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The aim of this article was to analyse the dynamics of sexual offense reports in Colombia over the period between 2010 and 2022. For this, a mixed methodology was applied in the following phases: first, the Colombian National Police registry which included 286 604 sexual crimes reported in the aforementioned period was analysed. Then, a causal loop diagram of System Dynamics was designed to highlight the role of reporting sexual crimes in the Colombian Penal System. The main findings of this article include that 85.73 % of the complaints are mostly associated with women and 68 % of the victims are minors or adolescents of both sexes. It must be noted that Colombian legislation divides these crimes into those that are aggravated by violence and those that are not. It was also found that when the victim was a woman, the crimes occurred in a higher proportion with the aggravating factor of violence. It can also be concluded that during the COVID-19 pandemic confinement, there was a decrease in the number of sexual offense reports due to its negative effect on the possibility of adult women reporting crimes. In addition, it was found that it is imperative to direct the criminal policies towards the general positive prevention of sexual crimes, without instrumentalising individuals, and aimed at completing a detailed follow-up of complaints.
El objetivo de este artículo fue analizar la dinámica de las denuncias por delitos sexuales en Colombia en el periodo comprendido entre 2010 y 2022. Para ello, se aplicó una metodología mixta en las siguientes fases: primero, se analizó el registro de la Policía Nacional de Colombia -que incluyó 286 604 delitos sexuales denunciados en el periodo mencionado-. Luego, se diseñó un diagrama de bucle causal de Dinámica de Sistemas para resaltar el papel de la denuncia de delitos sexuales en el Sistema Penal Colombiano. Entre los principales hallazgos de este artículo se destaca que el 85.73 % de las denuncias están asociadas mayoritariamente a mujeres y el 68 % de las víctimas son menores de edad o adolescentes de ambos sexos. Es de anotar que la legislación colombiana divide estos delitos en agravados por violencia y no agravados por violencia. También se encontró que cuando la víctima es mujer, los delitos se presentan en mayor proporción con el agravante de violencia. También se puede concluir que durante el encierro pandémico COVID-19, hubo una disminución en el número de denuncias de delitos sexuales debido a su efecto negativo en la posibilidad de que las mujeres adultas denuncien delitos. Además, se constató que es imperativo orientar las políticas criminales hacia la prevención general positiva de los delitos sexuales, sin instrumentalizar a los individuos, y dirigidas a completar un seguimiento detallado de las denuncias.
O objetivo deste artigo foi analisar a dinâmica das denúncias de crimes sexuais na Colômbia no período entre 2010 e 2022. Para isso, foi aplicada uma metodologia mista nas seguintes fases: primeiro, foi analisado o registro da Polícia Nacional da Colômbia, que incluía 286 604 crimes sexuais denunciados no período mencionado. Em seguida, foi elaborado um diagrama de loop causal do System Dynamics para destacar o papel da denúncia de crimes sexuais no sistema penal colombiano. As principais conclusões desse artigo incluem que 85.73 % das denúncias estão associadas principalmente a mulheres e 68 % das vítimas são menores ou adolescentes de ambos os sexos. Deve-se observar que a legislação colombiana divide esses crimes entre aqueles que são agravados pela violência e aqueles que não são. Também foi constatado que, quando a vítima era mulher, os crimes ocorreram em uma proporção maior com o agravante de violência. Também se pode concluir que, durante o confinamento da pandemia da COVID-19, houve uma diminuição no número de denúncias de crimes sexuais devido ao seu efeito negativo sobre a possibilidade de mulheres adultas denunciarem crimes. Além disso, constatou-se que é imprescindível direcionar as políticas criminais para a prevenção geral positiva dos crimes sexuais, sem instrumentalizar os indivíduos, e visando à conclusão de um acompanhamento detalhado das denúncias.
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Humains , ColombieRésumé
@#Hemodynamics plays a vital role in the development and progression of cardiovascular diseases, and is closely associated with changes in morphology and function. Reliable detection of hemodynamic changes is essential to improve treatment strategies and enhance patient prognosis. The combination of computational fluid dynamics with cardiovascular imaging technology has extended the accessibility of hemodynamics. This review provides a comprehensive summary of recent developments in the application of computational fluid dynamics for cardiovascular hemodynamic assessment and a succinct discussion for potential future development.
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In addition to providing energy for cells, mitochondria also participate in calcium homeostasis, cell information transfer, cell apoptosis, cell growth and differentiation. Therefore, maintaining mitochondrial homeostasis is very crucial for the body to carry out normal life activities. Ubiquitination, a post-translational modification of proteins, is involved in various physiological and pathological processes of cells by regulating mitochondrial homeostasis. However, the mechanism by which ubiquitination regulates mitochondrial homeostasis has not been summarized, especially the effect of Parkin protein on cardiovascular diseases. In this paper, the specific mechanism of mitochondrial homeostasis regulated by ubiquitination of Parkin protein is discussed, and the influence of mitochondrial homeostasis imbalance on cardiovascular diseases is reviewed, with a view to providing potential therapeutic strategies for the clinical treatment of cardiovascular diseases.
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ObjectiveTo study the effect and mechanism of Yixintai on mitochondrial fission proteins in the rat model of chronic heart failure. MethodTen of 60 SD rats were randomly selected as the sham operation group， and the remaining 50 rats were subjected to ligation of the left anterior descending coronary artery for the modeling of heart failure post myocardial infarction. The successfully modeled rats were randomized into model， low-， medium-， and high-dose （1.4， 2.8， and 5.6 g·kg-1， respectively） Yixintai， and trimetazidine （10 mg·kg-1） groups. The rats were administrated with corresponding doses of drugs by gavage， and the rats in the model group and sham operation group were given an equal volume of normal saline by gavage for 28 consecutive days. Enzyme-linked immunosorbent assay （ELISA） was then employed to measure the levels of amino-terminal pro-B-type natriuretic peptide （NT-pro BNP）， B-type natriuretic peptide （BNP）， and adenosine triphosphate （ATP） in the serum. Color Doppler ultrasound imaging was conducted to examine the cardiac function indicators. Hematoxylin-eosin staining and Masson staining were conducted to observe the pathological changes in the heart， and Image J was used to calculate collagen volume fraction （CVF）. Transmission electron microscopy was employed to observe the ultrastructural changes of myocardial cells. Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling （TUNEL） was employed to measure the apoptosis rate of myocardial cells. Western blot was employed to determine the protein levels of mitochondrial fission protein 1 （Fis1） and mitochondrial fission factor （Mff） in the outer mitochondrial membrane of the myocardial tissue. ResultCompared with the sham operation group， the model group showed elevated levels of NT-pro BNP and BNP in the serum， decreased ATP content， left ventricular ejection fraction （LVEF）， and left ventricular fraction shortening （LVFS）， increased left ventricular end-diastolic diameter （LVIDd） and left ventricular end-systolic diameter （LVIDs）， disarrangement of myocardial cells， inflammatory cell infiltration， increased collagen fibers and CVF， damaged myocardium and mitochondria， and increased apoptosis rate of myocardial cells， and up-regulated expression of Fis1 and Mff in the cardiac tissue （P<0.01）. Compared with the model group， different doses of Yixintai and trimetazidine lowered the serum levels of NT-pro BNP and BNP （P<0.05）， increased the ATP content （P<0.05）， increased LVEF and LVFS （P<0.01）， decreased LVIDd and LVIDs （P<0.01）. Moreover， the drugs alleviated the myocardial inflammatory damage and fibrosis， reduced CVF （P<0.01）， repaired the myocardial mitochondrial structure， and decreased the apoptosis rate of myocardial cells （P<0.01）. Medium- and high-dose Yixintai and trimetazidine down-regulated the expression of Fis1 and Mff in the myocardial tissue （P<0.05）. ConclusionYixintai can improve mitochondrial structure， reduce myocardial cell apoptosis， and improve cardiac function by inhibiting the expression of Fis1 and Mff in the myocardial tissue.
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Diabetic peripheral neuropathy（DPN） is a neurodegenerative disease of diabetes mellitus involving peripheral nervous system damage， which is characterized by axonal degenerative necrosis， Schwann cell apoptosis and demyelination of nerve myelin sheath as the main pathological features， this disease is highly prevalent and is a major cause of disability in diabetic patients. Currently， the pathogenesis of DPN may be related to oxidative stress， inflammatory response， metabolic abnormality， and microcirculation disorder. The treatment of DPN in modern medicine mainly starts from controlling blood glucose， nourishing nerves and improving microcirculation， which can only alleviate the clinical symptoms of patients， and it is difficult to fundamentally improve the pathological damage of peripheral nerves. Mitochondrial quality control refers to the physiological mechanisms that can maintain the morphology and functional homeostasis of mitochondria， including mitochondrial biogenesis， mitochondrial dynamics， mitochondrial oxidative stress and mitochondrial autophagy， and abnormal changes of which may cause damage to peripheral nerves. After reviewing the literature， it was found that traditional Chinese medicine（TCM） can improve the low level of mitochondrial biogenesis in DPN， maintain the balance of mitochondrial dynamics， inhibit mitochondrial oxidative stress and mitochondrial autophagy， and delay apoptosis of Schwann cells and neural axon damage， which has obvious effects on the treatment of DPN. With the deepening of research， mitochondrial quality control may become one of the potential targets for the research of new anti-DPN drugs， therefore， this paper summarized the research progress of TCM in treating DPN based on four aspects of mitochondrial quality control， with the aim of providing a theoretical research basis for the discovery of new drugs.
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Tumor cells adaptively reforge their metabolism to meet the demands of energy and biosynthesis. Mitochondria, pivotal organelles in the metabolic reprogramming of tumor cells, contribute to tumorigenesis and cancer progression significantly through various dysfunctions in both tumor and immune cells. Alterations in mitochondrial dynamics and metabolic signaling pathways exert crucial regulatory influence on the activation, proliferation, and differentiation of immune cells. The tumor microenvironment orchestrates the activation and functionality of tumor-infiltrating immune cells by reprogramming mitochondrial metabolism and inducing shifts in mitochondrial dynamics, thereby facilitating the establishment of a tumor immunosuppressive microenvironment. Stress-induced leakage of mitochondrial DNA contributes multifaceted regulatory effects on anti-tumor immune responses and the immunosuppressive microenvironment by activating multiple natural immune signals, including cGAS-STING, TLR9, and NLRP3. Moreover, mitochondrial DNA-mediated immunogenic cell death emerges as a promising avenue for anti-tumor immunotherapy. Additionally, mtROS, a crucial factor in tumorigenesis, drives the formation of tumor immunosuppressive microenvironment by changing the composition of immune cells within the tumor microenvironment. This review focuses on the intrinsic relationship between mitochondrial biology and anti-tumor immune responses from multiple angles. We expect to explore the core role of mitochondria in the dynamic interplay between the tumor and the host, in order to facilitate the development of targeted mitochondrial strategies for anti-tumor immunotherapy.
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Resumo Este estudo qualitativo visou compreender a experiência de oito casais de adultos jovens em coabitação durante a pandemia de covid-19 e as repercussões do período na vida conjugal. Foram realizadas entrevistas semiestruturadas, seis presenciais e duas online, com casais heterossexuais, sem filhos, que coabitavam há menos de três anos. A análise temática reflexiva gerou três temas: desafios e dificuldades na pandemia; aproximação entre o casal; ganhos e aprendizados. Níveis aumentados de estresse, insegurança e ansiedade, sensação de sobrecarga e de privação devido às medidas de distanciamento social, dificuldades na delimitação dos espaços individuais dentro de casa e aumento nos conflitos conjugais foram os principais desafios relatados. Apesar disso, o enfrentamento colaborativo resultou em maior intimidade e no fortalecimento do vínculo conjugal, aumentando o compromisso com a relação. Tais resultados ilustram como um contexto pandêmico pode impactar relacionamentos durante o início da coabitação.
Abstract This qualitative study investigated the cohabitation experience of eight young adult couples during in the pandemic and its repercussions on marital life. Semi structured interviews were conducted, six in-person and two online, with childfree heterosexual couples living together for less than three years. The reflexive thematic analysis generated three themes: pandemic-related challenges and difficulties, couple bonding, gains and learnings. Increased levels of stress, insecurity and anxiety, a sense of of overload and deprivation due to social distancing measures, difficulties in delimiting individual spaces within the home and an increase in marital conflicts were the main challenges reported. Conversely, the ability to collaboratively cope with these challenges resulted in more intimacy and strengthened the marital bond, generating greater couple commitment. These findings illustrate how pandemics can impact relationships during the beginning of cohabitation.
Resumen Este estudio cualitativo tuvo como objetivo comprender las experiencias de ocho parejas de adultos jóvenes en cohabitación en el transcurso de la pandemia del covid-19 y sus repercusiones en la vida conyugal. Se realizaron entrevistas semiestructuradas, seis presenciales y dos en línea, con parejas heterosexuales, sin hijos, que vivían en cohabitación hace menos de tres años. El análisis temático reflexivo generó tres temas: desafíos y dificultades en la pandemia, acercamiento entre la pareja, conquistas y aprendizajes. El aumento de los niveles de estrés, inseguridad y ansiedad, los sentimientos de sobrecarga y privación por las medidas de distanciamiento social, las dificultades para delimitar los espacios individuales dentro del hogar y el aumento de los conflictos conyugales fueron los principales desafíos informados. Además, afrontar estos desafíos de forma colaborativa redundó en mayor intimidad y en el fortalecimiento del vínculo conyugal, repercutiendo en el aumento del compromiso con la relación. Estos resultados muestran cómo el contexto pandémico puede impactar el comienzo de la convivencia de las relaciones de pareja.
Résumé Cette étude qualitative a examiné l'expérience de cohabitation de huit jeunes couples adultes pendant la pandémie et ses répercussions sur la vie conjugale. Des entretiens semi-directifs ont été réalisés, six face-à-face et deux en ligne, auprès de couples hétérosexuels sans enfants vivant ensemble depuis moins de trois ans. L'analyse thématique réflexive a dégagé trois thèmes: les défis et difficultés liés à la pandémie, le lien du couple, les acquis et les enseignements. Des niveaux accrus de stress, d'insécurité et d'anxiété, des sentiments de surcharge et de privation dus aux mesures de distanciation sociale, des difficultés à délimiter les espaces individuels chez eux et une augmentation des conflits conjugaux sont les principaux défis signalés. Cependant, la capacité à faire face ensemble à ces défis a permis d'accroître l'intimité et de renforcer le lien conjugal, générant ainsi un plus grand engagement du couple. Ces résultats illustrent l'impact que les pandémies peuvent avoir sur les relations au début de la cohabitation.
Sujets)
Humains , Mâle , Femelle , Adulte , Isolement social , Mariage/psychologie , COVID-19/psychologie , Relations interpersonnelles , Anxiété , Recherche qualitative , Conflit familial , Détresse psychologique , ApprentissageRésumé
Los Combinados Deportivos son instituciones de base del Sistema Deportivo Cubano. Su ubicación se corresponde con la demarcación territorial de los Consejos Populares. Como parte de su encargo social, deben contribuir a la calidad de vida de la población. El objetivo de este artículo consistió en diseñar una metodología que se sustente en una concepción teórica caracterizada por un enfoque transformador, para el perfeccionamiento de la dinámica participativa en la gestión del subsistema de Actividad Física Comunitaria (AFC) en el combinado deportivo. Su importancia radica en la aplicación de una metodología para perfeccionar la dinámica participativa en esta área, validada a partir de la experimentación en el combinado deportivo, como estructura básica del sistema deportivo del Instituto Nacional de Deportes, Educación Física y Recreación (Inder). Se emplearon métodos empíricos como: la revisión de documentos, recolección de datos, encuesta, entrevista, observación participante, taller de sensibilización y el preexperimento. Para su aplicación, se emplearon dos unidades de análisis: una destinada a evaluar el proceso de gestión con dos dimensiones y otra para evaluar la dinámica participativa con dos dimensiones, todas ellas con sus indicadores e instrumentos de medición. Los resultados obtenidos muestran fisuras e insuficiencias en la gestión de la dinámica participativa del subsistema de AFC, no obstante, la implementación de la metodología, aporta instrumentos diagnósticos para la labor de directivos y profesores, con vistas a evaluar la gestión de manera integral en el combinado. La fuerza técnica y la estructura de dirección del combinado consideran pertinentes los instrumentos que permiten diagnosticar la dinámica participativa en el subsistema de referencia, que develan las esencias de la participación comunitaria, las causas que limitan este proceso, sus resultados y los criterios relacionados con los temas, las formas y los involucrados en la participación comunitaria, en función de la gestión del combinado.
As Combinações Esportivas são instituições base do Sistema Desportivo Cubano. A sua localização corresponde à demarcação territorial dos Conselhos Populares. Como parte da sua responsabilidade social, devem contribuir para a qualidade de vida da população. O objetivo deste artigo foi desenhar uma metodologia baseada em uma concepção teórica caracterizada por uma abordagem transformadora, para a melhoria das dinâmicas participativas na gestão do subsistema de Atividade Física Comunitária (AFC) na equipe esportiva. Sua importância reside na aplicação de uma metodologia para aperfeiçoar a dinâmica participativa nesta área, validada a partir da experimentação na equipe esportiva, como estrutura básica do sistema esportivo do Instituto Nacional de Esporte, Educação Física e Recreação (Inder). Foram utilizados métodos empíricos como: revisão documental, coleta de dados, levantamento, entrevista, observação participante, oficina de sensibilização e pré-experimento. Para sua aplicação foram utilizadas duas unidades de análise: uma destinada a avaliar o processo de gestão com duas dimensões e outra para avaliar a dinâmica participativa com duas dimensões, todas elas com seus indicadores e instrumentos de medição. Os resultados obtidos mostram fissuras e insuficiências na gestão da dinâmica participativa do subsistema AFC, porém, a implementação da metodologia fornece instrumentos de diagnóstico para o trabalho de diretores e professores, com vistas a avaliar a gestão de forma abrangente no conjunto. A força técnica e a estrutura de gestão da equipa consideram relevantes os instrumentos que permitem diagnosticar a dinâmica participativa no subsistema de referência, que revelam as essências da participação comunitária, as causas que limitam este processo, os seus resultados e os critérios relativos aos temas, formas e dos envolvidos na participação comunitária, dependendo da gestão da equipe.
The Sports Complexes are base institutions of the Cuban Sports System. Its location corresponds to the territorial demarcation of the Popular Councils. As part of their social responsibility, they must contribute to the quality of life of the population. The objective of this article was to design a methodology that is based on a theoretical conception characterized by a transformative approach, for the improvement of the participatory dynamics in the management of the Community Physical Activity (AFC in Spanish) subsystem in the sports complexes. Its importance lies in the application of a methodology to improve the participatory dynamics in this area, validated from experimentation in the sports complex, as a basic structure of the sports system of the National Institute of Sports, Physical Education and Recreation (INDER). Empirical methods were used such as: document review, data collection, survey, interview, participant observation, awareness workshop and pre-experiment. For its application, two units of analysis were used: one intended to evaluate the management process with two dimensions and another to evaluate the participatory dynamics with two dimensions, all of them with their indicators and measurement instruments. The results obtained show fissures and insufficiencies in the management of the participatory dynamics of the AFC subsystem, however, the implementation of the methodology provides diagnostic instruments for the work of managers and teachers, with a view to evaluating the management in an integral way in the complex. The technical staff and the management structure of the sport complex consider the instruments are pertinent that allow diagnosing the participatory dynamics in the subsystem of reference, which reveal the essence of community participation, the causes that limit this process, its results and the criteria related to the results. themes, forms and those involved in community participation, depending on the management of the sport complex.
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Dyes are becoming more widely used around the world wide, but there is no effective bioremediation approach for removing them completely from the environment. Several dyes are mentioned to be degraded through bacteria; however, it's still unknown how the particular enzymes act throughout the dye degradation. The behavior and function of these enzymes in the biodegradation of azo dyes (Textile dyes) had been investigated experimentally by the numbers of the researchers, however, the molecular mechanisms remain unclear. Therefore, the interaction mechanisms of textile dye (methyl orange) with laccase from B. subtilis were explored through molecular docking and molecular dynamics simulations, the three selected dyes (methyl orange, malachite green, and acid blue 62) that interact positively with laccase on the basis of their maximum binding energy, molecular docking results indicate that one of the three dyes is more stable as a target for degradation through Bacillus subtilis laccase. Therefore, subsequent research focused solely on one substrate: methyl orange. Molecular Dynamics simulation study was applied after the molecular docking to determine the interaction between laccases and methyl orange dyes. The trajectory was proved with root mean square deviation and root mean square fluctuation analysis. According to the molecular dynamics simulation results, laccase-methyl orange complexes remain stable during the catalytic reaction. So, this study demonstrates how laccase is involved in methyl orange bioremediation.
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Leishmaniasis continues to be a neglected tropical disease, affecting people and animals and causing significant economic losses. Therefore, there is interest in the study and evaluation of new drug targets. In fact, it has been shown that by interfering with lysine-reading proteins such as bromodomain (BMD) there is a decrease in parasite survival. In this study, we researched the dynamics and energetics of the Leishmania donovani BMD in complex with bromosporin, which is considered to be a pan-inhibitor of BMDs, with the aim of understanding the molecular recognition mechanism. Molecular dynamics (MD) and non-equilibrium free energy calculation guided by steered molecular dynamics (SMD) simulations showed that the BMD has three flexible amino acid regions and bromosporin exhibiting various recognition states during the interaction. These results corroborate the promiscuity of bromosporin for energetically favourable sites, with the possibility of expanding its inhibition to other bromodomains. Furthermore, these results suggest that Van der Waals interactions have more relevance for complex recognition and residues ASN-87 and TRP-93 are key in forming hydrophobic and H-bond interactions, respectively. This research provides new insights for understanding the recognition mechanism, dynamics and energetics of the complex for the development of new therapeutic strategies.
La leishmaniasis sigue siendo una enfermedad tropical desatendida, que afecta a personas y animales y causa importantes pérdidas económicas. De ahí el interés por estudiar y evaluar nuevas dianas farmacológicas. De hecho, se ha demostrado que al interferir con proteínas lectoras de lisina como el bromodominio ("bromodomain", BMD) se produce una disminución de la supervivencia del parásito. En este artículo estudiamos la dinámica y la energética del BMD de Leishmania donovani en complejo con bromosporina, que se considera un pan-inhibidor de BMD, con el objetivo de comprender el mecanismo de reconocimiento molecular. Las simulaciones de dinámica molecular (DM) y el cálculo de energía libre de no-equilibrio guiado por dinámica molecular de estiramiento (DMS) mostraron que BMD tiene tres regiones de aminoácidos flexibles y la bromosporina presenta varios estados de reconocimiento durante la interacción. Estos resultados corroboran la promiscuidad de la bromosporina por sitios energéticamente favorables, siendo posible expandir su inhibición a otros bromodominios. Además, los resultados sugieren que las interacciones de Van der Waals tienen más relevancia para el reconocimiento del complejo y los residuos ASN-87 y TRP-93 son clave en la formación de interacciones hidrofóbicas y de puentes de hidrógeno, respectivamente. Esta investigación proporciona nuevos conocimientos para comprender el mecanismo de reconocimiento molecular, la dinámica y la energética del complejo para el desarrollo de nuevas estrategias terapéuticas.
A leishmaniose continua a ser uma doença tropical negligenciada, que afeta os seres humanos e os animais e causa perdas econômicas significativas. Daí o interesse em estudar e avaliar novos alvos de medicamentos. De fato, a interferência com proteínas leitoras de lisina, como o bromo domínio ("bromodomain", BMD), tem demonstrado diminuir a sobrevivência do parasita. Neste trabalho, estudamos a dinâmica e a energética do BMD de Leish-mania donovani em complexo com a bro-mosporina, considerada um pan-inibidor da BMDs, com o objetivo de compreender o mecanismo de reconhecimento molecular. As simulações de dinâmica molecular (MD) e cálculo de energia livre de não-equilíbrio guiada por dinâmica molecular esticamento (MDS) mostraram que o BMD tem três regiões de aminoácidos flexíveis e que a bromosporina apresenta vários estados de reconhecimento durante a interação. Esses resultados corroboram a promiscuidade da bromosporina para locais energeticamente favoráveis, possibilitando a expansão de sua inibição para outros bromodomínios. Além disso, os resultados sugerem que as interações de Van der Waals são mais relevantes no momento do reconhecimento do complexo e os resíduos ASN-87 e TRP-93 são fundamentais na formação de interações hidrofóbicas e de ligações de hidrogênio, respectivamente. Essa pesquisa fornece novos insights para compreender o mecanismo de reconhecimento, a dinâmica e a energética do complexo para o desenvolvimento de novas estratégias terapêuticas.
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Mitochondrial dynamics are a contraversal issue in hepatocellular carcinoma. The present study tries to illustrate the role of mitochondrial dynamics proteins (mitofusin-2 (Mfn2) and YME1L) in hepatocarcinogenesis. Five groups were used: the control group and three HCC groups (after 8, 16, and 24 weeks from DENA induction). The last group was treated with Sorafenib (SP) (10 mg/kg), via oral gavage for 4 weeks after cancer induction. This study revealed that Mfn-2 was downregulated and YME1l was overexpressed in different HCC groups. This dysregulation of mitochondrial dynamics proteins was associated with high hepatic levels of cyclin D1, MMP-9, and MDA and overexpression of ki67 as well as decreasing the hepatic expression of tissue inhibitor of matrix metalloproteinase-3 (Timp-3) and Bax. To confirm the possible role of Mfn2 and YME1L in HCC, we assessed the effect of sorafenib on these parameters and its related HCC characteristics. Sorafenib corrected the level of Mfn2 and YME1L and decreased tumor cell proliferation as well. We also elucidated that mitochondrial dynamics proteins (Mfn2 and YME1L) could be a good therapeutic target for HCC.
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@#This study aimed to investigate the irrigation dynamics of the positive pressure side-vented (SV) needle, EndoVac (micropores) needle and modified apical negative pressure (mANP) open-ended needle using computational fluid dynamics (CFD). A simulation of a prepared root canal (conical frustum) of 15 mm length with an apical diameter of 0.40 mm following Protaper F4 apical preparation was created using three-dimensional (3D) CAD software. The 3D simulated needle of SV 30G needle, EndoVac with micropores needle and mANP, 30G flat open-ended needle were also created. The irrigation dynamics were evaluated through transient CFD simulations. In addition, the irrigation dynamics of mANP at 0.2 mm, 0.5 mm, and 1.0 mm short from the working length were also assessed. The EndoVac and mANP showed negative apical static pressure and streamline patterns able to reach the apical region, thus indicating negligible extrusion. Meanwhile, SV showed positive apical static pressure and almost nonexistent streamlines beyond the needle tip. The SV showed the highest wall shear stress (WSS) magnitude of 1030Pa whereas Endovac (161 Pa) and mANP1 (258 Pa). However, SV revealed lower average WSS (10 Pa) compared to mANP1 (13 Pa) and mANP2 (11 Pa). This is due to SV developed a localised maximum WSS opposite the open vent area only therefore, uneven distribution of WSS. The EndoVac system developed a localised maximum WSS in the pair of micropores furthest away from the apical. CFD analysis of the EndoVac, mANP and SV showed different technique approach, needle design and needle depths insertion affect the irrigation dynamics pattern and magnitude.
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This study aims to gain insight into the DNA-specific recognition mechanism of c-Myb transcription factor during the regulation of cell early differentiation and proliferation. Therefore, we chose the chicken myeloid gene, mitochondrial import protein 1 (mim-1), as a target to study the binding specificity between potential dual-Myb-binding sites. The c-Myb-binding site in mim-1 is a pseudo-palindromic sequence AACGGTT, which contains two AACNG consensuses. Simulation studies in different biological scenarios revealed that c-Myb binding with mim-1 in the forward strand (complex F) ismore stable than that inthereverse strand (complex R). The principal component analysis (PCA) dynamics trajectory analyses suggested an opening motion of the recognition helices of R2 and R3 (R2R3), resulting in the dissociation of DNA from c-Myb in complex R at 330 K, triggered by the reduced electrostatic potential on the surface of R2R3. Furthermore, the DNA confirmation and hydrogen-bond interaction analyses indicated that the major groove width of DNA increased in complex R, which affected on the hydrogen-bond formation ability between R2R3 and DNA, and directly resulted in the dissociation of DNA from R2R3. The steered molecular dynamics (SMD) simulation studies also suggested that the electrostatic potential, major groove width, and hydrogen bonds made major contribution to the DNA-specific recognition. In vitro trials confirmed the simulation results that c-Myb specifically bound to mim-1 in the forward strand. This study indicates that the three-dimensional (3D) structure features play an important role in the DNA-specific recognition mechanism by c-Myb besides the AACNG consensuses, which is beneficial to understanding the cell early differentiation and proliferation regulated by c-Myb, as well as the prediction of novel c-Myb-binding motifs in tumorigenesis.
Sujets)
Simulation de dynamique moléculaire , Consensus , ADN , HydrogèneRésumé
Zearalenone is one of the most widely polluted Fusarium toxins in the world, seriously endangering livestock and human health. Zearalenone hydrolase (ZHD) derived from Clonostachys rosea can effectively degrade zearalenone. However, the high temperature environment in feed processing hampers the application of this enzyme. Structure-based rational design may provide guidance for engineering the thermal stability of enzymes. In this paper, we used the multiple structure alignment (MSTA) to screen the structural flexibility regions of ZHD. Subsequently, a candidate mutation library was constructed by sequence conservation scoring and conformational free energy calculation, from which 9 single point mutations based on residues 136 and 220 were obtained. The experiments showed that the thermal melting temperature (Tm) of the 9 mutants increased by 0.4-5.6 ℃. The S220R and S220W mutants showed the best thermal stability, the Tm of which increased by 5.6 ℃ and 4.0 ℃ compared to that of the wild type. Moreover, the thermal half-inactivation time at 45 ℃ were 15.4 times and 3.1 times longer, and the relative activities were 70.6% and 57.3% of the wild type. Molecular dynamics simulation analysis showed that the interaction force at and around the mutation site was enhanced, contributing to the improved thermal stability of ZHD. The probability of 220-K130 hydrogen bond of the mutants S220R and S220W increased by 37.1% and 19.3%, and the probability of K130-D223 salt bridge increased by 30.1% and 12.5%, respectively. This work demonstrated the feasibility of thermal stability engineering strategy where the structural and sequence alignment as well as free energy calculation of natural enzymes were integrated, and obtained ZHD variants with enhanced thermal stability, which may facilitate the industrial application of ZHD.
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Humains , Hydrolases , Zéaralénone , Trichothécènes , Banque de gènes , Liaison hydrogèneRésumé
AIM: To investigate the effects of modified Zhujing Pill on the mitochondrion structure and dynamin-related protein of retinal pigment epithelial cells(RPEs)in mice with form deprivation myopia.METHODS: 3-week-old C57BL/6J mice were randomly divided into control group, model group and Chinese medicine group, with 10 mice in each group. Myopia model of the right eye of mice was established by means of form deprivation in model and Chinese medicine groups. After 4wk, the Chinese medicine group were given intragastric administration of modified Zhujing Pill suspension 0.546g/(kg·d)(0.2mL/d)for 4wk, and same amount of saline was given to mice in other groups at the same time of modeling. The axial length and diopter of the right eye of the mouse were measured before and after the experiment by A-ultrasound and a strip retinoscope respectively. At the end of the experiment, the mitochondrial ultrastructure of RPEs was observed by transmission electron microscope. Western blot, and real-time fluorescent quantitative PCR(q-PCR)were used to detect quantitative and gene expression of mitofusin 1(MFN1), optic atrophy 1(OPA1), and dynamin-related protein 1(DRP1)in retinal tissues respectively.RESULTS: At the beginning of the experiment, there was no statistically significant difference in axial length and diopter of the right eye of the mouse in control, model and Chinese medicine groups(P>0.05). At the end of the experiment, compared with the control group, the mice in the model group and the Chinese medicine group had lower diopter and continuously prolonged axial length(all P<0.05), while the mice in the Chinese medicine group had significantly shorter axial length and higher diopter than the model group(all P<0.05). Western blot and q-PCR results showed that the relative expression of MFN1 and OPA1 decreased and DRP1 increased in both the model group and the Chinese medicine group compared with the control group(all P<0.05), and the relative expression of MFN1 and OPA1 increased in the Chinese medicine group compared with the model group(all P<0.05). The electron microscopic results showed that the mitochondria in the right retina of the mice were only mildly swollen in the Chinese medicine group, while the mitochondria in the model group were obviously swollen and disordered and empty.CONCLUSION: Modified Zhujing Pill could protect the retinal mitochondria by regulating the key proteins of mitochondrial dynamics(MFN1, OPA1, and DRP1), and it has a protective effect on the retina of axial myopic mice.
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@#Abstract: Objective To master the condition of cockroach population distribution, seasonal dynamics, cockroach density for different habitat, and to provide a basis for developing cockroach control strategies. Methods Six types of surveillance sites, including residential areas, hotels, restaurants, supermarkets, hospitals and farm product markets, were set up in 14 cities in Liaoning to monitor cockroaches using the sticky-trap method. The cockroach surveillance data from vector surveillance sites in fourteen cities of Liaoning Province in 2021 were collected and statistically analyzed using Excel 2010 and SPSS 23.0 software. The density and species composition of cockroaches were analyzed, and the density difference and seasonal dynamics trend of cockroaches in different habitats were compared. Results A total of 3 031 cockroaches were captured in 2021, of which Blattella germanica accounted for 94.66% (2 869/3 031) and was the dominant population. The total density of cockroaches was 0.230 0 cockroaches per sheet (3 031/13 234) and the total infestation rate of cockroaches was 5.59% (562/10 052). The density and infestation rate of cockroaches in different habitats were in the order of farm product markets, restaurants, and hotels and the difference in infestation rate between habitats was statistically significant (χ2=168.327, P<0.05). The seasonal dynamics trend of cockroach density and disoperation rate showed a unimodal curve, and the peaks were distributed in July. The seasonal dynamics of cockroach density and disoperation rate in different habitats showed a unimodal curve in the habitats of farm product markets, supermarkets, hotels, hospitals and residential areas all, while the habitats of restaurants were close to a double peak curve. Conclusions B. germanica is the dominant species of cockroaches in Liaoning Province in 2021. Compared with 2020 the density and disoperation rate of cockroach in 2021 showed a slight downward trend, and the seasonal dynamics trend of cockroach density and disoperation rate showed a unimodal curve. The farm product markets are the key places for cockroach prevention and control. According to the seasonal fluctuation trends in cockroach density and infestation rate in different habitats, comprehensive prevention and control measures should be taken before the peak periods to reduce cockroach density and control diseases.
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OBJECTIVES@#To investigate the role of brain functional connectivity and nonlinear dynamic analysis in brain function assessment for infants with controlled infantile spasm (IS).@*METHODS@#A retrospective analysis was performed on 14 children with controlled IS (IS group) who were admitted to the Department of Neurology, Anhui Provincial Children's Hospital, from January 2019 to January 2023. Twelve healthy children, matched for sex and age, were enrolled as the control group. Electroencephalogram (EEG) data were analyzed for both groups to compare the features of brain network, and nonlinear dynamic indicators were calculated, including approximate entropy, sample entropy, permutation entropy, and permutation Lempel-Ziv complexity.@*RESULTS@#Brain functional connectivity showed that compared with the control group, the IS group had an increase in the strength of functional connectivity, and there was a significant difference between the two groups in the connection strength between the Fp2 and F8 channels (P<0.05). The network stability analysis showed that the IS group had a significantly higher network stability than the control group at different time windows (P<0.05). The nonlinear dynamic analysis showed that compared with the control group, the IS group had a significantly lower sample entropy of Fz electrode (P<0.05).@*CONCLUSIONS@#Abnormalities in brain network and sample entropy may be observed in some children with controlled IS, and it is suggested that quantitative EEG analysis parameters can serve as neurological biomarkers for evaluating brain function in children with IS.
Sujets)
Enfant , Humains , Nourrisson , Dynamique non linéaire , Spasmes infantiles , Études rétrospectives , Encéphale , ÉlectroencéphalographieRésumé
A novel structural dynamics test method and device were designed to test the biomechanical effects of dynamic axial loading on knee cartilage and meniscus. Firstly, the maximum acceleration signal-to-noise ratio of the experimental device was calculated by applying axial dynamic load to the experimental device under unloaded condition with different force hammers. Then the experimental samples were divided into non-specimen group (no specimen loaded), sham specimen group (loaded with polypropylene samples) and bovine knee joint specimen group (loaded with bovine knee joint samples) for testing. The test results show that the experimental device and method can provide stable axial dynamic load, and the experimental results have good repeatability. The final results confirm that the dynamic characteristics of experimental samples can be distinguished effectively by this device. The experimental method proposed in this study provides a new way to further study the biomechanical mechanism of knee joint structural response under axial dynamic load.
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Animaux , Bovins , Phénomènes biomécaniques , Articulation du genou/physiologie , Ménisque , Phénomènes mécaniques , Mise en chargeRésumé
As one of the traditional computer simulation techniques, molecular simulation can intuitively display and quantify molecular structure and explain experimental phenomena from the microscopic molecular level. When the simulation system increases, the amount of calculation will also increase, which will cause a great burden on the simulation system. Coarse-grained molecular dynamics is a method of mesoscopic molecular simulation, which can simplify the molecular structure and improve computational efficiency, as a result, coarse-grained molecular dynamics is often used when simulating macromolecular systems such as drug carrier materials. In this article, we reviewed the recent research results of using coarse-grained molecular dynamics to simulate drug carriers, in order to provide a reference for future pharmaceutical preparation research and accelerate the entry of drug research into the era of precision drug design.
Sujets)
Simulation de dynamique moléculaire , Vecteurs de médicamentsRésumé
The binding of talin-F0 domain to ras-related protein 1b (Rap1b) plays an important role in the formation of thrombosis. However, since talin is a force-sensitive protein, it remains unclear whether and how force regulates the talin-F0/Rap1b interaction. To explore the effect of force on the binding affinity and the dynamics mechanisms of talin-F0/Rap1b, molecular dynamics simulation was used to observe and compare the changes in functional and conformational information of the complex under different forces. Our results showed that when the complex was subjected to tensile forces, there were at least two dissociation pathways with significantly different mechanical strengths. The key event determining the mechanical strength difference between the two pathways was whether the β4 sheet of the F0 domain was pulled away from the original β1-β4 parallel structure. As the force increased, the talin-F0/Rap1b interaction first strengthened and then weakened, exhibiting the signature of a transition from catch bonds to slip bonds. The mechanical load of 20 pN increased the interaction index of two residue pairs, ASP 54-ARG 41 and GLN 18-THR 65, which resulted in a significant increase in the affinity of the complex. This study predicts the regulatory mechanism of the talin-F0/Rap1b interaction by forces in the intracellular environment and provides novel ideas for the treatment of related diseases and drug development.