A Quantitative Theory of Mechanical Unfolding of a Homopolymer Globule

We propose the quantitative mean-field theory of mechanical unfolding of a globule formed by long flexible homopolymer chain collapsed in poor solvent and subjected to extensional deformation. We demonstrate that depending on the degree of polymerization and solvent quality (quantified by the Flory-Huggins $\chi$ parameter) the mechanical unfolding of the collapsed chain may either occur continuously (by passing a sequence of uniformly elongated configurations) or involves intra-molecular micro-phase coexistence of a collapsed and a stretched segment followed by an abrupt unraveling transition. The force-extension curves are obtained and quantitatively compared to our recent results of numerical self-consistent field (SCF) simulations. The phase diagrams for extended homopolymer chains in poor solvent comprising one- and two-phase regions are calculated for different chain length or/and solvent quality.Comment: 24 pages, 18 figure

Новый сорт лихниса корончатого (Lychnis coronaria (L.) Murray ex Desr.) Малиновый Рассвет селекции ФГБНУ ФНЦО

Relevance and methodology. Lychnis coronaria is a perennial herbaceous plant with high decorative properties, with prolonged flowering in the second or third year of vegetation. The pubescent leaves form beautiful rosettes. The plant is undemanding to the growing conditions. The research material was the varietal population of Lychnis coronaria. The study was carried out in the open ground of the Moscow region (2014- 2021) on experimental plots of the flower crops sector of the FSBSI FSVC.Results. The most aligned form according to decorative features was identified – LC 1-21 with high seed productivity of inflorescences, decorative and winter hardiness. A variety testing and preliminary reproduction of a promising cultivar of Lychnis coronaria was carried out. This variety was transferred to the FSBI "State Export Commission" in 2021 under the name “Malinovy Rassvet”. Such signs as "plant height", "bush diameter", "number of ornamental shoots", "flower diameter" had a low or average variation value, which characterizes this sample as the most aligned. Thus, the cv. “Malinovy Rassvet” of Lychnis coronaria is recommended for cultivation and use for decorative purposes. The leaves and the bright color of the flowers provide a contrast to the perennial borders and flower beds. It looks good both in single and group plantings, as well as in cutting. It is grown as a short-lived perennial. The main advantages of the variety are the color fastness of flowers when burned out in the sun, resistance to diseases and pests, high seed productivity.Актуальность и материал исследований. Лихнис корончатый – многолетнее травянистое растение, обладающее высокой декоративностью, с продолжительным цветением на второй, третий год вегетации. Опушённые листья образуют красивые розетки. Растение нетребовательное к условиям произрастания. Материалом исследований служила сортопопуляция лихниса корончатого. Изучение проводили в открытом грунте Московской области в 2014-2021 годах на опытных участках сектора цветочных культур ФГБНУ ФНЦО.Результаты. Выделена наиболее выровненная по декоративным признакам форма – ЛК 1-21 с высокой семенной продуктивностью соцветий, декоративностью и зимостойкостью. Проведено сортоиспытание и предварительное размножение перспективного сортообразца лихниса корончатого. Данный сортообразец передан в ФГБУ "Госсорткомиссия" в 2021 году под названием Малиновый Рассвет. Такие признаки как «высота растения», «диаметр куста», «число декоративных побегов», «диаметр цветка», имели низкое или среднее значение варьирования, что характеризует данный образец как наиболее выровненный. Таким образом, лихнис корончатый сорта Малиновый Рассвет рекомендован к выращиванию и использованию в декоративных целях. Листья и яркая окраска цветков обеспечивают контраст многолетним бордюрам и клумбам. Хорошо смотрится как в одиночных, так и групповых посадках, а также в срезке. Выращивается как недолговечный многолетник. Основные достоинства сорта – стойкость окраски цветков при выгорании на солнце, устойчивость к болезням и вредителям, высокая семенная продуктивность

Risk factors of adverse outcome of COVID-19 and experience of Tocilizumab administration in patients on maintenance hemodialysis due to diabetic kidney disease

BACKGROUND: Patients with Type 2 Diabetes (T2DM) and patients on maintenance hemodialysis (MHD) are at a high risk of adverse clinical course of COVID-19. To date, the causes of high mortality in these groups are not fully understood. Data about peculiarity of clinical course and Tocilizumab (TCZ) administration in patients with T2DM receiving MHD due to outcome of diabetic kidney disease (DKD) are not yet highlighted in current publications.AIMS: Identification of risk factors (RF) of adverse COVID-19 outcome and evaluation of TCZ administration in patients with T2DM receiving MHD due to DKD.MATERIALS AND METHODS: The patients treated in Moscow City Hospital No52 were included in retrospective observational study. The observation period was from 04.15 to 07.30 2020. The study endpoints were the outcomes of hospitalization — discharge or lethal outcome. Data were collected from electronic medical database. The following independent variables were analysed: gender, age, body mass index, time from the onset of symptoms to hospital admission, cardiovascular and general comorbidity (Charlson Index, CCI), cardiovascular event (CVE) during hospitalization, treatment in ICU, mechanical ventilation (MV), degree of lung damage according to CT data, level of prandial glycemia at admission, MHDassociated parameters (vintage, type of vascular access, frequency of complications). The autopsy reports were evaluated for the purpose of lethal structure investigation. In a subgroup treated TCZ the time from symptoms onset to TCZ administration and number of laboratory indicators were evaluated.RESULTS: 53 patients were included, mean age 68 ±9 y, males — 49%. General mortality in observation cohort was 45%, mortality in ICU — 81%, mortality on MV — 95%. High cardiovascular and general comorbidity was revealed (mean CCI — 8,3 ±1,5 points). The causes of outcomes according to autopsy reports data: CVE 37,5% (among them — acute myocardial infarction during hospitalization), severe respiratory failure — 62,5%. The independent predictors of lethal outcome were: MV (OR 106; 95% CI 11,5–984; р <0,001), 3-4 degree of lung damage according to CT data (ОR 6,2; 95% CI 1,803–21,449; р = 0,005), CVE during hospitalization (ОR 18,9; 95% CI 3,631–98,383; р <0,001); CCI ≥10 points (ОR 4,33; 95% CI 1,001–18,767; р = 0,043), level of prandial glycemia at admission ≥10 mmol/l (ОR 10,4; 95% CI 2,726–39,802; р <0,001). For risk identification of upcoming lethal outcome a predictive model was created with the use of discovered RF as variables. The predictive value of this model is 92,45% (positive prognostic value — 96,5%, negative prognostic value — 87,5%).In TCZ treated subgroup the laboratory markers of adverse outcome were detected with application of correlation analysis. Among them: increasing level of CPR 24-48 hours before lethal outcome (r = 0,82), the reduction of lymphocytes count after TCZ administration (r = -0,49), increasing of leukocytes and further reduction of lymphocytes count 24-48 hours before lethal outcome (r = 0,55 и r = -0,52, resp.)).CONCLUSIONS: The number of RF of adverse COVID-19 outcome in patients with T2DM receiving MHD due to DKD are identified. CVE is one of the leading causes of mortality in study cohort. According to our experience the preventive (instead of rescue) strategy of TCZ administration should be used

Granzyme A inhibition reduces inflammation and increases survival during abdominal sepsis

Aims: Peritonitis is one of the most common causes of sepsis, a serious syndrome characterized by a dysregulated systemic inflammatory response. Recent evidence suggests that Granzyme A (GzmA), a serine protease mainly expressed by NK and T cells, could act as a proinflammatory mediator and could play an important role in the pathogenesis of sepsis. This work aims to analyze the role and the therapeutic potential of GzmA in the pathogenesis of peritoneal sepsis. Methods: The level of extracellular GzmA as well as GzmA activity were analyzed in serum from healthy volunteers and patients with confirmed peritonitis and were correlated with the Sequential Organ Failure Assessment (SOFA) score. Peritonitis was induced in C57Bl/6 (WT) and GzmA-/- mice by cecal ligation and puncture (CLP). Mice were treated intraperitoneally with antibiotics alone or in combination serpinb6b, a specific GzmA inhibitor, for 5 days. Mouse survival was monitored during 14 days, levels of some proinflammatory cytokines were measured in serum and bacterial load and diversity was analyzed in blood and spleen at different times. Results: Clinically, elevated GzmA was observed in serum from patients with abdominal sepsis suggesting that GzmA plays an important role in this pathology. In the CLP model GzmA deficient mice, or WT mice treated with an extracellular GzmA inhibitor, showed increased survival, which correlated with a reduction in proinflammatory markers in both serum and peritoneal lavage fluid. GzmA deficiency did not influence bacterial load in blood and spleen and GzmA did not affect bacterial replication in macrophages in vitro, indicating that GzmA has no role in bacterial control. Analysis of GzmA in lymphoid cells following CLP showed that it was mainly expressed by NK cells. Mechanistically, we found that extracellular active GzmA acts as a proinflammatory mediator in macrophages by inducing the TLR4-dependent expression of IL-6 and TNFa. Conclusions: Our findings implicate GzmA as a key regulator of the inflammatory response during abdominal sepsis and provide solid evidences about its therapeutic potential for the treatment of this severe pathology

НАУЧНО-ИССЛЕДОВАТЕЛЬСКАЯ РАБОТА СТУДЕНТОВ В СИСТЕМЕ ВУЗОВСКОГО УПРАВЛЕНИЯ ПО ПРОБЛЕМАМ ФИЗКУЛЬТУРНО-ОЗДОРОВИТЕЛЬНОЙ ДЕЯТЕЛЬНОСТИ

Students’ research is an effective factor inpersonality self-organization, student management and university administration. The part of students’ scientific developments discovered in cooperation with scientific supervisors contributes to university science. Students’ research on the topics of physical training and healthy lifestyle is conducted at the chairs of Physical training. The article considers the experience of organization of research in the system of administrative university management and student self-government.Научно-исследовательская работа студентов является действенным фактором организации творческой деятельности личности, студенческого самоуправления и вузовского администрирования. Часть студенческих научных разработок, выполненных, как правило, совместно с ведущими преподавателями кафедр, может вносить определенный вклад в вузовскую науку. Научно-исследовательская работа студентов физкультурно-спортивной направленности и по поиску путей формирования здорового образа жизни индивидуального и коллективного характера осуществляется в вузах на кафедрах физической культуры, физического воспитания. В статье рассмотрен опыт организации научно-исследовательской работы студентов в системе административного вузовского управления и студенческого самоуправления

Fucans, but Not Fucomannoglucuronans, Determine the Biological Activities of Sulfated Polysaccharides from Laminaria saccharina Brown Seaweed

Sulfated polysaccharides from Laminaria saccharina (new name: Saccharina latissima) brown seaweed show promising activity for the treatment of inflammation, thrombosis, and cancer; yet the molecular mechanisms underlying these properties remain poorly understood. The aim of this work was to characterize, using in vitro and in vivo strategies, the anti-inflammatory, anti-coagulant, anti-angiogenic, and anti-tumor activities of two main sulfated polysaccharide fractions obtained from L. saccharina: a) L.s.-1.0 fraction mainly consisting of O-sulfated mannoglucuronofucans and b) L.s.-1.25 fraction mainly composed of sulfated fucans. Both fractions inhibited leukocyte recruitment in a model of inflammation in rats, although L.s.-1.25 appeared to be more active than L.s.-1.0. Also, these fractions inhibited neutrophil adhesion to platelets under flow. Only fraction L.s.-1.25, but not L.s.-1.0, displayed anticoagulant activity as measured by the activated partial thromboplastin time. Investigation of these fractions in angiogenesis settings revealed that only L.s.-1.25 strongly inhibited fetal bovine serum (FBS) induced in vitro tubulogenesis. This effect correlated with a reduction in plasminogen activator inhibitor-1 (PAI-1) levels in L.s.-1.25-treated endothelial cells. Furthermore, only parent sulfated polysaccharides from L. saccharina (L.s.-P) and its fraction L.s.-1.25 were powerful inhibitors of basic fibroblast growth factor (bFGF) induced pathways. Consistently, the L.s.-1.25 fraction as well as L.s.-P successfully interfered with fibroblast binding to human bFGF. The incorporation of L.s.-P or L.s.-1.25, but not L.s.-1.0 into Matrigel plugs containing melanoma cells induced a significant reduction in hemoglobin content as well in the frequency of tumor-associated blood vessels. Moreover, i.p. administrations of L.s.-1.25, as well as L.s.-P, but not L.s.-1.0, resulted in a significant reduction of tumor growth when inoculated into syngeneic mice. Finally, L.s.-1.25 markedly inhibited breast cancer cell adhesion to human platelet-coated surfaces. Thus, sulfated fucans are mainly responsible for the anti-inflammatory, anticoagulant, antiangiogenic, and antitumor activities of sulfated polysaccharides from L. saccharina brown seaweed

РЕЗУЛЬТАТЫ ПРИМЕНЕНИЯ СЕЛЕКТИВНОЙ АДСОРБЦИИ ЭНДОТОКСИНА ПРИ СЕПСИСЕ У ОНКОЛОГИЧЕСКИХ БОЛЬНЫХ

Objective: to study the clinical efficiency of using selective lipopolysaccharide (LPS) adsorption in postoperative gram negative sepsis in cancer patients.Subjects and methods. Examinations were made in 47 patients (11 women and 36 men) aged 47 to 84 years, who had been operated on for cancer and whose postoperative period had been complicated by gramnegative sepsis. The patients were divided into 2 groups: 1) 15 patents who received standard therapy (a control group); 2) 32 who had LPS adsorption using immobilized polymyxin B (a study group).Results. Upon completion of the selective LPS adsorption program, there was regression of the clinical signs of sepsis, statistically significantly lower peripheral blood leukocyte and neutrophil levels, and better blood biochemical parameters in 87.5% of cases. High baseline endotox in activity decreased from >0.6 to <0.4 units in 89% of the patients. After the final session of LPS adsorption, the need for vasopressor support reduced due to hemodynamic profile optimization. After selective endotoxin adsorption cycles, 15 of 26 cases did not need to continue organ replacement therapy. Twentyeightday mortality rates in the study and control groups were 25.0 and 53.3%, respectively.Conclusion. Incorporation of LPS adsorption into a set of intensive therapy for gramnegative sepsis is pathogenetically substantiated and can effectively abolish the manifestations of the systemic effects of bacterial endotoxin. The early and timely use of LPS adsorption provides inhibition of an initiating stimulus, which makes it possible to prevent the progression of a septic process and the development of severe sepsis and septic shock and improves the results of therapy in cancer inpatients.Цель. Изучить клиническую эффективность применения селективной ЛПСадсорбции при грамотрицательном сепсисе, развившимся в послеоперационном периоде у онкологических больных.Материал и методы. Обследовано 47 больных в возрасте от 47 до 84 лет (11 женщин и 36 мужчин), подвергнутых хирургическому вмешательству по поводу онкологических заболеваний, послеоперационный период которых осложнился развитием грамотрицательного сепсиса. Больные были разделены на 2 группы — контрольную и основную. Контрольная группа — 15 человек, получавших стандартную терапию, основная группа — 32, которым была применена ЛПСадсорбция с иммобили зированным полимиксином В. Результаты. После завершения программы селективной ЛПСадсорбции в 87,5% случаев наблюдали регресс клинических признаков сепсиса, статистически значимое снижение уровня лейкоцитов и нейтрофилов в периферической крови, улучшение биохимических показателей крови. У 89% больных регистрировали снижение исходно высоких показателей активности эндотоксина от >0,6 ед. до <0,4 ед. После заключительного сеанса ЛПСадсорбции отмечено снижение потребности в вазопрессорной поддержке в связи с оптимизацией «гемодинамического профиля». В 15 из 26 случаев после проведения курсов селективной адсорбции эндотоксина необходимости в продолжении органозаместительной терапии не было. Летальность (28дневная) в основной группе составила 25,0%, в контрольной — 53,3%.Заключение. Включение в комплекс интенсивной терапии грамотрицательного сепсиса метода ЛПСадсорбции является патогенетически обоснованным и позволяет эффективно купировать проявления системного воздействия бактериального эндотоксина. Раннее и своевременное применение метода ЛПСадсорбции обеспечивает ингибирование инициирующего стимула, что позволяет предупредить прогрессирование септического процесса, развитие тяжелого сепсиса и септического шока, улучшает результаты лечения госпитального периода онкологических больных

РАСПРОСТРАНЕННОСТЬ НЕАЛКОГОЛЬНОЙ ЖИРОВОЙ БОЛЕЗНИ ПЕЧЕНИ СРЕДИ ПАЦИЕНТОВ АМБУЛАТОРНО-ПОЛИКЛИНИЧЕСКОГО ЗВЕНА В ДАЛЬНЕВОСТОЧНОМ ФЕДЕРАЛЬНОМ ОКРУГЕ

The rapidly growing incidence of obesity and diabetes mellitus, especially in developed countries, stimulates medical experts to closely study the epidemiology of non-alcoholic fatty liver disease (NAFLD). According to the published results of the epidemiological study DIREG 2, the prevalence of NAFLD in outpatients inRussiaincreased over the period from 2007 to 2015 and amounted to 37.3%. In the present report, the population of patients with NAFLD in the Far East Federal District (FEFD) was studied as part of the multicentre epidemiological study DIREG 2.The aim. To analyze the data on FEFD obtained in the DIREG 2 study and compare those with the DIREG 2 data on the entireRussia.Materials and Methods. The prospective disease registry study: epidemiological, observational, cross-sectional, multicentre study on the prevalence of NAFLD in outpatients. The total number of participating patients in FEFD was 2500, including 900 males and 1600 females. Epidemiological data were collected within two routine patient visits to the participating research centers.Results. The major result of this study is that the prevalence of NAFLD in FEFD was significantly lower than that in the entireRussia (21.4% vs 37.3%). Although the rank distribution of the concomitant diseases in FEFD patients was comparable to that in the across-Russia population, the prevalence of metabolic syndrome, menopausal syndrome and hypertriglyceridemia was significantly higher in the FEFD population.Conclusion. Despite the lower prevalence of NAFLD there is a significantly higher prevalence of disorders associated with NAFLD in the FEFD patients as compared with the acrossRussian patients from DIREG2. A set of measures preventing these risk factors from converting into full-scale disease is needed. Стремительный рост заболеваемости такими патологиями, как ожирение и сахарный диабет, принимающий в развитых странах характер эпидемии, неминуемо ведет к увеличению уровня заинтересованности специалистов в изучении различных аспектов неалкогольной жировой болезни печени (НАЖБП). Согласно опубликованным результатам эпидемиологического исследования DIREG 2, распространенность НАЖБП у амбулаторных пациентов в России увеличилась за период с 2007 по2015 г. и достигла 37,3%. В данной работе в рамках многоцентрового эпидемиологического исследования DIREG 2 изучалась популяция пациентов с НАЖБП в Дальневосточном федеральном округе (ДФО).Цель. Анализ и обобщение полученных в рамках исследования DIREG 2 данных по ДФО в сравнении с данными DIREG 2 по России.Материалы и методы. Проспективный регистр заболевания: эпидемиологическое, наблюдательное, кросс-секциональное, мультицентровое исследование распространенности НАЖБП у амбулаторных пациентов. Общее число пациентов, принявших участие в исследовании в ДФО – 2500 пациентов, из них 900 мужчин и 1600 женщин. Эпидемиологические данные были получены в ходе двух рутинных визитов пациентов в исследовательские центры.Результаты. Ключевым результатом, выявленным в ходе данного исследования, является факт определения достоверно более низкой распространенности НАЖБП в ДФО по сравнению с общей популяцией исследованных пациентов в рамках DIREG 2. При общероссийском уровне распространенности данной патологии в 37,3% в популяции ДФО распространенность составила 21,4%. При сопоставимом ранговом распределении долей сопутствующих патологий пациентов в ДФО и общей популяции пациентов, принимавших участие в исследовании DIREG 2, достоверно чаще в популяции ДФО встречался метаболический синдром, климактерический синдром у женщин и гипертриглицеридемия.Заключение. Несмотря на меньший уровень распространенности НАЖБП на территории ДФО в сравнении с общей популяцией пациентов, принимавших участие в исследовании DIREG 2, выявлена достоверно более высокая распространенность ассоциированных с развитием НАЖБП патологий. Это требует разработки комплекса мер, который не позволит реализовать патогенный потенциал данных факторов риска

Rheumatoid Arthritis is an Autoimmune Disease Triggered by Proteus Urinary Tract Infection

Rheumatoid arthritis (RA) is a chronic and disabling polyarthritic disease, which affects mainly women in middle and old age

АНТИОКСИДАНТНЫЕ ХАРАКТЕРИСТИКИ ЗЕЛЕННЫХ И ПРЯНО-АРОМАТИЧЕСКИХ КУЛЬТУР

The characteristics that are typical for all leaved crops were identified in the studied green and spiced-aromatic crops. Maximal amount of the total antioxidants per 1 g of raw material is accumulated in juvenile leaves, flowers, and inflorescences. Total antioxidant content is decreased in old leaves of plants.В изученных зеленных и пряно вкусовых растениях обнаружены особенности, характерные для всех листовых культур: максимальное количество суммы антиоксидантов в расчете на 1 г сырой массы накапливается в ювенильных листьях, а также в цветках и соцветиях. В стареющих листьях наблюдается снижение содержания антиоксидантов