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AIMS: Limited data compared antiarrhythmic drugs (AADs) with concomitant non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients, hence the aim of the study. METHODS AND RESULTS: National health insurance database were retrieved during 2012-17 for study. We excluded patients not taking AADs, bradycardia, heart block, heart failure admission, mitral stenosis, prosthetic valve, incomplete demographic data, and follow-up <3 months. Outcomes were compared in Protocol 1, dronedarone vs. non-dronedarone; Protocol 2, dronedarone vs. amiodarone; and Protocol 3, dronedarone vs. propafenone. Outcomes were acute myocardial infarction (AMI), ischaemic stroke/systemic embolism, intracranial haemorrhage (ICH), major bleeding, cardiovascular death, all-cause mortality, and major adverse cardiovascular event (MACE) (including AMI, ischaemic stroke, and cardiovascular death). In Protocol 1, 2298 dronedarone users and 6984 non-dronedarone users (amiodarone = 4844; propafenone = 1914; flecainide = 75; sotalol = 61) were analysed. Dronedarone was associated with lower ICH (HR = 0.61, 95% CI = 0.38-0.99, P = 0.0436), cardiovascular death (HR = 0.24, 95% CI = 0.16-0.37, P < 0.0001), all-cause mortality (HR = 0.33, 95% CI = 0.27-0.42, P < 0.0001), and MACE (HR = 0.56, 95% CI = 0.45-0.70, P < 0.0001). In Protocol 2, 2231 dronedarone users and 6693 amiodarone users were analysed. Dronedarone was associated with significantly lower ICH (HR = 0.53, 95%=CI 0.33-0.84, P = 0.0078), cardiovascular death (HR = 0.20, 95% CI = 0.13-0.31, P < 0.0001), all-cause mortality (HR 0.27, 95% CI 0.22-0.34, P < 0.0001), and MACE (HR = 0.53, 95% CI = 0.43-0.66, P < 0.0001), compared with amiodarone. In Protocol 3, 812 dronedarone users and 2436 propafenone users were analysed. There were no differences between two drugs for primary and secondary outcomes. CONCLUSION: The use of dronedarone with NOACs was associated with cardiovascular benefits in an Asian population, compared with non-dronedarone AADs and amiodarone.
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Amiodarona , Fibrilación Atrial , Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Antiarrítmicos/efectos adversos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Propafenona/uso terapéutico , Administración Oral , Anticoagulantes/efectos adversos , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Amiodarona/efectos adversos , Dronedarona/efectos adversosRESUMEN
BACKGROUND: Patients with multivessel disease (MVD) often pursue complete revascularization (CR) during percutaneous coronary intervention (PCI) to improve prognosis. However, angiographic CR is not always feasible and is associated with some procedure-related complications in heart failure (HF) patients with MVD. Clinical selective incomplete revascularization (IR) may be reasonable for these high-risk patients, but its role in long-term outcomes remains uncertain. METHODS: Six hundred patients with HF and MVD submitted to PCI were enrolled. Major adverse cardiac events (MACEs) were defined as a composite of recurrent myocardial infarction, any revascularization, and all-cause mortality at 5 years. RESULTS: During a mean follow-up period of 3.7 ± 1.9 years, there was no significant difference in 5-year MACEs between selective IR and successful angiographic CR in HF patients with MVD. However, patients who failed CR had a significantly greater incidence of 5-year MACEs than those in the other two groups (failed CR: 46.4% vs. selective IR: 27.7% vs. successful CR: 27.8%, p < 0.001). CONCLUSIONS: Long-term outcomes of selective IR were comparable with those of successful angiographic CR in HF patients with MVD. However, patients that failed CR showed 2.53-fold increased risk of MACEs compared to patients undergoing either selective IR or successful angiographic CR. A more comprehensive planning strategy should be devised before PCI in HF patients with MVD.
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Angiografía Coronaria , Enfermedad de la Arteria Coronaria , Insuficiencia Cardíaca/complicaciones , Intervención Coronaria Percutánea , Anciano , Toma de Decisiones Clínicas , Angiografía Coronaria/efectos adversos , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/cirugía , Femenino , Humanos , Incidencia , Masculino , Evaluación de Procesos y Resultados en Atención de Salud , Selección de Paciente , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/métodos , Pronóstico , Índice de Severidad de la Enfermedad , Taiwán/epidemiología , Tiempo , Resultado del TratamientoRESUMEN
Acute statin therapy reduces myocardial ischemia/reperfusion (IR) injury-induced ventricular fibrillation (VF), but the underlying electrophysiological mechanisms remain unclear. This study sought to investigate the antiarrhythmic effects of a single bolus rosuvastatin injection in failing rabbit hearts with IR injury and to unveil the underlying molecular mechanisms. Rabbits were divided into rosuvastatin, rosuvastatin + L-NAME, control, and L-NAME groups. Intravenous bolus rosuvastatin (0.5 mg/kg) and/or L-NAME (10 mg/kg) injections were administered 1 hour and 15 minutes before surgery, respectively. Heart failure was induced using rapid ventricular pacing. Under general anesthesia with isoflurane, an IR model was created by coronary artery ligation for 30 minutes, followed by reperfusion for 15 minutes. Plasma NO end product levels were measured during IR. Then, hearts were excised and Langendorff-perfused for optical mapping studies. Cardiac tissues were sampled for Western blot analysis. Rosuvastatin increased plasma NO levels during IR, which was abrogated by L-NAME. Spontaneous VF during IR was suppressed by rosuvastatin (P < 0.001). Intracellular calcium (Cai) decay and conduction velocity were significantly slower in the IR zone. Rosuvastatin accelerated Cai decay, ameliorated conduction inhomogeneity, and reduced the inducibility of spatially discordant alternans and VF significantly. Western blots revealed significantly higher expression of enhancing endothelial NO-synthase and phosphorylated enhancing endothelial NO-synthase proteins in the Rosuvastatin group. Furthermore, SERCA2a, phosphorylated connexin43, and phosphorylated phospholamban were downregulated in the IR zone, which was attenuated or reversed by rosuvastatin. Acute rosuvastatin therapy before ischemia reduced IR-induced VF by improving SERCA2a function and ameliorating conduction disturbance in the IR zone.
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Antiarrítmicos/administración & dosificación , Señalización del Calcio/efectos de los fármacos , Calcio/metabolismo , Conexina 43/metabolismo , Insuficiencia Cardíaca/tratamiento farmacológico , Frecuencia Cardíaca/efectos de los fármacos , Ventrículos Cardíacos/efectos de los fármacos , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Rosuvastatina Cálcica/administración & dosificación , Fibrilación Ventricular/prevención & control , Potenciales de Acción , Animales , Proteínas de Unión al Calcio/metabolismo , Modelos Animales de Enfermedad , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/fisiopatología , Ventrículos Cardíacos/metabolismo , Ventrículos Cardíacos/fisiopatología , Preparación de Corazón Aislado , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/fisiopatología , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Fosforilación , Conejos , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/metabolismo , Factores de Tiempo , Fibrilación Ventricular/metabolismo , Fibrilación Ventricular/fisiopatologíaRESUMEN
BACKGROUND: Piceatannol, a grape-derived polyphenol, has been linked to proarrhythmic properties by aggravating inhomogeneous conduction delay in the ischemia-reperfusion (IR) zone to enhance arrhythmogenic alternans in heart failure (HF) rabbits. The underlying molecular mechanisms of piceatannol-induced conduction disturbance were unclear in this model. METHODS: HF was induced by 4 weeks' rapid ventricular pacing. IR injury was induced in vivo using a protocol of left coronary artery ligation and release. Left ventricular cardiomyocytes were isolated enzymatically for whole-cell patch-clamp studies. Piceatannol (10 µM) was administrated to test its inhibitory effect on sodium current (INa ). Immunoblots studies and immunoenzymological staining were conducted in tissues sampled from the IR and remote zones. RESULTS: Peak INa density was less in failing cardiomyocytes than control cardiomyocytes. IR injury further reduces peak INa density in both groups. Piceatannol showed a greater INa inhibitory effect in HF than control cardiomyocytes. Western blots showed reduced NaV 1.5 protein expression in the HF group compared to the control group but no significant difference between remote and IR zones. Immunostaining showed that IR led to cytosolic redistribution of NaV 1.5, especially in failing hearts. CONCLUSIONS: Downregulation of NaV 1.5 protein expression and reduced peak INa density are found in the failing hearts. Piceatannol exerts a greater inhibitory effect on peak INa in the failing cardiomyocytes than in the controls. IR injury further decreases peak INa density, which is more prominent in the failing hearts than in the control hearts.
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Canal de Sodio Activado por Voltaje NAV1.5/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Estilbenos/farmacología , Animales , Western Blotting , Regulación hacia Abajo , Insuficiencia Cardíaca/fisiopatología , Miocitos Cardíacos/metabolismo , Técnicas de Placa-Clamp , Conejos , Daño por Reperfusión/fisiopatologíaRESUMEN
BACKGROUND: Clinical trials have investigated efficacy of drug-eluting balloon (DEB) angioplasty for bare-metal stent (BMS) in-stent restenosis (ISR). Few studies have investigated predictors of long-term outcomes following BMS-ISR treatment with DEB. METHODS: From June 2011 to April 2015, 105 patients with 125 BMS-ISR lesions were enrolled from the Cardiovascular Atherosclerosis and Percutaneous TrAnsluminal INterventions (CAPTAIN) registry. All these lesions were treated with DEB angioplasty as final therapy. The major adverse cardiac events (MACEs) were recurrent clinically driven target lesion revascularisation (TLR), myocardial infarction, and cardiac death after DEB angioplasty. RESULTS: After DEB angioplasty, the angiographic stenosis decreased from 84.8%±12.4% to 22.6%±10.4%. Over a mean follow-up duration of 21.7±13.4months, the rates of TLR at 1-12 months and 12-48 months were 4.8% and 4.2%, respectively. The rates of MACEs at 1-12 months and 12-48 months were 6.7% and 6.1%, respectively. Chronic haemodialysis, calcified lesion, chronic total occlusion lesion before stenting, stent with metal-to-artery ratio >16.5%, and residual stenosis >25% after DEB angioplasty were potential risk factors for MACEs in univariate analysis. After adjustment in multivariate analysis, independent predictors of long-term MACEs were identified as chronic haemodialysis, chronic total occlusion lesion before stenting, and residual stenosis >25% after DEB angioplasty. CONCLUSIONS: The long-term results of DEB angioplasty for BMS-ISR are acceptable in this real-world registry. Patient (chronic haemodialysis), lesion (chronic total occlusion) and angioplasty (residual stenosis percentage) related factors predicted long-term outcomes following BMS-ISR treatment with DEB angioplasty.
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Angioplastia Coronaria con Balón/efectos adversos , Estenosis Coronaria/cirugía , Vasos Coronarios/diagnóstico por imagen , Stents Liberadores de Fármacos/efectos adversos , Oclusión de Injerto Vascular/epidemiología , Sistema de Registros , Medición de Riesgo/métodos , Angiografía Coronaria , Estenosis Coronaria/diagnóstico , Vasos Coronarios/cirugía , Femenino , Estudios de Seguimiento , Oclusión de Injerto Vascular/diagnóstico , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tasa de Supervivencia/tendencias , Taiwán/epidemiología , Factores de TiempoRESUMEN
The protozoan Giardia lamblia parasitizes the human small intestine to cause diseases. It undergoes differentiation into infectious cysts by responding to intestinal stimulation. How the activated signal transduction pathways relate to encystation stimulation remain largely unknown. During encystation, genes encoding cyst wall proteins (CWPs) are coordinately up-regulated by a Myb2 transcription factor. Because cell differentiation is linked to cell cycle regulation, we tried to understand the role of cell cycle regulators, cyclin-dependent kinases (Cdks), in encystation. We found that the recombinant Myb2 was phosphorylated by Cdk-associated complexes and the levels of phosphorylation increased significantly during encystation. We have identified a putative cdk gene (cdk2) by searching the Giardia genome database. Cdk2 was found to localize in the cytoplasm with higher expression during encystation. Interestingly, overexpression of Cdk2 resulted in a significant increase of the levels of cwp gene expression and cyst formation. In addition, the Cdk2-associated complexes can phosphorylate Myb2 and the levels of phosphorylation increased significantly during encystation. Mutations of important catalytic residues of Cdk2 resulted in a significant decrease of kinase activity and ability of inducing cyst formation. Addition of a Cdk inhibitor, purvalanol A, significantly decreased the Cdk2 kinase activity and the levels of cwp gene expression and cyst formation. Our results suggest that the Cdk2 pathway may be involved in phosphorylation of Myb2, leading to activation of the Myb2 function and up-regulation of cwp genes during encystation. The results provide insights into the use of Cdk inhibitory drugs in disruption of Giardia differentiation into cysts.
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Quinasa 2 Dependiente de la Ciclina/metabolismo , Giardia lamblia/metabolismo , Proteínas Oncogénicas v-myb/metabolismo , Proteínas Protozoarias/metabolismo , Factores de Transcripción/metabolismo , Quinasa 2 Dependiente de la Ciclina/genética , Citoplasma/genética , Citoplasma/metabolismo , Giardia lamblia/genética , Humanos , Proteínas Oncogénicas v-myb/genética , Fosforilación , Proteínas Protozoarias/biosíntesis , Proteínas Protozoarias/genética , Factores de Transcripción/genéticaRESUMEN
In this paper, a cobalt (Co)-chelated polynaphthalene imine (Co-PNIM) was calcined to become an oxygen reduction reaction (ORR) electrocatalyst (Co-N-C) as the cathode catalyst (CC) of an anion exchange membrane fuel cell (AEMFC). The X-ray diffraction pattern of CoNC-1000A900 illustrated that the carbon matrix develops clear C(002) and Co(111) planes after calcination, which was confirmed using high-resolution TEM pictures. Co-N-Cs also demonstrated a significant ORR peak at 0.8 V in a C-V (current vs. voltage) curve and produced an extremely limited reduction current density (5.46 mA cm-2) comparable to commercial Pt/C catalysts (5.26 mA cm-2). The measured halfway potential of Co-N-C (0.82 V) was even higher than that of Pt/C (0.81 V). The maximum power density (Pmax) of the AEM single cell upon applying Co-N-C as the CC was 243 mW cm-2, only slightly lower than that of Pt/C (280 mW cm-2). The Tafel slope of CoNC-1000A900 (33.3 mV dec-1) was lower than that of Pt/C (43.3 mV dec-1). The limited reduction current density only decayed by 7.9% for CoNC-1000A900, compared to 22.7% for Pt/C, after 10,000 redox cycles.
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In order to yield more Co(II), 2,6-diaminopyridine (DAP) was polymerized with 4,4-methylene diphenyl diisocyanates (MDI) in the presence of Co(II) to obtain a Co-complexed polyurea (Co-PUr). The obtained Co-PUr was calcined to become Co, N-doped carbon (Co-N-C) as the cathode catalyst of an anion exchange membrane fuel cell (AEMFC). High-resolution transmission electron microscopy (HR-TEM) of Co-N-C indicated many Co-Nx (Co covalent bonding with several nitrogen) units in the Co-N-C matrix. X-ray diffraction patterns showed that carbon and cobalt crystallized in the Co-N-C catalysts. The Raman spectra showed that the carbon matrix of Co-N-C became ordered with increased calcination temperature. The surface area (dominated by micropores) of Co-N-Cs also increased with the calcination temperature. The non-precious Co-N-C demonstrated comparable electrochemical properties (oxygen reduction reaction: ORR) to commercial precious Pt/C, such as high on-set and half-wave voltages, high limited reduction current density, and lower Tafel slope. The number of electrons transferred in the cathode was close to four, indicating complete ORR. The max. power density (Pmax) of the single cell with the Co-N-C cathode catalyst demonstrated a high value of 227.7 mWcm-2.
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Aromatic polyimide has good mechanical properties and high-temperature resistance. Based on this, benzimidazole is introduced into the main chain, and its intermolecular (internal) hydrogen bond can increase mechanical and thermal properties and electrolyte wettability. Aromatic dianhydride 4,4'-oxydiphthalic anhydride (ODPA) and benzimidazole-containing diamine 6,6'-bis [2-(4-aminophenyl)benzimidazole] (BAPBI) were synthesized by means of a two-step method. Imidazole polyimide (BI-PI) was used to make a nanofiber membrane separator (NFMS) by electrospinning process, using its high porosity and continuous pore characteristics to reduce the ion diffusion resistance of the NFMS, enhancing the rapid charge and discharge performance. BI-PI has good thermal properties, with a Td5% of 527 °C and a dynamic mechanical analysis Tg of 395 °C. The tensile strength of the NFMS increased from 10.92MPa to 51.15MPa after being hot-pressed. BI-PI has good miscibility with LIB electrolyte, the porosity of the film is 73%, and the electrolyte absorption rate reaches 1454%. That explains the higher ion conductivity (2.02 mS cm-1) of NFMS than commercial one (0.105 mS cm-1). When applied to LIB, it is found that it has high cyclic stability and excellent rate performance at high current density (2 C). BI-PI (120 Ω) has a lower charge transfer resistance than the commercial separator Celgard H1612 (143 Ω).
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Background: The optimal revascularization strategy for elderly patients with acute coronary syndrome (ACS) remains uncertain. We evaluated the impact of complete revascularization (CR) vs. incomplete revascularization (IR) in elderly ACS patients with multivessel disease (MVD) undergoing percutaneous coronary intervention (PCI). Methods: Using registry data from 2011 to 2019, we conducted a propensity-score matched cohort study. Elderly patients (≥75 years) with ACS and MVD who underwent PCI were divided into CR and IR groups based on angiography during index hospitalization. Major adverse cardiovascular events (MACEs), including all-cause mortality, recurrent non-fatal myocardial infarction, and any revascularization, were assessed at 3-year follow-up. Results: Among 1,018 enrolled patients, 496 (48.7%) underwent CR and 522 (51.3%) received IR. After 1:1 propensity-score matching, we analyzed 395 pairs. At 3-year follow-up, CR was significantly associated with lower MACE risk compared to IR (16.7% vs. 25.6%, HR = 0.65, 95% CI: 0.47-0.88, p = 0.006), driven by reduced all-cause mortality. This benefit was consistent across all pre-specified subgroups, particularly in ST segment elevation (STE)-ACS patients. In non-STE (NSTE)-ACS subgroup analysis, CR was also associated with a lower risk of cardiac mortality compared to IR (HR = 0.30, 95% CI: 0.12-0.75, p = 0.01). Conclusion: In elderly ACS patients with MVD undergoing PCI, CR demonstrates superior long-term outcomes compared to IR, irrespective of STE- or NSTE-ACS presentation.
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Background: Left ventricular systolic dysfunction (LVSD) characterized by a reduced left ventricular ejection fraction (LVEF) is associated with adverse patient outcomes. We aimed to build a deep neural network (DNN)-based model using standard 12-lead electrocardiogram (ECG) to screen for LVSD and stratify patient prognosis. Methods: This retrospective chart review study was conducted using data from consecutive adults who underwent ECG examinations at Chang Gung Memorial Hospital in Taiwan between October 2007 and December 2019. DNN models were developed to recognize LVSD, defined as LVEF <40%, using original ECG signals or transformed images from 190,359 patients with paired ECG and echocardiogram within 14 days. The 190,359 patients were divided into a training set of 133,225 and a validation set of 57,134. The accuracy of recognizing LVSD and subsequent mortality predictions were tested using ECGs from 190,316 patients with paired data. Of these 190,316 patients, we further selected 49,564 patients with multiple echocardiographic data to predict LVSD incidence. We additionally used data from 1,194,982 patients who underwent ECG only to assess mortality prognostication. External validation was performed using data of 91,425 patients from Tri-Service General Hospital, Taiwan. Results: The mean age of patients in the testing dataset was 63.7 ± 16.3 years (46.3% women), and 8,216 patients (4.3%) had LVSD. The median follow-up period was 3.9 years (interquartile range 1.5-7.9 years). The area under the receiver-operating characteristic curve (AUROC), sensitivity, and specificity of the signal-based DNN (DNN-signal) to identify LVSD were 0.95, 0.91, and 0.86, respectively. DNN signal-predicted LVSD was associated with age- and sex-adjusted hazard ratios (HRs) of 2.57 (95% confidence interval [CI], 2.53-2.62) for all-cause mortality and 6.09 (5.83-6.37) for cardiovascular mortality. In patients with multiple echocardiograms, a positive DNN prediction in patients with preserved LVEF was associated with an adjusted HR (95% CI) of 8.33 (7.71 to 9.00) for incident LVSD. Signal- and image-based DNNs performed equally well in the primary and additional datasets. Conclusion: Using DNNs, ECG becomes a low-cost, clinically feasible tool to screen LVSD and facilitate accurate prognostication.
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Background: The risk of mortality is relatively high among patients who visit the emergency department (ED), and stratifying patients at high risk can help improve medical care. This study aimed to create a machine-learning model that utilizes the standard 12-lead ECG to forecast acute mortality risk in ED patients. Methods: The database included patients who visited the EDs and underwent standard 12-lead ECG between October 2007 and December 2017. A convolutional neural network (CNN) ECG model was developed to classify survival and mortality using 12-lead ECG tracings acquired from 345,593 ED patients. For machine learning model development, the patients were randomly divided into training, validation and testing datasets. The performance of the mortality risk prediction in this model was evaluated for various causes of death. Results: Patients who visited the ED and underwent one or more ECG examinations experienced a high incidence of 30-day mortality [18,734 (5.42%)]. The developed CNN model demonstrated high accuracy in predicting acute mortality (hazard ratio 8.50, 95% confidence interval 8.20-8.80) with areas under the receiver operating characteristic (ROC) curve of 0.84 for the 30-day mortality risk prediction models. This CNN model also demonstrated good performance in predicting one-year mortality (hazard ratio 3.34, 95% confidence interval 3.30-3.39). This model exhibited good predictive performance for 30-day mortality not only for cardiovascular diseases but also across various diseases. Conclusions: The machine learning-based ECG model utilizing CNN screens the risks for 30-day mortality. This model can complement traditional early warning scoring indexes as a useful screening tool for mortality prediction.
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Giardia lamblia differentiates into resistant walled cysts for survival outside the host and transmission. During encystation, synthesis of cyst wall proteins is coordinately induced. The E2F family of transcription factors in higher eukaryotes is involved in cell cycle progression and cell differentiation. We asked whether Giardia has E2F-like genes and whether they influence gene expression during Giardia encystation. Blast searches of the Giardia genome database identified one gene (e2f1) encoding a putative E2F protein with two putative DNA-binding domains. We found that the e2f1 gene expression levels increased significantly during encystation. Epitope-tagged E2F1 was found to localize to nuclei. Recombinant E2F1 specifically bound to the thymidine kinase and cwp1-3 gene promoters. E2F1 contains several key residues for DNA binding, and mutation analysis revealed that its binding sequence is similar to those of the known E2F family proteins. The E2F1-binding sequences were positive cis-acting elements of the thymidine kinase and cwp1 promoters. We also found that E2F1 transactivated the thymidine kinase and cwp1 promoters through its binding sequences in vivo. Interestingly, E2F1 overexpression resulted in a significant increase of the levels of CWP1 protein, cwp1-3 gene mRNA, and cyst formation. We also found E2F1 can interact with Myb2, a transcription factor that coordinate up-regulates the cwp1-3 genes during encystation. Our results suggest that E2F family has been conserved during evolution and that E2F1 is an important transcription factor in regulation of the Giardia cwp genes, which are key to Giardia differentiation into cysts.
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Núcleo Celular/metabolismo , Factor de Transcripción E2F1/metabolismo , Evolución Molecular , Giardia lamblia/metabolismo , Proteínas Protozoarias/metabolismo , Transcripción Genética/fisiología , Núcleo Celular/genética , Factor de Transcripción E2F1/genética , Regulación de la Expresión Génica/fisiología , Giardia lamblia/genética , Proteínas Protozoarias/genética , Elementos de Respuesta/fisiologíaRESUMEN
Polyazomethine (PAM) prepared from the polycondensation between p-phenylene diamine (PDA) and p-terephthalaldehyde (PTAl) via Schiff reaction can physically crosslink (complex) with Co ions. Co-complexed PAM (Co-PAM) in the form of gel is calcined to become a Co, N-co-doped carbonaceous matrix (Co-N-C), acting as cathode catalyst of an anion exchange membrane fuel cell (AEMFC). The obtained Co-N-C catalyst demonstrates a single-atom structure with active Co centers seen under the high-resolution transmission electron microscopy (HRTEM). The Co-N-C catalysts are also characterized by XRD, SEM, TEM, XPS, BET, and Raman spectroscopy. The Co-N-C catalysts demonstrate oxygen reduction reaction (ORR) activity in the KOH(aq) by expressing an onset potential of 1.19-1.37 V vs. RHE, a half wave potential of 0.70-0.92 V, a Tafel slope of 61-89 mV/dec., and number of exchange electrons of 2.48-3.79. Significant ORR peaks appear in the current-voltage (CV) polarization curves for the Co-N-C catalysts that experience two-stage calcination higher than 900 °C, followed by double acid leaching (CoNC-1000A-900A). The reduction current of CoNC-1000A-900A is comparable to that of commercial Pt-implanted carbon (Pt/C), and the max power density of the single cell using CoNC-1000A-900A as cathode catalyst reaches 275 mW cm-2.
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A magnesium potassium phosphate hydrate-based flame-retardant coating (MKPC) is formulated by dead-burnt magnesium oxide (magnesia) and potassium dihydrogen phosphate (KH2PO4), behaving as a matrix. Constituents of the MKPC include wollastonite, vermiculite, aluminum fluoride, aluminum trihydroxide, and calcium carbonate. Some of the ingredients inter-react to produce mullite whiskers at high temperatures, despite an acid-base hydration induced reaction between magnesia and KH2PO4. The MKPC's thermal, corrosion-resistant, mechanical, and flame-resistant properties were analyzed using scanning electron microscopy, electrochemical corrosion testing, compression testing, thermogravimetric analysis, and freeze/thaw tests. The results show that with the molar ratio = 4 of magnesia to KH2PO4, MKPC demonstrates lower thermal conductivity (0.19 W/m K), along with better corrosion resistance, stronger compressive strength (10.5 MPa), and higher bonding strength (6.62 kgf/cm2) to the steel substrate. Furthermore, acceptable additives to the formulation could enhance its flame-retardancy and increase its mechanical strength as well. Mullite whisker formed from the interaction of wollastonite, aluminum trihydroxide, and aluminum fluoride acts as an outer ceramic shield that enhances mechanical strength and compactness. In addition, Mg-containing minerals with calcium carbonate treated at high temperatures, transform into magnesium calcium carbonate after releasing CO2. At the optimum composition of MKPC (magnesia/KH2PO4 molar ratio = 4; wollastonite:vermiculite = 20:10 wt.%; aluminum trihydroxide = 10 wt.%; and calcium carbonate = 5 wt.%), coated on a steel substrate, the flame-resistance limit results exhibit below 200 °C on the back surface of the steel substrate after one hour of flaming (ca. 1000 °C) on the other surface, and the flame-resistance rating results demonstrate only 420 °C on the back surface of the steel substrate after three hours of flaming (>1000 °C) on the other surface. Both requirements for the flame-resistance limit and three-hour flame-resistance rating are met with the optimum compositions, indicating that MKPC plays an effective role in establishing flame-retardancy.
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Background: Coronary perfusion pressure (CPP) and coronary artery stenosis are responsible for myocardial perfusion. However, how CPP-related survival outcome affects revascularization is unclear. Objective: The aim of this study is to investigate the prognostic role of CPP in patients with left ventricular systolic dysfunction (LVSD) undergoing percutaneous coronary intervention (PCI) with complete revascularization (CR) or reasonable incomplete revascularization (RIR). Methods: We retrospectively screened 6,076 consecutive patients in a registry. The residual synergy between percutaneous coronary intervention with Taxus and cardiac surgery (SYNTAX) score (rSS) was used to define CR (rSS = 0) and RIR (0
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Giardia lamblia differentiates into infectious cysts to survive outside of the host. It is of interest to identify factors involved in up-regulation of cyst wall proteins (CWPs) during this differentiation. Pax proteins are important regulators of development and cell differentiation in Drosophila and vertebrates. No member of this gene family has been reported to date in yeast, plants, or protozoan parasites. We have identified a pax-like gene (pax1) encoding a putative paired domain in the G. lamblia genome. Epitope-tagged Pax1 localized to nuclei during both vegetative growth and encystation. Recombinant Pax1 specifically bound to the AT-rich initiator elements of the encystation-induced cwp1 to -3 and myb2 genes. Interestingly, overexpression of Pax1 increased cwp1 to -3 and myb2 gene expression and cyst formation. Deletion of the C-terminal paired domain or mutation of the basic amino acids of the paired domain resulted in a decrease of the transactivation function of Pax1. Our results indicate that the Pax family has been conserved during evolution, and Pax1 could up-regulate the key encystation-induced genes to regulate differentiation of the protozoan eukaryote, G. lamblia.
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Giardia lamblia/citología , Giardia lamblia/genética , Factores de Transcripción Paired Box/genética , Factores de Transcripción Paired Box/metabolismo , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , Activación Transcripcional , Secuencia de Aminoácidos , Animales , Regulación de la Expresión Génica , Giardia lamblia/metabolismo , Giardia lamblia/patogenicidad , Humanos , Análisis por Micromatrices , Datos de Secuencia Molecular , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Alineación de SecuenciaRESUMEN
Transcription factor, Jun dimerization protein 2 (JDP2), binds directly to histones and DNAs and then inhibits the p300-mediated acetylation both of core histones and of reconstituted nucleosomes that contain JDP2 recognition DNA sequences. JDP2 plays a key role as a repressor of adipocyte differentiation by regulation of the expression of the gene C/EBPδ via inhibition of histone acetylation. Moreover, JDP2-deficient mouse embryonic fibroblasts (JDP2(-/-) MEFs) are resistant to replicative senescence. JDP2 inhibits the recruitment of polycomb repressive complexes (PRC1 and PRC2) to the promoter of the gene encoding p16(Ink4a), resulting from the inhibition of methylation of lysine 27 of histone H3 (H3K27). Therefore, it seems that chromatin-remodeling factors, including the PRC complex controlled by JDP2, may be important players in the senescence program. The novel mechanisms that underline the action of JDP2 in inducing cellular senescence and suppressing adipocyte differentiation are reviewed.
Asunto(s)
Diferenciación Celular/fisiología , Senescencia Celular/fisiología , Histonas/fisiología , Proteínas Represoras/fisiología , Animales , Humanos , RatonesRESUMEN
Calcination reduction reaction is used to prepare Pt/EB (emeraldine base)-XC72 (Vulcan carbon black) composites as the cathode material of a proton exchange membrane fuel cell (PEMFC). The EB-XC72 core-shell composite obtained from directly polymerizing aniline on XC72 particles is able to chelate and capture the Pt-ions before calcination. X-ray diffraction spectra demonstrate Pt particles are successfully obtained on the EB-XC72 when the calcined temperature is higher than 600 °C. Micrographs of TEM and SEM illustrate the affluent, Pt nanoparticles are uniformly distributed on EB-XC72 at 800 °C (Pt/EB-XC72/800). More Pt is deposited on Pt/EB-XC72 composite as temperatures are higher than 600 °C. The Pt/EB-XC72/800 catalyst demonstrates typical type of a cyclic voltammograms (C-V) curve of a Pt-catalyst with clear Pt-H oxidation and Pt-O reduction peaks. The highest number of transferred electrons during ORR approaches 3.88 for Pt/EB-XC72/800. The maximum power density of the single cell based on Pt/EB-XC72/800 reaches 550 mW cm-2.
RESUMEN
The presence of a Gore-Tex patch can create difficulty in performing transeptal puncture for atrial septal defect patients underwent atrial fibrillation ablation. The maneuverability and stability of using manually operated catheters via retrograde aortic approach could be overcome by a large-curved catheter to form a loop facilitating approachability to all parts of left atrium.