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High performance is a crucial factor in seeking a more competitive levelized cost of electricity for the extensive popularization of c-Si solar cells. Here, CsPbBr3 quantum dots (QDs) have been first applied as the light-converting layer to enhance the full-spectrum light response, resulting in an â¼71% enhancement of power conversion efficiency within silicon-based solar cells. Remarkably, even if the photon energy is smaller than the bandgap of CsPbBr3 QDs, the long-wavelength external quantum efficiency shows a significant increase. Such surprising results can be attributed to the nonradiative energy transfer (NRET) mechanism of CsPbBr3 QDs, which can transfer long-wavelength-generated dipoles into the Si base with the assistance of a Coulomb force. Furthermore, a dipole-transferring model, which considers that the Al2O3 passivation layer would play a negative role in the NRET process, is creatively but supportively proposed. These results highlight a simple, low-cost but promising strategy to improve the performance of c-Si solar cells.
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To enhance aerial image detection in complex environments characterized by multiple small targets and mutual occlusion, we propose an aerial target detection algorithm based on an improved version of YOLOv5 in this paper. Firstly, we employ an improved Mosaic algorithm to address redundant boundaries arising from varying image scales and to augment the training sample size, thereby enhancing detection accuracy. Secondly, we integrate the constructed hybrid attention module into the backbone network to enhance the model's capability in extracting pertinent feature information. Subsequently, we incorporate feature fusion layer 7 and P2 fusion into the neck network, leading to a notable enhancement in the model's capability to detect small targets. Finally, we replace the original PAN + FPN network structure with the optimized BiFPN (Bidirectional Feature Pyramid Network) to enable the model to preserve deeper semantic information, thereby enhancing detection capabilities for dense objects. Experimental results indicate a substantial improvement in both the detection accuracy and speed of the enhanced algorithm compared to its original version. It is noteworthy that the enhanced algorithm exhibits a markedly improved detection performance for aerial images, particularly under real-time conditions.
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Background: Our study aimed to develop machine learning algorithms capable of predicting red blood cell (RBC) transfusion during valve replacement surgery based on a preoperative dataset of the non-anemic cohort. Methods: A total of 423 patients who underwent valvular replacement surgery from January 2015 to December 2020 were enrolled. A comprehensive database that incorporated demographic characteristics, clinical conditions, and results of preoperative biochemistry tests was used for establishing the models. A range of machine learning algorithms were employed, including decision tree, random forest, extreme gradient boosting (XGBoost), categorical boosting (CatBoost), support vector classifier and logistic regression (LR). Subsequently, the area under the receiver operating characteristic curve (AUC), accuracy, recall, precision, and F1 score were used to determine the predictive capability of the algorithms. Furthermore, we utilized SHapley Additive exPlanation (SHAP) values to explain the optimal prediction model. Results: The enrolled patients were randomly divided into training set and testing set according to the 8:2 ratio. There were 16 important features identified by Sequential Backward Selection for model establishment. The top 5 most influential features in the RF importance matrix plot were hematocrit, hemoglobin, ALT, fibrinogen, and ferritin. The optimal prediction model was CatBoost algorithm, exhibiting the highest AUC (0.752, 95% CI: 0.662-0.780), which also got relatively high F1 score (0.695). The CatBoost algorithm also showed superior performance over the LR model with the AUC (0.666, 95% CI: 0.534-0.697). The SHAP summary plot and the SHAP dependence plot were used to visually illustrate the positive or negative effects of the selected features attributed to the CatBoost model. Conclusions: This study established a series of prediction models to enhance risk assessment of intraoperative RBC transfusion during valve replacement in no-anemic patients. The identified important predictors may provide effective preoperative interventions.
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Metal-organic frameworks (MOFs) have been regarded as a potential candidate with great application prospects in the field of gas sensing. Although plenty of previous efforts have been made to improve the sensitivity of MOF-based nanocomposites, it is still a great challenge to realize ultrafast and high selectivity to typical flammable gases in a wide range. Herein, porous xPd-NPs@ZnO were prepared by optimized heat treatment, which maintained the controllable morphology and high specific surface area of 471.08 m2g-1. The coupling effects of photoexcitation and thermal excitation on the gas-sensing properties of nanocomposites were systematically studied. An ultrafast high response of 88.37 % towards 200 ppm H2 was realized within 1.2 s by 5.0Pd-NPs@ZnO under UV photoexcitation. All xPd-NPs@ZnO exhibited favorable linearity over an extremely wide range (0.2-4000 ppm H2) of experimental tests, indicating the great potential in quantitative detection. The photoexcited carriers enabled the nanocomposites a considerable response at lower operating temperatures, which made diverse applications of the sensors. The mechanisms of high sensing performances and the photoexcitation enhancement were systematically explained by DFT calculations. This work provides a solid experimental foundation and theoretical basis for the design of controllable porous materials and novel photoexcited gas detection.
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Heterodyne-based continuous-variable source-independent quantum random number generator (CV-SI-QRNG) can produce true random numbers without any assumptions on source. However, practical implementations always contain imperfections, which will greatly influence the extractable randomness and even open loopholes for eavesdroppers to steal information about the final output. In this work, based on the theoretical model, we systematically analyzed the effects of imperfect implementations on the practical security of heterodyne-based CV-SI-QRNG. The influences of local oscillator (LO) fluctuation under imbalanced heterodyne detection are first analyzed. The simulation results show that the lower bound of extractable randomness will be overestimated without considering the influence of LO fluctuation, which will threaten the practical security of CV-SI-QRNG system. Moreover, we analyze the effects of the degree of imbalance and the magnitude of LO fluctuation on evaluating the extractable randomness. Finally, we investigate the impact of an imperfect phase modulator on the practical security of CV-SI-QRNG and find it will reduce the extractable randomness. Our analysis reveals that one should carefully consider the imperfections in the actual implementations of CV-SI-QRNGs.
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Low-dimensional networked organic-inorganic hybrid metal halide crystal has become an emerging hotspot material due to its opportunities and advantages in the development of white-light-emitting diodes. Therefore, its photoluminescence (PL) mechanism is important. Herein, we study the PL behavior of columniform TPP2MnBr4 crystals using multi-spectroscopy. The temperature-dependent PL data show that the PL of the TPP2MnBr4 crystal originates from the recombination of a self-trapping exciton. A polarization-dependent PL test suggests that the self-trapping exciton is anisotropic, which indicates that the distribution of self-trapping states is sensitive to the orientation of the crystal axis. Space-resolved PL spectroscopy shows that the anisotropy of PL gradually weakens along the orientation of the columniform crystal, which has a longer relaxation distance than traditional light-wave-guiding behavior. Thus, anisotropy of PL can exist before it disappears in the crystal. Our results elucidate the PL mechanism of low-dimensional networked organic-inorganic hybrid metal halide crystals and provide a foundation for advanced optical polarization devices based on them.
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Compostos de Cálcio , Dispositivos Ópticos , Óxidos , TemperaturaRESUMO
In this paper, we consider the optimization of the quantum circuit for discrete logarithm of binary elliptic curves under a constrained connectivity, focusing on the resource expenditure and the optimal design for quantum operations such as the addition, binary shift, multiplication, squaring, inversion, and division included in the point addition on binary elliptic curves. Based on the space-efficient quantum Karatsuba multiplication, the number of CNOTs in the circuits of inversion and division has been reduced with the help of the Steiner tree problem reduction. The optimized size of the CNOTs is related to the minimum degree of the connected graph.
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Although coronary artery recanalization after myocardial infarction improves patient outcomes, inadequate ventricular remodeling following ischemia-reperfusion (IR) injury and secondary cardiac fibrosis (CF) are common and can lead to heart failure. MicroRNAs (miRNAs) play an important role in cardiovascular disorders. However, the underlying molecular mechanism of miRNAs in the occurrence and progression of CF has not been fully elucidated. Herein, through the construction of an I/R rat model and an angiotensin II-induced CF cell model, we evaluated the role of miR-375-3p in the progression of CF. In the I/R rat model and CF cell model, miR-375-3p promoted fibrosis by accelerating the ferroptosis of cardiomyocytes through mediating glutathione peroxidase 4 (GPX4). Furthermore, we treated the rats or cell model with miR-375-3p antagomir (or inhibitor) and ferroptosis inhibitor Ferrostatin-1 (Fer-1). The results showed that miR-375-3p antagomir (or inhibitor) and Fer-1 promoted the antioxidant capacity of cardiac fibroblasts, reduced GPX4-mediated ferroptosis process and alleviated I/R-induced CF. In conclusion, this study revealed that miR-375-3p directly targeted GPX4-an inhibitor of the ferroptosis pathway. Meanwhile, miR-375-3p can be a new potential biomarker for the prevention and treatment of CF.
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Ferroptose , MicroRNAs , Animais , Antagomirs , Ferroptose/genética , Fibrose , Coração , MicroRNAs/genética , RatosRESUMO
Acute pulmonary embolism (PE) remains a significant cause of cardiovascular morbidity and mortality worldwide. Brain natriuretic peptide (BNP) combined with catheter-directed therapy (CDT) may improve right ventricular (RV) dysfunction and stabilize hemodynamics in acute PE.We retrospectively studied 159 patients with confirmed acute PE who were treated with CDT and admitted to the intensive care unit of our department between September 2016 and May 2020. The patients were divided into the control group and the rhBNP group based on whether to receive recombinant human BNP treatment (rhBNP) or not. The basic characteristics of the patients between the control group and the rhBNP group was systematically compared during admission and follow-up. Risk factors for all-cause mortality within 30 days were determined using multivariate logistic regression analysis.Respiratory rate was found to be significantly lower in the rhBNP group than in the control group. Patients in the rhBNP group had significantly lower levels of white blood cell, C-reactive protein (CRP), D-dimers, troponin I, creatinine, and N-terminal (NT) -proBNP compared with those in the control group. Levels of tricuspid annular plane systolic excursion were significantly higher in the rhBNP group than in the control group. The percentage of patients with rehospitalization readmission due to PE differed significantly between the control group and the rhBNP group. On the basis of the multivariate regression analysis, CRP, creatinine, troponin I, and NT-proBNP were independent factors of all-cause mortality in 30 days.rhBNP is effective in the treatment of patients with RV dysfunction caused by acute PE who underwent CDT, which may be an alternative treatment option for improving clinical prognosis.
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Cateterismo de Swan-Ganz , Natriuréticos/uso terapêutico , Peptídeo Natriurético Encefálico/uso terapêutico , Embolia Pulmonar/terapia , Disfunção Ventricular Direita/tratamento farmacológico , Doença Aguda , Idoso , Feminino , Humanos , Masculino , Trombólise Mecânica , Pessoa de Meia-Idade , Embolia Pulmonar/complicações , Embolia Pulmonar/diagnóstico , Proteínas Recombinantes , Estudos Retrospectivos , Terapia Trombolítica , Resultado do Tratamento , Disfunção Ventricular Direita/diagnóstico , Disfunção Ventricular Direita/etiologiaRESUMO
The variational quantum algorithm (VQA) is a hybrid classical-quantum algorithm. It can actually run in an intermediate-scale quantum device where the number of available qubits is too limited to perform quantum error correction, so it is one of the most promising quantum algorithms in the noisy intermediate-scale quantum era. In this paper, two ideas for solving the learning with errors problem (LWE) using VQA are proposed. First, after reducing the LWE problem into the bounded distance decoding problem, the quantum approximation optimization algorithm (QAOA) is introduced to improve classical methods. Second, after the LWE problem is reduced into the unique shortest vector problem, the variational quantum eigensolver (VQE) is used to solve it, and the number of qubits required is calculated in detail. Small-scale experiments are carried out for the two LWE variational quantum algorithms, and the experiments show that VQA improves the quality of the classical solutions.
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Quantum random number generator (QRNG) relies on the intrinsic randomness of quantum mechanics to produce true random numbers which are important in information processing tasks. Due to the presence of the superposition state, a quantum computer can be used as a true random number generator. However, in practice, the implementation of the quantum computer is subject to various noise sources, which affects the randomness of the generated random numbers. To solve this problem, we propose a scheme based on the quantum computer which is motivated by the source-independent QRNG scheme in optics. By using a method to estimate the upper bound of the superposition state preparation error, the scheme can provide certified randomness in the presence of readout errors. To increase the generation rate of random bits, we also provide a parameter optimization method with a finite data size. In addition, we experimentally demonstrate our scheme on the cloud superconducting quantum computers of IBM.
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The Src homology-2 domain containing-protein tyrosine phosphatase-2 (SHP2) is a convergent node for oncogenic cell-signaling cascades including the PD-L1/PD-1 pathway. As an oncoprotein as well as a potential immunomodulator, SHP2 has now emerged as an attractive target for novel anti-cancer agents. Although significant progress has been made in identifying chemotypes of SHP2 inhibitors, these specific compounds might not be clinically useful to inhibit frequently encountered mutated SHP2 variants. Consequently, it is highly desirable to develop chemically different SHP2 inhibitors sensitive to SHP2 mutants. This work developed a new type of SHP2 inhibitors with 2,5-diaryl-1,3,4-oxadiazole scaffold. The representative compound 6l exhibited SHP2 inhibitory activity with IC50 of 2.73 ± 0.20 µM, showed about 1.56-fold, 5.26-fold, and 7.36-fold selectivity for SHP2 over SHP1, PTP1B and TCPTP respectively. Further investigations confirmed that 6l behaved as mixed-type inhibitor sensitive to leukemia cell TF-1 and inhibited SHP2 mediated cell signaling and proliferation. Molecular dynamics simulation provided more detailed information on the binding modes of compounds and SHP2 protein. These preliminary results could provide a possible opportunity for the development of novel SHP2 inhibitors sensitive to SHP2 mutants with optimal potency and improved pharmacological properties.
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Antineoplásicos/farmacologia , Inibidores Enzimáticos/farmacologia , Oxidiazóis/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 11/antagonistas & inibidores , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Humanos , Simulação de Dinâmica Molecular , Estrutura Molecular , Oxidiazóis/síntese química , Oxidiazóis/química , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo , Relação Estrutura-AtividadeRESUMO
The large-scale exchange and spread of traditional Chinese medicine (TCM) in the West began in the 17th century. From the first English Chinese medicine book "gout collection" published in London in 1676, the British began to understand the mysterious and ancient oriental medicine of TCM. Britain is one of the earliest countries where TCM began to spread. TCM is an important carrier of China's excellent traditional culture. With the development of the world's medical technology and the continuous improvement of China's cultural soft power, the cross-cultural communication of TCM has become a characteristic business card for China to go to the world. For the research of a work, we must start from the source, so it is very important to first count the history of TCM external communication, and then systematically analyze and study the various phenomena in this history, so as to summarize the experience and inadequacy of TCM external communication process, and provide feasible guidance for future TCM research, And promote the effective development of TCM, and ultimately spread TCM culture to the international community more comprehensively and accurately. Although the greater than 300 hundred years' history of traditional Chinese medicine (TCM) spreading throughout Britain has been continuously mentioned in literature, studies on the historical development of TCM in Britain are rare. In this paper, the authors gathered information including the chronological statistics and stages of the 300 hundred years' dissemination of TCM in Britain, in order to provide more historical data and research materials for the spread of Chinese medicine in Britain.
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Comunicação , Medicina Tradicional Chinesa , China , LondresRESUMO
The aim of the present study was to investigate the neuroprotective effects of naringin on the memory impairment of hydrocortisone mice, and to elucidate the potential underlying molecular mechanisms. In the present study, a hydrocortisone model was constructed. Novel object recognition, Morris water maze and stepdown tests were performed in order to assess the learning and memory abilities of mice. Hematoxylin and eosin staining was used to observe pathological changes in the hippocampus and hypothalamus. Transmission electron microscopy was used to observe the ultrastructural changes in the hippocampus. Immunohistochemistry was used to detect the expression of ERα and ERß. Western blotting was performed to detect the expression of each protein in the relevant system. It was found that naringin can significantly improve cognitive, learning and memory dysfunction in mice with hydrocortisone memory impairment. In addition, naringin can exert neuroprotective effects through a variety of mechanisms, including amyloid ß metabolism, Tau protein hyperphosphorylation, acetylcholinergic system, glutamate receptor system, oxidative stress and cell apoptosis. Naringin can also affect the expression of phosphorylatedP38/P38, indicating that the neuroprotective effect of naringin may also involve the MAPK/P38 pathway. The results of the present study concluded that naringin can effectively improve the cognitive abilities of mice with memory impairment and exert neuroprotective effects. Thus, naringin may be a promising target drug candidate for the treatment of Alzheimer's disease.
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Doença de Alzheimer/tratamento farmacológico , Flavanonas/farmacologia , Transtornos da Memória/tratamento farmacológico , Proteínas tau/genética , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Animais , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Humanos , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/genética , Transtornos da Memória/patologia , Redes e Vias Metabólicas/efeitos dos fármacos , Camundongos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/genéticaRESUMO
Herein, we report a dia-type metal-organic hybrid network based on the [Ag4Br6] clusters and hexamethylenetetramine molecules wherein both the inorganic nodes and organic linkers feature adamantane-like geometry with a Td symmetry. The silver bromine complex presents a dual emission and exhibits an interesting luminescent thermochromism behavior. Remarkably, white-light emission can be readily realized through variation of the temperature. In addition, the title compound is expected to be competent as a luminescent thermometer for temperature identification.
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BACKGROUND: This study aims to appraise the clinical efficacy of traditional Chinese medicine (TCM) for the management of patients with primary dysmenorrhea (PD) in the UK. METHODS: We will comprehensively search electronic databases (Cochrane Library, PUBMED/MEDLINE, EMBASE, PsycINFO, AMED, Web of Science, and CNKI) and additional resources for original articles on randomized controlled trials published in English, Chinese, German, Spanish, Korean and Japanese. Outcomes will be the pain intensity, pain duration, menstrual cramps, amount of bleeding, and severity of dysmenorrhea symptoms, quality of life, and adverse events. Two authors will independently check all citations, extract data, and assess study quality. All potential conflicts will be solved through discussion by consulting another experienced author. A narrative synthesis will summarize the characteristics and findings of eligible trials. If it is possible, we will also pool the data and carry out meta-analysis. RESULTS: The available evidence of the clinical efficacy of TCM for the treatment of PD in UK will be assessed through outcome measurements. CONCLUSION: The findings of this study will determine whether or not TCM is effective and safe for the treatment of PD in UK. OSF REGISTRATION NUMBER:: osf.io/jyc95.
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Dismenorreia/terapia , Medicina Tradicional Chinesa , Feminino , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Reino UnidoRESUMO
RATIONALE: Polymyxin B has been used to treat extensively drug-resistant gram-negative bacteria and shown a better antibacterial effect in the clinic at present. Meanwhile, polymyxin B is associated with several adverse effects. However, there is a lack of awareness that polymyxin B can cause rhabdomyolysis. In this study, we firstly report a case of polymyxin B-induced rhabdomyolysis during antiinfection therapy. PATIENT CONCERNS: A 70-year-old woman suffering from rheumatic heart disease underwent aortic and mitral valve replacement at our institute. Subsequently, she developed bacteremia and pneumonia caused by extensively drug resistance-acinetobacter baumannii. Polymyxin B was administered for 5 days. During treatment, the patient complained of muscle pain and limb weakness, and her serum creatine phosphokinase and myoglobin levels rose. DIAGNOSIS: The clinical symptoms and laboratory examination confirmed rhabdomyolysis, and polymyxin B-induced rhabdomyolysis was considered. INTERVENTION: We ceased polymyxin B treatment and monitored the patient daily. OUTCOMES: Serum creatine phosphokinase levels returned to normal, myoglobin levels decreased, and muscle pain was significantly alleviated after cessation of polymyxin B. We identified this as a case of polymyxin B-induced rhabdomyolysis. LESSONS: Here, we report the first reported case of rhabdomyolysis induced by polymyxin B administration. The awareness of rare adverse reaction helps ensure the clinical safety of polymyxin B treatment.
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Antibacterianos/efeitos adversos , Polimixina B/efeitos adversos , Rabdomiólise/induzido quimicamente , Acinetobacter baumannii/isolamento & purificação , Idoso , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Conscientização , Bacteriemia/tratamento farmacológico , Creatina Quinase/sangue , Feminino , Humanos , Debilidade Muscular/etiologia , Mialgia/etiologia , Mioglobina/sangue , Pneumonia/tratamento farmacológico , Pneumonia/microbiologia , Polimixina B/administração & dosagem , Polimixina B/uso terapêutico , Rabdomiólise/diagnóstico , Suspensão de TratamentoRESUMO
BACKGROUND: Postoperative hypoxemia in acute type A aortic dissection (AADA) is a common complication and is associated with negative outcomes. This study aimed to analyze the efficacy of low-dose (5-10 ppm) inhaled nitric oxide (iNO) in the management of hypoxemia after AADA surgery. METHODS: In this retrospective observational study, Medical records of patients who underwent AADA surgery at two institutions between January 2015 and January 2018 were collected. Patients with postoperative hypoxemia were classified as iNO and control groups. Clinical characteristics and outcomes were compared using a propensity score-matched (PSM) analysis. RESULTS: Among 436 patients who underwent surgical repair, 187 (42.9%) had hypoxemia and 43 were treated with low-dose iNO. After PSM, patients were included in the iNO treatment (n = 40) and PSM control (n = 94) groups in a 1:3 ratio. iNO ameliorated hypoxemia at 6, 24, 48, and 72 h after initiation, and shortened the durations of ventilator support (39.0 h (31.3-47.8) vs. 69.0 h (47.8-110.3), p < 0.001) and ICU stay (122.0 h (80.8-155.0) vs 179.5 h (114.0-258.0), p < 0.001). There were no significant between-group differences in mortality, complications, or length of hospital stay. CONCLUSIONS: In this study, we found that low-dose iNO improved oxygenation in patients with hypoxemia after AADA surgery and shortened the durations of mechanical ventilation and ICU stay. No significant side effects or increase in postoperative mortality or morbidities were observed with iNO treatment. These findings warrant a randomized multicenter controlled trial to assess the exact efficiency of iNO for hypoxemia after AADA.
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Dissecção Aórtica/cirurgia , Broncodilatadores/administração & dosagem , Procedimentos Cirúrgicos Cardiovasculares/efeitos adversos , Hipóxia/tratamento farmacológico , Óxido Nítrico/administração & dosagem , Administração por Inalação , Adulto , Dissecção Aórtica/complicações , Cuidados Críticos , Feminino , Humanos , Hipóxia/etiologia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/tratamento farmacológico , Pontuação de Propensão , Respiração Artificial , Estudos RetrospectivosRESUMO
Atherosclerosis is a disorder occurring in the large arteries and the primary cause of heart diseases. Accumulating evidence has implicated long non-coding RNAs (lncRNAs) in atherosclerosis. This study aims to clarify the potential effects of lncRNA growth arrest-specific 5 (GAS5) on cholesterol reverse-transport and intracellular lipid accumulation in atherosclerosis. GAS5 was mainly localized in the nucleus and highly expressed in the human monocytic leukemia cell line (THP-1) macrophage-derived foam cells in coronary heart disease. Overexpressed GAS5 increased THP-1 macrophage lipid accumulation. Of note, GAS5 can inhibit the expression of ATP-binding cassette transporter A1 (ABCA1) by binding to enhancer of zeste homolog 2 (EZH2). Overexpression of EZH2 reduced cholesterol efflux and ABCA1 expression. EZH2 promoted triple methylation of lysine 27 (H3K27) in the ABCA1 promoter region. Subjected to overexpressed GAS5, overexpressed EZH2, or downregulated ABCA1, the Apolipoprotein E (ApoE)-/- mice with atherosclerosis showed increased total cholesterol (TC), free cholesterol (FC), cholesterol ester (CE), low-density lipoprotein (LDL) levels, aortic plaque, and lipid accumulation, accompanied by reduced high-density lipoprotein (HDL) level and cholesterol outflow. Altogether, knockdown of GAS5 can potentially promote reverse-transportation of cholesterol and inhibit intracellular lipid accumulation, ultimately preventing the progression of atherosclerosis via reducing EZH2-mediated transcriptional inhibition of ABCA1 by histone methylation.
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Mitochondrial dynamic disorder is involved in myocardial ischemia/reperfusion (I/R) injury. To explore the effect of mitochondrial calcium uniporter (MCU) on mitochondrial dynamic imbalance under I/R and its related signal pathways, a mouse myocardial I/R model and hypoxia/reoxygenation model of mouse cardiomyocytes were established. The expression of MCU during I/R increased and related to myocardial injury, enhancement of mitochondrial fission, inhibition of mitochondrial fusion and mitophagy. Suppressing MCU functions by Ru360 during I/R could reduce myocardial infarction area and cardiomyocyte apoptosis, alleviate mitochondrial fission and restore mitochondrial fusion and mitophagy. However, spermine administration, which could enhance MCU function, deteriorated the above-mentioned myocardial cell injury and mitochondrial dynamic imbalanced. In addition, up-regulation of MCU promoted the expression and activation of calpain-1/2 and down-regulated the expression of Optic atrophy type 1 (OPA1). Meantime, in transgenic mice (overexpression calpastatin, the endogenous inhibitor of calpain) I/R model and OPA1 knock-down cultured cell. In I/R models of transgenic mice over-expressing calpastatin, which is the endogenous inhibitor of calpain, and in H/R models with siOPA1 transfection, inhibition of calpains could enhance mitochondrial fusion and mitophagy, and inhibit excessive mitochondrion fission and apoptosis through OPA1. Therefore, we conclude that during I/R, MCU up-regulation induces calpain activation, which down-regulates OPA1, consequently leading to mitochondrial dynamic imbalance.