Notch1 Inhibits Rosiglitazone-Induced Adipogenic Differentiation in Primary Thymic Stromal Cells

Adipocyte deposition is believed to be a primary characteristic of age-related thymic involution. Herein, we cultured primary thymic stromal cells (TSCs), used rosiglitazone, a potent peroxisome proliferator-activated receptor γ (PPARγ) agonist, to induce adipogenic differentiation, and investigated the differentially expressed genes during adipogenic differentiation by using RNA-sequencing analysis. Furthermore, the effects of Notch1 on rosiglitazone-induced adipogenic differentiation of TSCs as well as the underlying mechanisms were also investigated. As a result, we identified a total of 1737 differentially expressed genes, among which 965 genes were up-regulated and 772 genes were down-regulated in rosiglitazone-treated cells compared with control cells. Gene ontology (GO) enrichment analysis showed that the GO terms were enriched in metabolic process, intracellular, and protein binding. Kyoto encyclopedia of genes and genomes (KEGG) analysis showed that a number of pathways, including ubiquitin mediated proteolysis, PPAR signaling pathway, and mammalian target of rapamycin (mTOR) signaling pathway were predominantly over-represented. Meanwhile, overexpression of Notch1 suppressed and inhibition of Notch1 promoted rosiglitazone-induced adipogenic differentiation in TSCs, and the pro-adipogenic effects of the Notch inhibitor DAPT were associated with the activation of autophagy. Taken together, our results suggest that Notch1 is a key regulator in thymic adipogenesis and may serve as a potential target to hinder thymic adiposity in age-related thymic involution

Loss of imprinting of insulin-like growth factor 2 is associated with increased risk of lymph node metastasis and gastric corpus cancer

Abstract Background The aim of this study was to determine the clinicopathological features of gastric cancers with loss of imprinting (LOI) of LIT1. Insulin-like growth factor 2 (IGF2) and H19 in Chinese patients. Methods DNA and RNA from tumours were amplified and then digested with RsaI, ApaI and HinfI, and RsaI respectively to determine the LOI status. The demographic and clinicopathological characteristics in LOI positive and LOI negative patients were compared and tested with Statistical analysis. Results Of the 89 patients enrolled for analysis, 22, 40 and 35 were heterozygous and thus informative for LIT1, IGF2 and H19 LOI analyses respectively. The positive rate of LIT1, IGF2 and H19 LOI of gastric cancer tissues were 54.6% (12/22), 45% (18/40) and 8.6% (3/32) in Chinese patients. Gastric corpus cancer (8/10, 80%) were more likely to have LOI of IGF2 in tumours than antrum cancers (10/30, 33.3%){odds ratio (OR) = 8, 95% confidence intervals (CI) = 1.425-44.920, p = 0.018)}. LOI of IGF2 in tumours was also associated with the lymph node metastasis (LNM) (OR = 4.5, 95% CI = 1.084-18.689, p = 0.038). Conclusion IGF2 LOI is present in high frequency in Chinese gastric cancer patients, especially those with gastric corpus cancer.</p

Effect of molecular asymmetry on the charge transport physics of high mobility n-type molecular semiconductors investigated by scanning Kelvin probe microscopy.

We have investigated the influence of the symmetry of the side chain substituents in high-mobility, solution processable n-type molecular semiconductors on the performance of organic field-effect transistors (OFETs). We compare two molecules with the same conjugated core, but either symmetric or asymmetric side chain substituents, and investigate the transport properties and thin film growth mode using scanning Kelvin probe microscopy (SKPM) and atomic force microscopy (AFM). We find that asymmetric side chains can induce a favorable two-dimensional growth mode with a bilayer structure, which enables ultrathin films with a single bilayer to exhibit excellent transport properties, while the symmetric molecules adopt an unfavorable three-dimensional growth mode in which transport in the first monolayer at the interface is severely hindered by high-resistance grain boundaries.This work was supported by the Engineering and Physical Sciences Research Council (EPSRC). Y. Hu thanks the Cambridge Overseas Trust and Chinese Scholarship Council for a postgraduate award.This is the author accepted manuscript. The final version is available at: http://pubs.acs.org/doi/abs/10.1021/nn500944f Copyright © 2014 American Chemical Societ

Tetracyanodibenzotetrathiafulvalene Diimides: Design, Synthesis, and Property Study

Tetracyanodibenzotetrathiafulvalene diimide (TCDBTTF-DI), an isomer of core-expanded naphthalene diimides bearing two 2-(1,3-dithiol-2-ylidene)­malononitrile moieties (NDI-DTYM2), has been designed and synthesized to explore the effect of its isomeric structure on the optical and electrochemical properties of the materials. UV–vis spectra show that TCDBTTF-DI exhibits variation in its absorption peaks while maintaining a similar optical band gap to NDI-DTYM2. Electrochemical studies indicate that TCDBTTF-DI can not only accept but also lose electrons, in contrast to the solely electron-accepting behavior of NDI-DTYM2

Naphthalenediimides Fused with 2‑(1,3-Dithiol-2-ylidene)acetonitrile: Strong Electron-Deficient Building Blocks for High-Performance n‑Type Polymeric Semiconductors

Naphthalenediimides (NDI) fused with two 2-(1,3-dithiol-2-ylidene)­acetonitrile moieties (NDI-DTYA2), a novel strong electron-deficient monomer, was designed and readily synthesized by aromatic nucleophilic substitution to develop n-type polymers. Two NDI-DTYA2 based donor–acceptor (D–A) polymers P­(NDI-DTYA2–1T) and P­(NDI-DTYA2–2T) have been prepared (1T = thiophene, 2T = 2,2′-bithiophene) and showed low-lying LUMO energies (<−4.2 eV) and near-infrared optical absorptions (optical band gap <1.3 eV). Although the film feature of these polymers is amorphous, pure electron transport with high mobility of up to 0.38 cm² V ^–1 s ^–1 could be achieved for their bottom gate organic thin film transistors, which was among the highest performances for unipolar n-type polymers. The results demonstrate that NDI-DTYA2 derivatives are promising building blocks for developing electron transport π-functional materials

1,2,5,6-Naphthalenediimide Based Donor–Acceptor Copolymers Designed from Isomer Chemistry for Organic Semiconducting Materials

Two new donor–acceptor (D–A) copolymers based on 1,2,5,6-naphthalenediimides (iso-NDI) and thiophene units, iso-P­(NDI2OD-T2) and iso-P­(NDI2OD-TT), were designed from isomer chemistry and compared with the reported isomeric copolymers P­(NDI2OD-T2) and P­(NDI2DT-TT) to investigate the influence of isomeric structure on their optoelectronic properties. DFT calculations reveal that iso-P­(NDI2OD-T2) and iso-P­(NDI2OD-TT) have higher HOMO and LUMO energies and better backbone planarity relative to their isomeric polymers. Iso-P­(NDI2OD-T2) and iso-P­(NDI2OD-TT) were synthesized by the Stille coupling polymerization and characterized by elemental analysis, ¹H NMR, GPC, UV–vis absorption, cyclic voltammetry, TGA, DSC, and organic thin film transistors (OTFTs). It was found that iso-P­(NDI2OD-T2) and iso-P­(NDI2OD-TT) had higher LUMO energies and broader band gaps than their isomeric ones and showed hole-dominated charge transport behavior, which is quite different from the electron-dominated charge transport feature of P­(NDI2OD-T2) and P­(NDI2DT-TT). In spite of the amorphous-like thin-film features, iso-P­(NDI2OD-T2) exhibited high hole mobility of up to 0.3 cm² V^–1 s^–1, and iso-P­(NDI2OD-TT) showed ambipolar property with hole and electron mobility of up to 0.02 and 4 × 10^–3 cm² V^–1 s^–1, respectively

One-Pot Synthesis of Core-Expanded Naphthalene Diimides: Enabling <i>N</i>-Substituent Modulation for Diverse n-Type Organic Materials

A mild and versatile one-pot synthesis of core-expanded naphthalene diimides has been developed, which undergoes a nucleophilic aromatic substitution reaction and then an imidization reaction, allowing an easy and low-cost access to diverse n-type organic materials. Some newly synthesized compounds by this one-pot operation exhibited high electron mobility of up to 0.70 cm² V^–1 s^–1 in ambient conditions

Critical Role of Alkyl Chain Branching of Organic Semiconductors in Enabling Solution-Processed N‑Channel Organic Thin-Film Transistors with Mobility of up to 3.50 cm² V^–1 s^–1

Substituted side chains are fundamental units in solution processable organic semiconductors in order to achieve a balance of close intermolecular stacking, high crystallinity, and good compatibility with different wet techniques. Based on four air-stable solution-processed naphthalene diimides fused with 2-(1,3-dithiol-2-ylidene)­malononitrile groups (NDI-DTYM2) that bear branched alkyl chains with varied side-chain length and different branching position, we have carried out systematic studies on the relationship between film microstructure and charge transport in their organic thin-film transistors (OTFTs). In particular synchrotron measurements (grazing incidence X-ray diffraction and near-edge X-ray absorption fine structure) are combined with device optimization studies to probe the interplay between molecular structure, molecular packing, and OTFT mobility. It is found that the side-chain length has a moderate influence on thin-film microstructure but leads to only limited changes in OTFT performance. In contrast, the position of branching point results in subtle, yet critical changes in molecular packing and leads to dramatic differences in electron mobility ranging from ∼0.001 to >3.0 cm² V^–1 s^–1. Incorporating a NDI-DTYM2 core with three-branched <i>N</i>-alkyl substituents of C_11,6 results in a dense in-plane molecular packing with an unit cell area of 127 Ų, larger domain sizes of up to 1000 × 3000 nm², and an electron mobility of up to 3.50 cm² V^–1 s^–1, which is an unprecedented value for ambient stable n-channel solution-processed OTFTs reported to date. These results demonstrate that variation of the alkyl chain branching point is a powerful strategy for tuning of molecular packing to enable high charge transport mobilities