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The aim of this study was to initiate calli formation and cell suspension cultures from some species of Agastache genus. These plants could be useful for a production of bioactive secondary metabolites in vitro. For the initiation of callogenesis, two explant types were tested: leaf and stem explants from 40–60 days old in vitro seedlings. Percentage of callus formation was used as criterion to evaluate the efficiency of callus induction. Leaf- and stem-derived friable calli of A. foeniculum and A. urticifolia cultivated on MS medium supplemented with 0.5 mg/L 2.4-dichlorophenoxyacetic acid and 0.1 mg/L kinetin were selected for the cell suspension cultures establishing. The cell suspension cultures of A. foeniculum characterized by growth indexes of 1.08 and 8.57 for MS and B5 media respectively. For A. urticifolia suspension cultures growth indexes were 3.01 for MS medium and 1.29 for B5 medium. The period of culturing was 28 days. Viability of cell suspension cultures varied 50–100 during the period of culturing. According to the growth characteristics for establishing A. foeniculum suspension culture is better to use MS medium, and for A. urticifolia – B5.

Dichlorodiphenyltrichloroethane (DDT) and its metabolite dichlorodiphenyldichloroethylene (DDE) are ubiquitous in the environment and detected in tissues of living organisms. Although DDT owes its insecticidal activity to impeding closure of voltage-gated sodium channels, it mediates toxicity in mammals by acting as an endocrine disruptor (ED). Numerous studies demonstrate DDT/DDE to be EDs, but studies examining muscle-specific effects mediated by nonhormonal receptors in mammals are lacking. Therefore, we investigated whether o,p'-DDT, p,p'-DDT, o,p'-DDE, and p,p'-DDE (DDx, collectively) alter the function of ryanodine receptor type 1 (RyR1), a protein critical for skeletal muscle excitation-contraction coupling and muscle health. DDx (0.01-10 µM) elicited concentration-dependent increases in [3H]ryanodine ([3H]Ry) binding to RyR1 with o,p'-DDE showing highest potency and efficacy. DDx also showed sex differences in [3H]Ry-binding efficacy toward RyR1, where [3H]Ry-binding in female muscle preparations was greater than male counterparts. Measurements of Ca2+ transport across sarcoplasmic reticulum (SR) membrane vesicles further confirmed DDx can selectively engage with RyR1 to cause Ca2+ efflux from SR stores. DDx also disrupts RyR1-signaling in HEK293T cells stably expressing RyR1 (HEK-RyR1). Pretreatment with DDx (0.1-10 µM) for 100 s, 12 h, or 24 h significantly sensitized Ca2+-efflux triggered by RyR agonist caffeine in a concentration-dependent manner. o,p'-DDE (24 h; 1 µM) significantly increased Ca2+-transient amplitude from electrically stimulated mouse myotubes compared with control and displayed abnormal fatigability. In conclusion, our study demonstrates DDx can directly interact and modulate RyR1 conformation, thereby altering SR Ca2+-dynamics and sensitize RyR1-expressing cells to RyR1 activators, which may ultimately contribute to long-term impairments in muscle health.

Relevance. In onion breeding, quickly obtain aligned material is an urgent target for create parent forms of heterosis hybrids. Using classical methods with helping of backcrosses, this is achieved in 10-12 years. Using the technology of doubled haploids, it is possible to reduce these terms several times, and also to avoid the manifestation of inbred depression when obtaining lines by self-pollination. At the same time, the most effective in the production of haploids is the use of whole flower buds as an explant, unlike ovules and ovaries, the production of which is more time-consuming and labor-intensive.Methods. The doubled onion haploids were obtained by the method of ovule culture on the basis of the biotechnology laboratory of the Gavrish Breeding Center using the technology that based on the methodological recommendations of Monakhos S.G. et al., 2014. DH–onion plants with a developed root system and leaf apparatus were planted in the open ground and grown according to the technology generally accepted for the zone at the sites of the Gavrish breeding center, Krymsk, Krasnodar Territory. The obtained commercial bulbs were evaluated according to the RTG/46/2 method.Results. It was obtain doubled haploids, which were tested for ploidness by flow cytometry. 40 digaploid onion plants have been created. As a result of further development after transplantation into the open ground, storage, springization and selection, 3 uterine bulbs were obtained for further reproduction and inclusion in the breeding process.

Currently, a number of external factors (in particular, sanctions pressure from the US and EU countries, the pandemic of a new coronavirus infection) have a strong negative impact on the socio-economic development of the constituent entities of the Russian Federation. Therefore, the head of almost any Russian region is forced to perform the functions of an anti-crisis manager. The modern system of stimulating the work of civil regional employees can help improve the efficiency of public administration, and as a result, ensure the socio-economic development of a constituent entity of the Russian Federation. The author's approach to this issue is based on the simultaneous application of a number of modern scientific methods, namely index, neural network technologies and mathematical game theory. The use of neural network technologies makes it possible to objectively assess the achieved level of socio-economic development of a constituent entity of the Russian Federation. Taking into account the positive foreign (Singapore and South Korean) experience in the field of civil service reform, it is proposed to make the amount of collective incentive payments (bonus fund) of regional civil servants directly dependent on the achieved level of socio-economic development of the subject of the Russian Federation. In turn, this implies the development of a hierarchical system of collective-individual stimulation of the work of regional civil servants. During the construction of the game-theoretic model, the correct establishment of the relationship between the level of collective incentive payments to regional civil servants and the socio-economic development of a constituent entity of the Russian Federation is ensured. After experimental refinement of the parameters of the game-theoretic model, there is a possibility of its practical application to stimulate the work of regional civil servants in Russia. The introduction of the author's approach into the practice of regional management, firstly, will allow coordinating the activities of ministries and departments, and secondly, will strengthen control over the targeted spending of budgetary funds on bonus payments to civil civil servants.

Objective ‒ to develop a technique of triple antiembolic protection with the simultaneous use of proximal antiembolic protection systems, distal antiembolic filters and two-layer micromesh carotid stents for carotid stenting of ultraembolic hazardous carotid stenosis. Evaluate its effectiveness and safety. Materials and methods. Since 2016, 23 carotid stenting of ultraembolic hazardous carotid stenoses has been performed using the technique of triple antiembolic protection (proximal antiembolic protection systems, distal antiembolic filters and two-layer micromesh carotid stents). All patients had symptomic stenosis: transient ischemic attacks in a certain carotid pool (n = 7), ischemic strokes (n = 16). The age of patients was from 57 to 84 years. Men prevailed among patients (n = 15). Postoperative follow-up included magnetic resonance imaging (MRI) of the brain on the first or second day after surgery with T2*, FLAIR and DWI sequences to determine the presence of «fresh» embolic ischemic foci and to exclude hemorrhagic complications. After 6 months, a control clinical examination, computed tomography or MRI of the brain, ultrasound angioscanning of the main arteries of the head were performed. Results. In all patients the patency of the carotid arteries was completely restored, and in the early postoperative period, no clinical signs of recurrent ischemic brain damage were detected in any of the cases. No signs of plaque prolapse through the stent were detected in any case. A significant amount of atheromatous debris was in 11 cases when aspirated on an external filter. In 3 cases, emboli were also detected in the distal protection filter. This fact indicates that the joint use of distal and proximal antiembolic systems reliably protects against the risk of embolism in such cases. According to MRI on the 1st or 2nd day there were no signs of «fresh» subclinical embolic ischemic foci, as well as hemorrhage. In 20 patients who underwent a follow-up examination, no signs of restenosis in the stent were recorded in any case, as well as repeated ischemic strokes. In 7 cases where the plaque had an ulcer, the ulcer resolved under the stent. Three patients are expected for a follow-up examination. According to the remote survey, these patients do not have new ischemic brain lesions. The effectiveness of the technique of triple antiembolic protection for the treatment of patients with subtotal ultraembolic hazardous carotid stenosis is indicated by the absence of clinical and neuroradiological signs of recurrent ischemic lesions. Conclusions. The technique of triple antiembolic protection for the treatment of patients with subtotal ultraembolic hazardous carotid stenoses is safe and highly effective. It is the improvement of carotid stenting results in this most dangerous group that gives reason to think about revealing the advantages of carotid stenting over carotid endarterectomy in general.

Chicory (Cichorium intybus L.) is a key source of valuable primary and secondary metabolites (inulin, vitamins, essential oil). The spectrum of medicinal action of chicory includes antimicrobial, antiinflammatory, choleretic, diuretic, sedative, and appetite stimulating activities. Plant tissue and cell culture allow the production of high yields of plants, biomass, and valuable metabolites throughout the year. In our research, we produced aseptic plants from two Russian breeding (Yaroslavsky and Petrovsky), performed their primary phytochemical screening, and established the quantitative content of particular elements and substance groups using IR spectroscopy. It has been found that a high yield of viable aseptic plants of the Yaroslavsky cultivar can be achieved by seed treatment with 8% sodium hypochlorite for 10 minutes or 37% hydrogen peroxide for 5 minutes. For the Petrovsky cultivar, it is advisable to germinate nonsterile seeds and then introduce them into the culture by washing the seedlings in a slightly pink solution of potassium permanganate, followed by sterilization with 8% sodium hypochlorite for 5 minutes and washing with plants the antibiotic solution (0.8% gentamicin) for 15 minutes. All studied classes of compounds (tannins and phenols, flavonoids, saponins, alkaloids, glycosides, reducing sugars, and proteins) are present in aseptic plants of C. intybus; however, differences appear depending on the extractants (water and ethanol). IR spectroscopy has shown a higher content of moisture, fiber, and starch in seeds and a higher content of macronutrients, fat, ash, and proteins in aseptic plants.

In world practice, one of the main features of integrated transport systems, is the delivery of goods «door-to-door», which is impossible without the road transport is being used at the final stage of transportation. Today, the situation on the Ukrainian roads has a negative trend in terms of traffic jams and accidents, which creates a risk of delay or damage to freight during the transportation process. The problem is how to optimize the urban transport network to meet the growing demand for transportation and reduce traffic congestion. Purpose. Investigate the root causes of traffic congestion and develop a tool in order to optimize the city network on the example of a traffic interchange. Analytical and experimental with the use of computer 3D-simulation. For a practical demonstration, a model of one of the most problematic, from the point of view of traffic jams, transport interchanges in Kyiv, was developed. An optimization experiment was conducted, which demonstrated an increase in interchange capacity by 26,2 % and reduction in average transportation time by 60,47 %. It is a difficult task to optimizing the transport network, because if you conduct an experiment with a real system, any changes could be catastrophic. In addition, it is necessary to anticipate the growth of traffic, take into account the economic, territorial and industrial characteristics of settlements. The research clearly demonstrates the possibilities of simulation computer modeling in this aspect. The purposed solution allows to optimize the city transport network without significant investment, and could reduce the risk of accidents, financial and time costs for transportation of goods by city in the global aspect.

Background: Mitochondrial dysfunction is considered an important mechanism in the pathogenesis of various diseases. Therefore, mitochondria are currently being considered as subjects for targeted therapies, particularly, phototherapy using 5-aminolevulinic acid. This study aimed to investigate the activity of mitochondria in cells with different mutation loads. Materials and Methods: The study was conducted using 11 cybrid lines obtained from the THP-1 cell line (a human monocytic leukemia cell line) and platelets of patients with different mitochondrial mutations. Results: Our results illustrate that 5-aminolevulinic acid was metabolized equally in all cell lines, however, there was a significant decrease in mitochondrial potential, which differed among lines. Conclusions: The results of this study can be used to develop a personalized therapeutic approach based on different mitochondrial activities.

Cancer is one of the leading causes of death worldwide, accounting for about 10 million deaths a year, or nearly one in six deaths. The most common types of cancer are breast, colorectal, lung, and prostate cancers. Prolonged application of hormone drugs leads to the development of resistance. The development of agents with high activity against resistant cells is a challenge. It is important to create novel targeted compounds and search for active molecules among those previously developed. The study aimed to evaluate the sensitivity of 4-hydroxytamoxifen-resistant cells to 5-fluorouracil (5-FU) and analyse the signalling pathways that are regulated by 5-FU in breast cancer cells. Antiproliferative activity of compounds was assessed by the MTT assay, and immunoblotting was used to evaluate the expression of proteins in breast cancer cells. Activity of 5-FU was evaluated on parental MCF7 cells and a cell subline with resistance to 4-hydroxytamoxifen (HT), named MCF7/HT. The MCF7/HT cells showed high sensitivity to 5-FU. Expression of oestrogen receptor α (ERα, a key driver of breast cancer growth) in MCF7 and MCF7/HT cells was not sensitive to 5-FU treatment. In both parental and resistant cells, 5-FU induced changes in the activity of several signalling proteins. 5-FU activated AKT, extracellular signal-regulated kinase 1/2 (ERK 1/2) and upregulated cyclin D1 expression. The data suggest that 5-FU should be further investigated as a chemotherapeutic for hormone-resistant cancers; the combination of 5-FU with novel apoptosis inducer LCTA-3344 is considered effective to inhibit the growth of breast cancer cells, including those that are hormone-resistant.

The article suggests a scientific base for using «green» and social bonds to solve environmental problems in water supply systems; numerous facts that encourage using social investment tools in the high-yield water sector are revealed. In particular, preconditions for intensifying economic activity in the construction field are appearing, as it is obvious that a constant threat of shelling faced by our country changes the requirements for all living conditions, and water supply systems as well. Emphasis is placed on the assumption that if the green bond market in Ukraine is implemented and developed, it will help to create a multiplier for attracting funds to implement various environmental projects and to increase guarantees for investors injecting funds in such projects. Both negative and positive factors of using social investment to modernize water supply systems in Ukraine are identified. It is concluded that it is necessary to intensify the development of the regulatory framework for «green» and social investment in order to offset the trend of debt accumulation among enterprises operating water supply systems in Ukrainian settlements, so that such enterprises could become monopolists in the market.

Abstract Brain systems dealing with multiple meanings of ambiguous stimuli are relatively well studied, while the processing of non-selected meanings is less investigated in the neurophysiological literature and provokes controversy between existing theories. It is debated whether these meanings are actively suppressed and, if yes, whether suppression characterizes any task that involves alternative solutions or only those tasks that emphasize semantic processing or the existence of alternatives. The current functional MRI event-related study used a modified version of the word fragment completion task to reveal brain mechanisms involved in implicit processing of the non-selected solutions of ambiguous fragments. The stimuli were pairs of fragmented adjectives and nouns. Noun fragments could have one or two solutions (resulting in two words with unrelated meanings). Adjective fragments had one solution and created contexts strongly suggesting one solution for ambiguous noun fragments. All fragmented nouns were presented twice during the experiment (with two different adjectives). We revealed that ambiguity resolution was associated with a reduced BOLD signal within several regions related to language processing, including the anterior hippocampi and amygdala and posterior lateral temporal cortex. Obtained findings were interpreted as resulting from brain activity inhibition, which underlies a hypothesized mechanism of suppression of non-selected solutions.

Background. According to the World Health Organization, about 50 million people worldwide suffer from epilepsy. Almost 1/3 of patients are diagnosed with drug-resistant epilepsy (DRE). There is a relationship between the intestinal microbiome (IM) and the central nervous system, which is carried out throughout life through a bidirectional dynamic network. There is evidence that IM changes in patients with DRE.Objective: to summarize the current literature data on the role of the microbiome-gut-brain axis in DRE, as well as to assess the value of changes in the composition of IM as a prognostic marker of the development of DRE.Material and methods. The authors conducted a search for publications in the electronic databases PubMed/MEDLINE and eLibrary, as well as Google Scholar search engine. The evaluation of the articles was carried out in accordance with the PRISMA recommendations. As a result of the search, 4,158 publications from PubMed/MEDLINE database, 173 publications from eLibrary, and 1,100 publications found with Google Scholar were extracted. After the selection procedure, 121 studies were included in the review.Results. The review provides convincing evidence of a correlation between IM and DRE. There were obvious differences in the composition of the intestinal microbiota in patients with epilepsy, depending on sensitivity to drugs. Dysbiosis of the intestinal microbiota can be corrected by exogenous interventions such as ketogenic diet, probiotic treatment and fecal microbiota transplantation, which subsequently leads to changes in neurochemical signaling in the brain and, consequently, to a decrease in epileptic activity.Conclusion. A ketogenic diet, probiotics and antibiotics may have some potential to influence epilepsy through the correction of dysbiosis of the intestinal microbiota, but the studies available to date do not provide an adequate level of evidence. Future clinical multicenter trials should use standardized protocols and a larger sample to provide more reliable evidence.In addition, further fundamental research is needed to elucidate potential mechanisms and therapeutic targets.