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The morphological and physiological characteristics of Bacillus thuringiensis strains were analyzed and conditions for obtaining culture fluid with maximum yield of secreted RNases were determined. Zymographic analysis showed that culture fluid of B. thuringiensis strains along with low-molecular-weight (15-20 kDa) RNases contained enzymes with a molecular weight ~55 kDa and their content depended on the duration and conditions of culturing. Preparations based on B. thuringiensis culture fluid were effective against human influenza virus A/Aichi/2/68 (H3N2). In experiments on mice infected with 10 LD50 influenza virus strain A/Aichi/2/68 (H3N2), we selected effective variants of preparations based on culture fluid of B. thuringiensi strains for preventive administration that provided reliable protection of infected animals (protection coefficient 50%), close to that of the reference drug Tamiflu.

The results of studies of a newly isolated Serratia species K-57 strain are presented. The strain is characterized by antiviral activity towards human influenza A/Aichi/2/68/H3N2, vaccinia, mouse smallpox, and herpes simplex-2 viruses. The detected characteristics of the strain, including the data on activities on nucleolytic enzymes, recommend it for the development of therapeutic and preventive antiviral drugs.

The antiviral properties of water extracts from pharmaceutical raw materials of the chaga mushroom, Inonotus obliquus, were studied against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). All studies with infectious materials were carried out in an isolated virological laboratory of the State Research Center of Virology and Biotechnology Vector of Rospotrebnadzor, which has a sanitary and epidemiological conclusion for the right to work with pathogenic biological agents of I-II pathogenicity groups. Antiviral activity was determined by the ability of I. obliquus water extracts to inhibit the replication of SARS-CoV-2 (nCoV/Victoria /1/2020 strain) in Vero E6 and Vero cell cultures. The results of these studies showed that water extracts of I. obliquus are characterized by low toxicity in Vero and Vero E6 cell cultures and have antiviral activity against SARS-CoV-2. The 50% inhibitory concentration ranged from 0.75 to 11.6 μg/mL. A patent for the invention was received (Patent RU, 2741714 C 1, 2021).

Purpose. The aim of this work was to analyze the complete genome of probiotic bacteria Lactobacillus plantarum 8 RA 3, Lactobacillus fermentum 90 TC-4, Lactobacillus fermentum 39, Bifidobacterium bifidum 791, Bifidobacterium bifidum 1, and Bifidobacterium longum 379 and to test their activity against influenza A and SARS-CoV-2 viruses. Methods. To confirm the taxonomic affiliation of the bacterial strains, MALDI TOF mass spectrometry and biochemical test systems were used. Whole genome sequencing was performed on the Illumina Inc. MiSeq platform. To determine the antiviral activity, A/Lipetsk/1V/2018 (H1N1 pdm09) (EPI_ISL_332798) and A/common gull/Saratov/1676/2018 (H5N6) (EPI_ISL_336925) influenza viruses and SARS-CoV-2 virus strain Australia/VIC01/2020 (GenBank: MT007544.1) were used. Results. All studied probiotic bacteria are nonpathogenic for humans and do not contain the determinants of transmission-type antibiotic resistance and integrated plasmids. Resistance to antibiotics of different classes is explained by the presence of molecular efflux pumps of the MatE and MFS families. Cultures of L. fermentum 90 TC 4, L. plantarum 8 RA 3, and B. bifidum 791 showed a pronounced activity against influenza A viruses in MDCK cells. Activity against the SARS-CoV-2 virus was demonstrated only by the L. fermentum 90 TC 4 strain in VERO cells. Conclusions. The studied probiotic bacteria are safe, have antiviral activity, and are of great importance for the prevention of diseases caused by respiratory viruses that can also infect the human intestine.

This is the first study to assess antiviral activity against human influenza virus A/Aichi/2/68 and bird influenza virus A/chicken/Kurgan/05/2005 and phytochemical characteristics of an ethanol extract of Cacalia hastata L. from wild populations growing in the vicinity of Tomsk, Russia (mixed forest). A log10 neutralization index—an indicator of inhibition of virus replication by the extract from C. hastata leaves—was ≤2 lg for each influenza virus. The extract reduced the infectivity of the human influenza virus by 1.5-fold and that of the avian influenza virus by 1.7-fold. The phytochemical characterization of C. hastata (its various organs) showed that the largest amount of the tested biologically active substances is present in leaves and rhizomes.

Nucleic-acid-based drugs are a promising class of novel therapeutics; however, their use in medicine is widely limited because of insufficient delivery into cells. This article proposes a new delivery strategy of nucleic acid fragments into cells as components of TiO2-based nanocomposites. For the first time, unmodified Dz molecules were non-covalently immobilized on TiO2 nanoparticles precovered with polylysine (TiO2•PL) with the formation of (TiO2•PL)•Dz nanocomposites. DNAzymes in the proposed nanocomposites were shown to retain their ability to cleave the RNA target in a cell-free system with the same selectivity as unbound Dz molecules. It was shown by confocal laser microscopy that the fluorescein-labelled (TiO2•PL)•DzFlu nanocomposites penetrate into eukaryotic cells, where DzFlu is internalized in the cytoplasm and predominantly in nuclei. Delivery of deoxyribozymes into cells in the proposed nanocomposites permits very efficient interactions with RNA targets inside cells. This was demonstrated by an example of inhibition of H5N1 influenza A virus replication (inhibition by a factor of ca. 3000). This effect was one order of magnitude higher than with using lipofectamine as the transfection agent. The proposed (TiO2•PL)•Dz nanocomposites demonstrated high antiviral activity and are thus potent as nucleic-acid-based drugs.

The paper presents the developed software tool for calculating the combustion process. Computational studies were performed for coal-water slurry fuel. Using the developed program the calorimetric efficiency and environmental performance of CWS combustion in experimental and industrial installations can be calculated in automatic mode.

Background:The development of new antiviral drugs based on nucleic acids is under scrutiny. An important problem in this aspect is to find the most vulnerable conservative regions in the viral genome as targets for the action of these agents. Another challenge is the development of an efficient system for their delivery into cells. To solve this problem, we proposed a TiO2·PL–DNA nanocomposite consisting of titanium dioxide nanoparticles and polylysine (PL)-containing oligonucleotides.Results:The TiO2·PL–DNA nanocomposites bearing the DNA fragments targeted to different conservative regions of (−)RNA and (+)RNA of segment 5 of influenza A virus (IAV) were studied for their antiviral activity in MDCK cells infected with the H1N1, H5N1, and H3N2 virus subtypes. Within the negative strand of each of the studied strains, the efficiency of DNA fragments increased in the direction of its 3’-end. Thus, the DNA fragment aimed at the 3’-noncoding region of (−)RNA was the most efficient and inhibited the reproduction of different IAV subtypes by 3–4 orders of magnitude. Although to a lesser extent, the DNA fragments targeted at the AUG region of (+)RNA and the corresponding region of (−)RNA were also active. For all studied viral subtypes, the nanocomposites bearing the DNA fragments targeted to (−)RNA appeared to be more efficient than those containing fragments aimed at the corresponding (+)RNA regions.Conclusion:The proposed TiO2·PL–DNA nanocomposites can be successfully used for highly efficient and site-specific inhibition of influenza A virus of different subtypes. Some patterns of localization of the most vulnerable regions in IAV segment 5 for the action of DNA-based drugs were found. The (−)RNA strand of IAV segment 5 appeared to be more sensitive as compared to (+)RNA.

The diagnostics of the thermal imaging device, consisting in obtaining a thermal image of test objects and comparing it with the thermal image of a reference thermal imaging device, is presented. Relative coordinates, radiation temperature of elements and other characteristics are determined on the thermal image of the test objects of the thermovision device to be diagnosed, then the thermal imaging of the test objects of the reference thermal imager is selected.

The hairy root culture of halophyte Nitraria schoberi was obtained by transforming seedlings' primary leaves with a wild strain of Agrobacterium rhizogenes 15834 SWISS (transformation frequency was 78.7%). The roots' transgenic status was confirmed by PCR analysis using rolB-, rolC-, virC-, virD1-specific primers. There was a significant increase in the biosynthesis of flavonoids, hydroxycinnamic acids, pectins, protopectins and saponins in hairy roots as compared to intact plant roots. The сatechin content in ethanol extracts of transformed roots' exceeded this factor 3.8 times in plant roots, but the compound composition of catechin nature in the latter was more diverse. The high antiviral activity of N. schoberi hairy root ethanol extracts against influenza virus subtypes A(H5N1), A(H3N2) was revealed, which manifested itself in the effective inhibition of infectivity both in vitro-in MDCK cell culture-and in vivo increasing survival of mice infected with them.

AIM To compare the efficacy and safety of once-weekly dulaglutide with that of insulin glargine in combination with metformin and/or a sulphonylurea in mainly Asian patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS In this 52-week, randomized, parallel-arm open-label study, we enrolled patients aged ≥18 years with T2DM for at least 6 months and a glycated haemoglobin (HbA1c) concentration ≥53.0 mmol/mol (7.0%) and ≤96.7 mmol/mol (11.0%). The primary outcome was change in HbA1c from baseline to week 26 to determine non-inferiority of dulaglutide 1.5 mg versus glargine. RESULTS A total of 774 patients from China, South Korea, Mexico and Russia were randomly assigned (1:1:1) to dulaglutide 1.5 mg, dulaglutide 0.75 mg or glargine treatment groups. The patients' mean age was 55 years and the average T2DM duration was ~8 years. The least squares mean (SE) changes from baseline in HbA1c at 26 weeks were - 18.9 (0.73) mmol/mol (-1.73 [0.067]%) for dulaglutide 1.5 mg and -14.5 (0.73) mmol/mol (-1.33 [0.067]%) for dulaglutide 0.75 mg, compared with -12.7 (0.73) mmol/mol (-1.16 [0.067]%) for glargine. Statistical criteria for superiority were met with both dulaglutide 1.5 mg and dulaglutide 0.75 mg. More patients in the dulaglutide 1.5 and 0.75 mg groups achieved HbA1c target

SummaryMetagenomic surveys of human microbiota are becoming increasingly widespread in academic research as well as in food and pharmaceutical industries and clinical context. Intuitive tools for exploration of experimental data are of high interest to researchers. Knomics-Biota is a Web-based resource for exploratory analysis of human gut metagenomes. Users can generate analytical reports that correspond to common experimental schemes (like case-control study or paired comparison). Statistical analysis and visualizations of microbiota composition are provided in association with the external factors and in the context of thousands of publicly available datasets.Availability and ImplementationThe Web-service is available at https://biota.knomics.ru.Contactanna.popenko@knomics.ru or a.tyakht@gmail.com.Supplementary informationSupplementary figures are available at Bioinformatics online.

The article presents data on the antiviral activity of ethanol and aqueous extracts isolated from the herb plants Dracocephalum nutans, Glechoma hederacea, Melissa officinalis, Berteroa incana, Aegopodium podagraria, and Veronica longifolia against the A/Aichi/2/68 (H3N2) and A/chicken/ Kurgan/05/2005 (H5N1) subtypes of influenza A virus (IAV) in MDCK cell culture. It was found that the ethanol extracts of Glechoma hederacea, Berteroa incana, and Aegopodium podagraria have the antiviral activity in vitro in MDCK cell culture against H3N2 subtype of IAV. The aqueous extracts of Glechoma hederacea, Melissa officinalis, Aegopodium podagraria, and Veronica longifolia and ethanol extracts of Berteroa incana and Veronica longifolia are active against H5N1 subtype of IAV. None of the extracts of Dracocephalum nutans showed significant activity against the studied subtypes. The greatest efficiency was shown by the ethanol extract of Aegopodium podagraria against the H5N1 subtype and aqueous extracts from Glechoma hederacea and Melissa officinalis.against the H3N2 subtype. The ethanol extract of Berteroa incana has a high activity against both IAV subtypes, which makes this sample the most promising for creating new drugs for the prevention and treatment of influenza virus.

In this work we consider coal-water slurry fuels as an alternative to the traditional types of fuels, in particular, coal. Assessment is performed using a software tool for calculating the combustion process of coal-water slurry fuels. The obtained results will allow one to perform computer-aided environmental calculations during CWS combustion in experimental and industrial plants.

In this paper we propose and examine a physical mechanism which can lead to the generation of noise in the mass accretion rate of low mass X-ray binaries on time-scales comparable to the orbital period of the system. We consider modulations of mass captured by the compact object from the companion star's stellar wind in binaries with late type giants, systems which usually have long orbital periods. We show that a hydrodynamical interaction of the wind matter within a binary system even without eccentricity results in variability of the mass accretion rate with characteristic time-scales close to the orbital period. The cause of the variability is an undeveloped turbulent motion (perturbed motion without significant vorticity) of wind matter near the compact object. Our conclusions are supported by 3D simulations with two different hydrodynamic codes based on Lagrangian and Eulerian approaches -- the SPH code GADGET and the Eulerian code PLUTO. In this work we assume that the wind mass loss rate of the secondary is at the level of $(0.5-1)\times10^{-7} M_\odot$/year, required to produce observable variations of the mass accretion rate on the primary. This value is higher than that, estimated for single giant stars of this type, but examples of even higher mass loss rate of late type giants in binaries do exist. Our simulations show that the stellar wind matter intercepted by the compact object might create observational appearances similar to that of an accretion disc corona/wind and could be detected via high energy resolution observations of X-ray absorption lines, in particular, highly ionized ions of heavy elements., 9 pages, 9 figures, 1 table