Combination treatment with highly bioavailable curcumin and NQO1 inhibitor exhibits potent antitumor effects on esophageal squamous cell carcinoma

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most intractable cancers, so the development of novel therapeutics has been required to improve patient outcomes. Curcumin, a polyphenol from Curcuma longa, exhibits various health benefits including antitumor effects, but its clinical utility is limited because of low bioavailability. Theracurmin® (THC) is a highly bioavailable curcumin dispersed with colloidal submicron particles. Methods: We examined antitumor effects of THC on ESCC cells by cell viability assay, colony and spheroid formation assay, and xenograft models. To reveal its mechanisms, we investigated the levels of reactive oxygen species (ROS) and performed microarray gene expression analysis. According to those analyses, we focused on NQO1, which involved in the removal of ROS, and examined the effects of NQO1-knockdown or overexpression on THC treatment. Moreover, the therapeutic effect of THC and NQO1 inhibitor on ESCC patient-derived xenografts (PDX) was investigated. Results: THC caused cytotoxicity in ESCC cells, and suppressed the growth of xenografted tumors more efficiently than curcumin. THC increased ROS levels and activated the NRF2–NMRAL2P–NQO1 expressions. Inhibition of NQO1 in ESCC cells by shRNA or NQO1 inhibitor resulted in an increased sensitivity of cells to THC, whereas overexpression of NQO1 antagonized it. Notably, NQO1 inhibitor significantly enhanced the antitumor effects of THC in ESCC PDX tumors. Conclusions: These findings suggest the potential usefulness of THC and its combination with NQO1 inhibitor as a therapeutic option for ESCC

Spectral evolution of GRB 060904A observed with Swift and Suzaku -- Possibility of Inefficient Electron Acceleration

We observed an X-ray afterglow of GRB 060904A with the Swift and Suzaku satellites. We found rapid spectral softening during both the prompt tail phase and the decline phase of an X-ray flare in the BAT and XRT data. The observed spectra were fit by power-law photon indices which rapidly changed from $\Gamma = 1.51^{+0.04}_{-0.03}$ to $\Gamma = 5.30^{+0.69}_{-0.59}$ within a few hundred seconds in the prompt tail. This is one of the steepest X-ray spectra ever observed, making it quite difficult to explain by simple electron acceleration and synchrotron radiation. Then, we applied an alternative spectral fitting using a broken power-law with exponential cutoff (BPEC) model. It is valid to consider the situation that the cutoff energy is equivalent to the synchrotron frequency of the maximum energy electrons in their energy distribution. Since the spectral cutoff appears in the soft X-ray band, we conclude the electron acceleration has been inefficient in the internal shocks of GRB 060904A. These cutoff spectra suddenly disappeared at the transition time from the prompt tail phase to the shallow decay one. After that, typical afterglow spectra with the photon indices of 2.0 are continuously and preciously monitored by both XRT and Suzaku/XIS up to 1 day since the burst trigger time. We could successfully trace the temporal history of two characteristic break energies (peak energy and cutoff energy) and they show the time dependence of $\propto t^{-3} \sim t^{-4}$ while the following afterglow spectra are quite stable. This fact indicates that the emitting material of prompt tail is due to completely different dynamics from the shallow decay component. Therefore we conclude the emission sites of two distinct phenomena obviously differ from each other.Comment: 19 pages, 9 figures, accepted for publication in PASJ (Suzaku 2nd Special Issue

Electrical switching of vortex core in a magnetic disk

A magnetic vortex is a curling magnetic structure realized in a ferromagnetic disk, which is a promising candidate of a memory cell for future nonvolatile data storage devices. Thus, understanding of the stability and dynamical behaviour of the magnetic vortex is a major requirement for developing magnetic data storage technology. Since the experimental proof of the existence of a nanometre-scale core with out-of-plane magnetisation in the magnetic vortex, the dynamics of a vortex has been investigated intensively. However, the way to electrically control the core magnetisation, which is a key for constructing a vortex core memory, has been lacking. Here, we demonstrate the electrical switching of the core magnetisation by utilizing the current-driven resonant dynamics of the vortex; the core switching is triggered by a strong dynamic field which is produced locally by a rotational core motion at a high speed of several hundred m/s. Efficient switching of the vortex core without magnetic field application is achieved thanks to resonance. This opens up the potentiality of a simple magnetic disk as a building block for spintronic devices like a memory cell where the bit data is stored as the direction of the nanometre-scale core magnetisation.Comment: 20 pages, 4 figures. Supplementary discussion included. Accepted for publication in Nature Material

Central object segmentation by deep learning for fruits and other roundish objects

We present CROP (Central Roundish Object Painter), which identifies and paints the object at the center of an RGB image. Primarily CROP works for roundish fruits in various illumination conditions, but surprisingly, it could also deal with images of other organic or inorganic materials, or ones by optical and electron microscopes, although CROP was trained solely by 172 images of fruits. The method involves image segmentation by deep learning, and the architecture of the neural network is a deeper version of the original U-Net. This technique could provide us with a means of automatically collecting statistical data of fruit growth in farms. As an example, we describe our experiment of processing 510 time series photos automatically to collect the data on the size and the position of the target fruit. Our trained neural network CROP and the above automatic programs are available on GitHub with user-friendly interface programs.Comment: The version 2 contains a new section about the automatic processing of time series photos. All the programs are available at https://github.com/MotohisaFukuda/CRO

Dependence of oxygen reduction reaction on temperature in (

Introduction Molten carbonate fuel cells (MCFCs) are in the beginning of commercialization due to their high energyconversion efficiency with a co-generation system. They have small activation loss due to their high operation temperature. In order to operate a MCFC at high pressure for the improvement of the energy conversion efficiency, there are some technological problems, mainly related to the durability of the materials. One of the most serious problems is the dissolution of NiO cathode. It causes Ni deposition and creates a short circuit. In order to prevent the Ni short circuit, La addition to the molten carbonate should be effective since it reduces the NiO solubility a lot. Furthermore, the oxygen solubility and the exchange current density of the oxygen reduction reaction (ORR) in the carbonate increase with La additive 2, 3 . However, temperature dependence of ORR has not been determined, and ORR has not been clarified enoug

An IL-27/Stat3 axis induces expression of programmed cell death 1 ligands (PD-L1/2) on infiltrating macrophages in lymphoma

Immune escape and tolerance in the tumor microenvironment are closely involved in tumor progression, and are caused by T-cell exhaustion and mediated by the inhibitory signaling of immune checkpoint molecules including programmed death-1 (PD-1), cytotoxic T-lymphocyte associated protein 4, and T-cell immunoglobulin and mucin domaincontaining molecule-3. In the present study, we investigated the expression of the PD-1 ligand 1 (PD-L1) in a lymphoma microenvironment using paraffin-embedded tissue samples, and subsequently studied the detailed mechanism of upregulation of PD-L1 on macrophages using cultured human macrophages and lymphoma cell lines. We found that macrophages in lymphoma tissues of almost all cases of adult T-cell leukemia/lymphoma (ATLL), follicular lymphoma and diffuse large B-cell lymphoma expressed PD-L1. Cell culture studies showed that the conditioned medium of ATL-T and SLVL cell lines induced increased expression of PD-L1/2 on macrophages, and that this PD-L1/2 overexpression was dependent on activation of signal transducer and activator of transcription 3 (Stat3). In vitro studies including cytokine array analysis showed that IL-27 (heterodimer of p28 and EBI3) induced overexpression of PD-L1/2 on macrophages via Stat3 activation. Because lymphoma cell lines produced IL-27B (EBI3) but not IL-27p28, it was proposed that the IL-27p28 derived from macrophages and the IL-27B (EBI3) derived from lymphoma cells formed an IL-27 (heterodimer) that induced PD-L1/2 overexpression. Although the significance of PD-L1/2 expressions on macrophages in lymphoma progression has never been clarified, an IL-27-Stat3 axis might be a target for immunotherapy for lymphoma patients