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Mitochondrial dynamics has emerged as an important target for neuronal protection after cerebral ischaemia/reperfusion. Therefore, the aim of this study was to investigate the mechanism by which ARMC10 regulation of mitochondrial dynamics affects mitochondrial function involved in ischaemic stroke (IS). Mitochondrial morphology was detected by laser scanning confocal microscopy (LSCM), and mitochondrial ultrastructural alterations were detected by electron microscopy. The expression of mitochondrial dynamics-related genes Drp1, Mfn1, Mfn2, Fis1, OPA1 and ARMC10 and downstream target genes c-Myc, CyclinD1 and AXIN2 was detected by RT-qPCR. Western blot was used to detect the protein expression of ß-catenin, GSK-3ß, p-GSK-3ß, Bcl-2 and Bax. DCFH-DA fluorescent probe was to detect the effect of ARMC10 on mitochondrial ROS level, Annexin V-FITC fluorescent probe was to detect the effect of ARMC10 on apoptosis, and ATP assay kit was to detect the effect of ARMC10 on ATP production. Mitochondrial dynamics was dysregulated in clinical IS samples and in the OGD/R cell model, and the relative expression of ARMC10 gene was significantly decreased in IS group (p < 0.05). Knockdown and overexpression of ARMC10 could affect mitochondrial dynamics, mitochondrial function and neuronal apoptosis. Agonist and inhibitor affected mitochondrial function and neuronal apoptosis by targeting Wnt/ß-Catenin signal pathway. In the OGD/R model, ARMC10 affected mitochondrial function and neuronal apoptosis through the mechanism that regulates Wnt/ß-catenin signalling pathway. ARMC10 regulates mitochondrial dynamics and protects mitochondrial function by activating Wnt/ß-catenin signalling pathway, to exert neuroprotective effects.
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Apoptosis , Proteínas del Dominio Armadillo , Accidente Cerebrovascular Isquémico , Mitocondrias , Dinámicas Mitocondriales , Vía de Señalización Wnt , Humanos , Proteínas del Dominio Armadillo/metabolismo , Proteínas del Dominio Armadillo/genética , beta Catenina/metabolismo , beta Catenina/genética , Isquemia Encefálica/metabolismo , Isquemia Encefálica/genética , Isquemia Encefálica/patología , Accidente Cerebrovascular Isquémico/metabolismo , Accidente Cerebrovascular Isquémico/genética , Accidente Cerebrovascular Isquémico/patología , Mitocondrias/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
BACKGROUND: Ventricular tachycardia (VT) is the primary cause of sudden cardiac death in patients with hypertrophic cardiomyopathy (HCM). However, the strategy for VT treatment in HCM patients remains unclear. This study is aimed to compare the effectiveness of catheter ablation versus antiarrhythmic drug (AAD) therapy for sustained VT in patients with HCM. METHODS: A total of 28 HCM patients with sustained VT at 4 different centers between December 2012 and December 2021 were enrolled. Twelve underwent catheter ablation (ablation group) and sixteen received AAD therapy (AAD group). The primary outcome was VT recurrence during follow-up. RESULTS: Baseline characteristics were comparable between two groups. After a mean follow-up of 31.4 ± 17.5 months, the primary outcome occurred in 35.7% of the ablation group and 90.6% of the AAD group (hazard ratio [HR], 0.29 [95%CI, 0.10-0.89]; P = 0.021). No differences in hospital admission due to cardiovascular cause (25.0% vs. 71.0%; P = 0.138) and cardiovascular cause-related mortality/heart transplantation (9.1% vs. 50.6%; P = 0.551) were observed. However, there was a significant reduction in the composite endpoint of VT recurrence, hospital admission due to cardiovascular cause, cardiovascular cause-related mortality, or heart transplantation in ablation group as compared to that of AAD group (42.9% vs. 93.7%; HR, 0.34 [95% CI, 0.12-0.95]; P = 0.029). CONCLUSIONS: In HCM patients with sustained VT, catheter ablation reduced the VT recurrence, and the composite endpoint of VT recurrence, hospital admission due to cardiovascular cause, cardiovascular cause-related mortality, or heart transplantation as compared to AAD.
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Antiarrítmicos , Cardiomiopatía Hipertrófica , Ablación por Catéter , Recurrencia , Taquicardia Ventricular , Humanos , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/fisiopatología , Taquicardia Ventricular/mortalidad , Taquicardia Ventricular/terapia , Taquicardia Ventricular/etiología , Taquicardia Ventricular/cirugía , Antiarrítmicos/uso terapéutico , Antiarrítmicos/efectos adversos , Ablación por Catéter/efectos adversos , Ablación por Catéter/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Cardiomiopatía Hipertrófica/mortalidad , Cardiomiopatía Hipertrófica/complicaciones , Cardiomiopatía Hipertrófica/diagnóstico , Cardiomiopatía Hipertrófica/fisiopatología , Cardiomiopatía Hipertrófica/cirugía , Cardiomiopatía Hipertrófica/terapia , Resultado del Tratamiento , Factores de Tiempo , Adulto , Estudios Retrospectivos , Factores de Riesgo , Anciano , Frecuencia Cardíaca , ChinaRESUMEN
Lithium-sulfur batteries (LSBs) are considered to be one of the most promising alternatives to the current lithium-ion batteries (LIBs) to meet the increasing demand for energy storage owing to their high energy density, natural abundance, low cost, and environmental friendliness. Despite great success, LSBs still suffer from several problems, including undermined capacity arising from low utilization of sulfur, unsatisfactory rate performance and poor cycling life owing to the shuttle effect of polysulfides, and poor electrical conductivity of sulfur. Under such circumstances, the design/fabrication of porous carbon-sulfur composite cathodes is regarded as an effective solution to overcome the above problems. In this review, different synthetic methods of porous carbon hosts and their corresponding integration into carbon-sulfur cathodes are summarized. The pore formation mechanism of porous carbon hosts is also addressed. The pore size effect on electrochemical performance is highlighted and compared. The enhanced mechanism of the porous carbon host on the sulfur cathode is systematically reviewed and revealed. Finally, the combination of porous carbon hosts and high-profile solid-state electrolytes is demonstrated, and the challenges to realize large-scale commercial application of porous carbon-sulfur cathodes is discussed and future trends are proposed.
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Due to the increasing demand of security and energy density, all-solid-state lithium ion batteries have become the promising next-generation energy storage devices to replace the traditional liquid batteries with flammable organic electrolytes. In this Minireview, we focus on the recent developments of sulfide inorganic electrolytes for all-solid-state batteries. The challenges of assembling bulk-type all-solid-state batteries for industrialization are discussed, including low ionic conductivity of the present sulfide electrolytes, high interfacial resistance and poor compatibility between electrolytes and electrodes. Many efforts have been focused on the solutions for these issues. Although some progresses have been achieved, it is still far away from practical application. The perspectives for future research on all-solid-state lithium ion batteries are presented.
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Herein an effective way for construction of all-solid-state lithium-sulfur batteries (LSBs) with sulfur/reduced graphene oxide (rGO) and Li9.54 Si1.74 P1.44 S11.7 Cl0.3 solid electrolyte is reported. In the composite cathode, the Li9.54 Si1.74 P1.44 S11.7 Cl0.3 powder is homogeneously mixed with the S/rGO composite to enhance the ionic conductivity. Coupled with a metallic Li anode and solid electrolyte, the designed S/rGO-Li9.54 Si1.74 P1.44 S11.7 Cl0.3 composite cathode exhibits a high specific capacity and good cycling stability. A high initial discharge capacity of 969â mAh g-1 is achieved at a current density of 80â mA g-1 at room temperature and the cell retains a reversible capacity of over 827â mAh g-1 after 60â cycles. The enhanced performance is attributed to the intimate contact between the S/rGO and Li9.54 Si1.74 P1.44 S11.7 Cl0.3 electrolyte, and high electrical conductivity of rGO and high ionic conductivity of the solid electrolyte.
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Developing high-performance solid-state electrolytes is crucial for the innovation of next-generation lithium-sulfur batteries. Herein, a facile method for preparation of a novel gel polymer electrolyte (GPE) based on poly(vinylidene fluoride-hexafluoropropylene) (PVDF-HFP) is reported. Furthermore, Li1.5 Al0.5 Ti1.5 (PO4 )3 (LATP) nanoparticles as the active fillers are uniformly embedded into the GPE to form the final PVDF-HFP/LATP composite gel polymer electrolyte (CPE). Impressively, the obtained CPE demonstrates a high lithium ion transference number of 0.51 and improved electrochemical stability as compared to commercial liquid electrolyte. In addition, the assembled solid-sate Li-S battery with the composite gel polymer electrolyte membrane presents a high initial capacity of 918â mAh g-1 at 0.05â C, and better cycle performance than the counterparts with liquid electrolyte. Our designed PVDF-HFP/LATP composite can be a promising electrolyte for next-generation solid-state batteries with high cycling stability.
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Background: Diabetic kidney disease (DKD) had been proposed as a contributor in the pathogenesis of coronary artery disease (CAD). However, the relationship of DKD and the long-term adverse outcomes in patients with CAD after percutaneous coronary intervention (PCI) was still undiscovered. Methods: Approximately 892 patients with CAD enrolled from January 2012 to December 2016. The patients were divided into two groups, the DKD group (n = 341) and the None DKD group (n = 551). The primary outcome was major adverse cardiac events (MACE) after PCI. The average follow-up time was 1,897 ± 1,276 days. Results: Baseline data showed that some factors were significantly different between the two groups, including age, body mass index, gender (female), hypertension, smoking, stroke history, heart failure, duration of diabetic mellitus (DM), low-density lipoprotein cholesterol, urinary protein/creatinine ratio, serum creatinine, hemoglobin, platelet, antiplatelet, beta blocker, statin, antihypertensive drugs, and insulin (all p < 0.005). There were significant differences between the two groups in MACE, 40.3% vs. 52.2% (p = 0.001), and in cardiovascular death events and all-cause death events (5.6% vs. 20.5%, p < 0.001 and 4.4% vs. 13.5%, p < 0.001, respectively). In the DKD group, the risk of MACE was elevated to 141.9% [hazard ratio (HR) = 1.419, 95% confidence interval (CI): 1.164-1.730, p = 0.001] in the Cox univariable regression analyses; after adjusting co-variables, the Cox multivariable regression analyses demonstrated that DKD was an independent predictor for MACE (HR = 1.291, 95% CI: 1.027-1.624, p = 0.029) in patients with CAD after PCI, as well as in cardiovascular death events (HR = 2.148, 95% CI: 1.292-3.572, p = 0.003) and all-cause death events (HR = 2.229, 95% CI: 1.325-3.749, p = 0.003). Conclusion: This study suggests that DKD is an independent and novel predictor of long-term adverse outcomes in patients with CAD and DM who underwent PCI.
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P2-type cobalt-free MnNi-based layered oxides are promising cathode materials for sodium-ion batteries (SIBs) due to their high reversible capacity and well chemical stability. However, the phase transformations during repeated (dis)charge steps lead to rapid capacity decay and deteriorated Na+ diffusion kinetics. Moreover, the electrode manufacturing based on polyvinylidene difluoride (PVDF) binder system has been reported with severely defluorination issue as well as the energy intensive and expensive process due to the use of toxic and volatile N-methyl-2-pyrrolidone (NMP) solvent. It calls for designing a sustainable, better performing, and cost-effective binder for positive electrode manufacturing. In this work, we investigated inorganic sodium metasilicate (SMS) as a viable binder in conjunction with P2-Na0.67Mn0.55Ni0.25Fe0.1Ti0.1O2 (NMNFT) cathode material for SIBs. The NMNFT-SMS electrode delivered a superior electrochemical performance compared to carboxy methylcellulose (CMC) and PVDF based electrodes with a reversible capacity of ~161â mAh/g and retaining ~83 % after 200 cycles. Lower cell impedance and faster Na+ diffusion was also observed in this binder system. Meanwhile, with the assistance of TEM technique, SMS is suggested to form a uniform and stable nanoscale layer over the cathode particle surface, protecting the particle from exfoliation/cracking due to electrolyte attack. It effectively maintained the electrode connectivity and suppressed early phase transitions during cycling as confirmed by operando XRD study. With these findings, SMS binder can be proposed as a powerful multifunctional binder to enable positive electrode manufacturing of SIBs and to overall reduce battery manufacturing costs.
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Pancreatic cancer (PC) is featured with low survival rate and poor outcomes. Herein, we found that the expression of caspase-recruitment domain-containing protein 9 (CARD9), predominantly expressed in innate immune cells, was positively related to the prognosis of PC patients. CARD9-deficient PC mice exhibited rapider cancer progression and poorer survival rate. CARD9 knockout decreased dendritic cell (DC) maturation and impaired DC ability to activate T cells in vivo and in vitro. Adoptive DC transfer confirmed that the role of CARD9 deficiency in PC relied on DCs. Creatine was identified as the most significant differential metabolite between WT DCs and CARD9-/- DCs wherein it played an essential role in maintaining DC maturation and function. CARD9 deficiency led to decreased creatine levels in DCs by inhibiting the transcription of the creatine-specific transporter, solute carrier family 6 member 8 (SLC6A8). Furtherly, CARD9 deletion blocked p65 activation by abolishing the formation of CARD9-BCL10-MALT1 complex, which prevented the binding between p65 and SLC6A8 promoter. These events decreased the creatine transport into DCs, and led to DC immaturity and impairment in antitumor immunity, consequently promoting PC progression.
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Neoplasias Pancreáticas , Transducción de Señal , Animales , Ratones , Creatina/metabolismo , Neoplasias Pancreáticas/genética , Células Dendríticas , Proteínas Adaptadoras de Señalización CARD/metabolismoRESUMEN
Bound solitons have become a hot topic in the field of nonlinear optics due to their potential applications in optical communication, information processing and radar systems. However, the trapping of the cascaded bound soliton is still a major challenge up to now. Here, we propose and experimentally demonstrate a multi-pulse bound soliton fiber laser based on MoTe2 saturable absorber. In the experiment, MoTe2 nanosheets were synthesized by chemical vapor deposition and transferred to the fiber taper by optical deposition. Then, by inserting the MoTe2 saturable absorber into a ring cavity laser, the two-pulse, three-pulse and four-pulse bound solitons can be stably generated by properly adjusting the pump strength and polarization state. These cascaded bound solitons are expected to be applied to all-optical communication and bring new ideas to the study of soliton lasers.