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This paper proposes a phase-only modulation method to improve the main lobe's efficiency of the Airy beam based on the truncated asymptotic expression of the Airy function. As the truncated asymptotic expression can greatly reduce the range of amplitude modulation, it can be applied to the equal-amplitude modulation method with less amplitude error, which simplifies the design difficulty of the device and improves the beam's efficiency. A transmissive metasurface with a relative bandwidth of 10% is further adapted to generate the Airy beam with characteristics of non-diffraction, self-bending, and high-efficiency, which benefits the practical application of the Airy beam.
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We experimentally and numerically propose an approach for implementing spike-based neuromorphic exclusive OR (XOR) operation using a single vertical-cavity semiconductor optical amplifier (VCSOA). XOR operation is realized based on the neuron-like inhibitory dynamics of the VCSOA subject to dual-polarized pulsed optical injections. The inhibitory dynamics based on the polarization-mode competition effect are analyzed, and the inhibitory response can be obtained in a suitable range of wavelength detuning. Here, all input and output bits are represented by spikes that are compatible with the photonic spiking neural network. The experimental and numerical results show that XOR operation can be realized in two polarization modes by adjusting the time offset in the inhibitory window and setting defined reference thresholds. In addition, the influences of delay time and input intensity ratio on XOR operation are studied experimentally. This scheme is energy efficient because VCSOA neuromorphic photonics computing and information processing.
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Redes Neurales de la Computación , Semiconductores , Óptica y Fotónica , FotonesRESUMEN
BACKGROUND: The peak inspiratory pressure (PIP) is crucial in mechanical ventilation with supraglottic airway device (SAD). Pressure-controlled ventilation volume-guaranteed (PCV-VG), delivering a preset tidal volume with the lowest required airway pressure, is being increasingly used during general anesthesia. In this study, we compared respiratory mechanics and circulatory parameters between volume-controlled ventilation (VCV) and PCV-VG in elderly patients undergoing laparoscopic surgery using the laryngeal mask airway supreme (LMA). METHODS: Eighty participants scheduled for laparoscopic surgery were enrolled in this prospective, randomized clinical trial. The participants were randomly assigned to receive VCV or PCV-VG. PIP, dynamic compliance (Cdyn) and mean inspiratory pressure (Pmean) were recorded at 5 min after induction of anesthesia (T1), 5 min after pneumoperitoneum(T2), 30 and 60 min after pneumoperitoneum (T3 and T4). Data including other respiratory variables, hemodynamic variables, and arterial blood gases were also collected. The difference in PIP between VCV and PCV-VG was assessed as the primary outcome. RESULTS: PIP was significantly lower at T2, T3, and T4 in both groups compared with T1 (all P < 0.0001), and it was significantly lower in the PCV-VG group than the VCV group at T2, T3, and T4 (all P < 0.001). Cydn was decreased at T2, T3, and T4 in two groups compared with T1 (all P < 0.0001), but it was higher in PCV-VG group than in VCV group at T2, T3, and T4 (all P < 0.0001). There were on statistically significant differences were found between the groups for other respiratory and hemodynamic variables. CONCLUSION: In elderly patients who underwent laparoscopic surgery using an LMA, PCV-VG was superior to VCV in its ability to provide ventilation with lower peak inspiratory pressure and greater dynamic compliance.
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Evaluación Geriátrica/métodos , Laparoscopía , Máscaras Laríngeas , Presiones Respiratorias Máximas/métodos , Respiración Artificial/instrumentación , Respiración Artificial/métodos , Anciano , Femenino , Humanos , Masculino , Estudios Prospectivos , Mecánica Respiratoria/fisiología , Volumen de Ventilación Pulmonar/fisiologíaRESUMEN
BACKGROUND: Dexmedetomidine is known to be a sedative. Recent studies suggest that administration of dexmedetomidine can prevent postoperative delirium (POD) which has been confirmed as a common complication after major surgery. However, its effects in patients undergoing oesophagectomy are scarce. OBJECTIVE: To investigate the efficacy and safety of dexmedetomidine in reducing POD in elderly patients after transthoracic oesophagectomy with total intravenous anaesthesia (TIVA). DESIGN: A randomised, double-blind, placebo-controlled trial. SETTING: Single-centre, tertiary care hospital, November 2016 to September 2018. PATIENTS: Eligible patients (nâ=â177) undergoing transthoracic oesophagectomy were randomly assigned to receive total intravenous anaesthesia (TIVA, nâ=â87) or dexmedetomidine with TIVA (DEX-TIVA, nâ=â90). INTERVENTIONS: Patients receiving DEX-TIVA received a loading dose of dexmedetomidine (0.4âµgâkg-1), over 15âmin, followed by a continuous infusion at a rate of 0.1âµgâkg-1âh-1 until 1âh before the end of surgery. Patients receiving TIVA received physiological saline with a similar infusion rate protocol. OUTCOME MEASURES: The primary outcome was the incidence of POD. The secondary endpoints were the incidence of emergence agitation, serum interleukin-6 (IL-6) levels and haemodynamic profile. RESULTS: All randomised patients were included with planned intention-to-treat analyses for POD. Delirium occurred in 15 (16.7%) of 90 cases given dexmedetomidine, and in 32 (36.8%) of 87 cases given saline (Pâ=â0.0036). The DEX-TIVA group showed less frequent emergence agitation than the TIVA group (22.1 vs. 48.0%, Pâ=â0.0058). The incremental change in surgery-induced IL-6 levels was greater in the TIVA group than DEX-TIVA group (Pâ<â0.0001). CONCLUSION: Adding peri-operative dexmedetomidine to a total intravenous anaesthetic safely reduces POD and emergence agitation in elderly patients undergoing open transthoracic oesophagectomy. These benefits were associated with a postoperative reduction in circulating levels of the pro-inflammatory cytokine IL-6 and stabilisation of the haemodynamic profile. TRIAL REGISTRATION: Chinese Clinical Trials Register Identifier: ChiCTR-IPR-17010881.
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Delirio , Dexmedetomidina , Anciano , Anestesia Intravenosa , Delirio/epidemiología , Delirio/prevención & control , Método Doble Ciego , Esofagectomía/efectos adversos , Humanos , Hipnóticos y Sedantes/efectos adversosRESUMEN
Cellular senescence is a key factor driving age-related diseases. Recent studies have revealed that senescence-associated secretory phenotype, telomere attrition, epigenetic changes, and mitochondrial autophagy damage may mediate the pathogenesis of senescence-related idiopathic pulmonary fibrosis (IPF). Reducing the level of cellular senescence or clearing senescent cells can down-regulate the expression of fibrosis factors and alleviate the symptoms of IPF. In this review, we outlined the role and mechanism of cellular senescence in IPF.
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Senescencia Celular , Fibrosis Pulmonar Idiopática , Autofagia , Epigénesis Genética , Expresión Génica , Humanos , Fibrosis Pulmonar Idiopática/fisiopatologíaRESUMEN
Diabetes is a major health problem worldwide. As well-known, diabetes greatly increases cardiac vulnerability to ischemia/reperfusion (I/R) injury, but the underlying mechanisms remain elusive. Nucleostemin (NS) is a nucleolar protein that controls ribosomal biogenesis and exerts cardioprotective effects against I/R injury. However, whether NS-mediated ribosomal biogenesis regulates ischemic vulnerability of diabetic hearts remains unanswered. Utilizing myocardial I/R mouse models, we found that cardiac NS expression significantly increased in response to I/R in normal diet (ND)-fed mice. Surprisingly, cardiac NS failed to be upregulated in high fat diet (HFD)-induced diabetic mice, accompanied by obvious ribosomal dysfunction. Compared with ND group, cardiac specific overexpression of NS by adenovirus (AV) injection significantly restored I/R-induced ribosomal function enhancement, reduced cardiomyocyte apoptosis, improved cardiac function, and decreased infarct sizes in diabetic mice. Notably, co-treatment of homoharringtonine (HHT), a selective inhibitor of ribosomal function, totally blocked NS-mediated cardioprotective effects against I/R injury. Furthermore, in cultured cardiomyocytes, saturated fatty acids treatment, but not high glucose exposure, significantly inhibited simulated I/R-induced NS upregulation and ribosomal function improvement. In conclusion, these data for the first time demonstrate that NS dysregulation induced by saturated fatty acids exposure might be an important cause of increased ischemic vulnerability to I/R injury in diabetic hearts. Targeting NS dysregulation and subsequent ribosomal dysfunction could be a promising therapeutic strategy for diabetic I/R injury management.
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Proteínas Portadoras/metabolismo , Complicaciones de la Diabetes , Isquemia Miocárdica/etiología , Isquemia Miocárdica/metabolismo , Proteínas Nucleares/metabolismo , Animales , Apoptosis , Proteínas Portadoras/genética , Línea Celular , Células Cultivadas , Diabetes Mellitus Experimental , Proteínas de Unión al GTP , Expresión Génica , Masculino , Ratones , Infarto del Miocardio/etiología , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Isquemia Miocárdica/patología , Daño por Reperfusión Miocárdica/etiología , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Miocitos Cardíacos/metabolismo , Proteínas Nucleares/genética , Proteínas de Unión al ARN , Ribosomas/metabolismoRESUMEN
Activation of κ-opioid receptor (KOR) ameliorates myocardial ischemia/reperfusion (I/R) injury; however, cardioprotective effects of KOR stimulation disappear in type 1 diabetic subjects with hyperglycemia. The molecular mechanisms underlying this phenomenon remain unknown. Here we found that KOR expression was obviously downregulated and KOR agonism-induced contractile-regulatory and cardioprotective effects were significantly impaired in hearts isolated from streptozotocin (STZ) injection-induced diabetic mice. These in vivo data identified cardiac KOR desensitization as a novel characteristic of the diabetic heart. In cultured cardiomyocytes, high glucose (HG) caused obvious KOR downregulation, accompanied by an upregulation of G protein coupled receptor kinase-2 (GRK2). We found that HG exposure increased the interaction between GRK2 and KOR. More importantly, HG-induced KOR downregulation was reversed by small interfering RNA (siRNA)-mediated GRK2 inhibition. GRK2 knockdown also restored KOR agonism-mediated protection against simulated I/R injury in cardiomyocytes. These in vitro data revealed an essential role of GRK2 in HG-induced KOR desensitization. Finally, cardiac-specific GRK2 knockdown by intramyocardial siRNA injection blocked KOR downregulation and restored contractile-regulatory and cardioprotective effects of KOR agonism in hearts of diabetic mice. In conclusion, these data for the first time demonstrate that GRK2 upregulation is largely responsible for cardiac KOR desensitization in diabetic individuals, which provides novel insights into the management of myocardial I/R injury in patients with diabetes.
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Diabetes Mellitus/metabolismo , Quinasa 2 del Receptor Acoplado a Proteína-G/metabolismo , Corazón/fisiología , Miocardio/metabolismo , Receptores Opioides kappa/metabolismo , Regulación hacia Arriba , Analgésicos Opioides/química , Animales , Apoptosis , Línea Celular , Regulación hacia Abajo , Glucosa/química , Masculino , Ratones , Ratones Endogámicos C57BL , Contracción Miocárdica , Infarto del Miocardio/metabolismo , Miocitos Cardíacos/metabolismo , Fosforilación , ARN Interferente Pequeño/metabolismo , Ratas , Daño por Reperfusión , EstreptozocinaRESUMEN
Cardiac metabolic remodeling is a central event during heart failure (HF) development following myocardial infarction (MI). It is well known that myocardial glucose and fatty acid dysmetabolism contribute to post-MI cardiac dysfunction and remodeling. However, the role of amino acid metabolism in post-MI HF remains elusive. Branched chain amino acids (BCAAs) are an important group of essential amino acids and function as crucial nutrient signaling in mammalian animals. The present study aimed to determine the role of cardiac BCAA metabolism in post-MI HF progression. Utilizing coronary artery ligation-induced murine MI models, we found that myocardial BCAA catabolism was significantly impaired in response to permanent MI, therefore leading to an obvious elevation of myocardial BCAA abundance. In MI-operated mice, oral BCAA administration further increased cardiac BCAA levels, activated the mammalian target of rapamycin (mTOR) signaling, and exacerbated cardiac dysfunction and remodeling. These data demonstrate that BCAAs act as a direct contributor to post-MI cardiac pathologies. Furthermore, these BCAA-mediated deleterious effects were improved by rapamycin cotreatment, revealing an indispensable role of mTOR in BCAA-mediated adverse effects on cardiac function/structure post-MI. Of note, pharmacological inhibition of branched chain ketoacid dehydrogenase kinase (BDK), a negative regulator of myocardial BCAA catabolism, significantly improved cardiac BCAA catabolic disorders, reduced myocardial BCAA levels, and ameliorated post-MI cardiac dysfunction and remodeling. In conclusion, our data provide the evidence that impaired cardiac BCAA catabolism directly contributes to post-MI cardiac dysfunction and remodeling. Moreover, improving cardiac BCAA catabolic defects may be a promising therapeutic strategy against post-MI HF.
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3-Metil-2-Oxobutanoato Deshidrogenasa (Lipoamida)/metabolismo , Aminoácidos de Cadena Ramificada/metabolismo , Insuficiencia Cardíaca/metabolismo , Infarto del Miocardio/metabolismo , Miocardio/metabolismo , Disfunción Ventricular Izquierda/metabolismo , Remodelación Ventricular , Animales , Western Blotting , Vasos Coronarios/cirugía , Ecocardiografía , Ácidos Grasos/metabolismo , Glucosa/metabolismo , Insuficiencia Cardíaca/etiología , Etiquetado Corte-Fin in Situ , Ligadura , Masculino , Ratones , Infarto del Miocardio/complicaciones , Péptido Natriurético Encefálico/metabolismo , Proteínas Quinasas/metabolismo , Proteína Fosfatasa 2C/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Disfunción Ventricular Izquierda/etiologíaRESUMEN
Sphingosine 1-phosphate (S1P) mediates multiple pathophysiological effects in the cardiovascular system. However, the role of S1P signaling in pathological cardiac remodeling following myocardial infarction (MI) remains controversial. In this study, we found that cardiac S1P greatly increased post-MI, accompanied with a significant upregulation of cardiac sphingosine kinase-1 (SphK1) and S1P receptor 1 (S1PR1) expression. In MI-operated mice, inhibition of S1P production by using PF543 (the SphK1 inhibitor) ameliorated cardiac remodeling and dysfunction. Conversely, interruption of S1P degradation by inhibiting S1P lyase augmented cardiac S1P accumulation and exacerbated cardiac remodeling and dysfunction. In the cardiomyocyte, S1P directly activated proinflammatory responses via a S1PR1-dependent manner. Furthermore, activation of SphK1/S1P/S1PR1 signaling attributed to ß1-adrenergic receptor stimulation-induced proinflammatory responses in the cardiomyocyte. Administration of FTY720, a functional S1PR1 antagonist, obviously blocked cardiac SphK1/S1P/S1PR1 signaling, ameliorated chronic cardiac inflammation, and then improved cardiac remodeling and dysfunction in vivo post-MI. In conclusion, our results demonstrate that cardiac SphK1/S1P/S1PR1 signaling plays an important role in the regulation of proinflammatory responses in the cardiomyocyte and targeting cardiac S1P signaling is a novel therapeutic strategy to improve post-MI cardiac remodeling and dysfunction.
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Cardiopatías/patología , Lisofosfolípidos/fisiología , Infarto del Miocardio/patología , Miocarditis/patología , Esfingosina/análogos & derivados , Animales , Animales Recién Nacidos , Citocinas/biosíntesis , Clorhidrato de Fingolimod/farmacología , Cardiopatías/diagnóstico por imagen , Masculino , Ratones , Ratones Endogámicos C57BL , Infarto del Miocardio/diagnóstico por imagen , Miocarditis/diagnóstico por imagen , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Fosfotransferasas (Aceptor de Grupo Alcohol)/antagonistas & inhibidores , Fosfotransferasas (Aceptor de Grupo Alcohol)/biosíntesis , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , ARN Interferente Pequeño/genética , Ratas Sprague-Dawley , Receptores de Lisoesfingolípidos/antagonistas & inhibidores , Receptores de Lisoesfingolípidos/biosíntesis , Receptores de Lisoesfingolípidos/genética , Transducción de Señal , Esfingosina/fisiología , Receptores de Esfingosina-1-Fosfato , Transfección , UltrasonografíaRESUMEN
Composting is widely adopted in livestock waste management, and the ventilation system control is essential for composting efficiency. For ventilation system, the airflow resistance is a major factor influencing the ventilation intensity and oxygen supply capacity. This study explored the variation law of airflow resistance, bulk density, specific gravity, particle size and total pressure throughout composting with cattle manure. The airflow resistance was calculated with Ergun equation, and contribution coefficients of different components were analyzed with principal component analysis (PCA). Results showed that the viscous airflow resistance was dominant throughout cattle manure composting. The average airflow resistance was 0.146 Pa/m, and resistance of pile at lower layer was higher than that at the upper layer by 18.1 %. For contribution coefficient affecting airflow resistance, the ranks were bulk density, average particle size and specific gravity. During composting process, the average airflow resistance decreased by 40.1 % and the total pressure reduced by 3.47 %. All parameters had the greatest variation at thermophilic phase, which accounted for more than 60 % of the total variation amplitude. Meanwhile, less than 10 % of the total pressure was used to overcome the airflow resistance. Therefore, reducing bulk density of pile should be considered preferentially to decrease the airflow resistance. During cattle manure composting process, the total pressure of ventilation system ought to be adjusted with the aerobic reaction to a lower level, especially at thermophilic phase with the most rapid descent rate. This study can provide support for reducing the energy consumption required for ventilation of composting.
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Compostaje , Administración de Residuos , Bovinos , Animales , Estiércol/análisis , Administración de Residuos/métodos , Ganado , SueloRESUMEN
Baihe Gujin decoction is one of the most commonly used decoction in traditional Chinese medicine for the treatment of lung cancer. It can nourish yin and moisten the lung as well as prevent phlegm from forming and stop coughing. On the one hand, Baihe Gujin decoction is characterized with extensive application, proven efficacy, a long history, and high safety. On the other hand, Baihe Gujin decoction can induce apoptosis of tumor cells, improve immune function and inhibit inflammation. The main anti-tumor components of this include kaempferol, quercetin, isorhamnetin, glycyrrhizin and ß-sitosterol. Clinically, Baihe Gujin decoction can improve the adverse reactions caused by radiotherapy, chemotherapy and immunotherapy for lung cancer, enhance the quality of life of patients, and prolong their survival time. At present, there are a large number of clinical and basic researches on the treatment of lung cancer with Baihe Gujin decoction. In this paper, we mainly discussed the treatment of lung cancer with Baihe Gujin decoction through analyzing basic and clinical researches at home and abroad in the past 20 years. Through the discussion, we aimed to probe deeper into Baihe Gujin decoction for the treatment of lung cancer, thereby providing a broader idea for clinical diagnosis and treatment of lung cancer.
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Anti-punching drilling robot (APDR) is the key equipment for underground rock burst relief in coal mine and the accurate position and attitude determination is the basis and premise for realizing unmanned pressure relief operation. In this paper, a novel positioning method of APDR based on spatial array inertial measurement units (IMUs) and visual image is proposed. Firstly, the spatial array layout of multiple IMUs is displayed creatively, and the data fusion model and the posture calculation process of spatial array IMUs are constructed. The superiority of proposed spatial array IMUs is verified through the motion trajectory simulation analysis and mobile carrier simulation experiments. Then, an image enhancement method (SSR-AF) is designed to overcome the problems of atomization, glare, uneven illumination and noise interference in coal mine images, so as to improve the accuracy of image feature extraction and matching. Accordingly, the positioning estimation model based on continuous frame images is established. Furthermore, the fusion positioning process of APDR is presented by using the loose coupling mode based on Kalman filtering algorithm. The position and attitude monitoring experimental platform of APDR is built in a simulated coal mine tunnel. The experimental results indicate that the calculation errors of displacement and attitude based on the proposed fusion positioning method is superior to the competing methods, which meet the actual positioning requirements, and verify the feasibility and practicability of the proposed positioning method for APDR.
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Aging is a major risk factor for many age-associated disorders, including neurodegenerative diseases. Both mitochondrial dysfunction and proteostatic decline are well-recognized hallmarks of aging and age-related neurodegeneration. Despite a lack of therapies for neurodegenerative diseases, a number of interventions promoting mitochondrial integrity and protein homeostasis (proteostasis) have been shown to delay aging-associated neurodegeneration. For example, many antioxidant polysaccharides are shown to have pharmacological potentials in Alzheimer's, Parkinson's and Huntington's diseases through regulation of mitochondrial and proteostatic pathways, including oxidative stress and heat shock responses. However, how mitochondrial and proteostatic mechanisms work together to exert the antineurodegenerative effect of the polysaccharides remains largely unexplored. Interestingly, recent studies have provided a growing body of evidence to support the crosstalk between mitostatic and proteostatic networks as well as the impact of the crosstalk on neurodegeneration. Here we summarize the recent progress of antineurodegenerative polysaccharides with particular attention in the mitochondrial and proteostatic context and provide perspectives on their implications in the crosstalk along the mitochondria-proteostasis axis.
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Antioxidantes , Proteostasis , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Estrés Oxidativo , Mitocondrias , Polisacáridos/uso terapéuticoRESUMEN
N6-methyladenosine (m6A) is one of the most important RNA modifications, which is involved in many biological activities. Computational methods have been developed to detect m6A sites due to their high efficiency and low costs. As one of the most widely utilized model organisms, many methods have been developed for predicting m6A sites of Saccharomyces cerevisiae. However, the generalization of these methods was hampered by the limited size of the benchmark datasets. On the other hand, over 60,000 low resolution m6A sites and more than 10,000 base resolution m6A sites of Saccharomyces cerevisiae are recorded in RMBase and m6A-Atlas, respectively. The base resolution m6A sites are often obtained from low resolution results by post calibration. In view of these, we proposed a two-stage deep learning method, named MTDeepM6A-2S, to predict RNA m6A sites of Saccharomyces cerevisiae based on RNA sequence information. In the first stage, a multi-task model with convolutional neural network (CNN) and bidirectional long short-term memory (BiLSTM) deep framework was built to not only detect the low resolution m6A sites but also assign a reasonable probability for the predicted site. In the second stage, a transfer-learning strategy was used to build the model to predict the base resolution m6A sites from those low resolution m6A sites. The effectiveness of our model was validated on both training and independent test sets. The results show that our model outperforms other state-of-the-art models on the independent test set, which indicates that our model holds high potential to become a useful tool for epitranscriptomics analysis.
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The antimicrobial effect of 21 nature spices essential oils (EOs) on marinated chicken was investigated and response surface analysis was applied to obtain the optimal combination. Cassia bark EO, cinnamon EO, tea tree EO, and angelica EO had the best antibacterial effect. Their inhibition zone diameters (IZD) were 23 mm, 21 mm, 15 mm, and 12 mm, and their minimal bactericidal concentrations (MBC) were 1.25 µL/mL, 1.25 µL/mL, 10.00 µL/mL, 20.00 µL/mL. Using the Box-Behnken Design model, with the minimum total number of spoilage bacteria as the evaluation index, the optimal mixture was cassia bark EO 2.40 µL/mL, cinnamon EO 1.00 µL/mL, tea tree EO 3.50 µL/mL, and angelica EO 9.00 µL/mL. Compared with the control group, the total number of colonies was reduced by 1.3 log unites at the 12th sampling day, and the protein degradation process was slowed down owing to the preservative addition. These results indicate the potential application of nature extracts in chicken and other meat preservation.
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Aceites Volátiles , Especias , Animales , Antibacterianos/farmacología , Pollos , Cinnamomum zeylanicum , Pruebas de Sensibilidad Microbiana/veterinaria , Aceites Volátiles/farmacología , Extractos Vegetales/farmacología , TéRESUMEN
Oxidative stress involves enormously in the development of chronic inflammatory bone disease, wherein the overproduction of reactive oxygen species (ROS) negatively impacts the bone remodeling via promoting osteoclastogenesis and inhibiting osteogenesis. Lacking effective therapies highlights the importance of finding novel treatments. Our previous study screened a novel bioactive peptide D7 and demonstrated it could enhance the cell behaviors and protect bone marrow mesenchymal stem cells (BMSCs). Since BMSCs are progenitor cells of osteoblast (OB), we therefore ask whether D7 could also protect against the progress of inflammatory osteolysis. To validate our hypothesis and elucidate the underlying mechanisms, we first performed network pharmacology-based analysis according to the molecule structure of D7, and then followed by pharmacological evaluation on D7 by in vitro lipopolysaccharide(LPS)-induced models. The result from network pharmacology identified 20 candidate targets of D7 for inflammatory osteolysis intervention. The further analysis of Gene Ontology (GO)/KEGG pathway enrichment suggested the therapeutic effect of D7 may primarily affect osteoclast (OC) differentiation and function during the inflammatory osteolysis. Through validating the real effects of D7 on OC and OB as postulated, results demonstrated suppressive effects of D7 on LPS-stimulated OC differentiation and resorption, via the inhibition on OC marker genes. Contrarily, by improving the expression of OB marker genes, D7 displayed promotive effects on OB differentiation and alleviated LPS-induced osteogenic damage. Further mechanism study revealed that D7 could reduce LPS-induced ROS formation and strengthen antioxidants expressions in both OC and OB precursors, ameliorating LPS-triggered redox imbalance in bone remodeling. Taken together, our findings unveiled therapeutic effects of D7 against LPS-induced inflammatory osteolysis through the suppression of oxidative stress and the restoration of the bone remodeling process, providing a new therapeutic candidate for chronic inflammatory bone diseases.
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Osteólisis , Animales , Remodelación Ósea , Diferenciación Celular , Lipopolisacáridos/farmacología , Ratones , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Farmacología en Red , Osteoclastos/metabolismo , Osteogénesis , Osteólisis/inducido químicamente , Osteólisis/tratamiento farmacológico , Estrés Oxidativo , Péptidos/metabolismo , Ligando RANK/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Background: Type 2 diabetes (T2DM) is a major risk factor for myocardial infarction. Thrombus aspiration was considered a good way to deal with coronary thrombus in the treatment of acute myocardial infarction. However, recent studies have found that routine thrombus aspiration is not beneficial. This study is designed to investigate whether intracoronary artery retrograde thrombolysis (ICART) is more effective than thrombus aspiration or percutaneous transluminal coronary angioplasty (PTCA) in improving myocardial perfusion in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). Methods/Design: IntraCoronary Artery Retrograde Thrombolysis (ICART) vs. thrombus aspiration or PTCA in STEMI trial is a single-center, prospective, randomized open-label trial with blinded evaluation of endpoints. A total of 286 patients with STEMI undergoing PPCI are randomly assigned to two groups: ICART and thrombus aspiration or PTCA. The primary endpoint is the incidence of >70% ST-segment elevation resolution. Secondary outcomes include distal embolization, myocardial blush grade, thrombolysis in myocardial infarction (TIMI) flow grade, and in-hospital bleeding. Discussion: The ICART trial is the first randomized clinical trial (RCT) to date to verify the effect of ICART vs. thrombus aspiration or PTCA on myocardial perfusion in patients with STEMI undergoing PPCI. Clinical Trial Registration: [https://www.chictr.org.cn/], identifier [ChiCTR1900023849].
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Background: The management of a large thrombus burden in patients with acute myocardial infarction and diabetes is still a worldwide problem. Case presentation: A 74-year-old Chinese woman presented with ST-segment elevation myocardial infarction (STEMI) complicated with diabetes mellitus and hypertension. Angiography revealed massive thrombus formation in the mid-segment of the right coronary artery leading to vascular occlusion. The sheared balloon was placed far from the occlusion segment and urokinase (100,000 u) was administered for intracoronary artery retrograde thrombolysis, and thrombolysis in myocardial infarction (TIMI) grade 3 blood flow was restored within 7 min. At last, one stent was accurately implanted into the culprit's vessel. No-reflow, coronary slow flow, and reperfusion arrhythmia were not observed during this process. Conclusion: Intracoronary artery retrograde thrombolysis (ICART) can be effectively and safely used in patients with STEMI along with diabetes mellitus and hypertension, even if the myocardial infarction exceeds 12 h (REST or named ICART ClinicalTrials.gov number, ChiCTR1900023849).
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Background: How to deal with large thrombus burdens of culprit's blood vessel remains a great challenge in the treatment of acute myocardial infarction. Case presentation: A 32-year-old Chinese man was diagnosed with ST-segment elevation myocardial infarction (STEMI). Coronary angiography revealed that the distal end of a tortuous left circumflex was completely occluded by a large amount of thrombus. Cutted balloon-directed intracoronary artery retrograde thrombolysis (ICART) with urokinase led to the restoration of coronary blood flow. Because there was no obvious plaque rupture or artery stenosis in the coronary artery, it was only dilated, and no stent was implanted. Conclusion: Cutted balloon-directed ICART can be performed effectively and safely in some STEMI patients with tortuous coronary vessels and large thrombus. (REST or named ICART ClinicalTrials.gov number, ChiCTR1900023849).
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Ferroptosis is an iron-dependent regulated cell death characterized by lipid peroxidation and iron overload, which is different from other types of programmed cell death, including apoptosis, necroptosis, autophagy, and pyroptosis. Over the past years, emerging studies have shown a close relation between ferroptosis and various cardiovascular diseases such as atherosclerosis, acute myocardial infarction, ischemia/reperfusion injury, cardiomyopathy, and heart failure. Herein, we will review the contributions of ferroptosis to multiple cardiovascular diseases and the related targets. Further, we discuss the potential ferroptosis-targeting strategies for treating different cardiovascular diseases.