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Relevance.Amonomorphic type of maculo-­papular cutaneous mastocytosis was allocated relatively recently. Inchildren and adolescents with amonomorphic type of MPCM (adult type pattern), clinical manifestations persist into adulthood and can transform into asystemic process, which determines the need for regular monitoring of this category of patients.Theaimwas to analyse the results of clinical, laboratory and instrumental examinations of an adolescent with amonomorphic type of MPCM.Materials and Methods. The study of an adolescent patient included data of laboratory examination, pathomorphological examination, ultrasound examination of the abdominal organs and cKIT gene of an adolescent with amonomorphic type of MPCM, observed at “Moscow Scientific and Practical Center of Dermatovenerology and Cosmetology”.Resultsand Discussion.The process was represented by multiple rashes on the skin of the trunk and limbs. Darier’s sign is positive. The patient’s serum tryptase level exceeded the age norm. The late onset (atthe age of 12)of the disease, elevated tryptase levels, neurological symptoms, and the risk of anaphylaxis caused alertness regarding the development of the systemic form, therefore an ultrasound examination of the abdominal organs was performed and the presence of amutation in the cKIT gene in peripheral blood was determined.Conclusion.Clinical report of an adolescent patient in Moscow Scientific and Practical Center of Dermatovenerology and Cosmetology was presented. Thus, the combination of clinical and laboratory data allows minimizing the number of invasive procedures in children with CM. Assessment of the tryptase level, mutation detection in the cKIT gene and ultrasound examination of abdominal organs can be useful for timely diagnosis of systemic mastocytosis, which allows to carry out the necessary correction of the disease status and drug therapy.

Relevance. The gasotransmitter hydrogen sulphide (H2S) is awell-known signalling molecule that is involved in the regulation of awide range of cellular functions in both health and disease. Its biological effects in obesity and metabolic syndrome (MetS) have been investigated. It is apromising pharmacological target for the correction of MetS and associated diseases.The aimof this study is to investigate the role of endogenously produced H2S in the pathogenesis of metabolic disorders in experimental Met S.Materials and Methods. Ahigh-fat and high-carbohydrate diet was used to induce MS in male Wistar rats. The body and adipose tissue weights of the animals were determined. The animals body and adipose tissue weights were measured. Indicators of carbohydrate and lipid metabolism in the blood serum were determined with the use of reagent kits. Additionally, the levels of reactive oxygen species (ROS) and reduced glutathione (GSH) were analyzed in adipose tissue through photometric analysis. The concentration of H2S in blood serum and adipose tissue, as well as H2S production by adipocytes, was measured spectrophotometrically.Results and Discussion. H2S concentrations in blood serum, adipose tissue and adipocyte H2S production were found to decrease in animals with hyperglycaemia and insulin resistance. Additionally, anegative correlation was observed between the H2S content and production in the adipose tissue of rats with the mass of visceral adipose tissue. Furthermore, anegative relationship was found between the concentrations of glucose, insulin, leptin, ROS and the level of H2S in blood serum and adipose tissue. In contrast, the increase in glutathione (GSH) in adipocytes was directly correlated with the increase in hydrogen sulfide (H2S) in serum and adipose tissue cells.Conclusions. The regulatory effect of H2S on target cell function has been extensively studied. However, its role in the development and progression of MetS remains unclear. Our work demonstrates that under conditions of metabolic pathology, there is adecrease in the serum concentration of H2S and its production in adipose tissue. This decrease correlates with the development of obesity, hyperglycemia, insulinemia, leptinemia, and redox imbalance.

Relevance. A key factor influencing the effectiveness of assisted reproductive technology programmes is the quality of the embryo transferred into the uterine cavity. The aim is to investigate the possibility of using quantitative assessment of genomic (gDNA), mitochondrial DNA (mtDNA) levels in spent culture medium (SCM) and mtDNA in the trophectoderm (TE) as a marker of successful implantation and pregnancy lasting more than 12 weeks. Materials and Methods. The study included 195 SCM samples from 93 couples with infertility. Frozen embryo transfer (FET) was performed in 43 patients. The level of gDNA, mtDNA in SCM by real-time PCR and mtDNA in TE by NGS was analysed depending on the chromosomal status of embryos and the outcome of FET. Statistical analyses were performed in Jamovi software. Results and Discussion. Depending on the outcome of transfer, the patients were divided into groups: Group 1—negative result, n=18; Group 2—pregnancy continuing for more than 12 weeks, n=25. mtDNA and gDNA in SCM were statistically significantly lower in group 2 compared to group 1 (p=0.007 and p=0.01, respectively). When mtDNA levels in SCM were 95 copies, the odds of pregnancy rate and ongoing pregnancy were increased 3.2-fold (95 % CI=1.1–31.6). Prediction formulas for the probability of ongoing pregnancy after FET were proposed for continuous (sensitivity was 67.0 %, specificity was 91 %, area under the curve (AUC) was 90.0 %) and binary (sensitivity was 75.0 %, specificity was 70 %, AUC was 83.8 %). Thus, the level of gDNA and mtDNA copy number in the embryo culture medium is a significant prognostic factor for the onset and prolongation of pregnancy in ART programmes. Depending on the ploidy of the blastocysts, we analysed the level of mtDNA in TE, gDNA and mtDNA in the SCM of embryos in groups 1.1. (euploid, n=98) and 2.1. (aneuploid, n=97). No differences were detected in the compared groups. Conclusion. Assessment of gDNA and mtDNA levels in SCM may be an additional non-invasive marker for selection of the most promising euploid embryo for transfer into the uterine cavity.

The mixed assessment by critics and theorists of the deus ex machina artistic device common in popular cinema requires a more thorough study of its dramatic and narrative functions in science fiction films. It is in the construction of film images of the future that this technique is combined with a fantastic assumption, expressing the narrator’s attitude towards artistic narration and becoming an argument in dialogue with the viewer. The study reveals, based on the analysis of empirical material, the multifunctionality of deus ex machina using the example of the development of the theme of technological singularity in cinema. The analysis of films significant for the development of the science fiction (Sci-Fi) genre and the most popular television series among science fiction fans today demonstrates the evolution of the deus ex machina technique. In addition to the trivial function of arbitrary resolution of peripeteia, it acquires various dramatic functions (accelerating or slowing down the rhythm of action, connecting parts of the plot in a large form), obtains the properties of scaling and fragmentation, synchrony and asynchrony with a fantastic assumption, adding complex narrative functions to the toolkit of expressive means, through which the narrator reveals or, on the contrary, conceals his attitude to artistic reality, involving the viewer into the game of probable meanings. The authors of the article come to the conclusion that the theme of technological singularity has been penetrating cinema since its appearance in the work of L. Lumiere and determines, depending on the narrator’s attitude to the topic, the vector of techno-skepticism or techno-optimism in the eschatological dilemma that characterizes the cosmogony of traditional religions. The article is of interest to researchers and film lovers and contributes to the study of artistic and scientific communication.

The article examines how issues of identity construction in Russian urban agglomerations are reflected in the Russian regional politicians’ discourse in mass media. The study concerns theoretical problems of identity construction and the role of regional government bodies in shaping the territorial identity of the population. The specificity of the Russian situation is the absence of governing bodies related to the agglomeration level in most urban agglomerations. The empirical basis of the study is the texts of subnational politicians posted on the official websites of regional government bodies: websites of governors and regional governments, official pages in the mass media. The empirical information on identity policy were collected from the Internet sources (official portals of regional executive authorities, media reports). Discourse analysis was carried out after monitoring social media materials (VKontakte web-pages of regional leaders). The article reflects five cases out of sixteen Russian ones related to the Ural and Siberian agglomerations with a megalopolis core. The empirical data cover the period from December 2022 to the end of 2023. The choice of the time period for analysis is determined by the fact that by this period the most significant factors influencing the policy of our state at present (the pandemic and the Special military operation) have already manifested themselves in full. It has been confirmed that the problems of agglomeration development in the public official subfederal discourse in most cases are reduced to economic problems; first of all, it concerns the development of industry, science (high technology), transport, and waste disposal. In all analyzed cases, insufficient attention was found out, paid to the role of the implemented socio-cultural projects of subfederal identity policy, and also distancing from the discussion of the problems of integration of labor migrants in the public space. Insignificant number of messages from representatives of the regional political and administrative elite about the socio-cultural meanings of the formed agglomerations can become a significant limitation of information support for the agglomeration development of modern contemporary Russia.

For the first time, this article presents a torn and discarded letter by Anna Akhmatova, which was glued and preserved by Pavel Luknitsky. Part of the letter and the appeal to the addressee are lost, so in the archive (Institute of Russian Literature of the Russian Academy of Sciences) the document is listed as a letter to an unidentified person. The publisher determines the addressee and date according to the content and presumably restores some lost words. Attribution and restoration of gaps are accompanied by a detailed justification. The letter, written on March 27, 1925, was addressed to Akhmatova’s mother, Inna Erasmovna Gorenko, who at that time lived with her sister Anna Erasmovna Vakar and her family in severe poverty in the former Vakar estate in Podolsk province (now Khmelnitsky region of Ukraine). The article describes the main characters in the letter and the difficult circumstances of Akhmatova’s life at this time, which are half-hidden behind a few lines of text. The article also provides comments on the names mentioned in the letter. It reveals the relationship between Akhmatova and the poet Maria Shkapskaya; it tells us about a little-known friend of Akhmatova to whom she dedicated her poem, “If the moon’s horror is splashing...” (1928), — about Mikhail Zimmerman, assistant director-administrator at the former Mariinsky Theatre. A study of his file in the fund of the Directorate of Academic Theatres (Central State Archive of Literature and Art) reveals several facts about his biography.

The notion of politeness is closely connected with communication control as one of its important mechanisms, which, however, has not been thoroughly researched in academic literature. In the present paper, we view this mechanism through the prism of communication monitoring, defined as a social negotiation instrument aimed at the speaker’s self-control and regulation of other people’s verbal and nonverbal behaviour. The study employs a complex of qualitative methods including observation, definition analysis, discourse analysis and introspection. Drawing upon the data of over 1500 communicative situations in English and Russian, we distinguish the prognostic, diagnostic, regulative, corrective, and reflexive functions of monitoring, as well as the function of conflict resolution. The connection between monitoring and politeness is determined by the existence of social constraints and the necessity to observe established rules and norms. The presence of multiple communication variables makes it possible to distinguish different types of monitoring: (i) horizontal vs. vertical monitoring; (ii) self-monitoring vs. monitoring of others; (iii) verbal vs. nonverbal monitoring; (iv) oral vs. written monitoring; (v) explicit vs. implicit monitoring; (vi) pre-monitoring vs. concurrent monitoring vs. post-monitoring; (vii) direct vs. mediated monitoring; and (viii) overt vs. covert monitoring. (Im)politeness is manifested in all the types through the choice of words and communication strategies, observance or violation of conversational rules, and different forms of nonverbal behaviour. These findings can lead to their practical application and help to enhance the effectiveness and quality of human interaction.

Although ellipsis has been extensively researched in theoretical linguistics, the pragmatic applications of ellipsis in corporate interactions remain largely unexplored. While previous studies have empirically established that the omission of noun phrases (NPE) and verb phrases (VPE) serves to economise and facilitate communication and create a different interpretation for the recipient, little is known about the pragmatic functions of these elliptical constructions within a corporate context and how the pragmatics of NPE and VPE can help contribute to achieving the communicative goals. The current study seeks to identify the pragmatic value of NPE and VPE in corporate communication in order to see how they contribute to the efficiency of the discourse and its emotional intensity. The study captures both qualitative and quantitative data. Data were gathered from 312 transcripts obtained from corporate communications (negotiations, meetings, presentations). During the qualitative phase, discourse analysis was used to analyse the function of NPE and VPE in achieving communicative functions such as clarity, emphasis, and rhetorical effect. For the quantitative phase, measuring the frequency of occurrence and contextual usage of these constructions contributed to discerning patterns and functions in the use of NPE and VPE in corporate discourse. Across both the qualitative and quantitative phases, results indicated that NPE and VPE improved discourse efficiency by eliminating redundancies and narrowing focus on strategic elements for an audience. It was additionally shown that NPE improved the emphasis on important content by eliminating redundancies while the use of VPE conveyed urgency and immediacy across communicative contexts. The quantitative phase also illustrated NPE and VPE as easily replicable constructs and that their strategic use influences an audience’s emotional reaction. Additionally, the analysis showed NPE and VPE may contribute to recipient’s perception of confidence and authority regarding their communicative competency in a corporate setting. The study thus challenges the traditional view of ellipsis from linguistic theory to be understood as a tool of pragmatics, not only for its ability to reduce language, but to direct attention and interpretation. The final conclusion of the research is NPE and VPE have specific value in building improved strategies of corporate communication, creating clarity, and emphasising information of importance.

In the academic landscape, where knowledge is constantly debated, reviews serve as crucial navigational tools. The critical analyses not only evaluate previous studies but also reveal the reviewer’s own stance towards them. Drawing upon a corpus of 124 philology thesis review reports published in 2020-2024, this study explores the process of stancetaking in evaluative academic discourse through the use of attitude markers. The aim of the study is to analyse the predominant types, frequencies and lexical-grammatical categories of linguistic items used by Russian thesis reviewers to take attitudinal stance. The instances of attitude were identified based on Mur-Dueñas’s typology, including three groups – significance, assessment, and affect. The findings revealed that attitude markers constitute an integral part of thesis reviews, helping verify scientific knowledge and conferring authority and authenticity upon dissertations by evaluating their quality and value to the field. The most frequent attitude markers found in the corpus were assessment resources predominantly realised through adjectives and adverbs. Significance markers ranked second and were presented by adjectives and nouns. Affective stance was infrequent in the corpus, and the range of emotions was not so wide, including a limited number of affective states such as interest, surprise, regret, disappointment, joy, and approval. Affective stance was realised through adjectives, adverbs, nouns, verbs, and nominal phrases. The analysis also showed that negative assessments were mitigated in most cases through the use of hedges, while positive attitudes were amplified through the use of boosters.

Background: Games are a promising strategy for rehabilitating older adults. The effect of games on promoting healthy lifestyles and preventing frailty remains uncertain. This article aims to describe the process of development and validation of the game “Bem-me-quer para a saúde”® to promote the acquisition of healthy lifestyles and prevent frailty in over 65-year-olds. Methods: This study comprised three distinct phases, spanning from December 2023 to June 2024. The first phase comprised a thorough review of the scientific literature on the frailty and lifestyles of older adults, a second phase of game design, and a third phase of content and semantic validation conducted by specialized nurses and older adults. Results: After revising literature, this study utilized an e-Delphi with a panel of 14 specialist nurses who underwent two rounds of evaluation. The “Bem-me-quer para a saúde”® game includes a puzzle board with 54 pieces and 30 educational cards. In the final phase, we evaluated the game on a cohort of 50 older adults, highlighting its reflective, interactive, and educational aspects. Conclusions: The game presented sufficient evidence of content validity and relevance to clinical practice. We should conduct additional research to evaluate its impact on lifestyle modification and frailty prevention.

Questions of the creative history of the homiletic heritage of Metropolitan Stefan Jaworski remain unexplored. The study of the unique manuscript of the first quarter of the 18th century and its comparison with later versions of solemn tales allowed us to conclude that the author undertook a significant content, stylistic, and lexical editing of the pieces. A comparative textual analysis of the lifetime autograph and later versions of sermons suggested that the author’s revision of the original draft could have been carried out by Metropolitan Stephen in the period from 1711 to 1718, during his preparation for publication of a collection of the most significant victory tales of the first decade of the 18th century. After Yavorsky’s death, Gabriel Buzhinsky collected and copied Yavorsky’s laudatory sermons, which gave researchers reason to assume that he was the editor and compiler of this collection. However, our textual analysis of the versions convincingly proved that Buzhinsky was not the editor of Yavorsky’s work but apparently relied on the versions of the sermon texts already edited by the author.

High entropy intermetallic compounds (HEICs) are an interesting class of materials combining the properties of multicomponent solid solutions and the ordered superlattices in a single material. In this work, microstructural and magnetic properties of (CoCuFeMnNi)Al, (CoCuFeMnNi)Zn3, (FeCoMnNiCr)3Sn2, (FeCoNiMn)3Sn2 and Cu3(InSnSbGaGe) HEICs fabricated by induction melting are studied. The magnetic properties of the HEICs was determined mainly by the nature of the magnetic momentum of the constituent elements. (CoCuFeMnNi)Al and (CoCuFeMnNi)Zn3 displayed ferromagnetic behavior at 5 K, while indicated linear dependency of magnetization vs. magnetic (i.e. paramagnetic or antiferromagnetic state) at 300 K. The magnetization of (FeCoMnNiCr)3Sn2, (FeCoNiMn)3Sn2 and Cu3(InSnSbGaGe) HEICs at 300 K exhibited a nearly linear dependency to magnetic field. Among all the investigated samples, (CoCuFeMnNi)Al exhibited the best magnetic properties with a saturation magnetization of about Ms = 6.5 emu/g and a coercivity of about Hc = 100 Oe.

The article presents modern approaches to the diagnosis and therapy of patients with allergic rhinitis. The document was developed by the professional association of pediatric specialists — the Union of Pediatricians of Russia — together with leading specialists of the Russian Association of Allergologists and Clinical Immunologists, the National Medical Association of Otorhinolaryngologists and is regularly updated taking into account the latest data on the effectiveness and safety of various medical interventions. The article provides information about the epidemiology of allergic rhinitis, provides characteristic diagnostic signs of the disease, allowing for establishment as timely as possible of a correct diagnosis and, taking into account a personalized approach, prescribe effective therapy.

Abstract Background The composition and distribution of fatty acids (FA) are important factors determining the quality, flavor, and nutrient value of meat. In addition, FAs synthesized in the body participate in energy metabolism and are involved in different regulatory pathways in the form of signaling molecules or by acting as agonist or antagonist ligands of different nuclear receptors. Finally, synthesis and catabolism of FAs affect adaptive immunity by regulating lymphocyte metabolism. The present study performed genome-wide association studies using FA profiles of blood, liver, backfat and muscle from 432 commercial Duroc pigs. Results Twenty-five genomic regions located on 15 Sus scrofa chromosomes (SSC) were detected. Annotation of the quantitative trait locus (QTL) regions identified 49 lipid metabolism-related candidate genes. Among these QTLs, four were identified in more than one tissue. The ratio of C20:4n-6/C20:3n-6 was associated with the region on SSC2 at 7.56–14.26 Mb for backfat, liver, and muscle. Members of the fatty acid desaturase gene cluster (FADS1, FADS2, and FADS3) are the most promising candidate genes in this region. Two QTL regions on SSC14 (103.81–115.64 Mb and 100.91–128.14 Mb) were identified for FA desaturation in backfat and muscle. In addition, two separate regions on SSC9 at 0 – 14.55 Mb and on SSC12 at 0–1.91 Mb were both associated with the same multiple FA traits for backfat, with candidate genes involved in de novo FA synthesis and triacylglycerol (TAG) metabolism, such as DGAT2 and FASN. The ratio C20:0/C18:0 was associated with the region on SSC5 at 64.84–78.32 Mb for backfat. Furthermore, the association of the C16:0 content with the region at 118.92–123.95 Mb on SSC4 was blood specific. Finally, candidate genes involved in de novo lipogenesis regulate T cell differentiation and promote the generation of palmitoleate, an adipokine that alleviates inflammation. Conclusions Several SNPs and candidate genes were associated with lipid metabolism in blood, liver, backfat, and muscle. These results contribute to elucidating the molecular mechanisms implicated in the determination of the FA profile in different pig tissues and can be useful in selection programs that aim to improve health and energy metabolism in pigs.

Abstract Mantle cell lymphoma (MCL) is genetically characterized by the IG::CCND1 translocation mediated by an aberrant V(D)J rearrangement. CCND1 translocations and overexpression have been identified in occasional aggressive B-cell lymphomas with unusual features for MCL. The mechanism generating CCND1 rearrangements in these tumors and their genomic profile are not known. We have reconstructed the IG::CCND1 translocations and the genomic profile of 13 SOX11-negative aggressive B-cell lymphomas using whole genome/exome and target sequencing. The mechanism behind the translocation was an aberrant V(D)J rearrangement in three tumors and by an anomalous IGH class-switch recombination (CSR) or somatic hypermutation (SHM) mechanism in ten. The tumors with a V(D)J-mediated translocation were two blastoid MCL and one high-grade B-cell lymphoma. None of them had a mutational profile suggestive of DLBCL. The ten tumors with CSR/SHM-mediated IGH::CCND1 were mainly large B-cell lymphomas, with mutated genes commonly seen in DLBCL and BCL6 rearrangements in 6. Two cases, which transformed from marginal zone lymphomas, carried mutations in KLF2, TNFAIP3 and KMT2D. These findings expand the spectrum of tumors carrying CCND1 rearrangement that may occur as a secondary event in DLBCL mediated by aberrant CSR/SHM and associated with a mutational profile different from that of MCL.

Abstract Proton therapy gives less dose to healthy tissue compared to conventional X-ray therapy, but systematic comparisons of normal tissue responses are lacking. The aim of this study was to investigate late tissue responses in the salivary glands following proton- or X-irradiation of the head and neck in mice. Moreover, we aimed at investigating molecular responses by monitoring the cytokine levels in serum and saliva. Female C57BL/6J mice underwent local fractionated irradiation with protons or X-rays to the maximally tolerated acute level. Saliva and serum were collected before and at different time points after irradiation to assess salivary gland function and cytokine expression. To study late responses in the major salivary glands, histological analyses were performed on tissues collected at day 105 after onset of irradiation. Saliva volume after proton and X-irradiation was significantly lower than for controls and remained reduced at all time points after irradiation. Protons caused reduced saliva production and fewer acinar cells in the submandibular glands compared to X-rays at day 105. X-rays induced a stronger inflammatory cytokine response in saliva compared to protons. This work supports previous preclinical findings and indicate that the relative biological effectiveness of protons in normal tissue might be higher than the commonly used value of 1.1.

Abstract The human microbiome emerges as a promising reservoir for diagnostic markers and therapeutics. Since host-associated microbiomes at various body sites differ and diseases do not occur in isolation, a comprehensive analysis strategy highlighting the full potential of microbiomes should include diverse specimen types and various diseases. To ensure robust data quality and comparability across specimen types and diseases, we employ standardized protocols to generate sequencing data from 1931 prospectively collected specimens, including from saliva, plaque, skin, throat, eye, and stool, with an average sequencing depth of 5.3 gigabases. Collected from 515 patients, these samples yield an average of 3.7 metagenomes per patient. Our results suggest significant microbial variations across diseases and specimen types, including unexpected anatomical sites. We identify 583 unexplored species-level genome bins (SGBs) of which 189 are significantly disease-associated. Of note, the existence of microbial resistance genes in one specimen was indicative of the same resistance genes in other specimens of the same patient. Annotated and previously undescribed SGBs collectively harbor 28,315 potential biosynthetic gene clusters (BGCs), with 1050 significant correlations to diseases. Our combinatorial approach identifies distinct SGBs and BGCs, emphasizing the value of pan-body pan-disease microbiomics as a source for diagnostic and therapeutic strategies.

Abstract During infection Mycobacterium tuberculosis (Mtb) forms physiologically distinct subpopulations that are recalcitrant to treatment and undetectable using standard diagnostics. These difficult to culture or differentially culturable (DC) Mtb are revealed in liquid media, their revival is often stimulated by resuscitation-promoting factors (Rpf) and prevented by Rpf inhibitors. Here, we investigated the role of nitric oxide (NO) in promoting the DC phenotype. Rpf-dependent DC Mtb were detected following infection of interferon-γ-induced macrophages capable of producing NO, but not when inducible NO synthase was inactivated. After exposure of Mtb to a new donor for sustained NO release (named NOD), the majority of viable cells were Rpf-dependent and undetectable on solid media. Gene expression analyses revealed a broad transcriptional response to NOD, including down-regulation of all five rpf genes. The DC phenotype was partially reverted by over-expression of Rpfs which promoted peptidoglycan remodelling. Thus, NO plays a central role in the generation of Rpf-dependent Mtb, with implications for improving tuberculosis diagnostics and treatments.

Abstract Background Chitosan oligosaccharides (COS) have great potential for applications in several fields, including agriculture, food industry or medicine. Nevertheless, the large-scale use of COS requires the development of cost-effective technologies for their production. The main objective of our investigation was to develop an effective method of enzymatic degradation of chitosan in a column reactor using Mucor circinelloides IBT-83 cells, immobilized in a polyurethane foam (PUF). These cells serve as a source of chitosanolytic enzymes. Results The study revealed that the process of freeze-drying of immobilized mycelium increases the stability of the associated enzymes during chitosan hydrolysis. The use of stabilized preparations as an active reactor bed enables the production of COS at a constant level for 16 reactor cycles (384 h in total), i.e. 216 h longer compared to non-stabilized mycelium. In the hydrolysate, oligomers ranging in structure from dimer to hexamer as well as D-glucosamine were detected. The potential application of the obtained product in agriculture has been verified. The results of phytotests have demonstrated that the introduction of COS into the soil at a concentration of 0.01 or 0.05% w/w resulted in an increase in the growth of Lepidium sativum stem and root, respectively (extensions by 38 and 44% compared to the control sample). Conclusions The research has verified that the PUF-immobilized M. circinelloides IBT-83 mycelium, which has been stabilized through freeze-drying, is a promising biocatalyst for the environmentally friendly and efficient generation of COS. This biocatalyst has the potential to be used in fertilizers.

Ribosomal RNA (18S, 5.8S, 28S) gene clusters in genomes form regions that consist of multiple tandem repeats. They are located on a single or several pairs of chromosomes and play an important role in the formation of the nucleolus responsible for the assembly of ribosome subunits. The rRNA gene cluster sequences are widely used for taxonomic studies, however at present, complete information on the avian rDNA repeat unit structure including intergenic spacer sequence is available only for the chicken (Gallus gallus domesticus Linnaeus, 1758). The GC enrichment and high-order repeats peculiarities within the intergenic spacer described for the chicken rDNA cluster may be responsible for these failures. The karyotype of the Japanese quail (Coturnix japonica Temminck et Schlegel, 1849) deserves close attention because, unlike most birds, it has three pairs of nucleolar organizer bearing chromosomes, two of which are microchromosomes enriched in repeating elements and heterochromatin that carry translocated terminal nucleolar organizers. Here we assembled and annotated the complete Japanese quail ribosomal gene cluster sequence of 21166 base pairs (GenBank under the registration tag BankIt2509210 Coturnix OK523374). This is the second deciphered avian rDNA cluster after the chicken. Despite the revealed high similarity with the chicken corresponding sequence, it has a number of specific features, which include a slightly lower degree of GC content and the presence of bendable elements in the content of both the transcribed spacer I and the non-transcribed intergenic spacer.

Cardiovascular diseases (CVDs) significantly exacerbate the severity and mortality of COVID-19. We aimed to investigate whether GWAS-significant SNPs correlate with CVDs in severe COVID-19 patients. DNA samples from 199 patients with severe COVID-19 hospitalized in intensive care units were genotyped using probe-based PCR for 10 GWAS SNPs previously implicated in severe COVID-19 outcomes. SNPs rs17713054 SLC6A20-LZTFL1 (risk allele A, OR = 2.14, 95% CI 1.06–4.36, p = 0.03), rs12610495 DPP9 (risk allele G, OR = 1.69, 95% CI 1.02–2.81, p = 0.04), and rs7949972 ELF5 (risk allele T, OR = 2.57, 95% CI 1.43–4.61, p = 0.0009) were associated with increased risk of coronary artery disease (CAD). SNPs rs7949972 ELF5 (OR = 2.67, 95% CI 1.38–5.19, p = 0.003) and rs61882275 ELF5 (risk allele A, OR = 1.98, 95% CI 1.14–3.45, p = 0.01) were linked to a higher risk of cerebral stroke (CS). No associations were observed with AH. Bioinformatics analysis revealed the involvement of GWAS-significant loci in atherosclerosis, inflammation, oxidative stress, angiogenesis, and apoptosis, which provides evidence of their role in the molecular mechanisms of CVDs. This study provides novel insights into the associations between GWAS-identified SNPs and the risk of CAD and CS.

Labor productivity is a key indicator of economic development and public well-being. This study assesses the structural shifts, regional dynamics, and sectoral trends in the domain of labor productivity in the Russian Arctic from 2011 to 2021, identifying aggregated economic sectors. The findings reveal that labor productivity levels in the Russian Arctic exceed the national average, primarily due to the resource-based nature of regional economies. However, a major issue is the persistently high level of interregional differentiation in labor productivity within the Arctic. The study demonstrates that an initially high level of labor productivity does not necessarily ensure long-term growth. An analysis of structural shifts in labor productivity over the past decade indicates a shift towards the market sector of the Arctic economy, evidenced by an increased share in gross regional product (GRP) and a decrease in time worked. Within the market sector, several trends are observed: the leading role of the extractive industry is maintained due to its expanding share in GRP; the role of agriculture is growing, reflected in a decreased share of hours worked; and the importance of other market sector branches, particularly transport, communication, and electric power, is diminishing as their share of total hours worked increases. The observed decline in labor productivity within the non-market sector suggests the potential for negative social consequences for the Arctic population. An analysis of labor productivity growth rates indicates that the leading sectors in terms of growth are mining, finance and business services, construction, and trade. These sectors can be considered sources of economic growth in the Arctic. Interregional differences in labor productivity growth rates within the same sector of the Arctic economy suggest the influence of regional factors, highlighting the potential for discovering unique reserves of productivity growth in each region.

Background: Galectins are a family of β-galactoside binding proteins that regulate the vast majority of cellular functions, including proliferation, migration, adhesion, and phagocytosis in both health and disease. More and more experimental and clinical evidence indicates that galectins are involved in many stages of carcinogenesis, including patients with renal cell carcinoma (RCC). Aim: To analyze the clinical significance of soluble forms of galectins -1, -3, -4, -7, -9 in patients with various histological RCC types. Materials and methods: We performed a retrospective analysis of the clinical significance of galectins -1, -3, -4, -7, -9 in the serum of 140 RCC patients (84 with clear cell RCC (ccRCC), 38 with papillary (papRCC), 18 with chromophobe (chrRCC)) and in 73 healthy donors (control group), who were examined and treated from 2019 to 2023 in the N. N. Blokhin National Medical Research Center of Oncology. Galectin levels were measured in serum (obtained according to standard methods before the initiation of specific treatment) with an enzyme-linked immunosorbent assay. Results: There was a significant increase in serum galectin -1, -3, -9 levels in the whole RCC patient group, compared to the healthy donor control group; no increase was found for galectins -4 and -7. Serum galectin-1 levels in the ccRCC and papRCC patients were significantly higher than those in the controls (p = 0.0003 and p = 0.0135, respectively). No association between the serum galectins -1 and -7 and the clinical and morphological characteristics of RCC was found; however, serum galectin-7 levels in the papRCC patients correlated with the grade of tumor differentiation (r = -0.592; p = 0.001). The area under the ROC curve (AUC) for galectin-1 in ccRCC was 0.721 (p 0.0001), in papRCC 0.673 (p = 0.0086), and in chrRCC 0.576 (p = 0.355). For galectin-7, the ROC AUC values were 0.527 (p = 0.634) in ccRCC, 0.513 (p = 0.845) in papRCC, and 0.566 (p = 0.425) in chrRCC. In all histological types of RCC, there was a significant increase in serum galectin-3 compared to the controls (ccRCC, p = 0.0208; papRCC, p = 0.0014; chrRCC, p = 0.0041). The ROC analysis for galectin-3 in patients with RCC of various histological types showed AUC = 0.721 (p 0.0001) for ccRCC, 0.673 (p = 0.0086) for papRCC, and 0.576 (p = 0.355) for chrRCC. Galectin-9 levels was directly and significantly associated with the tumor size, as well as with regional metastases (r = 0.251, p = 0.021; r = 0.239, p = 0.028, respectively). The AUC values for galectin-4 were 0.619 (p = 0.021) in ccRCC, 0.577 (p = 0.214) in papRCC, and 0.534 (p = 0.666) for chrRCC. For galectin-9, they were 0.649 (p = 0.0075), 0.613 (p = 0.087), and 0.539 (p = 0.637), respectively. Conclusion: The study has demonstrated a certain association between serum galectin -1, -3, -4, -7, and -9 in the patients with RCC of various histological types. Although the results of the ROC analysis indicated average quality of the model, which does not allow for the use of the obtained data for diagnostic purposes, it is necessary to continue the research for better understanding of the mechanisms of galectin functioning, before galectin-based therapeutic agents would be introduced into clinical practice for the treatment of RCC.

Research subject. The development of the global economy indicates the formation of a new trend in the formation of the smart economy, which currently covers both developed and developing countries. According to the analysis, developed countries are leaders in economic development precisely because of the development of technologies that are the basis for the formation of the smart economy and the smart intellectualisation of economic activity. The smart economy in Asia is actively developing due to the intensive introduction of the latest technologies, innovative management approaches, and increased resource efficiency. Asian countries such as China, Japan, South Korea, Singapore, and India are leaders in the development of the smart economy. At the same time, Asian countries have been demonstrating one of the highest rates of economic development since the beginning of the XXI century, which is primarily due to the active technologisation of production and the spread of communication technologies in all areas of economic activity. Several technology centres are emerging in Asia, concentrating technology companies and creating a favourable environment for the development of the smart economy. Methodology. The article conducts a comparative analysis of the factors contributing to the development of the smart economy in individual Asian countries, identifies the most influential factors and the degree of their impact on each country. The purpose of this study is to identify the factors influencing the development of the smart economy and compare their impact in the economies of China, India and Singapore. To achieve this goal, the following research objectives are envisaged: to identify factors that have a significant impact on the development of the smart economy in different countries; to assess the impact of individual factors on the development of the smart economy in China, India and Singapore; to compare the impact of individual factors of the smart economy on the economies of these countries; and to assess the models of smart economy development in China, India and Singapore. Conclusion. The smart economy in Asia is characterised by unique features that reflect the cultural, technological and economic conditions of the region. The key features of the Asian smart economy include a high level of digitisation and technological integration, active development of smart cities, financial technologies (FinTech), a focus on automation and robotics, innovation hubs and support for start-ups, environmental sustainability and green energy, and the digitalisation of governance and public services. Asian countries are also distinguished by the integration of smart technologies into the everyday life of citizens and the support of innovation ecosystems at the state level.

The lesser grain borer (Rhyzopertha dominica F.) and the rice weevil (Sitophilus oryzae L.) are stored grain pests that cause significant economic losses in grain storage. This study aimed to analyze the impact of the chemical composition of wheat and barley grain (e.g., protein, fatty acids and total antioxidant capacity) on the development of two species of storage pests and to determine the relationship between the analyzed variables. The study involved the evaluation of 10 wheat cultivars and 10 barley cultivars under laboratory conditions. The observations included assessing the beetles’ progeny abundance, dust mass produced after feeding, and grain mass loss. The chemical composition of the tested wheat and barley cultivars was also determined, and the influence of different chemical compositions on insect development was investigated. The results of the experiment revealed diversity of resistance among cultivars to pest feeding. Larger populations of the lesser grain borer were observed on barley grains, while rice weevil populations were higher on wheat. Cultivars with higher protein and fat content were more susceptible to pest attacks. A connection between the amount of dust, grain mass loss, and the type of pest was also identified, indicating differences in feeding mechanisms and selective food preferences of these insects. The grain chemistry of wheat cultivars, including the content of fatty acids and antioxidants, significantly influenced the progeny abundance of S. oryzae, suggesting the potential of these components as natural barriers against storage pests. This study provides valuable insights for developing breeding strategies to enhance the natural resistance of new grain cultivars to these pests, contributing to the reduction of pesticide use. Statistical analyses confirmed the significance of differences in grain composition in varied resistance to the studied pests. The conclusions drawn from this work may help establish new storage and breeding practices, promoting sustainable agriculture and protecting natural resources.

The article analyzes the landmark novel of Russian writer M.L. Stepnova, The Garden (2020), which has aroused the public’s and critic’s interest, continuing the “estate text” of Russian literature of the 19th–20th centuries. It is shown that the image of the garden in the work is both national (the whole tradition of the Russian “estate text”) and universal (the Bible, Voltaire, H.L. Borges, U. Eco, etc.). The key to an adequate reading of the postmodern novel with its “semantic insolubility,” narrative “nonselectio,” experiments on human identity, an invitation to the “alternative history,” etc. is an analysis of its intertextuality, generating original life-creating strategies. There are three concentric circles of intertextuality that diverge in the breadth of space-time coverage: character, author-narrative, and mythopoetic. If in character terms the protagonist of the work — the garden — directly participates in people’s lives, at the author-narrative level becomes an ideologeme, symbolizing with his death under the axes of hired workers the tragic fate of Russia at the turn of the 19th–20th centuries, then in the super-author’s mythopoetic sphere reveals the quality of practical immortality, indestructibility. The reason for the suicidal cutting down of the garden of the grown-up Princess Boryatinskaya is the excommunication of this heroine from fiction, primarily “estate,” with its powerful lifecreating potential. The scientific novelty of the research lies in the systematic analysis of the intertextual strategies of the iconic modern novel for the first time and the identification of their three-level structure. The article applies historical-literary and cultural approaches, methods of historical poetics, and structural-semiotic analysis and uses the modernist and postmodern thesaurus paradigms.

Abstract DNA-hypomethylating agents (HMAs) induce notable remission rates in AML/MDS patients with TP53 mutations; however, secondary resistance often develops rapidly. In the DECIDER trial (NCT00867672), elderly AML patients (also those with adverse genetics) randomized to all-trans retinoic acid (ATRA) added to decitabine (DEC) attained significantly delayed time-to-resistance. An 82-year-old patient with a non-disruptive, in-frame TP53 mutation (p.Cys238_Asn239delinsTyr, VAF 90%) and complex-monosomal karyotype attained a complete hematologic and cytogenetic remission with DEC + ATRA, with 3.7 years survival after 30 treatment cycles that were well-tolerated. Further HMA + ATRA studies appear warranted in AML/MDS patients of different genetic risk groups ineligible for more intensive treatment. Trial registration: This trial was registered at ClinicalTrials.gov identifier: NCT00867672

Abstract The formation of nuclear biomolecular condensates is often associated with local accumulation of proteins at a site of DNA damage. The key role in the formation of DNA repair foci belongs to PARP1, which is a sensor of DNA damage and catalyzes the synthesis of poly(ADP-ribose) attracting repair factors. We show here that biogenic cations such as Mg2+, Ca2+, Mn2+, spermidine3+, or spermine4+ can induce liquid-like assembly of poly(ADP-ribosyl)ated [PARylated] PARP1 into multimolecular associates (hereafter: self-assembly). The self-assembly of PARylated PARP1 affects the level of its automodification and hydrolysis of poly(ADP-ribose) by poly(ADP-ribose) glycohydrolase (PARG). Furthermore, association of PARylated PARP1 with repair proteins strongly stimulates strand displacement DNA synthesis by DNA polymerase β (Pol β) but has no noticeable effect on DNA ligase III activity. Thus, liquid-like self-assembly of PARylated PARP1 may play a critical part in the regulation of i) its own activity, ii) PARG-dependent hydrolysis of poly(ADP-ribose), and iii) Pol β–mediated DNA synthesis. The latter can be considered an additional factor influencing the choice between long-patch and short-patch DNA synthesis during repair.

Abstract Malignant transformation (MT) is commonly seen in IDH-mutant gliomas. There has been a growing research interest in revealing its underlying mechanisms and intervening prior to MT at the early stages of the transforming process. Here we established a unique pair of matched 3D cell models: 403L, derived from a low-grade glioma (LGG), and 403H, derived from a high-grade glioma (HGG), by utilizing IDH-mutant astrocytoma samples from the same patient when the tumor was diagnosed as WHO grade 2 (tumor mutational burden (TMB) of 3.96/Mb) and later as grade 4 (TMB of 70.07/Mb), respectively. Both cell models were authenticated to a patient’s sample retaining endogenous expression of IDH1 R132H. DNA methylation profiles of the parental tumors referred to LGG and HGG IDH-mutant glioma clusters. The immunopositivity of SOX2, NESTIN, GFAP, OLIG2, and beta 3-Tubulin suggested the multilineage potential of both models. 403H was more prompt to cell invasion and developed infiltrative HGG in vivo. The differentially expressed genes (DEGs) from the RNA sequencing analysis revealed the tumor invasion and aggressiveness related genes exclusively upregulated in the 403H model. Pathway analysis showcased an enrichment of genes associated with epithelial-mesenchymal transition (EMT) and Notch signaling pathways in 403H and 403L, respectively. Mass spectrometry-based targeted metabolomics and hyperpolarized (HP) 1-13C pyruvate in-cell NMR analyses demonstrated significant alterations in the TCA cycle and fatty acid metabolism. Citrate, glutamine, and 2-HG levels were significantly higher in 403H. To our knowledge, this is the first report describing the development of a matched pair of 3D patient-derived cell models representative of MT and temozolomide (TMZ)-induced hypermutator phenotype (HMP) in IDH-mutant glioma, providing insights into genetic and metabolic changes during MT/HMP. This novel in vitro model allows further investigation of the mechanisms of MT at the cellular level. Graphic Abstract

Background. The development of media communication technologies leads to the new ways of information exchange. Content takes compact forms which requires to transform cognitive sphere in order to better operate with the emerging forms of information. Memosphere seems to be one of the directions in the development of modern media content, in which ethnocultural, social, value and cognitive features of perception unfold. Objective. The study is aimed at identifying the characteristics of perception and cognitive processing of the meme as the most relevant media form. Ethnocultural aspect of processing and identification of a meme is revealed, as well as the peculiarities of the perception of memes under the condition of a conflict between the ethnocultural identity of the respondent and the memosphere in which a specific meme originated. Methods. The experimental study included two series in which cultural specifics of cognitive activity in respondents when perceiving memes belonging to the Russian and Chinese memospheres were analyzed. Registration of oculomotor activity was carried out with an SMI RED 250 Hz tracker, hardware and software “SMI Gaze & Eye-tracking System” were applied. The experimental task involved visual analysis of polycode text (image), followed by an assessment of the origin of the meme (Russian or Chinese media sphere), as well as by marking the most subjectively significant image elements. Respondents' self-reports on the key features in meme identification were subjected to content analysis. IBM SPSS Statistics 26 was used in statistical analysis of the data obtained. Study Participants. 39 respondents took part in the experimental study: undergraduates at the Faculty of Journalism, Lomonosov Moscow State University, average age 24.7 years (SD = 4.1), including 21 citizens of the Russian Federation and 18 citizens of the People's Republic of China. Results. Respondents from the two groups successfully completed the task of meme identification in 64% of cases. The text in Russian was designated as the most informative element of the meme in both groups. Data on eye movements revealed a general tendency towards focal perception of the stimulus among respondents from Russia and towards sliding viewing among students from China. The origin of the stimulus shows weaker effect on the characteristics of oculomotor activity. For Russian memes, successful identification is associated with a shorter scanning path, and for Chinese memes, on the contrary, with a longer scanning path, which suggests the existence of an optimal visual scanning method for the culture-specific graphic structure of a meme. Conclusions. The results showed that ethnocultural features are manifested both at the level of constructing memes and at the level of their perception and cognitive processing by respondents. The conflict of perception manifests itself in the impossibility to interpret ethnocultural references, which leads to a misunderstanding of the meaning and is reflected in the parameters of the respondents’ oculomotor activity.

Introduction. Uropathogenic Escherichia coli (UPEC) are the dominant bacterial pathogens of urinary tract infections (UTIs). UPEC belong to different phylogenetic groups and have many virulence factors, the study of which, in conjuction with the assessment of their relationship with clinical forms of UTI, is necessary for a better understanding of the pathogenesis of UTI and the development of new diagnostic algorithms. Aim: determination of the molecular genetic characteristics of uropathogenic Escherichia coli isolated from pregnant women with asymptomatic bacteriuria. Materials and methods. Clinical isolates of uropathogenic E. coli (n = 70) from pregnant women with asymptomatic bacteriuria were included in the study. The PCR method was used to determine the belonging to phylogenetic groups and detect 15 virulence markers — genes associated with adhesion (fimH, papC, sfa, afa, focG); toxin synthesis (cnf 1, hlyA, sat, vat, usp); siderophores (fyuA, iroN, iuc); capsular antigen (kpsMII). To assess the statistical significance of differences, Fisher's exact test was used. Differences were considered statistically significant at a confidence interval of 95% (p 0.05). Results. Most of the UPEC isolates belonged to phylogroup B2 (51,4%) and were characterized by the detection of all UPEC-associated virulence factors included in this study; genes associated with adhesion (sfa, focG), invasins (ibeA), synthesis of toxins (hlyA, cnf1, vat, usp) and capsule (kpsMII), siderophores (fyuA, iroN, hlyA) were detected significantly more frequently (p 0.05). Two or more virulence determinants were detected in 93% of isolates. Conclusion. The identification of key determinants of virulence and/or a combination of virulence genes can be a prognostic marker for predicting the course of UTI, especially in pregnant women, and will expand diagnostic capabilities taking into account the virulent properties of the uropathogen.

La investigación tiene como objetivo identificar aspectos importantes del género femenino en el mundo de la cultura. El estudio se enfocó en lo cualitativo, transversal y descriptivo. Se realizó una revisión sistemática mediante PRISMA en Scopus, Google Académico y EBSCO Host en el 2023. Los criterios de inclusión fueron artículos publicados en revista indexada, entre 2018 y 2023, palabras clave (role of women, mujer en la cultura, y mujer y cultura, y de acceso libre, etc.). Se analizaron14 artículos para el presente estudio de investigación. Los textos críticos comparten la necesidad de desafiar los roles de género tradicionales y abordan temas como la limitación del desarrollo profesional de las mujeres, la representación estereotipada en la publicidad, la autonomía sexual y reproductiva, y la persistencia de la violencia de género. Reflexionan sobre el papel de las mujeres en diferentes contextos, desde el ámbito laboral hasta cuestiones ambientales, subrayando la importancia de cambiar estructuras que perpetúan la desigualdad. Se concluye mostrando el impacto de los aportes de las mujeres en diferentes ámbitos (gerenciales, administrativas, gestión, política, religión y educación) permitiendo un cambio de paradigma rotundo sobre su importancia en la sociedad, generando un avance acelerado hacia el reconocimiento de sus derechos.

Abstract Globally, cancer is the second leading cause of death, with a growing burden also observed in Kazakhstan. This study evaluates the burden of common cancers in Almaty, Kazakhstan's major city, from 2017 to 2021, utilizing data from the Information System of the Ministry of Health. In Kazakhstan, most common cancers among men include lung, stomach, and prostate cancer, while breast, cervical, and colorectal cancers are predominant among women. Employing measures like disability-adjusted life years (DALYs), we found that selected cancer types accounted for a total DALY burden of 25,016.60 in 2021, with mortality contributing more than disability (95.2% vs. 4.7%) with the ratio of non-fatal to fatal outcomes being 1.4 times higher in women than in men. The share of non-fatal burden (YLD) proportion within DALYs increased for almost all selected cancer types, except stomach and cervical cancer over the observed period in Almaty. Despite the overall increase in cancer burden observed during the time period, a downward trend in specific cancers suggests the efficacy of implemented cancer control strategies. Comparison with global trends highlights the significance of targeted interventions. This analysis underscores the need for continuous comprehensive cancer control strategies in Almaty and Kazakhstan, including vaccination against human papillomavirus, stomach cancer screening programs, and increased cancer awareness initiatives.

Abstract Flow cytometry is a vital tool in biomedical research and laboratory medicine. However, its accuracy is often compromised by undesired fluctuations in fluorescence intensity. While fluorescence lifetime imaging microscopy (FLIM) bypasses this challenge as fluorescence lifetime remains unaffected by such fluctuations, the full integration of FLIM into flow cytometry has yet to be demonstrated due to speed limitations. Here we overcome the speed limitations in FLIM, thereby enabling high-throughput FLIM flow cytometry at a high rate of over 10,000 cells per second. This is made possible by using dual intensity-modulated continuous-wave beam arrays with complementary modulation frequency pairs for fluorophore excitation and acquiring fluorescence lifetime images of rapidly flowing cells. Moreover, our FLIM system distinguishes subpopulations in male rat glioma and captures dynamic changes in the cell nucleus induced by an anti-cancer drug. FLIM flow cytometry significantly enhances cellular analysis capabilities, providing detailed insights into cellular functions, interactions, and environments.

Background. At present, creating and testing pharmacological instruments for selective inhibition of Са2+-pump of the plasma membrane, which would become the foundation for medical preparations, for instance, for the treatment of the impaired excitability of the cardiac and smooth muscles, remains critically significant. We have demon­strated in our previous experiments that calix[4]arene С-956 is effective in inhibi­ting Са2+, Mg2+-ATPase activity of the plasma membrane of myometrium cells. The aim of this study was to investigate the regularities and mechanisms of the impact of calix[4]arene С-956 on Са2+-transporting activity of Са2+, Mg2+-ATPase of the plasma membrane (PM) and the contractile function of rat myometrium. Materials and Methods. The experiments were conducted using outbred white non-pregnant rats. Ca2+-transporting activity of myocytes PM preparations loaded with Ca2+-sensitive fluorescent probe fluo-4 AM was investigated. The registration of the contractile activity in the preparations of longitudinal smooth muscles of uterine horns with preserved endothelium was done in the isometric mode. Results. It was determined that calix[4]arene C-956 causes blocking of the transport function of the calcium pump of preparations of plasma membranes of uterine myocytes. The C-956 compound causes an increase in the amplitude of spontaneous contractions and a change in their mechanokinetic parameters during a short-term effect on multicellular preparations of rat myometrium. Calix[4]arene C-956 also significantly affects the contractions caused by high-potassium depolarization of the PM and oxytocin, increa­sing their amplitude and decreasing the rate of relaxation. Blocking the synthesis of nitric oxide significantly enhances the effects of C-956 on spontaneous and high-potassium- and oxytocin-induced contractions of the myometrium. Conclusions. The results of our research indicate that the main target of the action of calix[4]arene C-956 on myocytes is the calcium pump of the PM. With the preliminary inhibition of nitric oxide synthases followed by the use of C-956, we were able to fully demonstrate the contribution of the calcium pump of the PM to the regulation of uterine contractions.

Carbon nanomaterials (CNMs) have emerged as highly effective agents for the removal of heavy metals from contaminated water and environments, owing to their unique structural and chemical properties. However, the hydrophobic nature of CNMs and their tendency to aggregate in most solvents present significant challenges to their practical application. Functionalizing carbon-based nanomaterials with proteins offers a promising solution to these issues, potentially leading to systems with unprecedented performance. Before fabricating protein-CNM systems for heavy metal detection and removal, it is crucial to evaluate the metal-binding affinity and potential interaction modes using computational approaches. In this study, a molecular docking technique was employed to investigate the interactions among heavy metal salts (AsO₄, Cd(NO₃)₂, Fe(NO₃)₃, NiSO₄, PbSO₄, PtCl₄), carbon-based nanomaterials (fullerenes C₂₄ and C₆₀, and single-walled carbon nanotubes), and β-lactoglobulin. The docking results revealed that: 1) the size, shape, and surface properties of carbon-based materials significantly influence the ability of β-lactoglobulin-CNM complexes to interact with different heavy metals; 2) different heavy metal salts exhibit distinct preferences for the various nanosystems; 3) hydrogen bonding and hydrophobic interactions play a significant role in the complexation of heavy metal salts with β-lactoglobulin-carbon-based materials.

The longitudinal dependence of the behavior of ionospheric parameters has been the subject of a number of works where significant variations are discovered. This also applies to the prediction of the ionospheric total electron content (TEC), which neural network methods have recently been widely used. However, the results are mainly presented for a limited set of meridians. This paper examines the longitudinal dependence of the TEC forecast accuracy in the equatorial zone. In this case, the methods are used that provided the best accuracy on three meridians: European (30° E), Southeastern (110° E) and American (75° W). Results for the stations considered are analyzed as a function of longitude using the Jet Propulsion Laboratory Global Ionosphere Map (JPL GIM) for 2015. These results are for 2 h ahead and 24 h ahead forecast. It was found that in this case, based on the metric values, three groups of architectures can be distinguished. The first group included long short-term memory (LSTM), gated recurrent unit (GRU), and temporal convolutional networks (TCN) models as a part of unidirectional deep learning models; the second group is based on the recurrent models from the first group, which were supplemented with a bidirectional algorithm, increasing the TEC forecasting accuracy by 2–3 times. The third group, which includes the bidirectional TCN architecture (BiTCN), provided the highest accuracy. For this architecture, according to data obtained for 9 equatorial stations, practical independence of the TEC prediction accuracy from longitude was observed under the following metrics (Mean Absolute Error MAE, Root Mean Square Error RMSE, Mean Absolute Percentage Error MAPE): MAE (2 h) is 0.2 TECU approximately; MAE (24 h) is 0.4 TECU approximately; RMSE (2 h) is less than 0.5 TECU except Niue station (RMSE (2 h) is 1 TECU approximately); RMSE (24 h) is in the range of 1.0–1.7 TECU; MAPE (2 h)

The global economic crisis of 2008–2013 led to the emergence of the concept of resilience, which focuses on the ability of socio-economic system store cover socially, economically, and environmentally after external impacts. The COVID-19 pandemic spurred scholarly interest in regional resilience as a new conceptual framework for the sustainability theory. This paper aims to examine the influence of the pandemic on the trends and geography of regional resilience studies. We analyzed data derived from Science Direct and used VOSviewer to perform clustering and bibliometric network analysis. The countries that suffered the most from the pandemic and showed the largest regional socioeconomic disparities have become new centers of knowledge on regional resilience. Moreover, the pandemic has led to a visible shift in the research focus. Thus, after 2020, more attention has been paid to the structural and topological characteristics of regions that enable them to reorganize their resources more effectively in times of crisis. This study investigates the potential of the resilient development concept as a framework for gaining insights into the factors supporting regional adaptability.

Context: Ensuring the quality of a generic drug is essential for its commercialization. Propranolol hydrochloride is a drug in great demand on the market as it is widely used as an antihypertensive, antianginal, antiarrhythmic, and for the treatment of migraine, requiring a complete evaluation to determine equivalence. Aims: To evaluate the dissolution biopharmaceutical characteristic in multisource products marketed in the Peruvian market, taking Inderal® as a reference product. Methods: In vitro conditions are simulated using the USP apparatus II at 50 rpm and 900 mL of the dissolution media pH 1.2, 4.5, and 6.8 at 37°C. The dependent mathematical models were characterized by the Akaike information criterion, and the similarity was evaluated using the independent parameters (MDT, DE, and the similarity factor f2). Results: The average dissolution percentages demonstrate a difference between the multisource and the innovator in the three-dissolution media. The model that best characterizes the dissolution kinetics in all products is that of Hixson–Crowell. A significant difference was obtained in the MDT and DE between the innovative and multisource products and in the three-dissolution media. The similarity factor was not within the acceptable range for multisource products in the three-dissolution media. Conclusions: The 40 mg propranolol hydrochloride tablets included in the study are not equivalent in vitro to the innovative product and, therefore, are not interchangeable.

An effect of Mg introduction on efficiency of high-loaded nickel catalysts in dehydrogenation of decahydroquinoline (10HQ) was investigated. 10HQ dehydrogenation is key process for the liquid organic hydrogen carrier (LOHC) storage technology using the quinoline/10HQ pair as H2-lean/H2-rich substrates. An influence of synthesis technique of Ni/Mg/Al catalysts on their properties has been demonstrated. The catalysts were synthesized through coprecipitation of Ni, Mg, Al precursors to obtain layered double hydroxides (LDH) or via synthesis of (∼72 wt%) Ni-Al2O3 system – also through coprecipitation, followed by modifying with a magnesium-containing precursor. For the catalysts of the first series, the inclusion of magnesium into LDH lattice led to a significant increase in catalytic activity in hydrogen extraction (10HQ dehydrogenation reaction). Despite the decrease in the content of catalytically active nickel, a significant increase in the yield of the dehydrogenation product was observed. This regularity is presumably associated with appearance of basic sites, that accelerates the dehydrogenation reaction. In the case of the second series, activity of pre-reduced (600 °C, H2) catalysts in dehydrogenation of 10HQ also significantly depends on a MgO content and is maximal at Mg:Ni weight ratio 0.056. Using an in-depth study of structure of the original and reduced catalyst samples (Ni-Al2O3 and Ni-MgNiOx-Al2O3), it was shown that this regularity is associated with the increased resistance of catalytically active Ni particles to agglomeration during the reductive activation. Also, using the Ni-MgNiOx-Al2O3 catalyst for hydrogen storage process (hydrogenation reaction), the possibility of deep quinoline hydrogenation (up to 10HQ) in a flow-type reactor was demonstrated for the first time.

Abstract Background The previously underestimated effects of commensal gut microbiota on the human body are increasingly being investigated using omics. The discovery of active molecules of interaction between the microbiota and the host may be an important step towards elucidating the mechanisms of symbiosis. Results Here, we show that in the bloodstream of healthy people, there are over 900 peptides that are fragments of proteins from microorganisms which naturally inhabit human biotopes, including the intestinal microbiota. Absolute quantitation by multiple reaction monitoring has confirmed the presence of bacterial peptides in the blood plasma and serum in the range of approximately 0.1 nM to 1 μM. The abundance of microbiota peptides reaches its maximum about 5 h after a meal. Most of the peptides correlate with the bacterial composition of the small intestine and are likely obtained by hydrolysis of membrane proteins with trypsin, chymotrypsin and pepsin – the main proteases of the gastrointestinal tract. The peptides have physicochemical properties that likely allow them to selectively pass the intestinal mucosal barrier and resist fibrinolysis. Conclusions The proposed approach to the identification of microbiota peptides in the blood, after additional validation, may be useful for determining the microbiota composition of hard-to-reach intestinal areas and monitoring the permeability of the intestinal mucosal barrier.

New risks make bank marketing especially relevant in modern conditions, e.g., COVID-19 restrictions, political issues, economic sanctions, etc. These risks affect the activities of banks, which have to look for new ways to create and promote their services and products. Bank products are quite peculiar: on the one hand, they are difficult to perceive by potential customers; on the other hand, digital technologies provide banks with additional promotion andexpansion opportunities. Global trends in bank marketing include such new technologies as artificial intelligence and digital platforms, new mobile applications, new sales channels and competition with other banks in this sphere, cybersecurity, winning the trust of customers, etc. New risks force banks to fight for customers and expand their market share using bank marketing concepts and tools. Digital marketing includes not only new promotion channels but also such new approaches as brand performance. Banks strive to meet customers halfway and to conquer new age groups by using gamification and financial education. The authors used the 7P marketing model to analyze AO Bank.DOM.RF as an average Russian bank and to recommend new options of bank marketing in practice. The analysis included strengths, weaknesses, opportunities, and threats.

Glycogen storage disease refers to hereditary pathologies of carbohydrate metabolism, its cause is mutations of various genes encoding enzymes responsible for the synthesis and breakdown of glycogen. Due to enzyme defects, excessive glycogen deposition occurs in cells of various tissues, mainly in the liver and muscles. The authors present modern epidemiological data and features of the etiopathogenesis of glycogen storage disease, and give clinical characteristics of various types of this nosology. In accordance with the developed clinical guidelines, information is provided on laboratory, instrumental and morphological signs of glycogen storage disease in children, as well as on methods of treatment of glycogen storage disease. Due to the variety of clinical forms of glycogenosis, the article provides up-to-date information on three types of pathology that occur with predominant liver damage.

The article presents the results of a clinical investigation on the administration of the Grippol Quadrivalent vaccine (influenza tetravalent inactivated subunit adjuvant vaccine) in children from 6 months to 5 years old. The vaccine has demonstrated no less effectiveness in comparison with the Grippol plus vaccine (influenza trivalent inactivated polymer-subunit vaccine).comparable results were obtained for all evaluated indicators of immunological efficacy against matching strains of the influenza virus, while for additional strain B (Yamagata line) there was a statistically significant difference in the increase in the immune response in the Grippol Quadrivalent group. The results of the assessment of the reactogenicity and frequency of systemic adverse events indicated a favorable and comparable safety profile of the vaccines Grippol Quadrivalent and Grippol plus in children from 6 months to 5 years old. The data obtained allowed us to conclude that the immunological efficacy of the Grippol Quadrivalent vaccine is no less when compared to the Grippol plus vaccine, as well as a comparable safety and reactogenicity profile. According to the results of the clinical investigation, on 08/04/2023, the Ministry of Health of the Russian Federation amended the “Instructions for the medical use of the drug”: Grippol Quadrivalent is indicated for children from the age of 6 months.

Introduction. The traditional surveillance system for influenza and ARVI provides a general description of epidemics, but does not provide information on the age-related characteristics of the etiology and clinical peculiarities of severe acute respiratory diseases (SARI) in hospitalized patients. Aim. To monitor the etiology of SARI in hospitalized children and adults, assessing the impact of the COVID-19 pandemic on this process. Materials and methods. Standardized clinical and laboratory monitoring of SARI among 18,458 hospitalized patients was carried out in hospitals in three cities of Russia with weekly PCR detection of 11 types of pathogens. Results. According to the investigation of hospitalized patients with SARI for the period from 2018 to 2023, the viral etiology of respiratory diseases was deciphered in 58.3% of cases. Weekly monitoring showed a change in the etiological mosaic of SARI pathogens during the SARS-CoV-2 pandemic with a sharp decrease in the frequency of detection of influenza and respiratory syncytial virus (RSV) during the 2020–2021 season against the background of a significant increase of metapneumovirus and rhinovirus infections in children. During the 2022-2023 season an increase in the proportion of RSV infection in children under 6 years of age (up to 36.2%) was noted against the background of a significant decrease in the frequency of SARS-CoV-2. In the intensive care units (ICU), RSV infection was most often in children during the post-pandemic period (up to 30.1–53.6% of positive cases, p 0.001); in adults, SARS-CoV-2 was mostly detected (76,5–100% of cases, p 0.001). Conclusion. Hospital surveillance data significantly complements the epidemiological information obtained in the traditional surveillance system. Monitoring of infections has shown a continuously changing etiological infrastructure of SARI, with the disappearance of influenza and RSV during the COVID-19 pandemic and their return to circulation in the post-pandemic period.

Abstract The population of Russia consists of more than 150 local ethnicities. The ethnic diversity and geographic origins, which extend from eastern Europe to Asia, make the population uniquely positioned to investigate the shared properties of inherited disease risks between European and Asian ancestries. We present the analysis of genetic and phenotypic data from a cohort of 4,145 individuals collected in three metro areas in western Russia. We show the presence of multiple admixed genetic ancestry clusters spanning from primarily European to Asian and high identity-by-descent sharing with the Finnish population. As a result, there was notable enrichment of Finnish-specific variants in Russia. We illustrate the utility of Russian-descent cohorts for discovery of novel population-specific genetic associations, as well as replication of previously identified associations that were thought to be population-specific in other cohorts. Finally, we provide access to a database of allele frequencies and GWAS results for 464 phenotypes.

At present, the issue of obtaining a complex of biologically active substances with antioxidant activity from psychrophilic Psychrophilic microalgae and cyanobacteria are a prospective source of biologically active antioxidant substances. New antioxidant complexes could expand the scope of their industrial application. The research objective was to identify psychrophilic microalgae and cyanobacteria from the Baltic Sea in order to study their antioxidant properties. The research featured psychrophilic microalgae and cyanobacteria obtained from the Curonian Lagoon and the Baltic Bay in the Baltic Sea, Kaliningrad Region, Russia, in March – May 2022. The authors used the Pasteur method and the flow cytometry method to isolate pure cultures of psychrophilic microalgae and cyanobacteria. The method of spectrophotometry made it possible to study the antioxidant activity by analyzing radical scavenging, reducing ability, and chelating. The psychrophilic microalga Skeletonema pseudocostatum demonstrated the highest antioxidant activity in all three methods: 17.62 μmol/g trolox equivalents according to the ABTS method, 58.16 μmol/g trolox equivalents according to the DPPH method, and 3.91 μmol/g trolox equivalents according to the FRAP method. The psychrophilic microalga Thalassiosira pseudonana exhibited the following values of antioxidant activity: 12.08, 12.42, and 3.13 μmol/g trolox equivalents, respectively. The antioxidant activity of the psychrophilic microalgae Fragilariopsis kerguelensis was 13.53, 11.84, and 1.09 μmol/g trolox equivalents, respectively. The antioxidant activity of the psychrophilic cyanobacterium Aphanizomenon gracile was 15.73, 19.89, and 2.47 μmol/g trolox equivalents, respectively. The antioxidant activity of the psychrophilic cyanobacterium Anabaena cylindrica was 12.62, 13.16, and 2.16 μmol/g trolox equivalents, respectively. The samples of psychrophilic microalgae and cyanobacteria obtained from natural environment in the Russian Baltic Sea demonstrated good antioxidant properties, which makes them a potential raw material for new pharmaceutical substances.

Aim. To study the possibility of using hematological indices as markers of subclinical inflammation in very elderly patients and centenarians with coronary artery disease (CAD). Materials and Methods: The cross-sectional study enrolled 127 patients; 93 patients with CAD – in the study group, 34 patients without CAD – in the control group. The mean age of patients reached 88.2±5.3 years (76–98 years); 48.8% were over 90 years of age. The ratio of the number of neutrophils to lymphocytes (NLR), neutrophils to monocytes (NMR), platelets to lymphocytes (PLR), lymphocytes to monocytes (LMR) and the systemic immune-inflammation index (SII) were determined. Interleukin-6 (IL-6) was determined in all patients, tumor necrosis factor (TNF)-α – in 49 patients. Results. In patients with coronary artery disease, the mean content of leukocytes was significantly higher than in the control group (6.1±1.5 and 5.4±1.5×109/l, respectively, p=0.02), and platelets were less (212±60 and 243±78×109/l, respectively, p=0.02). The platelet-lymphocyte ratio (139±54 and 185±87, p=0.001), neutrophils-monocytes ratio (12.4±13.4 and 20.8±22.0; р=0.04) and systemic immune-inflammatory index (554±345 and 762±616; p=0.02) were lower in patients with CAD. In patients with heart failure, a significantly higher content of leukocytes was revealed (6.5±1.7 and 5.7±1.4×109/l, respectively, p=0.009). A direct correlation was established between NLR and the concentration of IL-6 (r=0.26; p=0.003), as well as an inverse correlation with the content of TNF-α (r=-0.3; p=0.03). Inverse correlation was registered between the NLR and functional abilities of patients (for Barthel index: r=-0.35; p

Abstract The thrust of the study was to determine the chemical composition of the essential oils extracted from Thymus pallescens de Noé and Cymbogon citratus Stapf. as well as to evaluate their efficacy in controlling Sitophilus zeamais Motschulsky and Tribolium castaneum (Herbst) in either single or combined populations. Carvacrol (56.04%) and geraniol (20.86%) were identified as the major constituents of T. pallescens and C. citratus respectively. The tested essential oils showed pronounced insecticidal activity against the pest species in relation with the applied doses. T. pallescens EO had the highest efficacy and S. zeamais was found to be more susceptible to both individual and combined treatments. With reference to the contact and fumigation assessments, T. pallescens EO effectuated corrected mortality rates ranging from 42.5–100% to 25–100% in S. zeamais with corresponding lethal concentration (LC50) values of 17.7 µl/ml and 15µL/L air respectively. Whereas, the T. pallescens EO exhibited corrected mortality rates of 42.5–100% and 20–100% with corresponding LC50 values of 18.1 µl/ml and 15.5 µL/L air against T. castaneum in contact and fumigation assessments, respectively. The corrected mortality rates increased for both insect species when using combination treatments, with significant increases in the LC50 values, ranging from 8.59 to 49.9% for both pest species. Analysis of energy biomarkers in the treated insects indicate significantly increased protein and carbohydrate contents and decreased lipids levels. The study therefore demonstrated the bio-insecticidal toxicity of the EOs from T. pallescens and C. citratus against two important maize post-harvest pests, concurrently revealing significant positive and negative insecticidal activity gradients in relation to single or combined populations.

Abstract Ovarian cancer often develops resistance to conventional therapies, hampering their effectiveness. Here, using ex vivo paired ovarian cancer ascites obtained before and after chemotherapy and in vitro therapy-induced secretomes, we show that molecules secreted by ovarian cancer cells upon therapy promote cisplatin resistance and enhance DNA damage repair in recipient cancer cells. Even a short-term incubation of chemonaive ovarian cancer cells with therapy-induced secretomes induces changes resembling those that are observed in chemoresistant patient-derived tumor cells after long-term therapy. Using integrative omics techniques, we find that both ex vivo and in vitro therapy-induced secretomes are enriched with spliceosomal components, which relocalize from the nucleus to the cytoplasm and subsequently into the extracellular vesicles upon treatment. We demonstrate that these molecules substantially contribute to the phenotypic effects of therapy-induced secretomes. Thus, SNU13 and SYNCRIP spliceosomal proteins promote therapy resistance, while the exogenous U12 and U6atac snRNAs stimulate tumor growth. These findings demonstrate the significance of spliceosomal network perturbation during therapy and further highlight that extracellular signaling might be a key factor contributing to the emergence of ovarian cancer therapy resistance.