{"title":"SYNTHESIS OF CALIX[4]ARENES WITH FIXED CONFORMATION AS POTENTIAL INHIBITORS OF FIBRIN POLYMERIZATION","authors":"D.M. Ahishev","doi":"10.15407/biotech16.02.007","DOIUrl":"https://doi.org/10.15407/biotech16.02.007","url":null,"abstract":"Aim. The purpose of the present study was to develop a method for the fixation of ‘fixed’ conformation for estimation of the impact of calix[4]arene structure on the efficacy of its anticoagulant activity. This was achieved by substitution of the lower rim of C-145 analogue. Methods.Calix[4]arene C-145F (compound 6) was obtained in 4 steps starting with Duff reaction. Calix[4]arene methylene-bis-phosphonic ester 3 was prepared via addition of diisopropylphosphite in presence of metallic sodium to the parent calix[4]arene aldehyde 2. Further steps included Mitsunobu reaction, that afforded dipropoxycalix[4]arene 5 with rather good yields (80%), following the hydrolysis step that resulted in compound 6 in almost quantitative yield. Modeling of 3D-structure of calix[4]arene C-145 and its analogue C-145F was performed in Maestro, Schrodinger software. Results. Using a 2D NMR-NOESY spectroscopy, we can observe a distinct cross-peak between an aromatic singlet with a chemical shift on 7.72 ppm and protons of isopropyl group with a chemical shift on 1.62 ppm, which are moved in the strong field. Conclusions. The easy method of the fixation of conus conformation of calix[4]arene cup will be useful for synthesis of novel functionally active compounds. We believe that further development and study of different calix[4]arenes will help scientists to obtain bioactive molecules that could be prospective anti-thrombotic drugs.","PeriodicalId":9267,"journal":{"name":"Biotechnologia Acta","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42783163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"RHODIOLA ROSEA AND FERULIC ACID ACTIVATE EXPRESSION OF GENES RELATED TO AUTOPHAGY AND RESISTANCE TO HEAT SHOCK IN MICE OF DIFFERENT AGE","authors":"O. Demianchuk","doi":"10.15407/biotech16.02.015","DOIUrl":"https://doi.org/10.15407/biotech16.02.015","url":null,"abstract":"The aim of our study was testing whether R. rosea extract and ferulic acid activate expression of targets of FoxO, regulators of energy metabolism and autophagy in livers of young and old mice, and to what extent the effects of R. rosea extract and ferulic acid on the genes studied coincide. Methods. . C57BL/6J mice were reared at 22 ± 2 °С, 50-60% humidity, and 12/12 hour light/dark cycle. All groups were reared on a standard chow (4,8% fats, 21,8% protein, and 3,9% fibre). Experimental groups consumed water, supplemented with either sodium ferulate or R. rosea during 12 weeks prior sacrificing. The amounts of ferulate and R. rosea were adjusted to provide 4 mg of phenol-containing substances per 100 g weight, for a mouse, for 24 hours. We tested three-month-old (“young”) and twelve-month-old males (“old”). The levels of messenger ribonucleic acid (mRNA) were assessed using AriaMx real-time polymerase chain reaction (RT-PCR) instrument (Agilent). Ribonucleic acid was purified using the Monarch Miniprep kit (New England BioLabs (NEB), T2010), complementary deoxyribonucleic acid synthesis was performed using the ProtoScript II kit (NEB, E6560), and quantitative RT-PCR (qRT-PCR) was performed using the Luna Universal kit (NEB, E3003). The expression of genes ATG5 (an autophagy marker), HSPB8 (a small heat shock protein, an FoxO target), UCP2 (uncoupling protein 2, a senescence marker), CDKN2 (cell cycle regulator, a senescence marker), PDK2 and PDK4 (pyruvate dehydrogenase kinases 2 and 4, regulators of oxidative metabolism), and TFEB (transcription factor EB, a transcriptional regulator of autophagy) was evaluated. Results. Livers of young mice that consumed food supplemented with either sodium ferulate or R. rosea extract had 3.2-fold and 3.6-fold higher levels of mRNA of the small heat shock protein HspB8 than control mice, respectively. In old mice, the levels of mRNA for this protein were 3.3-fold higher in mice reared on the diet containing R. rosea extract as compared with the control. However, there was no significant difference between control mice and those that consumed ferulate-supplemented food. In young mice, ferulate and R. rosea extract induced synthesis of mRNA of PDK4 by 4.3 and 6.6 times from the control level, respectively. Ferulate and R. rosea extract also affected the levels of mRNA of ATG5 and PDK2 in the livers of old mice. The levels of PDK2 were 1.5-fold higher in the livers of mice that consumed ferulate-supplemented food than in control mice. Conclusions. Both, R. rosea extract and one of its active components – ferulic acid – promote increasing in the levels of mRNA for genes HSPB8 and PDK4, coding for small heat shock protein and pyruvate dehydrogenase kinase 4, respectively. In old mice, R. rosea promote expression of HSPB8, ATG5, PDK2, and PDK4. Thus, ferulic acid and R. rosea exert similar effects on gene expression by supposed activation of heat shock response and autophagy, and concomitant inhibition of mitochond","PeriodicalId":9267,"journal":{"name":"Biotechnologia Acta","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41759755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"MICROGLIAL PHAGOCYTOSIS IN RATS WITH DIFFERENT MODELS OF ALZHEIMER'S DISEASE","authors":"A. Nefedova","doi":"10.15407/biotech16.01.057","DOIUrl":"https://doi.org/10.15407/biotech16.01.057","url":null,"abstract":"Neuroinflammation is a key feature of Alzheimer's disease (AD), a progressive neurodegenerative disorder. Microglia, the resident immune cells of the central nervous system, play a crucial role in the pathogenesis of AD and are active participants in neuroinflammation. Adequate reproduction of neuroinflammation in animal models is one of the main methodological approaches for studying AD pathogenesis and pathophysiology. The aim of the study was to conduct a comparative assessment of the phagocytic activity of microglia in rats with AD induced by intrahippocampal administration of beta-amyloid (Aβ) 1-40 and Aβ25-35. Materials and methods. Wistar male rats were used in the study. Intact and sham-operated animals were used as controls. The development of the disease was confirmed by the assessment of cognitive impairment in the Barnes maze behavioral test, as well as by the level of dopaminergic neurons (DN). The phagocytic activity of microglia, as well as oxidative metabolism and the expression of phenotypic markers CD80 and CD206 were determined by flow cytometry. Results. In animals with Aβ 1-40-induced AD, significant impairment of cognitive activity and loss of DN were registered, microglial cells were characterized by an increase in the proportion of phagocytic cells and an increase in their endocytic activity, augmented oxidative metabolism and overexpression of CD86 and CD206. In animals with Aβ 25-35-induced AD, moderate impairment of cognitive activity was observed, microglial cells were characterized only by an increase in the number of phagocytizing cells without changes in their endocytic activity, oxidative metabolism, and expression of phenotypic markers. Conclusion. Thus, in animals with Aβ1–40-induced AD, the pro-inflammatory functional profile of microglia, which is characteristic for neuroinflammation in the clinical course of the disease, is more adequately reproduced.","PeriodicalId":9267,"journal":{"name":"Biotechnologia Acta","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46091333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"MAIN ASPECTS OF THE MANUFACTURER OF ORGANIC PRODUCTS IN UKRAINE","authors":"Nataliia Оhоrоdnyk","doi":"10.15407/biotech16.01.040","DOIUrl":"https://doi.org/10.15407/biotech16.01.040","url":null,"abstract":"The article is devoted to highlighting the state and prospects for the development of organic production in Ukraine. The main requirements for the production, classification and labeling of organic products of animal and plant origin are presented. The current legal norms governing their certification and circulation are emphasized. The key provisions regarding evaluation and regulation in this field of activity are reflected. The stages of improvement of the domestic legislative framework of organic production are shown on the way of adaptation to European standards.Purpose. To highlight the state and prospects for the development of organic production in Ukraine and the improvement of the legislative framework of organic production on the way to adaptation to European standards. Materials and methods. Methodical analysis and abstract-logical method for summarizing the criteria for evaluating the formation, development and integration of domestic organic production into the structure of the world production of safe products of animal husbandry and crop production. Results. The article describes in detail the development of the organic movement, which is a promising lever for food security in Ukraine. Therefore, the work on the legal regulation of the activities of domestic producers of organic products does not stop. The legislation is improving in the direction of introducing effective state support in this area at the regional and national levels. Of course, organic feed production, animal husbandry and crop production will continue to exist in parallel with non-organic production. However, the principles and relationship of these systems will depend significantly on the availability of energy sources, plant protection products, fertilizers, soil fertility, care for the preservation of the natural environment, ensuring welfare population and its needs in healthy nutrition. In addition, for the restoration of agricultural lands, demining and bioremediation with the use of bacterial and phytoremediation of soil and water resources should be applied. For this, after the liberation of our state, a return to the peaceful management of the national economy is necessary. We believe in the victory and restoration of Ukraine with the help of allied states and people of good will.","PeriodicalId":9267,"journal":{"name":"Biotechnologia Acta","volume":"49 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135827611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"COMBINED NANOCHEMOTHERAPY USING DOXORUBICIN AND CURCUMIN AS AN EXAMPLE","authors":"M. Kaniuk","doi":"10.15407/biotech16.01.005","DOIUrl":"https://doi.org/10.15407/biotech16.01.005","url":null,"abstract":"The aim of the work was to review literature data on combined nanochemotherapy using the example of two drugs ̶doxorubicin and curcumin. Special attention was paid to the use of substances with synergistic properties in one nanoparticle, capable to penetrate into living cell. The method of combined chemotherapy of nanopreparations improves processing efficiency. The technique of using nanocontainers with synergistic drugs in combination with ligands reduces the side effects of chemotherapy drugs. Results. Literature data indicate that the use of nanopreparations contributes the rapid creation and use of synergistic combinations that were purposefully delivered to target cells, reducing dosage due to precise targeting. A promising direction of nanomedicine is the creation of multifunctional nanomaterials based on several active drugs having synergistic properties, with the simultaneous use of their enhancers and the strategy of active targeting. These structures enabled targeted and controlled penetration of medicinal compounds into the localization of pathological processes, reducing drugs toxicity for normal cells. Conclusions. Combined chemotherapy using polymers and nanoparticles with ligands, in which synergistic drugs are included, ensures to reduce side effects and doses of chemotherapy drugs, and helps to overcome multiple drug resistance as well.","PeriodicalId":9267,"journal":{"name":"Biotechnologia Acta","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43124878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"DETERMINING OF NUTRITIONAL VALUE OF CAVIAR OF SIBERIAN STURGEON IN UKRAINE","authors":"I. P. Palamarchuk","doi":"10.15407/biotech16.01.067","DOIUrl":"https://doi.org/10.15407/biotech16.01.067","url":null,"abstract":"Aim. The purpose of the work was to study the nutritional value of siberian sturgeon caviar Acipenser baerii, grown in aquaculture conditions in the Dnieper reservoirs of Ukraine, and to compare its quality indicators with this product produced abroad. Methods: There are identified organoleptic properties of siberian sturgeon caviar, and its energetic value, composition of amino acids in albumens and content of fatty acids in lipids of the product. The data obtained in the research were compared with the same indices of quality of caviar of sturgeons bred abroad. Results. The organoleptic properties of siberian sturgeon caviar bred in Ukraine (appearance, color, consistency, taste and aroma) conformed to its standardized indices of quality. The caviar contained all eight essential amino acids and belonged to category of products rich by albumen (21.54±2.13%),and fats eicosapentaenoic and docosahexaenoic ω-3 acids (3.46 % and 11.2 %, respectively). (13.20±0.93%). The big content of fat, especially of polyunsaturated fatty acids and 3 acids (the eicosapentaenoic and docosahexaenoic ones — 3.46 % and 11.2 %, respectively) is one more factor, which enables to identify thes siberian sturgeon caviar as the product of high biological value. It was shown that the caviar of siberian sturgeon produced in Ukraine is in close coincidence with those that were produced in other countries. Conclusions. The totality of studied characteristics of caviar of siberian sturgeon produced in Ukraine witnesses its high nutritional value. Therefore this product may be recommended in prophylactics of numerous illnesse and strengthening of state of health.","PeriodicalId":9267,"journal":{"name":"Biotechnologia Acta","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46058930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"MICROBIAL CO-CULTIVATION: DISCOVERY OF NOVEL SECONDARY METABOLITES WITH DIFFERENT BIOLOGICAL ACTIVITIES","authors":"T. Pirog","doi":"10.15407/biotech16.01.021","DOIUrl":"https://doi.org/10.15407/biotech16.01.021","url":null,"abstract":"In recent decades, overuse and misuse of antibiotics as well as social and economic factors have accelerated the spread of antibiotic-resistant bacteria, making them a major problem for humanity. One of the most effective approaches to the discovery of new secondary antimicrobial metabolites is co-cultivation of microorganisms, in which the producer of the target products is grown together with competitive microorganisms ( inductors), in response to the presence of which silent biosynthetic genes of the producer strain are activated and an increase in the biological activity of the synthesized secondary metabolites and/or even the synthesis of new metabolites is observed. The review summarizes the current literature data on the co-cultivation of antimicrobial substances producers with competitive microorganisms, which results in the synthesis of new metabolites with antimicrobial and cytotoxic activity, not typical for monocultures. During the co-cultivation of fungi, bacteria, and fungi with bacteria, the synthesis of new antimicrobial and anticancer metabolites, which are classified as alkaloids, phenylpropanoids, macrolides, polyketides, cyclopeptides, terpenoids, anthraquinones, and steroids, is observed. These data indicate that the mixed fermentation of microorganisms is a simple, cheap, and quite effective way to obtain new metabolites that are promising for use in medicine.","PeriodicalId":9267,"journal":{"name":"Biotechnologia Acta","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45870811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"ULTRASOUND-ASSISTED AND ENZYMATIC-BASED METHOD FOR ISOLATION OF β-GLUCANS FROM OAT BRAN","authors":"V. Korsa","doi":"10.15407/biotech16.01.051","DOIUrl":"https://doi.org/10.15407/biotech16.01.051","url":null,"abstract":"β-Glucans are a group of non-starchy polysaccharides, or (1,3),(1,4)-β-D-glucans, that can be found in the cell walls of several species of bacteria, algae, lichens, fungi, and cereal grains. These carbohydrates are extensively used in food industry, cosmetics, pharmaceuticals and healthcare, therefore optimization of the extraction and isolation of β-glucans from grain sources has an especial importance in various fields of biotechnology, drug design, food science and technology. The aim of the study was to develop an optimized technological scheme for isolation of β-glucans from oat bran based on ultrasonic and enzymatic processing of raw material. Materials and methods. β-Glucans were isolated from grinded oat cereals during multi-stage process, which includes extraction of grain fats, hydrobarothermic processing, ultrasonification, enzymatic hydrolysis of concomitant starch and proteins, precipitation of β-glucan fraction by ethanol, centrifugation, and dry-freezing. Yield of β-glucans from raw material and its concentration in the final product were determined after hydrolysis by sulfuric acid or enzymatic cleavage by endo-1,3(4)-β-glucanase. Results. As shown by acidic hydrolysis of the final product, the yield of β-glucans was 10.8 ± 0.23% and concentration was 79.6 ± 3.89%, while enzymatic hydrolysis gave 8.7 ± 0.82% and 65.1 ± 4.72%, respectively. Thus, the use of hydrobarothermic and ultrasound pre-treatment of raw material in combination with proteolytic digestion of ballast lipids and proteins allowed producing oat β-glucans in amounts comparable with those in case of acid- or alkali-based procedures. Conclusions. The described technological scheme of β-glucan isolation from oat bran based on sequential hydrobarothermic processing, ultrasonification, and enzymatic removing starch and proteins can be widely used for routine β-glucan production for various purposes in food technology, pharmacological industry, and medicine.","PeriodicalId":9267,"journal":{"name":"Biotechnologia Acta","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44833055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"IN VITRO ANTILEUKEMIC ACTIVITY OF EUPHORBIA ECHINUS EXTRACT","authors":"Sbayou Houda","doi":"10.15407/biotech15.06.070","DOIUrl":"https://doi.org/10.15407/biotech15.06.070","url":null,"abstract":"Aim. Cancer continues to pose a serious threat to human health. Euphorbia plants are rich in phenolics, aromatic esters, steroids and several bioactive compounds. Studies have shown the presence of a large number of bioactive compounds in E. echinus including flavonoids, phenolics, and proanthocyanins. Method. There it was investigated cytotoxic effects of E. echinus methanolic extract on K562, HL60, Ishikawa, Raji and SH-SY5Y cells. Results. The E. echinus extract was found to be highly cytotoxic against HL60 and K562 (79.78 and 76.44% cytotoxicity, respectively). DNA fragmentation was exclusively observed in K562 cells indicating that the reduction of viable cells following treatment with E. echinus extract is due to apoptosis. Conclusions. Our results suggest that E. echinus extract might have a drug potential against leukemic cells.","PeriodicalId":9267,"journal":{"name":"Biotechnologia Acta","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48908254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"THE EXPRESSION OF TLR4, IFN-γ, TGF-β AND TNF-αLL LINE OF HUMAN SMALL CELL LUNG CARCINOMA NCI-H69 AND IN CISPLATIN-RESISTANT SUBLINE NCI-H69/CPR","authors":"I. Stupak","doi":"10.15407/biotech15.06.055","DOIUrl":"https://doi.org/10.15407/biotech15.06.055","url":null,"abstract":"Aim: to investigate the effect of teichoic acid Staphylococcus aureus for expression of pro-inflammatory cytokines and of TLR4 in a human small cell lung carcinoma cell line NCI-H69, and cisplatin resistant subline NCI-H69/CPR. Methods. Incubation of cells with teichoic acid (1 ng/m) conducted for 2 days. Expression level of TLR4, TGF-β, INF-γ, TNF-α was evaluated by the real time PCR on 7500 Real-Time PCR System, using specific primers and fluorochrome SYBR Green. The reverse transcription reaction was performed with High-Capacity cDNA Reverse Transcription Kit carried out under the conditions: 25 °C - 10 min, 37 °C ‒ 120 min and 85 °C ‒ 5 min. Results. In cell line culture NCI-H69 addition of teichoic acid increased expression of TLR4 by 1.3 times, and IFN-γ – by 1,1 times. Expression of TGF-β and TNF-α was decreased 2.5 and 4.9 times respectively. In cell line culture NCI-H69/CPR the addition of teichoic acid inhibited the expression of all studied parameters. Expression TLR4 decreased by 4.2 times, IFN-γ – by 1.4 times. Expression TGF-β and TNF-α was depressed 1.6 and 1.2 times. The presented data indicate that teichoic acid of bacterial origin provided the effect of modulating the inflammatory effect in lung cancer cell culture, sensitive and resistant to cisplatin. Conclusions. Teichoic acid as a ligand of TLR4 modulates the expression of pro-inflammatory and anti-inflammatory cytokines in small cell lung cancer cell culture and suppresses the expression of TLR4 and all investigated cytokines in the cisplatin-resistant cell line NCI-H69.","PeriodicalId":9267,"journal":{"name":"Biotechnologia Acta","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41561440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}