Search

Hybrid nanocomposites based on poly(3,6-dianiline-2,5-dichloro-1,4-benzoquinone) (PDACB) in salt form and graphene oxide (GO) have been obtained for the first time, and the significant influence of the preparation method on the composition and structure of nanocomposites and their functional properties has been demonstrated. Nanocomposites were prepared in three ways: via ultrasonic mixing of PDACB and GO; via in situ oxidative polymerization of 3,6-dianiline-2,5-dichloro-1,4-benzoquinone (DACB) in the presence of GO; and by heating a suspension of previously prepared PDACB and GO in DMF with the removal of the solvent. The results of the study of the composition, chemical structure, morphology, thermal stability and electrical properties of nanocomposites obtained via various methods are presented. Nanocomposites obtained by mixing the components in an ultrasonic field demonstrated strong intermolecular interactions between PDACB and GO both due to the formation of hydrogen bonds and π-stacking, as well as through electrostatic interactions. Under oxidative polymerization of DACB in the presence of GO, the latter participated in the oxidative process, being partially reduced. At the same time, a PDACB polymer film was formed on the surface of the GO. Prolonged heating for 4 h at 85 °C of a suspension of PDACB and GO in DMF led to the dedoping of PDACB with the transition of the polymer to the base non-conductive form and the reduction of GO. Regardless of the preparation method, all nanocomposites showed an increase in thermal stability compared to PDACB. All nanocomposites were characterized by a hopping mechanism of conductivity. Direct current (dc) conductivity σdc values varied within two orders of magnitude depending on the preparation conditions.

Relevance. Caused by the need to increase production of light olefins. The use of advanced process control systems and Real–Time Optimization makes it possible to increase the efficiency of steam cracking plants, but requires a high-speed mathematical model of the process. Aim. To select a method for numerical solution of systems of ordinary differential equations, which provides the highest speed when calculating the reaction coil of a steam cracking furnace. Reducing the time spent on calculating each scenario will allow the proposed model to be used for real-time process optimization tasks. Object. Mathematical model of ethane steam cracking, numerical methods for ordinary differential equations systems solution. Methods. System analysis, mathematical modeling. To solve the ordinary differential equations systems, various explicit numerical methods were used, differing in approach to integration step determination. Results. The authors have developed and tested a steady-state model of ethane steam cracking. The developed model was used to compare the calculation time required for solving ordinary differential equations systems using different numerical methods. It was demonstrated, that the use of an adaptive integration step reduces calculation time by more than 20 times (from more than 11 hours to 34 minutes) while maintaining the accuracy of calculations. This is due to different reaction rates through the length of the reaction coil – in areas of high temperatures and high concentrations of reagents, a reduction in the integration step is required to obtain the desired accuracy. And in low reaction rates areas an increase in the step and reduction in the total calculated iterations are acceptable.

Introduction. The choice of coping behavior strategies is a factor in increasing the efficiency of professional activities of educators. Despite the large number of publications on this topic, there is a lack of research on teachers’ choice factors regarding coping strategies. The authors suggest that the choice of coping strategies is determined not only by the teaching experience, but also by the special subject a teacher has to teach. Materials and Methods. The methods, used in the study are the following: Ways of Coping by R. Lazarus and S. Folkman and Questionnaire by E. Heim. The survey group was 475 teaching employees with various lengths of teaching experience and teaching specialities. For statistical processing, MANOVA, the Kruskal-Wallis H-test, and the χ² criterion were used. Results. In the course of analysis of variance, it was found that the choice of preferred coping strategies depends not only on the length of teaching experience, but also on the speciality area taught. This refers to both specific strategies (Distancing, Self-control and Positive Revaluation) and productive, relatively productive and unproductive strategies in general. Based on the severity of coping behavior strategies, two groups of pedagogical workers were identified: with a more evident (preschool educators, psychologists and subject teachers) and less evident (primary school teachers and teachers of additional education) coping strategies. Discussion and Conclusion. The specificity of the choice of both productive and unproductive strategies for coping behavior is determined not only by the length of teaching experience, but also by the specialization taught. The authors have highlighted coping strategies that are most typical for various groups of teaching staff. The results obtained can be useful for educational psychologists who provide psychological support for teams of educational organizations. The revealed specificity of coping behavior of teaching staff can serve as a basis for the development of preventive measures to offset professional burnout.

Since recently an economically efficient method including IR heating has been used for the synthesis of polymer based functional carbon nanocrystalline materials. One of the most widely used polymers having a broadest range of physicochemical properties and various applications is polyacrylonitrile (PAN). Under IR heating PAN undergoes chemical and structural transformations and a polyconjugated system forms with an increase in heating intensity. However, there are still no data on the quantitative and qualitative effects of carbon, nitrogen, hydrogen or metal atoms on the structural stability and configuration of the PAN based carbon material. We have for the first time determined using the MNDO semiempirical quantum chemical model for a carbon material (CM) structure based on heat treated polyacrylonitrile (PAN) that an increase in the N content from 14 to 18 atoms in CM monoatomic layers C46N14H10, C44N16H12, and C42N18H14 and in the H content from 12 to 22 atoms in CM monoatomic layers C44N16H12 and C44N16H22 leads to a decrease in the binding energy (Eb) from 7.40 and 7.12 to 6.88 and 6.25 eV, respectively, and to an increase in the difference between the maximum and minimum bond length (Δl), between the maximum and minimum valence angle (Δθ), and between the maximum and minimum local charge (Δq) from 0.176 Е, 12.0°, and 0.487 to 0.238 Е, 20.8°, and 0.613, respectively, and promotes curving of the CM structure. Quantum chemical simulation results are confirmed by the element analysis of the CM specimens and FeNi3/C nanocomposite. When the IR heating temperature was increased from 30 to 500 °С, the concentrations of N (СN) and H (СH) in the CM and in the FeNi3/C nanocomposite decreased from 27 to 18 and 10 wt% and from 6 to 1 and 0.5 wt%, respectively.

Thalhammerite, Pd9Ag2Bi2S4, is a new sulphide discovered in galena-pyrite-chalcopyrite and millerite-bornite-chalcopyrite vein-disseminated ores from the Komsomolsky mine of the Talnakh and Oktyabrsk deposits, Noril’sk region, Russia. It forms tiny inclusions (from a few μm up to about 40–50 μm) intergrown in galena, chalcopyrite, and also in bornite. Thalhammerite is brittle and has a metallic lustre. In plane-polarized light, thalhammerite is light yellow with weak bireflectance, weak pleochroism, in shades of slightly yellowish brown and weak anisotropy; it exhibits no internal reflections. Reflectance values of thalhammerite in air (R1, R2 in %) are: 41.9/43.0 at 470 nm, 43.9/45.1 at 546 nm, 44.9/46.1 at 589 nm, and 46.3/47.5 at 650 nm. Three spot analyses of thalhammerite give an average composition: Pd 52.61, Bi 22.21, Pb 3.92, Ag 14.37, S 7.69, and Se 0.10, total 100.90 wt %, corresponding to the empirical formula Pd8.46Ag2.28(Bi1.82Pb0.32)Σ2.14(S4.10Se0.02)Σ4.12 based on 17 atoms; the average of five analyses on synthetic thalhammerite is: Pd 55.10, Bi 24.99, Ag 12.75, and S 7.46, total 100.30 wt %, corresponding to Pd8.91Ag2.03Bi2.06S4.00. The density, calculated on the basis of the empirical formula, is 9.72 g/cm3. The mineral is tetragonal, space group I4/mmm, with a 8.0266(2), c 9.1531(2) Å, V 589.70(2) Å3 and Z = 2. The crystal structure was solved and refined from the single-crystal X-ray-diffraction data of synthetic Pd9Ag2Bi2S4. Thalhammerite has no exact structural analogues known in the mineral system; chemically, it is close to coldwellite (Pd3Ag2S) and kravtsovite (PdAg2S). The strongest lines in the X-ray powder diffraction pattern of synthetic thalhammerite [d in Å (I) (hkl)] are: 3.3428(24)(211), 2.8393(46)(220), 2.5685(21)(301), 2.4122(100)(222), 2.3245(61)(123), 2.2873(48)(004), 2.2201(29)(132), 2.0072(40)(400), 1.7481(23)(332), and 1.5085(30)(404). The mineral honours Associate Professor Oskar Thalhammer of the University of Leoben, Austria.

The article analyzes the basic paradigms of psychology and put forward the thesis of the expansion of the subject area of psychology in the course of historical development, and describes the main features of integrative psychology. Highlighted in the article the new paradigm of psychology (transpersonal, communicative, integrative), make it possible to trace a vector of development of modern psychology as a multidimensional communicative environment that has intention to make a perusal of psychic reality.

Stem cell-based therapy is considered to be a new approach for the treatment of cerebral palsy (CP). Given the potent anti-inflammatory activity and high regenerative potential of M2 macrophages, these cells may be an alternative source for cell transplantation. To evaluate the safety and efficacy of autologous M2 macrophages, we conducted a pilot clinical trial in 21 children with severe CP. The primary outcome measure was safety, which included assessment of mortality of any cause, immediate adverse reactions, and serious adverse effects and comorbidities during 5-year follow-up. The secondary outcome measure was functional improvement in Gross Motor Function Measure (66-item GMFM) test, Peabody Developmental Motor Scale-Fine Motor (PDMS-FM) test, Ashworth scale, MRC scale, and an easy-to-understand questionnaire for evaluation of cognitive functions in our modification. Intradural injection of M2 cells (in mean dose of 0.8 × 10 6 /kg) into the lumbar spinal area did not induce any serious adverse events. No cases of mortality, psychomotor worsening, exacerbation of seizures, and long-term comorbidities, including tumors, were observed during a 5-year follow-up. After 3 months, GMFM score increased from 13.7 ± 7.8 to 58.6 ± 14.6, PDMS-FM score improved from 0.76 ± 0.42 to 5.05 ± 0.97, and the Ashworth score decreased from 3.8 ± 0.21 to 3.3 ± 0.24. Along with gross and fine motor function enhancement, an improvement of cognitive activity (from 1.62 ± 0.41 to 4.05 ± 0.64, according to questionnaire assessment) and reduction of seizure syndrome were registered as well. The neurological improvements did not diminish during the 5-year follow-up period. The data obtained suggest that cell therapy based on M2 macrophages is safe, does not induce early adverse effects and long-term comorbidities, and is accompanied with a significant improvement of motor and cognitive activities in severe CP patients. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation .

Introduction. The relevance of the study is determined by the negative consequences for the environment from the constant increase in the amount of municipal solid waste. The most vulnerable in this situation are small towns in the Arctic zone of the Russian Federation. The remoteness, inaccessibility, as well as the difficult socio-economic situation of these settlements are serious obstacles to achieving both the effectiveness of the implementation of the reform of production and consumption waste management, and the goals of sustainable development of the region. The purpose of the article is to identify the value foundations prevailing in environmental consciousness and the prevailing types of environmental behavior of the population of small towns in the European part of the Russian Arctic in the field of solid waste management. Materials and Methods. The article presents the results of an empirical study conducted by a questionnaire survey in August-November 2020 in the Arctic territories of the Republic of Karelia and the Murmansk region. The number of respondents is 1303. The questionnaire method is used to carry out a mass representative survey of residents of the Arctic territories on the problem of municipal solid waste. Statistical methods for processing quantitative data makes it possible to identify the main correlations between variables in relation to grassroots practices in the management of municipal solid waste by gender, age and place of residence of the respondents. Results. The paper shows the findings of a sociological study, during which the peculiarities of the perception of the population of small towns in the Republic of Karelia and the Murmansk region of environmental problems were identified and an assessment of the degree of threat to the environment from illegal dumps and household waste was given. The authors studied the direct practices of handling household waste and the willingness of respondents to change the traditional poorly environmentally oriented behavior to environmentally conscious actions. Discussion and Conclusion. The study showed that the problem of the increasing amount of MSW is relevant and causes a high degree of concern among the population. At the same time, the majority of respondents implement behavioral practices that indirectly affect the environment. The decisive problem for the population of remote areas of the Russian Arctic is the poor organization of the waste management process: lack of investment attractiveness for business, low level of infrastructure development, little funding, which determines low motivation and mobilization of the population to master various environmental practices. The results obtained can be used by regional and municipal authorities, regional operators and specialists of environmental nongovernment organizations.

The article analyzes the regional specifics of solid municipal waste management in the Arctic zone of the Russian Federation. The relevance of the topic is determined by the need to analyze the regional specifics of solid municipal waste management within the framework of the federal project "Integrated System of Solid Municipal Waste Management", included in the national project "Ecology". First of all, this request will allow us to achieve the most effective management decisions in the field of regulatory regulation and the introduction of mechanisms for economic regulation of MSW management activities, as well as to contribute the creation of an effective management system, and the development of infrastructure for MSW management. The statistical analysis of formation indicators, processing and utilization of MSW waste in the structure by region is presented in this paper. The factors determining the specificity of MSW handling in the Arctic regions are defined. The expert survey made it possible to identify the main problems of implementing the garbage reform in the Arctic in general and in inner regions in particular. The main methods in this study were: semi-formal telephone interviews with representatives of environmental organizations and associations (18 informants), as well as collecting and analysis of statistical indicators of the MSW handling in the Arctic regions.

Background: Russia has one of the highest lung cancer burdens globally, particularly in men. Mortality started to decline in the 1990s after the reduction in smoking prevalence. However, Russia's recent experience is largely unknown. This study aims to describe recent trends in the incidence and mortality of lung cancer in Russia along with the use of computed tomography (CT)., Methods: We obtained incidence data from national cancer reports covering 1993-2021 and mortality and population data from the Russian Fertility and Mortality Database covering 1965-2021. The number of CT scanners was obtained from the OECD. Changes in age-standardized rates (Segi-Doll, per 100,000) were assessed using segmented regression and temporal effects using age-period-cohort analysis., Results: Lung cancer rates in men have been substantially higher than in women and have declined sharply since their peak in the 1990s. The latest breakpoints in incidence in women were in 2012 (95 % CI: 2000; 2014) from stagnation with an annual change of 0.7 % (-0.2; 1.5) to 3.4 % (1.6; 5.2) increase. In men, the decrease in incidence stopped in 2013 (2011; 2014) from -1.8 % (-2.1; -1.4) to 0.3 % (-0.7; 1.3). The growing number of CT scans accompanied the recent changes in incidence rates. Incidence declined sharply in 2020 in men and women. There were no substantial changes in declining mortality trends. Period effects were visible after 2012 when incidence rates increased and deviated from mortality. After accounting for the period effect, generations born after the 1950s had lower risks., Conclusion: Increasing lung cancer incidence rates in Russia in the late 2010s, especially in women, and the stable mortality trends could be a possible sign of diagnostic or treatment period effect. The increased use of CT should be monitored for possible benefits and harms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Cucurbiturils are a family of macrocyclic oligomers capable of forming host-guest complexes with various molecules. Due to noncovalent binding to drug molecules and low toxicity, cucurbiturils has been extensively investigated as potential carriers for drug delivery. However, the immune system's interactions with different drug carriers, including cucurbiturils, are still under investigation. In this study, we focused on cucurbiturils' immunosafety and immunomodulation properties in vivo. We measured blood counts and lymphocyte subpopulations in blood, spleen, and bone marrow, and assessed the in vivo toxicity to spleen and bone marrow cells after intraperitoneal administration to BALB/c mice. When assessing the effect of cucurbit[6]uril on blood parameters after three intraperitoneal injections within a week in laboratory animals, a decrease in white blood cells was found in mice after injections of cucurbit[6]util, but the observed decrease in the number of white blood cells was within the normal range. At the same time, cucurbit[7]uril and cucurbit[8]uril did not affect the leukocyte counts of mice after three injections. Changes in the number of platelets, erythrocytes, and monocytes, as well as in several other indicators, such as hematocrit or erythrocyte volumetric dispersion, were not detected. We show that cucurbiturils do not have immunotoxicity in vivo, with the exception of a cytotoxic effect on spleen cells after сucurbit[7]uril administration at a high dosage. We also evaluated the effect of cucurbiturils on cellular and humoral immune responses. We founded that cucurbiturils in high concentrations affect the immune system in vivo, and the action of various cucurbiturils differs in different homologues, which is apparently associated with different interactions in the internal environment of the body.

This article concerns the effect of the chemical modification of short flax fiber on its sorption properties for heavy metal ions. The main purpose of the modification was to achieve the oxidation of flax cellulose with sodium metaperiodate to form dialdehyde cellulose. Additionally, the research shows the subsequent interaction of dialdehyde cellulose with 1-amino-8-hydroxynaphthalene-3,6-disulfonic acid and its transformation into a derivative capable of forming chelate complexes with heavy metal ions. Additionally, this article presents the results of equilibrium and kinetics studies of the sorption of Cu(II), Cd(II), and Fe(II) ions from aqueous solutions by primary and modified cellulose sorbents. SEM spectra indicate changes in the surface structure of the modified sorbents compared to the original one. IR spectra show the appearance of amino- and sulfogroups in short flax fibers in the process of their modification. The research revealed the efficiency of the method and the possibility of its use for the purification of aqueous solutions from heavy metal ions in industrial processes.

We suggest a novel approach for searching natural compounds with anti-aging and rejuvenation potential using cell cultures, with a high potential for the further in vivo applications. The present paper discusses ways of defining age for cell populations with large numbers of cells and suggests a method of assessing how young or old a cell population is based on a cell age profile approach. This approach uses experimental distributions of the cells over the cell cycle stages, acquired using flow cytometry. This paper discusses how such a profile should evolve under homeostatic maintenance of cell numbers in the proliferation niches. We describe promising results from experiments on a commercial substance claiming rejuvenating and anti-aging activity acting upon the cultures of human mononuclear cells and dermal fibroblasts. The chosen substance promotes a shift towards larger proportion of cells in synthesis and proliferation stages, and increases cell culture longevity. Further, we describe promising in vivo testing results of a selected food supplement. Based on the described concept of cell age profile and available test results, a strategy to search for natural compounds with regenerative, anti-aging and rejuvenation potential is suggested and proposed for wider and thorough testing. Proposed methodology of age assessment is rather generic and can be used for quantitative assessment of the anti-aging and rejuvenation potential of different interventions. Further research aimed at the tests of the suggested strategy using more substances and different interventions, and the thorough studies of molecular mechanisms related to the action of the substance used for testing the suggested search methodology, are needed.

Glioblastoma is a rapidly progressing tumor quite resistant to conventional treatment. These features are currently assigned to a self-sustaining population of glioblastoma stem cells. Anti-tumor stem cell therapy calls for a new means of treatment. In particular, microRNA-based treatment is a solution, which in turn requires specific carriers for intracellular delivery of functional oligonucleotides. Herein, we report a preclinical in vitro validation of antitumor activity of nanoformulations containing antitumor microRNA miR-34a and microRNA-21 synthetic inhibitor and polycationic phosphorus and carbosilane dendrimers. The testing was carried out in a panel of glioblastoma and glioma cell lines, glioblastoma stem-like cells and induced pluripotent stem cells. We have shown dendrimer-microRNA nanoformulations to induce cell death in a controllable manner, with cytotoxic effects being more pronounced in tumor cells than in non-tumor stem cells. Furthermore, nanoformulations affected the expression of proteins responsible for interactions between the tumor and its immune microenvironment: surface markers (PD-L1, TIM3, CD47) and IL-10. Our findings evidence the potential of dendrimer-based therapeutic constructions for the anti-tumor stem cell therapy worth further investigation.

Mainstream transcriptome profiling of susceptibility versus resistance to age-related diseases (ARDs) is focused on differentially expressed genes (DEGs) specific to gender, age, and pathogeneses. This approach fits in well with predictive, preventive, personalized, participatory medicine and helps understand how, why, when, and what ARDs one can develop depending on their genetic background. Within this mainstream paradigm, we wanted to find out whether the known ARD-linked DEGs available in PubMed can reveal a molecular marker that will serve the purpose in anyone's any tissue at any time. We sequenced the periaqueductal gray (PAG) transcriptome of tame versus aggressive rats, identified rat-behavior-related DEGs, and compared them with their known homologous animal ARD-linked DEGs. This analysis yielded statistically significant correlations between behavior-related and ARD-susceptibility-related fold changes (log 2 values) in the expression of these DEG homologs. We found principal components, PC1 and PC2, corresponding to the half-sum and the half-difference of these log 2 values, respectively. With the DEGs linked to ARD susceptibility and ARD resistance in humans used as controls, we verified these principal components. This yielded only one statistically significant common molecular marker for ARDs: an excess of Fcγ receptor IIb suppressing immune cell hyperactivation.

Short regulatory oligonucleotides are considered prospective tools for immunotherapy. However, they require an adequate carrier to deliver potential therapeutics into immune cells. Herein, we explore the potential of polycationic dendrimers as carriers for microRNAs in peripheral blood mononuclear cells of healthy donors. As an oligonucleotide cargo, we use a synthetic mimic and an inhibitor of miR-155, an important factor in the development and functioning of immunocompetent cells. Dendrimers bind microRNAs into low-cytotoxic polyelectrolyte complexes that are efficiently uptaken by immunocompetent cells. We have shown these complexes to affect the number of T-regulatory cells, CD14 + and CD19 + cell subpopulations in non-activated mononuclear cells. The treatment affected the expression of HLA-DR on T-cells and PD-1 expression on T- and B-lymphocytes. It also affected the production of IL-4 and IL-10, but not the perforin and granzyme B production. Our findings suggest the potential of dendrimer-mediated microRNA-155 treatment for immunotherapy, though the activity of microRNA-dendrimer constructions on distinct immune cell subsets can be further improved.

Tumor cells with stem cell properties are considered to play major roles in promoting the development and malignant behavior of aggressive cancers. Therapeutic strategies that efficiently eradicate such tumor stem cells are of highest clinical need. Herein, we performed the validation of the polycationic phosphorus dendrimer-based approach for small interfering RNAs delivery in in vitro stem-like cells as models. As a therapeutic target, we chose Lyn, a member of the Src family kinases as an example of a prominent enzyme class widely discussed as a potent anti-cancer intervention point. Our selection is guided by our discovery that Lyn mRNA expression level in glioma, a class of brain tumors, possesses significant negative clinical predictive value, promoting its potential as a therapeutic target for future molecular-targeted treatments. We then showed that anti-Lyn siRNA, delivered into Lyn-expressing glioma cell model reduces the cell viability, a fact that was not observed in a cell model that lacks Lyn-expression. Furthermore, we have found that the dendrimer itself influences various parameters of the cells such as the expression of surface markers PD-L1, TIM-3 and CD47, targets for immune recognition and other biological processes suggested to be regulating glioblastoma cell invasion. Our findings prove the potential of dendrimer-based platforms for therapeutic applications, which might help to eradicate the population of cancer cells with augmented chemotherapy resistance. Moreover, the results further promote our functional stem cell technology as suitable component in early stage drug development.

It is well known that the most important feature of adaptive immunity is the specificity that provides highly precise recognition of the self, altered-self, and non-self. Due to the high specificity of antigen recognition, the adaptive immune system participates in the maintenance of genetic homeostasis, supports multicellularity, and protects an organism from different pathogens at a qualitatively different level than innate immunity. This seemingly simple property is based on millions of years of evolution that led to the formation of diversification mechanisms of antigen-recognizing receptors and later to the emergence of a system of presentation of the self and non-self antigens. The latter could have a crucial significance because the presentation of nearly complete diversity of auto-antigens in the thymus allows for the "calibration" of the forming repertoires of T-cells for the recognition of self, altered-self, and non-self antigens that are presented on the periphery. The central role in this process belongs to promiscuous gene expression by the thymic epithelial cells that express nearly the whole spectrum of proteins encoded in the genome, meanwhile maintaining their cellular identity. This complex mechanism requires strict control that is executed by several transcription factors. One of the most important of them is AIRE. This noncanonical transcription factor not only regulates the processes of differentiation and expression of peripheral tissue-specific antigens in the thymic medullar epithelial cells but also controls intercellular interactions in the thymus. Besides, it participates in an increase in the diversity and transfer of presented antigens and thus influences the formation of repertoires of maturing thymocytes. Due to these complex effects, AIRE is also called a transcriptional regulator. In this review, we briefly described the history of AIRE discovery, its structure, functions, and role in the formation of antigen-recognizing receptor repertoires, along with other transcription factors. We focused on the phylogenetic prerequisites for the development of modern adaptive immunity and emphasized the importance of the antigen presentation system.

The most effective method of treating allergic diseases, aimed not at relieving symptoms, but at eliminating the cause of the disease, is allergen-specific immunotherapy (AIT). To reduce the risk of side effects and improve the delivery of allergens to the mucosa, various delivery systems, such as liposomes, dendrimers, nanoparticles, etc., can be used. To date, there are data on the creation of delivery systems based on glycyrrhizic acid (GA) and its derivatives, but such a delivery system has not been used for allergen-specific therapy until now. It is also known that GA has an anti-inflammatory effect, shifts the balance towards Th1, and increases the number of Treg cells, meaning that it could potentially enhance the anti-allergic effect of AIT and reduce the risk of unwanted side effects. Thus, the study of the immunomodulatory effect of the supramolecular complexes (micelles) of GA with extracts of allergens holds promise for the development of new drugs for AIT.

We consider an age-structured density-dependent population model on several temporally variable patches. There are two key assumptions on which we base model setup and analysis. First, intraspecific competition is limited to competition between individuals of the same age (pure intra-cohort competition) and it affects density-dependent mortality. Second, dispersal between patches ensures that each patch can be reached from every other patch, directly or through several intermediary patches, within individual reproductive age. Using strong monotonicity we prove existence and uniqueness of solution and analyze its large-time behavior in cases of constant, periodically variable and irregularly variable environment. In analogy to the next generation operator, we introduce the net reproductive operator and the basic reproduction number [Formula: see text] for time-independent and periodical models and establish the permanence dichotomy: if [Formula: see text], extinction on all patches is imminent, and if [Formula: see text], permanence on all patches is guaranteed. We show that a solution for the general time-dependent problem can be bounded by above and below by solutions to the associated periodic problems. Using two-side estimates, we establish uniform boundedness and uniform persistence of a solution for the general time-dependent problem and describe its asymptotic behaviour., (© 2021. The Author(s).)

In this review, we described the structure and organization of antigen-recognizing repertoires of B and T cells from the standpoint of modern immunology. We summarized the latest advances in bioinformatics analysis of sequencing data from T and B cell repertoires and also presented contemporary ideas about the mechanisms of clonal diversity formation at different stages of organism development. At the same time, we focused on the importance of the allelic variants of the HLA genes and spectra of presented antigens for the formation of T-cell receptors (TCR) landscapes. The main idea of this review is that immune equilibrium and proper functioning of immunity are highly dependent on the interaction between the recognition and the presentation landscapes of antigens. Certain changes in these landscapes can occur during life, which can affect the protective function of adaptive immunity. We described some mechanisms associated with these changes, for example, the conversion of effector cells into regulatory cells and vice versa due to the trans-differentiation or bystander effect, changes in the clonal organization of the general TCR repertoire due to homeostatic proliferation or aging, and the background for the altered presentation of some antigens due to SNP mutations of MHC, or the alteration of the presenting antigens due to post-translational modifications. The authors suggest that such alterations can lead to an increase in the risk of the development of oncological and autoimmune diseases and influence the sensitivity of the organism to different infectious agents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Shevyrev, Tereshchenko and Kozlov.)

Cucurbit[7]uril (CB[7]) is a molecular container that may form host-guest complexes with platinum(II) anticancer drugs and modulate their efficacy and safety. In this paper, we report our studies of the effect of CB[7]-oxaliplatin complex and the mixture of CB[7] and carboplatin (1:1) on viability and proliferation of a primary cell culture (peripheral blood mononuclear cells), two tumor cell lines (B16 and K562) and their activity in the animal model of melanoma. At the same time, we studied the impact of platinum (II) drugs with CB[7] on T cells and B cells in vitro. Although the stable CB[7]-carboplatin complex was not formed, the presence of cucurbit[7]uril affected the biological properties of carboplatin. In vivo, CB[7] increased the antitumor effect of carboplatin, but, at the same time, increased its acute toxicity. Compared to free oxaliplatin, its complex with CB[7] shows a greater cytotoxic effect on tumor cell lines B16 and K562, while in vivo, the effects of the free drug and encapsulated drug were comparable. However, in vivo studies also demonstrated that the encapsulation of oxaliplatin in CB[7] lowered the toxicity of the drug.

Using our previously published Web service SNP&#95;TATA&#95;Comparator, we conducted a genome-wide study of single-nucleotide polymorphisms (SNPs) within core promoters of 68 human rheumatoid arthritis (RA)-related genes. Using 603 SNPs within 25 genes clinically associated with RA-comorbid disorders, we predicted 84 and 70 candidate SNP markers for overexpression and underexpression of these genes, respectively, among which 58 and 96 candidate SNP markers, respectively, can relieve and worsen RA as if there is a neutral drift toward susceptibility to RA. Similarly, we predicted natural selection toward susceptibility to RA for 8 immunostimulatory genes (e.g., IL9R ) and 10 genes most often associated with RA (e.g., NPY ). On the contrary, using 25 immunosuppressive genes, we predicted 70 and 109 candidate SNP markers aggravating and relieving RA, respectively (e.g., IL1R2 and TGFB2 ), suggesting that natural selection can simultaneously additionally yield resistance to RA. We concluded that disruptive natural selection of human immunostimulatory and immunosuppressive genes is concurrently elevating and reducing the risk of RA, respectively. So, we hypothesize that RA in human could be a self-domestication syndrome referring to evolution patterns in domestic animals. We tested this hypothesis by means of public RNA-Seq data on 1740 differentially expressed genes (DEGs) of pets vs. wild animals (e.g., dogs vs. wolves). The number of DEGs in the domestic animals corresponding to worsened RA condition in humans was significantly larger than that in the related wild animals (10 vs. 3). Moreover, much less DEGs in the domestic animals were accordant to relieved RA condition in humans than those in the wild animals (1 vs. 8 genes). This indicates that the anthropogenic environment, in contrast to a natural one, affects gene expression across the whole genome (e.g., immunostimulatory and immunosuppressive genes) in a manner that likely contributes to RA. The difference in gene numbers is statistically significant as confirmed by binomial distribution ( p < 0.01), Pearson's χ 2 ( p < 0.01), and Fisher's exact test ( p < 0.05). This allows us to propose RA as a candidate symptom within a self-domestication syndrome. Such syndrome might be considered as a human's payment with health for the benefits received during evolution., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Klimova, Oshchepkova, Chadaeva, Sharypova, Ponomarenko, Drachkova, Rasskazov, Oshchepkov, Ponomarenko, Savinkova, Kolchanov and Kozlov.)

Currently, cucurbiturils are being actively researched all over the world. Research is focused on the ways of improving the solubility and selectivity of cucurbiturils, increasing the stability of the complexes with other particles in various media and enhancing their ability to bind and release various substances. The most significant area of our research is the assessment of safety, studying the biological properties and synergistic effects of cucurbiturils during complexation with drugs. In this article, the hemocompatibility of erythrocytes and leukocytes with cucurbiturils was investigated. We demonstrated that cucurbiturils have no cytotoxic effect, even at high concentrations (1 mM) and do not affect the viability of PBMCs. However, cucurbiturils can increase the level of the early apoptosis of lymphocytes and cucurbit[7]uril enhances hemolysis in biologically relevant media. Despite this, cucurbiturils are fairly safe organic molecules in concentrations up to 0.3 mM. Thus, we believe that it will become possible to use polymer nanostructures as drug delivery systems in clinical practice, since cucurbiturils can be modified to improve pharmacological properties.

Homeostatic proliferation (HP) is a physiological process that reconstitutes the T cell pool after lymphopenia involving Interleukin-7 and 15 (IL-7 and IL-15), which are the key cytokines regulating the process. However, there is no evidence that these cytokines influence the function of regulatory T cells (Tregs). Since lymphopenia often accompanies autoimmune diseases, we decided to study the functional activity of Tregs stimulated by HP cytokines from patients with rheumatoid arthritis as compared with that of those from healthy donors. Since T cell receptor (TCR) signal strength determines the intensity of HP, we imitated slow HP using IL-7 or IL-15 and fast HP using a combination of IL-7 or IL-15 with anti-CD3 antibodies, cultivating Treg cells with peripheral blood mononuclear cells (PBMCs) at a 1:1 ratio. We used peripheral blood from 14 patients with rheumatoid arthritis and 18 healthy volunteers. We also used anti-CD3 and anti-CD3 + IL-2 stimulation as controls. The suppressive activity of Treg cells was evaluated in each case by the inhibition of the proliferation of CD4 + and CD8 + cells. The phenotype and proliferation of purified CD3 + CD4 + CD25 + CD127 lo cells were assessed by flow cytometry. The suppressive activity of the total pool of Tregs did not differ between the rheumatoid arthritis and healthy donors; however, it significantly decreased in conditions close to fast HP when the influence of HP cytokines was accompanied by anti-CD3 stimulation. The Treg proliferation caused by HP cytokines was lower in the rheumatoid arthritis (RA) patients than in the healthy individuals. The revealed decrease in Treg suppressive activity could impact the TCR landscape during lymphopenia and lead to the proliferation of potentially self-reactive T cell clones that are able to receive relatively strong TCR signals. This may be another explanation as to why lymphopenia is associated with the development of autoimmune diseases. The revealed decrease in Treg proliferation under IL-7 and IL-15 exposure can lead to a delay in Treg pool reconstitution in patients with rheumatoid arthritis in the case of lymphopenia.