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Aim. To study the contribution of the Ala54Thr genetic polymorphism of the FABP2 gene to the risk of developing type 2 diabetes mellitus among the Yakut population. Materials and methods. The study included participants who filled out a questionnaire approved by the Local Committee on Biomedical Ethics at the Yakut Science Centre of complex medical problems and voluntarily signed an informed consent to conduct a genetic study. The sample consisted of 181 patients of the endocrinological department of the Republican Hospital No. 2 of the State Budgetary Institution “Center for Emergency Medical Care“ with a diagnosis of type 2 diabetes. The comparison group was a sample of 336 volunteers without chronic diseases of the Yakut ethnicity. For molecular genetic analysis, genomic DNA samples were isolated from whole blood. Single nucleotide polymorphism was determined by polymerase chain reaction followed by analysis of restriction fragment length polymorphism. Results. Study showed that polymorphism in the FABP2 gene has an impact on anthropometric parameters and blood biochemical parameters. The risk of developing type 2 diabetes was 1.7 times higher in carriers of the Ala/Thr genotype (odds ratio 1.755, 95% confidence interval – 1.212–2.542; p0.005) compared with carriers of other genotypes. When comparing the average biochemical values, the levels of aspartate transaminase, alanine aminotransferase, glucose and total bilirubin in homozygous carriers of the Ala/Ala genotype were significantly lower than in carriers of other genotypes (р0.05). Carriers of the heterozygous Ala/Thr genotype (р0.05) had the highest level in terms of aspartate aminotransferase and alanine aminotransferase. The highest indicator of the average level of HbA1c and an indicator of total bilirubin were carriers of the Thr/Thr genotype (р0.05). Conclusion. The high prevalence of the negative Thr allele among the Yakut population is probably associated with living conditions in the North, as well as in the traditional type of diet.

Relevance. Currently, the use of ultraviolet (UV) radiation for the disinfection of objects and the treatment for infectious diseases is considered as a promising alternative to chemical biocides and antibiotics. Shortwave — UV-C and UV-B -light emitting diodes (LED) are a relatively new type of UV radiation sources and potentially able to meet the requirements of current medical technologies. However, their possibilities for the treatment of wounds and infectious diseases have not been practically researched to date, which determines the relevance of experiments aimed at studying the biocidal and therapeutic properties of shortwavelength UV LEDs.Purpose. OF STUDY To evaluate the bactericidal efficacy of 272 nm LED radiation against hospital strains of Klebsiella pneumoniae bacteria characterized by multidrug resistance.Materials and Methods. The studies were carried out with an experimental sample of the LED apparatus for UV irradiation. In the irradiator of the device, 5 LEDs are installed with a maximum radiation at a wavelength of 272 nm and a total electrical power of 10 watts. The UV radiation dose achieved in one irradiation session (12 seconds) at a distance of 10 cm from the irradiator was 8 mJ/cm2 . In the experiments, a hospital strain of the bacterium Klebsiella pneumoniae, isolated from the patient’s blood, was used. The strain was characterized by multidrug resistance. A daily culture suspension of K. pneumoniae with a concentration of 108 CFU/ml in a volume of 100 µl was transferred into a Petri dish with a diameter of 9 cm with meat-peptone agar and evenly distributed over a surface with a diameter of 8 cm. Petri dishes were irradiated from a distance of 10 cm from the irradiator. The change in the dose of UV irradiation from 4 to 80 mJ/cm2 was carried out by varying the exposure time. Studies were carried out in 4 repetitions at each dose. After irradiation, the experimental and control (without irradiation) Petri dishes were placed in a thermostat at 37ºC for 24 hours, then the grown colonies were counted. A total of 60 experiments were carried out.Results. As a result of the research, it was shown that the LED device based on five 272 nm diodes provides deep and prompt disinfection of the surface from hospital strains of K. pneumoniae bacteria characterized by multidrug resistance. A dose of UV radiation of 8 mJ/cm2 reduces surface contamination with K. pneumoniae bacteria by more than a million times (decontamination efficiency over 99.9999%). At doses less than 10 mJ/cm2 , the efficiency of the 272 nm LED device in terms of inactivation of K. pneumoniae bacteria is 3–4 times higher than the bactericidal efficiency of mercury lamps.Conclusion.The prospects of using UV devices based on LEDs with a maximum radiation at a wavelength of 272 nm in systems for the operational disinfection of massively contaminated surfaces, potentially including wound surfaces, have been shown.

Organophosphorus chemical agents are included in the 1st List of the Annex on Chemicals of the Convention on the Prohibition of the Development, Production, Stockpiling and Use of Chemical Weapons and on Their Destruction (Chemical Weapons Convention, CWC). For the purposes of verification of compliance with the provisions of the CWC, special methods, which are considered the most informative at determining the retrospective effects of organophosphorus toxicants on the body, are necessary. Typical long-lived biomarkers of organophosphate toxic agents are tyrosine phosphorylation products, the presence of which in biomedical samples clearly indicates the exposure to sarin, soman, tabun and V-series agents. We have elaborated methods for the synthesis and isolation of tyrosine adducts derivatives of methylphosphonic and phosphoric acids, used as reference samples. The synthesis scheme included the consecutive protection of carboxyl and amino groups of tyrosine, its O-phosphorylation by the corresponding alkylphosphonates and phosphates, the removal of protective groups with the release of corresponding O-phosphorylated tyrosine adducts. Their purification from impurities was carried out, using column chromatography (SiO2, eluent: dichloromethane/ethyl acetate 1:1). The purity of the obtained products was more than 90 %, so it was possible to involve them in further transformations with the use of catalyst without the threat of its «poisoning». Benzyl and carboxybenzyl protection of phosphorylated L-tyrosines (12–17) was removed by means of catalytic hydrogenation by molecular hydrogen under atmospheric pressure. Target adducts of phosphorylated reagents and L-tyrosin were obtained (63–82 %) in form of crystal white substances, readily soluble in water and ethanol, and poorly – in dichloromethane and acetonitrile.

Rapid and specific diagnosis is necessary for both the treatment and prevention of infectious diseases. Bacteria and viruses that enter the bloodstream can trigger a strong immune response in infected animals and humans. The fluorescence polarization assay (FPA) is a rapid and accurate method for detecting specific antibodies in the blood that are produced in response to infection. One of the first examples of FPA is the non-competitive test for detecting brucellosis in animals, which was followed by the development of other protocols for detecting various infections. Fluorescently labeled polysaccharides (in the case of brucellosis and salmonellosis) or specific peptides (in the case of tuberculosis and salmonellosis, etc.) can be used as biorecognition elements for detecting infections. The availability of new laboratory equipment and mobile devices for fluorescence polarization measurements outside the laboratory has stimulated the development of new fluorescence polarization assays (FPAs) and the emergence of commercial kits on the market for the detection of brucellosis, tuberculosis, and equine infectious anemia viruses. It has been shown that, in addition to antibodies, the FPA method can detect both viruses and nucleic acids. The development of more specific and sensitive biomarkers is essential for the diagnosis of infections and therapy monitoring. This review summarizes studies published between 2003 and 2023 that focus on the detection of infections using FPA. Furthermore, it demonstrates the potential for using new biorecognition elements (e.g., aptamers, proteins, peptides) and the combined use of FPA with new technologies, such as PCR and CRISPR/Cas12a systems, for detecting various infectious agents.

A possible molecular mechanism of the ligand–receptor binding of Ac-Lys-Lys-Lys-NH2 (Ac-KKK-NH2) to the NaV1.8 channel that is responsible for nociceptive signal coding in the peripheral nervous system is investigated by a number of experimental and theoretical techniques. Upon Ac-KKK-NH2 application at 100 nM, a significant decrease in the effective charge carried by the NaV1.8 channel activation gating system Zeff is demonstrated in the patch-clamp experiments. A strong Ac-KKK-NH2 analgesic effect at both the spinal and supraspinal levels is detected in vivo in the formalin test. The distances between the positively charged amino groups in the Ac-KKK-NH2 molecule upon binding to the NaV1.8 channel are 11–12 Å, as revealed by the conformational analysis. The blind docking with the NaV1.8 channel has made it possible to locate the Ac-KKK-NH2 binding site on the extracellular side of the voltage-sensing domain VSDI. The Ac-KKK-NH2 amino groups are shown to form ionic bonds with Asp151 and Glu157 and a hydrogen bond with Thr161, which affects the coordinated movement of the voltage sensor up and down, thus modulating the Zeff value. According to the results presented, Ac-KKK-NH2 is a promising candidate for the role of an analgesic medicinal substance that can be applied for pain relief in humans.

The present study is devoted to the analysis of extreme sea level oscillations of the Laptev Sea using the ADCIRC model. The numerical modeling is performed on a high-resolution grid and verified for sea level observations from three tide gauges. We have revealed regional characteristics of extreme sea level oscillations for different parts of the Laptev Sea coast. The maximum total sea level range was 544 cm in Ebelyakh Bay, while the minimum was 267 cm in Khatanga Bay, where maximum tidal ranges were obtained. Some areas in Khatanga Bay and Anabar Bay had maximum tidal ranges exceeding 200 cm. The study provided an estimation of the possible magnitude of coastal flooding by calculating the extreme total and residual sea levels for different return periods: 1, 2, 5, 10, 20, 50, and 100 years. The amplitude of extreme surges calculated for the 100-year return period can exceed 300 cm for several sections of the Laptev Sea coast, with the maximum sea level range being about 680 cm for Anabar and Ebelyakh Bays.

Brucellosis in animals is an infectious disease caused by bacteria of the genus Brucella. Known methods for diagnosing brucellosis face some challenges, due to the difficulties in isolating and standardizing the natural brucellosis antigen. In this work, we investigated the possibility of using the fluorescence polarization assay (FPA) with synthetic glycoconjugate biosensing tracers to detect antibodies against Brucella as a new methodology for diagnosing brucellosis. Based on the received results, the synthetic fluorescein-labeled trisaccharide tracer is most effective for Brucellosis detection. This tracer is structurally related to the immune determinant fragment of the Brucella LPS buildup of N-formyl-d-perosamine units, connected via α-(1→3)-linkage at the non-reducing end and α-(1→2)-linkage at the reducing end. The sensitivity and specificity in the case of the use of trisaccharide tracer 3b were 71% and 100% (Yuden’s method) and 87% and 88% (Euclidean method), respectively, which is comparable with the diagnostic efficiency of traditionally used serological methods, such as the agglutination test (AT), complement fixation test (CFT), and Rose Bengal test (RBT). Given the known advantages of FPA (e.g., speed, compactness of the equipment, and standard reagents) and the increased specificity of the developed test system, it would be appropriate to consider its widespread use for the diagnosis of brucellosis in animals, including rapid testing in the field.

This review is devoted to the consideration of prospects and directions for the development of methods and approaches to the analysis of high-purity industrial gases and volatile hydrides, chlorides, fluorides, and organoelement compounds with natural and isotopically enriched compositions. The currently known capabilities for the determination of impurities in them using mass spectrometry, IR spectroscopy, gas chromatography, and chromatography-mass spectrometry are analyzed., Author(s): A. Yu. Sozin [sup.1] , V. A. Krylov [sup.2] , O. Yu. Chernova [sup.1] , T. G. Sorochkina [sup.1] , A. D. Bulanov [sup.1] , A. P. Kotkov [sup.3] [...]

The features of the behavior of steel-plate composite walls for static loads are considered. Based on the analysis of modern technical and regulatory documentation, the rationale for the chosen research topic is given. A review of the literature is performed, and the features of development are noted. A detailed description and features of the experimental structures under study and the materials used are presented. The features of the test are considered, and the test equipment is described. Analytical and numerical calculations of structures for eccentric compression have been performed. The description of the calculation complex and the used models of materials is presented; the description of numerical models, the features of their construction and calculation are given, the results of calculations are presented – stress distributions, deformations, features of cracking. The general types of experimental eccentric compression wall models are presented, the nature of the loss of bearing capacity of experimental structures is described, and a picture of destruction is presented. The analysis of the experimental data obtained and their comparison with analytical and numerical calculations are performed.

Goal. Creation of a vector control system with improved characteristics for an active rectifier-voltage source operating in the bidirectional energy flow mode with a with a fixed modulation frequency. Methodology. The physical prerequisites for the active rectifier - voltage source operation in the system of a medium-power frequency electric drive are considered. A vector control system with a fixed modulation frequency is constructed, the principles of forming the signals acting in it and the influence on its operation of the converter power circuit parameters and the power consumed by it are considered. Mathematical modeling of the converter with the developed control system in MATLAB/Simulink made it possible to verify the correctness of the operation of the power circuit and the control system. Results. A new structure of a vector control system operating with a fixed modulation frequency is proposed, and the performance characteristics of the circuit in a wide range of changes in the magnitude and sign of the output power are obtained. The advantages of the new control system over the existing ones are shown. Originality. The physical prerequisites for the functioning of the power scheme and the vector control system of the ARVS proposed by the authors with a fixed frequency of modulation, the principles of forming the signals operating within it are considered in detail. Practical significance. New structure of the vector control system operating with a fixed modulation frequency is proposed and the advantages of the new control system over the existing ones are shown.

The Mekong River is the 10th largest river in the world. It is recognised as the most productive river in Southeast Asia and economically essential to the region, with an estimated 60-65 million people living in the lower Mekong Basin. The Mekong Delta within Vietnam is considered a highly vulnerable ecosystem under threat from increasing anthropogenic pressure, such as dam construction and, as a consequence, the Delta is sinking and altering the natural hydrological cycle. Dams also lead to eutrophication and pollution of downstream water from regulated water flux and water stagnation. Another threat is climate change coupled with the lower rainfall, which could lead to an increased risk of drought in the Mekong Delta Basin. Thus, these project data represent an important baseline reference. The ecological health of the Mekong Delta’s environment, as indicated by the quality and availability of its water and biological resources, largely determines the economic and social development of the region, which produces about half of the agriculture and aquaculture products of Vietnam.This paper reports quantitative data on the biodiversity of six groups of aquatic organisms: bottom and pelagic fish, macrozoobenthos, microorganisms, phyto- and zooplankton in the Mekong Delta within Vietnam, as well as data on the physicochemical parameters of water and bottom sediments. The data were collected during 2018-2022 as part of the Ecolan E-3.4 programme within the framework of the research plan of the Joint Russian-Vietnamese Tropical Research and Technological Center. All presented datasets are published for the first time.

In recent years, more and more data have emerged confirming the contribution of non-HLA genetic markers to the predisposition to thedevelopment of Sjögren's syndrome (SS) and its severe complication, MALT-lymphoma. Objective: to study the association of polymorphisms of IRF5 (rs2004640), STAT4 (rs7574865), and TNFAIP3 (rs6920220, rs2230926) genes with predisposition to the development of SS and MALT-lymphoma. Materials and methods. The study included 80 patients with SS and 103 individuals in the control group. Sixteen patients were diagnosed with MALT-lymphoma. Genotyping of polymorphisms of IRF5 (rs2004640), STAT4 (rs7574865), TNFAIP3 (rs6920220, rs2230926) genes was performed by real-time polymerase chain reaction using original allele-specific probes labeled with different fluorescent labels. Results and discussion. The distribution of genotypes and alleles of the STAT4 gene differed statistically significantly in the study and control groups of patients (p = 0.0005 and p = 0.0001, respectively). The presence of the homozygous TT genotype increased the risk of developing SS more than eightfold compared to TG+GG genotypes (odds ratio, OR=8.2; 95 % confidence interval, CI 2.5–30.0; p=0.0001)]. The polymorphism of the TNFAIP3 rs2230926 gene was also associated with the risk of developing SS: the presence of the TG genotype significantly increased the probability of developing SS compared to the TT genotype (OR 6.4; 95% CI 1.2–44.3; p = 0.01). The development of MALT-lymphoma was associated with the rs6920220 polymorphism of the TNFAIP3 gene. In 10 out of 16 patients with MALT-lymphoma (62.5 %) at least one minor A allele (AA+GA) was detected, while in patients without MALT-lymphoma only in 32.8 % of patients at least one minor A allele was detected (OR=3.4, CI 1.1–10.7; p=0.03). In addition, a correlation was found between the rs7574865 TT genotype of the STAT4 gene and the risk of developing severe leukopenia in SS, which was significantly more frequent in carriers of the TT genotype than in individuals with the GG + GT genotype (OR 4.9; 95 % CI 1.7–14.4; p = 0.004). Polymorphism of the IRF5 gene (rs2004640) was not associated with risk of developing SS or with clinical manifestations of the disease. Conclusion. Polymorphisms rs7574865 of STAT4 gene, rs6920220, rs2230926 of TNFAIP3 gene are associated either with the risk of developing SS or with severe complications of the disease, MALT-lymphoma and leukopenia.

Abstract The calcium-selective oncochannel TRPV6 is an important driver of cell proliferation in human cancers. Despite increasing interest of pharmacological research in developing synthetic inhibitors of TRPV6, natural compounds acting at this channel have been largely neglected. On the other hand, pharmacokinetics of natural small-molecule antagonists optimized by nature throughout evolution endows these compounds with a medicinal potential to serve as potent and safe next-generation anti-cancer drugs. Here we report the structure of human TRPV6 in complex with tetrahydrocannabivarin (THCV), a natural cannabinoid inhibitor extracted from Cannabis sativa. We use cryo-electron microscopy combined with electrophysiology, calcium imaging, mutagenesis, and molecular dynamics simulations to identify THCV binding sites in the portals that connect the membrane environment surrounding the protein to the central cavity of the channel pore and to characterize the allosteric mechanism of TRPV6 inhibition. We also propose the molecular pathway taken by THCV to reach its binding site. Our study provides a foundation for the development of new TRPV6-targeting drugs.