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Tuning intermediate adsorption energy by shifting the d-band center offers a powerful strategy to tailor the reactivity of metal catalysts. Here we report a potential sweep method to grow Pd layer-by-layer on Au with the capability to in situ measure the surface structure through an ethanol oxidation reaction. Spectroscopic characterizations reveal charge-transfer induced valence band restructuring in the Pd overlayer, which shifts the d-band center away from the Fermi level compared to bulk Pd. Precise overlayer control gives the optimal bimetallic surface of two monolayers (ML) Pd on Au, which exhibits more than 370-fold mass activity enhancement in oxygen reduction reaction (at 0.9 V vs. reversible hydrogen electrode) and 40 mV increase in half-wave potential compared to the Pt/C. Tested in a homemade Zn-air battery, the 2-ML-Pd/Au/C exhibits a maximum power density of 296 mW/cm2 and specific activity of 804 mAh/gZn, much higher than Pt/C with the same catalyst loading amount.
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To investigate the role of death-associated protein kinase 1 (DAPK1) in cardiac ischemia reperfusion (I/R) in vivo, and to determine whether the process is regulated by nuclear factor E2-associated factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (keap1). Western blot analysis was used to analyze the expression level of DAPK1 at different time points. The hemodynamic parameters and apoptosis of cardiac I/R injury in vivo were observed using DAPK1 knockdown lentivirus. The oxidative stress of I/R in vivo was observed. Nrf2-IN-1 was applied to determine whether the role of DAPK was regulated by Nrf2/keap1. Results show that the DAPK1 expression increased to a peak after 12 h of I/R. Moreover, the level of DAPK1 expression decreased, as determined by Western blot, after DAPK1 knockdown lentivirus administration. In addition, the hemodynamic parameters of the DAPK1-shRNA group were improved. The apoptosis level (Bax, Bcl-2, cleaved caspase-3, and TUNEL staining) increased in the I/R group, and the DAPK1 knockdown lentivirus could reverse the injury. The oxidative stress indices (CK, cTn-1, CAT, LDH, GSH-PX, MDA, and SOD) also improved in the DAPK1-shRNA group. Finally, Nrf2-IN-1 inhibited tNrf2, nNrf2, and Bcl-2 expression and boosted keap1, Bax, and cleaved caspase-3 expression after DAPK1 lentivirus administration. These findings suggest that DAPK1 may regulate the oxidative stress in cardiac I/R, and Nrf2/keap1 may be the downstream target factor of DAPK1.
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Fator 2 Relacionado a NF-E2 , Traumatismo por Reperfusão , Apoptose , Proteínas Quinases Associadas com Morte Celular/genética , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Transdução de SinaisRESUMO
Hepatocellular carcinoma (HCC) is the fifth most frequent malignancy and the second leading cause of cancer-related death worldwide. Proteasome 26S subunit ATPase 3 interacting protein (PSMC3IP) is an oncogene in breast cancer, while its role in HCC remains unclear. Here, we found that PSMC3IP was critical for the cell proliferation and tumorigenic capacity of HCC cells. Upregulation of PSMC3IP was observed in HCC specimens, and high PSMC3IP expression predicted poor overall survival of HCC patients. In vitro, knockdown of PSMC3IP blunted the proliferation and colony formation of BEL-7404 and SMMC-7721 cells. Likewise, PSMC3IP silencing suppressed the xenografted tumor development of BEL-7404 cells. Mechanistically, apoptosis was enhanced after PSMC3IP knockdown in both BEL-7404 and SMMC-7721 cells. At the molecular level, TP53 and GNG4 were upregulated and eukaryotic translation initiation factor 4E (EIF4E) and insulin like growth factor 1 receptor (IGF1R) were downregulated in shPSMC3IP compared with shCtrl BEL-7404 cells. Therefore, targeting PSMC3IP maybe a promising strategy for HCC.
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Carcinogênese/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Proteínas Nucleares/genética , Transativadores/genética , Animais , Apoptose/genética , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Fator de Iniciação 4E em Eucariotos/genética , Regulação Neoplásica da Expressão Gênica/genética , Xenoenxertos , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Receptor IGF Tipo 1/genética , Proteína Supressora de Tumor p53/genéticaRESUMO
An easy, effective and sensitive analytical method for the simultaneous determination of a novel fungicide pyrametostrobin and its two metabolites pyrametostrobin-M1 and pyrametostrobin-M2 in cucumber and soil was developed using a quick, easy, cheap, effective, rugged, and safe method with high-performance liquid chromatography and tandem mass spectrometry. The extraction solvent was acetonitrile, and cleanup sorbents were primary secondary amine and graphitized carbon black for cucumber samples and primary secondary amine for soil samples. The three target compounds were successfully separated between 3.2 and 3.9 min using a Waters CORTECS™ C18 column connected to an electrospray ionization source. All the matrix-matched samples at three fortified levels (10, 100 and 1000 µg/kg) provided satisfactory recoveries in the range of 78.8-93.8% with relative standard deviations below 6.9%. The limits of quantitation for the three compounds were below 0.183 µg/kg. The proposed method was validated by analyzing real samples.
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Cucumis sativus/química , Fungicidas Industriais/análise , Solo/química , Verduras/química , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas em TandemRESUMO
Auxins and their analogs are widely used to promote root growth, flower and fruit development, and yield in crops. The action characteristics and application scope of various auxins are different. To overcome the limitations of existing auxins, expand the scope of applications, and reduce side effects, it is necessary to screen new auxin analogs. Here, we identified 3,4-dichlorophenylacetic acid (Dcaa) as having auxin-like activity and acting through the auxin signaling pathway in plants. At the physiological level, Dcaa promotes the elongation of oat coleoptile segments, the generation of adventitious roots, and the growth of crop roots. At the molecular level, Dcaa induces the expression of auxin-responsive genes and acts through auxin receptors. Molecular docking results showed that Dcaa can bind to auxin receptors, among which TIR1 has the highest binding activity. Application of Dcaa at the root tip of the DR5:GUS auxin-responsive reporter induces GUS expression in the root hair zone, which requires the PIN2 auxin efflux carrier. Dcaa also inhibits the endocytosis of PIN proteins like other auxins. These results provide a basis for the application of Dcaa in agricultural practices.
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Proteínas de Arabidopsis , Arabidopsis , Ácidos Indolacéticos/farmacologia , Ácidos Indolacéticos/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Simulação de Acoplamento Molecular , Raízes de Plantas/metabolismoRESUMO
Tissue-engineered articular cartilage constructs are currently not able to equal native tissues in terms of mechanical and biological properties. A major cause lies in the deficiency in engineering the biomechanical microenvironment (BMME) of articular chondrocytes. In this work, to engineer the BMME of articular chondrocytes, heterogeneous hydrogel structures of gelatin methacrylated (GelMA) containing differential-stiffness domains were first fabricated, and then periodic dynamic mechanical stimulations were applied to the hydrogel structures. The chondrocyte phenotype of ATDC5 cells was enhanced as the spatial differentiation in stiffness was increased in the hydrogel structures and was further strengthened by dynamic mechanical stimulation. It was speculated that the mechanical signals generated by the engineered BMME were sensed by the cells through the integrin ß1-FAK signaling pathway. This study revealed the key role of the combined effects of differential and dynamic BMME on the chondrocyte phenotype, which could provide theoretical guidance for highly active tissue-engineered articular cartilage.
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Cartilagem Articular , Condrócitos , Condrócitos/metabolismo , Hidrogéis/análise , Gelatina , Cartilagem Articular/fisiologia , Engenharia TecidualRESUMO
BACKGROUND: Thoracic aortic aneurysm or dissections (TAADs) represent a group of life-threatening diseases. Genetic aetiology can affect the age of onset, clinical phenotype, and timing of intervention. We conducted a prospective trial to determine the prevalence of pathogenic variants in TAAD patients and to elucidate the traits related to harbouring the pathogenic variants. One hundred and one unrelated TAAD patients underwent genetic sequencing and analysis for 23 TAAD-associated genes using a targeted PCR and next-generation sequencing-based panel. RESULTS: A total of 47 variants were identified in 52 TAAD patients (51.5%), including 5 pathogenic, 1 likely pathogenic and 41 variants of uncertain significance. The pathogenic or likely pathogenic (P/LP) variants in 4 disease-causing genes were carried by 1 patient with familial and 5 patients with sporadic TAAD (5.9%). In addition to harbouring one variant causing familial TAAD, the FBN1 gene harboured half of the P/LP variants causing sporadic TAAD. Individuals with an age of onset less than 50 years or normotension had a significantly increased genetic risk. CONCLUSIONS: TAAD patients with a younger age at diagnosis or normotension were more likely to carry a P/LP variant; thus, routine genetic testing will be beneficial to a better prognosis through genetically personalized care prior to acute rupture or dissection.
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Aneurisma da Aorta Torácica , Dissecção Aórtica , Humanos , Estudos Prospectivos , Aneurisma da Aorta Torácica/genética , Dissecção Aórtica/genética , ChinaRESUMO
Tissue engineering holds great promise in the generation of cartilage analogues for cartilage injury repair and replacement. However, for a long time, a variety of issues have remained unsolved in articular cartilage tissue engineering concerning immunogenicity, stability, and mechanical strength, among others. One of the most remarkable reasons lies in the lack or insufficiency of recapitulating the chondrocyte biomechanical microenvironment (BME) in the articular cartilage tissue engineering. In recent years, an increasing number of studies have disclosed the crucial role of the BME in chondrocyte phenotype and cartilage functions, which has inspired more precise and individualized research in articular cartilage tissue engineering by engineering the chondrocyte BME. This review first takes an in-depth look into the chondrocyte BME and its crucial effects on chondrocytes and articular cartilage tissues. Then, as the core of this work, the principal strategies and their approaches of engineering the chondrocyte BME towards articular cartilage tissue engineering were comprehensively discussed, from the perspectives of simulating the main characteristics of chondrocyte BME including engineering the heterogeneous matrix and the dynamic mechanical stimulation. The current limitations in this emerging area and potential strategies were also proposed to shed some light on the future directions in this field. Although there are still challenges to obtaining engineered articular cartilages with desired performance, the road ahead is bright under the constant efforts in engineering the chondrocyte BME at higher levels towards articular cartilage tissue engineering.
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Cartilagem Articular , Condrócitos , Condrócitos/fisiologia , Cartilagem Articular/fisiologia , Engenharia Tecidual , FenótipoRESUMO
BACKGROUND: To investigate the prenatal ultrasound diagnosis and management of patients with aortopulmonary septal defects (APSDs). METHODS: A total of 8 fetuses with APSDs who underwent fetal echocardiography at our hospital from January 2015 to January 2019 were retrospectively included in this study. RESULTS: Among the 8 fetuses, there were 4 cases of type I APSD, 3 cases were type II, and 1 case was type III. Among the 8 cases, there were 2 cases of simple APSD. There were echocardiographic characteristics that were common to all 3 types of APSD. This included defects between the ascending aorta and the trunk of the pulmonary artery in the short-axis section of the aorta, and in the three vessels and the three-vessel trachea section. Furthermore, the "V"-shaped structure confluence point of all APSD cases was positioned more forward than normal in the three-vessel trachea section. Type I APSD can be better characterized by the cross-section of the double outflow tract of the aorta and the pulmonary artery, which is close to the aortic valve and pulmonary valve. Type II APSD can be clearly diagnosed by the short-axis view of the aorta. Since the defect between the aorta and the pulmonary artery is distant from the aortic valve and pulmonary valve, the defect does not involve the bifurcation of the pulmonary artery and may be associated with an ectopic origin of the right pulmonary artery. Type III APSD is similar to a permanent arterial trunk, and the space between the ascending aorta and the trunk of the pulmonary artery is completely missing. Color and pulse Doppler showed shunt flow in the defects. CONCLUSIONS: APSD can be diagnosed and classified by fetal echocardiography. This, together with the presence or absence of fetal intracardiac and extracardiac deformities, can provide valuable prenatal information to pregnant women and their families, which may facilitate timely diagnosis and timely surgical treatment after birth.
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Vertically aligned noble metal nanowire arrays were grown on conductive electrodes based on a solution growth method. They show significant improvement of electrocatalytic activity in ethanol oxidation, from a re-deposited sample of the same detached nanowires. The unusual morphology provides open diffusion channels and direct charge transport pathways, in addition to the high electrochemically active surface from the ultrathin nanowires. Our best nanowire arrays exhibited much enhanced electrocatalytic activity, achieving a 38.0 fold increase in specific activity over that of commercial catalysts for ethanol electrooxidation. The structural design provides a new direction to enhance the electrocatalytic activity and reduce the size of electrodes for miniaturization of portable electrochemical devices.
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Owing to the properties of low density, large surface areas, excellent loading capacity, high permeability, and interstitial hollow spaces, hollow nanostructures have been widely applied in many important research fields, such as catalysis, drug-controlled release, confined synthesis, optics and electronics, and energy storage. This work provided a simple platform for hollow Cu2O nanostructure synthesis based on the surfactant controlling methodology, which is under the supposed mechanism of ion-pairing behavior at the initial nucleation stage. Thus here, we explore our system in two different directions: (1) we get different types of hollow Cu2O nanoparticles by controlling the surfactant concentration during the synthesis step in colloids, which is critical to the novel structure design and potential application in many different areas and (2) we explore the method to Cu2O hollow particle synthesis to test the hypothesis of the ion-pairing behavior during the initial nucleation by tuning the solvent ratio, cation concentration (such as NH4NO3 addition amount difference in the synthetic step), and selective etching. By tuning the synthetic conditions as well as designing control experiments, we hope to provide a solid understanding of the crystal growth mechanism. Our improved understanding in similar systems (both Cu2O and ZnO systems) will make it easier for interpreting nanostructure formation in new discoveries and, more importantly, in rationally designing various complex nanostructures based on a bottom-up strategy.
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A hierarchical electrode is prepared with Au nanowires grown on nickel foam. With large specific active surface area, it is used for producing syngas (H2/CO) with controllable ratio, through electrochemical process in DMF. The synthetic innovation lies in the use of 3-cyanopropyltriethoxysilane, to achieve the adsorption of appropriate amount of Au seeds for the one-dimensional growth of ultrathin Au nanowires (d ≈ 5 nm). With the nanowires forest on the three-dimensional porous nickel foam substrate, syngas is produced by electro-catalysis with high overall Faradic efficiency and tunable H2/CO ratios. This synthetic strategy opens a facile way to synthesize the hierarchical nanostructured materials, and broaden the choice of the catalysts for electrochemical applications.
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The sodium-water transport system is crucial for alveolar fluid clearance. The pulmonary edema caused by extracorporeal circulation is mainly due to increased alveolar capillary permeability and reduced fluid clearance. We previously demonstrated that pre-B-cell colony enhancing factor (PBEF) increases alveolar capillary permeability and inhibits the sodium-water transport system. However, the specific mechanism by which PBEF inhibits the sodium-water transport system is unclear. In this study, we used HPAEpiC (alveolar type II epithelial cells) to construct an anoxia-reoxygenation model and simulate the extracorporeal circulation microenvironment. The impact of PBEF on the expression of genes and proteins implicated in sodium transport and its effect on the activation status of the ERK, P38, and AKT signaling pathways were explored in HPAEpiC by real-time fluorescent PCR and western blotting. Specific inhibitors were employed to verify the role of the three signaling pathways in the regulation of the sodium-water transport system. PBEF was substantially non-toxic to alveolar epithelial cells, inhibited the expression of ENaC, NKA, and AQP1, and affected the ERK, P38, and AKT signaling pathways. ERK pathway inhibitors attenuated PBEF-induced downregulation of EnaC, NKA, and AQP1, and increased NKA activity. P38 pathway inhibitors only attenuated PBEF-induced suppression of NKA expression. AKT pathway inhibitors potentiated the inhibitory effects of PBEF, reducing EnaC, AQP1, and NKA expression, as well as NKA activity. In conclusion, PBEF inhibited the sodium-water transport system by activation of ERK and suppression of AKT signaling.
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Background: Macrophages play important roles in the immune response to, and successful implantation of, biomaterials. Titanium nanotubes are considered promising heart valve stent materials owing to their effects on modulation of macrophage behavior. However, the effects of nanotube-regulated macrophages on endothelial cells, which are essential for stent endothelialization, are unknown. Therefore, in this study we evaluated the inflammatory responses of endothelial cells to titanium nanotubes prepared at different voltages. Methods and results: In this study we used three different voltages (20, 40, and 60 V) to produce titania nanotubes with three different diameters by anodic oxidation. The state of macrophages on the samples was assessed, and the supernatants were collected as conditioned media (CM) to stimulate human umbilical vein endothelial cells (HUVECs), with pure titanium as a control group. The results indicated that titanium dioxide (TiO2) nanotubes induced macrophage polarization toward the anti-inflammatory M2 state and increased the expression of arginase-1, mannose receptor, and interleukin 10. Further mechanistic analysis revealed that M2 macrophage polarization controlled by the TiO2 nanotube surface activated the phosphatidylinositol 3-kinase/AKT and extracellular signal-regulated kinase 1/2 pathways through release of vascular endothelial growth factor to influence endothelialization. Conclusion: Our findings expanded our understanding of the complex influence of nanotubes in implants and the macrophage inflammatory response. Furthermore, CM generated from culture on the TiO2 nanotube surface may represent an integrated research model for studying the interactions of two different cell types and may be a promising approach for accelerating stent endothelialization through immunoregulation.
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Biomarcadores/análise , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Nanotubos/química , Neovascularização Fisiológica/efeitos dos fármacos , Titânio/farmacologia , Células Cultivadas , Humanos , Macrófagos/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Titânio/química , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Decellularized valve stents are widely used in tissue-engineered heart valves because they maintain the morphological structure of natural valves, have good histocompatibility and low immunogenicity. However, the surface of the cell valve loses the original endothelial cell coverage, exposing collagen and causing calcification and decay of the valve in advance. In this study, poly ε-caprolactone (PCL) nanoparticles loaded with osteoprotegerin (OPG) were bridged to a decellularized valve using a nanoparticle drug delivery system and tissue engineering technology to construct a new anti-calcification composite valve with sustained release function. The PCL nanoparticles loaded with OPG were prepared via an emulsion solvent evaporation method, which had a particle size of 133 nm and zeta potential of -27.8 mV. Transmission electron microscopy demonstrated that the prepared nanoparticles were round in shape, regular in size, and uniformly distributed, with an encapsulation efficiency of 75%, slow release in vitro, no burst release, no cytotoxicity to BMSCs, and contained OPG nanoparticles in vitro. There was a delay in the differentiation of BMSCs into osteoblasts. The decellularized valve modified by nanoparticles remained intact and its collagen fibers were continuous. After 8 weeks of subcutaneous implantation in rats, the morphological structure of the valve was almost complete, and the composite valve showed anti-calcification ability to a certain extent.
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This study was undertaken to investigate the effect of pre-B cell colony enhancing factor (PBEF) on Na+ and fluid transport in lung epithelial cells. METHODS: Type 1 and 2 cells were isolated from lung epithelium. After hypoxia reoxygenation treatment, the primary cell cultures were transfected with a plasmid over-expressing PBEF. Sodium-potassium ATPase (NKA), epithelial sodium channel (ENaC), type I cell marker rT140, surfactant protein (SP) and PBEF protein were analyzed at mRNA and protein levels using PCR and Western blot analysis. Immunofluorescence assays showed type 1 and 2 cells were successfully isolated. After the transfection with PBEF over-expression vector, PBEF and RTI40 levels were increased, while ENaC and SP as well as NKA, were decreased in both cells. It is clear that PBEF negatively regulates the expression of ENaC and NKA in the Na+ and fluid transport in lung epithelial cells.
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CdSe and CdS nanoparticles (NPs) are type I II-VI semiconductor materials with excellent optical properties. Usually various shapes of these NPs show a strong emission only from a CdSe or CdS single domain, while the emission from a CdSe core combined with a CdS shell is effectively suppressed due to the ultrafast hole relaxation from the CdS shell into the CdSe core. Therefore, the design and synthesis of heteronanostructures based on CdSe or CdS is of paramount importance in designing the ways of integrating these useful semiconductor materials into complex hybrid structures. Here we demonstrate the ligand-combination inducing growth method to prepare anisotropic core-shell (semiconductor-semiconductor) heteronanostructures, as well as anisotropic Au-semiconductor heteronanostructures. The NPs' anisotropic shape was confirmed by tilting a grid in TEM and their elemental composition was ascertained using EDX mapping in STEM mode. Furthermore, the photoluminescence excitation spectra were studied showing potential applications based on their unique optical properties. We believe that the mechanism investigation, the synthetic control, the obtained novel hybrid nanostructures and their optical properties will open doors to future studies on heterostructures based on semiconductors.
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A tetrasaccharide, corresponding to the heparan sulfate heparanase substrate, namely beta-D-GlcA(2S)-(1-->4)-alpha-D-GlcN(NS,6S)-(1-->4)-beta-D-GlcA-(1-->4)-alpha-D-GlcN(NS,6S)-OMe, was synthesized in a convergent manner via coupling of a pair of the disaccharide building blocks as a key step.