ABSTRACT
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.
Subject(s)
Humans , ColombiaABSTRACT
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.
ABSTRACT
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.
ABSTRACT
@#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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
Subject(s)
Humans , Male , Female , Adult , Social Isolation , Marriage/psychology , COVID-19/psychology , Interpersonal Relations , Anxiety , Qualitative Research , Family Conflict , Psychological Distress , LearningABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
Objective: The spatial distribution model of particulate matter based on time change in a specific place was established to analyze the spatial and temporal distribution characteristics and movement of particulate matter. Methods: A convenience store was selected as the research subject. The micro-climate and particle number concentration (PNC) of the site were detected, and numerical simulation was carried out by computational fluid dynamics (CFD) simulation method. Based on the discrete phase model, the temporal and spatial distribution characteristics and movement rules of simulated particles were analyzed. Results: The wind speed at the entrance of the convenience store was low and almost unchanged during the detection, while the wind speeds outside and inside outlets were high and changed sharply. The PNC of particle size of 0.02-1.00 μm was higher than that of particle size >1.00 μm (all P<0.05). The PNC with particle size of 0.02-1.00 μm from high to low were checkout counter, entrance, outer outlet and inner outlet (all P<0.05). The PNC of the checkout counter and entrance varies greatly, while the PNC of the outer outlet and inner outlet was relatively steady. The CFD simulation results showed that particles exhaled by individuals near the entrance of the checkout counter of the convenience store could be expelled outdoors more quickly with the influence of airflow. However, particles exhaled by individuals in the middle of the shelves remained suspended indoors for a longer period of time compared to those near the checkout counter. Particles emitted from the air conditioning outlet diffuse throughout the entire store and reach a steady state in 300 seconds. Conclusion: The particulate matter in the convenience store was mainly small particle with the size less than 1.00 μm. The residence time, downward trend and number of suspended particulates of human exhaled particles were related to air flow. The particulates escaped from the air conditioner could quickly spread to almost the entire convenience store.
ABSTRACT
Objective:To observe the temporal variability of functional connectivity between the bilateral inferior frontal gyrus and rest of the brain in persons with Broca′s aphasia (BA) and to compare the connectivity between Uygur and Chinese aphasics.Methods:Thirty Chinese and Uygur BA patients (the patient group) and 30 healthy people speaking Uygur and Chinese (the healthy group) were included. rs-fMRI images were acquired, and the patient group was divided then into a Uygur language patient group (9 cases) and a Chinese language patient group (12 cases). The healthy group was divided into a Uygur language healthy group (13 cases) and a Chinese language healthy group (15 cases). Dynamic functional connectivity (dFC) calculations were performed, and a two-factor analysis of covariance was used to obtain the brain regions in which there was an interaction between language and aphasia and to analyze the correlation between the brain regions with abnormal dFCs and linguistic behavior.Results:Interaction between the bilateral inferior frontal gyrus and the left medial and paracentral cingulate gyrus and the right postcentral gyrus dFC was observed to vary. Temporal variability among the Uygur patients was significantly less than among the Uygur healthy and Chinese patient groups. The temporal variability of Broca′s mirror area and the right postcentral gyrus in the Chinese patient group was significantly greater than in the Chinese healthy group or the Uygur patient group. Variability of Broca′s area and the left medial and paracingulate cingulate gyrus in the Uygur patients group correlated positively with oral fluency, reading comprehension and writing.Conclusion:There are differences in the temporal variability of the dFC in the bilateral inferior frontal gyrus between Uygur and Chinese BA patients. The lower variability of Broca′s area with the left medial and paracingulate and cingulate gyrus may help to identify impaired language function in BA patients. The enhanced variability of the Broca′s mirror image area with the right postcentral gyrus may be the result of reorganization of the linguistic network in Chinese BA patients.
ABSTRACT
Objective:To evaluate the relationship between mitochondrial calcium uniporter protein (MCU)-mediated mitochondrial dynamics and intestinal ischemia-reperfusion (I/R) injury in mice.Methods:Twenty-four wild-type adult male C57BL/6J mice, aged 6-8 weeks, weighing 18-20 g, were divided into 4 groups ( n=6 each) using a random number table method: sham operation group (S group), intestinal I/R group (IIR group), sham operation+ MCU inhibitor Ru360 group (S+ Ru360 group) and intestinal I/R + Ru360 group (IIR+ Ru360 group). The mouse model of intestinal I/R injury was prepared by clamping the root of the superior mesenteric artery for 45 min followed by 2 h of reperfusion in anesthetized animals. Small intestinal tissues were obtained at the end of reperfusion for examination of the intestinal mucosal injury which was scored according to Chiu and for determination of the content of malondialdehyde (MDA) (TBA method), activity of superoxide dismutase (SOD) (WST-8 method), content of lactic dehydrogenase (LDH) (colorimetric method), and expression of MCU, dynamin-related protein 1 (Drp1), recombinant human mitochondrial fission 1 protein (Fis1), mitofusin-1 (Mfn1) and Mfn2 (by Western blot). Results:Compared with S and S+ Ru360 groups, the Chiu′s score and contents of MDA and LDH were significantly increased, the activity of SOD was decreased, the expression of MCU, Drp1 and Fis1 was up-regulated, and the expression of Mfn1 and Mfn2 was down-regulated in IIR and IIR+ Ru360 groups ( P<0.05). Compared with IIR group, the Chiu′s score and contents of MDA and LDH were significantly decreased, the activity of SOD was increased, the expression of MCU, Drp1 and Fis1 was down-regulated, and the expression of Mfn1 and Mfn2 was up-regulated in IIR+ Ru360 group ( P<0.05). Conclusions:The mechanism underlying intestinal I/R injury may be related to MCU-induced promotion of mitochondrial fission, reduction of mitochondrial fusion and mediation of imbalance in mitochondrial dynamics in mice.
ABSTRACT
Objective:To quantitatively evaluate and compare the morphology and dynamics parameters of mitral valve devices in patients with atrial functional mitral regurgitation (AFMR) and ventricular functional mitral regurgitation (VFMR) by real-time three-dimensional ultrasound, in order to provide theoretical basis for diagnosis and clinical treatments of the two types of regurgitation patients.Methods:A retrospective study was conducted on 20 AFMR patients (AFMR group) and 20 VFMR patients (VFMR group) who underwent transesophageal echocardiography at Wuhan University People′s Hospital from May to November 2022. Additionally, 20 patients who underwent transesophageal echocardiography at our hospital during the same period due to patent foramen ovale or non cardiac surgery monitoring were selected as the control group. All subjects were measured mitral annulus anteroposterior diameter (AP diameter), anterolateral posteromedial diameter (ALPM diameter), anteroposterior diameter/anterolateral posteromedial diameter (AP/ALPM), commissural width (CW), annular area (AA), annular circumference (AC), annular height (AH), coaptation depth (CD), tenting volume (TV), non-planar angle (NPA) and posterior leaflet angle at isovolumic relaxation time, early diastole, mid diastole, late diastole, isovolumic contraction time, early systole, mid systole, and late systole. The total change rate and systolic change rate of the above parameters were calculated, the differences in structure and dynamic changes of the mitral valve device among three groups were compared, and the correlations between the change rate of mitral annular parameters and left ventricular long axis strain (GLS) were analyzed.Results:①The GLS of three groups were as follows: control group>AFMR group>VFMR group, and the differences between the groups were statistically significant (all P<0.05). ②Static structure: The AP diameter, ALPM diameter, AA, AC, and total leaflet area (TLA) of the AFMR group and VFMR group were significantly larger than those of the control group (all P<0.05), but there was no statistically significant difference between the AFMR group and VFMR group (all P>0.05). Compared with the other two groups, the TV, CD, and posterior leaflet angle of the VFMR group were significantly increased, exhibiting the mitral valve tethering; the control group had the largest AH/CW and the deepest saddle shape; the AFMR group had the smallest TLA/AA and the least mitral valve remodeling; there was no statistically significant difference in the junction area among the three groups (all P>0.05). ③Dynamic changes: AP diameter, ALPM diameter, AA and AC in the control group showed regular changes throughout the cardiac cycle, gradually decreased from isovolumic relaxation time to late diastole, and gradually increased from isovolumic contraction time to late systole; The changes in the above parameters in the AFMR and VFMR groups appeared more disordered. In addition, compared with the control group, the total change rate and systolic change rate of AP diameter in the AFMR group were significantly reduced, but the total change rate of ALPM diameter was significantly increased (all P<0.05). ④The total change rate of AA, ALPM diameter and AP diameter were moderately correlated with GLS ( r=0.353, P=0.006; r=-0.304, P=0.018; r=0.300, P=0.020), while the systolic change rate of posterior leaflet angle was weakly correlated with GLS ( r=0.267, P=0.039). Conclusions:There are differences in the morphology and dynamics parameters of mitral valve device in patients with AFMR and VFMR.Different clinical strategies can be used for the two kinds of functional mitral regurgitation.
ABSTRACT
OBJECTIVE Mitochondria plays a crucial role in cellular homeostasis by regulating various pro-cesses,including calcium signaling and mitophagy.This study aimed to explore the involvement of prohibitin 2(PHB2),an inner mitochondrial membrane protein,in the modulation of mitochondrial calcium dynamics and mitoph-agy.METHODS HEK293T cells were used as the experi-mental cells and were divided into control,PHB2 knock-down,and PHB2 overexpression groups.To evaluate mitochondrial calcium dynamics,Rhod-2 AM and Mito-Tracker Green fluorescence dyesrhod-2 staining and laser confocal microscopy were employed to visualize mito-chondrial calcium imaging.Additionally,Green-5N was utilized to measure the rate of mitochondrial calcium uptake.The mitochondrial membrane potential was assessed using JC-10 staining and laser confocal micros-copy,while cellular ATP levels were determined using ATP assay kits.Furthermore,mitochondrial autophagy was induced by treatment with CCCP,and the expression lev-els of TOM20,LC3,and PARKIN,key mitophagy-related proteins,were analyzed using Western blotting.RESULTS The results demonstrated that compared to the control group,the overexpression of PHB2 increased mitochon-drial calcium concentration,mitochondrial calcium uptake rate,ATP level and expression levels of LC3 and PAR-KIN,but decreased mitochondrial membrane potential and TOM20 expression.In contrast,PHB2 knockdown reduced mitochondrial calcium concentration,ATP level and expression levels of LC3 and PARKIN,but elevated mitochondrial membrane potential,and TOM20 expres-sion.CONCLUSION This study provides evidence that PHB2 plays a vital role in regulating mitochondrial calci-um dynamics,which in turn influences mitochondrial func-tion and modulates mitochondrial autophagy.These find-ings contribute to our understanding of the molecular mechanisms underlying the interplay between PHB2,mitochondrial calcium signaling,and mitophagy.
ABSTRACT
Long-term exposure to risk factors will lead to coronary atherosclerosis, which will lead to the formation and progression of coronary plaque. Early identification of high-risk plaque characteristics will help prevent plaque rupture or erosion, thus avoiding the occurrence of acute cardiovascular events. Biomechanical stress plays an important role in progression and rupture of atherosclerotic plaques. In recent years, non-invasive coronary computed tomography angiography (CCTA) computational fluid dynamics (CFD) modeling has made it possible to acquire the corresponding biomechanical stress parameters. These coronary biomechanical stress parameters, especially wall shear stress (WSS), will aid in the development of a more accurate clinical model for predicting plaque progression and major adverse cardiovascular events ( MACE ). In this review, the biomechanical stress and the role of WSS from CCTA in atherosclerosis were introduced, and the researches on the relationship between biomechanical stress from CCTA and coronary artery diseases were discussed.
ABSTRACT
Objective To investigate the effects of banding width on hemodynamic characteristics of pulmonary artery (PA) by constructing pulmonary artery banding (PAB) models with different widths. Methods Based on clinical practice, with the same banding position and degree, computer-aided design (CAD) was utilized to reconstruct three-dimensional PAB models with different banding widths (2, 3, 4, 5 mm). Hemodynamic characteristics of the models with different banding widths, including pressure, streamlines, energy loss, energy efficiency and blood flow distribution ratio, were compared and analyzed through computational fluid dynamics (CFD). Results The pressure of PA decreased significantly, while the change of banding width had no significant effects on the pressure drop level at banding position. With the increase of banding width, the energy loss decreased, and the energy efficiency showed an upward trend. The blood flow of the left PA raised, and the ratio of blood flow distribution between the left PA and right PA increased, with the maximum reaching up to 2.28 : 1. Conclusions The increase of banding width can reduce the energy loss of PA and improve the energy efficiency of blood flow, but it will lead to the imbalance of blood flow distributions between the left and right lungs. Both the balance of blood flow distribution and the energy loss should be considered in choice for banding width of PAB. The virtual design of PAB surgery based on CAD and CFD will assist individualized banding width selection in future.
ABSTRACT
Objective To explore hemodynamics of the aortic arch and supraarch vessels after thoracic endovascular aortic repair with fenestration and parallel grafts techniques, and compare the differences of these techniques. Methods Four patients with aortic arch lesions whose supraarch vessels were reconstructed by different surgical techniques (fenestration, chimney and periscope) were studied, and three-dimensional (3D) geometric models were established based on postoperative image data. The physiological flow obtained from two dimensional (2D) phase contrast magnetic resonance imaging were imposed on the ascending aorta inlet and the supraarch vessels outlets. The pressure waveform of 3-element Windkessel model was imposed on the descending aorta outlet. Through computational fluid dynamics ( CFD ) simulations, the hemodynamic parameters were obtained, including the pressure of supraarch vessels, the velocity vector of the stent inlet, and the relative residence time. Results The pressure change of the periscope stent was the largest, followed by the fenestration stent, and the pressure change of the chimney stent was the smallest. The velocity of the fenestration and periscope stent inlet was uneven, which might form vortex. The velocity of the chimney stent inlet was even. The high relative residence time concentrated in distal end of the fenestration stent outer wall, the ‘gutter’ part, and the place where the chimney and periscope stent adhered to the vessel wall. Conclusions The pressure difference between the inner and outer walls of the fenestration and periscope stent was high, so it was recommended to use the balloon-expandable stent. The pressure difference between the inner and outer walls of the chimney stent was low, so it was recommended to use the self-expanding stent. The predicted location of thrombosis was consistent with the clinical follow-up data, so it may be used for surgical planning and risk assessment of interventional treatment of aortic arch lesions.
ABSTRACT
Objective To investigate the effect of different optimization algorithms on accurate reconstruction of traffic accidents. Methods Non-dominated sorting genetic algorithm-II ( NSGA-II), neighborhood cultivation genetic algorithm (NCGA) and multi-objective particle swarm optimization (MOPSO) were used to optimize the multi-rigid body dynamic reconstruction of a real case. The effects of different optimization algorithms on convergence speed and optimal approximate solution were studied. The optimal initial impact parameters were simulated as boundary conditions of finite element method, and the simulated results were compared with the actual injuries. Results NCGA had a faster convergence speed and a better result in optimization process. The kinematic response of pedestrian vehicle collision reconstructed by the optimal approximate solution was consistent with the surveillance video. The prediction of craniocerebral injury was basically consistent with the cadaver examination. Conclusions The combination of optimization algorithm, rigid multibody and finite element method can complete the accurate reconstruction of traffic accidents and reduce the influence of human factors.