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Uniform small-sized MOF-Ti nanoparticles were prepared by a one-step hydrothermal method, and then a 5-10 nm TiO2 shell was coated onto them by using the sol-gel method, and MOF-Ti/TiO2 with a specific surface area of 50.2 m2 g-1 was successfully prepared. The nanoparticles were characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), nitrogen adsorption-desorption isotherms (BET), and X-ray photoelectron spectroscopy (XPS). The above-analyses have elaborated the experimental study of their morphology, elements, and energy of organic functional groups. At the same time, through the use of a high-voltage rotary rheometer to test their rheological properties, the analysis of shear stress, ER efficiency, shear viscosity, etc. was performed and their dielectric constant and dielectric loss were studied by using a broadband dielectric spectrometer. Finally, we found that MOF-Ti/TiO2 is a new core-shell nanocomposite particle with a small particle size and good electrorheological properties.
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Herein, a simple hydrothermal method is employed to synthesize anatase TiO2 with dominant (100) facets, as a precursor, using titanate nanofibers derived from alkali treatment. Scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-ray diffraction (XRD) are carried out to confirm the surface morphology and phase structure of the TiO2 product. The formation mechanism of TiO2 enclosed by (100) and (101) facets is deduced to be the selective adsorption of OH- on the (100) facets of anatase TiO2. Electroheological (ER) experiments indicate that the tetragonal-facet-rod anatase TiO2 with exposed (100) facets exhibits an excellent ER performance with a high ER efficiency of up to 52.5, which results from the anisotropy of its special morphology. In addition, the effect of shape on its dielectric property is investigated via broadband dielectric spectroscopy.
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Bowl-like titanium oxide nanoparticles were successfully prepared by a simple solvothermal method using absolute ethanol and isopropanol as the cosolvent. Ostwald ripening coupled with the inner-stress-induce effect were assumed to play an important role in the formation of this unique bowl-like morphology. The morphological evolution from solid nanosphere to bowl-like nanoparticle was investigated by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Besides, the structural characteristics of the as-synthesized TiO2 nanoparticles were confirmed by X-ray diffraction (XRD), Fourier transform infrared (FT-IR) and thermogravimetric analysis (TGA). Moreover, a rotational rheometer was operated to examine the electrorheological (ER) effect. Excellent ER properties were achieved when the TiO2 particles were dispersed in silicone oil under an external electric field.
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Monodisperse SiO2/TiO2 yolk-shell nanospheres (YSNSs) with different SiO2 core sizes were fabricated and adopted as dispersing materials for electrorheological (ER) fluids to investigate the influence of the gradual structural change of disperse particles on ER properties. The results showed that the ER performance of the YSNS-based ER fluid prominently enhanced with the decrease of SiO2 core size, which was attributed to the enhancement of electric field force between YSNSs. Combined with the analysis of dielectric spectroscopy, it was found that the increase of permittivity at low frequency (10(-2)-10(0) Hz) was due to the increase of polarized charges caused by secondary polarization (Psp). Moreover, the number of Psp closely related to the distributing change of polarized particles in ER fluid was a critical factor to assess the ER performance. Additionally, a parameter K (the absolute value of the slope of permittivity curves at 0.01 Hz) could be utilized to characterize the efficiency of structural evolution of polarized particles in ER fluid. Compared with the ER performance, it could be concluded that the value of Δε(100Hz-100kHz)' just demonstrated the initial intensity of the interface polarization in the ER fluid as the electric field was applied, which ignored the distributing evolution of polarized disperse particles in ER fluid. The polarizability Δε(0.01Hz-100kHz)' obtained in the frequency range of 10(-2)-10(5) Hz should be more suitable for analyzing the system of ER fluid. The relationships between polarizability of disperse particles, parameter K and ER properties were discussed in detail.
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Espectroscopía Dieléctrica , Electricidad , Nanosferas/química , Reología , Dióxido de Silicio/química , Titanio/químicaRESUMEN
Crosslinked polyethylene (XLPE) is an important polyethylene modification material which is widely used in high-voltage direct current (HVDC) transmission systems. Low-density polyethylene (LDPE) was used as a matrix to improve the thermal and electrical properties of XLPE composites through the synergistic effect of a crosslinking agent and nanopore structure molecular sieve, TS-1. It was found that the electrical and thermal properties of the matrices were different due to the crosslinking degree and crosslinking efficiency, and the introduction of TS-1 enhanced the dielectric constants of the two matrices to 2.53 and 2.54, and the direct current (DC) resistivities were increased to 3 × 1012 and 4 × 1012 Ω·m, with the enhancement of the thermal conductivity at different temperatures. As the applied voltage increases, the DC breakdown field strength is enhanced from 318 to 363 kV/mm and 330 to 356 kV/mm. The unique nanopore structure of TS-1 itself can inhibit the injection and accumulation in the internal space of crosslinked polyethylene composites, and the pore size effect of the filler can limit the development of electron impact ionization, inhibit the electron avalanche breakdown, and improve the strength of the external applied electric field (breakdown field) that TS-1/XLPE nanocomposites can withstand. This provides a new method for the preparation of nanocomposite insulating dielectric materials for HVDC transmission systems with better performance.
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BACKGROUND: Isocitrate dehydrogenase-wildtype (IDHwt) glioblastoma (GBM) is one of the most aggressive primary brain tumors. The recurrence of GBM is almost inevitable. As an adjuvant option to surgery, intraoperative radiotherapy (IORT) is gaining increasing attention in the treatment of glioma. This study is aimed to evaluate the therapeutic efficacy of IORT on recurrent IDHwt GBM. METHODS: In total, 34 recurrent IDHwt GBM patients who received a second surgery were included in the analysis (17 in the surgery group and 17 in the surgery + IORT group). RESULTS: The progression-free survival and overall survival after the second surgery were defined as PFS2 and OS2, respectively. The median PFS2 was 7.3 months (95% CI: 6.3-10.5) and 10.6 months (95% CI: 9.3-14.6) for those patients who received surgery and surgery + IORT, respectively. Patients in the surgery + IORT group also had a longer OS2 (12.8 months, 95% CI: 11.4-17.2) than those in the surgery group (9.3 months, 95% CI: 8.9-12.9). The Kaplan-Meier survival curves, analyzed by log-rank test, revealed a statistically significant difference in PFS2 and OS2 between both groups, suggesting that IORT plays an active role in the observed benefits for PFS2 and OS2. The effects of IORT on PFS2 and OS2 were further confirmed by multivariate Cox hazards regression analysis. Two patients in the surgery group developed distant glioma metastases, and no radiation-related complications were observed in the IORT group. CONCLUSIONS: This study suggests that low-dose IORT may improve the prognosis of recurrent IDHwt GBM patients. Future prospective large-scale studies are needed to validate the efficacy and safety of IORT.
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Glioblastoma , Humanos , Glioblastoma/genética , Glioblastoma/radioterapia , Glioblastoma/cirugía , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/cirugía , Pronóstico , Estudios RetrospectivosRESUMEN
Thermal management plays a vital role in technology (electronic and electrical equipment) and life (high-temperature injury). Therefore, thermal regulation has attracted worldwide attention. This review addresses the applications of electrospinning (e-spinning) in the thermal management of polymer matrix composites, mainly involving enhanced thermal conductivity (TC), thermal insulation, and passive daytime radiative cooling (PDRC). In particular, in the regulation of TC, e-spinning can uniformly distribute active fillers in the composites to achieve bidirectional control. The types of active filler and its connection forms in the composites are discussed emphatically. In addition, PDRC without energy consumption is also highlighted. Finally, the current challenges and future development are addressed.
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BACKGROUND: RecQ-mediated genome instability 2 (RMI2) maintains genome stability by promoting DNA damage repair. It has been reported to accelerate the progression of several tumors. However, the functional mechanism of RMI2 in breast cancer remains unclear. METHODS: Gene expression profiles were obtained from TCGA, GTEx, and GEO databases. The expression of RMI2 and its prognostic value in breast cancer was explored. In addition, we calculated pooled standardized mean deviation (SMD) and performed a summary receiver operating characteristic (sROC) curve analysis to further determine RMI2 expression status and diagnostic significance. The functions and related signaling pathways were investigated based on GO and KEGG analyses. The PPI network was constructed by combining the STRING database and Cytoscape software. Subsequently, in vitro assays were conducted to detect the effect of RMI2 on the proliferation and migration of breast cancer cells. RESULTS: The expression of RMI2 was markedly upregulated in breast cancer tissues relative to that in normal tissues. Moreover, pooled SMD further confirmed the overexpression of RMI2 in breast cancer (SMD = 1.29, 95% confidence interval (CI): 1.18-1.41, p = 0.000). The sROC curve analysis result suggested that RMI2 had a relatively high diagnostic ability in breast cancer (AUC = 0.87, 95% CI: 0.84-0.90). High RMI2 expression was associated with poor prognosis. GO and KEGG analyses revealed that RMI2 was closely related to cell adhesion, various enzyme activities, and PI3K/AKT signaling pathway. PPI analysis showed that RMI2 had interactions with proteins involved in DNA damage repair. knockdown of RMI2 remarkably inhibited the proliferation and migration of breast cancer cells, while overexpression of RMI2 exerted the opposite effects. Furthermore, we identified that RMI2 accelerates the proliferation and migration of breast cancer cells via activation of the PI3K/AKT pathway. CONCLUSION: The results suggest that RMI2 is a potential diagnostic and prognostic biomarker associated with cell proliferation and migration, and may be used as a novel therapeutic target for breast cancer in the future.
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Neoplasias de la Mama , Humanos , Femenino , Pronóstico , Neoplasias de la Mama/patología , Proteínas Proto-Oncogénicas c-akt , Fosfatidilinositol 3-Quinasas/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Proteínas de Unión al ADN/genéticaRESUMEN
Although electrospinning (e-spinning) has witnessed rapid development in recent years, it has also been criticized by environmentalists due to the use of organic solvents. Therefore, aqueous e-spinning (green e-spinning) is considered a more attractive technique. However, considering the poor water resistance and mechanical properties of electrospun (e-spun) nanofibers, cross-linking is a perfect solution. In this review, we systematically discuss the cross-linking e-spinning system for the first time, including cross-linking strategies (in situ, liquid immersion, vapor, and spray cross-linking), cross-linking mechanism (physical and chemical cross-linking) of e-spun nanofibers, and the various applications (e.g., tissue engineering, drug delivery, water treatment, food packaging, and sensors) of cross-linked e-spun nanofibers. Among them, we highlight several cross-linking methods, including UV light cross-linking, electron beam cross-linking, glutaraldehyde (and other commonly used cross-linking agents) chemical cross-linking, thermal cross-linking, and enzymatic cross-linking. Finally, we confirm the significance of cross-linking e-spinning and reveal the problems in the construction of this system.
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Heteroatom-doped three-dimensional (3D) porous carbons possess great potential as promising electrodes for high-performance supercapacitors. Inspired by the inherent features of intumescent flame retardants (IFRs) with universal availability, rich heteroatoms and easy thermal-carbonization to form porous carbons, herein we proposed a self-assembling and template self-activation strategy to produce N/P dual-doped 3D porous carbons by nano-CaCO3 template-assistant carbonization of IFRs. The IFRs-derived carbon exhibited large specific surface area, well-balanced hierarchical porosity, high N/P contents and interconnected 3D skeleton. Benefitting from these predominant characteristics on structure and composition, the assembled supercapacitive electrodes exhibited outstanding electrochemical performances. In three-electrode 6 M KOH system, it delivered high specific capacitances of 407 F g-1 at 0.5 A g-1, and good rate capability of 61.2% capacitance retention at 20 A g-1. In two-electrode organic EMIMBF4/PC system, its displayed high energy density of 62.8 Wh kg-1 at a power density of 748.4 W kg-1, meanwhile it had excellent cycling stability with 84.7% capacitance retention after 10,000 cycles. To our best knowledge, it is the first example to synthesize porous carbon from IFRs precursor. Thus, the current work paved a novel and low-cost way for the production of high-valued carbon material, and expanded its application for high-performance energy storage devices.
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Retardadores de Llama , Carbono , Capacidad Eléctrica , Electrodos , PorosidadRESUMEN
The semi-conductive layer located between the wire core and the insulation layer in high voltage direct current (HVDC) cable plays a vital role in uniform electric field and affecting space charges behaviors. In this work, the research idea of adding ionic conductive particles to semi-conductive materials to improve the conductive network and reduce the energy of the moving charge inside it and to suppress charge injection was proposed. Semi-conductive composites doped with different La0.8Sr0.2MnO3 (LSM) contents were prepared. Resistivity at different temperatures was measured to investigate the positive temperature coefficient (PTC) effect. Pulse electro-acoustic (PEA) method and thermal-stimulation depolarization currents (TSDC) tests of the insulation layers were carried out. From the results, space charge distribution and TSDC currents in the insulation samples were analyzed to evaluate the inhibitory effect on space charge injection. When LSM content is 6 wt. %, the experimental results show that the PTC effect of the specimen and charge injection are both being suppressed significantly. The maximum resistivity of it is decreased by 53.3% and the insulation sample has the smallest charge amount, 1.85 × 10-7 C under 10 kV/mm-decreased by 40%, 3.6 × 10-7 C under 20 kV/mm-decreased by 45%, and 6.42 × 10-7 C under 30 kV/mm-decreased by 26%. When the LSM content reaches 10 wt. %, the suppression effect on the PTC effect and the charge injection are both weakened, owing to the agglomeration of the conductive particles inside the composites which leads to the interface electric field distortion and results in charge injection enhancement.
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This paper describes the effects of α-Al2O3 nanosheets on the direct current voltage breakdown strength and space charge accumulation in crosslinked polyethylene/α-Al2O3 nanocomposites. The α-Al2O3 nanosheets with a uniform size and high aspect ratio were synthesized, surface-modified, and characterized. The α-Al2O3 nanosheets were uniformly distributed into a crosslinked polyethylene matrix by mechanical blending and hot-press crosslinking. Direct current breakdown testing, electrical conductivity tests, and measurements of space charge indicated that the addition of α-Al2O3 nanosheets introduced a large number of deep traps, blocked the charge injection, and decreased the charge carrier mobility, thereby significantly reducing the conductivity (from 3.25 × 10-13 S/m to 1.04 × 10-13 S/m), improving the direct current breakdown strength (from 220 to 320 kV/mm) and suppressing the space charge accumulation in the crosslinked polyethylene matrix. Besides, the results of direct current breakdown testing and electrical conductivity tests also showed that the surface modification of α-Al2O3 nanosheets effectively improved the direct current breakdown strength and reduced the conductivity of crosslinked polyethylene/α-Al2O3 nanocomposites.
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The exploration of flexible supercapacitors with high energy density is a matter of considerable interest to meet the demand of wearable electronic devices. In this work, with carbon nanotubes (CNTs) grown on carbon cloth (CC) as flexible substrate, NiCoP nanoflake-surrounded CNT nanoarrays (NiCoP/CNT) and N-doped carbon coated CNT nanoarrays (CNT@N-C) were synthesized on CC and utilized as cathode and anode materials for constructing flexible all-solid-state hybrid supercapacitor. Both them exhibit excellent electrochemical performance. NiCoP/CNT/CC composites can deliver a specific capacitance of 261.4 mAh g-1, and CNT@N-C/CC exhibits a high capacitance of 256 F g-1 at the current density of 0.5 A g-1. The hybrid supercapacitor built from the two well designed electrodes can provide a specific capacitance of 123.3 mAh g-1 at current density 1 mA g-1 within a potential window of 0-1.5 V and retain almost 85% of its initial capacitance after 5000 cycles. Furthermore, the flexible devices show the maximum energy density of 138.7 Wh kg-1 and a power density of 6.25 kW kg-1, obviously superior to some recent reported supercapacitor devices, indicating its potential in practical application.
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BACKGROUND: Radioresistance of some non-small cell lung cancer (NSCLC) types increases the risk of recurrence or metastasis in afflicted patients, following radiotherapy. As such, further improvements to NSCLC radiotherapy are needed. The expression of oncogene TP53-regulated inhibitor of apoptosis 1 (TRIAP1) in NSCLC is increased following irradiation. Furthermore, gene set enrichment analysis (GSEA) has suggested that TRIAP1 might be involved in maintaining redox homeostasis. This in turn might enhance cell radioresistance. METHODS: In this study we irradiated human NSCLC cell lines (A549 and H460), while knocking down TRIAP1, to determine whether a disrupted redox homeostasis could attenuate radioresistance. RESULTS: Irradiation notably increased both mRNA and protein levels of TRIAP1. In addition, TRIAP1 knockdown decreased the expression of several antioxidant proteins, including thioredoxin-related transmembrane protein (TMX) 1, TMX2, thioredoxin (TXN), glutaredoxin (GLRX) 2, GLRX3, peroxiredoxin (PRDX) 3, PRDX4, and PRDX6 in A549 and H460 cells. In addition, silencing TRIAP1 impaired the radiation-induced increase of the aforementioned proteins. Continuing along this line, we observed a radiation-induced reduction of cell viability and invasion, as well as increased apoptosis and intracellular reactive oxygen species following TRIAP1 knockdown. CONCLUSIONS: In summary, we identified TRIAP1 as a key contributor to the radioresistance of NSCLC by maintaining redox homeostasis.
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Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Regulación Neoplásica de la Expresión Génica/efectos de la radiación , Homeostasis , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neoplasias Pulmonares/patología , Radiación Ionizante , Apoptosis , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Proliferación Celular , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/radioterapia , Oxidación-Reducción , Pronóstico , Tasa de Supervivencia , Células Tumorales Cultivadas , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
Accumulating evidence suggests that radiation treatment causes an adaptive response of lung adenocarcinoma (LUAD), which in turn attenuates the lethal effect of the irradiation. Previous microarray assays manifested the change of gene expression profile after irradiation. Bioinformatics analysis of the significantly changed genes revealed that VANGL1 may notably influence the effect of radiation on LUAD. To determine the role of VANGL1, this study knocked down or overexpressed VANGL1 in LUAD. M6A level of VANGL1 mRNA was determined by M6A-IP-qPCR assay. Irradiation caused the up-regulation of VANGL1 with the increase of VANGL1 m6A level. Depletion of m6A readers, IGF2BP2/3, undermined VANGL1 mRNA stability and expression upon irradiation. miR-29b-3p expression was decreased by irradiation, however VANGL1 is a target of miR-29b-3p which was identified by Luciferase report assay. The reduction of miR-29b-3p inhibited the degradation of VANGL1 mRNA. Knockdown of VANGL1 enhanced the detrimental effect of irradiation on LUAD, as indicated by more severe DNA damage and increased percentage of apoptotic cells. Immunocoprecipitation revealed the interaction between VANGL1 with BRAF. VANGL1 increased BRAF probably through suppressing the protein degradation, which led to the increase of BRAF downstream effectors, TP53BP1 and RAD51. These effectors are involved in DNA repair after the damage. In summary, irradiation caused the up-regulation of VANGL1, which, in turn, mitigated the detrimental effect of irradiation on LUAD by protecting DNA from damage probably through activating BRAF/TP53BP1/RAD51 cascades. Increased m6A level of VANGL1 and reduced miR-29b-3p took the responsibility of VANGL1 overexpression upon irradiation.
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Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/radioterapia , Proteínas Portadoras/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/radioterapia , Proteínas de la Membrana/metabolismo , MicroARNs/metabolismo , Proteínas de Unión al ARN/metabolismo , Adenina/análogos & derivados , Adenina/metabolismo , Adenocarcinoma del Pulmón/genética , Adulto , Anciano , Proteínas Portadoras/genética , Daño del ADN , Humanos , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Neoplasias Pulmonares/genética , Proteínas de la Membrana/genética , MicroARNs/genética , Persona de Mediana Edad , ARN Mensajero/genética , ARN Mensajero/metabolismo , Regulación hacia Arriba/efectos de la radiaciónRESUMEN
Semi-conductive composites composed of carbon black-polymer play an important role in uniform electric field in high voltage direct current (HVDC) cable. They also affect space charge behaviors in the insulation material. However, the charge injection characteristics of semi-conductive composites are not detailed. In this work, the electrode structure of 'Semi-conductive composites- Insulation material- Metal bottom' (S-I-M) is proposed, and the currents formed by injected charges from semi-conductive composites are characterized by the thermally stimulated depolarization current (TSDC) method. Further, the experimental results based on the structure of S-I-M are compared with the traditional electrode structure of M-I-M (Metal upper electrode- Insulation material- Metal bottom electrode) and the simplified cable electrode structure of MS-I-M (Metal upper electrode-Semi-conductive electrode- Insulation material- Metal bottom electrode), respectively. The experimental results show that the semi-conductive composite plays an important role in the charge injection process and it presents a different tendency under different compound modes of temperature and electric field. For the low electric field (E ≤ 5 kV/mm) and the low temperature (T ≤ 50 °C), the current caused by the accumulated charges follows the rule, IS > IMS > IM. For the low electric field and high temperature (T > 50 °C), the current caused by the injected charges follows the rule, IMS > IM > IS. This phenomenon is closely related to the interface characterization and contact barrier.
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For high voltage direct current (HVDC) cable, a semi-conductive layer lies between the conductor and the insulation layer; as the charge migrates the path from the conductor to the insulation material, it will affect space charge injection. In this work, the research idea of changing the injection path of moving charges within semi-conductive layer by magnetic particles was proposed. Semi-conductive composites with different SrFe12O19 contents of 1 wt.%, 5 wt.%, 10 wt.%, 20 wt.%, and 30 wt.% were prepared, and the amount of injected charges in the insulation sample was characterized by space charge distribution, polarization current, and thermally-stimulated depolarization current. The experimental results show that a small amount of SrFe12O19 can significantly reduce charge injection in the insulation sample, owing to the deflection of the charge migration path, and only part of the electrons can enter the insulation sample. When the content is 5 wt.%, the insulation sample has the smallest charge amount, 0.89 × 10-7 C, decreasing by 37%, and the steady-state current is 6.01 × 10-10 A, decreasing by 22%. When SrFe12O19 content exceeds 10 wt.%, the charge suppression effect is not obvious and even leads to the increase of charge amount in the insulation sample, owing to the secondary injection of charges. Most moving charges will deflect towards the horizontal direction and cannot direct access to the insulation sample, resulting in a large number of charges accumulation in the semi-conductive layer. These charges will seriously enhance the interface electric field near the insulation sample, leading to the secondary injection of charges, which are easier to inject into the insulation sample.
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A novel core-shell-type electrorheological (ER) composite material was fabricated via using polyaniline as an insulating layer to the outer surface of the core conductive metal-organic framework (MIL-125) with controlled size and morphology. MIL-125 was firstly synthesized by a solvothermal method, and then polyaniline was synthesized in a polar solvent and a tight coating was successfully achieved to form a MIL-125@PANI core-shell nanocomposite. This core-shell structure greatly enhances the polarization ability of dispersed particles, thereby improving their rheological properties. The morphology of pure MIL-125 and MIL-125@PANI has been characterized by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Their structure was characterized by X-ray powder diffraction. Moreover, the ER activity of MIL-125-based and MIL-125@PANI-based ER fluids by dispersing the particles into silicone oil was studied using a rotational rheometer. The results show that the MIL-125@PANI composite particles have higher ER properties.
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Radiation treatment remains one of the major modalities in the treatment of lung cancer. Although the majority of patients initially respond to treatment with radiation, resistance inevitably develops and leads to treatment failure. Therefore, the identification of the underlying molecular mechanisms of radiation resistance may facilitate the development of novel approaches for overcoming resistance, and enhance the efficacy of treatment with radiation in lung and other types of cancer. In the present study we established three radiation-resistant sub-cell lines derived from the radiation-sensitive lung cancer cell line HCC827. Using a polymerase chain reaction microRNA (miRNA) array, multiple miRNAs were identified to be markedly downregulated in radiation-resistant cells, including miRNA (miR)-124, miR-191 and miR-205. It was observed that overexpression of miR-124 sensitized the resistant cells to treatment with radiation and that thioredoxin reductase 1 (TXNRD1) is a novel target of miR-124. Furthermore, it was demonstrated that knockdown of TXNRD1 using small interfering RNA increased the basal level of reactive oxygen species and sensitized the cells to radiation treatment. The results of the present study demonstrated that multiple miRNAs are downregulated in radiation-resistant lung cancer cells and that downregulation of miR-124 mediates radiation resistance through the targeting of TXNRD1 mRNA expression. The present study revealed a novel molecular mechanism of miRNA-mediated radiation resistance and identified miR-124-regulated TXNRD1 as a novel therapeutic target for overcoming radiation resistance in the treatment of lung cancer.
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We have previously demonstrated that radiation induced cell death in PKR (-/-) deficient mouse embryo fibroblasts (MEFs) but not in PKR (+/+) wild type MEFs. Our study indicated that PKR can also be involved in survival pathways following radiation therapy through activation of the AKT survival pathways in these MEFs is mediated in part through PKR. The role of PKR on radiation sensitivity in cancer cells has not been evaluated. In this study, we demonstrated that radiation treatment causes nuclear translocation of PKR in human lung cancer cells. The transduction of lung cancer cells with a dominant negative adenoviral PKR vector blocks nuclear translocation of PKR and leads to the reversal of radiation resistance. Plasmid transduction of lung cancer cells with nuclear targeted wild type PKR vectors also increased radiation resistance. This effect is selectively abrogated by plasmid transduction of dominant negative PKR vectors which restore radiation sensitivity. These findings suggest a novel role for PKR in lung cancer cells as a mediator of radiation resistance possibly through translocation of the protein product to the nucleus.