissue. Pathogenic mechanisms that account for neural phenotypes associated with GM3SD are not known. To explore how loss of GM3 impacts neural-specific glycolipid glycosylation and cell signaling, GM3SD patient fibroblasts bearing one of two different ST3GAL5 variants were reprogrammed to induced pluripotent stem cells (iPSCs) and then differentiated to neural crest cells (NCCs). GM3 and GM3-derived gangliosides were undetectable in iPSCs and NCCs from both variants, while LacCer precursor levels were elevated compared to wildtype (WT). NCCs of both variants synthesized elevated levels of neutral lacto- and globo-series, as well as minor alternatively sialylated, GSLs compared to WT. Shifts in ceramide profiles associated with iPSC and NCC GSLs were also detected in GM3SD variants. Altered GSL profiles in the GM3SD cells were accompanied by dynamic changes in the cell surface proteome, protein O-GlcNAcylation, and receptor tyrosine kinase abundance. GM3SD cells also exhibited increased apoptosis and sensitivity to erlotnib, an inhibitor of epidermal growth factor receptor signaling. Pharmacologic inhibition of O-GlcNAcase increased protein O-GlcNAcylation and significantly rescued baseline and erlotnib-induced apoptosis. Collectively, these findings indicate broad effects on cell signaling during differentiation of GM3SD patient-derived iPSCs to NCCs. Thus, human GM3SD cells provide a novel platform to investigate structure/function relationships that connect GSL diversity to cell signaling, cell survival, and neural differentiation.

Patients with diabetes mellitus (DM) type 1 and 2 are at a higher risk of cognitive decline and dementia; however, the underlying pathology is poorly understood. Kynurenic acid (KYNA), endogenous kynurenine metabolite, displays pleiotropic effects, including a blockade of glutamatergic and cholinergic receptors. Apart from well-known glial origin, kynurenic acid is robustly synthesized in the endothelium and its serum levels correlate with homocysteine, a risk factor for cognitive decline. Studies in an experimental DM model suggest that a selective, hippocampal increase of the kynurenic acid level may be an important factor contributing to diabetes-related cognitive impairment. The aim of this study was to assess the effects of chronic, four-week administration of losartan, angiotensin receptor blocker (ARB), on the brain KYNA in diabetic rats. Chromatographic and rt-PCR techniques were used to measure the level of KYNA and the expression of genes encoding kynurenine aminotransferases, KYNA biosynthetic enzymes, in the hippocampi of rats with streptozotocin-induced DM, treated with losartan. The effect of losartan on KYNA synthesis de novo was also evaluated in vitro, in brain cortical slices. The hippocampal increase of KYNA content occurred in diabetic rats treated and nontreated with insulin. Losartan did not affect KYNA levels when administered per se to naïve or diabetic animals but normalized KYNA content in diabetic rats receiving concomitantly insulin. The expression of CCBL1 (kat 1), AADAT (kat 2), and KAT3 (kat 3) genes did not differ between analyzed groups. Low concentrations of losartan did not affect KYNA production in vitro. The neuroprotective effect of ARBs in diabetic individuals may be, at least partially, linked to modulation of KYNA metabolism. The ability of ARB to modulate synthesis of KYNA in diabetic brain does not seem to result from changed expression of genes encoding KATs. We propose possible involvement of angiotensin AT4 receptors in the observed action of losartan.

We performed in-situ X-ray diffraction measurements of polycrystalline cubic silicon nitride samples at high temperatures under atmospheric pressure and at simultaneous high-pressure-temperature conditions. In air, cubic silicon nitride survives metastably up to 1733 K without oxidation. The temperature dependence of the thermal expansion coefficient was determined to be α(T) = a1 + a2T – a3T−2 where a1 = 1.34(6) × 10−5 K−1, a2 = 5.06(44) × 10−9 K−2, and a3 = 0.20(10) K. Using all the experimental data obtained under atmospheric and high pressures, a complete set of parameters of the high-temperature third-order Birch Murnaghan equation of state was obtained: K300,0 = 303(5) GPa, K′300,0 = 5.1(8), and (∂KT,0/∂T)P = –0.017(1) GPa K−1, where K0, K′0, and (∂KT,0/∂T)P are the isothermal bulk modulus, its pressure derivative, and its temperature derivative, respectively. These parameters are necessary to calculate the equilibrium phase boundary between the β and cubic phases in silicon nitride.

Search for the “structure-reactivity” correlations of the thermally stimulated reactions of cinnamic acids on the surface of catalysts is important for the development of pyrolytic conversion methods of lignocellulosic biomass components into products with high added value, in particular, into styrene. Therefore, in this work, the kinetics of pyrolysis of the reaction series of para-substituted derivatives of trans-cinnamic acid (Н, -СН 3 , -С(СН 3 ) 3 , -ОСН 3 , -F) on the surface of nanosized silica by the method of thermoprogrammed desorption mass spectrometry (TPD MS) was investigated. The products of pyrolytic reactions on the surface are identified ‒ the corresponding, para-substituted vinylbenzenes, phenylacetylenes, and phenylketenes. The kinetic parameters of the decarboxylation, ketenization, and decarbonylation reactions were calculated. The correlations "structure-reactivity" between the kinetic parameters (activation energy) and thermodynamic parameters (Hammett substituents constants) have been obtained, which indicate that electron-donor substituents reduce the activation energy of these three reactions while the electron-acceptor substituents increase it. That is, in the transitional state of the rate-limiting step, a decrease in the electron density is observed at the reaction center. The calculated values of the reaction constants ρ show that the studied reactions dependent on the sensitivity to the effect of the substituents are placed in a sequence: decarbonylation> decarboxylation> ketenization. The formation of phenylacetylenes is the most sensitive to structural changes in the molecule and proceeds through the most polar transition state.

Pyrones comprise a structurally diverse class of compounds. Although they are widespread in nature, their specific physiological functions remain unknown in most cases. We recently described that triketide pyrones mediate the sulfotransfer in caprazamycin biosynthesis. Herein, we report the identification of conexipyrones A-C, three previously unrecognized tetra-substituted α-pyrones, from the soil actinobacterium Conexibacter woesei. Insights into their biosynthesis via a type III polyketide synthase were obtained by feeding studies using isotope-enriched precursors. In vitro assays employing the genetically associated 3'-phosphoadenosine-5'-phosphosulfate (PAPS)-dependent sulfotransferase CwoeST revealed conexipyrones as the enzymes' genuine sulfate acceptor substrates. Furthermore, conexipyrones were determined to function as sulfate shuttles in a two-enzyme assay, because their sulfated derivatives were accepted as donor molecules by the PAPS-independent arylsulfate sulfotransferase (ASST) Cpz4 to yield sulfated caprazamycin intermediates.

In continuation of a series of studies on a new generation of microbathogen sorbents based on electrically conductive polymers: polyaniline and polypyrrole, the possibility of regeneration and reuse of polypyrrole for water purification through the sorption of bacteria and viruses from aqueous media was investigated. For example, the binding of polypyrrole and polypyrrole modified with silver nanoparticles of the pandemicinfluenza virus strain A/South Carolina / 02/2010 (H1N1) pdm09 and epidemiologically and pathogenetically significant bacteria: Staphylococcus aureus (Gram +) and Shigella flexneri (Gram -) shown: During primary sorption, sorbents almost completely neutralize concentrated virus solutions (GAE 512) and epidemically dangerous solutions of bacteria with CFU 2 * 105.• Sorbent regeneration consists of a short-term warming up in an aquatic environment with subsequentexposure to ultrasound.• Secondary sorption of micropathogens leads to almost complete removal of Staphylococcus, and a significant decrease in the concentration of Shigella and viruses The results indicate the possibility of repeated, and possibly repeated use of sorbents. The advantages of these sorbents in their use for the purification of aqueous media from biological contaminants are: 1. theability to effectively sorb a wide range of micropathogens: both bacteria and viruses; 2. suppression of the infectious activity of associated micropathogens, i.e. complete infectious safety of the sorbent + pathogen complexes; 3. possibility of regeneration and repeated use of the sorbent. At the same time, the sorbentsthemselves are non-toxic and relatively cheap.

Infrared-reflection and transmission spectroscopy was used to study the mineral composition of a shear fracture surface in a core recovered from a well in the seismically active Koyna-Varna region in western India, which is associated with reservoir-induced seismicity. Methods for conducting comprehensive experimental studies of the mineral composition of shear fracture surfaces in rocks are described. The experiments demonstrated the wide possibilities of these techniques and allowed us to obtain new results on shear fractures, which are important for further research on the physics of earthquake foci. It is established that the shear fracture surface is a three-layer structure. The upper layer contains only glauconite nanocrystals. The layer beneath it contains, in addition to glauconite, calcite and montmorillonite crystals. The total thickness of these layers is about 600 µm. Below these layers is the host rock, which contains calcite, dolomite, and glauconite. The number of illite–smectite layers in glauconite nanocrystals has been determined. The upper layer contains nanocrystals consisting of ∼30 layers. In the second layer, the crystals of this mineral contain ∼25 layers. Finally, in the host rock, glauconite crystals make up ∼20 layers.

Methyl transferases (MTases) are a well-studied class of enzymes for which competing enzymatic enhancement mechanisms have been suggested, ranging from structural methyl group CH···X hydrogen bonds (HBs) to electrostatic- and charge-transfer-driven stabilization of the transition state (TS). We identified all Class I MTases for which reasonable resolution (2.0 Å) crystal structures could be used to form catalytically competent ternary complexes for multiscale (i.e., quantum-mechanical/molecular-mechanical or QM/MM) simulation of the S

Modern thermodynamic assessment studies of multicomponent systems typically employ the Compound Energy Formalism (CEF) to describe phases of variable composition, which may show effects of chemical ordering. In CEF, the ordering is described by splitting a crystallographic site in which several components can substitute for each other into subsites (sublattices) and by allowing fractional occupancies of these subsites to vary. This type of component redistribution over subsites (sublattices) is classified in solid solution theories as long-range order (LRO). A well-known shortcoming of CEF is the absence of a direct description of the effects of short-range order (SRO), which do not involve a redistribution of components between sublattices, but reveal themselves in various modes of clustering. Here we show that SRO can be taken into account within CEF as an additional (fictive) LRO effect driven by an extra negative excess enthalpy term. We argue that the mathematical form of this term should be constrained such that it ensures its vanishing both in low- and high-temperature limits. Including such a term into CEF allows a significant improvement in the description of phase relations in the system of calcite-magnesite, CaCO3-MgCO3. The modified CEF model with SRO emulation is made available in the GEM-Selektor software.

The aim of this study was to determine the relationship between the surface textural features of wheat kernels and the quantity of DNA of fungi of the genus Fusarium. The images of kernels of four wheat cultivars were acquired on the ventral side and dorsal side with a flatbed scanner. Fungal DNA was quantified with specific TaqMan probes for F. culmorum and F. graminearum sensu stricto. In images acquired on the ventral side, the quantity of fungal DNA was most highly correlated with texture aHVariance from channel a in cultivar 1 (0.86), with one texture from channel R in cultivar 2 (0.80), with one texture from channel L (0.69) and one texture from channel X (− 0.69) in cultivar 3, and with one texture from channel b in cultivar 4 (0.70). In the images acquired on the dorsal side, the quantity of fungal DNA was most highly correlated with one texture from channel V in cultivar 3 (0.89), two textures from channel B in cultivar 1 (− 0.74), one texture from channel R (− 0.77), and two textures from channel Z (0.77) in cultivar 2, and one texture from channel a and textures from channel S (0.74) in cultivar 4. The results of this study indicate the usefulness of image analysis for detecting fungal infections in grain. The findings make a valuable contribution to the development of rapid, inexpensive, non-invasive, and effective methods for preliminary screening of infected and healthy kernels and for evaluating the severity of fungal infections in kernels.

β-N-Acetylhexosaminidases (EC 3.2.1.52) are typical of their dual activity encompassing both N-acetylglucosamine and N-acetylgalactosamine substrates. Here we present the isolation and characterization of a selective β-N-acetylhexosaminidase from the fungal strain of Aspergillus versicolor. The enzyme was recombinantly expressed in Pichia pastoris KM71H in a high yield and purified in a single step using anion-exchange chromatography. Homologous molecular modeling of this enzyme identified crucial differences in the enzyme active site that may be responsible for its high selectivity for N-acetylglucosamine substrates compared to fungal β-N-acetylhexosaminidases from other sources. The enzyme was used in a sequential reaction together with a mutant β-N-acetylhexosaminidase from Talaromyces flavus with an enhanced synthetic capability, affording a bioactive disaccharide bearing an azido functional group. The azido function enabled an elegant multivalent presentation of this disaccharide on an aromatic carrier. The resulting model glycoconjugate is applicable as a selective ligand of galectin-3 - a biomedically attractive human lectin. These results highlight the importance of a general availability of robust and well-defined carbohydrate-active enzymes with tailored catalytic properties for biotechnological and biomedical applications.

It has been shown that adsorption of natural antioxidants, such as 3-phenylpropenic (cinnamic), 3-(4-hydroxyphenyl)propenic (coumaric), and 3-(3-methoxy-4-hydroxyphenyl)propenic (ferulic) acids, on the surface of cerium dioxide is characterized by S-type isotherms, while adsorption of 3-(3,4-dihydroxyphenyl)propenic (caffeic) acid is described by an H-type isotherm. A linear correlation between adsorption values and hydrophobicity parameter logP has been found in initial regions of the S-type isotherms, with such correlation being typical for parallel orientation of adsorbed molecules relative to an adsorbent surface. The maximum adsorption values (≈2.9 × 10–4 mol/g), as well as dissociation constants (pKCOOH = 4.4–4.6), are almost identical for all acids, thereby suggesting that adsorbate molecules are predominantly bound to the adsorbent surface via carboxyl groups. The presence of hydroxyl groups in molecules of coumaric, ferulic, and caffeic acids widens the рН range of their adsorption as compared with cinnamic acid and promotes their oxidation on the cerium dioxide surface.