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OBJECTIVE: Lung adenocarcinoma (LUAD) is the most common type of lung cancer. However, predictive biomarkers for early efficacy and prognosis evaluation in patients with surgically resected LUAD are not completely explained. METHODS: Differentially expressed genes (DEGs), gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were identified by RNA sequencing (RNA-Seq) between thirteen LUAD tissues and five normal lung tissues. The expression of DEGs was confirmed by qRT-PCR and a validated cohort from GEPIA. Protein-protein interaction (PPI) network of the top 5% DEGs was constructed by STRING and visualized in Cytoscape. Immunofluorescence results were acquired from clinical specimens from LUAD patients. The expression of FHL1 was analyzed by ImageJ. Survival analysis was performed using the GEPIA dataset. RESULTS: Consistent with the RNA-Seq data, validation of DEGs expression by qRT-PCR and GEPIA cohort showed that FHL1 and SLIT3 were down-regulated in LUAD patient tissues compared with non-tumor tissues. Moreover, FHL1 was significantly reduced in LUAD cell lines compared to the bronchial epithelium cell line (P < 0.01). However, SLIT3 was elevated in A549 and H1299 cells (wide type EGFR) (P < 0.05) while decreased in HCC827 and PC9 cells (mutant EGFR) compared to BESA-2B cells (P < 0.01). PPI network revealed the most significant cluster with 10 nodes and 43 edges. Immunofluorescent staining also showed that the expression of FHL1 was lower in LUAD tissues compared with that in normal lung tissues (P < 0.01). The expressions of SLIT3 and FHL1 were positively correlated. Specifically, the higher expression level of SLIT3 and FHL1 independently predicted a better prognosis (P < 0.01 or P < 0.05). CONCLUSION: Our findings provide two novel candidates, FHL1 and SLIT3, for prognostic evaluation and treatments after surgery.
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Adenocarcinoma del Pulmón , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/cirugía , Adenocarcinoma del Pulmón/metabolismo , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirugía , Adenocarcinoma/genética , Pulmón/metabolismo , Pulmón/patología , Receptores ErbB/metabolismo , Regulación Neoplásica de la Expresión Génica , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas con Dominio LIM/genética , Proteínas con Dominio LIM/metabolismo , Proteínas de la Membrana/genéticaRESUMEN
We theoretically propose a coupled-topological-edge-state waveguide (CTESW), which is composed of stacked binary one-dimensional (1D) photonic crystals with opposite topological properties. The CTESW modes originate from the coupling between a sequence of topological edge states (TESs), which can be verified by the coupled mode theory (CMT). Based on finite element method (FEM), the tunable multiple transmission peaks due to CTESW modes are obtained, and the optical properties of the system can be modulated by the geometric parameters. Besides, the CTESW modes can also be tuned by changing incident angle from 0° to 60° under TE and TM polarization. Moreover, considering the relationship between channel spacing and the frequency spectrum utilization, a dense wavelength division multiplex (DWDM) filter with 50 GHz channel spacing based on CTESW is designed in communication band.
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As one of the crystal phases of titania, TiO2(B) was first utilized as a catalyst carrier for the oxidation of formaldehyde (HCHO). The mesoporous TiO2(B) loaded with Pt nanoparticles enhanced the HCHO oxidation reaction whose reaction rate was 4.5-8.4 times those of other crystalline TiO2-supported Pt catalysts. Simultaneously, Pt/TiO2(B) exhibited long-term stable HCHO oxidation performance. The structural characterization results showed that in comparison with Pt/anatase, Pt/TiO2(B) had more abundant hydroxyls, facilitating increasing the content of oxygen species. Studies on the role of hydroxyls in HCHO oxidation of Pt/TiO2(B) illustrated that synergistic involvement of terminally bound hydroxyls and bridging hydroxyls in HCHO oxidation accelerated the transformation from HCHO to formate via dioxymethylene. Moreover, hydroxyls could avoid the accumulation of excessive formate on Pt/TiO2(B) and promote the rapid oxidation of CO. Accordingly, the hydroxyl groups could accelerate each substep of formaldehyde oxidation, which enabled Pt/TiO2(B) to exhibit excellent formaldehyde oxidation performance.
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Hepatocellular carcinoma (HCC) inevitably developed oxaliplatin (OXA) resistance after long-term treatment, but the mechanism remains unclear. Here, we found that LncRNA UCA1 was upregulated in most of OXA-resistant HCC tissues and cells (HepG2/OXA and SMMC-7721/OXA). Follow-up analysis and online Kaplan-Meier Plotter revealed that HCC patients with high UCA1 level had a shorter survival compared with those with low expression. Overexpression of UCA1 increased OXA IC50 in HepG2 and SMMC-7721 cells, whereas knockdown of UCA1 decreased OXA IC50 in resistant counterparts. Moreover, dual luciferase reporter assay showed that co-transfection of UCA1-WT plasmid with miR-138-5p mimics enhanced fluorescence signals, whereas co-transfection of UCA1-Mut plasmid and miR-138-5p mimics did not induce any changes. Consistently, UCA1 levels in HepG2/OXA and SMMC-7721/OXA cells were downregulated after transfected with miR-138-5p mimics. UCA1 silencing or transfection of miR-138-5p mmics inhibited the activation of AKT and mTOR in HepG2/OXA and SMMC-7721/OXA cells, whereas UCA1 overexpression increased the phosphorylated AKT and mTOR levels in parental counterparts. Rapamycin or miR-138-5p mimics similarly suppressed the activation of AKT and mTOR, whereas UCA1 overexpression exert opposite roles. Interestingly, administration of rapamycin or miR-138-5p mimics apparently antagonized the effects of UCA1 on AKT and mTOR activation. Besides, depletion of UCA1 triggered more dramatic regression of HepG2 xenografts than that of HepG2/OXA xenografts with OXA treatment and impaired the p-AKT and p-mTOR levels in vivo. In conclusion, our findings provide the evidence that UCA1 may contribute to OXA resistance via miR-138-5p-mediated AK /mTOR activation, suggesting that UCA1 is a potential therapeutic target for HCC.
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Antineoplásicos/farmacología , Carcinoma Hepatocelular/genética , Resistencia a Antineoplásicos/genética , Neoplasias Hepáticas/genética , Oxaliplatino/farmacología , ARN Largo no Codificante/genética , Animales , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidad , Línea Celular , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidad , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Largo no Codificante/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Regulación hacia ArribaRESUMEN
PURPOSE: Lung adenocarcinoma (LUAD) accounts for approximately half of patients in lung cancer. Cancer-associated fibroblasts (CAFs) are the major component in the tumor microenvironment (TME). Targeting CAFs is a promising therapeutic strategy for cancer treatment. However, therapeutic targets of CAFs in LUAD remains largely unclear. METHODS: Seven CAFs and nine normal fibroblasts (NFs) were isolated from tumor and paratumor tissues of LUAD patients undergoing surgery, respectively. RNA-seq and bioinformatics analysis were performed to identify the differentially expressed genes (DEGs) and their functions in CAFs compared with NFs. DEGs of ten overlaying were obtained from RNA-seq, our previously reported lncRNA microarray and public datasets (E-MTAB-6149, E-MTAB-6653) and validated by RT-qPCR. Nik-related kinase (NRK) was further validated by RT-qPCR, immunofluorescence (IF), Western Blot (WB) in vitro, and in Cancer Cell Line Encyclopedia (CCLE) database. Survival analysis was performed on Kaplan-Meier plotter. RESULTS: A total of 1799 DEGs were identified, including 650 upregulated DEGs and 1149 downregulated DEGs. The upregulated and downregulated DEGs were mostly enriched in extracellular matrix (ECM) functions and in glycolysis/gluconeogenesis pathways. Interestingly, NRK was the most significantly upregulated overlaying DEGs which was rarely associated with CAFs before. NRK was predominantly expressed in CAFs, but weakly expressed in NFs, normal lung bronchial epithelial cell line BEAS-2B, LUAD cell lines A549 and H1299, as well as in the majority of 191 lung cancer cell lines including LUAD. Moreover, elevated NRK predicted poor survival in LUAD patients. CONCLUSION: Here, we first report that NRK is significantly elevated in LUAD-associated CAFs and may function as a promising therapeutic target for cancer combination treatment. Besides, modulation of ECM and glycolysis/gluconeogenesis pathways may be an efficient approach to alter CAFs functionality in LUAD.
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Adenocarcinoma del Pulmón/patología , Biomarcadores de Tumor/metabolismo , Fibroblastos Asociados al Cáncer/patología , Regulación Neoplásica de la Expresión Génica , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neoplasias Pulmonares/patología , Proteínas Serina-Treonina Quinasas/metabolismo , Microambiente Tumoral , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/metabolismo , Biomarcadores de Tumor/genética , Fibroblastos Asociados al Cáncer/metabolismo , Femenino , Estudios de Seguimiento , Redes Reguladoras de Genes , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Persona de Mediana Edad , Pronóstico , Mapas de Interacción de Proteínas , Proteínas Serina-Treonina Quinasas/genética , RNA-Seq , Tasa de Supervivencia , Células Tumorales CultivadasRESUMEN
PURPOSE: Metastasis is an unavoidable event happened among almost all small cell lung cancer (SCLC) patients. However, the molecular driven factors have not been elucidated. Recently, a novel hydrolase called cell migration inducing hyaluronidase (CEMIP) triggered both migration and invasion in many tumors but not SCLC. Therefore, in this study, we verified that CEMIP promoted migration and invasion in SCLC and applied proteomics analysis to screen out potential target profiles and the signaling pathway related to CEMIP regulation. METHOD: Immunofluorescence was conducted to exam the expression of CEMIP on SCLC and paired adjacent normal tissues among enrollment. RT-qPCR and Western blot (WB) assays were conducted to valuate cellular protein and mRNA expression of CEMIP and EMT markers. Lentivirus-CEMIP-shRNAs and CEMIP plasmid were used for expression manipulating. Changes of cellular migration and invasion were tested through transwell assays. Tandem Mass Tag (TMT) peptide labeling coupled with LC-MS/MS was used for quantifying proteins affected by reducing expression of CEMIP on H446 cells. RESULTS: The expression of CEMIP showed 1.64 ± 0.16-fold higher in SCLC tissues than their normal counterpart. Decreasing the expression of CEMIP on SCLC cells H446 regressed both cellular migration and invasion ability, whereas the promoting cellular migration and invasion was investigated through over-expressing CEMIP on H1688. Proteomic and bioinformatics analysis revealed that total 215 differentially expressed proteins (DEPs) that either their increasing or decreasing relative expression met threshold of 1.2-fold changes with p value ≤ 0.05. The dramatic up-regulated DEPs included an unidentified peptide sequence (encoded by cDNA FLJ52096) SPICE1 and CRYAB, while the expression of S100A6 was largely down-regulated. DEPs mainly enriched on caveolae of cellular component, calcium ion binding of biological process and epithelial cell migration of molecular function. KEGG enrichment indicated that DEPs mainly exerted their function on TGF-ß, GABAergic synapse and MAPK signaling pathway. CONCLUSION: It is the first report illustrating that CEMIP might be one of the metastatic triggers in SCLC. And also, it provided possible molecular mechanism cue and potential downstream target on CEMIP-induced cellular migration and invasion on SCLC.
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Hialuronoglucosaminidasa/metabolismo , Neoplasias Pulmonares/metabolismo , Proteoma/metabolismo , Carcinoma Pulmonar de Células Pequeñas/metabolismo , Anciano , Línea Celular Tumoral , Movimiento Celular/fisiología , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Hialuronoglucosaminidasa/biosíntesis , Hialuronoglucosaminidasa/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estudios Retrospectivos , Transducción de Señal , Carcinoma Pulmonar de Células Pequeñas/genética , Carcinoma Pulmonar de Células Pequeñas/patologíaRESUMEN
Herein, we present a tunable multifunctional reflection polarizer, based on a graphene metasurface, which is composed of an array of cross double-ellipse graphene patches. A dual band of linear-to-linear (LTL) polarization conversions is achieved due to the superimposition of the two reflection components with a near 0° or 180° phase difference, in the mid-infrared region. By carefully choosing the parameters, linear-to-circular polarization conversion and broadband of LTL polarization conversion (about 0.7 THz) are also realized. Also, the tunable responses of the proposed reflection polarizer are discussed under a different Fermi energy and electron scattering time. It is believed that our proposed polarizer can be widely used for multifunctional and tunable polarization conversion.
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Selecting high-protein peanut cultivar KB008, high-fat cultivar Hual7, and high O/L cultivar Nongda818 as test materials, a field experiment was conducted in 2011 and 2012 to study the effects of foliar spraying paclobutrazol (PBZ) at late flowering stage on the kernel yield and quality and the activities of leaf carbon and nitrogen metabolism enzymes of the cultivars. Spraying PBZ increased the pod yield of the cultivars significantly via increasing the pod number per plant, decreasing the pod number per kilogram, and increasing the percentage of double kernel. Spraying PBZ also increased the kernel fat and soluble sugar contents but decreased the kernel protein content to varying degrees, and increased the O/L ratio of high-fat cultivar Hual7 significantly. PBZ increased the kernel fat content while decreased the kernel protein content of Nongda818 significantly, but had little effects on the kernel protein or fat content of the other two cultivars. Spraying PBZ decreased the leaf nitrate reductase activity of the three cultivars at their pod setting stage, and the leaf glutamine synthetase and glutamate dehydrogenase activities at pod setting and filling stages, with the largest decrement for Nongda818 and the smaller one for KB008 and H17. Spraying PBZ decreased the leaf glutamate oxaloacetic transaminase and glutamate pyruvate transaminase activities of the three cultivars at their pod setting and filling stages, illustrating that the decrease of the nitrogen metabolism enzyme activities after spraying PBZ was the main reason of the decreased kernel protein content of the cultivars. PBZ increased the leaf sucrose synthase and sucrose phosphate synthase activities at pod setting and filling stages, being significant for Nongda818. PBZ improved the leaf phosphoenolpyruvate carboxylase and ribulose bisphosphate carboxylase activities of the three cultivars at their pod setting and filling stages, being most significant for Nongda818. It was suggested that the increase of the carbon metabolism enzyme activities was the physiological basis of the improvement of kernel fat content after spraying PBZ.