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Apr 2019 • Frontiers in pharmacology

Zinc-doped copper oxide nanocomposites inhibit the growth of pancreatic cancer by inducing autophagy through AMPK/mTOR pathway

Xiao Li, Huanli Xu, Cong Li, Gan Qiao, Ammad Ahmad Farooqi, Aharon Gedanken, Xiaohui Liu, Xiukun Lin

Zinc doped copper oxide nanocomposites (Zn-CuO NPs) is a novel doped metal nanomaterial synthesized by our group using the sonochemical method. Our previous studies have shown that Zn-CuO NPs could inhibit cancer cell proliferation by inducing apoptosis via ROS-mediated pathway. In the present study, we studied the anticancer effect of Zn-CuO NPs on human pancreatic cancer cells. MTS assay revealed that Zn-CuO NPs was able to inhibit cancer cell growth. TEM, flow cytometry and fluorescence microscope analysis showed that Zn-CuO NPs induced autophagy significantly; the number of autophagosomes increased obviously in cells treated with Zn-CuO NPs. Western blot analysis revealed that treatment with the NPs resulted in activation of AMPK/mTOR pathway in both AsPC-1 and MIA Paca-2 cells in dose dependent manners. Moreover, in the presence of AMPK activator AMPKinone, the protein level of p-AMPK, p-ULK1, Beclin-1 and LC3-II/LC3-I increased, while the protein expression of p-AMPK, p-ULK1, Beclin-1 and LC3-II/LC3-I decreased in the presence of AMPK inhibitor Compound C. In vivo study using xenograft mice revealed that Zn-CuO NPs significantly inhibited tumor growth with low toxicity. Our study confirms that Zn-CuO NPs inhibit the tumor growth both in vitro and in vivo for pancreatic cancer. AMPK/mTOR pathway plays an important role in the NPs induced inhibition of tumor growth.

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Apr 2019 • Nano letters

Nanostructures, faceting, and splitting in nanoliter to yoctoliter liquid droplets

Shani Guttman, Ellina Kesselman, Avi Jacob, Orlando Marin, Dganit Danino, Moshe Deutsch, Eli Sloutskin

Contrary to everyday experience, where all liquid droplets assume rounded, near-spherical shapes, the temperature-tuning of liquid droplets to faceted polyhedral shapes and to spontaneous splitting has been recently demonstrated in oil-in-water emulsions. However, the elucidation of the mechanism driving these surprising effects, as well as their many potential applications, ranging from faceted nanoparticle synthesis through new industrial emulsification routes to controlled-release drug delivery within the human body, have been severely hampered by the micron-scale resolution of the light microscopy employed to date in all in situ studies. Thus, the thickness of the interfacially frozen crystalline monolayer, suggested to drive these effects, could not be directly measured, and the low limit on the droplet size still showing these effects remained unknown. In this study, we employ a combination of super-resolution …

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Apr 2019 • Solid state nuclear magnetic resonance

Dynamics in hydrophilic and hydrophobic molecular chains tethered to MCM41-type mesoporous silica upon wetting and dehydration processes

Lee Ghindes-Azaria, Ofer Melamed, Merav Nadav-Tsubery, Esthy Levy, Keren Keinan-Adamsky, Gil Goobes

Surface modified mesoporous silica materials are important materials for heterogeneous catalysis and are attracting attention as potential drug carriers. The functionality of these materials relies on the physical and chemical properties of the tethers attached to MCM41 silica surface. These chemically linked tails act as molecular brushes, that can capture pollutant molecules, anchor points for catalysts and can host drug molecules. To utilize the full potential of the tailored silica surfaces, one should infer their properties at different levels of solvation. Here, 1H MAS NMR spectroscopy is used to monitor the dynamic properties of two modified MCM41 materials, an aminopropyl tethered MCM41 and an octyl tethered MCM41, through the process of controlled hydration. The surface site resolved measurements demonstrate how the chemical nature of the two tethers governs the way water molecules are directed to the …

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Apr 2019 • Macromolecular Chemistry and Physics

Functionalization of WS2 Nanotubes with Fluorescent C‐dots and Conductive Polythiophenes

Vijay Bhooshan Kumar, Yifat Harel, Rivka Ben‐Ishay, Jean‐Paul Lellouche, Aharon Gedanken

Multifunctional nanoparticles have attracted significant interest for their multifunctional applications. Described herein is the building of a new hybrid nanocomposite particle, conjugating tungsten disulfide (WS2) nanotubes (NTs) to fluorescent carbon dots (C‐dots). Hybrid WS2‐C‐dots hyb‐NTs nanomaterials are prepared by a hydrothermal reaction of PEDOTAc‐WS2 NTs, where the PEDOTAc (poly 2,3‐dihydrothieno[3,4‐b][1,4]dioxine‐2‐carboxylic acid) polymer serves as the C‐dots precursor. The physical and chemical properties of the as‐synthesized WS2‐C‐dots hyb‐NTs are determined by X‐ray powder diffraction (XRD), transmission electron microscopy (TEM), CHNSO analysis, and fluorescence, Raman, and UV–vis absorption spectroscopy. The WS2‐C‐dots hyb‐NTs are shown to be very stable at normal room temperature and pressure and could be useful for multicolor cell imaging and targeted cell …

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Apr 2019 • The FASEB Journal

Zn‐doped CuO nanocomposites inhibit tumor growth in vitro and in vivo: Involvement of reactive oxygen species‐dependent autophagy and apoptosis cross‐linked …

Huanli Xu, Ru Yuan, Xiaohui Liu, Aharon Gedanken, Xiukun Lin

Zn‐doped CuO nanocomposites (Zn‐CuO NPs) are novel nanoparticles synthesized by sonochemical method. This study aimed to investigate the in vitro and in vivo antitumor effects and mechanism of Zn‐CuO NPs, as well as the exact roles of reactive oxygen species (ROS) in Zn‐CuO NPs‐induced cell death using N‐acetylcysteine, an ROS scavenger. The antitumor effects of Zn‐CuO NPs were evaluated by 3‐(4, 5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium assay and orthotopic transplantation tumor model in nude mice. The effects of Zn‐CuO NPs with or without N‐acetylcysteine on ROS production, DNA damage, apoptosis, mitochondrial damage, autophagy, lysosome impairment, and endoplasmic reticulum and Golgi stress were determined. Western blot was used to detect apoptosis and autophagy related proteins, as well as NF‐κB pathway related proteins. Also …

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Apr 2019 • The Journal of chemical physics

Identity ordering and metastable clusters in fluids with random interactions

Itay Azizi, Yitzhak Rabin

We use Langevin dynamics simulations to study dense two-dimensional systems of particles where all binary interactions are different in the sense that each interaction parameter is characterized by a randomly chosen number. We compare two systems that differ by the probability distributions from which the interaction parameters are drawn: uniform (U) and exponential (E). Both systems undergo neighborhood identity ordering and form metastable clusters in the fluid phase near the liquid-solid transition, but the effects are much stronger in E than in U systems. Possible implications of our results for the control of the structure of multicomponent alloys are discussed.

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Apr 2019 • Optics & Laser Technology

A visible light RGB wavelength demultiplexer based on silicon-nitride multicore PCF

Rami Dadabayev, Nadav Shabairou, Zeev Zalevsky, Dror Malka

One of the main obstacles that limited the performances in visible light networking system is the ability to transmit high data communication rate. In order to overcome this obstacle, we propose a novel design for an RGB demultiplexer based on silicon-nitride (Si3N4) multicore photonic crystal fiber (PCF) structure. The new design is based on replacing several air-holes zones with Si3N4 rods along the fiber length that enable the controlling of the coupling length size between neighboring cores. The locations of the Si3N4 rods and the geometrical parameters of the PCF were analyzed and simulated utilizing the beam propagation method (BPM) combined with Matlab codes. Results show that RGB operated wavelengths can be demultiplexed after light propagation of 5.5 mm with an excellent crosstalk of −20.766 to −23.95 dB and a large bandwidth of 5.9–16.3 nm.

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Apr 2019 • Nature communications

RNA editing is abundant and correlates with task performance in a social bumblebee

Hagit T Porath, Esther Hazan, Hagai Shpigler, Mira Cohen, Mark Band, Yehuda Ben-Shahar, Erez Y Levanon, Eli Eisenberg, Guy Bloch

Colonies of the bumblebee Bombus terrestris are characterized by wide phenotypic variability among genetically similar full-sister workers, suggesting a major role for epigenetic processes. Here, we report a high level of ADAR-mediated RNA editing in the bumblebee, despite the lack of an ADAR1-homolog. We identify 1.15 million unique genomic sites, and 164 recoding sites residing in 100 protein coding genes, including ion channels, transporters, and receptors predicted to affect brain function and behavior. Some edited sites are similarly edited in other insects, cephalopods and even mammals. The global editing level of protein coding and non-coding transcripts weakly correlates with task performance (brood care vs. foraging), but not affected by dominance rank or juvenile hormone known to influence physiology and behavior. Taken together, our findings show that brain editing levels are high in naturally …

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Apr 2019 • Nature communications

Specific inhibition of splicing factor activity by decoy RNA oligonucleotides

Polina Denichenko, Maxim Mogilevsky, Antoine Cléry, Thomas Welte, Jakob Biran, Odelia Shimshon, Georgina D Barnabas, Miri Danan-Gotthold, Saran Kumar, Eylon Yavin, Erez Y Levanon, Frédéric H Allain, Tamar Geiger, Gil Levkowitz, Rotem Karni

Alternative splicing, a fundamental step in gene expression, is deregulated in many diseases. Splicing factors (SFs), which regulate this process, are up-or down regulated or mutated in several diseases including cancer. To date, there are no inhibitors that directly inhibit the activity of SFs. We designed decoy oligonucleotides, composed of several repeats of a RNA motif, which is recognized by a single SF. Here we show that decoy oligonucleotides targeting splicing factors RBFOX1/2, SRSF1 and PTBP1, can specifically bind to their respective SFs and inhibit their splicing and biological activities both in vitro and in vivo. These decoy oligonucleotides present an approach to specifically downregulate SF activity in conditions where SFs are either up-regulated or hyperactive.

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Apr 2019 • Sensors and Actuators A: Physical

In-liquid durable sensing with fused microknot optical transmission resonators: Folded versus straight configuration on hydrophilic and hydrophobic substrates

Alexandra Blank, Moti Fridman, Yoav Linzon

On-fiber micro-structures are favorable platforms for sensing in aqueous environments. Durable in-liquid operation with NIR light transmitted through fused optical microknot fibers defined on adiabatic tapers is presented in straight versus folded configurations. We suggest and demonstrate two schemes for OMF deployment: folded configuration which is intended for remote sensing, and straight configuration on either hydrophilic or hydrophobic substrate, the latter of which is useful in packaged geometries. We study experimentally the OMF preparation methods in folded, straight on glass surface and straight on PDMS surfaces. The persistent detection of NIR light transmission resonances in the presence of volatile liquid capabilities are experimentally demonstrated in the various configurations.

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Apr 2019 • Nature Reviews Materials 4 (4), 269-285, 2019

Photovoltaic solar cell technologies: analysing the state of the art

Pabitra K Nayak, Suhas Mahesh, Henry J Snaith, David Cahen

The remarkable development in photovoltaic (PV) technologies over the past 5 years calls for a renewed assessment of their performance and potential for future progress. Here, we analyse the progress in cells and modules based on single-crystalline GaAs, Si, GaInP and InP, multicrystalline Si as well as thin films of polycrystalline CdTe and CuIn x Ga 1− x Se 2. In addition, we analyse the PV developments of the more recently emerged lead halide perovskites together with notable improvements in sustainable chalcogenides, organic PVs and quantum dots technologies. In addition to power conversion efficiencies, we consider many of the factors that affect power output for each cell type and note improvements in control over the optoelectronic quality of PV-relevant materials and interfaces and the discovery of new material properties. By comparing PV cell parameters across technologies, we appraise how far …

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Apr 2019 • Beilstein journal of nanotechnology

Tungsten disulfide-based nanocomposites for photothermal therapy

Tzuriel Levin, Hagit Sade, Rina Ben-Shabbat Binyamini, Maayan Pour, Iftach Nachman, Jean-Paul Lellouche

Nanostructures of transition-metal dichalcogenides (TMDC) have raised scientific interest in the last few decades. Tungsten disulfide (WS 2) nanotubes and nanoparticles are among the most extensively studied members in this group, and are used for, eg, polymer reinforcement, lubrication and electronic devices. Their biocompatibility and low toxicity make them suitable for medical and biological applications. One potential application is photothermal therapy (PTT), a method for the targeted treatment of cancer, in which a light-responsive material is irradiated with a laser in the near-infrared range. In the current article we present WS 2 nanotubes functionalized with previously reported ceric ammonium nitrate–maghemite (CAN-mag) nanoparticles, used for PTT. Functionalization of the nanotubes with CAN-mag nanoparticles resulted in a magnetic nanocomposite. When tested in vitro with two types of cancer cells, the functionalized nanotubes showed a better PTT activity compared to non-functionalized nanotubes, as well as reduced aggregation and the ability to add a second-step functionality. This ability is demonstrated here with two polymers grafted onto the nanocomposite surface, and other functionalities could be additional cancer therapy agents for achieving increased therapeutic activity.

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Apr 2019 • Phase Transitions

Magnetic phase transitions around room temperature in Cu9S5

Annette Setzer, Pablo D Esquinazi, Lukas Botsch, Oliver Baehre, Eti Teblum, Anat Itzhak, Olga Girshevitz, Gilbert Daniel Nessim

We have studied the magnetization of a recently synthesized CuS compound and found two phase transitions around room temperature. The phase transitions in the crystalline structure, characterized by XRD studies, are accompanied by changes also in the electrical resistivity. A hysteretic first-order phase transition has been found between 260 and 320 K, from a low-temperature paramagnetic anilite phase to a diamagnetic high-temperature low-digenite phase. A second order phase transition was recognized at ≃ 352 K from low digenite to a paramagnetic high-digenite structure at high temperatures.

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Mar 2019 • Nanoscale Imaging, Sensing, and Actuation for Biomedical Applications XVI …, 2019

Calibration iso-pathlength point in cylindrical tissue geometry: comparing steady state photon diffusion to Monte Carlo simulation

Hamootal Duadi, Daqing Piao, Dror Fixler

Light-tissue interactions are commonly studied for near infra-red (NIR) spectroscopy for imaging and diagnosis. While imaging is bound to the surface due to the high tissue scattering, many diagnosis methods, such as the photoplethysmograph (PPG) and pulse oximeter, focus on sensing instead of imaging. There are two approaches for the investigation of light-tissue interactions: one numerical and the other analytical. The most common numerical method is the Monte Carlo (MC) simulation, which is a statistical study of photon migration from the optical properties of the different tissue regions. However, the yield of such statistical approaches is limited. Analytical methods are commonly based on the diffusion theory, yet they are inaccurate near the light source. There are several solution methods, where extrapolated boundary conditions lead to a more accurate solution. Previously, we proposed measuring the …

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Mar 2019 • Nanoscale Imaging, Sensing, and Actuation for Biomedical Applications XVI …, 2019

Metal-based nanoparticles as carriers of mTHPC drug for effective photodynamic therapy

Elina Haimov, Yifat Harel, Shlomi Polani, Hana Weitman, David Zitoun, Jean-Paul Lellouche, Orit Shefi

Photodynamic therapy (PDT) is a promising therapeutic modality for cancer treatment. It considered to be minimallyinvasive and nontoxic. Clinical PDT involves systemic administration of photosensitizer drugs, which accumulate at the tumor area and are light sensitive. When laser illuminates the tumor area in the presence of molecular oxygen, highly reactive singlet oxygen is generated, causing to direct killing of the tumor. Despite the advantages of the classical PDT, it suffers from several limitations, impeding its clinical outcome. Thus, developing targeted delivery systems for photosensitizer drugs that will enhance the selectivity is urgently needed. We develop functionalized metal nanoparticles (NPs) as carriers of mTHPC photosensitizer drug. Herein we use NPs composed of either gold or magnetically responsive carries like Ce-doped and Yb-doped -γ-Fe2O3 maghemite NPs (MNPs). All nanocomposites form …

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Mar 2019 • Bioinformatics

A cluster robustness score for identifying cell subpopulations in single cell gene expression datasets from heterogeneous tissues and tumors

Itamar Kanter, Piero Dalerba, Tomer Kalisky

Motivation A major aim of single cell biology is to identify important cell types such as stem cells in heterogeneous tissues and tumors. This is typically done by isolating hundreds of individual cells and measuring expression levels of multiple genes simultaneously from each cell. Then, clustering algorithms are used to group together similar single-cell expression profiles into clusters, each representing a distinct cell type. However, many of these clusters result from overfitting, meaning that rather than representing biologically meaningful cell types, they describe the intrinsic ‘noise’ in gene expression levels due to limitations in experimental precision or the intrinsic randomness of biochemical cellular processes. Consequentially, these non-meaningful clusters are most sensitive to noise: a slight shift in gene expression levels due to a repeated measurement will rearrange the grouping of data points …

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Mar 2019 • Journal of colloid and interface science

Self-faceting of emulsion droplets as a route to solid icosahedra and other polyhedra

Orlando Marin, Maria Alesker, Shani Guttman, Gregory Gershinsky, Eitan Edri, Hagay Shpaisman, Rodrigo E Guerra, David Zitoun, Moshe Deutsch, Eli Sloutskin

Hypothesis Temperature-controlled self-faceting of liquid droplets has been recently discovered in surfactant-stabilized alkane-in-water emulsions. We hypothesize that similar self-faceting may occur in emulsion droplets of UV-polymerizable linear hydrocarbons. We further hypothesize that the faceted droplet shapes can be fixed by UV-initiated polymerization, thus providing a new route towards the production of solid polyhedra. Experiments Temperature-induced shape variations were studied by optical microscopy in micron-size emulsion droplets of UV-polymerizable alkyl acrylate. When polymerized, the resultant solid particles’ 3D shape and internal structure were determined by combined scanning electron microscopy (SEM) and focused ion beam (FIB) slicing. The SEM and FIB nanoscale resolution provided a far greater detail imaging than that achievable for the liquid droplets, which could only be studied …

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Mar 2019 • Silicon Photonics XIV 10923, 1092309, 2019

Direct thermo-optical tuning of silicon photonic devices (Conference Presentation)

Paul Chevalier, Lara Koehler, Euijae Shim, Boris Desiatov, Amirhassan Shams-Ansari, Marco Piccardo, Marko Loncar, Michal Lipson, Alexander Gaeta, Federico Capasso

Thanks to its high Kerr non-linearity and its low linear absorption, silicon is a material of choice for optical devices in the mid-infrared (from 3 to 5 microns) such as microresonators. In this wavelength range, the available optical sources such as quantum cascade lasers have a limited tunability. Tuning the refractive index of silicon can be achieved by a temperature change of the chip and has been previously demonstrated on ring resonators using integrated heaters or thermo-electric elements. We present a new method for thermo-optical tuning of silicon devices by directly using the light from a laser diode operating at 450 nm. The blue light focused on the silicon induces a local elevation of temperature and thus the refractive index locally increases. When applying this method on silicon ring resonator, the elevation of temperature leads to a decreasing free-spectral range and thus shift the resonances to lower …

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Mar 2019 • FlatChem

Electrochemical intercalation of sodium in vertically aligned molybdenum disulfide for hydrogen evolution reaction

Victor Shokhen, David Zitoun

The intercalation of alkaline cations such as lithium and sodium into two-dimensional (2D) van der Waals materials effectively modifies their electronic structure. Here, we show an electrochemical intercalation process of an alkaline ion (Li+ or Na+), into vertically aligned molybdenum disulfide (MoS2) thin films by using a three-electrode flooded vessel cell, and its application as electrocatalyst for hydrogen evolution reaction. The electrochemical intercalation method is controlled by the applied current density. After electrochemical insertion, the vertically alligned MoS2 layers display an extended Wan der Waals gap. The Li and Na intercalated vertically alligned MoS2 layers demonstrate an overpotential of 0.29 V at 10 mA cm−2 towards hydrogen evolution reaction (HER) in 0.5 M H2SO4. The intercalation of Li+ or Na+ leads to the partial exfoliation of the 2D layered material. Nevertheless, the Na intercalated …

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Mar 2019 • Optica

Ultra-low-loss integrated visible photonics using thin-film lithium niobate

Boris Desiatov, Amirhassan Shams-Ansari, Mian Zhang, Cheng Wang, Marko Lončar

Integrated photonics is a powerful platform that can improve the performance and stability of optical systems while providing low-cost, small-footprint, and scalable alternatives to implementations based on free-space optics. While great progress has been made on the development of low-loss integrated photonics platforms at telecom wavelengths, the visible wavelength range has received less attention. Yet, many applications utilize visible or near-visible light, including those in optical imaging, optogenetics, and quantum science and technology. Here we demonstrate an ultra-low-loss integrated visible photonics platform based on thin-film lithium niobate on an insulator. Our waveguides feature ultra-low propagation loss of 6 dB/m, while our microring resonators have an intrinsic quality factor of 11 million, both measured at 637 nm wavelength. Additionally, we demonstrate an on-chip visible intensity modulator …

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Mar 2019 • Journal of Membrane Science

Modification of a polypropylene feed spacer with metal oxide-thin film by chemical bath deposition for biofouling control in membrane filtration

Chidambaram Thamaraiselvan, Yacov Carmiel, Gary Eliad, Chaim N Sukenik, Raphael Semiat, Carlos G Dosoretz

Surface modification of polypropylene feed spacers typical of spiral wound membrane modules was studied by generation of crystalline ZnO nanorods. A seeding layer made by deposition of ZnO nanoparticles (20–40–60 nm diameter) from aqueous dispersions served as nucleation centers for crystallization. A uniform layer of ZnO nanorods was grown on the seeding layer by chemical bath deposition from a zinc acetate solution. Biocidal activity was estimated by antibacterial tests in static liquid culture against Escherichia coli and antibiofouling tests in flow-through/cross-flow mode against a mixture of Pseudomonas fluorescens and Bacillus subtilis. Best biocidal activity was displayed by 20 nm ZnO particles, suggesting a tradeoff between surface coverage, roughness and particle size. Although the seed layer itself displayed acceptable antibacterial activity, a marked improvement was achieved by the …

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