Current State and Prospects of Russia – China Trade Development in the BRICS Format

Motivation: The substantiation of the scientific problem and the practical value of the study are determined by the enhanced cooperation of the BRICS countries, in particular the growing weight of Russia and China on the world stage. The main objective of the study: is to analyze the problems of the development of bilateral trade between China and Russia and to provide a statistically proven forecast for this trade for 2019-2020, as well as to develop recommendations for the improvement of bilateral trade relations. Novelty: The author's statistical model was developed and its testing was presented through confirming the 24-month forecast of bilateral trade between Russia and China. The model involves solving various problems of bilateral trade. Recommendations for improvement of bilateral trade relations are proposed through formation of an investment and innovation model of bilateral trade.Methodology and Methods: The work used the method of forecasting time series, which suggested the use of a model to predict future values based on previously observed values. To evaluate the modern prospects of the trade between the countries, the authors produced a forecast of the goods turnover trend for 2019-2020. The forecast was issued via the software tool Statgraphics Centurion 18. A reasonable model of the 24-month forecast based on the statistical model Random Walk is developed. The adequacy of the proposed forecast model was subjected to statistical tests. To verify the statistical adequacy of the model the relevant tests were done to determine the compliance of the model with the informational criteria ME (Mean Error), MSE (Mean Squared Error), ÐœÐЕ (Mean Absolute Error), ÐœÐРЕ (Mean Absolute Percentage Error), МРЕ (Mean Percentage Error). However, it should be noted that the forecast was issued in accordance with the trends which had been identified in the preceding periods. Data and empirical analysis: The factors influencing bilateral trade are analyzed, as well as examples of implemented projects of international cooperation between Russia and China are presented. The current dynamics of sales turnover between Russia and China for the period of 2010-2018 with the use of various statistical and analytical methods is studied, and a reasonable model of the 24-month forecast based on the statistical model Random Walk is developed. The adequacy of the proposed forecast model was subjected to statistical tests. The basic hypothesis is suggested for the upward trend based on reference time series. Policy considerations: It can be said with certainty that the level of technological development of BRICS countries will help Russia and China to start building their cooperation in many fields at a completely new level, taking into account their joint experience in overcoming global crises and Western sanctions. International cooperation between Russia and China in the innovation field will help them unite their efforts and achieve significant synergy. Coordination of countries on this issue will help to reduce production costs, cooperation of production, joint research and development, as well as increase bilateral trade turnover

Genetics of psycho-emotional well-being: genome-wide association study and polygenic risk score analysis

BackgroundPsycho-emotional well-being is essential for living a life of satisfaction and fulfillment. However, depression and anxiety have become the leading mental health issues worldwide, according to the World Health Organization. Both disorders have been linked to stress and other psychological factors. Their genetic basis remains understudied.MethodsIn 2020–2021, the psycho-emotional well-being of 30,063 Russians with no known psychiatric history was assessed using the Hospital Anxiety and Depression Scale (HADS) for general mental health and the HADS subscale A (anxiety) for anxiety. Following the original instructions, an anxiety score of ≥11 points was used as the anxiety threshold. A genome-wide association study was performed to find associations between anxiety and HADS/HADS-A scores using linear and logistic regressions based on HADS/HADS-A scores as binary and continuous variables, respectively. In addition, the links between anxiety, sociodemographic factors (such as age, sex, and employment), lifestyle (such as physical activity, sleep duration, and smoking), and markers of caffeine and alcohol metabolism were analyzed. To assess the risk of anxiety, polygenic risk score modeling was carried out using open-access software and principal component analysis (PCA) to simplify the calculations (ROC AUC = 89.4 ± 2.2% on the test set).ResultsThere was a strong positive association between HADS/HADS-A scores and sociodemographic factors and lifestyle. New single-nucleotide polymorphisms (SNPs) with genome-wide significance were discovered, which had not been associated with anxiety or other stress-related conditions but were located in genes previously associated with bipolar disorder, schizophrenia, or emotional instability. The CACNA1C variant rs1205787230 was associated with clinical anxiety (a HADS-A score of ≥11 points). There was an association between anxiety levels (HADS-A scores) and genes involved in the activity of excitatory neurotransmitters: PTPRN2 (rs3857647), DLGAP4 (rs8114927), and STK24 (rs9517326).ConclusionOur results suggest that calcium channels and monoamine neurotransmitters, as well as SNPs in genes directly or indirectly affecting neurogenesis and synaptic functions, may be involved in the development of increased anxiety. The role of some non-genetic factors and the clinical significance of physiological markers such as lifestyle were also demonstrated

Assessment of yield and quality of double-spore champignon mushrooms

The article presents the results of experimental data characterizing the yield and quality of double-spore champignon mushrooms obtained by their cultivation on the substrate with the use of organic additives of plant and animal origin - waste of food and processing industries: sunflower husks, meat and buckwheat meal and coarse grains. The yield of mushrooms is estimated by periods of substrate preparation (winter and summer) and fruit-bearing waves. Higher yield of mushrooms of mushrooms of double-spore champignon was obtained on the substrate prepared in summer for two waves of fruiting. Assessment of the quality of mushrooms involved studying the content of protein, fiber, fat and ash elements (potassium, phosphorus, calcium, sodium and magnesium). The results show that sunflower husk and meat and bone meal are the best organic additives that not only increase the yield of mushrooms, but also their quality. The study shows that the quality of mushrooms obtained in the second wave is significantly higher than the quality of mushrooms obtained in the previous wave. Positive is the fact that the use of organic waste in industrial mushroom production contributes to the efficient management of, as a rule, little used by-products of food and processing industries

Cytoprotective Activity of Polyamines Is Associated with the Alternative Splicing of RAD51A Pre-mRNA in Normal Human CD4+ T Lymphocytes

Physiological polyamines are ubiquitous polycations with pleiotropic biochemical activities, including regulation of gene expression and cell proliferation as well as modulation of cell signaling. They can also decrease DNA damage and promote cell survival. In the present study, we demonstrated that polyamines have cytoprotective effects on normal human CD4+ T lymphocytes but not on cancer Jurkat or K562 cells. Pretreatment of lymphocytes with polyamines resulted in a significant reduction in cells with DNA damage induced by doxorubicin, cisplatin, or irinotecan, leading to an increase in cell survival and viability. The induction of RAD51A expression was in response to DNA damage in both cancer and normal cells. However, in normal cells, putrescin pretreatment resulted in alternative splicing of RAD51A and the switch of the predominant expression from the splice variant with the deletion of exon 4 to the full-length variant. Induction of RAD51A alternative splicing by splice-switching oligonucleotides resulted in a decrease in DNA damage and cell protection against cisplatin-induced apoptosis. The results of this study suggest that the cytoprotective activity of polyamines is associated with the alternative splicing of RAD51A pre-mRNA in normal human CD4+ T lymphocytes. The difference in the sensitivity of normal and cancer cells to polyamines may become the basis for the use of these compounds to protect normal lymphocytes during lymphoblastic chemotherapy

Novel aminochromone derivative inhibits tumor growth on xenograft model of lung cancer in mice

2-Amino-4H-chromene derivatives possess anticancer property proved on different in vivo and in vitro models of malignancies such breast, nasopharyngeal, bladder, ovary carcinomas, astrocytoma, and osteosarcoma. We assumed it might be effective to apply one of the derivatives as promising approach to lung carcinoma treatment. to evaluate how novel 4-aryl substituted 2-amino-4H-chromene derivative AX-554 impacts tumor growth and progression, as well as possible mechanisms for anticancer effect development on in vivo patient-derived heterotopic xenograft model of lung carcinoma in mice. This was an experimental in vivo study. 40 nu/nu BALB/c female mice were randomly allocated into four equal groups: Intact, control, reference, and main group. Animals of three latter groups were ingrafted with human-derived lung adenocarcinoma. Antitumor and antimetastatic action of AX-554 novel aminochromone derivative as a substance were studied. Mice survival was registered. Kinase of anaplastic lymphoma (ALK), tubulin Beta-3 (TUBB3), and c-mesenchymal-epithelial transition (MET) concentrations in the prime tumor nodes homogenates were determined by quantitative enzyme-linked immunosorbent assay. Dannet's parametric criterion and the nonparametric exact Fisher test were used. The normality of the distribution was determined using ANOVA. The survival curve was analyzed using Gehan's criterion with the Yates's correction. Aminochromone derivative possesses an inhibitory effect on human lung adenocarcinoma transplanted into nu/nu BALB/c female mice, as well as significant antimetastatic activity. About 50 mg/kg/day AX-554 intragastric course increases animals' life expectancy of more than 3.3 times when compared with the control and induces remission in 60% of cases. The anticancer effect of the derivative is due to anti-ALK-mediated activation of tumor cells apoptosis and suppression TUBB3-dependent cell proliferation

The Study of Viral RNA Diversity in Bird Samples Using De Novo Designed Multiplex Genus-Specific Primer Panels

Advances in the next generation sequencing (NGS) technologies have significantly increased our ability to detect new viral pathogens and systematically determine the spectrum of viruses prevalent in various biological samples. In addition, this approach has also helped in establishing the associations of viromes with many diseases. However, unlike the metagenomic studies using 16S rRNA for the detection of bacteria, it is impossible to create universal oligonucleotides to target all known and novel viruses, owing to their genomic diversity and variability. On the other hand, sequencing the entire genome is still expensive and has relatively low sensitivity for such applications. The existing approaches for the design of oligonucleotides for targeted enrichment are usually involved in the development of primers for the PCR-based detection of particular viral species or genera, but not for families or higher taxonomic orders. In this study, we have developed a computational pipeline for designing the oligonucleotides capable of covering a significant number of known viruses within various taxonomic orders, as well as their novel variants. We have subsequently designed a genus-specific oligonucleotide panel for targeted enrichment of viral nucleic acids in biological material and demonstrated the possibility of its application for virus detection in bird samples. We have tested our panel using a number of collected samples and have observed superior efficiency in the detection and identification of viral pathogens. Since a reliable, bioinformatics-based analytical method for the rapid identification of the sequences was crucial, an NGS-based data analysis module was developed in this study, and its functionality in the detection of novel viruses and analysis of virome diversity was demonstrated

ON THE QUESTION OF THE SAFETY OF A 4-ALKYL-SUBSTITUTED COMPOUND WITH ANTI-TUMOUR ACTION

The aim was to investigate the acute toxicity of the AX-554 compound following its intragastric administration, as well as to determine the effective cytotoxic concentration and dose of this preparation.Materials and methods. The study was performed using 76 nonlinear white laboratory mice of both sexes weighing 18–22 g, 150 male mice of C57BL/6 line and LCC tumour cell culture. The acute toxicity of the AX-554 4-alkyl-substituted compound in the form of granulated pellet mass was studied following its intragastric administration, with the results being analysed according to Litchfield and Wilcoxon. The effective dose of the substance was determined using a syngeneic tumour model in C57Bl/6 male mice with inoculated Lewis lung carcinoma. The effective concentration of the compound was determined in a tumour cell culture.Results. Our study of the acute toxicity of AH-554 after its intragastric administration in the form of granulate tablet mass have confirmed AH-554 to be a non-toxic substance. In doses ranging from 21.2 to 384 mg/kg, AH-554 is observed to suppress tumour growth in mice with syngeneic lung carcinoma at a level from 20 to 90%, with the highest therapeutic dose exceeding the minimum effective one by more than 18 times. This pattern is also observed when AH554 is applied in the culture of tumour cells. The results of this study can be used for developing a pharmaceutical based on the AH-554 compound.Conclusion. The AH-554 compound, 2-amino-4H-chromene derivative, is characterized by an optimal safety profile due its low toxicity and a wide range of anti-tumour action

Novel Dimethylacetamide-Containing Formulation Improves Infraorbital Anaesthesia Efficacy in Rats with Periodontitis

Background. To evaluate acute toxicity and local anaesthetic activity of a formulation containing a novel dimethylacetamide derivative, antioxidant, and vasoconstrictor in rats with chronic periodontitis. Methods. Novel anaesthetic dimethylacetamide-containing formulation LHT-15-32 was studied as 2% water solution. Its acute intravenous and subcutaneous toxicity was determined in mice. Pain sensitivity threshold of the upper second molar was determined in rats with experimental periodontitis. Oxidative stress activity and total antioxidant capacity were determined in rats’ gingival mucosa by induced chemiluminescence. Local changes were evaluated in periodontal tissue by morphological examination. Tissue IL-1β, IL-10, and TNF-α concentration was quantitatively assessed by an enzyme-linked immunosorbent assay. LHT-15-31 Na-blocking activity was studied on isolated neurons of Limnaea stagnalis’ parapharyngeal ganglion. Isolated sciatic nerve of Rana radibunda was perfused with different concentrations of LHT-15-32 to assess its conductivity. Statistical analysis was used, and continuous variables were presented as mean ± square deviation. The normality of distribution was determined using ANOVA. Newman–Keuls parametric criterion was used for intergroup comparison. LD50 indexes were calculated by probit analysis. Results. LHT-15-32 acute intravenous and subcutaneous toxicity was lower than that of its active substance. The formulation by infraorbital administration induced deep dental anaesthesia which lasted over 70 min and activated the local antioxidant defense system and decreased IL-1β level in gingival tissue. LHT-15-32 triggered tissue reparation around the impacted upper molar in rats assessed five days after administration. At 10−6 to 10−3 M concentration, LHT-15-32 inhibited sciatic nerve conductivity and blocked Na+ channels of isolated neurons in a dose-dependent manner. Conclusions. The formulation may be considered as an effective and safe approach to anaesthetize upper molars with periodontitis

Data_Sheet_2_Genetics of psycho-emotional well-being: genome-wide association study and polygenic risk score analysis.docx

BackgroundPsycho-emotional well-being is essential for living a life of satisfaction and fulfillment. However, depression and anxiety have become the leading mental health issues worldwide, according to the World Health Organization. Both disorders have been linked to stress and other psychological factors. Their genetic basis remains understudied.MethodsIn 2020–2021, the psycho-emotional well-being of 30,063 Russians with no known psychiatric history was assessed using the Hospital Anxiety and Depression Scale (HADS) for general mental health and the HADS subscale A (anxiety) for anxiety. Following the original instructions, an anxiety score of ≥11 points was used as the anxiety threshold. A genome-wide association study was performed to find associations between anxiety and HADS/HADS-A scores using linear and logistic regressions based on HADS/HADS-A scores as binary and continuous variables, respectively. In addition, the links between anxiety, sociodemographic factors (such as age, sex, and employment), lifestyle (such as physical activity, sleep duration, and smoking), and markers of caffeine and alcohol metabolism were analyzed. To assess the risk of anxiety, polygenic risk score modeling was carried out using open-access software and principal component analysis (PCA) to simplify the calculations (ROC AUC = 89.4 ± 2.2% on the test set).ResultsThere was a strong positive association between HADS/HADS-A scores and sociodemographic factors and lifestyle. New single-nucleotide polymorphisms (SNPs) with genome-wide significance were discovered, which had not been associated with anxiety or other stress-related conditions but were located in genes previously associated with bipolar disorder, schizophrenia, or emotional instability. The CACNA1C variant rs1205787230 was associated with clinical anxiety (a HADS-A score of ≥11 points). There was an association between anxiety levels (HADS-A scores) and genes involved in the activity of excitatory neurotransmitters: PTPRN2 (rs3857647), DLGAP4 (rs8114927), and STK24 (rs9517326).ConclusionOur results suggest that calcium channels and monoamine neurotransmitters, as well as SNPs in genes directly or indirectly affecting neurogenesis and synaptic functions, may be involved in the development of increased anxiety. The role of some non-genetic factors and the clinical significance of physiological markers such as lifestyle were also demonstrated.</p