High quality n-ZnO/p-SiC heterojunction diodes have been fabricated and their photoresponse properties have been investigated. X-ray diffraction (XRD) ¿-2¿ patterns show that highly c-axis oriented ...ZnO films were epitaxially grown on 4H-SiC. The RMS roughness is observed as low as 2 nm by atomic force microscope (AFM). Current-voltage (I-V) characteristics of the fabricated heterojunction diodes have a good rectifying characteristics, and a leakage current less than 10 -9 A at -10 V, with a forward current of ~10 -5 A at +10 V. The responsivity is measured for different UV wavelengths. As the intensity of UV wavelength is decreased from 365 nm to 254 nm, the photocurrent increased 1.7×10 -5 A to 3×10 -5 A.
중앙아시아의 역사에서 15세기 이후 나타나는 우즈베크와 카자흐에 대한 이해는 오늘날의 중앙아시아를 이해하는데 바탕이 된다. 국내의 중앙아시아에 대한 인식의 대부분은 역사적인 측면이나 그 변천과정에서 서로 유사한 속성을 지닌 집단으로 인식하고 있고, 중앙아시아의 대표적인 두 집단인 우즈베크와 카자흐가 보여주는 이질성의 요소들에 대한 이해는 이루어지지 않고 ...있다. 티무르 제국시기에 오늘날의 중앙아시아로 유입된 우즈베크는 분열기의 티무르제국과 경쟁을 통해 중앙아시아 중심세력으로 자리 잡을 수 있었다. 그러나 우즈베크 역시 중앙아시아 유입이후 내부적인 분열의 시기를 거치면서 15세기부터 카자흐가 분리되어 유목민의 독자적인 영역을 구축하게 되면서 투르크계이면서 중앙아시아를 대표하는 중심 집단으로 우즈베크 공동체와 카자흐 공동체가 상이한 발전과정을 거쳤다.
오늘날의 우즈베키스탄에 해당되는 당시 중앙아시아에서는 15세기까지 역내 공 동체들간으로 교섭활동이 제한되다가 16세기 제정러시아의 중앙아시아 진출이 시도되면서 제정러시아-중앙아시아간 교섭으로 확대되었다. 우즈베크와 제정러시아간의 교섭은 카라반으로 대표되는 통상활동의 파트너 차원에서 주로 이루어졌으며, 15세기 우즈베크 공동체로부터 이탈하여 유목민으로서의 특성을 그대로 지켜온 카자흐와의 대외교섭을 제정러시아는 당시의 중앙아시아로 진출하기 위한 교두보 차원에서 시도하여 지속성이 없었다. 제정러시아의 우즈베크에 대한 교섭은 통상 파트너로 교역 활성화 측면, 그리고 러시아의 팽창에 대한 우즈베크 칸국들의 견제와 이로 인한 갈등이 외교의 주요 안건이었던 반면, 카자흐는 우즈베크의 교역도시들로 가는 러시아 카라반들의 안전을 보장하기 위한 보장수단의 차원에서 대외교섭이 이루어졌다. 또한 카자흐의 쥬즈들이 러시아의 보호를 요청하는 과정에서 지배층 중심으로 러시아에 대한 접근과 외교활동이 이루어졌다는 점에서 상이성을 드러내고 있다. KCI Citation Count: 6
Despite intensive attempts to fabricate polypyrrole nanoparticles (PPy–NPs) incorporated nanofibrous scaffolds, a low-cost facile strategy is still demanded. Herein, we developed a novel strategy- ...in-situ polymerization of PPy-NPs and immobilized them into the PCL polymeric matrix in a single step. For the in-situ polymerization of PPy–NPs, ferric chloride hexahydrate (FeCl3.6H2O) was introduced as an oxidant into the blended solution of PCL and pyrrole monomers. Due to the chemical oxidative polymerization process, the clear solution changed into a black PCL/PPy solution. After electrospinning the solution, PCL/PPy composite nanofibers were fabricated. The immobilization of PPy-NPs into PCL matrix was clearly revealed by Bio-TEM images. The Field emission scanning electron microscopy (FESEM) results exhibited that the PCL/PPy scaffolds showed significantly decreased fiber diameter. The atomic force microscopy (AFM) study showed increased surface roughness in the PCL/PPy scaffolds. The mechanical strength test of PCL/PPy scaffolds showed improved Young's Modulus (YM = 2 to 4-folds) and tensile strength (TS = 3 to 4-folds). As well as the YM and TS were gradually increased with increased concentration of PPy–NPs in composite scaffolds. The conductivity measurement conducted on polymeric solution and electrospun scaffolds showed an increasing trend of conductive property in the PCL/PPy solution and scaffolds too. The surface wettability test exhibited decreased water contact angle measurement from 126° for pure PCL to 93° for the PCL/PPy-200 composite scaffold. The biomineralization test conducted by simulated body fluid (SBF) incubation showed enhanced calcium–phosphate crystal deposition on the PCL/PPy scaffolds. The CCK-8 assay and confocal laser scanning microscopic (CLSM) imaging conducted without and with electrical stimulation (ES) displayed enhanced cell adhesion, growth, and proliferation of MC3T3-E1 cells on the PCL/PPy conductive scaffolds. Furthermore, ALP and ARS staining assays showed significant enhancement of the calcium–phosphate deposition on the PCL/PPy scaffolds after ES treatment. Hence, the current study provides a novel strategy for the fabrication of PCL/PPy conductive scaffolds with enhanced bioactivity, biocompatibility, and osteogenic differentiation under electrical stimulation confirmed its promising application towards bone tissue engineering.
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•The aim was to induce the conductive property in PCL nanofibrous scaffold.•Immobilization of in-situ polymerized PPy-NPs induced the conductive property in PCL/PPy electrospun scaffold.•PCL/PPy conductive scaffolds showed increased SBF-biomineralization.•PCL/PPy exhibited enhanced MC3T3-E1 cell adhesion, proliferation, and differentiation in electrical stimulation conditions.•Results showed the PCL/PPy is a suitable conductive scaffold for bone tissue engineering application.
•Bio-actuated Ti(HPO4)2/Zn3(PO4)2(0.1).nH2O bioceramic was synthesized.•Bone-mimicking structure of phosphate-rich bioceramic improved bone cells proliferation.•Controlled released of Zn++ stimulates ...cells for up-regulation of osteogenic genes expression.•Osteoinduction of the bioceramic increased bone mineralization and new bone formation.
In this work, we describe the synthesis of an ideal bioceramic to which cells can easily respond that has geometry and composition that are similar to those of bone-like apatite. The successful preparation of bone-inspired titanium hydrate phosphate with an optimized weight percentage (∼1.1 wt%) of zinc in (Ti(HPO4)2/Zn3(PO4)2·nH2O) bioceramic could represent a potential regenerative framework for bone defect repair and bone void filler that would be useful for various clinical approaches. We have for the first time demonstrated the detailed physicochemical and biological characterizations of the bioceramic required to achieve a biocompatible and porous architecture that is similar to hydroxyapatite. In vitro studies have shown that the phosphate-rich titanium and zinc nanocomposite promote bone regeneration after stimulating MC3T3 − E1 and hBM-MSCs cells activity. The metallic ions and phosphate had the effects of enhancing the cell viability and osteogenic differentiation of the cells, as confirmed by the expression of bone-related markers that included ALP, Col1a1, RUNX2, OPN/Spp1, and OCN through qRT-PCR, Western blotting, and immunocytochemistry. Moreover, the bioceramic has been shown to significantly improves new bone growth in critical size calvarial defect in rat model. The findings of the present work are the first that show the bone regeneration effect of bioceramic, which could be crucial for subsidies of Ca–P-based artificial bone implant materials. Our results provide insight into the Ti(HPO4)2/Zn3(PO4)2(0.1)·nH2O bioceramic in osteogenesis which can help to establish a therapeutic strategy in bone tissue regenerative medicine.
Abstract
An implantable anticancer device (IAD) that can eradicate local regional breast cancer recurrence (LRR), inhibit metastasis as well as to enhance the breast reconstruction during/after ...therapy is proposed. The IAD is developed by combining nanofiber-based chemo-photothermal therapy platform with check point blockade immunotherapy. Here we developed a coreshell electrospun nanofiber encapsulated with drug conjugated MoS2 as chemo-photothermal agent along with imiquimod as an immune response modifier. The near-infrared laser exposure to IADs can generate tumor-associated antigens from primary tumors, which in the presence of released imiquimod from IADs can show vaccine-like functions. Moreover, the nanofiber matrix will enable the sustained and tumor-specific anticancer drug release with a minimum initial burst release and the repeated photothermal capability to ensure the synergistic inhibition of tumor recurrence. In addition to that, the checkpoint-blockade using anti-cytotoxic T-lymphocyte antigen-4 (CTLA4) in combination with the generated immunologic responses will be able to attack remaining tumor cells causing metastasis inhibition with strong immunologic memory effect, which can shield against the tumor recurrence after the post elimination of initial tumors. The IAD nanofiber morphology resembles the extra cellular matrix (ECM) enrich the reconstruction of poor breast cosmesis resulted from the surgical treatment, by supporting the lipofilling of the surgical residual cavity to induce the adipogenic process. So, in this work we propose that the tumor associated antigens created in situ after photothermal therapy by the immune adjuvant nanofiber IAD could show vaccine-like functions, which in combination with checkpoint blockade show strong antitumor immune responses for effective cancer immunotherapy as a potential platform for synergistic inhibition of LRR and a great promise for the in situ breast reconstruction ability for better breast cosmesis.
Citation Format: Afeesh Rajan Unnithan, Arathyram Ramachandra Kururp Sasikala, Chan Hee Park, Cheol Sang Kim. Electrospun implantable anticancer device comprising immune adjuvant photo-responsive nanoparticles with checkpoint blockade for effective cancer therapy abstract. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B040.
Abstract
The advancement in nanotechnology has created a wealth of new possibilities for treating cancer with multifunctional nanosystem holding various therapeutic strategies in a single platform. ...It has been reported that magnetic nanoparticle hyperthermia can induce antitumor immunity whereas the immunotherapy can naturally trigger the immune system with the help of an appropriate stimulator to control cancer. Therefore the present study investigates the effectiveness of a hybrid nanocomposite system to effectively exterminating the tumor associated immune cells (TICs) as well as inducing an inflammatory immune response by activating killer T-cells by combining magnetic hyperthermia with an immunostimulatory agent. Here we report an injectable magnetic nanogels conjugating a checkpoint inhibitor (T-lymphocyte antigen-4 CTLA4) and a Toll-like receptor (TLR) agonists (imiquimod) for generating an effective antitumoral immune response for postsurgical glioma treatment. The injectable conductive magnetic hydrogel system enables the tracing and deterring of the recurrent tumor cells via magnetic nanoparticle-mediated hyperthermia with the strong immunologic memory effect. The superparamagnetic iron oxide nanoparticles encapsulated nanogels exhibit an induced heating ability in an alternating magnetic field (AMF) and thereby trigger the tumor cells to undergo a burst release of heat shock proteins to recruit immune cells to generate tumor-allied antigens. These antigens along with the released imiquimod from the hydrogel can generate vaccine-like functionalities. Moreover, the introduction of anti-cytotoxic T-lymphocyte antigen-4 (CTLA4) as a checkpoint-blockade will generate memory T-cells, which in turn will attack the metastatic and recurrent tumor cells. Above all, the conductive bioactive scaffold will support the neuronal regeneration and reactivation of brain cells. Thus our multifunctional novel hydrogel system will be able to fill the surgical residual cavity to prevent the glioma recurrence and will improve the local neuronal tissue reconstruction along with hyperthermic-immunotherapy.
Citation Format: Arathyram Ramachandra Kururp Sasikala, Afeesh Rajan Unnithan, Chan Hee Park, Cheol Sang Kim. An injectable magnetic nanogel system for filling surgical residual cavity with effective cancer immunotherapy combined hyperthermic capability abstract. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B041.
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Here, we report multi-component plasmonic core–shell nanodendrites (Pt@rGO-AuNPs) composed of nano-sized reduced graphene oxide coated gold nanoparticles as a multiple photo-system ...modality. The prepared Pt@rGO-AuNPs took 40, 60, and 75min with the pseudo first-order rate constants 0.112min−1 0.069min−1 and 0.048min−1 to completely degrade (≥98%) methylene blue, methyl red, and methyl orange, respectively, at room temperature. Pt@rGO-AuNPs also showed a high photothermal effect (temperature ≥43°C in 5min, 808nm laser, 6W/cm2) and found to have robust morphology during recyclability for at least five cycles in both photocatalytic and photothermal processes.
•Ag and ZnO particles were hydrothermally deposited on nylon-6 fibers.•One-step deposition of metal and metal oxide particles on fiber surface was carried out.•The composite has good antibacterial ...and photocatalytic efficiency.•It can be applied for potential water filter media.
Silver-doped zinc oxide rods were incorporated in a nylon-6 electrospun mat by a facile hydrothermal process. The rods exhibited excellent characteristics as a durable filter media with good antibacterial properties. ZnO nano-seeds blended with a nylon-6 solution were typically able to form ZnO-NPs-embedded spider-web-like nanonets during electrospinning. The simultaneous crystal growth of Ag NPs and ZnO rods from their precursor solutions on the surface of as-fabricated electrospun ZnO/nylon-6 fibers was carried out via a hydrothermal process. FE-SEM, TEM, UV–visible spectra, and photoluminescence spectra not only confirmed the formation of ZnO-nano-seeds-loaded electrospun nylon-6 composite fibers but also showed that ZnO rods doped with Ag NPs (approximately 50nm in size) were grown on the surface of the nylon-6 composite fibers during hydrothermal treatment. The antibacterial properties of different mats were tested against Escherichia coli. The as-synthesized Ag-NP-loaded nanocomposite revealed better antibacterial properties than those of composite mat without Ag NPs. The excellent stability of Ag-loaded ZnO rods (caused by ZnO nano-seeds) on the surface of electrospun fibers provides a new dimension in the fabrication of inorganic/organic nanocomposite.
Fabricating bioartificial bone graft ceramics retaining structural, mechanical, and bone induction properties akin to those of native stem-cell niches is a major challenge in the field of bone tissue ...engineering and regenerative medicine. Moreover, the developed materials are susceptible to microbial invasion leading to biomaterial-centered infections which might limit their clinical translation. Here, we successfully developed biomimetic porous scaffolds of polyurethane-reinforcedL-cysteine-anchored polyaniline capped strontium oxide nanoparticles to improve the scaffold's biocompatibility, osteo-regeneration, mechanical, and antibacterial properties. The engineered nanocomposite substrate PU/L-Cyst-SrO
@PANI (0.4 wt%) significantly promotes bone repair and regeneration by modulating osteolysis and osteogenesis. ALP activity, collagen-I, ARS staining, as well as biomineralization of MC3T3-E1 cells, were used to assess the biocompatibility and cytocompatibility of the developed scaffolds in vitro, confirming that the scaffold provided a favorable microenvironment with a prominent effect on cell growth, proliferation, and differentiation. Furthermore, osteogenic protein markers were studied using qRT-PCR with expression levels of runt-related transcription factor 2 (RUNX2), secreted phosphoprotein 1 (Spp-I), and collagen type I (Col-I). The overall results suggest that PU/L-Cyst-SrO
@PANI (0.4 wt%) scaffolds showed superior interfacial biocompatibility, antibacterial properties, load-bearing ability, and osteoinductivity as compared to pristine PU. Thus, prepared bioactive nanocomposite scaffolds perform as a promising biomaterial substrate for bone tissue regeneration.
The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for pancreatic neuroendocrine tumor (PNET) included several significant changes. We aim to evaluate this staging system ...compared to the 7th edition AJCC staging system and European Neuroendocrine Tumors Society (ENETS) system.
We used Korean nationwide surgery database (2000-2014). Of 972 patients who had undergone surgery for PNET, excluding patients diagnosed with ENETS/World Health Organization 2010 grade 3 (G3), only 472 patients with accurate stage were included.
Poor discrimination in overall survival rate (OSR) was noted between AJCC 8th stage III and IV (p=0.180). The disease-free survival (DFS) curves of 8th AJCC classification were well separated between all stages. Compared with stage I, the hazard ratio of II, III, and IV was 3.808, 13.928, and 30.618, respectively (p=0.007, p < 0.001, and p < 0.001). The curves of OSR and DFS of certain prognostic group in AJCC 7th and ENETS overlapped. In ENETS staging system, no significant difference in DFS between stage IIB versus IIIA (p=0.909) and IIIA versus IIIB (p=0.291). In multivariable analysis, lymphovascular invasion (p=0.002), perineural invasion (p=0.003), and grade (p < 0.001) were identified as independent prognostic factors for DFS.
This is the first large-scale validation of the AJCC 8th edition staging system for PNET. The revised 8th system provides better discrimination compared to that of the 7th edition and ENETS TNM system. This supports the clinical use of the system.
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