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In this study, the copper-nickel (Cu-Ni) bimetallic electrocatalysts for electrochemical CO2 reduction reaction(CO2RR) are fabricated by taking the finely designed poly(ionic liquids) (PIL) containing abundant Salen and imidazolium chelating sites as the surficial layer, wherein Cu-Ni, PIL-Cu and PIL-Ni interaction can be readily regulated by different synthetic scheme. As a proof of concept, Cu@Salen-PIL@Ni(NO3)2 and Cu@Salen-PIL(Ni) hybrids differ significantly in the types and distribution of Ni species and Cu species at the surface, thereby delivering distinct Cu-Ni cooperation fashion for the CO2RR. Remarkably, Cu@Salen-PIL@Ni(NO3)2 provides a C2+ faradaic efficiency (FEC2+) of 80.9% with partial current density (jC 2+) of 262.9 mA cm-2 at -0.80 V (versus reversible hydrogen electrode, RHE) in 1 m KOH in a flow cell, while Cu@Salen-PIL(Ni) delivers the optimal FEC2+ of 63.8% at jC2+ of 146.7 mA cm-2 at -0.78 V. Mechanistic studies indicates that the presence of Cu-Ni interfaces in Cu@Salen-PIL@Ni(NO3)2 accounts for the preserve of high-valence Cu(I) species under CO2RR conditions. It results in a high activity of both CO2-to-CO conversion and C-C coupling while inhibition of the competitive HER.
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The electrocatalytic transformation of carbon dioxide (CO2 ) to formate is a promising route for highly efficient conversion and utilization of CO2 gas, due to the low production cost and the ease of storage of formate. In this work, porous poly(ionic liquid) (PPIL)-based tin-silver (Sn-Ag) bimetallic hybrids (PPILm -Snx Ag10- x ) are prepared for high-performance formate electrolytic generation. Under optimal conditions, an excellent formate Faradaic efficiency of 95.5% with a high partial current density of 214.9 mA cm-2 is obtained at -1.03 V (vs reversible hydrogen electrode). Meanwhile, the high selectivity of formate (>≈83%) is maintained in a wide potential range (>630 mV). Mechanistic studies demonstrate that the presence of Ag-species is vital for the formation, maintenance, and high dispersion of tetravalent Sn(IV)-species, which accounts for the active sites for CO2 -to-formate conversion. Further, the introduction of Ag-species significantly enhances the activity by increasing the electron density near the Fermi energy level.
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PURPOSE: To summarize experience with and the efficacy of fenestrated/branched thoracic endovascular repair (F/B-TEVAR) using physician-modified stent-grafts (PMSGs) under 3D printing guidance in triple aortic arch branch reconstruction. MATERIALS AND METHODS: From February 2018 to April 2022, 14 cases of aortic arch aneurysms and 30 cases of aortic arch dissection (22 acute aortic arch dissection and 8 long-term aortic arch dissection)were treated by F/B-TEVAR in our department, including 34 males and 10 females, with an average age of 59.84 ± 11.72 years. Three aortic arch branches were affected in all patients. A 3D-printed model was made according to computed tomography angiography images and used to guide the fabrication of PMSGs. All patients were followed up. RESULTS: A total of 132 branches were successfully reconstructed with no case of conversion to open surgery. The average operation time was 4.97 ± 1.40 hours, including a mean 44.05 ± 7.72 minutes for stent-graft customization, the mean postoperative hospitalization duration was 9.91 ± 4.47 days, the average intraoperative blood loss was 480.91 mL (100-2810 mL), and the mean postoperative intensive care unit monitoring duration was 1.02 days (0-5 days). No deaths occurred within 30 days of surgery. Postoperative neurological complications occurred in 1 case (2.3%), and retrograde type A dissection occurred in 1 case (2.3%). CONCLUSION: Compared with conventional surgery, triple aortic arch branch reconstruction under the guidance of 3D printing is a minimally invasive treatment method with the advantages of accurate positioning, rapid postoperative recovery, few complications, and reliable short- to mid-term effects. CLINICAL IMPACT: At present the PMSG usually depend on imaging data and software calculation. With the guidance of 3D printing technology, image data could be transformed into 3D model, which has improved the accuracy of the positioning of the fenestrations. The diameter reduction technique and the internal mini cuff technique have made a complement to the slimed-down fenestration selection process and the low rate of endoleak. As reproducible study, our results may provide reference for TEVAR in different cases.
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The widespread occurrence of tire tread particles (TPs) has aroused increasing concerns over their impacts. However, how they affect the soil fauna remains poorly understood. Here, based on systematically assessing the toxicity of TPs on soil model speciesEnchytraeus crypticusat environmentally relevant concentrations through both soil and food exposure routes, we reported that TPs affected gut microbiota, intestinal histopathology, and metabolites of the worms both through particulate- and leachate-induced effects, while TP leachates exerted stronger effects. The dominant role of TP leachates in TP toxicity was further explained by the findings that worms did not ingest TPs with a particle size of over 150 µm and actively avoided consuming TP particles. Moreover, by comparing the effects of different brands of TPs as well as new and aged TPs, we demonstrated that it was mainly TP leachates that resulted in the ubiquity of the disturbance in the worm's gut microbiota among different brands of TPs. Notably, the large variations in leachate compositions among different brands of TPs provided us a unique opportunity to identify the determinants of TP toxicity. These results provide novel insights into the toxicity of TPs to soil fauna and a reference for toxicity reduction of tires.
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Microbioma Gastrointestinal , Poeira , Tamanho da Partícula , SoloRESUMO
OBJECTIVE: To first induce chronic deep venous thrombosis in the left iliac veins of canines and porcines and then compare these two models to validate endovascular treatment devices. METHODS: Thrombin and fibrinogen were used to produce a solid thrombus in the left iliac veins of a stenosis model. The researchers used venous angiography and histological staining to investigate the progression of thrombosis. RESULTS: A left iliac vein thrombus was successfully formed in all experimental animals, including six Labrador dogs and three Bama miniature pigs, and there was minimal surgical bleeding. All dogs survived until 90 days, and three pigs died on Days 29, 33, and 58. CONCLUSION: The researchers first established the models and then observed the progression of chronic deep venous thrombosis of the iliac vein in large animals for up to 90 days. Dogs are better suited for chronic deep venous thrombosis models due to their uncomplicated anatomy, excellent obedience, and proneness to physical activity compared with pigs.
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CONTEXT: Salvia miltiorrhizae Bunge (Lamiaceae) is a traditional Chinese medicine (TCM) for the treatment of 'thoracic obstruction'. Transient receptor potential canonical channel 1 (TRPC1) is a important target for myocardial injury treatment. OBJECTIVE: This work screens the active component acting on TRPC1 from Salvia miltiorrhizae. MATERIALS AND METHODS: TCM Systems Pharmacology Database and Analysis Platform (TCMSP) was used to retrieve Salvia miltiorrhiza compounds for preliminary screening by referring to Lipinski's rule of five. Then, the compound group was comprehensively scored by AutoDock Vina based on TRPC1 protein. Surface plasmon resonance (SPR) was used to determine the affinity of the optimal compound to TRPC1 protein. Western blot assay was carried out to observe the effect of the optimal compound on TRPC1 protein expression in HL-1 cells, and Fura-2/AM detection was carried out to observe the effect of the optimal compound on calcium influx in HEK293 cells. RESULTS: Twenty compounds with relatively good characteristic parameters were determined from 202 compounds of Salvia miltiorrhiza. Rosmarinic acid (RosA) was obtained based on the molecular docking scoring function. RosA had a high binding affinity to TRPC1 protein (KD value = 1.27 µM). RosA (50 µM) could reduce the protein levels (417.1%) of TRPC1 after oxygen-glucose deprivation/reperfusion (OGD/R) in HL-1 cells and it could inhibit TRPC1-mediated Ca2+ influx injury (0.07 ΔRatio340/380) in HEK293 cells. DISCUSSION AND CONCLUSIONS: We obtained the potential active component RosA acting on TRPC1 from Salvia miltiorrhizae, and we speculate that RosA may be a promising clinical candidate for myocardial injury therapy.
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Salvia miltiorrhiza , Humanos , Salvia miltiorrhiza/química , Simulação de Acoplamento Molecular , Células HEK293 , Cinamatos/farmacologia , Ácido RosmarínicoRESUMO
Protein tyrosine phosphatase non-receptor type 21 (PTPN21) has been recognised as a new tumour-associated protein that is implicated in diverse tumours. However, the correlation between PTPN21 and glioma remains unaddressed. This investigation focused on the relevance of PTPN21 in glioma. The Cancer Genome Atlas (TCGA) analysis identified PTPN21 as being up-regulated in glioma tissue. The elevation of PTP21 in glioma was validated by evaluating clinical specimen. Kaplan-Meier plot analysis revealed that a high PTPN21 level predicted poor survival rate in glioma patient. Silencing of PTPN21 produced remarkable anticancer effects in glioma cells including proliferation inhibition, cell cycle arrest, metastasis suppression and enhanced chemosensitivity. Mechanistic studies uncovered that PTPN21 contributes to mediation of the phosphatidyl-inositole-3 kinase (PI3K)/AKT pathway via the regulation of epidermal growth factor receptor (EGFR). Restraint of EGFR diminished PTPN21 overexpression-induced promoting effect on PI3K/AKT pathway. Reactivation of AKT reversed PTPN21 silencing-evoked antitumor effect. The tumorigenic potential of PTPN21-silenced glioma cells in vivo was markedly compromised. In summary, this study demonstrates that silencing of PTPN21 produces remarkable anticancer effects in glioma by restraining the EGFR/PI3K/AKT pathway.
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Glioma , Fosfatidilinositol 3-Quinases , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células , Receptores ErbB/genética , Receptores ErbB/metabolismo , Glioma/tratamento farmacológico , Glioma/genética , Glioma/metabolismo , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Proteínas Tirosina Fosfatases não Receptoras/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de SinaisRESUMO
Cardiac dysfunction is a vital complication of endotoxemia (ETM) with limited therapeutic options. Transient receptor potential canonical channel (TRPC)1 was involved in various heart diseases. While, the role of TRPC1 in ETM-induced cardiac dysfunction remains to be defined. In this study, we found that TRPC1 protein expression was significantly upregulated in hearts of lipopolysaccharide (LPS)-challenged mice. What's more, TRPC1 knockdown significantly alleviated LPS-induced cardiac dysfunction and injury. Further myocardial mRNA-sequencing analysis revealed that TRPC1 might participate in pathogenesis of ETM-induced cardiac dysfunction via mediating myocardial apoptosis and autophagy. Data showed that knockdown of TRPC1 significantly ameliorated LPS-induced myocardial apoptotic injury, cardiomyocytes autophagosome accumulation, and myocardial autophagic flux. Simultaneously, deletion of TRPC1 reversed LPS-induced molecular changes of apoptosis/autophagy signaling pathway in cardiomyocytes. Moreover, TRPC1 could promote LPS-triggered intracellular Ca2+ release, subsequent calpain activation and caveolin-1 degradation. Either blocking calpain by PD150606 or enhancing the amount of caveolin-1 scaffolding domain that interacts with TRPC1 by cell-permeable peptide cavtratin significantly alleviated the LPS-induced cardiac dysfunction and cardiomyocytes apoptosis/autophagy. Furthermore, cavtratin could inhibit LPS-induced calpain activation in cardiomyocytes. caveolin-1 could directly interact with calpain 2 both in vivo and in vitro. Importantly, cecal ligation and puncture-stimulated cardiac dysfunction and mortality were significantly alleviated in Trpc1-/- and cavtratin-treated mice, which further validated the contribution of TRPC1-caveolin-1 signaling axis in sepsis-induced pathological process. Overall, this study indicated that TRPC1 could promote LPS-triggered intracellular Ca2+ release, mediate caveolin-1 reduction, and in turn activates calpain to regulate myocardial apoptosis and autophagy, contributing to ETM-induced cardiac dysfunction of mice.
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Endotoxemia , Cardiopatias , Canais de Cátion TRPC/metabolismo , Animais , Apoptose , Autofagia , Calpaína/metabolismo , Calpaína/farmacologia , Caveolina 1/metabolismo , Endotoxemia/induzido quimicamente , Cardiopatias/metabolismo , Lipopolissacarídeos , Camundongos , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/metabolismoRESUMO
Radioactive iodine (129I and 131I), produced or released from nuclear-related activities, posed severe effects on both human health and environment. The efficient removal of radioiodine from aqueous medium and vapor phase is of paramount importance for the sustainable development of nuclear energy. Herein, a metal-organic framework (MOF) nanosheet with a positive charge was constructed for the capture of iodine for the first time. The as-synthesized ultrathin nanosheets, with a thickness of 4.4 ± 0.1 nm, showed a record-high iodine adsorption capacity (3704.08 mg g-1) from aqueous solution, which is even higher than that from the vapor phase (3510.05 mg g-1). It can be ascribed to the fully interactions between the extensive accessible active sites on the largely exposed surface of 2D MOF nanosheets and the target pollutants, which also gave rise to fast adsorption kinetics with relative high removal efficiencies in the low concentrations, even in seawater. Moreover, a facile recyclability with fast desorption kinetics can also be achieved for the MOF nanosheets. The excellent iodine removal performance in aqueous solution demonstrated that the electrostatic attraction between MOF nanosheets with a positive charge and the negatively charged triiodide (I3-, the dominant form of iodine in aqueous solution) is the driving force in adsorption, which endows the adsorbents with the characteristics of fast adsorption and desorption kinetics. The adsorption mechanism was systematically verified by the studies of ζ potential, Fourier transform infrared, X-ray photoelectron spectroscopy, and Raman spectra.
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Iodo , Estruturas Metalorgânicas , Neoplasias da Glândula Tireoide , Poluentes Químicos da Água , Adsorção , Humanos , Iodetos , Radioisótopos do Iodo , Estruturas Metalorgânicas/química , Água , Poluentes Químicos da Água/análiseRESUMO
Objective To investigate the correlations among brain functional connectivity,hippocampal subregion volume and cognitive score in the patients with carotid artery stenosis(CAS)based on resting state functional magnetic resonance imaging.Methods Forty CAS patients treated in the Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University from January to December in 2019 and 31 healthy volunteers were enrolled in this study.All the participants underwent cognitive assessment,structural MRI for the measurement of hippocampal volume,and resting state functional magnetic resonance imaging for the examination of brain functional connectivity(FC).We compared the cognitive function,hippocampal subregion volumes,and brain functional connectivity between the two groups and investigated the correlations between the three indicators.Results The CAS patients had lower mini-mental state examination(MMSE)(F=13.346,P=0.001)and Montreal cognitive assessment(MoCA)(F=52.005,P<0.001)scores than the healthy volunteers.Compared with healthy volunteers,CAS patients showed small whole hippocampus(right side:t=2.176,P=0.033;left side:t=2.881,P=0.005;especially on the left side),small hippocampal tail(right side:t=2.394,P=0.019;left side:t=3.158,P=0.002),small hippocampal body(right side:t=2.336,P=0.022;left side:t=3.165,P=0.002),small subiculum(right side:t=2.211,P=0.030;left side:t=2.430;P=0.018),and small molecular layer(right side:t=2.103,P=0.039;left side:t=2.702,P=0.009).The whole hippocampal volume was positively correlated with MoCA and MMSE scores(left MoCA:r=0.289,P=0.015;right MMSE:r=0.249,P=0.038;left MMSE:r=0.316,P=0.008).The volume changes in the subiculum,presubiculum,and left molecular layer were positively correlated with MoCA(right subiculum:r=0.290,P=0.015;left subiculum:r=0.382,P=0.001;right presubiculum:r=0.293,P=0.014;left presubiculum:r=0.440,P<0.001;left molecular layer:r=0.259,P=0.031)and MMSE scores(right subiculum:r=0.278,P=0.020;left subiculum:r=0.419,P<0.001;right presubiculum:r=0.296,P=0.013;left presubiculum:r=0.506,P<0.001;left molecular layer:r=0.298,P=0.012),while the volume changes in the remaining hippocampal subregions were not correlated with cognitive scores(all P>0.05).Compared with healthy volunteers,the CAS patients presented low FC values of the left hippocampus to the occipital lobe and frontal lobe and of right hippocampus to the occipital lobe,temporal lobe,prefrontal lobe,and middle frontal gyrus(Gaussian random field correction,voxel P<0.01,cluster P<0.05).The volume changes of the left whole hippocampus,hippocampal head,and cornu ammonis 1(CA1)were positively correlated with the FC value of right hippocampus to the temporal lobe(left whole hippocampus:r=0.358,P=0.025;right hippocampal head:r=0.325,P=0.044;left hippocampal head:r=0.360,P=0.024;right CA1:r=0.326,P=0.043;left CA1:r=0.341,P=0.034).MoCA and MMSE scores were positively correlated with the FC value of right hippocampus to the frontal lobe(MoCA middle frontal gyrus:r=0.389,P=0.014;MoCA prefrontal lobe:r=0.363,P=0.023;MMSE prefrontal lobe:r=0.321,P=0.046).Conclusions CAS patients have different levels of cognitive impairment.Hippocampal atrophy and a decline in the FC value of hippocampus to the occipital lobe may play a role in cognitive impairment in CAS patients.This discovery lays a foundation for the future research on the mechanism of cognitive dysfunction in CAS patients.
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Estenose das Carótidas , Disfunção Cognitiva , Humanos , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/patologia , Encéfalo , Imageamento por Ressonância Magnética/métodos , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Cognição , Disfunção Cognitiva/diagnóstico por imagemRESUMO
Electroreduction of CO2 on a polymer-modified Cu-based catalyst has shown high multi-electron reduction (>2 e- ) selectivity, however, most of the corresponding current densities are still too small to support industrial applications. In this work, we designed a poly(ionic liquid) (PIL)-based Cu0 -CuI tandem catalyst for the production of C2+ products with both high reaction rate and high selectivity. Remarkably, a high C2+ faradaic efficiency (FE C 2 + ) of 76.1 % with a high partial current density of 304.2â mA cm-2 is obtained. Mechanistic studies reveal the numbers and highly dispersed Cu0 -PIL-CuI interfaces are vital for such reactivity. Specifically, Cu nanoparticles derived Cu0 -PIL interfaces account for high current density and a moderate C2+ selectivity, whereas CuI species derived PIL-CuI interfaces exhibit high activity for C-C coupling with the local enriched *CO intermediate. Furthermore, the presence of the PIL layer promotes the C2+ selectivity by lowering the barrier of C-C coupling.
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BACKGROUND: The impact of the number of examined lymph nodes (ELNs) on stage correction and prognostication in patients with esophageal squamous cell carcinoma (ESCC) who underwent right transthoracic esophagectomy is still unclear. METHODS: Patients with ESCC who underwent right transthoracic esophagectomy at Sun Yat-sen University Cancer Center between January 1997 and December 2013 were retrospectively enrolled. The Cox proportional hazards regression model was used to determine the effect of ELN count on overall survival. The impact of ELN count on stage correction was evaluated using the hypergeometric distribution and Bayes theorem and ß-binomial distribution estimation, respectively. The threshold of ELNs was determined using the LOWESS smoother and piecewise linear regression. RESULTS: Among the 875 included patients, greater ELNs were associated with a higher rate of nodal metastasis. Significant association between staging bias and the number of ELNs is only observed through the Bayes method. The ELN count did not impact 90-day mortality but significantly impacted long-term survival (adjusted hazard ratio [aHR] 0.986), especially in those patients with node-negative disease (aHR 0.972). In patients with node-negative disease, cut-point analysis showed a threshold ELN count of 21. CONCLUSIONS: A greater number of ELNs is associated with more accurate node staging and better long-term survival in resected ESCC patients. We recommended harvesting at least 21 LNs to acquire accurate staging and long-term survival information for patients with declared node-negative disease using the right thoracic approach.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Neoplasias de Cabeça e Pescoço , Teorema de Bayes , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Esofagectomia , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND Traditional Chinese medicine has widely used Bolbostemma paniculatum to treat diseases, including cancer, but its underlying mechanisms remain unclear. The present study aimed to elucidate the potential pharmacological mechanisms of "Tu Bei Mu" (TBM), the Chinese name for Bolbostemmatis Rhizoma, the dry tuber of B. paniculatum, for the treatment of hepatocellular carcinoma (HCC). MATERIAL AND METHODS The active components and putative therapeutic targets of TBM were explored using SwissTargetPrediction, Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and Search Tool for Interactions of Chemicals (STITCH). The HCC-related target database was built using DrugBank, DisGeNet, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Database (TTD). A protein-protein interaction network of the common targets was constructed, based on the matches between TBM potential targets and HCC-related targets, using Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the cluster networks were used to elucidate the biological functions of TBM. RESULTS Pharmacological network diagrams of the TBM compound-target network and HCC-related target network were successfully constructed. A total of 22 active components, 191 predicted biological targets of TBM, and 3775 HCC-related targets were identified. Through construction of an HCC-related target database and a protein-protein interaction network of the common targets, TBM was predicted to be effective in treating HCC mainly through the PI3K-Akt, HIF-1, p53, and PPAR signaling pathways. CONCLUSIONS The PI3K/Akt, HIF1, p53, and PPAR pathways may play vital roles in TBM treatment of HCC. Also, the potential anti-cancer effect of TBM on HCC appears to stem from the synergetic effect of multiple targets and mechanisms.
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Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Biologia de Sistemas/métodos , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Bases de Dados de Compostos Químicos , Bases de Dados Genéticas , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Mapas de Interação de Proteínas/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacosRESUMO
OBJECTIVE: This study aims to investigate the mechanism of transforming growth factor-ß1 (TGF-ß1) in promoting angiogenesis through endothelial-to-mesenchymal transition (EndMT). METHODS: The mesenchymal transition of human umbilical vein endothelial cells (HUVECs) was induced by TGF-ß1. The angiogenesis, migration, and proliferation of HUVECs undergoing EndMT were examined by tube formation assay, scratch assay, Transwell assay, and CCK-8 assay. RESULTS: The outcomes revealed that EndMT promoted angiogenesis, migration, and proliferation of HUVECs and the secretion of the vascular endothelial growth factor (VEGF) of HUVECs. Phosphorylated AKT (p-AKT) increased in EndMT by inhibiting the mitigation of angiogenesis. CONCLUSION: EndMT induces angiogenesis by promoting the secretion of VEGF, and p-AKT participates in this regulation.
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Indutores da Angiogênese/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos , Fator de Crescimento Transformador beta1/farmacologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Endothelial progenitor cells (EPCs) have emerged as a promising therapeutic choice for thrombi recanalization. However, this role of EPCs is confined by some detrimental factors. The aim of this study was to explore the role of the miR-9-5p in regulation of the proliferation, migration and angiogenesis of EPCs and the subsequent therapeutic role in thrombosis event. Wound healing, transwell assay, tube formation assay and in vivo angiogenesis assay were carried out to measure cell migration, invasion and angiogenic abilities, respectively. Western blot was performed to elucidate the relationship between miR-9-5p and TRPM7 in the autophagy pathway. It was found that miR-9-5p could promote migration, invasion and angiogenesis of EPCs by attenuating TRPM7 expression via activating PI3K/Akt/autophagy pathway. In conclusion, miR-9-5p, targets TRPM7 via the PI3K/Ak/autophagy pathway, thereby mediating cell proliferation, migration and angiogenesis in EPCs. Acting as a potential therapeutic target, miR-9-5p may play an important role in the prognosis of DVT.
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Células Progenitoras Endoteliais/metabolismo , MicroRNAs/genética , Neovascularização Patológica/genética , Proteínas Serina-Treonina Quinases/genética , Canais de Cátion TRPM/genética , Trombose/genética , Animais , Autofagia/genética , Movimento Celular/genética , Proliferação de Células/genética , Células Progenitoras Endoteliais/patologia , Regulação da Expressão Gênica/genética , Humanos , Camundongos , Morfogênese/genética , Invasividade Neoplásica/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Trombose/patologia , Trombose/terapia , Cicatrização/genéticaRESUMO
Purpose: To summarize the experience and outcomes of total endovascular repair of thoracoabdominal aortic disease using 3-dimensional (3D) printed models to guide on-site creation of fenestrations in aortic stent-grafts. Materials and Methods: From April 2018 to March 2019, 34 patients (mean age 58±14 years; 24 men) with thoracoabdominal aortic disease were treated in our department. Nineteen patients had thoracoabdominal aortic dissection and 15 had thoracoabdominal aortic aneurysm. Preoperatively, a 3D printed model of the aorta was made according to computed tomography images. In the operating room, the main aortic stent-graft was completely released in the 3D printed model, and the position of each fenestration or branch was marked on the stent-graft. The fenestrations were then made using an electric pen. Wires were sewn to the edge of the fenestrations using nonabsorbable sutures. After customization, the aortic stent-graft was reloaded into the delivery sheath and deployed. Results: The printing process took ~5 hours (1 hour for image reconstruction, 3 hours for printing, and 1 hour for postprocessing). The physician-modified stent-grafts had a total of 107 fenestrations secured by 102 bridging stent-grafts, including 73 covered stents and 29 bare stents. The average procedure time was 5.6±1.2 hours, including a mean 1.3 hours for stent-graft customization. No renal insufficiency or paraplegia occurred. Two branch arteries were lost during the operation. One patient (3%) died 1 week after surgery from a retrograde dissection rupture. One patient developed a minor cerebral infarction postoperatively. The mean follow-up time was 8.5 months. There was 1 endoleak from a fenestration (coil embolized) and 4 distal ruptures of the aortic dissection (3 treated and 1 observed). Conclusion: Three-dimensional printing can be used to guide creation of fenestrated stent-grafts for the treatment of thoracoabdominal aortic diseases involving crucial branches. This technique appears to be more accurate than the traditional measurement method, with short-term follow-up demonstrating the safety and reliability of the method. However, further research and development are needed.
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Aneurisma da Aorta Abdominal/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Desenho Assistido por Computador , Procedimentos Endovasculares/instrumentação , Impressão Tridimensional , Desenho de Prótese , Stents , Adulto , Idoso , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/fisiopatologia , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/fisiopatologia , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/fisiopatologia , Aortografia , Implante de Prótese Vascular/efeitos adversos , Angiografia por Tomografia Computadorizada , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Anatômicos , Modelos Cardiovasculares , Modelagem Computacional Específica para o Paciente , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Fluxo de TrabalhoRESUMO
A novel synthesis methodology for the construction of functionalized dihydropyrones has been developed with amines, glyoxylic acid, and 4-substituted-1,2-oxaborol-2(5H)-ols from the Petasis reaction. Mechanistic investigation indicated the intermolecular SN2 cyclization to provide 3,6-dihydro-2H-pyran-2-ones (3,6-DHP) and 5,6-dihydro-2H-pyran-2-ones (5,6-DHP) in one step with moderate to excellent yields.
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Previous studies have shown that melatonin (Mel) can effectively ameliorate myocardial ischemia/reperfusion (MI/R) injury, but the mechanism is yet to be fully elucidated. Mel receptors are expressed in the paraventricular nucleus (PVN), which is also involved in regulating cardiac sympathetic nerve activity. The aim of this study was to examine whether Mel receptors in the PVN are involved in the protective effects of Mel against MI/R injury. The results of quantitative polymerase chain reaction, western blot, and immunofluorescence assays indicated that Mel receptor 2 (MT2) expression in the PVN was upregulated after MI/R. Intraperitoneal administration of Mel significantly improved post-MI/R cardiac function and reduced the infarct size, whereas shRNA silencing of MT2 in the PVN partially blocked this effect. Intraperitoneal administration of Mel reduced sympathetic nerve overexcitation caused by MI/R, whereas shRNA silencing of MT2 in the PVN partially diminished this effect. Furthermore, enzyme-linked immunosorbent assay and western blot results indicated that intraperitoneal administration of Mel lowered the levels of inflammatory cytokines in the PVN after MI/R injury, whereas the application of sh-MT2 in the PVN reduced this effect of Mel. Mel significantly reduced the levels of NF-κB after astrocyte oxygen and glucose deprivation/reoxygenation injury, and this effect was offset when MT2 was silenced. The above experimental results suggest that MT2 in the PVN partially mediated the protective effects of Mel against MI/R injury, and its underlying mechanisms may be related to postactivation amelioration of PVN inflammation and reduction of cardiac sympathetic nerve overexcitation.
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Astrócitos/efeitos dos fármacos , Coração/inervação , Melatonina/farmacologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/patologia , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Receptor MT2 de Melatonina/agonistas , Sistema Nervoso Simpático/fisiopatologia , Animais , Astrócitos/metabolismo , Astrócitos/patologia , Hipóxia Celular , Células Cultivadas , Modelos Animais de Doenças , Glucose/deficiência , Masculino , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Núcleo Hipotalâmico Paraventricular/metabolismo , Núcleo Hipotalâmico Paraventricular/patologia , Núcleo Hipotalâmico Paraventricular/fisiopatologia , Receptor MT2 de Melatonina/genética , Receptor MT2 de Melatonina/metabolismo , Transdução de SinaisRESUMO
BACKGROUND: Myopic eyes are longer than nonmyopic eyes and have thinner choroids. The purpose of present study was to investigate whether a thinner subfoveal choroid at 11 years of age predicted axial eye elongation and myopia during adolescence. METHODS: Longitudinal, population-based observational study. Axial length was measured using an interferometric device and choroidal thickness was measured by spectral-domain optical coherence tomography. Myopia was defined as non-cycloplegic subjective spherical equivalent refraction ≤ - 0.50 diopters. RESULTS: Right eyes of 714 children (317 boys) were examined at age (median (IQR)) 11.5 (0.6) years and 16.6 (0.3) years during which axial length (median (IQR)) increased by 243 (202) µm in eyes without myopia (n = 630) at baseline compared with 454 (549) µm in eyes with myopia (n = 84) at baseline, p < 0.0001. A thicker baseline subfoveal choroid was associated with increased five-year axial elongation after adjustment for baseline axial length in nonmyopic eyes (ß = 27 µm/100 µm, 95%CI 6 to 48, p = 0.011) but not in myopic eyes (p = 0.34). Subfoveal choroidal thickness at 11 years of age did not predict incident myopia at 16 years of age (p = 0.11). Longer baseline axial length was associated with greater five-year axial elongation in both myopic (ß = 196 µm/mm, 95%CI 127 to 265, p < 0.0001) and nonmyopic eyes (ß = 28 µm/mm, 95%CI 7 to 49, p = 0.0085) and the odds for incident myopia increased with 1.57 (95%CI 1.18 to 2.09, p = 0.0020) per mm longer axial length at baseline. CONCLUSION: A thin subfoveal choroid at age 11 years did not predict axial eye elongation and incident myopia from age 11 to 16 years. A longer eye at age 11 years was associated with greater subsequent axial eye elongation and with increased risk of incident myopia at age 16 years.
Assuntos
Comprimento Axial do Olho/patologia , Corioide/patologia , Miopia/epidemiologia , Adolescente , Criança , Corioide/diagnóstico por imagem , Dinamarca/epidemiologia , Feminino , Humanos , Interferometria , Estudos Longitudinais , Masculino , Miopia/diagnóstico , Tamanho do Órgão , Tomografia de Coerência Óptica , Testes Visuais , Acuidade Visual/fisiologiaRESUMO
MicroRNAs (MiRNAs, MiRs) represent a class of conserved small non-coding RNAs that affect post-transcriptional gene regulation and play a vital role in angiogenesis, proliferation, apoptosis, migration and invasion. They are essential for a wide range of physiological and pathological processes, especially for vascular diseases. However, data concerning miRNAs in endothelial progenitor cells (EPCs) and deep vein thrombosis (DVT) remain incomplete. We explored miRNAs that modulate angiogenesis in EPCs and thrombolysis, and analysed their underlying mechanisms using a DVT model, dual-luciferase reporter assay, qRT-PCR, Western blot, immunofluorescence staining, flow cytometry analysis, CCK-8 assay, angiogenesis assay, wound healing and Transwell assay. We found that miR-205 enhanced the homing ability of EPCs to DVT sites and promoted thrombosis resolution and recanalization, which significantly reduced venous thrombus. Additionally, we demonstrated that miR-205 overexpression significantly enhanced angiogenesis in vivo and in vitro, migration, invasion, F-actin filaments and proliferation in EPCs, and inhibited cell apoptosis. Conversely, down-regulation of miR-205 played the opposite role in EPCs. Importantly, this study demonstrated that miR-205 directly targeted PTEN to modulate the Akt/autophagy pathway and MMP2 expression, subsequently playing a key role in EPC function and DVT recanalization and resolution. These results elucidated the pro-angiogenesis effects of miR-205 in EPCs and established it as a potential target for DVT treatment.