ABSTRACT
Abstract Tiliroside is a glycosidic flavonoid present in many plants species including Helicteres velutina K. Schum (Malvaceae sensu lato), commonly known in Brazil as "pitó". This molecule has been shown to have many biological activities, however no study has been carried out to investigate the toxicity of this substance. The present work aimed to evaluate the possible cellular toxicity in silico, in vitro and ex-vivo of the kaempferol-3-O-β-D-(6"-E-p-coumaroyl) glucopyranoside (tiliroside), through chemical structure analysis, toxicity assessment and predictive bioactive properties, using human samples for in vitro and ex-vivo tests. The in silico analysis suggests that tiliroside exhibited great absorption index when penetrating biological membranes. In addition, it also displayed considerable potential for cellular protection against free radicals, and anticarcinogenic, antioxidant, antineoplastic, anti-inflammatory, anti-hemorrhagic and antithrombotic activities. The assessment of the hemolytic and genotoxic effects of tiliroside showed low hemolysis rates in red blood cells and absence of cellular toxicity in the oral mucosa cells. The data obtained indicate that this molecule could be a promising therapeutic approach as a possible new drug with biotechnological potential.
Resumo O tilirosídeo é um flavonóide glicosídico presente em muitas espécies de plantas, incluindo Helicteres velutina K. Schum (Malvaceae sensu lato), conhecida no Brasil como "pitó". Esta molécula mostrou ter muitas atividades biológicas, porém nenhum estudo foi realizado para investigar a toxicidade dessa substância. O presente trabalho teve como objetivo avaliar a possível toxicidade celular in silico, in vitro e ex-vivo do kaempferol-3-O-β-D- (6 "-Ep-coumaroil) glucopiranosídeo (tilirosídeo), por meio de análises de estrutura química, toxicidade avaliação e propriedades bioativas preditivas, utilizando amostras humanas para testes in vitro e ex-vivo. A análise in silico sugere que o tilirosídeo exibe bom índice de absorção para penetrar nas membranas biológicas. Além disso, apresentou considerável potencial de proteção celular contra os radicais livres e com atividades anticarcinogênica, antioxidante, antineoplásica, antiinflamatória, anti-hemorrágica e antitrombótica. A avaliação dos efeitos hemolíticos e genotóxicos do tilirosídeo mostrou baixas taxas de hemólise nas hemácias e ausência de toxicidade em células da mucosa oral. Os dados obtidos indicam que esta molécula pode possuir uma abordagem terapêutica promissora como uma possível nova droga com potencial biotecnológico.
Subject(s)
Humans , Plant Extracts , Kaempferols/toxicity , Flavonoids , Computer Simulation , BrazilABSTRACT
Abstract Novel coronavirus (nCoV) namely "SARS-CoV-2" is being found responsible for current PANDEMIC commenced from Wuhan (China) since December 2019 and has been described with epidemiological linkage to China in about 221 countries and territories until now. In this study we have characterized the genetic lineage of SARS-CoV-2 and report the recombination within the genus and subgenus of coronaviruses. Phylogenetic relationship of thirty nine coronaviruses belonging to its four genera and five subgenera was analyzed by using the Neighbor-joining method using MEGA 6.0. Phylogenetic trees of full length genome, various proteins (spike, envelope, membrane and nucleocapsid) nucleotide sequences were constructed separately. Putative recombination was probed via RDP4. Our analysis describes that the "SARS-CoV-2" although shows great similarity to Bat-SARS-CoVs sequences through whole genome (giving sequence similarity 89%), exhibits conflicting grouping with the Bat-SARS-like coronavirus sequences (MG772933 and MG772934). Furthermore, seven recombination events were observed in SARS-CoV-2 (NC_045512) by RDP4. But not a single recombination event fulfills the high level of certainty. Recombination mostly housed in spike protein genes than rest of the genome indicating breakpoint cluster arises beyond the 95% and 99% breakpoint density intervals. Genetic similarity levels observed among "SARS-CoV-2" and Bat-SARS-CoVs advocated that the latter did not exhibit the specific variant that cause outbreak in humans, proposing a suggestion that "SARS-CoV-2" has originated possibly from bats. These genomic features and their probable association with virus characteristics along with virulence in humans require further consideration.
Resumo O novo coronavírus (nCoV), nomeadamente "SARS-CoV-2", foi considerado responsável pela pandemia atual iniciada em Wuhan (China) desde dezembro de 2019 e foi descrito com ligação epidemiológica à China em cerca de 221 países e territórios até agora. Neste estudo, caracterizamos a linhagem genética do SARS-CoV-2 e relatamos a recombinação dentro do gênero e subgênero dos coronavírus. A relação filogenética de 39 coronavírus pertencentes a seus quatro gêneros e cinco subgêneros foi analisada usando o método de Neighbour-joining usando MEGA 6.0. Árvores filogenéticas do genoma de comprimento total, várias proteínas (espícula, envelope, membrana e nucleocapsídeo), sequências de nucleotídeos foram construídas separadamente. A recombinação putativa foi testada via RDP4. Nossa análise descreve que o "SARS-CoV-2", embora mostre grande semelhança com as sequências de Bat-SARS-CoVs em todo o genoma (dando semelhança de sequência de 89%), exibe agrupamento conflitante com as sequências de coronavírus do tipo Bat-SARS (MG772933 e MG772934) Além disso, sete eventos de recombinação foram observados em SARS-CoV-2 (NC045512) por RDP4. Mas nem um único evento de recombinação preenche o alto nível de certeza. A recombinação está alojada mais em genes de proteína de pico, principalmente, do que no resto do genoma, indicando que o cluster de ponto de interrupção surge além dos intervalos de densidade de ponto de interrupção de 95% e 99%. Os níveis de similaridade genética observados entre "SARS-CoV-2" e Bat-SARS-CoVs defendem que o último não exibe a variante específica que causa surto em humanos, sugerindo que "SARS-CoV-2" tenha se originado possivelmente de morcegos. Essas características genômicas e sua provável associação com as características do vírus, juntamente com a virulência em humanos, requerem uma consideração mais aprofundada.
Subject(s)
Humans , Animals , Chiroptera , COVID-19 , Phylogeny , Computer Simulation , Genome, Viral/genetics , SARS-CoV-2ABSTRACT
:The reaction of plants to ultra-high dilute substances (UHD) is well known, however, the signaling of the immediate effect still doesn't have a widely accepted methodology. The objective of this experiment was to use non-destructive sampling to find signs of UHD soon after application to plants. Methods:The control consisted of untreated purslane [Pilea microphylla (L.) Liebm] plants and imaged with a digital cameraMobius (CMOS 1270x720 pixels) directed at a laser beam (±680 nm) emitted over the plant canopy for 220 seconds, with 6-second intervals. Then, the same plants were treated with Fluoricum acidum30CH (Fl. ac.30),and ten minutes later, new images of the leaves were taken to verify the possible existence of reaction patterns of the plants generated by Biospeckle Laser (1,2). Results:Several types of imaging were performed to choose the image pattern, and the NIR type was chosen, generated by the Mobius camera connected directly to a laptop (Figure 1). The images were treated using the THSP algorithm, which generated data to compare the variation of pixel intensity with and without the presence of UHD. Conclusion:Research has shown that "Fl. ac. 30" is identified in purslane plants soon after application and this sign persists for at least 180 minutesafter application, with a significant difference from the control at the 1% probability level.
Subject(s)
Computer Simulation , Dynamic Disease in HomeopathyABSTRACT
Objetivo: Determinar los momentos de fuerza del haz superficial del masetero (SMH) obtenidos por modelos lineal y vectorial. Métodos: Investigación comparati-va in silico. Se obtuvo la fuerza del SMH con dinamó-metro en 12 pacientes varones adultos jóvenes para calcular el momento de la fuerza y trabajo mecánico a través de simulaciones en JAVA+ con NetBeans8.2. La descomposición de la fuerza fue F.cos α(x,y) y F.cos α(x,y,z) en el modelo lineal y vectorial respectivamen-te. Los momentos de fuerza fueron comparados por ANOVA (p<0,05). Resultados: La fuerza del SMH unila-teral obtenida con dinamómetro (2,5±0,1N) no difirió significativamente del modelo lineal (2,6±0,05N), pero difirió (p<0,001) del vectorial: 1,7, 2,2, 4,2N en x,y,z (general 2,7±0,02N). El momento medio de la fuerza en el modelo vectorial fue -17,9, -15,5, +14,3N.m-2, apuntando a la inclinación mandibular en el eje lateral en dirección caudal anterior, movimiento de inclina-ción en el eje lateral en la dirección cráneo-medial, e inclinación en el eje craneal en la dirección lateral-an-terior. El modelo lineal mostró momento de fuerza de 13,5N.m-2 apuntando un movimiento traslacional en dirección caudal-craneal en el eje anterior-posterior y menor trabajo mecánico del SMH (p=0,012). Con-clusión: Los modelos vectoriales son más eficientes proporcionando datos detallados para estimar los momentos de fuerza y el trabajo mecánico del SMH, y deben incluirse en los algoritmos de cálculo utilizados por dinamómetros (AU)
Objective: to determine the moments of force exerted by the superficial masseter head (SMH) obtained through linear models and vector ones. Methods: comparative in silico research. Data of SMH force obtained with dynamometer in 12 young adult male patients was used to calculate the moment of the force and mechanical work through simulations in JAVA+ performed with NetBeans8.2. Force decomposition was F.cos α(x,y) and F.cos α(x,y,z) in the linear and vector model respectively. The moments of force were compared by ANOVA (p<0.05). Results: Dynamometrical unilateral SMH force (2.5±0.1N) did not differ significantly from the linear model (2.6±0.05N), but differed (p<0.001) from the vector model: 1.7, 2.2, 4.2N on x,y,z (overall 2.7±0.02N). The mean moment of the force in the vector model was -17.9, -15.5, +14.3N.m-2, pointing to mandible's inclination on the lateral axis in anterior-caudal direction, inclination movement on the lateral axis in the cranio-medial direction and inclination on the cranial axis in the lateral-anterior direction. The linear model showed a moment of force of 13.5N.m-2 pointing to translational motion on caudal-cranial direction on the anterior-posterior axis and lower SMH mechanical work (p=0,012). Conclusion: Vector models are more efficient to provide detailed data to estimate the moments of force and mechanical work of SMH and should be included in the calculation algorithms used by dynamometers (AU)
Subject(s)
Humans , Male , Adult , Biomechanical Phenomena/physiology , Linear Models , Mandible/physiology , Masseter Muscle/physiology , Temporomandibular Joint/physiology , Computer Simulation , Stomatognathic System/physiology , Analysis of VarianceABSTRACT
Abstract Objective: to evaluate the facilitators, barriers and perceptions of Nursing students in learning about home visiting and child care through Telesimulation during the COVID-19 pandemic. Method: a qualitative study to evaluate Telesimulation via computers, grounded on Kolb's theoretical model. A semi-structured questionnaire and the Student Satisfaction and Self-Confidence in Learning Scale were applied, with descriptive analysis and qualitative thematic analysis on the perceptions of 41 Nursing students. Results: the contextualized Telesimulation provided learning opportunities in dimensions of the pedagogical strategy, telesimulated scenario, communication and specificities of child care in home visits. It was considered a safe and dynamic activity that helped knowledge consolidation and reflective attitudes, proximity to reality, and develop interaction, observation and types of approaches. There were restrictions due to Internet connection failures. A large percentage of the students indicated good satisfaction and self-confidence level with learning in the scale applied. Conclusion: the real clinical situation with remote immersion allowed observation, decision-making, reflection and elaboration of conclusions, inherent to the experiential learning cycle. The set of elements of this Telesimulation created an environment that stimulated the interest of Nursing students for other learning stages, suggesting a space that strengthens knowledge and maintains dialogue with face-to-face practices.
Resumo Objetivo: avaliar as facilidades, barreiras e percepções de estudantes de enfermagem na aprendizagem sobre visita domiciliar e cuidado infantil por telessimulação na pandemia da COVID-19. Método: estudo qualitativo avaliativo de telessimulação por computador, fundamentado no modelo teórico de Kolb. Foram aplicados um questionário semiestruturado e a Escala de Satisfação de Estudantes e Autoconfiança na Aprendizagem, com análise descritiva e análise qualitativa temática sobre percepções de 41 graduandos de enfermagem. Resultados: a telessimulação contextualizada proporcionou oportunidades de aprendizagem em dimensões da estratégia pedagógica, cenário telessimulado, comunicação e especificidades do cuidado infantil em visita domiciliar. Atividade segura e dinâmica, auxiliou a solidificar conhecimentos e atitudes reflexivas, aproximação à realidade, desenvolvimento da interação, observação e tipos de abordagens. Houve restrições por falhas de conexão. Grande parte dos estudantes indicou níveis bons de satisfação e autoconfiança com a aprendizagem na escala aplicada. Conclusão: a situação clínica real com imersão remota permitiu observação, tomada de decisão, reflexão e elaboração de conclusões inerentes ao ciclo de aprendizagem experiencial. O conjunto de elementos desta telessimulação criou um ambiente que estimulou o interesse dos estudantes de enfermagem para outras etapas de aprendizagem, sugerindo um espaço que fortalece conhecimentos e que guarda interlocução com as práticas presenciais.
Resumen Objetivo: evaluar las facilidades, barreras y percepciones de estudiantes de enfermería en el aprendizaje sobre visita domiciliaria y cuidado infantil por telesimulación en la pandemia de COVID-19. Método: estudio cualitativo que evalúa la telesimulación por computadora, basado en el modelo teórico de Kolb. Se aplicó un cuestionario semiestructurado y la Escala de Satisfacción de los Estudiantes y Autoconfianza en el Aprendizaje, con análisis descriptivo y análisis temático cualitativo sobre las percepciones de 41 estudiantes de enfermería. Resultados: la telesimulación contextualizada brindó oportunidades de aprendizaje en los aspectos estrategia pedagógica, escenario telesimulado, comunicación y especificidades del cuidado infantil en visitas domiciliarias. Es una actividad segura y dinámica, que contribuyó a consolidar conocimientos y actitudes reflexivas, permitió un acercamiento a la realidad, el desarrollo de la interacción, observación y tipos de acercamientos. Hubo restricciones por fallas en la conexión. La mayoría de los estudiantes indicaron buenos niveles de satisfacción y confianza en sí mismos con el aprendizaje en la escala aplicada. Conclusión: la situación clínica real con participación a distancia permitió la observación, toma de decisiones, reflexión y elaboración de conclusiones inherentes al ciclo de aprendizaje experiencial. El conjunto de elementos de esta telesimulación creó un ambiente que estimuló el interés de los estudiantes de enfermería por otras etapas de aprendizaje, por lo que se considera un espacio que fortalece el conocimiento y dialoga con las prácticas presenciales.
Subject(s)
Humans , Students, Nursing , Computer Simulation , Child Care , Education, Nursing , COVID-19 , House CallsABSTRACT
To explore the influence of bionic texture coronary stents on hemodynamics, a type of bioabsorbable polylactic acid coronary stents was designed, for which a finite element analysis method was used to carry out simulation analysis on blood flow field after the implantation of bionic texture stents with three different shapes (rectangle, triangle and trapezoid), thus revealing the influence of groove shape and size on hemodynamics, and identifying the optimal solution of bionic texture groove. The results showed that the influence of bionic texture grooves of different shapes and sizes on the lower wall shear stress region had a certain regularity. Specifically, the improvement effect of grooves above 0.06 mm on blood flow characteristics was poor, and the effect of grooves below 0.06 mm was good. Furthermore, the smaller the size is, the better the improvement effect is, and the 0.02 mm triangular groove had the best improvement effect. Based on the results of this study, it is expected that bionic texture stents have provided a new method for reducing in-stent restenosis.
Subject(s)
Bionics , Computer Simulation , Coronary Vessels , Hemodynamics/physiology , Models, Cardiovascular , Stents , Stress, MechanicalABSTRACT
The finite element method is a new method to study the mechanism of brain injury caused by blunt instruments. But it is not easy to be applied because of its technology barrier of time-consuming and strong professionalism. In this study, a rapid and quantitative evaluation method was investigated to analyze the craniocerebral injury induced by blunt sticks based on convolutional neural network and finite element method. The velocity curve of stick struck and the maximum principal strain of brain tissue (cerebrum, corpus callosum, cerebellum and brainstem) from the finite element simulation were used as the input and output parameters of the convolutional neural network The convolutional neural network was trained and optimized by using the 10-fold cross-validation method. The Mean Absolute Error (MAE), Mean Square Error (MSE), and Goodness of Fit ( R 2) of the finally selected convolutional neural network model for the prediction of the maximum principal strain of the cerebrum were 0.084, 0.014, and 0.92, respectively. The predicted results of the maximum principal strain of the corpus callosum were 0.062, 0.007, 0.90, respectively. The predicted results of the maximum principal strain of the cerebellum and brainstem were 0.075, 0.011, and 0.94, respectively. These results show that the research and development of the deep convolutional neural network can quickly and accurately assess the local brain injury caused by the sticks blow, and have important application value for understanding the quantitative evaluation and the brain injury caused by the sticks struck. At the same time, this technology improves the computational efficiency and can provide a basis reference for transforming the current acceleration-based brain injury research into a focus on local brain injury research.
Subject(s)
Brain , Brain Injuries , Computer Simulation , Finite Element Analysis , Humans , Neural Networks, ComputerABSTRACT
An auxiliary dining robot is designed in this paper, which implements the humanoid feeding function with theory of inventive problem solving (TRIZ) theory and aims at the demand of special auxiliary nursing equipment. Firstly, this robot simulated the motion function of human arm by using the tandem joints of the manipulator. The end-effector used a motor-driven spoon to simulate the feeding actions of human hand. Meanwhile, the eye in hand installation style was adopted to instead the human vision to realize its automatic feeding action. Moreover, the feeding and drinking actions of the dining robot were considered comprehensively with the flexibility of spatial movement under the lowest degree of freedom (DOF) configuration. The structure of the dining robot was confirmed by analyzing its stresses and discussing the specific application scenarios under this condition. Finally, the simulation results demonstrate high-flexibility of the dining robot in the workspace with lowest DOF configuration.
Subject(s)
Computer Simulation , Equipment Design , Hand , Humans , Movement , Robotics/methodsABSTRACT
Background Eugenol shows both antibacterial and antiparasitic activities, suggesting that it might be evaluated as an option for the treatment of praziquantel-resistant schistosome. Methods The in vitro activities of three eugenol derivatives (FB1, FB4 and FB9) on adult worms from Schistosoma mansoni were examined by fluorescence and scanning electron microscopy to analyze effects on the excretory system and integument damage, respectively. Biochemical tests with verapamil (a calcium channel antagonist) and ouabain (a Na+/K+-ATPase pump inhibitor) were used to characterize eugenol derivative interactions with calcium channels and the Na+/K+-ATPase, while in silico analysis identified potential Na+/K+-ATPase binding sites. Results The compounds showed effective doses (ED50) of 0.324 mM (FB1), 0.167 mM (FB4), and 0.340 mM (FB9). In addition, FB4 (0.322 mM), which showed the lowest ED50, ED90 and ED100 (p < 0.05), caused the most damage to the excretory system and integument, according to both fluorescence and scanning electron microscopy analysis. The death of adult worms was delayed by ouabain treatment plus FB1 (192 versus 72 hours) and FB9 (192 versus 168 hours), but the response to FB4 was the same in the presence or absence of ouabain. Besides, no changes were noted when all of the eugenol derivatives were combined with verapamil. Moreover, FB1 and FB9 inhibited Na+/K+-ATPase activity according to in silico analysis but FB4 did not show a time-dependent relationship and may act on targets other than the parasite Na+/K+-ATPase. Conclusion Eugenol derivatives, mainly FB4 when compared to FB1 and FB9, seem to act more effectively on the integument of adult S. mansoni worms.(AU)
Subject(s)
Schistosoma/drug effects , Schistosomiasis/drug therapy , Schistosomicides/analysis , In Vitro Techniques , Computer Simulation , Eugenol/analogs & derivatives , Neglected Diseases/drug therapyABSTRACT
Computational medicine is an emerging discipline that uses computer models and complex software to simulate the development and treatment of diseases. Advances in computer hardware and software technology, especially the development of algorithms and graphics processing units (GPUs), have led to the broader application of computers in the medical field. Computer vision based on mathematical biological modelling will revolutionize clinical research and diagnosis, and promote the innovative development of Chinese medicine, some biological models have begun to play a practical role in various types of research. This paper introduces the concepts and characteristics of computational medicine and then reviews the developmental history of the field, including Digital Human in Chinese medicine. Additionally, this study introduces research progress in computational medicine around the world, lists some specific clinical applications of computational medicine, discusses the key problems and limitations of the research and the development and application of computational medicine, and ultimately looks forward to the developmental prospects, especially in the field of computational Chinese medicine.
Subject(s)
Algorithms , Computer Simulation , HumansABSTRACT
OBJECTIVE@#In daily life, the movement of the neck will cause certain deformation of the blood vessel and the stent. This study explores the quantitative influence of the torsion deformation of the blood vessel on the mechanical properties of the stent.@*METHODS@#In the finite element simulation software Abaqus, the numerical simulation of the crimping and releasing process of the stent, the numerical simulation of the torsion process of the blood vessel with the stent, and the numerical simulation of the pressure loading process of the outer wall of the blood vessel were carried out.@*RESULTS@#After the stent was implanted, when a load was applied to the outer surface of the blood vessel wall, when the applied load did not change, as the torsion angle increased, the smallest cross-sectional area in the blood vessel decreased.@*CONCLUSIONS@#After the stent is placed, when the external load is fixed, the radial support capacity of the stent will decrease as the torsion angle increases.
Subject(s)
Computer Simulation , Finite Element Analysis , Humans , Stents , Stress, MechanicalABSTRACT
Indirect energy metabolism measurement is the gold standard for providing nutritional support for critical illness. The accuracy of the measurement data directly affects the outcome of the disease. In order to study the influence of sampling delay on the accuracy of energy metabolism measurement under mechanical ventilation, the Matlab/Simulink platform and respiratory electrical model were used for simulation and quantitative analysis. The results show that the error of indirect energy metabolism measurement increases with the increase of sampling delay, the error of sampling delay in mechanical ventilation mode is larger than that of spontaneous breathing, and the error of sampling delay in PCV mode of mechanical ventilation is larger than that in VCV mode. Therefore, there should be different sampling delay compensation strategies under severe mechanical ventilation and its different control modes.
Subject(s)
Computer Simulation , Critical Illness , Energy Metabolism , Humans , Respiration, ArtificialABSTRACT
The pulse amplitude of fingertip volume could be improved by selecting the vascular dense area and applying appropriate pressure above it. In view of this phenomenon, this paper used Comsol Multiphysics 5.6 (Comsol, Sweden), the finite element analysis software of multi-physical field coupling simulation, to establish the vascular tissue model of a single small artery in fingertips for simulation. Three dimensional Navier-Stokes equations were solved by finite element method, the velocity field and pressure distribution of blood were calculated, and the deformation of blood vessels and surrounding tissues was analyzed. Based on Lambert Beer's Law, the influence of the longitudinal compression displacement of the lateral light surface region and the tissue model on the light intensity signal is investigated. The results show that the light intensity signal amplitude could be increased and its peak value could be reduced by selecting the area with dense blood vessels. Applying deep pressure to the tissue increased the amplitude and peak of the signal. It is expected that the simulation results combined with the previous experimental experience could provide a feasible scheme for improving the quality of finger volume pulse signal.
Subject(s)
Computer Simulation , Fingers , Finite Element Analysis , Skin , SoftwareABSTRACT
OBJECTIVE@#To study the binding target of photosensitizer and bacteria in antimicrobial photodynamic therapy with computer-simulated target prediction and molecular docking research methods and to calculate the binding energy.@*METHODS@#The protein names of Porphyromonas gingivalis (Pg) were obtained and summarized in Uniprot database and RCSB PDB database; the structure diagrams of methy-lene blue were screened in SciFinder database, PubChem database, ChemSpider database, and Chemical Book, and ChemBioDraw software was used to draw and confirm the three-dimensional structure for target prediction and Cytoscape software was used to build a visual network diagram; a protein interaction network was searched and built between the methylene blue target and the common target of Pg in the String database; then we selected FimA, Mfa4, RgpB, and Kgp K1 proteins, used AutoDock software to calculate the docking energy of methylene blue and the above-mentioned proteins and performed molecular docking.@*RESULTS@#The target prediction results showed that there were 19 common targets between the 268 potential targets of methylene blue and 1 865 Pg proteins. The 19 targets were: groS, radA, rplA, dps, fabH, pyrG, thyA, panC, RHO, frdA, ileS, bioA, def, ddl, TPR, murA, lepB, cobT, and gyrB. The results of the molecular docking showed that methylene blue could bind to 9 sites of FimA protein, with a binding energy of -6.26 kcal/mol; with 4 sites of Mfa4 protein and hydrogen bond formation site GLU47, and the binding energy of -5.91 kcal/mol, the binding energy of LYS80, the hydrogen bond forming site of RgpB protein, was -5.14 kcal/mol, and the binding energy of 6 sites of Kgp K1 protein and the hydrogen bond forming site GLY1114 of -5.07 kcal/mol.@*CONCLUSION@#Computer simulation of target prediction and molecular docking technology can initially reveal the binding, degree of binding and binding sites of methylene blue and Pg proteins. This method provides a reference for future research on the screening of binding sites of photosensitizers to cells and bacteria.
Subject(s)
Computer Simulation , Methylene Blue , Molecular Docking Simulation , Photosensitizing Agents , Porphyromonas gingivalisABSTRACT
Objective: Using CFD technology to grasp the distribution and diffusion of hydrogen fluoride in an electrolytic fluorine plant, provide guidance and scientific basis for enterprises to carry out occupational health management in enterprises, install hazardous substance alarm devices, and protect workers' occupational health. Methods: In July 2019, the diffusion law of hydrogen fluoride gas produced in an electrolytic fluorine plant is selected as the research object. Through the establishment of models and grids, the Fluent numerical simulation method is finally used to simulate the diffusion and distribution of hydrogen fluoride gas under ventilation conditions. Results: The results showed that the average concentration of hydrogen fluoride was 0.045 mg/m(3) in the workplace, and the absorbed zone height (1.5 m) was 0.02 mg/m(3) in the inspection channel, which was in accordance with the national standard. However, there is eddy current above the electrolyzer near the inlet, may lead to the accumulation of hydrogen fluoride gas. Conclusion: The research of CFD numerical simulation method on the distribution and diffusion of hydrogen fluoride concentration in electrolytic fluorine plant can be applied to the prevention, control and management of occupational hazards in electrolytic fluorine plant.
Subject(s)
Computer Simulation , Fluorides , Humans , Hydrofluoric Acid , Occupational Exposure/prevention & control , Occupational HealthABSTRACT
Objective: To introduce and compare four analysis methods of multiple parallel mediation model, including pure regression method, method based on inverse probability weighting, extended natural effect model method and weight-based imputation strategies. Methods: For the multiple parallel mediation model, the simulation experiments of three scenarios were carried out to compare the performance of different methods in estimating direct and indirect effects in different situations. Dataset from UK Biobank was then analyzed by using the four methods. Results: The estimation biases of the regression method and the inverse probability weighting method were relatively small, followed by the extended natural effect model method, and the estimation results of the weight-based imputation strategies were quite different from the other three methods. Conclusions: Different multiple parallel mediation analysis methods have different application situations and their own advantages and disadvantages. The regression method is more suitable for continuous mediator, and the inverse probability weighting method is more suitable for binary mediator. The extended natural effect model method has better performances when the residuals of two parallel mediators are positively correlated and the correlation degree is small. The weight-based imputation strategies might not be appropriate for parallel mediation analysis. Therefore, appropriate methods should be selected according to the specific situation in practice.
Subject(s)
Bias , Computer Simulation , Humans , Mediation Analysis , Models, Statistical , Probability , Regression Analysis , Research DesignABSTRACT
Among kinds of methods for causal inference in observational studies, the propensity score (PS) method to control measured confounding is more widely used. PS method usually consists of two critical steps: first, estimating the propensity score, followed by calculating the causal parameters of interest by regression, weighting, matching, and stratification. Unlike the traditional dichotomous treatment, the generalized propensity scoring estimator used for continuous treatment has been proposed in recent years. Many methods have been developed to estimate the generalized propensity score or even estimate the balancing weight directly. This paper introduces the existing estimators from both the model-based and balance-based perspectives.
Subject(s)
Causality , Computer Simulation , Humans , Propensity Score , Research DesignABSTRACT
OBJECTIVE@#To propose a new method for mining complexes in dynamic protein network using spatiotemporal convolution neural network.@*METHODS@#The edge strength, node strength and edge existence probability are defined for modeling of the dynamic protein network. Based on the time series information and structure information on the graph, two convolution operators were designed using Hilbert-Huang transform, attention mechanism and residual connection technology to represent and learn the characteristics of the proteins in the network, and the dynamic protein network characteristic map was constructed. Finally, spectral clustering was used to identify the protein complexes.@*RESULTS@#The simulation results on several public biological datasets showed that the F value of the proposed algorithm exceeded 90% on DIP dataset and MIPS dataset. Compared with 4 other recognition algorithms (DPCMNE, GE-CFI, VGAE and NOCD), the proposed algorithm improved the recognition efficiency by 34.5%, 28.7%, 25.4% and 17.6%, respectively.@*CONCLUSION@#The application of deep learning technology can improve the efficiency in analysis of dynamic protein networks.
Subject(s)
Algorithms , Cluster Analysis , Computer Simulation , Neural Networks, Computer , Research DesignABSTRACT
Introdução: o sistema RANKL (receptor-ativador do fator nuclear-ligante κB)/RANK (receptor ativador do NF-kB)/OPG (osteoprotegrina) Introdução: o sistema OPG (osteoprotegrina)/RANK (receptor ativador do NF-kB)/RANKL (receptor-ativador do fator nuclear-ligante κB) regula os processos fisiológicos e patológicos da remodelação óssea. Polimorfismos genéticos nos genes OPG, RANK e RANKL têm sido associados a doenças, em diferentes populações. Objetivo: Descrever a frequência e o potencial regulatório dos polimorfismos do sistema OPG, RANK e RANKL em uma população brasileira; avaliar o seu potencial como marcadores genéticos informativos de ancestralidade; comparar com patologias associadas em outras populações. Metodologia: neste estudo, 506 indivíduos adultos, participantes de uma coorte acometidos de asma e periodontite, tiveram o DNA genômico extraído e genotipado, utilizando-se a plataforma Illumina. As plataformas NCBI, RegulomeDB, Haploview 4.2 e rSNPBase foram consultadas e utilizadas para análises. Resultados e Discussão: os polimorfismos mais frequentes na população estudada foram o rs3102724 no gene OPG, com frequência de menor alelo (MAF) de 46%; o rs4941129 em RANK, MAF 50%; e o rs9525641 em RANKL, MAF 46%. Os rs3134063 (1f) em OPG, rs17069898 (1f) em RANK e rs2200287 (1d) em RANKL apresentaram maior impacto funcional. Em OPG e RANK, nove polimorfismos se caracterizaram como marcadores genéticos informativos de ancestralidade, com predomínio nas populações YRI (africanos) e CEU (europeus). Os nove polimorfismos, com função intrônica, apresentaram MAF entre 2 a 46% na população-alvo e foram associados a patologias do metabolismo ósseo em outras populações. Conclusão: polimorfismos dos genes estudados se mostraram frequentes na população estudada e tiveram seus alelos mais frequentes associados a doenças em populações ancestrais. Sugere-se que sejam realizados mais estudos.
Introduction: The OPG (osteoprotegerin)/ RANK (NF-kB activating receptor)/ RANKL (nuclear-binding factor κB receptor-activating system regulates the physiological and pathological processes of bone remodeling. Genetic polymorphisms (SNPs) in OPG, RANK and RANKL genes have been associated with diseases in different populations. Objective: Describe the regulatory frequency and potential of SNPs in OPG, RANK and RANKL in a Brazilian population; assess their potential as informative genetic markers of ancestry; compare with pathologies associated with these polymorphisms in other populations. Methods: in this study, 506 adult individuals, participating in a cohort involving asthma and periodontitis, had genomic DNA extracted and genotyped using the Illumina platform. The NCBI, RegulomeDB, Haploview 4.2 and rSNPBase platforms were consulted and used for analysis. Results and discussion: the most frequent polymorphisms in the studied population were the rs3102724 in the OPG gene, with the lowest allele frequency (MAF) of 46%; rs4941129 in RANK, MAF 50% and rs9525641 in RANKL, MAF 46%. The rs3134063 (1f) in OPG, rs17069898 (1f) in RANK and rs2200287 (1d) in RANKL, had greater functional impact. In OPG and RANK, 9 SNPs were characterized as informative genetic markers of ancestry, predominantly in YRI (African) and CEU (European) populations. These 9 SNPs, with intronic function, presented MAF between 2 and 46% in our population, and were associated with pathologies in bone metabolism in other populations. Conclusion: SNPs of the studied genes were found to be frequent in the studied population and had their most frequent alleles associated with diseases in ancestral populations. It is suggested that further studies be carried out
Subject(s)
Humans , Male , Female , Adult , Polymorphism, Genetic , RANK Ligand , Genes , Periodontitis , Asthma , Computer SimulationABSTRACT
Abstract Objective Abnormalities in the eutopic endometrium of women with endometriosis may be related to disease-associated infertility. Although previous RNA-sequencing analysis did not show differential expression in endometrial transcripts of endometriosis patients, other molecular alterations could impact protein synthesis and endometrial receptivity. Our aim was to screen for functional mutations in the transcripts of eutopic endometria of infertile women with endometriosis and controls during the implantation window. Methods Data from RNA-Sequencing of endometrial biopsies collected during the implantation window from 17 patients (6 infertile women with endometriosis, 6 infertile controls, 5 fertile controls) were analyzed for variant discovery and identification of functional mutations. A targeted study of the alterations found was performed to understand the data into disease's context. Results None of the variants identified was common to other samples within the same group, and no mutation was repeated among patients with endometriosis, infertile and fertile controls. In the endometriosis group, nine predicted deleterious mutations were identified, but only one was previously associated to a clinical condition with no endometrial impact. When crossing the mutated genes with the descriptors endometriosis and/or endometrium, the gene CMKLR1 was associated either with inflammatory response in endometriosis or with endometrial processes for pregnancy establishment. Conclusion Despite no pattern of mutation having been found, we ponder the small sample size and the analysis on RNA-sequencing data. Considering the purpose of the study of screening and the importance of the CMKLR1 gene on endometrial
Resumo Objetivo Anormalidades no endométrio eutópico de mulheres com endometriose podem estar relacionadas à infertilidade associada à doença. Embora a análise prévia de sequenciamento de RNA não tenha evidenciado expressão diferencial em transcritos endometriais de pacientes com endometriose, outras alterações moleculares poderiam afetar a síntese de proteínas e a receptividade endometrial. Nosso objetivo foi rastrear mutações funcionais em transcritos de endométrios eutópicos de mulheres inférteis com endometriose e de controles durante a janela de implantação. Métodos Os dados do sequenciamento de RNA de biópsias endometriais coletados durante a janela de implantação de 17 pacientes (6 mulheres inférteis com endometriose, 6 controles inférteis, 5 controles férteis) foram analisados para a descoberta de variantes e a identificação de mutações funcionais. Um estudo direcionado das alterações encontradas foi realizado para compreender os dados no contexto da doença. Resultados Nenhuma das variantes identificadas foi comuma outras amostras dentro do mesmo grupo, assim como nenhuma mutação se repetiu entre pacientes com endometriose, controles inférteis e férteis. No grupo de endometriose, foram identificadas nove mutações deletérias preditas, mas apenas uma foi previamente associada a uma condição clínica sem impacto endometrial. Ao cruzar os genes mutados com os descritores endometriose e/ou endométrio, o gene CMKLR1 foi associado a resposta inflamatória na endometriose e a processos endometriais para estabelecimento da gravidez. Conclusão Apesar de nenhum padrão de mutação ter sido encontrado, ponderamos o pequeno tamanho da amostra e a análise dos dados de sequenciamento de RNA. Considerando o objetivo do estudo de triagem e a importância do gene CMKLR1 na modulação endometrial, este poderia ser um gene candidato para estudos adicionais que avaliem mutações no endométrio eutópico de pacientes com endometriose.