Snake venom phospholipase A2s exhibit strong virucidal activity against SARS-CoV-2 and inhibit the viral spike glycoprotein interaction with ACE2.

The COVID-19 pandemic caused by SARS-CoV-2 requires new treatments both to alleviate the symptoms and to prevent the spread of this disease. Previous studies demonstrated good antiviral and virucidal activity of phospholipase A2s (PLA2s) from snake venoms against viruses from different families but there was no data for coronaviruses. Here we show that PLA2s from snake venoms protect Vero E6 cells against SARS-CoV-2 cytopathic effects. PLA2s showed low cytotoxicity to Vero E6 cells with some activity at micromolar concentrations, but strong antiviral activity at nanomolar concentrations. Dimeric PLA2 from the viper Vipera nikolskii and its subunits manifested especially potent virucidal effects, which were related to their phospholipolytic activity, and inhibited cell-cell fusion mediated by the SARS-CoV-2 spike glycoprotein. Moreover, PLA2s interfered with binding both of an antibody against ACE2 and of the receptor-binding domain of the glycoprotein S to 293T/ACE2 cells. This is the first demonstration of a detrimental effect of PLA2s on β-coronaviruses. Thus, snake PLA2s are promising for the development of antiviral drugs that target the viral envelope, and could also prove to be useful tools to study the interaction of viruses with host cells

A study of CP violation in B-+/- -> DK +/- and B-+/- -> D pi(+/-) decays with D -> (KSK +/-)-K-0 pi(-/+) final states

A first study of CP violation in the decay modes $B^\pm\to [K^0_{\rm S} K^\pm \pi^\mp]_D h^\pm$ and $B^\pm\to [K^0_{\rm S} K^\mp \pi^\pm]_D h^\pm$, where $h$ labels a $K$ or $\pi$ meson and $D$ labels a $D^0$ or $\overline{D}^0$ meson, is performed. The analysis uses the LHCb data set collected in $pp$ collisions, corresponding to an integrated luminosity of 3 fb$^{-1}$. The analysis is sensitive to the CP-violating CKM phase $\gamma$ through seven observables: one charge asymmetry in each of the four modes and three ratios of the charge-integrated yields. The results are consistent with measurements of $\gamma$ using other decay modes

Measurement of Upsilon production in collisions at root s=2.76 TeV

The production of $\Upsilon(1S)$, $\Upsilon(2S)$ and $\Upsilon(3S)$ mesons decaying into the dimuon final state is studied with the LHCb detector using a data sample corresponding to an integrated luminosity of 3.3 $pb^{-1}$ collected in proton-proton collisions at a centre-of-mass energy of $\sqrt{s}=2.76$ TeV. The differential production cross-sections times dimuon branching fractions are measured as functions of the $\Upsilon$ transverse momentum and rapidity, over the ranges $p_{\rm T} Upsilon(1S) X) x B(Upsilon(1S) -> mu+mu-) = 1.111 +/- 0.043 +/- 0.044 nb, sigma(pp -> Upsilon(2S) X) x B(Upsilon(2S) -> mu+mu-) = 0.264 +/- 0.023 +/- 0.011 nb, sigma(pp -> Upsilon(3S) X) x B(Upsilon(3S) -> mu+mu-) = 0.159 +/- 0.020 +/- 0.007 nb, where the first uncertainty is statistical and the second systematic

Study of forward Z + jet production in pp collisions at √s=7 TeV

A measurement of the $Z(\rightarrow\mu^+\mu^-)$+jet production cross-section in $pp$ collisions at a centre-of-mass energy $\sqrt{s} = 7$ TeV is presented. The analysis is based on an integrated luminosity of $1.0\,\text{fb}^{-1}$ recorded by the LHCb experiment. Results are shown with two jet transverse momentum thresholds, 10 and 20 GeV, for both the overall cross-section within the fiducial volume, and for six differential cross-section measurements. The fiducial volume requires that both the jet and the muons from the Z boson decay are produced in the forward direction ($2.0<\eta<4.5$). The results show good agreement with theoretical predictions at the second-order expansion in the coupling of the strong interaction.A measurement of the $Z(\rightarrow\mu^+\mu^-)$+jet production cross-section in $pp$ collisions at a centre-of-mass energy $\sqrt{s} = 7$ TeV is presented. The analysis is based on an integrated luminosity of $1.0\,\text{fb}^{-1}$ recorded by the LHCb experiment. Results are shown with two jet transverse momentum thresholds, 10 and 20 GeV, for both the overall cross-section within the fiducial volume, and for six differential cross-section measurements. The fiducial volume requires that both the jet and the muons from the Z boson decay are produced in the forward direction ($2.0<\eta<4.5$). The results show good agreement with theoretical predictions at the second-order expansion in the coupling of the strong interaction

Selective Destruction of Soluble Polyurethaneimide as Novel Approach for Fabrication of Insoluble Polyimide Films

Polymeric coatings and membranes with extended stability toward a wide range of organic solvents are practical for application in harsh environments; on the other hand, such stability makes their processing quite difficult. In this work, we propose a novel method for the fabrication of films based on non-soluble polymers. The film is made from the solution of block copolymer containing both soluble and insoluble blocks followed by selective decomposition of soluble blocks. To prove this concept, we synthesized copolymer [(imide)n-(polyurethane)]m, in which the imide blocks were combined with polyurethane blocks based on polycaprolactone. By selective hydrolysis of urethane blocks in the presence of acid, it was possible to obtain the insoluble polyimide film for the first time. It was shown that the combination of thermal and acid treatment allowed almost complete removal of urethane blocks from the initial copolymer chains. IR spectroscopy, TGA, DSC and DMA methods were used to study the evaluation of the structure and properties of polymeric material as a result of thermal oxidation and hydrolysis by acid. It was shown that the polymeric films obtained by controlled decomposition were not soluble in aprotic solvent, such as dimethylformamide, n-methylpyrrolidone and dimethyl sulfoxide, and showed very close similarity to the homopolymer consisting of the same imide monomer, poly-(4,4′oxydiphenylene)pyromellitimide, confirming the feasibility of the proposed concept and its perspectives for fabrication of organic solvent-resistant membranes

Ефективність підготовки студентів на заняттях фізичними вправами в вузах різних відомств

Purpose. To make a comparative analysis and evaluate the effectiveness of physical exercises in a technical university and departmental university of the Ministry of Internal Affairs of Russia. Material and methods. The study involved male students (1 functional group of health) of the Irkutsk National Research Technical University (Russia, n = 1380) and cadets of the East Siberian Institute of the Ministry of Internal Affairs of Russia (Russia, n = 762). Cadets studied at 1, 2 and 3 courses. The characteristics of physical preparation and the functional condition of students and cadets were analyzed. Results. During the training period, most indicators of cadets' physical preparation significantly exceed their values ​​in students. This is due to the preliminary selection of candidates for training in educational institutions of the Ministry of Internal Affairs of Russia. It is also associated with a expressed training orientation of the process of physical preparation. The dynamics of the values of the indicators of the functional condition of the body of cadets is characterized by a high price of adaptation to physical activity. This can lead to the occurrence of pre-pathological conditions and pathological processes of the cardiovascular system. Conclusions. The dynamics of the values of indicators of physical preparation of students and cadets cannot be the only objective criterion for the effectiveness of the system of their physical education. For its full assessment, it is necessary to analyze the parameters of the functional condition of the body, characterizing the reaction to physical activity. Cadets have a great adaptation to physical activity. In this case, it cannot be concluded that the physical training of cadets is more effective.Цель. Дать сравнительную характеристику и провести оценку эффективности занятий физическими упражнениями в техническом вузе и ведомственном вузе системы МВД России. Материал и методы. В исследовании приняли участие студенты мужского пола (1 функциональная группа здоровья) Иркутского национального исследовательского технического университета (Россия, n=1380) и курсанты Восточно-Сибирского института МВД России (Россия, n=762). Курсанты учились на 1, 2 и 3 курсе. Анализировались характеристики физической подготовленности и функционального состояния студентов и курсантов. Результаты. В течение периода обучения большинство показателей физической подготовленности курсантов, значительно превышают их величины у студентов. Это связано с проведением предварительного отбора кандидатов для обучения в образовательных организациях системы МВД России. Также связано с выраженной тренировочной направленностью процесса физической подготовки. Динамика значений показателей функционального состояния организма курсантов характеризуется высокой ценой адаптации к физическим нагрузкам. Это может привести к возникновению предпатологических состояний и патологических процессов сердечно-сосудистой системы. Выводы. Динамика значений показателей физической подготовленности студентов и курсантов не может выступать единственным объективным критерием эффективности системы их физического воспитания. Для ее полноценной оценки необходим анализ параметров функционального состояния организма, характеризующих реакцию на физические нагрузки. Курсанты имеют большую адаптацию к физическим нагрузкам. В данном случае нельзя сделать вывод о большей эффективности занятий по физической подготовке курсантов.Мета. Дати порівняльну характеристику і провести оцінку ефективності занять фізичними вправами в технічному вузі і відомчому виші системи МВС Росії. Матеріал і методи. У дослідженні взяли участь студенти чоловічої статі (1 функціональна група здоров'я) Іркутського національного дослідницького технічного університету (Росія, n = 1380) і курсанти Східно-Сибірського інституту МВС Росії (Росія, n = 762). Курсанти вчилися на 1, 2 і 3 курсі. Аналізувалися характеристики фізичної підготовленості та функціонального стану студентів і курсантів. Результати. Протягом періоду навчання більшість показників фізичної підготовленості курсантів, значно перевищують їх величини у студентів. Це пов'язано з проведенням попереднього відбору кандидатів для навчання в освітніх організаціях системи МВС Росії. Також пов'язано з вираженою тренувальної спрямованістю процесу фізичної підготовки. Динаміка значень показників функціонального стану організму курсантів характеризується високою ціною адаптації до фізичних навантажень. Це може привести до виникнення передпатологічних станів і патологічних процесів серцево-судинної системи. Висновки. Динаміка значень показників фізичної підготовленості студентів і курсантів не може виступати єдиним об'єктивним критерієм ефективності системи їх фізичного виховання. Для її повноцінної оцінки необхідний аналіз параметрів функціонального стану організму, що характеризують реакцію на фізичні навантаження. Курсанти мають велику адаптацію до фізичних навантажень. В даному випадку не можна зробити висновок про більшу ефективність занять з фізичної підготовки курсантів

<i>ALDH3A2</i>, <i>ODF2</i>, <i>QSOX2</i>, and MicroRNA-503-5p Expression to Forecast Recurrence in <i>TMPRSS2-ERG</i>-Positive Prostate Cancer

Following radical surgery, patients may suffer a relapse. It is important to identify such patients so that therapy tactics can be modified appropriately. Existing stratification schemes do not display the probability of recurrence with enough precision since locally advanced prostate cancer (PCa) is classified as high-risk but is not ranked in greater detail. Between 40 and 50% of PCa cases belong to the TMPRSS2-ERG subtype that is a sufficiently homogeneous group for high-precision prognostic marker search to be possible. This study includes two independent cohorts and is based on high throughput sequencing and qPCR data. As a result, we have been able to suggest a perspective-trained model involving a deep neural network based on both qPCR data for mRNA and miRNA and clinicopathological criteria that can be used for recurrence risk forecasts in patients with TMPRSS2-ERG-positive, locally advanced PCa (the model uses ALDH3A2 + ODF2 + QSOX2 + hsa-miR-503-5p + ISUP + pT, with an AUC = 0.944). In addition to the prognostic model’s use of identified differentially expressed genes and miRNAs, miRNA–target pairs were found that correlate with the prognosis and can be presented as an interactome network

Peptides from the Sea Anemone <i>Metridium senile</i> with Modified Inhibitor Cystine Knot (ICK) Fold Inhibit Nicotinic Acetylcholine Receptors

Nicotinic acetylcholine receptors (nAChRs) play an important role in the functioning of the central and peripheral nervous systems, and other organs of living creatures. There are several subtypes of nAChRs, and almost all of them are considered as pharmacological targets in different pathological states. The crude venom of the sea anemone Metridium senile showed the ability to interact with nAChRs. Four novel peptides (Ms11a-1–Ms11a-4) with nAChR binding activity were isolated. These peptides stabilized by three disulfide bridges have no noticeable homology with any known peptides. Ms11a-1–Ms11a-4 showed different binding activity towards the muscle-type nAChR from the Torpedo californica ray. The study of functional activity and selectivity for the most potent peptide (Ms11a-3) revealed the highest antagonism towards the heterologous rat α9α10 nAChR compared to the muscle and α7 receptors. Structural NMR analysis of two toxins (Ms11a-2 and Ms11a-3) showed that they belong to a new variant of the inhibitor cystine knot (ICK) fold but have a prolonged loop between the fifth and sixth cysteine residues. Peptides Ms11a-1–Ms11a-4 could represent new pharmacological tools since they have structures different from other known nAChRs inhibitors

The Effect of Meclofenoxate on the Transcriptome of Aging Brain of Nothobranchius guentheri Annual Killifish

Annual fish of the genus Nothobranchius are promising models for aging research. Nothobranchius reproduces typical aspects of vertebrate aging, including hallmarks of brain aging. Meclofenoxate (MF) is a well-known compound that can enhance cognitive performance. The drug is prescribed for asthenic conditions, trauma, and vascular diseases of the brain. It is believed that MF is able to delay age-dependent changes in the human brain. However, until now, there has been no study of the MF effect on the brain transcriptome. In the present work, we performed an RNA-Seq study of brain tissues from aged Nothobranchius guentheri, which were almost lifetime administered with MF, as well as young and aged control fish. As expected, in response to MF, we revealed significant overexpression of neuron-specific genes including genes involved in synaptic activity and plasticity, neurotransmitter secretion, and neuron projection. The effect was more pronounced in female fish. In this aspect, MF alleviated age-dependent decreased expression of genes involved in neuronal activity. In both treated and untreated animals, we observed strong aging-associated overexpression of immune and inflammatory response genes. MF treatment did not prevent this effect, and moreover, some of these genes tended to be slightly upregulated under MF treatment. Additionally, we noticed upregulation of some genes associated with aging and cellular senescence, including isoforms of putative vascular cell adhesion molecule 1 (VCAM1), protein O-GlcNAcase (OGA), protein kinase C alpha type (KPCA), prolow-density lipoprotein receptor-related protein 1 (LRP1). Noteworthy, MF treatment was also associated with the elevated transcription of transposons, which are highly abundant in the N. guentheri genome. In conclusion, MF compensates for the age-dependent downregulation of neuronal activity genes, but its effect on aging brain transcriptome still cannot be considered unambiguously positive