► We investigated functionalized NGO for cancer targeted chemo-photothermal therapy. ► We developed FA–NGO–PVP loading with doxorubicine (DOX). ► FA–NGO–PVP was proved to be an ideal pH-responsive ...nanocarrier. ► We investigated the cell death induced by FA–NGO–PVP/DOX with 808nm laser in vitro. ► FA–NGO–PVP/DOX under laser irradiation shown an excellent anticancer efficacy.
Nanographene oxide (NGO), a new type of nanomaterial for anticancer drugs delivery and near-infrared (NIR)-mediated photothermal ablation of tumors, has been used in the combination of photothermal therapy and chemotherapy. Herein, targeted chemo-photothermal therapy based on polyvinylpyrrolidone (PVP) functionalized NGO was achieved. Folic acid (FA), a common target molecule to cancer cells, was conjugated to NGO via covalent amide bond. The obtained FA–NGO–PVP was proved to be an ideal pH-responsive nanocarrier for delivery of an anticancer drug doxorubicin (DOX) with the loading ratio more than 100%. In vitro experiments were then performed with the combination of chemotherapy and NIR photothermal therapy. The results demonstrated that the targeted chemo-photothermal therapy could specifically deliver drug and heat to tumor sites and showed excellent efficacy of anticancer therapy. Thus, FA–NGO–PVP could be used as a novel nanomaterial for selective chemo-photothermal therapy.
Isogeometric analysis (IGA) coupled with boundary element method, i.e. IGABEM, received a lot of attention in recent years. In this paper, we extend the IGABEM to solve 3D potential problems. This ...method offers a number of key improvements compared with conventional piecewise polynomial formulations. Firstly, the models for analysis in the IGABEM are exact geometrical representation no matter how coarse the discretization of the studied bodies is, thus the IGABEM ensures that no geometrical errors are produced in the analysis process. Secondly, a meshing process is no longer required, which means redundant computations are eliminated to allow analysis to be carried out with greatly reduced pre-processing. To accurately evaluate the singular integrals appearing in our method, the power series expansion method is employed. The integration surface is on the real surface of the model, rather than the interpolation surface, i.e. no geometrical errors. Thus, the value of integral is more accurate than the traditional boundary element method, which can improve the computation accuracy of the IGABEM. Some numerical examples for 3D potential problems are used to validate the solutions of the present method with analytical and numerical solutions available.
Using a data sample collected with the BESIII detector operating at the BEPCII storage ring, we observe a new neutral state Z_{c}(3900)^{0} with a significance of 10.4σ. The mass and width are ...measured to be 3894.8±2.3±3.2 MeV/c^{2} and 29.6±8.2±8.2 MeV, respectively, where the first error is statistical and the second systematic. The Born cross section for e^{+}e^{-}→π^{0}π^{0}J/ψ and the fraction of it attributable to π^{0}Z_{c}(3900)^{0}→π^{0}π^{0}J/ψ in the range E_{c.m.}=4.19-4.42 GeV are also determined. We interpret this state as the neutral partner of the four-quark candidate Z_{c}(3900)^{±}.
A challenge in the management of severely brain-damaged patients with altered states of consciousness is the differential diagnosis between the vegetative state (VS) and the minimally conscious state ...(MCS), especially for the gray zone separating these clinical entities.
To evaluate the differences in brain activation in response to presentation of the patient's own name spoken by a familiar voice (SON-FV) in patients with VS and MCS.
By using fMRI, we prospectively studied residual cerebral activation to SON-FV in seven patients with VS and four with MCS. Behavioral evaluation was performed by means of standardized testing up to 3 months post-fMRI.
Two patients with VS failed to show any significant cerebral activation. Three patients with VS showed SON-FV induced activation within the primary auditory cortex. Finally, two patients with VS and all four patients with MCS not only showed activation in primary auditory cortex but also in hierarchically higher order associative temporal areas. These two patients with VS showing the most widespread activation subsequently showed clinical improvement to MCS observed 3 months after their fMRI scan.
The cerebral responses to patient's own name spoken by a familiar voice as measured by fMRI might be a useful tool to preclinically distinguish minimally conscious state-like cognitive processing in some patients behaviorally classified as vegetative.
•The fatigue strength increased 27% after heat treatment.•The fatigue crack origins primarily involve the printing defects.•The defect area is pretty larger in fracture surface than in bulk ...samples.•The fatigue strength could be predicted using the defect size prior to fatigue test.
Microstructure, defects and their effects on the fatigue properties of Inconel 718 alloy after laser-based power bed fusion and subsequent heat treatment were extensively investigated. A large number of γ′ and γ″ phases were produced in the heat-treated samples while little changes in grain morphology and texture occurred. The hardness, tensile strength, and fatigue limit increased by 46%, 41%, and 27%, respectively, after heat treatment. The fatigue limit could be predicted using defects based on optical microscopy measurement of the bulk samples and examination of SEM fatigue crack origins via a combination of Murakami model and extreme value statistics.
Let-7 is one of the earliest discovered microRNAs(miRNAs) and has been reported to be down-regulated in multiple malignant tumors. The effects and molecular mechanisms of let-7i in bladder cancer are ...still unclear. This study was to investigate the effects and potential mechanisms of let-7i on bladder cancer cells.
Total RNA was extracted from bladder cancer cell lines. The expression levels of let-7i and HMGA1 were examined by quantitative real-time PCR. Cell viability was detected using the CCK-8 and colony formation assays, while transwell and wound healing assays were used to evaluate migration ability. Luciferase reporter assay and western blot were used to confirm the target gene of let-7i.
Compared with the SV-40 immortalized human uroepithelial cell line (SV-HUC-1), bladder cancer cell lines T24 and 5637 had low levels of let-7i expression, but high levels of high mobility group protein A1 (HMGA1) expression. Transfection of cell lines T24 and 5637 with let-7i mimic suppressed cell proliferation and migration. Luciferase reporter assay confirmed HMGA1 may be one of the target genes of let-7i-5p. Protein and mRNA expression of HMGA1 was significantly downregulated in let-7i mimic transfected cell lines T24 and 5637.
Up-regulation of let-7i suppressed proliferation and migration of the human bladder cancer cell lines T24 and 5637 by targeting HMGA1. These findings suggest that let-7i might be considered as a novel therapeutic target for bladder cancer.
CD63 is a member of the four-transmembrane-domain protein superfamily and is the first characterized tetraspanin protein. In the present study, we cloned the common carp (Cyprinus Carpio) CD63 ...(ccCD63) sequence and found that the ccCD63 ORF contained 711 bp and encoded a protein of 236 amino acids. Homology analysis revealed that the complete ccCD63 sequence had 84.08% amino acid similarity to CD63 of Sinocyclocheilus anshuiensis. Subcellular localization analysis revealed that ccCD63 was localized in the cytoplasm. Quantitative real-time PCR (qRT-PCR) analysis indicated that ccCD63 was expressed in the gill, intestine, liver, spleen, brain and kidney, with higher expression in spleen and brain tissues than in the other examined tissues. After koi herpesvirus (KHV) infection, these tissues exhibited various expression levels of ccCD63. The expression level was the lowest in the liver and highest in the brain; the expression level in the brain was 8.7-fold higher than that in the liver. Furthermore, knockdown of ccCD63 promoted KHV infection. Moreover, ccCD63 was correlated with the regulation of RIG-I/MAVS/TRAF3/TBK1/IRF3 and may be involved in the antiviral response through the RIG-I viral recognition signalling pathway in a TRAF3/TBK1-dependent manner. Taken together, our results suggested that ccCD63 upregulated the interaction of KHV with the host immune system and suppressed the dissemination of KHV.
•We cloned the common carp CD63 sequence (ccCD63), and the ORF has a length of 711 bp and encodes 236 amino acids. Subcellular localization analysis revealed that ccCD63 is localized in the cytoplasm.•CcCD63 plays a crucial role in innate immune responses and can specifically stimulate the RIG-1 signaling pathway to regulate IFN production and suppress the early stage of KHV replication.•Knockdown of ccCD63 could increase ORF136 levels and promote KHV infection.•CcCD63 was correlated with the regulation of RIG-I/MAVS/TRAF3/TBK1/IRF3 and may be involved in the antiviral response through the RIG-I viral recognition signaling pathway in a TRAF3/TBK1-dependent manner.•We speculate that ccCD63 has a dual function in virus infection and host immune interactions.
•Correctness of vibration and buckling behaviors of composite laminates with laminated stiffeners has been verified.•Flexible refinements based on the PHT isogeometric analysis help improve the ...computational accuracy and efficiency.•The vibration and buckling behaviors of stiffened composite laminates were optimized by changing the stiffener geometry.
Isogeometric analysis (IGA) with the polynomial splines over hierarchical T-meshes (PHT-splines) is used to provide an efficient tool capable of carrying out the vibration and buckling analyses of the stiffened laminates. IGA offers increased accuracy and efficiency using the PHT-splines, which represent exact geometry of the stiffeners and make the refinement more flexible near the areas where the stiffeners and composite plate are connected. Numerical examples are given to validate the correctness and superiority of the present method, comparing with the results from existing literatures and commercial softwares. Besides, the influences of the orientation, curvature, location and cross-section size of the stiffeners on the natural frequencies and buckling loads are also studied. The results show that the optimization of the shape and size of the stiffeners has an important effect on the vibration and buckling characteristics of stiffened laminates.
Titanium alloy Ti-6Al-4V processed by electron beam melting (EBM) has a great potential for orthopedic and aerospace applications. However, the process induced porosity and microstructure anisotropy ...will have a significant impact on the material properties. This work has found that spherical and elongated pores with strong size effect are common characteristics for the as-EBM samples made with horizontal, diagonal, and vertical orientations w.r.t. the substrate. Furthermore, the major axis of the elongated pores is perpendicular to build direction for samples with different build orientations. The microstructure consists of columnar prior β grains delineated by grain boundary α and transformed α/β structures with α’ marteniste and basket weave morphology. Of note is that a high fraction of twin boundaries are prevalent in α (α’) phase. The configuration of the applied load w.r.t. the major axis of the elongated pores is the most significant influencing factor to mechanical properties, while the columnar prior β grain structure is secondary. Fractography reveals that microcracks tend to originate from elongated pores for cleavage fracture. In addition, the co-existing local terrace-like and shallow dimples are attributed to the intergranular crack propagation from the lamella α grain boundaries. Thus, the anisotropy of porosity and microstructure is of significance to enhance mechanical properties in process development.
Discontinuities of the shear force, bending moment, slope, and deflection can be caused by span supports, valves, and cracks etc. For arbitrary discontinuities appearing in the oil-conveying pipe ...resting on Pasternak foundation, the general analytical solution for vibrations of this structure is presented in this paper. To deal with discontinuity terms, generalized functions are employed to express the model displacement of the entire pipe as a single function. This function is then solved by Laplace transform. Continuity conditions at discontinuity points are also given. In addition, the generalized boundary condition (BC), which can be degenerated to many classical BCs, is considered. Numerical section testifies the feasibility and the validity of present solutions, and discusses the effects of some physical parameters on natural frequencies. It is shown that the closer the cracks are to the nearest nodes of mode shapes, the less effects they have on the corresponding natural frequencies; locations of support springs change effects of cracks on natural frequencies by affecting positions of structural nodes; foundation parameters have different effects on natural frequencies. The present method can be applied in maintaining safety and integrity of structures of pipes.
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