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The development of lithium-sulfur batteries (LSBs) is impeded by the shuttle effect of polysulfides (LiPSs) and the sluggish nucleation of Li2S. To address these challenges, incorporating electrocatalysts into sulfur host materials represents an effective strategy for promoting polysulfide conversion, in tandem with the rational design of multifunctional sulfur host materials. In this study, Pt nanoparticles are integrated into biomass-derived carbon materials by solution deposition method. Pt, as an electrocatalyst, not only enhances the electrical conductivity of sulfur cathodes and effectively immobilizes LiPSs but also catalyzes the redox reactions of sulfur species bidirectionally. Additionally, Pt helps regulate the 3D deposition and growth of Li2S while reducing the reaction energy barrier. Consequently, this accelerates the conversion of LiPSs in LSBs. Furthermore, the catalytic ability of Pt for the redox reactions of sulfur species, along with its influence on the 3D deposition and growth of Li2S, is elucidated using electrochemical kinetic analyses and classical models of electrochemical deposition. The cathodes exhibit a high initial specific capacity of 1019.1 mAh g-1 at 1 C and a low decay rate of 0.045% over 1500 cycles. This study presents an effective strategy to regulate Li2S nucleation and enhance the kinetics of polysulfide conversion in LSBs.
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PURPOSE: Cancer survivors have a high risk of mortality, and vitamin D (VD) is associated with the risk of mortality. This study is aim to examine the impact of VD on mortality in cancer survivors. METHODS: A prospective study was conducted using data from the National Health and Nutrition Examination Survey. Participants were obtained information on their baseline characteristics, dietary habits, comorbidities, lifestyle, and serum 25-hydroxy VD [25(OH)D] concentrations. The weighted Cox proportional hazard and competing risk regression models were used to estimate the hazard ratio and 95% confidence intervals (HR, 95% CI) of mortality for different serum 25(OH)D concentrations. Restricted cubic spline (RCS) curves were utilized to illustrate the dose-response relationship between serum 25(OH)D concentrations and mortality. RESULTS: The study encompassed 2,495 participants with cancer diagnoses. Multivariate models indicated that, compared to serum 25(OH)D concentrations below 58.5 nmol/L, concentrations exceeding 81.6 nmol/L were associated with reduced HRs for all-cause mortality (HR = 0.70; 95% CI: 0.56-0.87), cardiovascular mortality (HR = 0.53; 95% CI: 0.32-0.86), and cancer-specific mortality (HR = 0.66; 95% CI: 0.45-0.99). RCS curves revealed "L-shaped" associations between serum 25(OH)D concentration and both all-cause and cancer-specific mortality, with threshold effects at 87.9 nmol/L and 84.6 nmol/L, respectively. Conversely, the relationship between serum 25(OH)D concentration and cardiovascular mortality exhibited a more linear pattern, with a threshold at 88.7 nmol/L. Subgroup analyses highlighted a gender-specific interaction that elevated serum 25(OH)D concentrations were significantly more protective against mortality in males than in females, especially regarding cancer-specific mortality (P-interaction = 0.009). CONCLUSION: Elevated serum 25(OH)D concentrations were correlated with decreased risks of all-cause, cardiovascular, and cancer-specific mortality in cancer survivors, with benefit thresholds at 87.9, 88.7, and 84.6 nmol/L, respectively. These findings suggested that cancer survivors might benefit from higher vitamin D recommendations than the general population.
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Sobreviventes de Câncer , Neoplasias , Inquéritos Nutricionais , Vitamina D , Vitamina D/análogos & derivados , Humanos , Vitamina D/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Sobreviventes de Câncer/estatística & dados numéricos , Estados Unidos/epidemiologia , Estudos Prospectivos , Neoplasias/mortalidade , Neoplasias/sangue , Idoso , Adulto , Fatores de Risco , Modelos de Riscos Proporcionais , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/sangueRESUMO
INTRODUCTION: The dysfunction of natural killer (NK) cells has been widely reported in malignancies, including in solid tumours. Gastric cancer mesenchymal stem cells (GCMSCs) are one of the vital elements of stromal cells in the tumour environment (TME) which possess immunosuppressive activity. This study aimed to determine whether GCMSCs are involved in the inhibition of NK cell immune function and explore its underlying mechanism. MATERIAL AND METHODS: CD107a and perforin expression of GCMSCs conditioned medium (GCMSCs-CM)-primed NK cells were detected by flow cytometry. To determine NK cell cytotoxicity, the CytoTox96 Non-Radioactive Cytotoxicity Assay kit was used. Glucose uptake and lactate production assay were performed to evaluate the metabolism state of NK cells treated with GCMSCs-CM. The expression of FBP1 in NK cells was analysed by immunoblotting. RESULTS: GCMSCs inhibited the degranulation capacity, perforin production and cytotoxicity of NK cells. GCMSCs-CM restrained NK cell glucose uptake and lactate production, thus weakening their glycolytic metabolism. FBP1 expression of NK cells was upregulated in the presence of GCMSCs-CM. Using FBP1 inhibitor could reverse the dysfunctional state of NK cells. CONCLUSIONS: This study indicated that GCMSCs could exert immunosuppressive effects on NK cells by up-regulating FBP1 expression, opening up new avenues for NK cell-based GC immunotherapy.
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BACKGROUND: Contemporarily authoritative algorithms for the prediction of acute pulmonary embolism (PE) comprise the Standard algorithm, the Age-adjusted algorithm, the YEARS algorithm, the PERC algorithm, and the PEGeD algorithm. To date, little is known with respect to which algorithm is most appropriate for the PE prediction in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: The patients with AECOPD who underwent the confirmed chest imaging investigations of PE due to the likelihood of PE predicted by the Standard algorithm were retrospectively reviewed. The patients were reassessed by the other four algorithms to reveal which algorithm had the best diagnostic accuracy for the likelihood prediction of PE for patients with AECOPD. RESULTS: The results showed that the PEGeD algorithm(88.6, 80.7, 50.4, 97.0%, 4.591, 0.141, 0.693, 82.1%) performed better overall in the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, Youden index, and diagnostic accuracy, in comparison with the Age-adjusted algorithm (78.6, 74.1, 40.1, 94.0%, 3.034, 0.289, 0.527, 74.9%), the YEARS algorithm (71.4, 76.6, 40.3, 92.4%, 3.051, 0.373, 0.480,75.6%), the PERC algorithm (98.6, 1.6, 18.2, 83.3%, 1.002, 0.875, 0.002, 19.2%). The difference of number of patients who were necessary to undergo chest imaging examinations and missed diagnoses resulted from each algorithm between the PEGeD algorithm and the Standard algorithm, the Age-adjusted algorithm, the YEARS algorithm, as well as the PERC algorithm were [- 789 (- 68.1%), N/A], [- 42 (- 3.6%),-21 (- 1.8%)], [- 3 (- 0.3%),-36 (- 3.1%)],[- 771 (- 66.6%), 21 (1.8%)], respectively. CONCLUSIONS: To date, the PEGeD algorithm is the most appropriate strategy among the authoritative algorithms for the likelihood prediction of pulmonary embolism in patients with AECOPD.
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Algoritmos , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/epidemiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Tomografia Computadorizada por Raios X/normasRESUMO
BACKGROUND: A deep learning computer artificial intelligence system is helpful for early identification of ground glass opacities (GGOs). METHODS: Images from the Lung Image Database Consortium and Image Database Resource Initiative (LIDC-IDRI) database were used in AlexNet and GoogLeNet to detect pulmonary nodules, and 221 GGO images provided by Xinhua Hospital were used in ResNet50 for detecting GGOs. We used computed tomography image radial reorganization to create the input image of the three-dimensional features, and used the extracted features for deep learning, network training, testing, and analysis. RESULTS: In the final evaluation results, we found that the accuracy of identification of lung nodule could reach 88.0%, with an F-score of 0.891. In terms of performance and accuracy, our method was better than the existing solutions. The GGO nodule classification achieved the best F-score of 0.87805. We propose a preprocessing method of red, green, and blue (RGB) superposition in the region of interest to effectively increase the differentiation between nodules and normal tissues, and that is the innovation of our research. CONCLUSIONS: The method of deep learning proposed in this study is more sensitive than other systems in recent years, and the average false positive is lower than that of others.
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Aprendizado Profundo , Diagnóstico por Computador/métodos , Pulmão/diagnóstico por imagem , Nódulo Pulmonar Solitário/diagnóstico por imagem , Algoritmos , Bases de Dados Factuais , Reações Falso-Positivas , Humanos , Processamento de Imagem Assistida por Computador , Neoplasias Pulmonares/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Radiologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: The diagnostic criteria for asthma-chronic obstructive pulmonary disease overlap have not been unified. Different studies have used different criteria, and this has led to diagnostic inconsistencies. METHODS: We collected data of patients who were older than 40 years and hospitalised because of chronic bronchial diseases. One hundred and seventy-one patients were included in this study. We compared seven different diagnostic criteria, examined their consistency, and analysed differences among groups classified with each set. RESULTS: The prevalence of ACO ranged between 7.02 and 27.49% depending on the criteria applied. The patients who met the Soler-Cataluna et al. criteria also met the GesEPOC criteria. Rhee has proposed the strictest diagnostic criteria; hence, the number of patients who met these criteria was the smallest, and those patients also met the diagnostic criteria proposed by the other studies. We found that applying the different sets of criteria did not lead to the selection of the same population, while there were no statistical differences in age, disease duration, allergens, and inflammatory markers. CONCLUSIONS: The diagnostic criteria of ACO have not been unified, which hinders the design and progress of clinical studies that would investigate the ACO phenotypes and underlying mechanisms.
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Síndrome de Sobreposição da Doença Pulmonar Obstrutiva Crônica e Asma/diagnóstico , Idoso , Síndrome de Sobreposição da Doença Pulmonar Obstrutiva Crônica e Asma/epidemiologia , Síndrome de Sobreposição da Doença Pulmonar Obstrutiva Crônica e Asma/metabolismo , Síndrome de Sobreposição da Doença Pulmonar Obstrutiva Crônica e Asma/fisiopatologia , Testes Respiratórios , China/epidemiologia , Feminino , Volume Expiratório Forçado , Humanos , Interleucina-2/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , Prevalência , Espirometria , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND AND OBJECTIVE: Statins have been widely used in inflammatory diseases including asthma, because of their anti-inflammatory and immunomodulatory properties. It has been shown that simvastatin induces autophagy and cell death in some circumstances. However, the possible cross-talk between simvastatin and autophagic processes in lung disease is largely unknown. Thus, we investigated the impact of simvastatin on airway inflammation and airway remodelling and the possible relationship of these processes to a simvastatin-induced autophagic pathway in mouse models of asthma. METHODS: Ovalbumin (OVA)-sensitized and challenged mice were treated with simvastatin and sacrificed. The autophagy-related proteins Atg5, LC3B and Beclin1 were quantified, as well as the autophagy flux in bronchial smooth muscle cells (BSMCs). The relationship between airway inflammation and the autophagic process was investigated. RESULTS: We show that simvastatin treatment mediates activation of autophagy in BSMCs, which is correlated with airway inflammation and airway remodelling in mouse models of asthma. Simvastatin increases autophagy-related protein Atg5, LC3B and Beclin1 expression and autophagosome formation in lung tissue. Simvastatin-induced autophagy is associated with increased interferon-gamma (IFN-γ) and decreased IL-4, IL-5 and IL-13 cytokines production in BSMCs, as well as reversed extracellular matrix (ECM) deposition. In contrast, autophagy inhibitor 3-methyladenine (3-MA) eliminates the therapeutic effect of simvastatin. CONCLUSION: These findings demonstrate that simvastatin inhibits airway inflammation and airway remodelling through an activated autophagic process in BSMCs. We propose a crucial function of autophagy in statin-based therapeutic approaches in asthma.
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Remodelação das Vias Aéreas/efeitos dos fármacos , Asma/tratamento farmacológico , Autofagia/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inflamação/tratamento farmacológico , Miócitos de Músculo Liso/metabolismo , Sinvastatina/farmacologia , Adenina/análogos & derivados , Adenina/farmacologia , Animais , Asma/fisiopatologia , Autofagossomos , Proteína 5 Relacionada à Autofagia/metabolismo , Proteína Beclina-1/metabolismo , Citocinas/biossíntese , Modelos Animais de Doenças , Matriz Extracelular/metabolismo , Feminino , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Interferon gama/biossíntese , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Associadas aos Microtúbulos/metabolismo , Miócitos de Músculo Liso/fisiologia , Ovalbumina/farmacologia , Sinvastatina/uso terapêutico , Regulação para CimaRESUMO
Video-assisted mediastinoscopy (VAM) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are the two most commonly used invasive methods for mediastinal staging of lung cancer. The objective of this review is to assess and compare the overall diagnostic values of VAM and EBUS-TBNA. PubMed, Embase, Web of Science and the Cochrane Library were searched for studies that evaluated EBUS-TBNA or VAM accuracy. Quantitative meta-analysis was used to pool sensitivity and specificity, and study quality was evaluated. Meta-regression was applied to indirectly compare EBUS-TBNA and VAM after adjusting quality score, study design, and station number. A total of ten studies with 999 EBUS-TBNA patients and seven studies with 915 VAM patients were included. Since the pooled specificity was 100% for both modalities, sensitivity was mainly analyzed. The pooled sensitivities for EBUS-TBNA and VAM were 0.84 (95% CI 0.79-0.88) and 0.86 (95% CI 0.82-0.90), respectively. Subgroup analyses of quality score, study design, station number and rapid on-site cytologic evaluation showed no significant influence on the overall sensitivity of the two modalities. After adjusting quality score, study design, and station number, the pooled sensitivities of VAM and EBUS-TBNA were not significantly different. However, more procedural complications and fewer false negatives (FN) were found with VAM than EBUS-TBNA. VAM and EBUS exhibited equally high diagnostic accuracy for mediastinal staging of lung cancer. Due to lower morbidity with EBUS-TBNA and fewer FN with VAM, EBUS-TBNA should be performed first, followed by VAM in the case of a negative needle result.
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Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Neoplasias Pulmonares/patologia , Mediastinoscopia/métodos , Broncoscopia/efeitos adversos , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/efeitos adversos , Reações Falso-Negativas , Humanos , Mediastinoscopia/efeitos adversos , Mediastino , Estadiamento de Neoplasias , Sensibilidade e Especificidade , Cirurgia Vídeoassistida/efeitos adversosRESUMO
Cigarette smoke has been shown to cause chronic inflammation of the lungs, eventually leading to chronic obstructive pulmonary disease (COPD). Additionally, recent studies have suggested that mesenchymal stem cells (MSCs) can mediate local inflammatory responses in the lungs. Thus, the aim of the present study was to test the effects of rat MSCs (rMSCs) on inflammation of the lungs and destructive pulmonary function induced by cigarette smoke in rats. Rats were exposed to cigarette smoke for 7 weeks. rMSCs were cultured in vitro and infused intratracheally into cigarette smoke-exposed rats. The total and differential cell counts in the bronchoalveolar lavage fluid (BALF), histological changes, pro-inflammatory cytokines, transforming growth factor-ß1 (TGF-ß1) expression, and pulmonary function were evaluated. Additionally, human peripheral blood mononuclear cells and human MSCs were cocultured in vitro to detect cytokines and TGF-ß1 levels. We found that rMSC administration resulted in downregulation of pro-inflammatory cytokines in the lungs while increasing TGF-ß1 expression, reducing total inflammatory cell numbers in the BALF, and improving pulmonary histopathology and airflow obstruction. Coculture revealed that human MSCs mediated an anti-inflammatory effect partly via upregulation of TGF-ß1. These findings suggested that MSCs may have therapeutic potential in cigarette smoke-induced inflammation and airflow obstruction, partly via upregulation of TGF-ß1.
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Inflamação/induzido quimicamente , Leucócitos Mononucleares/imunologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/imunologia , Nicotiana/efeitos adversos , Fumaça/efeitos adversos , Fator de Crescimento Transformador beta1/imunologia , Animais , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Contagem de Células , Técnicas de Cocultura , Citocinas/imunologia , Humanos , Inflamação/imunologia , Mediadores da Inflamação/imunologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/imunologia , TraqueiaRESUMO
Muscle atrophy is a common extrapulmonary co-morbidity affecting about 20% of patients with COPD. However, the mechanism of muscle atrophy in COPD remains unclear. This study investigated the role of the ubiquitin-proteasome system (UPS) and the autophagy system in COPD muscle atrophy and its mechanism. A COPD rat model was established to evaluate the in vitro effects of the UPS and the autophagy system in muscle atrophy. In addition, the role of the UPS, autophagy systems, and the expressions of the PI3K/AKT/FOXO3a pathway were studied in the CSE-induced L6 myoblast cells. Furthermore, we evaluated the effect of FOXO3a in the CSE-induced L6 myoblast cells using siRNA-FOXO3a. The results showed that the expression of ubiquitin-related proteins and autophagy-related proteins were significantly increased in the COPD rat model and CSE-induced L6 myoblast cells. At the same time, there was a concurrent decrease in the phosphorylation protein expression of PI3K and AKT, but the transcriptional activity of FOXO3a was increased in CSE-induced L6 myoblast cells. And siRNA-FOXO3a significantly decreased the expression level of the UPS and the autophagy system in CSE-induced L6 myoblast cells. These results suggest that PI3K/AKT/FOXO3a participates in COPD muscle atrophy by regulating the UPS and the autophagy systems.
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Autofagia , Atrofia Muscular , Fosfatidilinositol 3-Quinases , Complexo de Endopeptidases do Proteassoma , Doença Pulmonar Obstrutiva Crônica , Transdução de Sinais , Ubiquitina , Animais , Masculino , Ratos , Linhagem Celular , Modelos Animais de Doenças , Proteína Forkhead Box O3/metabolismo , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Mioblastos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Ratos Sprague-Dawley , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Ubiquitina/metabolismoRESUMO
High-entropy alloys (HEAs) have attracted considerable attention, owing to their exceptional characteristics and high configurational entropy. Recent findings demonstrated that incorporating HEAs into sulfur cathodes can alleviate the shuttling effect of lithium polysulfides (LiPSs) and accelerate their redox reactions. Herein, we synthesized nano Pt0.25Cu0.25Fe0.15Co0.15Ni0.2 HEAs on hollow carbons (HCs; denoted as HEA/HC) by a facile pyrolysis strategy. The HEA/HC nanostructures were further integrated into hypha carbon nanobelts (HCNBs). The solid-solution phase formed by the uniform mixture of the five metal elements, i.e., Pt0.25Cu0.25Fe0.15Co0.15Ni0.2 HEAs, gave rise to a strong interaction between neighboring atoms in different metals, resulting in their adsorption energy transformation across a wide, multipeak, and nearly continuous spectrum. Meanwhile, the HEAs exhibited numerous active sites on their surface, which is beneficial to catalyzing the cascade conversion of LiPSs. Combining density functional theory (DFT) calculations with detailed experimental investigations, the prepared HEAs bidirectionally catalyze the cascade reactions of LiPSs and boost their conversion reaction rates. S/HEA@HC/HCNB cathodes achieved a low 0.034% decay rate for 2000 cycles at 1.0 C. Notably, the S/HEA@HC/HCNB cathode delivered a high initial areal capacity of 10.2 mAh cm-2 with a sulfur loading of 9 mg cm-2 at 0.1 C. The assembled pouch cell exhibited a capacity of 1077.9 mAh g-1 at the first discharge at 0.1 C. The capacity declined to 71.3% after 43 cycles at 0.1 C. In this work, we propose to utilize HEAs as catalysts not only to improve the cycling stability of lithium-sulfur batteries, but also to promote HEAs in energy storage applications.
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Progressive pulmonary inflammation and emphysema have been implicated in the progression of chronic obstructive pulmonary disease (COPD), while current pharmacological treatments are not effective. Transplantation of bone marrow mesenchymal stem cells (MSCs) has been identified as one such possible strategy for treatment of lung diseases including acute lung injury (ALI) and pulmonary fibrosis. However, their role in COPD still requires further investigation. The aim of this study is to test the effect of administration of rat MSCs (rMSCs) on emphysema and pulmonary function. To accomplish this study, the rats were exposed to cigarette smoke (CS) for 11 weeks, followed by administration of rMSCs into the lungs. Here we show that rMSCs infusion mediates a down-regulation of pro-inflammatory mediators (TNF-α, IL-1ß, MCP-1, and IL-6) and proteases (MMP9 and MMP12) in lung, an up-regulation of vascular endothelial growth factor (VEGF), VEGF receptor 2, and transforming growth factor (TGFß-1), while reducing pulmonary cell apoptosis. More importantly, rMSCs administration improves emphysema and destructive pulmonary function induced by CS exposure. In vitro co-culture system study of human umbilical endothelial vein cells (EA.hy926) and human MSCs (hMSCs) provides the evidence that hMSCs mediates an anti-apoptosis effect, which partly depends on an up-regulation of VEGF. These findings suggest that MSCs have a therapeutic potential in emphysematous rats by suppressing the inflammatory response, excessive protease expression, and cell apoptosis, as well as up-regulating VEGF, VEGF receptor 2, and TGFß-1.
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Lesão Pulmonar , Transplante de Células-Tronco Mesenquimais , Receptores de Fatores de Crescimento do Endotélio Vascular , Fator de Crescimento Transformador beta , Fator A de Crescimento do Endotélio Vascular , Animais , Modelos Animais de Doenças , Enfisema/induzido quimicamente , Enfisema/terapia , Regulação da Expressão Gênica , Humanos , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/terapia , Células-Tronco Mesenquimais , Pneumonia/induzido quimicamente , Pneumonia/terapia , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Doença Pulmonar Obstrutiva Crônica/terapia , Ratos , Receptores de Fatores de Crescimento do Endotélio Vascular/genética , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Fumar/efeitos adversos , Produtos do Tabaco/toxicidade , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Lithium-sulfur (Li-S) batteries have been considered one of the most promising candidates for next-generation energy storage devices due to their high theoretical energy density and low cost. Nonetheless, the practical application of Li-S batteries is still inhibited by their lithium polysulfide (LiPS) shuttling and sluggish redox kinetics, which cause rapid capacity decay and inferior rate performance. Hence, anchoring LiPSs and catalyzing their conversion reactions are imperative to enhance the performance of Li-S batteries. In this work, one-dimensional (1D) porous carbon-encapsulated CoS2 (CoS2@C) fiber structures were prepared through a simple two-step hydrothermal reaction and they exhibited a robust LiPS trapping ability and rapid catalytic conversion of LiPSs. The formed three-dimensional (3D) architecture (CoS2@C/MWCNT) facilitates the physical adsorption of LiPSs and rapid ion transport. The electrode exhibited a high initial capacity of 1329.5 mA h g-1 at a current density of 0.1 C and a reversible capacity of 1060.6 mA h g-1 after 100 cycles, with an 80% capacity retention rate. Meanwhile, the decay rate of the electrode is 0.048% per cycle at 1 C and after 500 cycles. With a sulfur loading of 3 mg cm-2, the capacity retention rate is approximately 83.7% after 80 cycles.
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The ATP-adenosine pathway functions as a key modulator of innate and adaptive immunity within the tumor microenvironment, and cancer immune evasion largely involves the generation of high amounts of immunosuppressive extracellular adenosine (eADO). Consequently, inhibition of eADO-generating enzymes and/or eADO receptors can effectively restore the antitumor immunity of multiple immune cells. With several clinical strategies currently being explored to modulating the eADO pathway in patients with cancer, recent clinical data with antagonists targeting CD73 and A2A receptor have demonstrated a promising therapeutic potential in cancer. Recent findings reveal that the ectonucleotidase CD39, the limiting enzyme been viewed as "immunological switch", converts ATP-driven pro-inflammatory milieu to an anti-inflammatory state mediated by adenosine. Owing to its superior feature of CD39 antagonism that rely not only on preventing the accumulation of adenosine but also on the stabilization of extracellular ATP to restore antitumor immunity, several inhibitors and clinical trials based on CD39 are being evaluated. Consequently, there is currently a focus on understanding the role of CD39 in governing immunity and how therapeutic strategies targeting this pathway alter the antitumor potential. We herein review the impact of CD39 on tumor microenvironment with a focus on treatment preference. Additionally, we also discuss the implication for rational combination therapies, molecular regulation, as well as potential limitations.
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Apirase , Neoplasias , 5'-Nucleotidase/metabolismo , Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Apirase/metabolismo , Humanos , Imunoterapia , Neoplasias/tratamento farmacológico , Microambiente TumoralRESUMO
Lithium-sulfur (Li-S) batteries have the potential to become the future energy storage system, yet they are plagued by sluggish redox kinetics. Therefore, enhancing the redox kinetics of polysulfides is key for the development of high-energy density and long-life Li-S batteries. Herein, a Ketjen Black (KB)/V2CTX modified separator (KB/V2CTX-PP) based on the catalytic effect in continuous solid-to-liquid-to-solid reactions is proposed to accelerate the conversion of sulfur species during the charge/discharge process in which the V2CTX can enhance the redox kinetics and inhibit polysulfide shuttling. The cells assembled with KB/V2CTX-PP achieve a gratifying first discharge capacity of 1236.1 mA h g-1 at 0.2C and the average capacity decay per cycle reaches 0.049% within 1000 cycles at 1C. The work provides an efficient idea to accelerate redox conversion and suppress shuttle effects by designing a multifunctional catalytic separator.
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Ubiquitin-specific proteases (USPs) deubiquitinate ubiquitin-protein conjugates in the ubiquitin-proteasome system. Previous research shows that ubiquitin-specific protease-19 (USP-19) is up-regulated in mammalian skeletal muscle in some degradative conditions, such as including fasting, diabetes, dexamethasone treatment, and cancer, and its function is associated with muscle atrophy. However, it is still unclear whether USP-19 is involved in muscle atrophy induced by chronic obstructive pulmonary disease. Rats exposed to chronic cigarette smoke and L6 myotubes incubated with cigarette smoke extract (CSE) were studied here. Using western blot analysis and quantitative real-time polymerase chain reaction (qPCR), we observed over-expression of USP-19 and down-regulation of myosin heavy chain (MHC) in both models. Moreover, CSE exposure inhibited myogenic differentiation and myotube formation in L6 myotubes. To explore the mechanism underlying these effects, we investigated the levels of phosphorylated mitogen-activated protein kinases (MAPKs) and total MAPKs. Exposing myotubes to CSE resulted in the general activation of MAPKs such as p38, JNK, and ERK1/2. The ERK inhibitor PD98059 and the p38 inhibitor SB203580 significantly blocked the increase in USP-19 gene expression induced by CSE. Our findings suggest that USP-19 is associated with muscle atrophy in response to cigarette smoke and is a potential therapeutic target. CSE promotes myotube wasting in culture partly by inhibiting myogenic differentiation and acts via p38 and ERK MAPK to stimulate expression of USP-19 in vitro.
Assuntos
Endopeptidases/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Atrofia Muscular/etiologia , Músculo Quadríceps/patologia , Fumar/efeitos adversos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Linhagem Celular , Endopeptidases/genética , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , Expressão Gênica , Masculino , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patologia , Fibras Musculares Esqueléticas/ultraestrutura , Atrofia Muscular/metabolismo , Cadeias Pesadas de Miosina/genética , Cadeias Pesadas de Miosina/metabolismo , Fosforilação , Inibidores de Proteínas Quinases/farmacologia , Músculo Quadríceps/metabolismo , Ratos , Ratos Sprague-Dawley , Regulação para Cima , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidoresRESUMO
BACKGROUND: This study aimed to reveal the correlation between serum soluble interleukin-2 receptor (sIL-2R) and prognosis in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: A total of 315 patients diagnosed with AECOPD between December 2017 and June 2020 were enrolled. The patients were divided into the good and adverse groups based on the outcomes. An adverse outcome in COPD exacerbation was defined by the presence of at least one of the following: (1) death from a respiratory cause during hospitalisation or within 1 month of follow-up; (2) intensive care unit admission; (3) invasive or non-invasive mechanical ventilation; and (4) COPD-related emergency visit or readmission within 1 month of follow-up. A good outcome was considered as the absence of all the aforementioned issues. The patients underwent lung function (spirometry) assessment, and clinical and inflammatory profiles were collected. Univariate and multivariate analyses were performed to identify the correlation between serum sIL-2R concentration and other variables related to adverse outcomes of AECOPD. The receiver operating characteristic curve was used to show the predictive ability of sIL-2R for adverse outcomes of AECOPD. RESULTS: We enrolled 315 patients, of whom 161 and 154 had good and adverse outcomes, respectively. We demonstrated that patients with adverse outcomes of AECOPD had a higher concentration of serum sIL-2R than patients with good outcomes (p < 0.001). The increased serum sIL-2R was positively associated with mMRC scores (p < 0.001), GLOD grades (p < 0.001), frequent exacerbation (p < 0.001), and smoking (p < 0.001) in patients with AECOPD and negatively correlated with pulmonary function (p < 0.001). An elevated sIL-2R level was a predictor for the risk of adverse outcomes in AECOPD with a cut-off value of 860 U/mL. CONCLUSION: Increased serum sIL-2R concentration correlated with the risk of the adverse outcomes in AECOPD, indicating that it can be a predictive factor contributing to the diagnosis and assessment of adverse outcomes in patients with AECOPD.
Assuntos
Doença Pulmonar Obstrutiva Crônica , Doença Aguda , Progressão da Doença , Hospitalização , Humanos , Pulmão , Prognóstico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/terapia , Receptores de Interleucina-2RESUMO
OBJECTIVE: To provide an overview of the existing international and Chinese evidence regarding dual bronchodilator inhalation therapy and to make recommendations for the further improvement of chronic obstructive pulmonary disease (COPD) management in clinical practice in China. BACKGROUND: COPD is a progressive lung disease that is characterized by persistent airflow limitation and is a major contributor to the disease burden in China. Symptoms in Chinese patients are relatively more severe. Currently, many Chinese COPD patients are undertreated. Dual bronchodilator therapy consisting of a long-acting muscarinic antagonist (LAMA) and a long-acting ß agonist (LABA) is considered a good choice for COPD patients due to the increased bronchodilation without an increase in adverse events; these combinations can fill in the gap in currently available COPD treatments and provide new pharmacotherapy options for Chinese patients. LAMA/LABA fixed-dose combinations (FDCs) have become more important in clinical practice and guidelines in China regarding their therapeutic effects and safety. METHODS: Clinical trials on LAMA/LABA in COPD were retrieved in ClinicalTrials.gov, while important COPD guidelines published in English or Chinese were found in PubMed and Wanfang Database. CONCLUSIONS: We recommend the adoption of a clinical pathway in China that includes an assessment and management algorithm that considers the clinical characteristics in China and classifies the phenotypic characteristics of COPD according to a suitable system. Based on the current information, we can conclude that LAMA/LABA FDCs are a suitable and economically viable choice to reduce symptoms and improve the quality of life (QoL) of patients.
RESUMO
The dysfunction of natural killer (NK) cells has been increasingly reported in malignancies, especially in solid tumours. Mesenchymal stem cells (MSCs) exhibit pleiotropic functions that include mediating immune cell exhaustion which is implicated in cancer progression. However, the association of MSCs derived from gastric cancer (gastric cancer mesenchymal stem cells: GCMSCs) with the dysfunction of NK cells remains poorly understood. In this study, we demonstrated that GCMSCs effectively contributed to the exhaustion of NK cells through the release of soluble factors. Furthermore, passivation of the antitumour effect in NK cells was closely associated with their dysfunctional state. The GCMSC-conditioned medium prevented the frequency and effector function of infiltrating NK cells in tumour-bearing mouse models, thus promoting tumour growth. Mechanistically, mammalian target of rapamycin (mTOR) signalling, a critical regulator of cellular metabolism that mediates the function of immune cells, was inhibited in NK cells treated with GCMSCs. However, the checkpoint receptor PD-1 was still present at minimal levels with or without GCMSCs. The study results revealed that GCMSCs contributed to dysfunctional NK cells involved at least partially in the inhibition of mTOR signalling, suggesting potential directions for NK cell-based cancer immunotherapy.
RESUMO
BACKGROUND: Chronic obstructive pulmonary disease (COPD) often coexists with multiple comorbidities which may have a significant impact on acute exacerbations of patients. At present, what kind of comorbidities affects acute exacerbations and how comorbidities lead to poor prognosis are still controversial. The purpose of our study is to determine the impact of comorbidities on COPD exacerbation and establish an acute exacerbation risk assessment system related to comorbidities. METHODS: A total of 742 COPD patients participated in the Shanghai COPD Investigation on Comorbidity Program (SCICP, ChiCTR2000030911). Finally, the baseline information of 415 participants and one-year follow-up data were involved in the analysis. We collected hemogram indices, pulmonary function tests and acute exacerbation of COPD with regular medical follow-up. Q-type cluster analysis was used to determine the clusters of participants. Receiver operating characteristic (ROC) analysis was constructed to assess the ability of indicators in predicting acute exacerbations. RESULTS: Almost 65% of the population we investigated had at least one comorbidity. The distribution and incidence of comorbidities differed between exacerbation group and non-exacerbation group. Three comorbidity clusters were identified: (1) respiratory, metabolic, immune and psychologic disease (non-severe cases); (2) cardiovascular and neoplastic disease (severe cases); (3) less comorbidity. Different sub-phenotypes of COPD patients showed significant distinction in health status. Anxiety (OR=5.936, P=0.001), angina (OR=10.155, P=0.025) and hypertension (OR=3.142, P=0.001) were found to be independent risk factors of exacerbation in a year. The novel risk score containing BODEx and four diseases showed great prognostic value of COPD exacerbation in developing sample. CONCLUSION: Our study detailed the major interaction between comorbidities and exacerbation in COPD. Noteworthily, a novel risk score using comprehensive index - BODEx - and comorbidity parameters can identify patients at high risk of acute exacerbation.