17 research outputs found

    High‐Performance Doped Silver Films: Overcoming Fundamental Material Limits for Nanophotonic Applications

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137336/1/adma201605177-sup-0001-S1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137336/2/adma201605177_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137336/3/adma201605177.pd

    Human Hepatocytes with Drug Metabolic Function Induced from Fibroblasts by Lineage Reprogramming

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    SummaryObtaining fully functional cell types is a major challenge for drug discovery and regenerative medicine. Currently, a fundamental solution to this key problem is still lacking. Here, we show that functional human induced hepatocytes (hiHeps) can be generated from fibroblasts by overexpressing the hepatic fate conversion factors HNF1A, HNF4A, and HNF6 along with the maturation factors ATF5, PROX1, and CEBPA. hiHeps express a spectrum of phase I and II drug-metabolizing enzymes and phase III drug transporters. Importantly, the metabolic activities of CYP3A4, CYP1A2, CYP2B6, CYP2C9, and CYP2C19 are comparable between hiHeps and freshly isolated primary human hepatocytes. Transplanted hiHeps repopulate up to 30% of the livers of Tet-uPA/Rag2−/−/γc−/− mice and secrete more than 300 μg/ml human ALBUMIN in vivo. Our data demonstrate that human hepatocytes with drug metabolic function can be generated by lineage reprogramming, thus providing a cell resource for pharmaceutical applications

    A two-step lineage reprogramming strategy to generate functionally competent human hepatocytes from fibroblasts

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    Terminally differentiated cells can be generated by lineage reprogramming, which is, however, hindered by incomplete conversion with residual initial cell identity and partial functionality. Here, we demonstrate a new reprogramming strategy by mimicking the natural regeneration route, which permits generating expandable hepatic progenitor cells and functionally competent human hepatocytes. Fibroblasts were first induced into human hepatic progenitor-like cells (hHPLCs), which could robustly expand in vitro and efficiently engraft in vivo. Moreover, hHPLCs could be efficiently induced into mature human hepatocytes (hiHeps) in vitro, whose molecular identity highly resembles primary human hepatocytes (PHHs). Most importantly, hiHeps could be generated in large quantity and were functionally competent to replace PHHs for drug-metabolism estimation, toxicity prediction and hepatitis B virus infection modeling. Our results highlight the advantages of the progenitor stage for successful lineage reprogramming. This strategy is promising for generating other mature human cell types by lineage reprogramming.</p

    Long-term functional maintenance of primary human hepatocytes in vitro

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    The maintenance of terminally differentiated cells, especially hepatocytes, in vitro has proven challenging. Here we demonstrated the long-term in vitro maintenance of primary human hepatocytes (PHHs) by modulating cell signaling pathways with a combination of five chemicals (5C). 5C-cultured PHHs showed global gene expression profiles and hepatocyte-specific functions resembling those of freshly isolated counterparts. Furthermore, these cells efficiently recapitulated the entire course of hepatitis B virus (HBV) infection over 4 weeks with the production of infectious viral particles and formation of HBV covalently closed circular DNA. Our study demonstrates that, with a chemical approach, functional maintenance of PHHs supports long-term HBV infection in vitro, providing an efficient platform for investigating HBV cell biology and antiviral drug screening.</p

    Dilatancy Characteristics and Constitutive Modelling of the Unsaturated Soil Based on Changes in the Mass Water Content

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    Most soil mechanics theories are limited to strain hardening and shrinkage under high compressive stresses, and there are some shortcomings in the selection of suction or degree of saturation as the water content state varies in the constitutive models of unsaturated soil. Based on the triaxial shear tests of unsaturated compacted soil (a silt of high plasticity) with different water content and confining pressure (low-confining), a shear dilatancy model of unsaturated soil based on the mass water content is proposed in this paper. The influence of the water content on the shear deformation characteristics of the unsaturated soil is analysed. The stress–dilatancy relationship and the prediction equation of the minimum dilatancy rate of the unsaturated soil under different water content and different confining pressure are provided. Selecting the mass water content as the state variable, a constitutive model suitable for the dilatancy of unsaturated soil is established. The method of determining model parameters based on the mass water content is analysed. The applicability of the model is verified by comparisons between the predicted and experimental results

    Boosting the Oxygen Evolution Reaction by Controllably Constructing FeNi<sub>3</sub>/C Nanorods

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    Transition bimetallic alloy-based catalysts are regarded as attractive alternatives for the oxygen evolution reaction (OER), attributed to their competitive economics, high conductivity and intrinsic properties. Herein, we prepared FeNi3/C nanorods with largely improved catalytic OER activity by combining hydrothermal reaction and thermal annealing treatment. The temperature effect on the crystal structure and chemical composition of the FeNi3/C nanorods was revealed, and the enhanced catalytic performance of FeNi3/C with an annealing temperature of 400 °C was confirmed by several electrochemical tests. The outstanding catalytic performance was assigned to the formation of bimetallic alloys/carbon composites. The FeNi3/C nanorods showed an overpotential of 250 mV to afford a current density of 10 mA cm−2 and a Tafel slope of 84.9 mV dec−1, which were both smaller than the other control samples and commercial IrO2 catalysts. The fast kinetics and high catalytic stability were also verified by electrochemical impendence spectroscopy and chronoamperometry for 15 h. This study is favorable for the design and construction of bimetallic alloy-based materials as efficient catalysts for the OER

    Engineering Light at the Nanoscale: Structural Color Filters and Broadband Perfect Absorbers

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    Recent advances in fabrication and processing methods have spurred many breakthroughs in the field of nanostructures that provide novel ways of manipulating light interaction on a well controllable manner, thereby enabling a wide variety of innovative applications. Structural colors have shown great promise as an alternative for existing colorantâ based filters due to their noticeable advantages, which open up diverse potential applications such as energyâ efficient displays, ultrahighâ resolution imaging, ultrahighâ sensitivity biosensors, and buildingâ integrated photovoltaics. Broadband perfect absorbers, which exploit extraordinary optical phenomena at subwavelength scale, have also received increasing attention due to their capability of improving efficiency and performance characteristics of various applications including thermoelectrics, invisibility, solarâ thermalâ energy harvesting, and imaging. This review highlights some recent progress in these two related fields. The structural colors based on optical resonances in thinâ film structures, guidedâ mode resonances in slab waveguide gratings, and surface plasmon resonances in plasmonic nanoresonators are described. Representative achievements associated with the broadband perfect absorbers, which include schemes employing highly absorbing media, multiâ cavity resonances, and broadband impedance matching are investigated.Subwavelength nanostructures featuring extraordinary optical properties have received considerable research interest in the field of structural color filters and broadband perfect absorbers due to their unique advantages over conventional counterparts. This review summarizes recent work in these areas with a detailed discussion of design principles, characteristic performances, implementation approaches, and practical applications, aiming to inspire further investigations in nanotechnology
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