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Type-3 cardiorenal syndrome (CRS-3) is acute kidney injury followed by cardiac injury/dysfunction. Mitochondrial injury may impair myocardial function during CRS-3. Since dual-specificity phosphatase 1 (DUSP1) and prohibitin 2 (PHB2) both promote cardiac mitochondrial quality control, we assessed whether these proteins were dysregulated during CRS-3-related cardiac depression. We found that DUSP1 was downregulated in heart tissues from a mouse model of CRS-3. DUSP1 transgenic (DUSP1Tg) mice were protected from CRS-3-induced myocardial damage, as evidenced by their improved heart function and myocardial structure. CRS-3 induced the inflammatory response, oxidative stress and mitochondrial dysfunction in wild-type hearts, but not in DUSP1Tg hearts. DUSP1 overexpression normalized cardiac mitochondrial quality control during CRS-3 by suppressing mitochondrial fission, restoring mitochondrial fusion, re-activating mitophagy and augmenting mitochondrial biogenesis. We found that DUSP1 sustained cardiac mitochondrial quality control by binding directly to PHB2 and maintaining PHB2 phosphorylation, while CRS-3 disrupted this physiological interaction. Transgenic knock-in mice carrying the Phb2S91D variant were less susceptible to cardiac depression upon CRS-3, due to a reduced inflammatory response, suppressed oxidative stress and improved mitochondrial quality control in their heart tissues. Thus, CRS-3-induced myocardial dysfunction can be attributed to reduced DUSP1 expression and disrupted DUSP1/PHB2 binding, leading to defective cardiac mitochondrial quality control.
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Síndrome Cardiorrenal , Fosfatasa 1 de Especificidad Dual , Prohibitinas , Animales , Ratones , Síndrome Cardiorrenal/metabolismo , Corazón , Ratones Transgénicos , Miocardio/metabolismo , Prohibitinas/metabolismo , Fosfatasa 1 de Especificidad Dual/metabolismo , MitocondriasRESUMEN
Cardiovascular diseases (CVDs) are currently the leading cause of death worldwide. In 2022, the CVDs contributed to 19.8 million deaths globally, accounting for one-third of all global deaths. With an aging population and changing lifestyles, CVDs pose a major threat to human health. Mitochondria-associated endoplasmic reticulum membranes (MAMs) are communication platforms between cellular organelles and regulate cellular physiological functions, including apoptosis, autophagy, and programmed necrosis. Further research has shown that MAMs play a critical role in the pathogenesis of CVDs, including myocardial ischemia and reperfusion injury, heart failure, pulmonary hypertension, and coronary atherosclerosis. This suggests that MAMs could be an important therapeutic target for managing CVDs. The goal of this study is to summarize the protein complex of MAMs, discuss its role in the pathological mechanisms of CVDs in terms of its functions such as Ca2+ transport, apoptotic signaling, and lipid metabolism, and suggest the possibility of MAMs as a potential therapeutic approach.
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Objective: Although extensive research has explored the link between mental disorders and asthma, the characteristics and patterns of this association are still unclear. Our study aims to examine the genetic causal links between common mental disorders (specifically, anxiety and depression) and asthma. Methods: We conducted genetic analyses including linkage disequilibrium score regression (LDSC) and bidirectional two-sample Mendelian randomization (MR) analyses, and utilized summary statistics from recent large-scale Genome-Wide Association Studies (GWASs) in European populations, covering sensation of anxiety or depression, anxiety sensation, depression sensation, anxiety disorders, major depression disorder (MDD), and asthma. Results: LDSC revealed significant genetic correlations among sensation of anxiety or depression, MDD and asthma (P < 0.017), highlighting potential genetic correlation between anxiety disorders and asthma (P < 0.05 yet > 0.017). In bidirectional two-sample MR, inverse-variance weighted (IVW) analyses suggested that genetic liability to asthma was significantly associated with an increased risk of sensation of anxiety or depression (OR = 4.760, 95%CI: 1.645-13.777), and MDD (OR = 1.658, 95%CI: 1.477-1.860). Conversely, IVW analyses indicated that genetic liability to anxiety disorders was not associated with an increased risk of asthma (P > 0.01), nor was genetic liability to asthma associated with an increased risk of anxiety disorders (P > 0.01). Furthermore, no significant genetic causal relationships were observed for other studied traits. Multivariate MR, after adjusting for body mass index and alcohol consumption, further corroborated the independent causal effect of genetic predisposition to MDD on the risk of asthma (OR = 1.460, 95% CI: 1.285-1.660). Conclusion: Our study establishes MDD as a predisposing factor for asthma. Meanwhile, anxiety disorders are not causal risk factors for asthma, nor is the reverse true. It is recommended to closely monitor asthma symptoms in patients with MDD.
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Currently, the level of economic globalisation is expanding, which gives organizations more room to grow while also subjecting them to an increasing amount of pressure from the market. Companies are forced to deal with an increasing number of unclear aspects due to the unstable internal and external environments, which also increases the risks they confront. A management system for corporate financial risk is according to studies on early warning systems for financial risks. Its goals are to raise the standard of corporate financial management and boost economic advantages, identify concerns and potential hazards in the corporate financial management process, stop corporate financial crises in their tracks, and lessen the losses brought on by such crises. The financial risk management of the organization is predicted and examined in this research using the logistic regression model. The use of a logistic regression model allows for the simultaneous analysis of various risk factors, such as discrete and continuous variables, as well as the analysis of external variables' interactions and confounding. This method is suited for widespread usage in practice because it has shown exceptional outcomes in study that are 16.24% better than those of the conventional method.
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Algoritmos , Organizaciones , Modelos Logísticos , Medición de Riesgo , IncertidumbreRESUMEN
To evaluate the measurement method of passive dosemeters for terrestrial gamma radiation measurements. An inter-comparison of passive dosemeters for terrestrial gamma radiation measurements was organized alternately by the Japan Chemical Analysis Center, National Institute for Radiological Protection of Chinese Center for Disease Control and Prevention and Radiation Monitoring Technical Center of Ministry of Environmental Protection every 2 years. The procedures and exposure conditions of the field-exposure and reference irradiation test were provided by the organizer. During 2019-2020, the En values of Field-1 and Field-2 in three laboratories were lower than 1.0 and assigned 'acceptable' according to inter-comparison criteria. After the correction of the fading effect of dosemeter material, the En values of reference irradiation test (0.301 mGy, 1.000 mGy) in three laboratories were lower than 1.0 and assigned 'acceptable'.
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Exposición Profesional , Monitoreo de Radiación , Protección Radiológica , Rayos gamma , Exposición Profesional/análisis , Dosis de Radiación , Dosímetros de Radiación , Monitoreo de Radiación/métodos , Protección Radiológica/métodosRESUMEN
The ESR radiation dosimetric properties of tooth enamel samples from cows and goats were investigated and compared with those of human samples. Samples were prepared first mechanically, and then chemically. The study results showed that the native signals from cow and goat samples were weaker than those from human samples; the radiation sensitivities for cow and goat samples were very close to those of human tooth enamel samples. These results indicated that cow and goat teeth could be alternative materials for radiation dose estimation.
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Esmalte Dental/química , Esmalte Dental/efectos de la radiación , Radiometría/métodos , Adolescente , Adulto , Animales , Bovinos , Espectroscopía de Resonancia por Spin del Electrón , Cabras , Humanos , Técnicas In Vitro , Persona de Mediana Edad , Tolerancia a Radiación , Especificidad de la Especie , Adulto JovenRESUMEN
Sucrose is a convenient, common, tissue-equivalent material suitable for electron paramagnetic resonance (EPR) dosimetry of ionising radiation. A number of publications have reported on the dosimetric properties of sucrose and their use in radiation accident dose reconstruction. However, previous studies did not include specially the description of measurement methods of sucrose by EPR. The aim of this work is to introduce particularly the EPR measurement methods of sucrose. In this regard, practical considerations of sample size, microwave power, modulation amplitude, EPR spectrum and signal stability are discussed.
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Radioisótopos de Cesio , Espectroscopía de Resonancia por Spin del Electrón , Dosis de Radiación , Liberación de Radiactividad Peligrosa , Radiometría , Sacarosa/efectos de la radiación , Rayos gamma , Humanos , Microondas , Protección Radiológica , Marcadores de SpinRESUMEN
Gold nanoparticles are promising as a kind of novel radiosensitizer in radiotherapy. If gold nanoparticles are shown to have good irradiation stability and biocompatibility, they would play an important role in radiotherapy. In this work, we investigated irradiation effects of gold nanoparticles under 2-10 kR gamma irradiation and cytotoxicity of gold nanoparticles with human K562 cells by using Cell Titre-Glo luminescent cell viability assay. The results revealed that gamma irradiation had not induced any obvious instability and size variations in gold nanoparticles. We found that gold nanoparticles showed excellent radiation hardness with an absorbed dose conversation factor of 9.491 rad/R. Meanwhile, the surface plasmon resonance of gold nanoparticles was enhanced obviously after 2-10 kR gamma irradiation. Subsequently, cytotoxicity tests indicated that the extremely high concentration of gold nanoparticles could cause a sharp decrease in K562 cell viability, while the low concentration of gold nanoparticles had no obvious influence on the cell viability. Our results revealed that gold nanoparticles were stable under high-energy ray irradiation and showed concentration-dependent cytotoxicity.