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Background: For people with advanced hepatocellular carcinoma (HCC), systemic chemotherapy remains the only choice of palliative treatment. However, chemotherapy efficacy is not effective due to its short blood circulation times, nonspecific cell and tissue biodistribution, and rapid metabolism or excretion from the body. Therefore, a targeted nanomedicine delivery system is urgently needed. Methods: In order to improve the treatment efficiency of HCC, based on in situ growth of a copper metal organic framework on mesoporous organic silica nanoparticles, dual pH- and glutathione (GSH)-responsive multifunctional nanocomposites were synthesized as nanocarriers for enhanced HCC therapy. In this research, cellular uptake studies were performed using CLSM and Bio-TEM observations. Flow cytometry, AO-EB fluorescent staining, EdU test and Western blot were utilized to explore the apoptosis and proliferation process. In vivo imaging was employed to research the distribution of the nanocomposites in HCC tumor-bearing nude mice and the xenograft model of HCC tumor-bearing nude mice was applied to investigate the anti-tumor effects of drug-loaded nanocomposites in vivo. Results: This newly constructed degradable nanocomposite DOX/SOR@SP94 and mPEG-anchored MONs@MOF199 (D/S@SPMM) has the benefits of controllable pore size, high encapsulation efficiency, and precise targeting. According to the results of in vivo imaging and anti-tumor studies, as well as pharmacokinetic research, D/S@SPMM possessed precise HCC tumor targeting and long-lasting accumulation properties at the tumor region. Compared with traditional chemotherapy and non-targeted drug delivery systems, anti-tumor efficiency was increased by approximately 10- and 5-fold, respectively. The nanocomposites exhibited excellent anti-tumor properties without inducing observable systemic toxicity, owing to efficient DOX and SOR loading and release as well as the HCC specific targeting peptide SP94. Conclusions: The in vitro and in vivo anti-tumor results indicated that these nanocomposites could be an efficient nanomedicine for targeting HCC therapy. [ABSTRACT FROM AUTHOR]

Background: Abnormal expression of long non-coding RNAs (lncRNAs) has been associated with the initiation and progression of hepatocellular carcinoma but, as yet, the clinicopathologic significance and potential role of Linc02154 in HCC remains to be determined. Here, we aimed to investigate the potential role and mode of action of Linc02154 in HCC. Methods: The expression of Linc02154 in 20 pairs of HCC/normal tissues and 7 HCC cell lines was detected by qRT-PCR. The localization of Linc02154 in HCC cells was detected using fluorescence in situ hybridization and nuclear-plasma separation assays. MTS, EdU incorporation, colony formation, flow cytometry, scratch wound-healing and transwell assays were performed to assess the role of Linc02154 in HCC cell proliferation, migration and invasion in vitro, and BALB/c nude mice xenografts were used to evaluate its role in vivo. RNA sequencing and Western blotting were used to evaluate the regulatory effect of Linc02154 on SPC24 gene expression. A dual-luciferase reporter assay was used to assess a putative interaction of Linc02154 with the SPC24 promoter. Results: We identified a new lncRNA, Linc02154, that is highly expressed in HCC cells and tissues of patients with a poor overall survival. Functional experiments revealed that exogenous Linc02154 expression in MHCC-97H and SK-Hep1 cells promoted their proliferation, migration and invasion in vitro and their tumorigenesis in vivo. Using a dual luciferase reporter assay we found that Linc02154 can enhance SPC24 promoter (-500 bp ~ -1000 region) activity. Exogenous over-expression of Linc02154 led to up-regulation of SPC24 by activating PI3K/AKT and its downstream signals, including cell cycle progression and EMT-associated gene expression. Conclusion: Our data suggest that Linc02154 may serve as a valuable biomarker of HCC and as a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Background: Inherent limitations of single cancer therapy are overcome by multi-therapy modality, which integrates characteristics of each therapeutic modality and material chemistry. The multi-modal method has the potential for becoming one of the next generation options for cancer treatments. Photothermal therapy (PTT) is an efficient, non-invasive treatment method that can be used on various cancer types. We propose an acid-triggered self-destructing nano-biocatalyst integrated starvation/chemical/photothermal triple therapy that is based on design principles and biomedical applications of GOx cancer treatment methods. Methods: Scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potentials were used to analyze the physical as well as chemical properties of MoS2@DOX/GOx@MnO2 (M@D/G@M). Further, Fourier transform infra-red (FTIR), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD) were used to assess the compositions of the nanocatalysts. The biological effects of M@D/G@M on cells were studied in vitro by inverted fluorescence microscopy, confocal laser scanning microscopy (CLSM), flow cytometry, CCK-8 test, and hemolysis test. Treatment effects of the nanocatalysts were evaluated in MHCC-97H tumor BALB/c mice, whose body weights, tumor local temperature, tumor volumes, and tumor histological changes were evaluated. Results: There was a high DOX encapsulation efficiency of M@D/G@M (90.233%). The photothermal conversion efficiency (η) of M@D/G@M is 25.2%, and its oxygen production within 5 min reached 27.5 mg L−1. Cell internalization analysis showed that within 4 h, M@D/G@M was almost completely absorbed by HepG2 cells. Further, the highest red fluorescence and apoptosis effects of dead cells (59.07% apoptosis) as well as the lowest tumor volume index of mice (0.2862%) were observed in the M@D/G@M + pH6.0 + NIR treatment group. Conclusions: Our findings inform the development and applications of multi-modal methods in tumor therapy. [ABSTRACT FROM AUTHOR]

One of the challenges in the study of generative adversarial networks (GANs) is the difficulty of its performance control. Lipschitz constraint is essential in guaranteeing training stability for GANs. Although heuristic methods such as weight clipping, gradient penalty and spectral normalization have been proposed to enforce Lipschitz constraint, it is still difficult to achieve a solution that is both practically effective and theoretically provably satisfying a Lipschitz constraint. In this paper, we introduce the boundedness and continuity (BC) conditions to enforce the Lipschitz constraint on the discriminator functions of GANs. We prove theoretically that GANs with discriminators meeting the BC conditions satisfy the Lipschitz constraint. We present a practically very effective implementation of a GAN based on a convolutional neural network (CNN) by forcing the CNN to satisfy the BC conditions (BC–GAN). We show that as compared to recent techniques including gradient penalty and spectral normalization, BC–GANs have not only better performances but also lower computational complexity. [ABSTRACT FROM AUTHOR]

In this study, ZnO-based varistors with a high breakdown field were obtained through BaCO doping and sintering at a low temperature of 950 °C. The grain size of the ZnO samples decreased to 1.28 μm, and the breakdown field was enhanced to 3845 V/mm, which is approximately one order of magnitude higher than that of ordinary ZnO-based varistors. The dielectric responses of the ZnO-based varistors were measured in a wide frequency and temperature range. At 193 K, two dielectric relaxation peaks with activation energies of 0.22 and 0.35 eV were observed and considered intrinsic defects; these peaks did not vary with the preparation process. Another dielectric relaxation peak observed in a wide temperature range (283-463 K) was characterized in an impedance plot. This relaxation peak was ascribed to extrinsic defects related to the grain boundary. The resistance values of the grain boundary increased by two orders of magnitude through BaCO doping and lowering of the sintering temperature. The corresponding activation energy also increased from 0.53 to 0.74 eV. A parallel resistance-capacitance circuit model was proposed to interpret the variation in the electrical properties of ZnO-based varistors. [ABSTRACT FROM AUTHOR]