48 research outputs found

    Global Phosphoproteomic Analysis of Insulin/Akt/mTORC1/S6K Signaling in Rat Hepatocytes

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    Insulin resistance is a hallmark of type 2 diabetes. Although multiple genetic and physiological factors interact to cause insulin resistance, deregulated signaling by phosphorylation is a common underlying mechanism. In particular, the specific phosphorylation-dependent regulatory mechanisms and signaling outputs of insulin are poorly understood in hepatocytes, which represents one of the most important insulin-responsive cell types. Using primary rat hepatocytes as a model system, we performed reductive dimethylation (ReDi)-based quantitative mass spectrometric analysis and characterized the phosphoproteome that is regulated by insulin as well as its key downstream kinases including Akt, mTORC1, and S6K. We identified a total of 12 294 unique, confidently localized phosphorylation sites and 3805 phosphorylated proteins in this single cell type. Detailed bioinformatic analysis on each individual data set identified both known and previously unrecognized targets of this key insulin downstream effector pathway. Furthermore, integrated analysis of the hepatic Akt/mTORC1/S6K signaling axis allowed the delineation of the substrate specificity of several close-related kinases within the insulin signaling pathway. We expect that the data sets will serve as an invaluable resource, providing the foundation for future hypothesis-driven research that helps delineate the molecular mechanisms that underlie the pathogenesis of type 2 diabetes and related metabolic syndrome

    Rational Design of Ternary-Phase Polymer Solar Cells by Controlling Polymer Phase Separation

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    In this article, we report a novel route to control the ternary-phase morphology of the active layer of polymer solar cells (PSCs). Two typical polymers with complementary absorption ranges, i.e. poly­(3-hexylthiophene) (P3HT) and poly­[(4,4′-bis­(2-ethylhexyl)­dithienol­[3,2-<i>b</i>:2′,3′-<i>d</i>]­silole)-2,6-diyl-<i>alt</i>-(2,1,3-benzothiadiazole)-4,7-diyl] (PSBTBT), are selected to obtain ternary phase system by blending with (6,6)-phenyl-C71 butyric acid methyl ester (PC<sub>71</sub>BM). A more than three times increase of power conversion efficiency is observed by tuning the morphologies of ternary phase with high second polymer loading. Different from the traditional disordered intermixing morphologies, the existence of submicrometer scale domains of polymer-rich phases are observed for P3HT and PSBTBT, respectively. The measurements of photoluminescence quenching demonstrate that with the morphology varying from intermixed to hierarchical morphology, the interactions between two polymers changing from charge transfer (CT) to fluorescence resonant energy transfer (FRET); at the same time charge transfer mainly occurs at polymers and PC<sub>71</sub>BM interfaces. The photophysical process here is different from previous reports. A model named hierarchical interpenetrating networks model (HINM) is proposed to describe the optimal active layer of ternary-phase PSCs. Further Kelvin probe force microscopy (KPFM) results demonstrate the reason for our relatively low efficiency is limited by PSBTBT charge transport in blend matrix. We believe that this novel route for controlling morphology could be further optimized and would provide new thoughts and opportunities in the area of PSCs

    Protein Nanocages for Delivery and Release of Luminescent Ruthenium(II) Polypyridyl Complexes

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    In this report, noncovalent encapsulation of hydrophobic ruthenium­(II) polyridyl complexes, Ru­(bpy)<sub>2</sub>dppz<sup>2+</sup> and Ru­(phen)<sub>2</sub>dppz<sup>2+</sup>, into apoferritin cavity was achieved with high loading contents by effective prevention of Ru complex-induced protein aggregation, without disruption of protein native architecture. The Ru-loaded luminescent nanocomposites have demonstrated improved water solubility, easy manipulation, reduced cytotoxicity, and enhanced cellular uptake as compared to the nontreated Ru complexes

    Protein Nanocages for Delivery and Release of Luminescent Ruthenium(II) Polypyridyl Complexes

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    In this report, noncovalent encapsulation of hydrophobic ruthenium­(II) polyridyl complexes, Ru­(bpy)<sub>2</sub>dppz<sup>2+</sup> and Ru­(phen)<sub>2</sub>dppz<sup>2+</sup>, into apoferritin cavity was achieved with high loading contents by effective prevention of Ru complex-induced protein aggregation, without disruption of protein native architecture. The Ru-loaded luminescent nanocomposites have demonstrated improved water solubility, easy manipulation, reduced cytotoxicity, and enhanced cellular uptake as compared to the nontreated Ru complexes

    Robot-Assisted Right Middle Lobectomy

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    Robot-assisted thoracoscopic lobectomy is a feasible procedure, based on the authors’ previous experience. Their hospital has carried out robot-assisted thoracic surgery since May 2015, and accomplished over 400 cases of thoracic surgery through June 2017. This includes, but is not limited to, benign and malignant lung tumors, benign and malignant esophageal disease, mediastinal masses, and thymoma. This video demostrates a successful robot-assisted right middle lobectomy for non-small cell lung cancer.<div>The patient was a 73-year-old woman who was admitted for a nodule in the right lung, which was found during a health checkup two years ago. She had no symptoms such as fever, chest pain, shortness of breath, or hoarseness. Recent CT scanning showed the nodule had enlarged to 1.8 cm, with lobulated edges and pleural indentation. Moreover, it had an abnormally high metabolic performance on PET/CT. The surgery time was about 50 minutes. The patient was discharged on postoperative day four without any perioperative complications. The pathological stage was T1bN0M0 (invasive adenocarcinoma, stage IA2).<br></div

    Transduction efficiency of Ad-eGFP, pc-Ad-eGFP and ACPP-pc-Ad-eGFP with A549 cells.

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    <p>(A) A549 cells were seeded into 96-well plates (10<sup>4</sup> cells/well) and infected after 24 h incubation with 10<sup>4</sup> particles per cell of Ad-eGFP, pc-Ad-eGFP and ACPP-pc-Ad-eGFP in DMEM/10% fetal calf serum (FCS). Cellular GFP fluorescence was visualized 48 h post-infection using a Nikon TI-S microscope and photographed with a Nikon camera. (i) Uninfected cells; infection with (ii) Ad-eGFP, (iii) pc-Ad-eGFP, and (iv) ACPP-pc-Ad-eGFP. (B) After A549 cells were infected for 48 h as described above, the medium was removed, the cells lysed with 100 ml Triton X-100 (0.2% in H<sub>2</sub>O) and GFP fluorescence was measured (λ<sub>ex</sub> 488 nm and λ<sub>em</sub> 538 nm) with a Fluoroskan fluorescence plate reader (Multiskan GO, Thermo Scientific). The columns depict the following: (i) uninfected cells, (ii) Ad-eGFP, (iii) pc-Ad-eGFP, and (iv) ACPP-pc-Ad-eGFP. Data are the means ± SEM. *P<0.05 compared with i, <sup>#</sup>P<0.05 compared with iii (C) A549 cells were trypsinized, aliquoted at (2×10<sup>5</sup> cells)/(2 ml DMEM/10% FCS) and incubated in 6-well plates at 37°C until 90% confluence was reached; subsequently, 10<sup>9</sup> particles Ad-eGFP, pc-Ad-eGFP or ACPP-pc-Ad-eGFP labeled with PI were added. Cells were trypsinized, centrifuged (2 min, 1500 g) and washed in PBS 48 h later. Association of PI-labeled virus with cells was measured using a Coulter EPICS XL flow cytometer with an argon laser (λ<sub>ex</sub> 540 nm and λ<sub>em</sub> 625 nm). The fluorescence profile of control cells (black line) or cells infected with virus (red line), pc-virus (yellow line) or ACPP-pc-virus (purple line).</p

    Conjugated Polymer–Small Molecule Alloy Leads to High Efficient Ternary Organic Solar Cells

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    Ternary organic solar cells are promising candidates for bulk heterojunction solar cells; however, improving the power conversion efficiency (PCE) is quite challenging because the ternary system is complicated on phase separation behavior. In this study, a ternary organic solar cell (OSC) with two donors, including one polymer (PTB7-Th), one small molecule (<i>p</i>-DTS­(FBTTH<sub>2</sub>)<sub>2</sub>), and one acceptor (PC<sub>71</sub>BM), is fabricated. We propose the two donors in the ternary blend forms an alloy. A notable averaged PCE of 10.5% for ternary OSC is obtained due to the improvement of the fill factor (FF) and the short-circuit current density (<i>J</i><sub>sc</sub>), and the open-circuit voltage (<i>V</i><sub>oc</sub>) does not pin to the smaller <i>V</i><sub>oc</sub> of the corresponding binary blends. A highly ordered face-on orientation of polymer molecules is obtained due to the formation of an alloy structure, which facilitates the enhancement of charge separation and transport and the reduction of charge recombination. This work indicates that a high crystallinity and the face-on orientation of polymers could be obtained by forming alloy with two miscible donors, thus paving a way to largely enhance the PCE of OSCs by using the ternary blend strategy

    Selective infection of ACPP-pc-Ad-eGFP in MMP-overexpressing cells and control.

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    <p>HBE(control), A549, MDA-MB-231 and HepG2 cells were seeded into 96-well plates (10<sup>4</sup> cells per well) and after 24 h were infected with 10<sup>4</sup> particles per cell of ACPP-pc-Ad-eGFP in DMEM/10% FCS (A549, MDA-MB-231) or RRPMI-1640/10% FCS (HBE, HepG2). The supernatant was removed 4 h after infection and incubated with 200 µl DMEM/10% FCS (A549, MDA-MB-231) or RRPMI-1640/10% FCS (HBE, HepG2) for an additional 48 h before fluorescence was measured. The columns depict the following: i, HBE; ii, A549; iii, MDA-MB-231; and iv, HepG2. Data are the means ± SEM. *P<0.05 compared with the HBE cell.</p

    Targeted Gene Delivery to Macrophages by Biodegradable Star-Shaped Polymers

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    In this report, two biodegradable star-shaped polyasparamide derivatives and four analogues modified with either mannose or folic acid moiety for preferential targeting of a difficult-to-transfect immune cell type, i.e., macrophage, have been synthesized. Each of the prepared star polymers complexes with plasmid DNA to form nanosized particles featuring a core–shell-like morphology. Mannose or folate functionalized star polymers can greatly improve the transfection performance on a macrophage cell line RAW 264.7. As a result, a combination of targeting ligand modification and topological structures of gene carriers is a promising strategy for immune cells-based gene therapy
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