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Objective. To describe molecular and clinical characteristics of patients with high-grade recurrent ovarian carcinoma (HGOC) who had long-term responses to the poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib. Methods. This post hoc analysis pooled patients from Study 10 (NCT01482715; Parts 2A and 2B; n = 54) and ARIEL2 (NCT01891344; Parts 1 and 2; n = 491). Patients with investigator-assessed complete or partial response per RECIST were classified based on duration of response (DOR): long (≥1 year), intermediate (6 months to

Continuing the studies of proton sponge-based oligo(arylene-ethynylenes), the protonation of the para-ortho-para-linked trimer (POP-trimer) has been investigated. For the first time, selective mono...

Abstract Tris[2-(3′-cyanopropoxy)phenyl]phosphine oxide has been obtained via the alkylation of tris(2hydroxyphenyl)phosphine oxide with 4-bromobutyronitrile in the presence of K2CO3. The product structure has been elucidated by means of X-ray diffraction analysis. The terminal cyano groups in the obtained phosphine oxide have been converted into tetrazole rings via the click-reaction with NH4N3 to give a new hybrid tripodal propeller ligand, tris{2-[3′-(tetrazol-5′′-yl)propoxy]phenyl}phosphine oxide. Palladium(II) complexes of the prepared ligand and its short-linker analog, tris[2-(tetrazol-5′-ylmethoxy)phenyl]phosphine oxide, have been synthesized. Cytotoxicity of the ligands and their Pd(II) complexes has been studied.

In this work the effect of millimeter range electromagnetic waves (MM EMW) with the frequency 64.5 GHz on the complexes of Hoechst 33258 (H33258) with DNA and human serum albumin (HSA) has been studied by the methods of absorption and fluorescence spectroscopies. It was shown that the irradiation results in weakening of H33258 interaction with both macromolecules, which is connected with the fact that the frequency 64.5 GHz, being resonant for water, leads to the structurizing of water component around DNA and HSA, due to which the binding becomes weaker. This conclusion is based on the values of both binding constants and Stern–Volmer constants.

The fluorescent properties of products obtained by the hydrothermal treatment of organic raw materials are of great interest. Such products are usually colloidal stability in water, have low cytotoxicity, and high photostability. One of their advantages is a wide choice of starting materials and the relative simplicity of synthesis. The use of folic acid as a precursor for fluorescent nanostructures opens up the possibility of targeted imaging. This article shows a one-step synthesis of fluorescent nanostructures from folic acid and citrates. The effect of citrate concentration in the range from 0.05 to 2 mol/l on the optical properties of the synthesized structures is also studied.

Background and Aims Plant diseases caused by Pectobacterium atrosepticum are often accompanied by extensive rot symptoms. In addition, these bacteria are able to interact with host plants without causing disease for long periods, even throughout several host plant generations. There is, to date, no information on the comparative physiology/biochemistry of symptomatic and asymptomatic plant–P. atrosepticum interactions. Typical (symptomatic) P. atrosepticum infections are associated with the induction of plant responses mediated by jasmonates, which are one of the products of the lipoxygenase cascade that gives origin to many other oxylipins with physiological activities. In this study, we compared the functioning of the lipoxygenase cascade following typical and latent (asymptomatic) infections to gain better insight into the physiological basis of the asymptomatic and antagonistic coexistence of plants and pectobacteria. Methods Tobacco plants were mock-inoculated (control) or infected with the wild type P. atrosepticum (typical infection) or its coronafacic acid-deficient mutant (latent infection). The expression levels of the target lipoxygenase cascade-related genes were assessed by Illumina RNA sequencing. Oxylipin profiles were analysed by GC-MS. With the aim of revising the incorrect annotation of one of the target genes, its open reading frame was cloned to obtain the recombinant protein, which was further purified and characterized using biochemical approaches. Key Results The obtained data demonstrate that when compared to the typical infection, latent asymptomatic P. atrosepticum infection is associated with (and possibly maintained due to) decreased levels of 9-lipoxygenase branch products and jasmonic acid and increased level of cis-12-oxo-10,15-phytodienoic acid. The formation of 9-oxononanoic acid and epoxyalcohols in tobacco plants was based on the identification of the first tobacco hydroperoxide lyase (HPL) with additional epoxyalcohol synthase (EAS) activity. Conclusions Our results contribute to the hypothesis of the oxylipin signature, indicating that different types of plant interactions with a particular pathogen are characterized by the different oxylipin profiles of the host plant. In addition, the tobacco LOC107825278 gene was demonstrated to encode an NtHPL (CYP74C43) enzyme yielding volatile aldehydes and aldoacids (HPL products) as well as oxiranyl carbinols (EAS products).

The paper describes the synthesis of novel luminescent composite system, based on lithium-borate glass matrix with addition of rare-earth elements and yttrium-aluminum garnet finely divided powder. The new chemical composition of glass has been selected, composite’s fabrication technology was developed, the temperature conditions of glass and luminophore sintering as well. The spectral characteristics of the obtained luminescent composites are measured, and chromaticity diagrams are considered. The radiation spectra showed a maximum of about 560 nm, the maximum spectral intensity of the radiation is about 90 μw/cm2/nm. Powerful energy saving source of white light was produced.

In this work, a rather rare (morbidity of about 12 cases per 1 million of adult population per year) and interesting clinical case of the diagnosis of idiopathic pulmonary artery hypertension (IPAH) was described. This case was also known as Ayerza disease or AyerzaArilago syndrome. At the initial stage, this pathology was characterized by an asymptomatic course that caused certain difficulties in making a correct diagnosis. In general, this disease had a poor prognosis. The main cause of death was decompensated right ventricular failure. The occurrence of complications could be significantly reduced and the life quality of such patients could be improved by the timely diagnosis and correct approach.

Introduction : Hyaluronic acid (hyaluronan, HA) has become the most popular tool for improving the skin condition during aging, correcting wrinkles and other cosmetic defects. Objective : Analysis of the results of studies that reflect the pharmacogenomics of the synthesis, degradation, and reception of HA. Materials and methods : We searched for full-text publications in Russian and English in the E-Library, PubMed, Springer, Clinical keys, Google Scholar databases, using keywords and combined word searches (hyaluronic acid, hyaluronan, synthesis, degradation, reception, receptor, genetics), over the past decade. In addition, the review included earlier publications of historical interest. Despite our comprehensive searches of these commonly used databases and search terms, it cannot be excluded that some publications may have been missed. Results : The lecture examines: the role of ha in normal and aging human; genes involved in the synthesis ( HAS1, HAS2, HAS3 ), degradation ( HYAL1, HYAL2, HYAL3 ) and reception of ha ( CD44, HARE, RHAMM ); as well as the expression of their encoded proteins and enzymes in the skin. Conclusion : Expanding our knowledge of the pharmacogenomics of endogenous ha and increasing the exogenous HA drugs (used in anti-aging therapy and medical cosmetology) on the pharmaceutical market requires taking into account individual, including genetically determined, characteristics of the body of each individual patient to ensure an optimal balance of effectiveness/safety of exogenous HA from the point of view of personalized medicine

Abstract New polymer brushes with an ester backbone and poly(methyl methacrylate) side chains are synthesized by polycondensation and polymerization methods. The initiating groups are sulfonyl chloride groups laterally attached to the polyester chain. PMMA side chains are grafted by the ATRP method according to the “grafting from” multicenter macroinitiator strategy. The conditions for the polymerization processes in a controlled mode are selected, and the ways of targeted regulation of the degree of polymerization of methacrylate side chains are determined. Using the synthesized copolymers self-supporting films are obtained, and their physical and mechanical properties are studied.

Visual polythermal method in the bynary system of water-2-(2-butoxyethoxy) ethanol in the range of –25÷0° C the ice melting line is determined and the phase equilibria in the ternary system potassium nitrate–water–2-(2-butoxyethoxy) ethanol are studied in the range of 10.0–90.0° C. The ice melting line in the water–2-(2-butoxyethoxy) ethanol binary system is a flat, smooth line. This form of the melting line shows a hidden separation in liquid mixtures. It has been found that potassium nitrate salts out 2-(2-butoxyethoxy)ethanol from water-organic mixtures, and at 31.7° C in the ternary system of potassium nitrate–water–2-(2-butoxyethoxy)ethanol, separation begins. The compositions of the solutions corresponding to the critical solubility points at several temperatures have been determined. The isothermal phase diagrams of the ternary system at 10.0, 25.0, 30.0, 31.7, 35.0, 50.0, 90.0° С have been plotted. The distribution coefficients of 2-(2-butoxyethoxy) ethanol between the liquid phases of monotectic state have been calculated. It is shown that the effect of salting-out 2-(2-butoxyethoxy) ethanol from aqueous solutions with potassium nitrate increases with increasing temperature. The concentration of 2-(2-butoxyethoxy) ethanol in the organic phase of monotectics at 90.0° C is 90 wt.% with a distribution coefficient of 897.

Introduction. Patients with Alzheimer’s disease (AD) have reduced cerebral vascular density (VD), which impairs blood flow to neurons and may contribute to progression of AD. Earlier we showed that prior adaptation to intermittent hypobaric hypoxia (IHH) prevented memory loss and degeneration of cortical neurons in rats with experimental AD (EAD). The aim of this study was to test if IHH might prevent EAD-induced vascular rarefaction in rats. Materials and methods. EAD was induced with bilateral injection of neurotoxic beta-amyloid peptide fragment (A) (25–35) into n. basalis magnocellularis. IHH was simulated at a 4,000 m altitude, for 4 hours a day, for 14 days. Brain blood vessels were stained by transcardiac infusion of Indian ink; brain sections were stained with 0.3 % cresyl violet by Nissle method. Vascular density was assessed in the cortex and hippocampus using the Infinity Analysis Software. Results. In the EAD rats, VD was significantly decreased in the hippocampus (13.3±0.9 vs 17.8±1.0 in field of view, FOV, pConclusion. One of the mechanisms of AIH beneficial effect in AD-related neurodegeneration is preserving the capability for compensatory angiogenesis in brain.

Lysosomes are important sites for macromolecular degradation, defined by an acidic lumenal pH of ∼4.5. To better understand lysosomal pH, we designed a novel, genetically encoded, fluorescent protein (FP)-based pH biosensor called Fluorescence Indicator REporting pH in Lysosomes (FIRE-pHLy). This biosensor was targeted to lysosomes with lysosomal-associated membrane protein 1 (LAMP1) and reported lumenal pH between 3.5 and 6.0 with monomeric teal fluorescent protein 1 (mTFP1), a bright cyan pH-sensitive FP variant with a pKa of 4.3. Ratiometric quantification was enabled with cytosolically oriented mCherry using high-content quantitative imaging. We expressed FIRE-pHLy in several cellular models and quantified the alkalinizing response to bafilomycin A1, a specific V-ATPase inhibitor. In summary, we have engineered FIRE-pHLy, a specific, robust, and versatile lysosomal pH biosensor, that has broad applications for investigating pH dynamics in aging- and lysosome-related diseases, as well as in lysosome-based drug discovery.

In this study, we considered thermal processes in liquid and frozen water droplets with added dye molecules and metal nanoparticles at the moment of supercontinuum generation. We studied optical non-linear processes in a water droplet with a diameter of 1.92 mm, cooled (+2 °C) and frozen to -17 °C, with eosin molecules and ablative silver nanoparticles upon femtosecond laser treatment.When we exposed a cooled water droplet and a piece of ice containing eosin molecules and ablative silver nanoparticles to a femtosecond laser beam (l = 1030 nm), we recorded two-photon fluorescence, enhanced by plasmon processes. Also, supercontinuum generation took place, with a period of decay t = 0.02 s. The geometry of non-linear large -scale self-focusing (LLSS ~ 0.45–0.55 mm) was studied. The value of microscale self-focusing (LSSS ~ 0.1 mm) of SC radiation in the laser channel was determined experimentally. The study shows that the energy dissipation in the SC channel increases when the thermal non-linearity exceeds the electronic non-linearity. We modelled the thermal processes and determined the temperaturegradient of the heating of the frozen droplet exposed to a femtosecond pulse. Based on the experimental data, the heat wave propagation velocity was calculated to be n = 0.11 m/s.

Pregnancy in patients with advanced chronic kidney disease (CKD) is associated with a high risk of adverse outcomes for the mother and the fetus, but data on the characteristics of the course of pregnancy in these women is limited.To analyse of the course and outcomes of pregnancy in patients with CKD stages 3a4.Thirty five pregnant women with CKD stages 34 were included: 3a 12 (34.3%) patients, stage 3b 10 (28.6%), stage 4 13 (37.1%).Proteinuria, serum creatinine, blood pressure in dynamics, the presence of a physiological response were investigated. Pregnancy management included blood pressure correction, antianemic, antiplatelet, anticoagulant therapy, prevention and treatment of urinary infection, correction of metabolic disorders. All pregnant women had proteinuria of varying severity, which increased towards the end of pregnancy. Seventeen (51.5%) patients had hypertension, successfully corrected with antihypertensive drugs. The average delivery term was 34.6 weeks. Preeclampsia developed in 14 (42.4%) cases, an inverse relationship was found between the presence of a physiological response and preeclampsia (p=0.009; rs=-0.463). All children were born alive and viable. After delivery in patients with CKD 3a creatinine values returned to the pre-gestational level, in patients with grade 3b and 4 progression of CKD was noted.A favorable pregnancy outcome in women with late stages of CKD is possible with constant monitoring by a multidisciplinary team of doctors with mandatory monitoring of renal function, proteinuria, blood pressure, coagulation, markers of preeclampsia and indicators of fetal health. It was proposed to consider the physiological response of the kidneys to pregnancy as a predictor of a favorable outcome.Обоснование. Беременность у пациенток с поздними стадиями хронической болезни почек (ХБП) сопряжена с высоким риском неблагоприятных исходов для матери и плода, однако данные об особенностях течения беременности у этих женщин ограничены. Цель. Проанализировать течение и исходы беременности у пациенток с ХБП стадий 3а4. Материалы и методы. Включены 35 беременных с ХБП стадий 34: со стадией 3а 12 (34,3%) пациенток, стадией 3б 10 (28,6%), стадией 4 13 (37,1%). Результаты. Исследованы в динамике протеинурия (ПУ), креатинин крови, артериальное давление (АД), наличие физиологического ответа почек на беременность. Ведение беременности включало в себя коррекцию АД, антианемическую, антиагрегантную, антикоагулянтную терапию, профилактику и лечение мочевой инфекции, коррекцию метаболических нарушений. Все беременные имели ПУ различной выраженности, которая увеличилась к концу беременности. У 17 (51,5%) пациенток отмечена АГ, успешно корригированная антигипертензивными препаратами. Средний срок родоразрешения составил 34,6 нед. Преэклампсия (ПЭ) развилась у 14 (42,4%) пациенток. Обнаружена обратная связь между наличием физиологического ответа и ПЭ (p=0,009; rs=-0,463). Все дети родились живыми и жизнеспособными. После родоразрешения у пациенток с ХБП 3а показатели креатинина крови вернулись на догестационный уровень, у пациенток со стадиями 3б и 4 отмечалось прогрессирование ХБП. Заключение. Благоприятный исход беременности у женщин с поздними стадиями ХБП возможен при постоянном наблюдении мультидисциплинарной командой врачей с обязательным контролем показателей функции почек, ПУ, АД, коагулограммы, маркеров ПЭ и показателей состояния плода. Предлагается рассматривать физиологический ответ на беременность как предиктор благоприятного исхода.

New zinc(II) compounds with cyclobutane-1,1-dicarboxylic acid (H2Cbdc) anions and calcium [CaZn(Cbdc)2(H2O)3]n (I) and barium [BaZn(Cbdc)2(H2O)2]n (II) cations were obtained. According to X-ray diffraction data (CIF files CCDC nos. 2055176 (I), 2055177 (II)), compounds I and II are coordination polymers in which zinc atoms are connected by bridging and chelating-bridging acid dianions to form 2D architectures with a square lattice topology. Alkaline earth metal atoms do not affect the dimensionality of compound packing.

It was advised to use aliphatic, cycloaliphatic, aromatic petroleum resins and their derivatives obtained by oxidation of resins with a mixture of hydrogen peroxide and acetic acid as bitumen polymer-modifiers. Petroleum resins were obtained by ionic polymerization of unsaturated compounds of liquid pyrolysis products under the influence of titanium tetrachloride-diethylaluminium chloride catalyst. It was established that the maximum values of adhesion of modified bitumen coatings to metal substrates, corresponding to the minimum values of the wetting angle of the metal surface coated with solutions of bitumen compositions with different content of the polymer modifier were achieved using oxidized resins. All modified bitumen coatings have low water absorptivity and high acid resistance, alkali resistance and salt resistance, which allow using them as protective coatings

The cyclocondensation of cross-conjugated enynones, dienynones, and trienynones (easily available due to low-cost starting compounds) with arylhydrazines leads to the regioselective synthesis of pyrazole derivatives (dihetaryl-substituted ethens, buta-1,3-diens, and hexa-1,3,5-triens) or results in 4,5-dihydro-1H-pyrazoles in good yield. The reaction path is controlled by the character of the substituent in enynone: the pyrazoles are obtained from the reaction of substrates that contain five-membered heteroaromatic substituents with arylhydrazines, and the 4,5-dihydro-1H-pyrazoles are obtained from the reaction of 1,5-diphenylpent-1-en-4-yn-3-one with arylhydrazines consistently. Despite the presence of a substituent, cyclocondensation of 2-hydrazinylpyridine with all of examined cross-conjugated enynones leads to the formation of pyrazoles. The reaction does not require special conditions (temperature, catalyst, inert atmosphere). The cyclocondensation pathways are determined by the electronic effect of an electron-rich five-membered heteroaromatic ring in the substrate. The synthesis allows use of various substituents and functional groups in enynone and hydrazine. The present method features high yields and simplicity of the product purification. The obtained pyrazoles possess fluorescent properties with a quantum yield up to 31%.

Antidepressant activities of the original compounds GSB-106 [bis(N-monosuccinyl-L-seryl-L-lysine) hexamethylenediamide], a mimetic of the fourth loop of brain-derived neurotrophic factor (BDNF); GML-3(N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide), a ligand of 18 kDa translocator protein (TSPO); and GZK-111 (N-phenylacetylglycyl-L-proline ethyl ester), a substitute dipeptide that is biotransformed into the neuropeptide cyclo-L-prolylglycine that affects AMPA receptors; were previously revealed at V. V. Zakusov Institute of Pharmacology in experimental models of the depressive state caused by unescapable stress conditions. The present article studied the antidepressant effects of GSB-106, GML-3, and GZK-111 in an inflammatory model of the depressive state induced by lipopolysaccharide (LPS) in male C57Bl/6 mice with an assessment of anhedonia based on the consumption of sucrose solution. LPS in a single dose of 0.5 mg/kg intraperitoneally (i.p.) caused a marked decrease of 39% (p ≤ 0.01) in the consumption of 1% sucrose solution as compared to the control group. GSB-106 administered perorally at a dose of 0.5 mg/kg 24 h after LPS increased by 20% (p ≤ 0.05) sucrose consumption reduced by LPS in mice. GML-3 administered once perorally at doses of 0.5 and 1.0 mg/kg increased sucrose consumption by 29 and 21% (p ≤ 0.01), respectively. GZK-111 administered once i.p. at a dose of 1.0 mg/kg increased sucrose consumption by 17% (p ≤ 0.05). The obtained data confirmed the antidepressant properties of GSB-106, GML-3, and GZK-111.

Relevance. Data on the efficacy of endocrine and chemotherapy regimens in patients with hormone-resistant metastatic breast cancer (mBC) after progression with CDK4/6 inhibitors are limited; the search for an effective therapy regimen in this clinical situation is an urgent task of clinical oncology. Aim. Evaluate the efficacy and safety of eribulin therapy in patients with HR+/HER2- mBC after progression with CDK4/6 inhibitors; compare the results of the Russian study and the EMPOWER observational study in the USA. Materials and methods. The Russian observational study included 54 patients (pts) with HR+/HER2- mBC, who were treated with eribulin after CDK4/6 inhibitors in 24 Russian Cancer hospitals. The median age of pts was 56 years; 75.9% of them had recurrent BC, 24.1% de novo BC stage IV; 51.9% of pts had progression with CDK4/6 inhibitors in the first 6 months of therapy (primary endocrine resistance); 48.1% of patients had progression in the period from 6 to 38 months; 89.1% had visceral site of metastases (liver MTS 65.5%, lung MTS 52.8%, brain MTS in 7.5%). Eribulin was used after anthracyclines and taxanes in 94.4% of cases. The efficacy and safety of eribulin therapy in patients with HR+/HER2- mBC after progression with CDK4/6 inhibitors was studied, as well as subgroup analysis according to age, sites of metastasis, and previously treatment options. Results. Eribulin was prescribed in the standard regimen of 1.4 mg/m2 on days 1 and 8, the interval between cycles was 21 days, the number cyclys of chemotherapy was 144 (median 8, the mean number of cycles 10.5). With a median follow-up of 11.5 months (from 3 to 36 months), 30 patients (55.6%) continue therapy with eribulin at present; therapy was cancelled in 24 patients due to progression in 22 (40.7%) cases, and due to intolerable toxicity in 2 (3.7%) patients. The maximum response to eribulin therapy included partial response (in 11 cases, 24.4%), stable disease (in 30 cases, 66.7%) and progression in 4 (8.9%) patients. Median PFS with eribulin therapy was 10.0 months; the 6-month, 1-year, and 2-year PFS were 79.5%, 44.8% and 26.5%, respectively. Eribulin therapy was equally effective in different subgroups (p0.05) and did not depend on the age of patients, the previously received treatment, the presence of visceral MTS and liver damage. The best response to chemotherapy with eribulin was observed in lung metastases: median PFS 24 months vs 9.1 months, p=0.056. The safety profile was favorable; adverse events were registered in 34.5% of patients, which required dose adjustment in 18.5% of cases. With a median follow-up of 11.5 months, 92.6% of patients remain alive. Conclusion. Eribulin has demonstrated high efficacy and favorable safety profile in hormone-resistant HER2- mBC in patients with progression when receiving CDK4/6 inhibitor.

The worldwide rapid spread of the COVID-19 disease necessitates the search for fast and effective treatments. The repurposing of existing drugs seems to be the best solution in this situation. In this study, the molecular docking method was used to test 248 drugs against the receptor-binding domain (RBD) of spike glycoprotein of SARS-CoV-2, which is responsible for viral entry into the host cell. Among the top-ranked ligands are drugs that are used for hepatitis C virus (HCV) treatments (paritaprevir, ledipasvir, simeprevir) and a natural biflavonoid amentoflavone. The binding sites of the HCV drugs and amentoflavone are different. Therefore, the ternary complexes of the HCV drug, amentoflavone, and RBD can be created. For the 5 top-ranked ligands, the validating molecular dynamics simulations of binary and ternary complexes with RBD were performed. According to the MMPBSA-binding free energies, the HCV drugs ledipasvir and paritaprevir (in a neutral form) are the most efficient binders of the RBD when used in combination with amentoflavone. Communicated by Ramaswamy H. Sarma

The adsorption activity of soils largely depends on their composition and properties and, first of all, on the specific surface area and energy potential of clay particles. For the formation of "specified" properties, including adsorption, various methods of clay activation have been developed: thermal, ultraviolet, ultrasonic, mechanical, acidic, alkaline. However, despite the published data, the issues of the influence of heat treatment on the formation of the clays properties, including adsorption ones, have not been sufficiently studied. In this regard, an assessment was made of the of clays thermal activation effect on their adsorption activity for the methylene blue dye. Experimental and theoretical studies have shown that the change in the adsorption activity of clays is associated with the degree of their heat treatment. When clays are treated with temperatures up to 200° C, energy centers on the surface of structural elements are activated, which leads to an increase in the clays adsorption in terms of methylene blue by 12–24%; with an increase in the processing temperature of clays to 450–960° С, the processes of their (clays) structural transformation change, which reduces the adsorption activity of clays by 11–16 times. In addition, the influence of the clays saturation degree with water vapor on their adsorption activity has been established. During the heat treatment of clays and their partial saturation with water vapor, water molecules occupy part of the energy centers on the surface of the particles; therefore, the particles have a sufficient energy potential, which is realized in the form of high values of their adsorption to methylene blue. During the clays thermal treatment and their complete saturation with water vapor, the charges on the surface of the particles are mostly compensated by water molecules. Water molecules, entering the inter-package space, compensate charges on the surface of the packages and minerals, which are realized in the form of clay swelling processes. Swelling processes lead to an increase in the size of structural elements, which manifests itself in the form of a decrease in the specific surface of clays. Therefore, clays completely saturated with water vapor are less active adsorption than clays partially saturated with water vapor.

Lung cancer is among the most common malignant diseases in Russia. In 80–90%, its morphological type is nonsmall cell lung cancer. Stage IV primary advanced lung cancer is diagnosed in 41% of patients. Median overall survival in stage IV patients receiving chemotherapy is 7–12 months. Treatment for stage IV lung adenocarcinoma is based on predictive and prognostic factors. Chemotherapy, chemoimmunotherapy or immunotherapy is recommended in the absence of driver mutations in the EGFR (exons 19 and 21) and BRAF genes, ALK and ROS1 translocations.Platinum- based regimens are preferred as the fi rst-line chemotherapy. Stabilization, partial or complete response after 4–6 chemotherapy cycles allow for maintenance therapy with pemetrexed to increase progression-free survival and overall survival.Purpose of the study. Using a real clinical case, to confirm the efficacy of pemetrexed in the treatment for stage IV lung adenocarcinoma in the second-line therapy in combination with platinum- based agents and in a maintenance therapy.A clinical case of a patient with central cancer of the lower lobe of the right lung St IV (cT3N2M1) is presented; the first treatment stage involved 3 cycles of the fi rst-line polychemotherapy (paclitaxel 175 mg/m² intravenously on day 1, carboplatin AUC 5 intravenously on day 1, every 3 weeks), and 6 cycles of the second-line polychemotherapy (pemetrexed 500 mg/m2 intravenously on day 1, cisplatin 75 mg/m² intravenously on day 1 of the 21-day cycle). Stabilization of the disease was achieves, and 20 cycles of maintenance therapy with pemetrexed followed; the achieved effect persisted and was confirmed by spiral X-ray computed tomography every 3 months. The objective effect of anticancer therapy was assessed according to the RECIST 1.1 criteria. It took 20 months from the beginning of the second-line anticancer medical therapy to progression, and 16 months from the start of maintenance pemetrexed to progression. The safety profile was satisfactory, and the ECOG performance status 0 maintained. Only one adverse effect, degree I general weakness, was noted, which did not have a negative impact on the patient's quality of life.

The present work shows results of studying acid-base properties of the surface by the methods of pH-metry and Hammett of amorphous silicon dioxide from rice husks and straw obtained by various schemes: oxidative firing; oxidative roasting with preliminary treatment with 0.1 M hydrochloric acid solution; precipitation from alkaline solutions. The samples obtained by the thermal method contain impurities of alkali, alkaline earth metals, aluminum, and aluminum and practically do not contain water. The composition of the deposited samples contains a small fraction of impurities (0.05%) and water - from 8.2 to 10.2%. The pH value of an aqueous suspension of silicon dioxide has a neutral, alkaline or acidic environment depending on the content of impurities of alkali and alkaline earth metals. Distribution of acid-base centers on the surface of the samples is nonmonotonic and heterogeneous, and manifests itself in discreteness with a fairly clear differentiation of sorption bands with maxima of different intensities corresponding to a certain pKa value. Distribution curves of the adsorption centers of the indicators on the surface of the samples of amorphous silicon dioxide are similar to each other. There are four types of active centers on their surface: acidic Lewis (pKa + 16.80), Bransted main (pKa +7.15 and +9.45) and acid (pKa + 2.50). The number of active centers depends on the preparation scheme and is determined by the content of impurity elements and water in the oxide samples.

The intensity of delayed fluorescence and kinetics processes of eosin molecules in a hanging drop of water solution with ablative silver nanoparticles and without them during phase change have been...

A new ionic cyclopropanation process involving the addition of diazo esters to donor-acceptor cyclopropanes (DAC) activated by GaCl3 has been developed. The reactions occur via 1,2-zwitterionic gallium complexes with elimination of nitrogen in all cases to give 1,1,2,3-tetrasubstituted cyclopropanes as the main products. Also, a number of related processes with the formation of various polysubstituted cyclopropanes, alkenes, and cyclobutanes, including products of multiple diazo ester addition, have been developed. Obtained by the developed method tetrasubstituted cyclopropanes are activated cyclopropanes such as DAC and can be used for further synthesis in this capacity. Their new reaction with benzaldehyde promoted by TiCl4 and involving one of the additional functional groups has been demonstrated, which leads to five-membered lactones. The mechanisms of the occurring processes, as well as the structures and stereochemistry of a rich range of products formed, are discussed in detail.

The new anionic dimethylmalonate complex {Ni36(H2O)12(OH)20(HMe2Mal)(Me2Mal)29@ [Mg(H2O)6]}5– (Me2Mal2– is the dimethylmalonate anion) containing the internal aquated [Mg(H2O)6]2+ ion and the external [Mg3(OH)(H2O)10(C2H5OH)3]5+ cation was prepared by hydrothermal synthesis. The crystalline compound isolated from the reaction mixture and characterized by X-ray diffraction had the formula [Mg3(OH)(H2O)10(C2H5OH)3]{Ni36(H2O)12(OH)20(HMe2Mal)(Me2Mal)29@[Mg(H2O)6]}·25H2O (I) (CIF file CCDC no. 2038910). The new anionic complex {Ni36(H2O)12(OH)19(O)(Cbdc)30@[Na(H2O)6]}8– (Cbdc2– is the cyclobutane-1,1-dicarboxylate anion) containing the internal aquated [Na(H2O)6]+ ion and outer-sphere tetrabutylammonium cations was prepared from an ethanol–acetonitrile solution. The crystals isolated from the reaction mixture were characterized by X-ray diffraction and were described the formula (NBu4)8{Ni36(H2O)12(OH)19(O)(Cbdc)30@[Na(H2O)6]} (CIF file CCDC no. 2038909) (II). It was found that the magnetic behavior of complex I is due to competing ferro- and antifferromagnetic exchange interactions between paramagnetic nickel(II) ions.

The ApGGP1 coding sequences, encoding GDP-L-galactose phosphorylase, the key enzyme of the L-galactose pathway of vitamin C biosynthesis, have been identified and characterized in a wide range of leek (Allium porrum L.) cultivars, differing in vitamin C content. Analysis of ApGGP1 polymorphism in 35 leek cultivars revealed 29 allelic variants, corresponding to 11 variants of the ApGGP1 protein. It was found that leek and other Allium species ApGGP1 sequences contained a specific C-terminal motif (50 a.a.). The ApGGP1 expression pattern was determined in various leek organs and tissues (roots, stem, white pseudo stem, and green leaves (young and mature)). ApGGP1 transcripts were detected in all analyzed tissues. The maximum expression level was observed in leaves, and the minimum was in stem. The level of gene expression in roots (non-photosynthetic tissue) was quite high and comparable with that in young green leaves.

The title compound, C23H19BrN4O2, is a product of an azo coupling reaction between 3,4-bis(4-methoxyphenyl)imidazole and 4-bromophenyldiazonium tetrafluoroborate. Its crystal structure was determined using data collected at 120 K. The molecule adopts a trans configuration with respect to the N=N double bond. The imidazole and aryl rings attached to the azo linkage are coplanar within 12.73 (14)°, which indicates significant electron delocalization within the molecule. In the crystal, the molecules form centrosymmetric dimers via pairs of N—H...O hydrogen bonds.

A new family of protic ammonium ionic liquids (ILs) with various inorganic anions was synthesized from bio-derived 5-HMF. Starting with cellulose biomass, a complete preservation of the C₆ unit was achieved throughout the synthetic sequence (no carbon loss). Evaluation of green metrics showed a significant advantage of the developed bio-derived pathway to access ILs from a natural renewable source, depending on feasible routes to 5-HMF manufacturing. The reduced number of synthetic steps and availability of the starting materials were the key advantages. Experimental physicochemical and biological studies, as well as computational modeling revealed a unique multifunctional intrinsic organization of these bio-derived ILs. The nature of interactions between the cations and anions of the novel ILs was mapped at the molecular level. The substituents in the cationic core and the nature of the original building blocks had a prominent impact on cytotoxicity of the novel ILs. The obtained results suggest possible sustainable applications of the least toxic ILs, while the regulation of biological activity of the ILs via the corresponding structural adjustments can find biological and medicinal applications. The 5-HMF-derived IL with a sulfate anion demonstrated potentially useful properties in dissolution of microcrystalline cellulose.

BACKGROUND: Less than a year has passed since the start of the new coronavirus infection COVID-19 pandemic caused by SARS-CoV-2 First published research results demonstrate a frequent increase in glycemia in patients without previously diagnosed carbohydrate metabolism disorders A possible relationship between the carbohydrate metabolism state and the course of COVID-19 is considered AIM: To identify the incidence of known and newly diagnosed diabetes mellitus (DM) in hospitalized patients with COVID-19 and evaluate the relationship between glycated hemoglobin (HbA1c), inflammation markers and infectious disease severity METHODS: A single-center, cross-sectional, retrospective study included 155 patients with confirmed COVID-19 and bilateral polysegmental viral pneumonia hospitalized in the Endocrinology Research Centre, Russian Federation Diagnosis of carbohydrate metabolism disorders was based on the HbA1c level, blood glucose level at admission (BGA) and fasting plasma glucose (FPG) Patients were divided into 2 groups: without the previously diagnosed DM (n=129, 83 3%) and with known history of DM (n=26, 16,7%) Patients without previously diagnosed DM were divided into subgroups according to HbA1c levels: ≤6,0% (Group A), >6,0% HbA1c

The thermostable endo-processive xyloglucanase MtXgh74 from Myceliophthora thermophila was used to study the influence of aromatic amino acids in the catalytic cleft on the mode of action and the ability of enzyme to reduce xyloglucan viscosity. The enzyme derivative Mut I with mutations W64A/W67A in the "negative" subsites of the catalytic cleft resulted in a 5.5-fold increase of the Km value. Mut I produced oligosaccharides of various lengths in addition to xyloglucan building blocks. The W320A/W321A substitutions in the "positive" subsites of the mutated enzyme Mut II catalytic cleft increased the Km value 54-fold and resulted in an endo-dissociative mode of action. The ability of Mut II to reduce the viscosity of xyloglucan at 50 °C was much better than that of other MtXgh74 variants. Besides, Mut II efficiently reduced viscosity of a natural substrate, the pulp of xyloglucan-containing tamarind seed flour. The Km, Vmax, and kcat values and viscosity reduction ability of the enzyme derivative Mut III (W320A/W321A/G446Y) returned to levels close to that of MtXgh74. The pattern of xyloglucan hydrolysis by Mut III was typical for endo-processive xyloglucanases. The thermostability of Mut I and Mut II at 60 °C decreased significantly compared to the wild type, whereas the thermostability of Mut III at 60 °C restored almost to the MtXgh74-wt value. All mutants lost the ability to cleave the backbone of xyloglucan building blocks which was a characteristic of MtXgh74. Instead they acquired a low branch removing activity. Molecular dynamics simulations revealed the role of mutated amino acids in the complex action mechanism of GH74 enzymes. KEY POINTS: • Endo-processive mode of action of the xyloglucanase MtXgh74 was altered by rational design. • The endo-dissociative mutant Mut II (W320A/W321A) efficiently reduced XyG viscosity. • The substitutions W320A/W321A/G446Y in Mut III recovered the endo-processive mode. • Mut II can be used to reduce the viscosity of biomass slurries containing tamarind seed flour.

Starch degradation in plants is mediated by amylases, the activity of which is post-translationally regulated by inhibitors. It is assumed that the SbAI amylase inhibitor activity is associated with potato cold stress resistance. The study of possible correlations of the SbAI variability with the cold resistance of potato species will improve the understanding of the starch metabolism regulation during plant development and stress response. In the present study, the genome sequences homologous to SbAI were identified in 12 potato species of section Petota. In total, 36 allelic variants of the gene and 31 variants of the protein were revealed. Comparison with data on S. tuberosum cultivars showed that the SbAI cultivar polymorphism is 1.4–1.7 times higher than the interspecific, but the species possess a larger number of allelic variants. Phylogenetic analysis revealed that, for S. demissum, S. acaule, and S. stoloniferum, each species SbAI allelic variants did not get into one clade. The SbAI gene expression pattern was determined in various organs of the species S. tuberosum (cv. Nadezhda), S. rybinii, S. chacoense, and S. kurtzianum. In leaves, S. chacoense SbAI expression level was 13, 50, and 250 times higher than in S. tuberosum, S. kurtzianum, and S. rybinii, respectively. Varied levels of SbAI expression in the species may be due to different initial contents of both synthesized starch and reducing sugars in the leaves. In tubers, S. tuberosum SbAI expression was 5.2, 8.6, and 430 times higher than in S. kurtzianum, S. chacoense, and S. rybinii. In roots, S. rybinii SbAI expression was 2.4 times higher than in S. chacoense and 42.3 times higher than in S. kurtzianum and S. tuberosum. The absence of correlation between the SbAI expression level and the species cold resistance was shown. The obtained expression data suggest that different potato species and cultivars may differently regulate tuber starch content.

In this article, the functional group composition of the spruce (Picea abies) and birch (Betula pendula) phloem lignin is described. The features of the chemical structure were studied by analyzing dioxane lignin using the elemental analysis, UV-Vis, FT-IR, and 1D NMR spectroscopy. For comparison, samples of xylem dioxane lignin isolated from the corresponding wood species were also analyzed. FT-IR spectroscopy data suggest that the lignins of birch phloem and xylem are similar in chemical structure. However, there are differences in absorption bands in the spectra of spruce dioxane lignin, which indicate the opposite. Quantitative analysis of the functional group composition was performed using 13C and 31P NMR data. It was found that free phenolic hydroxyl groups of catechol and p-hydroxyphenyl types are dominated in the composition of spruce phloem lignin. Birch phloem lignin has a qualitative and quantitative composition of functional groups characteristic of hardwood lignins. However, the content of G-units is greater than S-units, in contrast to the birch xylem lignin, where S-units predominate. The revealed differences are relevant from the point of view of plant physiology. The practical significance of the study is connected with understanding the reactivity of lignins when considering the chemical processing of tree bark.

Mycobacterium tuberculosis cells contain two apurinic/apyrimidinic (AP) endonucleases, endonuclease IV (MtbEnd) and exonuclease III (MtbXthA), the former playing a dominant role in protecting mycobacterial DNA from oxidative stress. Mycobacterial endonuclease IV substantially differs from its homologs found in Escherichia coli and other proteobacteria in a number of conserved positions important for DNA binding and AP site recognition. The M. tuberculosis end gene was cloned, and recombinant MtbEnd purified and characterized. The protein efficiently hydrolyzed DNA at the natural AP site and its 1'-deoxy analog in the presence of divalent cations, of which Ca^(2+), Mn^(2+), and Co^(2+) supported the highest activity. Exonuclease activity was not detected in MtbEnt preparations. The pH optimum was estimated at 7.0-8.0; the ionic strength optimum, at ~50 mM NaCl. Enzymatic activity of MtbEnd was suppressed in the presence of methoxyamine, a chemotherapeutic agent that modifies AP sites. Based on the results, MtbEnd was assumed to provide a possible target for new anti-tuberculosis drugs.

Novel carbazole-based [6]helicenes fused with an azine ring (pyridine, pyrazine or quinoxaline) have been prepared through a five-step synthetic sequence in good overall yields. Commercially available 2,3-dihaloazines were used as starting materials. To discern the effect of merging an azine moiety within a helical skeleton, the X-ray structures, UV–vis absorption and fluorescence spectra of the helicenes were investigated and compared to that of the parent carbazole-based [6]helicene (7H-phenanthro[3,4-c]carbazole).

It is becoming increasingly urgent to develop and utilize novel, more efficient and stable materials for mobile and stationary emission control applications as the deleterious consequences of anthropogenic air pollution are becoming more evident and pressing. Tightening regulations, particularly related to automotive exhaust treatment, together with continued improvements in engine design, that result in lowering the engine operating temperatures and inadvertently lead to the release of an overwhelming proportion of pollutants during the cold start, present new challenges for materials design, specifically for oxidation catalysts. In particular, improvements in the low-temperature activity while maintaining catalyst stability at high temperatures are required from the next-generation catalyst. Typical catalysts for removal of pollutants from automotive exhaust streams incorporate platinum group metals (PGMs). They tend to be inefficient at low temperatures (below 250 °C), thus accounting for the cold start problem, yet sinter and lose their activity at high temperatures that are frequently encountered during catalyst operation. High PGM loadings are often employed to compensate for catalyst inefficiencies and fast degradation, ultimately resulting in high-cost catalytic converters. We have developed a new approach for the design and formation of catalytic materials that allows for both significantly more efficient PGM incorporation and improved overall catalyst performance at reduced PGM loadings. The method provides control over the composition and geometry of the support through self-assembly of sacrificial composite template — “raspberry” polymeric colloids decorated with catalytic particles — accompanied by infiltration with metal-oxide precursor and subsequent removal of the colloids. This method simultaneously structures the porous network and organizes the catalytic particles within it. Uniquely, the resulting catalytic particles are partially embedded in the support matrix and partially exposed to the pore interior, producing catalytic sites that are both stable and accessible. Herein, the feasibility of this novel and versatile approach for automotive catalytic conversion is demonstrated: the studies include testing alumina-based raspberry-colloid-templated (RCT) catalysts containing Pd nanoparticles (RCT Pd/Al2O3) for oxidation of propane and carbon monoxide under simulated diesel exhaust conditions and hydrothermal aging at 800 °C for 50 h in the simulated stream. The RCT Pd/Al2O3 catalysts exhibit exceptional activity toward CO oxidation, reduced reaction onset temperature, and high stability to elevated temperatures (demonstrated through prolonged exposure to temperatures up to 950 °C) and reactive gas streams, without migration, sintering or loss of the precious metal NPs. Notably, the novel catalyst shows the same or slightly better performance than the commercial catalysts even when the PGM load is reduced by ∼80 % compared to the commercial counterparts. These results provide confidence for the utilization of the RCT approach for the fabrication of robust nanostructured catalysts for next-generation, energy-efficient catalytic converters with improved performance at low and high temperatures and reduced costs. The RCT methodology is, in addition, highly generalizable, and can thus be applied for the design of a wide range of catalytic systems in the automotive sector and beyond.

Peculiarities of self-organization of 1,6-dimethyl(diethyl)-3a,6a-diphenylglycolurils in crystals were studied. Glycolurils were synthesized and crystals of 16 solid forms (two pure substances and fourteen solvates) were obtained by crystallization from different solvents. The effect of solvent on the dimensionality of H-bonding architectures and crystal morphology was revealed. The most widespread experimentally observed H-bonding synthon is the chain based on the amide–amide R22(8) motif, and solvent molecules typically act as terminal groups toward these chains. This is in accordance with results of pairwise interaction energy calculation between glycolurils and glycoluril/solvent pairs. Parallel packing of these H-bonded chains in some cases results in crystal morphology facetted by hydrophobic alkyl and aryl moieties and provides materials with a superhydrophobic surface. It was proposed that bulk water is repelled due to the corrugation of surfaces formed by the alkyl and aryl groups.

We conducted an observational descriptive study evaluating the effectiveness of therapeutic modification of lifestyle with adding of 1000 mg of myo-inositol and 200 mg of D-chiro inositol combination (ratio 5:1) for nutritional support in 104 women of reproductive age with polycystic ovary syndrome (classic phenotype and nonclassical phenotypes in the presence of hyperandrogenism) for 6 months. Revealed changes in anthropometric parameters (decrease in body mass index by 0.89 kg/m 2 ; p

—A comparative analysis of the ability of G. mellonella larvae to wreak biodamage on polyethylene of various types was carried out. Fifteen polyethylene (PE) samples of three types differing in their characteristics were studied: type 1 (PE-1) was a package for food products (Petrothene LR 7340), type 2 (PE-2) was an AIRplus air package for nonfood goods (Hostalen GF 4750), and type 3 (PE-3) was a household package for purchases (NPE 953). The eating rate of these types of polyethylene was up to 1.078 mg larva–1 day–1 (by weight) and up to 61.8 mm2 larva–1 day–1 (by square). The largest number of perforations formed was observed in the PE-1 sample—0.857 units larva–1 day–1. Although PE-1 was preferred in this experiment, the greater wax moth larvae ate all PE types. The majority of larvae in the control and experimental groups were active without stimulation, but some larvae showed activity after stimulation. No processes of melanization of the external integument of G. mellonella larvae were observed in any of the groups. The results of survival rates, mobility, weight gain, and melanization processes indicate no negative effects on the health of larvae when eating polyethylene. The use of samples with various characteristics made it possible to assess more widely the ability of the greater wax moth larvae to wreak biodamage on polyethylene wastes.

A high-resolution single-crystal X-ray diffraction study of abiraterone acetate (1) has been carried out. The charge density distribution in the crystal of this anticancer drug is reconstructed from experimental data. The nature and the contributions of various intermolecular interactions to the total crystal energy are studied by means of the quantum theory `Atoms-in-Molecules', a non-covalent interactions method and energy framework plots. In general, dispersion C—H...H—C and C—H...π interactions play the main role in crystal packing of 1. The Voronoi tessellation analysis of 1 confirmed that contribution of hydrophobic and hydrophilic interactions to the molecular surface is close to their contribution to the total crystal energy. Similar analysis of abiraterone complexes with the cytochrome P450 family demonstrated that contribution of the C—H...H—C and C—H...π interactions to the molecular surface of the drug remains unchanged to fit the binding pocket, despite the presence of water and heme molecules, and hydrophilic groups within the pocket.

Genes homologous to PSY1 and PSY2 that encode phytoene synthase isoforms in Capsicum species C. baccatum, C. chinense, C. frutescens, C. tovarii, C. eximium, and C. chacoense were identified. High conservatism of functionally significant sites of phytoene synthases of the analyzed accessions was revealed. It was found that only PSY1-based clustering of pepper species corresponds to the traditional Capsicum phylogeny; C. eximium was a part of the Purple corolla complex, and C. chacoense was equidistant from Annuum and Baccatum clades. The absence of significant differences between PSY1 and PSY2 of yellow-fruited C. chinense and red-fruited pepper accessions was shown. The yellow color of C. chinense fruit may be the result of both decreased PSY1 expression and increased PSY2 transcription. Thus, it was demonstrated that the acquired fruit pigmentation retains strict phylogenetic limitations, which, however, can be overcome using artificial selection for the activity of phytoene synthase PSY1.