bluuebunny/crossref_metadata_2025 huggingface dataset:
On some import substitution mechanisms in the second sphere of the Russian agro-industrial complex
Authors:   Ural State University of Economics, Yekaterinburg, Russia, Semin Alexander N. , Gusmanov Rasul U. ,   Bashkir State Agrarian University, Ufa, Russia, Chernogor Irina A. ,   Omsk Academy of the Ministry of Internal Affairs of Russia, Omsk, Russia, Subkhangulov Rustem R. ,   Ufa Law Institute of the Ministry of Internal Affairs of Russia, Ufa, Russia
Published: April 2024

In this work, an analysis of a possible option for introducing the “sandbox mechanism” into agriculture of the Russian Federation was carried out; the authors investigated the possible economic consequences of this implementation. The emphasis is placed on the fact that this step will allow our country to enter a completely new innovative path of agricultural development. The following research results were obtained: failures in imports and exports due to large-scale disruptions in food supply chains are the results of Western sanctions pressure on the Russian food market. Russia is still dependent on imports, so the main thesis is that exports and import substitution are complementary strategies. In order to level out the problem of import substitution, the authors propose the use of a “sandbox mechanism”; it is quite obvious that, through a certain methodology, we will reduce the time and costs of entering export-oriented products into the national market, and then world markets and, subsequently, expanding production capabilities for domestic manufacturers. The key directions of state policy in the field of import substitution have been identified - ensuring technological sovereignty in the country through the production of import-substituting and export-oriented products. The main threats to food security for 2024-2025 are formulated: the further use of parallel imports will only worsen the already difficult relations with the West, and new risks will also appear - an uncontrolled rise in food prices and, as a result, a loss of confidence of the domestic consumer. Specific models of import substitution are proposed with an emphasis on domestic high-tech developments and scientific competencies in the food market.
Inclusão de pessoas com deficiências em grupos de dança no cenário internacional
Authors: Conselho Ana Carla Pereira Martins , Lima Artur Gomes Dias , Santos Carlos Alberto Batista dos
Published: April 2024

Este estudo tem como objetivo principal identificar os processos de inclusão das Pessoas com Deficiências (PcD) em grupos de dança no cenário internacional, com enfoque na pesquisa bibliográfica, que adota os métodos de coleta de dados da revisão sistemática integrativa por meio de buscas online de periódicos, teses e dissertações, nas bases: ERIC, Web of Science, Scopus, CAPES, Google Acadêmico e SciELO, publicados entre 2015 e 2021. As análises dos dados foram realizadas com o software Rayyan e ATLAS.ti. Os resultados apresentam evidências sobre o cenário no mundo da inclusão em pesquisas locais, do público participante dos estudos, das temáticas e dos passos metodológicos seguidos, além de apontar o processo de inclusão em danças e os tipos de deficiências presentes nessas investigações, demonstrando a utilização da dança como instrumento educativo culturalmente inclusivo.
OVERCOMING PSYCHOLOGICAL PROBLEMS OF STUDENTS AFFECTED BY MARTIAL LAW
Authors: Dostatnii Rodion
Published: April 2024

In response to the military invasion by Russian forces in Ukraine educational sector faces multiple trials threatening the quality of it’s processes and acquisition of professional skills among Ukraine higher education institutions’ graduates. The primary challenges include psychological uncertainty and increased fear for the future among youth, significantly complicating new profession mastery. The novelty of this work lies in a comprehensive approach to the psychological adaptation of educational processes, incorporating curriculum modification, stress-resilient practice integration and focusing on providing emotional support for students. The article aims not merely to spotlight the issues, but also to offer effective solutions for improving educational seekers’ psychological health, ultimately enhancing education quality in extreme conditions. It seeks to identify optimal adaptation paths for the educational process amidst wartime challenges in Ukraine, ensuring uninterrupted educational activities and strengthening educational seekers’ psychological health. Moreover, it explores strategies enabling educational institutions to maintain instructional quality that meets students’ needs, facilitates their support and ensures psychological stability when traditional teaching methods become limited or irrelevant. Through extensive literature review and methodology analysis this paper highlights the necessity for immediate attention to the issues and fills the existing gap, emphasizing deeper investigation into specific challenges students face during the wartime and developing overcoming strategies. Special attention is paid to adapting educational programs to crisis conditions induced by external factors, aiming for effective psychological support for students and developing approaches to sustain their capability to assimilate and apply knowledge and skills in rapidly changing conditions. This study underscores the importance of developing comprehensive approaches to support students’ mental health and adapting the educational process under the wartime conditions, covering both the educational processes theoretical and practical aspects.
INTEREST OF FUTURE TEACHERS IN BEHAVIOR RISK FACTORS OF NICOTINE ADDICTION
Authors: Ivanchuk Anatolii , Shymkova Iryna , Hlukhaniuk Vitalii
Published: April 2024

The article examines the didactic problem of increasing the cognitive interest of future teachers in the content of educational material about nicotine addiction. The purpose of the research is to select the content of educational material about nicotine addiction in accordance with the concept of competence in behavioral safety and to check its influence on the formation of students’ cognitive interest. A total of 292 students of Vinnytsia State Pedagogical University named after Mykhailo Kotsiubinsky took part in the pedagogical experiment. At the ascertaining stage of the pedagogical experiment, the nature of the interest of first-year students of the Faculty of Physical Education and Sports and the Faculty of History to the behavioral risk factors of nicotine addiction was assessed. According to the results of the ascertainment stage of the pedagogical experiment, the division was made into experimental and control groups. At the formative stage of the pedagogical experiment, the formation of the competence of safe behavior in the experimental groups was carried out on the basis of educational material on the regularities of the process of the formation of nicotine dependence of the individual. In the control groups, the formation of competence in the safety of behavior was carried out on the basis of typical educational material that corresponded to the concept of intimidation by the consequences of smoking tobacco. At the control stage of the pedagogical experiment, the nature of the change in students’ cognitive interest in the content of the educational material on the behavioral risk factors of nicotine addiction was evaluated and compared with the results obtained at the formative stage of the pedagogical experiment. The data processing of the pedagogical research was carried out to assess the significance of the shift in the values of the indicators of the cognitive interests of the students of the experimental and control groups using the statistical G-criterion (McNemar’s test). For the experimental groups, the hypothesis that the typical direction of the shift in the indicators of students’ cognitive interest is non-random was confirmed. This hypothesis was not confirmed for the control groups. The main results of the study can be used to develop programs to prevent the impact of behavioral risk factors of nicotine addiction on students. The results of the study can also be used in the development of risk management algorithms when engaging a person in any addictive behavior.
PROJECT METHOD AS A PROVISIONAL CONCEPT OF TECHNOLOGICAL IMPROVEMENT IN STUDENTS OF A NEW UKRAINIAN SCHOOL
Authors: Tereshchuk Andriy
Published: April 2024

The article reveals the possibilities of the project method as a pedagogical technology for the modernization of the content of labor education of secondary school students. The main stages of the implementation of the project method in the content of labor training have been studied, the methodological features of the organization of students’ educational activities in the conditions of the knowledge paradigm and the relevant standards of education have been characterized.Person-oriented, activity approach, competence training, formation of subject competence ‒ these and other issues of modernization of the educational process through the organization of project activities of schoolchildren have, over the past decades, become the subject of attention of a large number of scientists.Traditionally, on-the-job training is aimed only at the formation of technical and technological knowledge and skills in students, which are inherent in the main types of production activities and industry as a whole. Instead, in the conditions of project activities, students not only study technical and technological processes, but also perform activities of a creative nature, which takes into account the individual characteristics and abilities of schoolchildren. So, in particular, the project method allows to develop competences and inherent cross-cutting skills (soft skills), to take into account the individual abilities of students as much as possible, to construct the educational process independently or with the help of a teacher, which lays the foundations of an activity approach in education.The article defines the main features that appear in the work of a teacher of labor education during the organization of project activities of schoolchildren in the New Ukrainian School. It is substantiated that the method of projects in the students’ study of technologies allows the implementation of the basic concepts of the New Ukrainian School: the development of competences, cross-cutting skills, develops research competence.
Geochemistry of Upper Vendian and Lower Cambrian Clay Rocks of the Moscow Syneclise (Some Traditional and Modern Approaches)
Authors: Maslov A. V. , Podkovyrov V. N.
Published: April 2024

The article discusses some geochemical characteristics of Upper Vendian and Lower Cambrian clay rocks that form the base of the Moscow syneclise. It is shown that during the several tens of millions of years of geological history we are considering, there was no significant change in the composition of clay rocks. Based on the Zr/Sc and Th/Sc values characteristic of argillites and argillite-like clays, the petrogenic nature of the fine-grained aluminosiliciclastics composing them is substantiated. This conclusion is also confirmed by the values of the CIA/WIP ratio. In general, according to some parameters of their composition, the Upper Vendian and Lower Cambrian clay rocks of the Moscow syneclise are closer to granitoids, according to others, to basic igneous rocks. Thus, compared with the average Late Proterozoic basalts, they contain noticeably more K2O and Rb, Th, Zr, Hf, Nb, and Ta, while the average Archean granitoids have noticeably lower concentrations of TiO2, FeO, and MgO, Sc, V, Cr, Co, and Ni. The position of the data points for Upper Vendian and Lower Cambrian clay rocks on the La/Sc–Th/Co, La/Th–Th/Yb, Sc–Th/Sc and other plots confirms what has been said. Chondrite-normalized lanthanide distribution spectra in clay rocks are close to the PAAS lanthanide spectrum. It has been suggested that the transportation of suspended material to the area of sedimentation was carried out by: 1) large rivers with source areas composed of rock complexes of different composition, and 2) rivers that drained provenances composed mainly of sedimentary rocks. The average CIA values inherent in the Upper Vendian and Lower Cambrian clay rocks of the Moscow syneclise are comparable to those typical for the suspended particulate matter of modern large rivers of a humid subtropical and tropical climate, as well as rivers of dry tropical climate regions. The localization of the data points of argillites and argillite-like clays on the SiO2–(Na2O + K2O + MgO + CaO), Al2O3–(Na2O + K2O + MgO + CaO) and CIA–WIP diagrams suggests that it was the paleoclimate that determined the main characteristics of their composition. The series of α-coefficients characteristic of clay rocks of the Upper Vendian–Lower Cambrian of the Moscow syneclise is quite close to the similar series for fine-grained suspended particulate matter of modern large river systems in southern Africa.
Thermobaric Conditions of Organic Matter Catagenesis in the Russian Segment of Barents Region Archipelagos (Franz Josef Land, Novaya Zemlya)
Authors: Nikitin D. S. , Khutorskoy M. D. , Samsonova O. S.
Published: April 2024

The natural bitumen (NB) localization finds in the archipelagos of Russian Arctic Western segment is considered. The nature of their appearance in connection with the geothermal regime of the subsurface is discussed. Based on numerical simulation, temperatures and heat flow density are calculated in 2D geometry along seismogeological profiles and in 3D geometry for the Franz Josef Land isometric structure. It is concluded that all the noted NB manifestations are genetically related to hydrothermal activity, the signs of which are adequately recorded in the geotemperature field.
Chemical Composition of the Indian Ocean Pleistocene Sediments
Authors: Levitan M. A. , Antonova T. A. , Domaratskaya L. G. , Koltsova A. V. , Syromyatnikov K. V.
Published: April 2024

Geochemical review of Pleistocene sediments from the Indian Ocean has been performed based on reports of deep-sea drilling cruises and other literature references. We created the data base including more than 2000 chemical analyses of sediment samples. As result we compiled a number of tables concerning the mean ariphmetic composition of lithogenic and biogenic sediments. All data have been normalized on PAAS (PostArchean Australean shales). We revealed the dominant role of terrigenous clastics in formation of chemical composition of noncarbonate sediments and noncarbonated matter of planktic carbonates as well. Main geochemical associations have been established together with three main factors determinating sediment composition: terrigenous, carbonate and hydrogenous. We managed to calculate meanwheighted chemical composition, accumulation rates of elements in the studied sediments and their mass accumulation rates. All these parameters of the chemical composition can be used later for comparative analysis with analog para-meters from other ocean sediments within frames of Pleistocene straton in the World Ocean.
Landscape of KRAS, BRAF, PIK3CA Genes Mutations and Clinical Features of EBV-Associated and MSI Gastric Cancer
Authors: Danishevich A. M. , Pospehova N. I. , Stroganova A. M. , Golovina D. A. , Nikulin M. P. , Kalinin A. E. , Nikolaev S. E. , Stilidi I. S. , Lyubchenko L. N.
Published: April 2024

Personalization of gastric cancer treatment is an urgent problem due to clinical heterogeneity and aggressive course of the disease. In 2014, Cancer Genome Atlas researchers divided gastric cancers into four subtypes based on molecular characteristics: Epstein–Barr virus positive (EBV+), microsatellite instability (MSI), chromosomal instability, genomically stable. To date, there is no single method for detecting chromosomal instability and genomically stable subtypes, while MSI analysis and EBV assessment are used in routine practice and are of the greatest clinical importance. We analyzed 159 gastric cancer samples for the presence of MSI, EBV DNA, and somatic mutations in codons 12–13 (exon 2), 61 (exon 3), and 146 (exon 4) of the KRAS gene, codons 597–601 (exon 15) of the BRAF gene and codons 542–546 (exon 9), 1047–1049 (exon 20) of the PIK3CA gene. As a result, the EBV+ gastric cancer was detected in 8.2% of samples, MSI – in 13.2%. MSI and EBV+ were found to be mutually exclusive. The mean age of patients with EBV+ and MSI cancers was 54.8 and 62.1 years, respectively. In 92.3% of EBV+ cancer was detected in men, of which 76.2% were older than 50 years. diffuse and intestinal adenocarcinomas in EBV+ cancer accounted for 6 (46.2%) and 5 (38.5%) cases, respectively. MSI occurred in almost equal proportions in men and women (n = 10; 47.6%, n = 11; 52.4%), with a predominance of intestinal histological type (71.4%) and lesion of the lesser curvature (28.6%). One case of EBV+ cancer was diagnosed with the E545K variant in the PIK3CA gene. A combination of variants in the KRAS and PIK3CA genes was found in all MSI cases. The EBV+ subtype was associated with a better prognosis. Overall five-year survival rates for MSI and EBV+ cancers were 100.0 and 54.7%, respectively.
Association of the Level of Serum Prolactin and Polymorphic Variants of the GRIN2A, GPM3, GPM7 GENES in Patients with Schizophrenia Taking Conventional and Atypical Antipsychotics
Authors: Tiguntsev V. V. , Gerasimova V. I. , Kornetova E. G. , Fedorenko O. Yu. , Kornetov A. N. , Goncharova A. A. , Poltavskaya E. G. , Boyko A. S.
Published: April 2024

Dopamine, serotonin and glutamate systems are jointly involved in the pathogenesis and pharmacotherapy of schizophrenia. We formulated a hypothesis that polymorphic variants of the GRIN2A, GRM3, and GRM7 genes may be associated with the development of hyperprolactinemia in patients with schizophrenia taking conventional and atypical antipsychotics as basic treatment. 432 Caucasian patients diagnosed with schizophrenia were examined. DNA was isolated from peripheral blood leukocytes by the standard phenol-chloroform method. For pilot genotyping, 12 SNPs in the GRIN2A gene, 4 SNPs in the GRM3 gene, and 6 SNPs in the GRM7 gene were selected. Allelic variants of the studied polymorphisms were determined by real-time PCR. The level of prolactin was determined by enzyme immunoassay. Among persons taking conventional antipsychotics, there were statistically significant differences in the distribution of genotype and allele frequencies in groups of patients with normal and elevated prolactin levels for the GRIN2A rs9989388 and GRIN2A rs7192557 polymorphic variants, as well as differences in serum prolactin levels depending on the genotypes of the GRM7 rs3749380 polymorphic variant. Among persons taking atypical antipsychotics, statistically significant differences were found in the frequencies of genotypes and alleles of the GRM3 rs6465084 polymorphic variant. For the first time, an association of polymorphic variants of the GRIN2A, GRM3, and GRM7 genes with the development of hyperprolactinemia in patients with schizophrenia taking conventional and atypical antipsychotics has been established. They not only confirm the close connection of the dopaminergic, serotonergic, and glutamatergic systems in the development of schizophrenia, but also demonstrate the potential of taking into account the genetic component for its therapy.
Methylophiopogonanone A Inhibits LPS/ATP-Induced Macrophage Pyroptosis via ROS/NLRP3 Pathway
Authors: Zeng H. B. , Zhang L. H. , Yuan D. P. , Wang W. , Su X. M. , Weng W. X. , Miao R. , Xu J. Y. , Long J. , Song Y. H.
Published: April 2024

As a byproduct of mitochondrial respiration or metabolism, reactive oxygen species (ROS) can act as a signaling molecule to activate NLR family pyrin domain containing 3 (NLRP3) inflammasome, thereby triggering immune response. NLRP3 inflammasome acts as a sensor of various danger signals and is central to the control of pyroptosis occurrence. Macrophage pyroptosis is closely related to atherosclerosis, arthritis, pulmonary fibrosis and other inflammatory diseases. Methylophiopogonanone A (MO-A) is a main homoisoflavonoid in Chinese herb Ophiopogonis Radix, which has antioxidant effect. However, it is not clear whether MO-A can alleviate macrophage pyroptosis by inhibiting oxidative stress. Here we have shown that MO-A increases the activities of superoxide dismutase (SOD) and catalase (CAT), inhibits the production of ROS, reduces the activation of NLRP3 inflammasome and the release of lactate dehydrogenase (LDH), and inhibits pyroptosis in macrophages induced by lipopolysaccharides (LPS) and adenosine triphosphate (ATP). These effects can be reversed by the ROS promoter hydrogen peroxide (H2O2). Therefore, MO-A can inhibit macrophage pyroptosis through the ROS/NLRP3 pathway and may be considered as a candidate drug for the treatment of inflammatory diseases.
Comparative Analysis of DNA-Polymerases from Family A as a Tool to Search for Enzymes with New Properties
Authors: Bulygin A. A. , Kuznetsova A. A. , Fedorova O. S. , Kuznetsov N. A.
Published: April 2024

DNA-polymerases catalyze DNA synthesis during DNA replication, repair, and recombination. A number of DNA-polymerases, such as the Taq enzyme from Thermus aquaticus, are used in various applications of molecular biology and biotechnology, in particular as DNA amplification tools. However, the efficiency of these enzymes depends on factors such as DNA origin, primer composition, template length, GC-content, and the ability to form stable secondary structures. Such limitations in the use of currently known DNA-polymerases leave the problem of searching for new enzymes with improved properties. This review summarizes the main structural and molecular-kinetic features of the functioning of DNA-polymerases belonging to the structural family A, including Taq polymerase. A phylogenetic analysis of these enzymes was carried out, which made it possible to establish a highly conserved consensus sequence containing 62 amino acid residues distributed over the structure of the enzyme. A comparative analysis of these amino acid residues among poorly studied DNA-polymerases revealed 7 enzymes that potentially have the properties necessary for their use for DNA amplification.
Influence of Poly(ADP-ribose)polymerase 1 Level on the Status of Base Excision Repair in Human Cells
Authors: Ilina E. S. , Kochetkova A. S. , Belousova E. A. , Kutuzov M. M. , Lavrik O. I. , Khodyreva S. N.
Published: April 2024

The base excision repair (BER) system is aimed at repair of the largest group of DNA lesions, namely of damaged bases. The main steps in BER are: recognition and removal of the aberrant base, cutting the DNA sugar-phosphate backbone, gap processing (including dNMP insertion), and DNA ligation. The precise functioning of BER depends on the regulation of each step of the process by regulatory/accessory proteins, the most important of which is poly(ADP-ribose)polymerase 1 (PARP1). PARP1 plays an important role in various processes of DNA repair, maintenance of genome integrity, and regulation of mRNA stability and decay. In this regard, PARP1 can affect BER both at the level of proteins involved in the process and at the level of expression of the mRNAs encoding them. There are no systematic data on the effect of various amounts of PARP1 on the activity of key BER proteins and the levels of mRNAs encoding them in human cells. In our work, using whole-cell extracts and RNA preparations obtained from the parental HEK293T cell line and its derivative HEK293T/P1-KD cell line with reduced PARP1 expression (shPARP1-expressing cells, PARP1 knockdown), we assessed the levels of mRNA encoding BER proteins: PARP1, PARP2, uracil DNA glycosylase (UNG2), AP endonuclease 1 (APE1), DNA polymerase β (POLβ), DNA ligase III (LIG3), and XRCC1. In parallel, the catalytic activity of these enzymes was evaluated. No significant effect of the PARP1 amount of on the mRNA levels of UNG2, APE1, POLβ, LIG3, and XRCC1 was found. At the same time, in HEK293T/P1-KD cells, the amount of PARP2 mRNA was reduced by 2 times. The activities of these enzymes in whole-cell extracts of HEK293T and HEK293T/P1-KD cells also did not differ significantly. Under the conditions of poly(ADP-ribose) synthesis, the efficiency of the reactions catalyzed by UNG2, APE1, POLβ, and LIG3 also did not change significantly. In addition, it was shown that a reduced amount of PARP1 in the extract of HEK293T/P1-KD cells does not cause fundamental changes in the nature of DNA PARylation compared to the extract of the parental HEK293T cell line.
Increased Frequencies of ‒174G and ‒572C IL6 Alleles in Populations of Indigenous Peoples of Siberia Compared to Russians
Authors: Tabikhanova L. E. , Osipova L. P. , Churkina T. V. , Kovalev S. S. , Filipenko M. L. , Voronina E. N.
Published: April 2024

The study of immune response and inflammation gene polymorphism in a genogeographic context is a relevant direction in the study of human populations. Here, in the indigenous populations of Siberia the frequencies of polymorphic variants ‒174G/C (rs1800795) и ‒572C/G (rs1800796) of the IL6 gene encoding the proinflammatory cytokine IL-6 were determined. For the first time, it was shown that the frequencies of ‒174G and ‒572C alleles, which determine increased inflammatory response and also associated with several diseases were statistically significantly higher in ethnic groups of Buryats, Teleuts, Yakuts, Dolgans and Tuvinians than in Russians living in Siberia. These values were in the intermediate position between those in European and East-Asian groups. We suppose the adaptive role of these IL6 genetic variants in the human settlement from Africa to the Eurasian continent. However, due to the departure from the traditional way of life and increasing anthropogenic environmental pollution, the risk of diseases whose pathogenesis is based on inflammation in indigenous Siberian populations is probably increased.
Abnormal mTOR Signaling Pathway Activity in Autism Spectrum Disorders: Prospects of Mechanism-Based Therapy
Authors: Trifonova E. A. , Kotliarova А. А. , Kochetov A. V.
Published: April 2024

Autism spectrum disorder (ASD) is a developmental disorder characterized by the early onset of communication, learning, and behavioral problems. The syndromic form of ASD is caused by monogenic mutations, in the case when it is not possible to find genetic or other known mechanisms, the term “idiopathic autism” is used. A significant part of both syndromic and idiopathic autism is associated with translational deregulation dependent on the mechanistic target of rapamycin (mTOR). In this review, we present both bioinformatic and experimental data that link the mTOR signaling pathway to maternal autoantibody-induced autism and childhood autoimmune neuropsychiatric disorders such as Sydenham’s chorea and pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS). The need for ASD subtyping and the possibility of mechanism-based therapy with inhibitors of the mTOR signaling pathway are also discussed.
Involvement of the Gagr Gene, a Domesticated gag Gene of Retrovirus, in the Stress Response Pathway in Different Drosophila Species
Authors: Gigin A. N. , Nefedova L. N.
Published: April 2024

The Gagr gene is a domesticated gag retroelement gene in Drosophila melanogaster, whose function is associated with a stress response. The protein products of the Gagr gene and its homologues in different Drosophila species have a highly conserved structure; however, they demonstrate a certain variability in the promoter region of the gene, apparently associated with the gradual acquisition of a new function and involvement in new signaling pathways. In this work we studied the effect of oxidative stress caused by ammonium persulfate on the survival of various species of the genus Drosophila (D. melanogaster, D. mauritiana, D. simulans, D. yakuba, D. teissieri, D. pseudoobscura), analyzed the correlation between the structure of promoter regions and stress-induced changes in the expression of the Gagr gene and its homologues in different Drosophila species and comparison of stress-induced changes in the expression of oxidative stress markers: Jak-STAT signaling pathway activator gene upd3, Jak-STAT pathway effector vir-1, and signaling pathway target IMD Rel. It was found that in D. simulans and D. mauritiana sensitivity to ammonium persulfate is significantly increased, which correlates with a reduced level of transcription of vir-1 gene orthologues. The latter is due to a decrease in the number of binding sites for the transcription factor STAT92E, a component of the Jak-STAT signaling pathway, in the vir-1 promoter region. Consistent changes in the expression of the Gagr, upd3, vir-1 genes are observed in all species of the melanogaster subgroup, except D. pseudoobscura, which indicates an increase in the role of Gagr in the regulation of stress response pathways during the phylogenesis of the genus Drosophila.
Molecular and Cellular Aspects of Endothelial-Mesenchymal Transition in Cardiovascular Diseases
Authors: Strelnikova E. A. , Kalinin R. E. , Suchkov I. A. , Korotkova N. V. , Mzhavanadze N. D.
Published: April 2024

Endothelial cells (ECs), which form the inner surface of the blood vessels, contact with blood, withstand mechanical pressure, and demonstrate heterogeneous reactions to exogenous and endogenous stimuli. ECs have unique properties in accordance with their niche, and play an important role in regulating vascular homeostasis. Endothelial cells may undergo a dynamic phenotypic switch in terms of its heterogeneity, which may lead to endothelial dysfunction and a number of associated pathologies. Endothelial-mesenchymal transition (EndMT) is one of the possible molecular and cellular mechanisms of such kind. EndMT is characterized by phenotypic changes in ECs through which the cells obtain new properties, i.e. start producing mesenchymal markers such as alpha-SMA and vimentin, change morphology, and become able to migrate. EndMT is a complex biological process, which may be induced by inflammation, hypoxia or oxidative stress, and be involved in pathogenesis of cardiovascular disease. This manuscript presents the key markers, inhibitors, inducers of endothelial-mesenchymal transition, and overall state-of-the-art of EndMT in cardiovascular diseases.
Identification of Functionally Significant Polymorphic Variants in miRNA Genes in Carotid Atherosclerosis
Authors: Zarubin A. A. , Mannanova K. V. , Koroleva I. A. , Sleptсov A. A. , Kuznetsov M. S. , Kozlov B. N. , Nazarenko M. S.
Published: April 2024

miRNAs are vital molecules of gene expression. They are involved in the pathogenesis of various common diseases, including atherosclerosis, its risk factors and complications. A detailed characterization of the spectrum of functionally significant polymorphisms of miRNA genes of patients with advanced carotid atherosclerosis is an actual research task. We analyzed miRNA expression and exome sequencing data of carotid atherosclerotic plaques of the same male patients (n = 8, 66–71 years of age, 67‒90% degree of carotid artery stenosis). For further study and analysis of the association between rs2910164 polymorphism of the MIR146A gene and advanced carotid atherosclerosis, we recruited 112 patients and 72 relatively healthy Slavic residents of Western Siberia. 321 and 97 single nucleotide variants (SNVs) were detected in the nucleotide sequences of pre- and mature miRNAs in carotid atherosclerotic plaques. These variants were located in 206 and 76 miRNA genes, respectively. Integration the data of exome sequencing and miRNA expression revealed 24 SNVs of 18 miRNA genes which were processed to mature form in carotid atherosclerotic plaques. SNVs with the greatest potential functional significance for miRNA expression predicted in silico were rs2910164:CG (MIR146A), rs2682818:AC (MIR618), rs3746444:AG (MIR499A), rs776722712:CT (MIR186), rs199822597:GA (MIR363). The expression of miR-618 was lower in carotid atherosclerotic plaques of patients with the AC rs2682818 genotype of the MIR618 gene compared with the CC genotype (log2FC = 4.8; p = 0.012). We also found the association of rs2910164:C (MIR146A) with the risk of advanced carotid atherosclerosis (OR = 2.35; 95% CI: 1.43–3.85; p = 0.001). Integrative analysis of polymorphism in miRNA genes and miRNA expression is informative for identifying functionally significant polymorphisms in miRNA genes. The rs2682818:AC (MIR618) is a candidate for regulating miRNA expression in carotid atherosclerotic plaques. The rs2910164:C (MIR146A) is associated with the risk of advanced carotid atherosclerosis.
Mathematical Modeling of HIV Replicaton and the Response of the Interferon System
Authors: Gainova I. A. , Soboleva A. E. , Grebennikov D. S. , Bocharov G. A.
Published: April 2024

Developing physiologically meaningful mathematical models that describe multilevel regulation in a complex network of immune processes, in particular, of the system of interferon-regulated virus reproduction processes, is a fundamental scientific problem, within the framework of an interdisciplinary systematic approach to research in immunology. Here, we have presented a detailed high-dimensional model describing HIV (human immunodeficiency virus) replication, the response of type I interferon (IFN) to penetration the virus into cell, and suppression of the action of IFN-induced proteins by HIV accessory ones. As a result, developed model for the first time includes interactions of all three processes. The mathematical model is a system of 37 non-linear ordinary differential equations including 78 parameters. The peculiarity of the model is that it describes not only the processes of the IFN response of the cell to virus infection, but also the mechanisms used by the virus to prevent effects of the IFN system.
Overexpression of MKRN2 Inhibits the Growth of Ovarian Cancer Cells
Authors: Jiang F. Z. , Xia Q. J. , Wu L. , Zhang Y. M.
Published: April 2024

Ovarian cancer has a high mortality with low five-year survival rates. The role of the E3 ligase Makorin ring finger protein 2 (MKRN2) in ovarian cancer is unknown. This study investigated the impact of MKRN2 on the growth of ovarian cancer. MKRN2 expression in ovarian cancer tissue was analyzed by immunohistochemistry. Overexpression of MKRN2 was induced in two ovarian cancer cell lines (SKOV3 and CAOV3) by lentivirus transfection, and expression levels were verified by western blotting. Proliferation and growth were determined by CCK-8 and colony formation assays, while migration was examined using transwell assays and apoptosis by flow cytometry. Xenograft tumors of transfected SKOV3 cells were established in mice, and immunohistochemistry and TUNEL assays measured MKRN2 levels and apoptosis in tumor cells. Reduced levels of MKRN2 in cancerous tissue relative to non-cancerous ovarian tissues. Lentiviral-based MKRN2 overexpression in SKOV3 and CAOV3 cells reduced tumor-associated behavior while inducing apoptosis in vitro. In xenograft tumors, MKRN2 overexpression inhibited ovarian cancer growth and increased apoptosis in vivo. These findings imply the MKRN2 involvement in ovarian carcinogenesis and suggest its potential for treating the disease.
Random Integration Analysis of Recombinant Adeno-Associated Virus 6 Packaged in Sf9 Insect Cells
Authors: Zhang M. H. , Liu X. M. , Zhang C.
Published: April 2024

Recently, there have been growing concerns over the integration of recombinant adeno-associated virus (rAAV) used in gene therapy. Wild-type adeno-associated virus (AAV) site specifically integrates into AAVS1 site of human genome, while rAAV randomly integrates into host chromosomes at low frequencies. This research aims to study the random integration events of rAAV6-EGFP packaged in Sf9 insect cells. Baculo-Sf9 manufacturing platform has the advantages of high-density suspension culture of Sf9 insect cells and large-scale production of rAAV vectors. In this study, we used different doses of Baculo-Sf9 produced rAAV6-EGFP to transduce HEK293T cells and A549-implanted tumors in vitro and in vivo. Using flow cytometry and fluorescence microscopy, we studied their EGFP gene expression efficiencies and EGFP fluorescence intensities. Using inverse nested PCR and DNA sequencing, random integration sites of rAAV6-EGFP genome into human chromosomes were identified. In vitro results showed that gene expression efficiencies became stable after 20 days and random integration frequencies were 0.2‒4.2%. Both in vitro and in vivo results indicated that random integration of Baculo-Sf9 rAAV6 was dose-dependent. Sequencing results showed two random integration sites, which were on human chromosomes 8 and 12. The findings suggest that we should use as low dose of rAAV vector as possible for safe gene therapy.
Cancer-Associated Fibroblasts: Heterogeneity and Bimodality in Oncogenesis
Authors: Lunina N. A. , Safina D. R. , Kostrov S. V.
Published: April 2024

Malignant tumors are characterized by high cellular heterogeneity, including cancerous and non-malignant cells, as well as non-cellular components that are part of the tumor microenvironment. Cancer-associated fibroblasts often form a major component of the microenvironment, providing the very “soil” in which cancer cells thrive. Cancer-associated fibroblasts may contribute to tumor growth, invasion, metastasis, and resistance to therapy. However, clinical trials of treatment strategies targeting cancer-associated fibroblasts have largely failed. Moreover, there is evidence that cancer-associated fibroblasts are able to inhibit tumor development. In this review, we aimed to present the current understanding of the functional heterogeneity of cancer-associated fibroblasts, their bimodality in tumor development, and tumor progression. Understanding the tumor-promoting and tumor-inhibiting activities of cancer-associated fibroblasts may contribute to the development of new diagnostic and therapeutic approaches.
The Role of Mitochondrial in Intestinal Epithelial Barrier Dysfunction during Inflammatory Bowel Disease
Authors: Chernyavskij D. A. , Galkin I. I. , Pavlyuchenkova A. N. , Fedorov A. V. , Chelombitko M. A.
Published: April 2024

Inflammatory bowel diseases are widely spread in industrial countries with every 20th citizen being affected. Dysregulation of epithelial barrier function is considered to play a key role in the development of inflammatory bowel diseases. Intestinal epithelium permeability depends mostly on the condition of intercellular contacts and epithelial cells' renewal ability. Mitochondria participate in the regulation of various intracellular processes besides performing the energetic function. Recent data indicate the potential role of mitochondria in intestinal epithelial barrier regulation and inflammatory bowel diseases onset. Mitochondrial dysfunction may be one of the reasons for disruption of the structure of tight junctions and the cytoskeleton of intestinal epithelial cells, as well as a decrease in the ability of the epithelial lining to self-renewal. All this leads to a decrease in the barrier function of the intestinal epithelium and the development of inflammatory bowel diseases. Nevertheless, the mechanisms of these processes are still unclear and further research is required.
Ischemia-Reperfusion Injury: Molecular Mechanisms of Pathogenesis and Methods of Their Correction
Authors: Goncharov R. G. , Sharapov M. G.
Published: April 2024

Ischemia-reperfusion is a cascade of complex and interrelated pathological processes underlying many human diseases, including such socially significant as stroke, myocardial infarction, acute renal failure, etc. The present review considers modern ideas about the main biochemical and signal-regulatory processes occurring in the cell under conditions of ischemia-reperfusion. Both generally accepted and newly developed ways of ischemia-reperfusion lesion correction aimed at different chains of this pathological process are considered.
Regulation of Metabolism and the Role of Redox Factors in the Energy Control of Quiescence and Proliferation of Hematopoietic Cells
Authors: Kalashnikova M. V. , Polyakova N. S. , Belyavsky A. V.
Published: April 2024

One of the key regulators of hematopoietic stem cell (HSC) maintenance is cellular metabolism. Resting HSCs use anaerobic glycolysis as the main source of energy. During expansion and differentiation under conditions of steady state hematopoiesis, the energy needs of activated HSC increase many fold. To meet the increased demands, cells switch to mitochondrial oxidative phosphorylation, which is accompanied by the increase in reactive oxygen species (ROS) production. Here, the molecular mechanisms maintaining glycolysis in HSCs as well as the factors determining the increase in metabolic activity and the transition to mitochondrial biogenesis during HSC activation are considered. We focus on the role of HIF (hypoxia-inducible factor) proteins as key mediators of the cellular response to hypoxia, and also consider the phenomenon of extraphysiological oxygen shock (EPHOSS), leading to the forced differentiation of HSCs as well as methods of overcoming it. Finally, the role of fatty acid oxidation (FAO) in hematopoiesis is discussed. Understanding the metabolic needs of normal HSCs and precursors is crucial for the development of new treatments for diseases related to the hematopoietic and immune systems.
Redox-Catalytic Properties of Cobalamins
Authors: Shatalin Yu. V. , Shubina V. S. , Solovieva M. E. , Akatov V. S.
Published: April 2024

Vitamin B12, or cobalamin, is essential for normal body function and used in the therapy of different diseases. A several studies have shown that vitamin B12 has anti-inflammatory and antioxidant properties that can play an important role in the prevention of some diseases. On the other hand, it has been reported that vitamin B12 in combination with such reducing agents as ascorbate (vitamin C) and thiols showed prooxidant activity. This review provides information on the roles of vitamin B12 in diseases accompanied by inflammation and oxidative stress and the effects of vitamin B12 administrated alone and in combinations with different reducing agents such as ascorbate and thiols on oxidative stress. In addition, the mechanisms of prooxidant actions of combinations of vitamin B12 with these reducing agents depending on the form of vitamin B12 (hydroxocobalamin and cyanocobalamin) are discussed. Understanding the mechanisms of prooxidant action of vitamin B12 is necessary for developing strategies for therapeutic administration of vitamin B12.
Protective Action of HSP70 and Hydrogen Sulfide Donors in THP-1 Macrophages at Lipopolysaccharide-Induced Inflammatory Response by Modulating Endocytosis
Authors: Yurinskaya M. M. , Garbuz D. G. , Evgen’ev M. B. , Vinokurov M. G.
Published: April 2024

Hsp70 and hydrogen sulfide donors reduce inflammatory processes in human and animal cells. The biological action mediated by Hsp70 and H2S donors (GYY4137 and sodium thiosulfate) depends on their protection kinetics from cell activation by lipopolysaccharides. However, the molecular mechanisms of action of Hsp70 and H2S are not well understood. We studied the effect of human recombinant Hsp70 and H2S donors on the formation of reactive oxygen species and tumor necrosis factor-alpha induced in human cells (THP-1) by lipopolysaccharides. Transcriptomic changes occurring in these cells after LPS administration in combination with GYY4137 pretreatment were investigated. The results obtained showed that Hsp70 and hydrogen sulfide donors reduce inflammatory processes in cells activated by the action of LPS. Hsp70 and H2S donors differed in the kinetics of the protective action, while hydrogen sulfide donors turned out to be more effective. The role of endocytosis in the mechanisms of protection of cells by H2S and Hsp70 donors from the action of LPS was studied. It has been found that GYY4137 pretreatment of LPS-exposed cells reduces the LPS-induced induction of various pro-inflammatory genes and affects the expression of genes of various intracellular signaling pathways.
Molybdenum-Containing Catalysts Based on Porous Aromatic Frameworks as Catalysts of Oxidation of Sulfur-Containing Compounds
Authors: Akopyan A. V , Eseva E. A , Lukashov M. O , Kulikov L. A
Published: April 2024

New molybdenum-containing catalysts based on PAF-30 mesoporous carbon material for oxidation of sulfur-containing compounds (SCs) in a model fuel were synthesized. The PAF-30 support was modified with functional groups containing a positively charged nitrogen atom with various substituents. The modified supports were studied by the methods of low-temperature nitrogen adsorption/desorption, IR spectroscopy, and elemental analysis. The major factors affecting the oxidation were considered: reaction temperature and time, oxidant amount, catalyst dosage, and kind of sulfur-containing substrate. For the Мо/PAF-30-NEt3 catalyst, optimum conditions were found for oxidation of various classes of SCs in model mixtures: H2O2 : S molar ratio 6 : 1, 60°С, 60 min. The Мо/PAF-30-NEt3 catalyst operates in dibenzothiophene (DBT) oxidation during five cycles without appreciable activity loss.
Oxidation of Sulfur Compounds by Sodium Hypochlorite over Molybdenum-Based Amphiphilic Catalysts
Authors: Gevorgyan K. P. , Polikarpova P. D.
Published: April 2024

The study reports on the oxidation of sulfur compounds by sodium hypochlorite over molybdenum-based amphiphilic catalysts. The conversion of dibenzothiophene (DBT) was investigated as a function of the catalyst composition and reaction conditions. When sodium hypochlorite was used in combination with the heptamolybdate-anion-containing amphiphilic catalyst, sulfur compounds were found to be effectively oxidized even at room temperature. Under optimum process conditions (an oxidant to sulfur molar ratio of 4 : 1, a catalyst concentration of 0.5 wt %, and an acetonitrile volume of 1 mL), 100% conversion of DBT to sulfone had already been achieved after ten min of oxidation. The addition of acetonitrile to the reaction mixture was found to minimize the aggregation of catalyst particles and enhance the process performance. The catalyst demonstrated sustained activity over five oxidation cycles without regeneration.
Oxidation of the Styrene Epoxide–Sulfuric Acid Binary System in an Alcohol Solution
Authors: Petrov L. V. , Spirin M. G. , Solyanikov V. M.
Published: April 2024

Oxygen uptake by the styrene epoxide (SE)–sulfuric acid (SA) binary system in a solution consisting of 90 vol % tert-butanol and 10 vol % chlorobenzene (BUC solvent) was studied. The equation for the reaction rate as a function of reactant concentrations and the Arrhenius equation for the effective oxidation rate constant are presented. Comparison of the results obtained with the data on oxidation in related binary systems SE–perchloric acid (PCA) and SE–p-toluenesulfonic acid (TSA) shows that the specific features of the oxidation of these systems are determined by the kind of the acid catalyst.
Filtration Performance of 3D-Printed Ceramic Pellets: Investigation Using CFD and Computed Tomography
Authors: Dorokhov V. S. , Ovsienko O. L. , Chugunov S. S. , Rogozina M. V. , Anikeev N. A. , Nikul'shin P. A.
Published: April 2024

This study demonstrates the potential for computer-aided engineering and additive manufacturing techniques to fabricate protective layer materials with a novel design of filtration channels. Using computational fluid dynamics (CFD) simulation for channels of various geometries, potential locations of the capture of solid dust particles in ceramic filter pellets were identified. The filter pellets were fabricated from ceramic material using laser stereolithography. The printed samples were subjected to a filtration test. The CFD simulation of the pellet channels to identify potential filtration locations, followed by a comparative assessment of the simulation results and the post-test X-ray computed tomography (CT) scan of the 3D-printed pellets, demonstrated the feasibility of CFD models for the design of filter materials. The study findings are intended for the development of innovative protective materials with filtering capabilities to be implemented in specific industrial refining applications