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Achieving the conversion from surface waves (SWs) to propagating waves has captivated long-standing interest, and various ingenious metasurfaces benefiting from the powerful control capability for electromagnetic waves are able to realize efficient SWs directional radiation. Nevertheless, most existing schemes still suffer from the bottlenecks of single radiation channel, uncontrollable radiation intensity, and immutable radiation pattern, which immensely hinder their practical application in high-integration intelligent devices. Herein, a series of appealing strategies are proposed to achieve the dual-channel SWs directional radiation with customizable radiation intensity and switchable radiation pattern. The dual-channel SWs radiation metadevice based on the phase modulation metasurface is designed to directionally radiate SWs in left-handed circular polarized channel and right-handed circular polarized channel and possesses the broadband frequency scanning characteristic. More strikingly, the intensity-customizable dual-channel SWs radiation metadevice loaded with lumped resistors can control the realized gain of two circular polarized radiation beams, and the pattern-switchable dual-channel SWs radiation metadevice loaded with PIN diodes can dynamically adjust the radiation direction of the radiation beams. Numerous simulations and experiments of the proof-of-concept prototypes with modular design corroborate the theoretical predictions. Our methodology shows unprecedented flexibility in regulating SWs directional radiation and has enormous potential in engineering applications.
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BACKGROUND: Cardia adenocarcinoma (CA) is a distinct form of gastric cancer, and the optimal means of treating it remains controversial. At present, the role of the condensation complex gene non-SMC condensin I complex subunit G (NCAPG) in CA is uncertain, and as such the present study was designed to elucidate its importance in this oncogenic context. METHODS: We first used bioinformatics approaches to assess NCAPG expression profiles in CA using public databases. Protein profiling was also used to examine the expression of this protein in CA tumors and adjacent tissues from 20 patients. Then the expression of NCAPG in CA samples was quantified via qRT-PCR and Western blotting. NCAPG knockdown and overexpression in the SGC-7901 and AGS cell lines were subsequently performed, after which the expression of key proteins associated with epithelial-mesenchymal transition (EMT; E-cadherin, vimentin, N-cadherin, Snail, Slug) and the regulation of apoptotic responses (caspase-3, Bax, Bcl-2) was measured. The mechanistic role of NCAPG in CA was additionally studied by analyzing proteins associated with Wnt/ß-catenin signaling including Wnt1, phosphorylated GSK3ß, ß-catenin, and phosphorylated ß- catenin. The impact of NCAPG on the migration, survival, and invasion of CA cells was further examined. RESULTS: CA samples exhibited high NCAPG expression. When this gene was overexpressed in cell lines, it reduced caspase-3, Bax, and E-cadherin levels whereas it elevated Bcl-2, vimentin, N-cadherin, Snail, and Slug levels. NCAPG overexpression also resulted in the enhanced expression of Wnt1, phosphorylated GSK3ß, and total ß-catenin and the reduced expression of phosphorylated ß-catenin. The knockdown of NCAPG, in contrast, yielded the opposite phenotype. At a functional level, the overexpression of NCAPG improved the apoptotic resistance of CA cells while driving them to undergo EMT and to become more invasive and migratory. CONCLUSIONS: NCAPG overexpression can promote EMT and suppress tumor cell apoptosis via the activation of Wnt/ß-catenin signaling.
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Adenocarcinoma/genética , Apoptose/genética , Cárdia/patologia , Proteínas de Ciclo Celular/genética , Transição Epitelial-Mesenquimal/genética , Neoplasias Gástricas/genética , Via de Sinalização Wnt/genética , beta Catenina/genética , Adenocarcinoma/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Oncogenes/genética , Neoplasias Gástricas/patologia , Vimentina/genéticaRESUMO
PURPOSE: Previous studies have shown that non-SMC condensin I complex subunit G (NCAPG) overexpression is correlated to poor prognosis of multiple cancer types. Herein, we explored the underlying mechanism of NCAPG-mediated cardia adenocarcinoma (CA) proliferation and cell cycle regulation. METHODS: The protein profiling technology was used to analyze the gene expression in 20 CA and adjacent tissue samples. Differential genes were identified by bioinformatic analysis. Western blot and qRT-PCR-based analysis assessed the NCAPG expression levels in multiple CA cell lines. CA cell lines, SGC-7901 and AGS, were transfected with Lip 2000, and stably transfected cell lines were screened for NCAPG overexpression and downregulation. MTT and clone formation assays were employed to detect cell proliferation, and cell cycle phases were analyzed using flow cytometry. Western blot was performed to determine the NCAPG gene expression levels. Finally, we studied the tumorigenic effects of NCAPG in the mouse model and validated the cell experiment results using immunohistochemistry. RESULTS: A significant overexpression of NCAPG was found in CA tissues and CA cell lines. The outcomes of MTT and clone formation assays showed that NCAPG upregulation promoted cell proliferation. The outcomes of these analyses were further validated using nude mice as an in vivo tumor model. As per the outcome of Western blot and flow cytometry analysis, NCAPG regulated the G1 phase through the cyclins (CDK4, CDK6, and cyclin D1) overexpression and cell cycle inhibitors (P21 and P27) downregulation. Overexpressed NCAPG and silenced NCAPG, both in vitro and in vivo, resulted in abnormal activation of the PI3K/AKT signaling pathway in CA cells. We observed that NCAPG overexpression increased the levels of phosphorylated PI3K, AKT, and GSK3ß; however, their total protein levels remained unchanged in CA cells. CONCLUSION: As a CA oncogene, NCAPG promoted cell proliferation and regulated cell cycle through PI3K/AKT signaling pathway activation.
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BACKGROUND: Nanog and CD133 are biomarkers of cancer stem cells (CSCs) that regulate cancer progression. The WW domain-containing oxidoreductase (WWOX) is a tumor suppressor protein that can inhibit tumor cell proliferation. The purpose of this study was to investigate the expression and clinical significance of Nanog, CD133, and WWOX in infiltrating breast cancer (IBC). METHODS: Expressions of Nanog, CD133, and WWOX in 204 IBC specimens and their corresponding control specimens were detected by immunohistochemistry. Patients' clinicopathologic and follow-up data were also collected. RESULTS: The rates of positive expression of Nanog and CD133 were significantly higher in IBC specimens than in control specimens, and their expression was positively associated with tumor size, grade, and tumor stages, lymph node metastasis (LNM), and tumor-node-metastasis (TNM) stage. The rate of positive expression of WWOX was significantly lower in IBC specimens than in control specimens, and its expression was inversely associated with tumor size, grade, and tumor stages, LNM, and TNM stage. Patients whose specimens expressed Nanog, CD133, or HER2 had a reduced overall survival (OS) when compared with patients not expressing these proteins. However, patients whose specimens expressed WWOX, ER, or PR had an increased OS when compared with patients who did not show expression. Multivariate analysis demonstrated that expression of Nanog, CD133, WWOX, ER, and HER2, and the TNM stage were independent prognostic factors for IBC patients. CONCLUSIONS: Therefore, Nanog, CD133, and WWOX should be considered as promising prognostic factors and therapeutic targets in IBC.
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OBJECTIVE: To compared the differentiation capacity of rat adipose-derived stem cells (ASCs) and bone marrow mesenchymal stem cells (BMSCs) into endothelial cells. METHODS: Rat BMSCs and ASCs were isolated, cultured and identified for cell surface markers using flow cytometry. The cell growth curves were drawn by CCK-8 assay, and the cells in active growth were induced for endothelial differentiation following standard protocols. On day 21 of induction, the cells were examined for mRNA expressions of endothelial cell specific markers CD31, KDR, and vWF using qPCR. Immunostaining was performed to observe the expression of CD31 on the cells. The induced cells were also tested for Dil-labeled acetylated low-density lipoprotein (ac-LDL) uptake ability. The tube-forming ability of the induced cells was verified on Matrigel. RESULTS: We successfully isolated rat ASCs and BMSCs. Morphologically, ASCs were similar with BMSCs, both having long spindle-shaped and fibroblast-like morphology. Flow cytometry showed that both BMSCs and ASCs had high expressions of mesenchymal markers CD29 and CD90 and a low expression of hematopoietic cell surface markers CD45. CCK-8 assay showed that ASCs proliferated more quickly than BMSCs. The cells with induced endothelial differentiation exhibited increased levels of CD31, KDR, and vWF mRNA expressions and immunofluorescent staining identified CD31 antigen expression on the cell membrane. Fluorescence microscopy revealed red fluorescence in the induced cells suggesting uptake of Dil-Ac-LDL by the cells. The induced cells were capable of forming tube on Matrigel, confirming their identity of endothelial cells. CONCLUSION: Both rat BMSCs and ASCs can be induced to differentiate into endothelial cells, but ASCs differentiate more quickly into endothelial cells and possess a stronger proliferation ability, suggesting its greater potential than BMSCs in future applications.
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Tecido Adiposo/citologia , Diferenciação Celular , Células Endoteliais/citologia , Células-Tronco Mesenquimais/citologia , Células-Tronco/citologia , Animais , Células da Medula Óssea , Células Cultivadas , RatosRESUMO
To determine serum cytokine profiles in Graves' disease (GD) patients with or without active and inactive thyroid associated ophthalmopathy (TAO), we recruited 65 subjects: 10 GD only (without TAO), 25 GD + active TAO, 20 GD + TAO, and 10 healthy controls. Liquid chip assay was used to measure serum Th1/Th2/Th17 cytokines including IFN-γ (interferon-gamma), TNF-α (tumor necrosis factor-alpha), IL-1α (interleukin-1 alpha), IL-1Ra (IL-1 receptor antagonist), IL-2, IL-4, IL-6, and IL-17 and two chemokines: RANTES (regulated upon activation, normal T cell expressed and secreted) and IP-10 (IFN-γ-induced protein 10). Serum levels of TSH (thyroid stimulating hormone) receptor autoantibodies (TRAb) were measured using an enzyme linked immunosorbent assay. Compared with healthy controls, TAO patients showed significantly elevated serum levels of IFN-γ, TNF-α, IL-1α, IL-4, IL-6, IL-17, and IP-10. Comparing active and inactive TAO, serum Th1 cytokines IFN-γ and TNF-α were elevated in active TAO, while serum Th2 cytokine IL-4 was elevated in inactive TAO. Serum Th17 cytokine IL-17 was elevated in GD but reduced in both active and inactive TAO. A positive correlation was found between TRAb and IFN-γ, TNF-α, IL-1α, IL-2, IL-4, and IL-6. Taken together, serum Th1/Th2/Th17 cytokines and chemokines reflect TAO disease activity and may be implicated in TAO pathogenesis.
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Citocinas/sangue , Doença de Graves/imunologia , Oftalmopatia de Graves/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Adulto , Feminino , Doença de Graves/sangue , Oftalmopatia de Graves/sangue , Humanos , Imunoglobulinas Estimuladoras da Glândula Tireoide/sangue , Masculino , Pessoa de Meia-Idade , Células Th1/imunologia , Células Th17/imunologia , Células Th2/imunologia , Adulto JovemRESUMO
We report a case of hypereosinophilic syndrome in a 47-year-old man who had acute pneumothorax as the initial presentation. Peripheral blood eosinophil count increased continuously over a period of 1 month and was associated with pulmonary changes and appearance of skin lesions on the right chest wall. Idiopathic hypereosinophilic syndrome was confirmed by bone marrow aspiration biopsy and skin lesion biopsy after exclusion of all possible secondary etiologies. The clinical status and chest radiographs showed marked improvement after treatment with corticosteroids.
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Pneumotórax/etiologia , Eosinofilia Pulmonar/complicações , Biópsia , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Pneumotórax/diagnóstico , Eosinofilia Pulmonar/diagnóstico , Radiografia Torácica , Tomografia Computadorizada por Raios XRESUMO
Acyclovir (ACV) is an effective and widely used antiviral agent. However, its clinical application is limited by severe nephrotoxicity. We assessed ACV-induced nephrotoxicity and identified the differentially expressed proteins using mass spectrometry-based proteomic analysis. In total, 30 ICR mice were intraperitoneally administrated ACV (150 or 600 mg/kg per day) for 9 days. After administration of ACV, levels of serum creatinine and urea nitrogen increased significantly. In addition, mouse kidneys exhibited histopathological changes and reduced expression levels of vascular endothelial growth factor (VEGF) and its receptor VEGFR2. In the proteomic analysis, more than 1,000 proteins were separated by two-dimensional polyacrylamide gel electrophoresis, and a total of 20 proteins were up- or down-regulated in the ACV group compared with the saline group. Among these, six proteins (MHC class II antigen, glyoxalase 1, peroxiredoxin 1, αB-crystallin, fibroblast growth factor receptor 1-IIIb, and cytochrome c oxidase subunit Vb) were identified in association with ACV-induced nephrotoxicity. These findings were confirmed by Western blotting analysis. The differential expression levels of α-BC, Prx1, Glo I and CcO Vb suggest that oxidative damage and mitochondrial injury may be involved in ACV-induced nephrotoxicity. Furthermore, VEGF and FGF may play a role in tissue repair and the restoration process following ACV nephrotoxicity.
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Aciclovir/toxicidade , Antivirais/toxicidade , Nefropatias/induzido quimicamente , Rim/efeitos dos fármacos , Rim/patologia , Proteoma/análise , Animais , Creatinina/sangue , Modelos Animais de Doenças , Rim/metabolismo , Rim/fisiopatologia , Nefropatias/sangue , Nefropatias/metabolismo , Nefropatias/patologia , Nefropatias/fisiopatologia , Testes de Função Renal , Camundongos , Camundongos Endogâmicos ICR , Proteoma/metabolismo , Proteômica , Fator A de Crescimento do Endotélio Vascular/análise , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/análiseRESUMO
Picorna-like viruses in the Picornavirales order are a large group of positive-strand RNA viruses that include numerous important pathogens for plants, insects, and humans. In these viruses, nonstructural protein 2C is one of the most conserved proteins and contains ATPase activity and putative RNA helicase activity. Here we expressed 2C protein of Ectropis obliqua picorna-like virus (EoV; genus Iflavirus, family Iflaviridae, order Picornavirales) in a eukaryotic expression system and determined that EoV 2C displays ATP-independent nucleic acid helix destabilizing and strand annealing acceleration activity in a concentration-dependent manner, indicating that this picornaviral 2C is more like an RNA chaperone than like the previously predicted RNA helicase. Our further characterization of EoV 2C revealed that divalent metal ions, such as Mg(2+) and Zn(2+), inhibit 2C-mediated helix destabilization to different extents. Moreover, we determined that EoV 2C also contains ATPase activity like that of other picornaviral 2C proteins and further assessed the functional relevance between its RNA chaperone-like and ATPase activities using mutational analysis as well as their responses to Mg(2+). Our data show that, when one of the two 2C activities was dramatically inhibited or almost abolished, the other activity could remain intact, showing that the RNA chaperone-like and ATPase activities of EoV 2C can be functionally separated. This report reveals that a picorna-like virus 2C protein displays RNA helix destabilizing and strand annealing acceleration activity, which may be critical for picornaviral replication and pathogenesis, and should foster our understanding of picorna-like viruses and viral RNA chaperones.
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Adenosina Trifosfatases/metabolismo , DNA Viral/metabolismo , RNA Helicases/metabolismo , Vírus de RNA/enzimologia , RNA Viral/metabolismo , Proteínas não Estruturais Virais/metabolismo , Adenosina Trifosfatases/genética , Sequência de Aminoácidos , DNA Viral/química , DNA Viral/genética , Dados de Sequência Molecular , Conformação de Ácido Nucleico , RNA Helicases/genética , Vírus de RNA/genética , RNA Viral/química , RNA Viral/genética , Alinhamento de Sequência , Proteínas não Estruturais Virais/genéticaRESUMO
This study investigated the impact of incretin on early-phase insulin secretion and glucose excursion. The normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM) groups included 16, 8, and 19 subjects, respectively. Subjects underwent continuous glucose monitoring for 3 days, followed by an oral glucose tolerance test. Plasma glucose, insulin, glucagon, total glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide-l (GLP-1) levels were measured at 30-min increments for 2 h after glucose intake. Differences with P < 0.05 were considered statistically significant. The area under the curve (AUC) of total GIP (120-min GIP-AUC) of the T2DM group was significantly lower than those of the NGT and IGT groups. The 120-min GLP-1-AUC of the NGT group was significantly larger than those of the T2DM and IGT groups. The early-phase insulin secretion index (ΔI30/ΔG30) of the T2DM group was significantly lower than those of the NGT and IGT groups. Mean amplitudes of glycemic excursions (MAGEs) went in the order of NGT < IGT < T2DM (P < 0.01, IGT vs. NGT; P < 0.001, T2DM vs. IGT). The 120-min GIP-AUC was negatively correlated with MAGE (r = -0.464), but uncorrelated with ΔI30/ΔG30. The 120-min GLP-1-AUC was positively correlated with ΔI30/ΔG30 (r = 0.580), but negatively correlated with MAGE (r = -0.606). Incretin may ameliorate glucose excursions, and GLP-1 may exert them by promoting early-phase insulin secretion. No correlation was observed between GIP secretion and early-phase insulin secretion.
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Glicemia/metabolismo , Incretinas/sangue , Incretinas/fisiologia , Insulina/metabolismo , Adulto , Estudos de Coortes , Diabetes Mellitus Tipo 2/sangue , Feminino , Polipeptídeo Inibidor Gástrico/sangue , Glucagon/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Intolerância à Glucose/sangue , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Secreção de Insulina , Masculino , Pessoa de Meia-IdadeRESUMO
Dendrolimus punctatus tetravirus (DpTV) belongs to the genus omegatetravirus of the Alphatetraviridae family. Sequence analysis predicts that DpTV replicase contains a putative helicase domain (Hel). However, the helicase activity in alphatetraviruses has never been formally determined. In this study, we determined that DpTV Hel is a functional RNA helicase belonging to superfamily-1 helicase with 5'-3' dsRNA unwinding directionality. Further characterization determined the length requirement of the 5' single-stranded tail on the RNA template and the optimal reaction conditions for the unwinding activity of DpTV Hel. Moreover, DpTV Hel also contains NTPase activity. The ATPase activity of DpTV Hel could be significantly stimulated by dsRNA, and dsRNA could partially rescue the ATPase activity abolishment caused by mutations. Our study is the first to identify an alphatetravirus RNA helicase and further characterize its dsRNA unwinding and NTPase activities in detail and should foster our understanding of DpTV and other alphatetraviruses.
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Vírus de Insetos/enzimologia , RNA Helicases/metabolismo , Vírus de RNA/enzimologia , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Sequência de Aminoácidos , Substituição de Aminoácidos , Animais , Sequência de Bases , Vírus de Insetos/genética , Cinética , Dados de Sequência Molecular , Mariposas/virologia , Mutagênese Sítio-Dirigida , Nucleosídeo-Trifosfatase/genética , Nucleosídeo-Trifosfatase/metabolismo , RNA/química , RNA/genética , RNA/metabolismo , RNA Helicases/genética , Vírus de RNA/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Homologia de Sequência de Aminoácidos , Células Sf9 , Spodoptera , Especificidade por SubstratoRESUMO
OBJECTIVE: To evaluate the quality of life (QOL) in patients with esophageal carcinoma after thoracoscopic and laparoscopic esophagectomy and circular stapled cervical esophagogastric anastomosis via retrosternal route or three-incision open surgery. METHODS: A total of 63 patients with middle-upper esophageal carcinoma who underwent radical surgical resection from January 2009 to October 2010 were enrolled in this study. Thirty-three patients underwent combined laparoscopic and thoracoscopic surgery and 30 three-incision open surgery. The EORTC questionnaire QLQ-C30 and QLQ-OES18 were used to evaluate the QOL. RESULTS: There were no significant differences in the clinical data between the two groups except for anastomosis method(P>0.05). In the endoscopy group, there was one patient developed anastomotic leakage(3.0%, 1/33), 1 postoperative wound infection in the neck (3.0%, 1/33), and 1 anastomotic stricture(3.0%, 1/33). In the open group, 8 patients had anastomotic leakage (26.7%, 8/30), 2 had anastomotic stricture (6.7%, 2/30), 1 had wound infection in the neck (3.3%, 1/30), and 6 had pulmonary infection (20.0%, 6/30). All the complications were managed by conservative treatment. The two groups differed in dysphagia, food intake, pain, obstruction, dyspnea, anorexia, fatigue, financial condition, physical function, role function, emotional function, cognitive function, social function and global health level and were more favorable in the endoscopy group(P<0.05), while there were no significant differences in the other dimensions. CONCLUSIONS: The postoperative complication rate is low after thoracoscopic and laparoscopic esophagectomy. Stapled anastomosis is associated with lower rate of anastomotic leak. QOL is better in patients following thoracoscopic and laparoscopic esophagectomy as compared to those following three-incision open surgery.