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Radiation-induced heart damage caused by low-dose X-rays has a significant impact on tumour patients' prognosis, with cardiac hypertrophy being the most severe noncarcinogenic adverse effect. Our previous study demonstrated that mitophagy activation promoted cardiac hypertrophy, but the underlying mechanisms remained unclear. In the present study, PARL-IN-1 enhanced excessive hypertrophy of cardiomyocytes and exacerbated mitochondrial damage. Isobaric tags for relative and absolute quantification-based quantitative proteomics identified NDP52 as a crucial target mediating cardiac hypertrophy induced by low-dose X-rays. SUMOylation proteomics revealed that the SUMO E3 ligase MUL1 facilitated NDP52 SUMOylation through SUMO2. Co-IP coupled with LC-MS/MS identified a critical lysine residue at position 262 of NDP52 as the key site for SUMO2-mediated SUMOylation of NDP52. The point mutation plasmid NDP52K262R inhibited mitophagy under MUL1 overexpression, as evidenced by inhibition of LC3 interaction with NDP52, PINK1 and LAMP2A. A mitochondrial dissociation study revealed that NDP52K262R inhibited PINK1 targeting to endosomes early endosomal marker (EEA1), late/lysosome endosomal marker (LAMP2A) and recycling endosomal marker (RAB11), and laser confocal microscopy confirmed that NDP52K262R impaired the recruitment of mitochondria to the autophagic pathway through EEA1/RAB11 and ATG3, ATG5, ATG16L1 and STX17, but did not affect mitochondrial delivery to lysosomes via LAMP2A for degradation. In conclusion, our findings suggest that MUL1-mediated SUMOylation of NDP52 plays a crucial role in regulating mitophagy in the context of low-dose X-ray-induced cardiac hypertrophy. Two hundred sixty-second lysine of NDP52 is identified as a key SUMOylation site for low-dose X-ray promoting mitophagy activation and cardiac hypertrophy. Collectively, this study provides novel implications for the development of therapeutic strategies aimed at preventing the progression of cardiac hypertrophy induced by low-dose X-rays.
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Mitofagia , Proteínas Nucleares , Proteínas Quinasas , Humanos , Cardiomegalia/genética , Cromatografía Liquida , Lisina/metabolismo , Mitofagia/genética , Proteínas Quinasas/genética , Proteínas Quinasas/metabolismo , Proteínas Modificadoras Pequeñas Relacionadas con Ubiquitina/genética , Proteínas Modificadoras Pequeñas Relacionadas con Ubiquitina/metabolismo , Sumoilación , Espectrometría de Masas en Tándem , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Rayos X , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismoRESUMEN
BACKGROUND: The hypoxic tumor microenvironment is a key factor that promotes metabolic reprogramming and vascular mimicry (VM) in ovarian cancer (OC) patients. ESM1, a secreted protein, plays an important role in promoting proliferation and angiogenesis in OC. However, the role of ESM1 in metabolic reprogramming and VM in the hypoxic microenvironment in OC patients has not been determined. METHODS: Liquid chromatography coupled with tandem MS was used to analyze CAOV3 and OV90 cells. Interactions between ESM1, PKM2, UBA2, and SUMO1 were detected by GST pull-down, Co-IP, and molecular docking. The effects of the ESM1-PKM2 axis on cell glucose metabolism were analyzed based on an ECAR experiment. The biological effects of the signaling axis on OC cells were detected by tubule formation, transwell assay, RTâPCR, Western blot, immunofluorescence, and in vivo xenograft tumor experiments. RESULTS: Our findings demonstrated that hypoxia induces the upregulation of ESM1 expression through the transcription of HIF-1α. ESM1 serves as a crucial mediator of the interaction between PKM2 and UBA2, facilitating the SUMOylation of PKM2 and the subsequent formation of PKM2 dimers. This process promotes the Warburg effect and facilitates the nuclear translocation of PKM2, ultimately leading to the phosphorylation of STAT3. These molecular events contribute to the promotion of ovarian cancer glycolysis and vasculogenic mimicry. Furthermore, our study revealed that Shikonin effectively inhibits the molecular interaction between ESM1 and PKM2, consequently preventing the formation of PKM2 dimers and thereby inhibiting ovarian cancer glycolysis, fatty acid synthesis and vasculogenic mimicry. CONCLUSION: Our findings demonstrated that hypoxia increases ESM1 expression through the transcriptional regulation of HIF-1α to induce dimerization via PKM2 SUMOylation, which promotes the OC Warburg effect and VM.
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Proteínas Portadoras , Ácidos Grasos , Proteínas de la Membrana , Proteínas de Neoplasias , Neoplasias Ováricas , Proteínas de Unión a Hormona Tiroide , Hormonas Tiroideas , Microambiente Tumoral , Femenino , Humanos , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Neoplasias Ováricas/genética , Animales , Hormonas Tiroideas/metabolismo , Ratones , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Línea Celular Tumoral , Ácidos Grasos/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/genética , Proteínas Portadoras/metabolismo , Proteínas Portadoras/genética , Efecto Warburg en Oncología , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Regulación Neoplásica de la Expresión Génica , Neovascularización Patológica/metabolismo , Neovascularización Patológica/genética , Neovascularización Patológica/patología , Ensayos Antitumor por Modelo de Xenoinjerto , Proliferación Celular , ProteoglicanosRESUMEN
BACKGROUND: In the USA, the prolonged effective survival of cancer population has brought significant attention to the rising risk of cardiometabolic morbidity and mortality in this population. This heightened risk underscores the urgent need for research into effective pharmacological interventions for cancer survivors. Notably, metformin, a well-known metabolic regulator with pleiotropic effects, has shown protective effects against cardiometabolic disorders in diabetic individuals. Despite these promising indications, evidence supporting its efficacy in improving cardiometabolic outcomes in cancer survivors remains scarce. METHODS: A prospective cohort was established using a nationally representative sample of cancer survivors enrolled in the US National Health and Nutrition Examination Survey (NHANES), spanning 2003 to 2018. Outcomes were derived from patient interviews, physical examinations, and public-access linked mortality archives up to 2019. The Oxidative Balance Score was utilized to assess participants' levels of oxidative stress. To evaluate the correlations between metformin use and the risk of cardiometabolic diseases and related mortality, survival analysis of cardiometabolic mortality was performed by Cox proportional hazards model, and cross-sectional analysis of cardiometabolic diseases outcomes was performed using logistic regression models. Interaction analyses were conducted to explore the specific pharmacological mechanism of metformin. RESULTS: Among 3995 cancer survivors (weighted population, 21,671,061, weighted mean [SE] age, 62.62 [0.33] years; 2119 [53.04%] females; 2727 [68.26%] Non-Hispanic White individuals), 448 reported metformin usage. During the follow-up period of up to 17 years (median, 6.42 years), there were 1233 recorded deaths, including 481 deaths from cardiometabolic causes. Multivariable models indicated that metformin use was associated with a lower risk of all-cause (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.47-0.81) and cardiometabolic (HR, 0.65; 95% CI, 0.44-0.97) mortality compared with metformin nonusers. Metformin use was also correlated with a lower risk of total cardiovascular disease (odds ratio [OR], 0.41; 95% CI, 0.28-0.59), stroke (OR, 0.44; 95% CI, 0.26-0.74), hypertension (OR, 0.27; 95% CI, 0.14-0.52), and coronary heart disease (OR, 0.41; 95% CI, 0.21-0.78). The observed inverse associations were consistent across subgroup analyses in four specific cancer populations identified as cardiometabolic high-risk groups. Interaction analyses suggested that metformin use as compared to non-use may counter-balance oxidative stress. CONCLUSIONS: In this cohort study involving a nationally representative population of US cancer survivors, metformin use was significantly correlated with a lower risk of cardiometabolic diseases, all-cause mortality, and cardiometabolic mortality.
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Supervivientes de Cáncer , Enfermedades Cardiovasculares , Metformina , Humanos , Metformina/uso terapéutico , Femenino , Masculino , Supervivientes de Cáncer/estadística & datos numéricos , Persona de Mediana Edad , Estados Unidos/epidemiología , Enfermedades Cardiovasculares/mortalidad , Estudios Prospectivos , Hipoglucemiantes/uso terapéutico , Anciano , Estudios Transversales , Encuestas Nutricionales , Estudios de Cohortes , Neoplasias/mortalidadRESUMEN
Unveiling the inherent link between polysulfide adsorption and catalytic activity is key to achieving optimal performance in Lithium-sulfur (Li-S) batteries. Current research on the sulfur reaction process mainly relies on the strong adsorption of catalysts to confine lithium polysulfides (LiPSs) to the cathode side, effectively suppressing the shuttle effect of polysulfides. However, is strong adsorption always correlated with high catalysis? The inherent relationship between adsorption and catalytic activity remains unclear, limiting the in-depth exploration and rational design of catalysts. Herein, the correlation between "d-band center-adsorption strength-catalytic activity" in porous carbon nanofiber catalysts embedded with different transition metals (M-PCNF-3, M = Fe, Co, Ni, Cu) is systematically investigated, combining the d-band center theory and the Sabatier principle. Theoretical calculations and experimental analysis results indicate that Co-PCNF-3 electrocatalyst with appropriate d-band center positions exhibits moderate adsorption capability and the highest catalytic conversion activity for LiPSs, validating the Sabatier relationship in Li-S battery electrocatalysts. These findings provide indispensable guidelines for the rational design of more durable cathode catalysts for Li-S batteries.
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BACKGROUND: Ovarian cancer (OC) is a malignant neoplasm that displays increased vascularization. Angiopoietin-like 4 (ANGPTL4) is a secreted glycoprotein that functions as a regulator of cell metabolism and angiogenesis and plays a critical role in tumorigenesis. However, the precise role of ANGPTL4 in the OC microenvironment, particularly its involvement in angiogenesis, has not been fully elucidated. METHODS: The expression of ANGPTL4 was confirmed by bioinformatics and IHC in OC. The potential molecular mechanism of ANGPTL4 was measured by RNA-sequence. We used a series of molecular biological experiments to measure the ANGPTL4-JAK2-STAT3 and ANGPTL4-ESM1 axis in OC progression, including MTT, EdU, wound healing, transwell, xenograft model, oil red O staining, chick chorioallantoic membrane assay and zebrafish model. Moreover, the molecular mechanisms were confirmed by Western blot, Co-IP and molecular docking. RESULTS: Our study demonstrates a significant upregulation of ANGPTL4 in OC specimens and its strong association with unfavorable prognosis. RNA-seq analysis affirms that ANGPTL4 facilitates OC development by driving JAK2-STAT3 signaling pathway activation. The interaction between ANGPTL4 and ESM1 promotes ANGPTL4 binding to lipoprotein lipase (LPL), thereby resulting in reprogrammed lipid metabolism and the promotion of OC cell proliferation, migration, and invasion. In the OC microenvironment, ESM1 may interfere with the binding of ANGPTL4 to integrin and vascular-endothelial cadherin (VE-Cad), which leads to stabilization of vascular integrity and ultimately promotes angiogenesis. CONCLUSION: Our findings underscore that ANGPTL4 promotes OC development via JAK signaling and induces angiogenesis in the tumor microenvironment through its interaction with ESM1.
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Cistadenocarcinoma Seroso , Janus Quinasa 2 , Neoplasias Ováricas , Factor de Transcripción STAT3 , Animales , Femenino , Humanos , Microambiente Tumoral , Simulación del Acoplamiento Molecular , Angiogénesis , Pez Cebra/metabolismo , Carcinogénesis , Proliferación Celular , Carcinoma Epitelial de Ovario , Neoplasias Ováricas/genética , Línea Celular Tumoral , Proteína 4 Similar a la Angiopoyetina/genética , Proteínas de Neoplasias , ProteoglicanosRESUMEN
Venetoclax, a highly selective BCL-2 inhibitor, combined with hypomethylating agents (HMAs) azacitidine or decitabine, is approved for the treatment of newly diagnosed acute myeloid leukemia (ND AML) in patients who are ineligible to receive intensive chemotherapy. Previous clinical studies initiated venetoclax plus HMA in an inpatient setting owing to concerns of tumor lysis syndrome (TLS). This study (NCT03941964) evaluated the efficacy and safety of venetoclax plus HMA in a United States community-based outpatient setting in patients with ND AML (N = 60) who were treatment naïve for AML, ineligible to receive intensive chemotherapy, had no evidence of spontaneous TLS at screening, and were deemed as appropriate candidates for outpatient initiation of venetoclax plus HMA by the investigator. Patients received venetoclax in combination with azacitidine (75 mg/m2) or decitabine (20 mg/m2) for up to 6 cycles during the study. With a median time on study of 18.3 weeks, the best response rate of composite complete remission was 66.7%, and the overall post-baseline red blood cell (RBC) and platelet transfusion independence rate was 55.0%, consistent with results of studies in which treatment was initiated in an inpatient setting. Key adverse events included nausea, anemia, thrombocytopenia, neutropenia, and white blood cell count decrease of any grade (≥50% of patients). The observed safety profile was generally consistent with that of venetoclax plus HMA observed in inpatient AML studies. With close monitoring, 2 cases of TLS were identified, appropriately managed, and the patients were able to continue study treatment. CLINICAL TRIALS REGISTRATION: This study is registered at ClinicalTrials.gov. The registration identification number is NCT03941964.
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Protocolos de Quimioterapia Combinada Antineoplásica , Azacitidina , Compuestos Bicíclicos Heterocíclicos con Puentes , Decitabina , Leucemia Mieloide Aguda , Sulfonamidas , Humanos , Sulfonamidas/administración & dosificación , Sulfonamidas/uso terapéutico , Sulfonamidas/efectos adversos , Azacitidina/administración & dosificación , Azacitidina/uso terapéutico , Azacitidina/efectos adversos , Leucemia Mieloide Aguda/tratamiento farmacológico , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Compuestos Bicíclicos Heterocíclicos con Puentes/efectos adversos , Decitabina/administración & dosificación , Decitabina/uso terapéutico , Decitabina/efectos adversos , Femenino , Masculino , Anciano , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Anciano de 80 o más Años , Adulto , Pacientes AmbulatoriosRESUMEN
Multimodal luminescence involves color-tunable and wavelength manageable photon emissions upon variable luminescence pathways in response to different external stimuli, which provides clear visualization and high-level confidentiality for information encryption technologies. Integrating multimodal luminescence into a single matrix is regarded as a feasible strategy but remains a big challenge. In this work, multimodal (photoluminescence, persistent luminescence, upconversion luminescence, and thermally stimulated luminescence) and multicolor luminescence (green, yellow, orange, pink to red) is achieved in CaWO4:Yb3+,Er3+,Eu3+ phosphor by employing an interplay of traps and rare earth emission centers. Bright emission in a wide color gamut is achieved dynamically in response to thermal disturbance and light illumination, which further allows for on-demand emission manipulation in space and time dimensions. The compatible coexistence of multiple rare earth emissive centers together with abundant photoactive traps contributes to the excellent integration of multimodal photon emissions in calcium tungstate. This work provides a good example of integrating multimodal luminescence into one single matrix and indicates potential in advanced high-level information encryption applications.
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Pseudohemocyanin is a member of the hemocyanin superfamily, but little research is available on its function in immunology. In this study, a Portunus trituberculatus pseudohemocyanin gene, named PtPhc1, was obtained by gene cloning. The PtPhc1 cDNA was 2312 bp in length, encoding 684 amino acids while exhibiting a characteristic hemocyanin structural domain. Tissue expression analysis revealed ubiquitous expression of PtPhc1 across all tissues, with the highest level of expression observed in the hepatopancreas. The expression pattern of PtPhc1 in response to Vibrio parahaemolyticus infection was clarified using RT-qPCR in swimming crabs. Notably, the expression peaked at 24 h, and increased 1435-fold compared to the control group in the hepatopancreas. While the expression level reached the maximum value at 72 h, which was 3.24 times higher than that of the control group in hemocytes. Remarkably, the reduction in PtPhc1 expression led to a noteworthy 30% increase in the mortality rate of P. trituberculatus when exposed to V. parahaemolyticus. In addition, in vitro bacterial inhibition assays exhibited a dose-dependent suppression of bacterial proliferation by recombinant PtPhc1 protein, with a notable inhibition rate of 48.33% against V. parahaemolyticus at a concentration of 0.03 mg/mL. To the best of our knowledge, the results establish the function of pseudohaemocyanin in immunity for the first time, contributing to a deeper comprehension of innate immune regulatory mechanisms in aquatic organisms and advancing strategies for disease-resistant breeding.
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Braquiuros , Vibrio parahaemolyticus , Animales , Secuencia de Bases , Secuencia de Aminoácidos , Vibrio parahaemolyticus/genética , Hemocianinas/genética , Natación , FilogeniaRESUMEN
BACKGROUND: Left bundle branch block (LBBB) and atrial fibrillation (AF) are commonly coexisting conditions. The impact of LBBB on catheter ablation of AF has not been well determined. This study aims to explore the long-term outcomes of patients with AF and LBBB after catheter ablation. METHODS: Forty-two patients with LBBB of 11,752 patients who underwent catheter ablation of AF from 2011 to 2020 were enrolled as LBBB group. After propensity score matching in a 1:4 ratio, 168 AF patients without LBBB were enrolled as non-LBBB group. Late recurrence and a composite endpoint of stroke, all-cause mortality, and cardiovascular hospitalization were compared between the two groups. RESULTS: Late recurrence rate was significantly higher in the LBBB group than that in the non-LBBB group (54.8% vs. 31.5%, p = .034). Multivariate analysis showed that LBBB was an independent risk factor for late recurrence after catheter ablation of AF (hazard ratio [HR] 2.19, 95% confidence interval [CI] 1.09-4.40, p = .031). LBBB group was also associated with a significantly higher incidence of the composite endpoint (21.4% vs. 6.5%, HR 3.98, 95% CI 1.64-9.64, p = .002). CONCLUSIONS: LBBB was associated with a higher risk for late recurrence and a higher incidence of composite endpoint in the patients underwent catheter ablation.
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Fibrilación Atrial , Ablación por Catéter , Accidente Cerebrovascular , Humanos , Bloqueo de Rama/etiología , Factores de Riesgo , Accidente Cerebrovascular/etiología , Ablación por Catéter/efectos adversos , Resultado del Tratamiento , RecurrenciaRESUMEN
Government governance reform is not only a vital motivation for high economic quality but also an important factor in stimulating the government's environmental governance responsibility. The article empirically examines the fiscal Province-Managing-County (PMC) pilot reform on the synergic governance of haze and carbon reduction and its mechanism. The results show that the policy helps to realize the synergic governance of haze and carbon reduction, and the reform of fiscal Province-Managing-County promotes regional haze and carbon reduction mainly through structural effect, innovation effect, and fiscal expenditure responsibility effect. The heterogeneity analysis shows that the policy has an asymmetric effect on haze and carbon reduction under different administrative structures, economic structures and levels of government intervention. Further analysis shows a policy linkage effect between this policy and the Green Fiscal Policy. The policy has the situation of blood-sucking in the provincial capital city and leads to an increase in financial funds. The above results prove that the policy can help to realize haze and carbon reduction and provide practical ideas for the further expansion of the policy. At the same time, it provides the direction for the local government to realize the double-carbon goal.
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Contaminación del Aire , Contaminación del Aire/prevención & control , Contaminación del Aire/economía , Contaminación del Aire/legislación & jurisprudencia , Carbono , Política Ambiental/economía , Política Ambiental/legislación & jurisprudencia , Política , Gobierno LocalRESUMEN
BACKGROUND: Septic cardiomyopathy (SCM), a common cardiovascular comorbidity of sepsis, has emerged among the leading causes of death in patients with sepsis. SCM's pathogenesis is strongly affected by mitochondrial metabolic dysregulation and immune infiltration disorder. However, the specific mechanisms and their intricate interactions in SCM remain unclear. This study employed bioinformatics analysis and drug discovery approaches to identify the regulatory molecules, distinct functions, and underlying interactions of mitochondrial metabolism and immune microenvironment, along with potential interventional strategies in SCM. METHODS: GSE79962, GSE171546, and GSE167363 datasets were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and module genes were identified using Limma and Weighted Correlation Network Analysis (WGCNA), followed by functional enrichment analysis. Machine learning algorithms, including support vector machine-recursive feature elimination (SVM-RFE), least absolute shrinkage and selection operator (LASSO) regression, and random forest, were used to screen mitochondria-related hub genes for early diagnosis of SCM. Subsequently, a nomogram was developed based on six hub genes. The immunological landscape was evaluated by single-sample gene set enrichment analysis (ssGSEA). We also explored the expression pattern of hub genes and distribution of mitochondria/inflammation-related pathways in UMAP plots of single-cell dataset. Potential drugs were explored using the Drug Signatures Database (DSigDB). In vivo and in vitro experiments were performed to validate the pathogenetic mechanism of SCM and the therapeutic efficacy of candidate drugs. RESULTS: Six hub mitochondria-related DEGs [MitoDEGs; translocase of inner mitochondrial membrane domain-containing 1 (TIMMDC1), mitochondrial ribosomal protein S31 (MRPS31), F-box only protein 7 (FBXO7), phosphatidylglycerophosphate synthase 1 (PGS1), LYR motif containing 7 (LYRM7), and mitochondrial chaperone BCS1 (BCS1L)] were identified. The diagnostic nomogram model based on the six hub genes demonstrated high reliability and validity in both the training and validation sets. The immunological microenvironment differed between SCM and control groups. The Spearman correlation analysis revealed that hub MitoDEGs were significantly associated with the infiltration of immune cells. Upregulated hub genes showed remarkably high expression in the naive/memory B cell, CD14+ monocyte, and plasma cell subgroup, evidenced by the feature plot. The distribution of mitochondria/inflammation-related pathways varied across subgroups among control and SCM individuals. Metformin was predicted to be the most promising drug with the highest combined score. Its efficacy in restoring mitochondrial function and suppressing inflammatory responses has also been validated. CONCLUSIONS: This study presents a comprehensive mitochondrial metabolism and immune infiltration landscape in SCM, providing a potential novel direction for the pathogenesis and medical intervention of SCM.
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Cardiomiopatías , Sepsis , Humanos , Reproducibilidad de los Resultados , Mitocondrias , Cardiomiopatías/genética , ADN Mitocondrial , Biología Computacional , Inflamación , Sepsis/genética , Proteínas del Complejo de Importación de Proteínas Precursoras Mitocondriales , ATPasas Asociadas con Actividades Celulares Diversas , Complejo III de Transporte de Electrones , Chaperonas Moleculares , Proteínas MitocondrialesRESUMEN
Dual specificity phosphatase 1 (DUSP1) and valosin-containing protein (VCP) have both been reported to regulate mitochondrial homeostasis. However, their impact on mitochondrial quality control (MQC) and myocardial function during LPS-induced endotoxemia remains unclear. We addressed this issue by modeling LPS-induced endotoxemia in DUSP1 transgenic (DUSP1TG) mice and in cultured DUSP1-overexpressing HL-1 cardiomyocytes. Accompanying characteristic structural and functional deficits, cardiac DUSP1 expression was significantly downregulated following endotoxemia induction in wild type mice. In contrast, markedly reduced myocardial inflammation, cardiomyocyte apoptosis, cardiac structural disorder, cardiac injury marker levels, and normalized systolic/diastolic function were observed in DUSP1TG mice. Furthermore, DUSP1 overexpression in HL-1 cells significantly attenuated LPS-mediated mitochondrial dysfunction by preserving MQC, as indicated by normalized mitochondrial dynamics, improved mitophagy, enhanced biogenesis, and attenuated mitochondrial unfolded protein response. Molecular assays showed that VCP was a substrate of DUSP1 and the interaction between DUSP1 and VCP primarily occurred on the mitochondria. Mechanistically, DUSP1 phosphatase domain promoted the physiological DUSP1/VCP interaction which prevented LPS-mediated VCP Ser784 phosphorylation. Accordingly, transfection with a phosphomimetic VCP mutant abolished the protective actions of DUSP1 on MQC and aggravated inflammation, apoptosis, and contractility/relaxation capacity in HL-1 cardiomyocytes. These findings support the involvement of the novel DUSP1/VCP/MQC pathway in the pathogenesis of endotoxemia-caused myocardial dysfunction.
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Cardiomiopatías , Endotoxemia , Animales , Ratones , Cardiomiopatías/metabolismo , Fosfatasa 1 de Especificidad Dual/genética , Fosfatasa 1 de Especificidad Dual/metabolismo , Endotoxemia/inducido químicamente , Endotoxemia/genética , Endotoxemia/complicaciones , Lipopolisacáridos/metabolismo , Mitocondrias/metabolismo , Miocitos Cardíacos/metabolismo , Proteína que Contiene Valosina/genética , Proteína que Contiene Valosina/metabolismoRESUMEN
OBJECTIVE: To compare the application of sequential embryo transfer, cleavage embryo transfer, and blastocyst transfer combined with intrauterine perfusion in frozen-thawed embryo transfer cycles in patients with recurrent implantation failure to provide a reference for reproductive clinicians. METHODS: The 166 patients who underwent frozen-thawed embryo transfer due to recurrent implantation failure in the reproductive center from January 2021 to March 2022 were retrospectively analyzed. According to the different embryos transferred, they were divided into cleavage embryo transfer groups (72 cases in Group A), blastocyst transfer group (29 cases in Group B), and sequential transfer group (65 cases in Group C). All three groups were treated with intrauterine perfusion 5 days before embryo transfer. The general data and clinical pregnancy outcome indicators, such as embryo implantation rate, clinical pregnancy rate, ongoing pregnancy rate, live birth rate, twin rate, were compared among the three groups. RESULTS: The embryo implantation rate (53.1%), clinical pregnancy rate (76.9%), ongoing pregnancy rate (67.7%) and live birth rate(66.15%) in the sequential transfer group were significantly higher than those in the other two groups (P < 0.05), and the ectopic pregnancy rate was lower in the sequential transfer group. CONCLUSION: Sequential transfer combined with intrauterine perfusion partially improves clinical pregnancy outcomes and reduces the risk of ectopic pregnancy in frozen embryo cycle transfers in patients with recurrent implantation failure, which may be a favourable transfer reference strategy for patients with recurrent implantation failure.
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Resultado del Embarazo , Embarazo Ectópico , Femenino , Embarazo , Humanos , Estudios Retrospectivos , Transferencia de Embrión , Implantación del Embrión , Índice de Embarazo , Embarazo Ectópico/etiología , Perfusión , Fertilización In VitroRESUMEN
Z-scheme heterojunction Bi2WO6/g-C3N4 was obtained by a novel hydrothermal process; its photocatalysis-persulfate (PDS) activation for tetracycline (TC) removal was explored under solar light (SL). The structure and photoelectrochemistry behavior of fabricated samples were well characterized by FT-IR, XRD, XPS, SEM-EDS, UV-vis DRS, Mott-Schottky, PL, photocurrent response, EIS and BET. The critical experimental factors in TC decomposition were investigated, including the Bi2WO6 doping ratio, catalyst dosage, TC concentration, PDS dose, pH, co-existing ion and humic acid (HA). The optimum test conditions were as follows: 0.4 g/L Bi2WO6/g-C3N4 (BC-3), 20 mg/L TC, 20 mg/L PDS and pH = 6.49, and the maximum removal efficiency of TC was 98.0% in 60 min. The decomposition rate in BC-3/SL/PDS system (0.0446 min-1) was 3.05 times higher than that of the g-C3N4/SL/PDS system (0.0146 min-1), which might be caused by the high-efficiency electron transfer inside the Z-scheme Bi2WO6/g-C3N4 heterojunction. Furthermore, the photogenerated hole (h+), superoxide (O2â¢-), sulfate radical (SO4â¢-) and singlet oxygen (1O2) were confirmed as the key oxidation factors in the BC-3/SL/PDS system for TC degradation by a free radical quenching experiment. Particularly, BC-3 possessed a wide application potential in actual antibiotic wastewater treatment for its superior catalytic performance that emerged in the experiment of co-existing components.
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Photocatalytic CH4 oxidation to CH3OH emerges as a promising strategy to sustainably utilize natural gas and mitigate the greenhouse effect. However, there remains a significant challenge for the synthesis of methanol by using O2 at low temperature. Inspired by the catalytic structure in soluble methane monooxygenase (MMO) and the corresponding reaction mechanism, we prepared a biomimetic photocatalysts with the decoration of Fe2O3 nanocluster and satellite Fe single atom immobilized on carbon nitride. The catalyst demonstrates an excellent CH3OH productivity of 5.02 mmol·gcat-1·h-1 with methanol selectivity of 98.5%. Mechanism studies reveal that the synergy between Fe2O3 nanocluster and Fe single atom establishes a dual-Fe site as MMO for O2 activation and subsequent CH4 partial oxidation. Moreover, the light excitation of Fe2O3 nanoclusters with a relative narrow bandgap could deliver the electrons and protons to atomic Fe that facilitating the oxygen reduction kinetics for the robust of methanol synthesis.
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Producing solar fuels over photocatalysts under light irradiation is a considerable way to alleviate energy crises and environmental pollution. To develop the yields of solar fuels, photocatalysts with broad light absorption, fast charge carrier migration, and abundant reaction sites need to be designed. Electrospun 1D nanofibers with large specific areas and high porosity have been widely used in the efficient production of solar fuels. Nevertheless, it is challenging to do in-depth mechanism research on electrospun nanofiber-based photocatalysts since there are multiple charge transfer routes and various reaction sites in these systems. Here, the basic principles of electrospinning and photocatalysis are systemically discussed. Then, the different roles of electrospun nanofibers played in recent research to boost photocatalytic efficiency are highlighted. It is noteworthy that the working principles and main advantages of in situ irradiated photoelectron spectroscopy (ISI-XPS), a new technique to investigate migration routes of charge carriers and identify active sites in electrospun nanofibers based photocatalysts, are summarized for the first time. At last, a brief summary on the future orientation of photocatalysts based on electrospun nanofibers as well as the perspectives on the development of the ISI-XPS technique are also provided.
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The main obstacles for the commercial application of Lithium-Sulfur (Li-S) full batteries are the large volume change during charging/discharging process, the shuttle effect of lithium polysulfide (LiPS), sluggish redox kinetics, and the indisciplinable dendritic Li growth. Especially the overused of metal Li leads to the low utilization of active Li, which seriously drags down the actual energy density of Li-S batteries. Herein, an efficient design of dual-functional CoSe electrocatalyst encapsulated in carbon chain-mail (CoSe@CCM) is employed as the host both for the cathode and anode regulation simultaneously. The carbon chain-mail constituted by carbon encapsulated layer cross-linking with carbon nanofibers protects CoSe from the corrosion of chemical reaction environment, ensuring the high activity of CoSe during the long-term cycles. The Li-S full battery using this carbon chain-mail catalyst with a lower negative/positive electrode capacity ratio (N/P < 2) displays a high areal capacity of 9.68 mAh cm-2 over 150 cycles at a higher sulfur loading of 10.67 mg cm-2 . Additionally, a pouch cell is stable for 80 cycles at a sulfur loading of 77.6 mg, showing the practicality feasibility of this design.
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MgAl2O4:Mn2+ transparent ceramics were fabricated by reactive spark plasma sintering (SPS). The ceramic samples show narrow-band green emission under the 450â nm blue light excitation, which is corresponding to 4T1(4â G)-6A1(6S) transition of Mn2+ in the tetrahedral site. The emission peak of the Mg0.93Al2O4:0.07Mn2+ ceramic sample was located at 525â nm with the full-width at half-maximum (FWHM) value of 36â nm. The internal quantum yield (IQY) of Mg0.93Al2O4:0.07Mn2+ reached 63%. The emission intensity remained â¼98% at 150 °C compared to its initial value at room temperature, showing excellent thermal quenching performance. The results indicated that MgAl2O4:Mn2+ ceramic phosphor is a promising candidate for high brightness, wide gamut display backlight applications.
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In animal studies, sodium-glucose co-transporter-2 inhibitors-such as empagliflozin-have been shown to improve heart failure and impaired cardiac contractility induced by anthracyclines-including doxorubicin-although the therapeutic mechanism remains unclear. Moreover, abnormalities in Ca2+ handling within ventricular myocytes are the predominant feature of heart failure. Accordingly, this study aimed to investigate whether empagliflozin can alleviate Ca2+ handling disorders induced by acute doxorubicin exposure and elucidate the underlying mechanisms. To this end, ventricular myocytes were isolated from C57BL/6 mice. Contraction function, Ca2+ handling, and mitochondrial reactive oxygen species (ROS) generation were then evaluated using IonOptix or confocal microscopy. Ca2+ handling proteins were detected by western blotting. Results show that incubation with 1 µmol/L of doxorubicin for 120-min impaired cardiac contractility in isolated myocytes, which was significantly alleviated by pretreatment with 1 µmol/L of empagliflozin. Doxorubicin also markedly induced Ca2+ handling disorders, including decreased Ca2+ transients, prolonged Ca2+ transient decay time, enhanced frequency of Ca2+ sparks, and decreased Ca2+ content in the sarcoplasmic reticulum. These dysregulations were improved by pretreatment with empagliflozin. Moreover, empagliflozin effectively inhibited doxorubicin-induced mitochondrial ROS production in isolated myocytes and rescued doxorubicin-induced oxidation of Ca2+/calmodulin-dependent protein kinase II (ox-CaMKII) and CaMKII-dependent phosphorylation of RyR2. Similarly, preincubation with 10 µmol/L Mito-TEMPO mimicked the protective effects of empagliflozin. Collectively, Empagliflozin ameliorated the doxorubicin-induced contraction malfunction and Ca2+-handling disorders. These findings suggest that empagliflozin alleviates Ca2+-handling disorders by improving ROS production in the mitochondria and alleviating the enhanced oxidative CaMKII signaling pathway induced by doxorubicin.
RESUMEN
OBJECTIVE: This study aimed to evaluate the feasibility of real-time visualization and mapping of the right phrenic nerve (RPN) by using intracardiac echocardiography (ICE) during atrial fibrillation (AF) ablation. BACKGROUND: RPN injury is a complication associated with the ablation of AF. Multiple approaches are currently being used to prevent and detect RPN injuries. However, none of these approaches can directly visualize the RPN in real-time during the ablation procedure. METHODS AND RESULTS: The RPN was detected using ICE. The RPN and its adjacent structures were analysed. The relationship between the RPN's distance from the superior vena cava (SVC) and its pacing capture threshold was quantified. The safety of SVC isolation guided by the ICE-visualized RPN was evaluated. Thirty-eight people were enrolled in this study. The RPN was visualized by ICE in 92% of patients. It ran through the space between the SVC and the mediastinal pleura and had a 'straw'-like appearance upon ICE imaging. The course of the RPN was close to the SVC (minimum 1.0 ± 0.4 mm) and the right superior pulmonary vein (minimum 14.1 ± 7.3 mm). There was a positive linear correlation between the RPN's capture threshold and its distance from the SVC (Spearman's correlation coefficient = 0.728, < 0.001). SVC isolation was guided by the RPN; none of the patients developed an RPN injury. CONCLUSIONS: RPN can be visualized by ICE in most patients, thus providing a novel approach for the real-time detection of RPN during AF ablation.