Recently, the fields of organic light‐emitting diodes (OLEDs) and light‐emitting electrochemical cells (LECs) have improved tremendously with regard to tunable emission, efficiency, brightness, and ...thermal stability. Imidazole derivatives are excellent deep blue‐green light‐emitting layers in the OLED or LEC devices. This Review summarizes the major breakthroughs of various electroluminescence (EL) layers with imidazole‐containing organic or organometallic derivatives, the molecular design principles, and their light‐emitting performances as effective EL materials. The highly tunable chemical structures and flexible molecular design strategies of imidazole‐based compounds are advantages that provide great opportunities for researchers. They can provide a good basis for the design and development of new EL materials with narrower emission and higher efficiency. Moreover, imidazole compounds have demonstrated breakthrough performances in thermally activated delayed fluorescence (TADF) properties where triplet excitons are utilized to inhibit anti‐intersystem quenching, showing great promise in breaking the theoretical external quantum efficiencies (EQE) limits in traditional fluorescent devices.
Imidazole emitters: In recent years, electroluminescent devices have flourished, and maximizing the efficiency of organic light‐emitting diodes (OLEDs) and light‐emitting electrochemical cells (LECs) has become the driving force and goal of a great deal of research. Imidazole derivatives have developed many excellent electroluminescent devices due to their structural diversity. This Review article discusses imidazole derivatives for fluorescent emitters and ligands as phosphorescent emitters and demonstrates their properties.
Recognition of modified histone species by distinct structural domains within 'reader' proteins plays a critical role in the regulation of gene expression. Readers that simultaneously recognize ...histones with multiple marks allow transduction of complex chromatin modification patterns into specific biological outcomes. Here we report that chromatin regulator tripartite motif-containing 24 (TRIM24) functions in humans as a reader of dual histone marks by means of tandem plant homeodomain (PHD) and bromodomain (Bromo) regions. The three-dimensional structure of the PHD-Bromo region of TRIM24 revealed a single functional unit for combinatorial recognition of unmodified H3K4 (that is, histone H3 unmodified at lysine 4, H3K4me0) and acetylated H3K23 (histone H3 acetylated at lysine 23, H3K23ac) within the same histone tail. TRIM24 binds chromatin and oestrogen receptor to activate oestrogen-dependent genes associated with cellular proliferation and tumour development. Aberrant expression of TRIM24 negatively correlates with survival of breast cancer patients. The PHD-Bromo of TRIM24 provides a structural rationale for chromatin activation through a non-canonical histone signature, establishing a new route by which chromatin readers may influence cancer pathogenesis.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Pruritus is associated with multiple liver diseases, particularly those with cholestasis, but the mechanism remains incompletely understood. Our aim was to evaluate serum IL-31 as a putative ...biomarker of pruritus in clinical trials of an farnesoid X receptor (FXR) agonist, cilofexor, in patients with NASH, primary sclerosing cholangitis (PSC), and primary biliary cholangitis (PBC).
Serum IL-31 was measured in clinical studies of cilofexor in NASH, PSC, and PBC. In patients with PSC or PBC, baseline IL-31 was elevated compared to patients with NASH and healthy volunteers (HVs). IL-31 correlated with serum bile acids among patients with NASH, PBC, and PSC. Baseline IL-31 levels in PSC and PBC were positively correlated with Visual Analog Scale for pruritus and 5-D itch scores. In patients with NASH, cilofexor dose-dependently increased IL-31 from Week (W)1 to W24. In patients with NASH receiving cilofexor 100 mg, IL-31 was higher in those with Grade 2-3 pruritus adverse events (AEs) than those with Grade 0-1 pruritus AEs. IL-31 weakly correlated with C4 at baseline in patients with NASH, and among those receiving cilofexor 100 mg, changes in IL-31 and C4 from baseline to W24 were negatively correlated. IL-31 messenger RNA (mRNA) was elevated in hepatocytes from patients with PSC and NASH compared to HVs. In a humanized liver murine model, obeticholic acid increased IL-31 mRNA expression in human hepatocytes and serum levels of human IL-31.
IL-31 levels correlate with pruritus in patients with cholestatic disease and NASH, with FXR agonist therapy resulting in higher serum levels in the latter group. IL-31 appears to derive in part from increased hepatocyte expression. These findings have therapeutic implications for patients with liver disease and pruritus.
Trim24 targets endogenous p53 for degradation Allton, Kendra; Jain, Abhinav K; Herz, Hans-Martin ...
Proceedings of the National Academy of Sciences - PNAS,
07/2009, Letnik:
106, Številka:
28
Journal Article
Recenzirano
Odprti dostop
Numerous studies focus on the tumor suppressor p53 as a protector of genomic stability, mediator of cell cycle arrest and apoptosis, and target of mutation in 50% of all human cancers. The vast ...majority of information on p53, its protein-interaction partners and regulation, comes from studies of tumor-derived, cultured cells where p53 and its regulatory controls may be mutated or dysfunctional. To address regulation of endogenous p53 in normal cells, we created a mouse and stem cell model by knock-in (KI) of a tandem-affinity-purification (TAP) epitope at the endogenous Trp-53 locus. Mass spectrometry of TAP-purified p53-complexes from embryonic stem cells revealed Tripartite-motif protein 24 (Trim24), a previously unknown partner of p53. Mutation of TRIM24 homolog, bonus, in Drosophila led to apoptosis, which could be rescued by p53-depletion. These in vivo analyses establish TRIM24/bonus as a pathway that negatively regulates p53 in DROSOPHILA: The Trim24-p53 link is evolutionarily conserved, as TRIM24 depletion in human breast cancer cells caused p53-dependent, spontaneous apoptosis. We found that Trim24 ubiquitylates and negatively regulates p53 levels, suggesting Trim24 as a therapeutic target to restore tumor suppression by p53.
A series of donor–acceptor–donor triazine‐based molecules with thermally activated delayed fluorescence (TADF) properties were synthesized to obtain highly efficient blue‐emitting OLEDs with ...non‐doped emitting layers (EMLs). The targeted molecules use a triazine core as the electron acceptor, and a benzene ring as the conjugated linker with different electron donors to alternate the energy level of the HOMO to further tune the emission color. The introduction of long alkyl chains on the triazine core inhibits the unwanted intermolecular D–D/A–A‐type π–π interactions, resulting in the intermolecular D–A charge transfer. The weak aggregation‐caused quenching (ACQ) effect caused by the suppressed intermolecular D–D/A–A‐type π–π interaction further enhances the emission. The crowded molecular structure allows the electron donor and acceptor to be nearly orthogonal, thereby reducing the energy gap between triplet and singlet excited states (ΔEST). As a result, blue‐emitting devices with TH‐2DMAC and TH‐2DPAC non‐doped EMLs showed satisfactory efficiencies of 12.8 % and 15.8 %, respectively, which is one of the highest external quantum efficiency (EQEs) reported for blue TADF emitters (λpeak<475 nm), demonstrating that our tailored molecular designs are promising strategies to endow OLEDs with excellent electroluminescent performances.
Getting the blues: A series of donor–acceptor–donor triazine‐based molecules with thermally activated delayed fluorescence (TADF) properties were synthesized to obtain highly efficient blue‐emitting OLEDs with non‐doped emitting layers (EMLs). The targeted molecules use a triazine core as the electron acceptor, and a benzene ring as the conjugated linker with different electron donors to alternate the energy level of the HOMO to further tune the emission color.
In recent years, owing to the demand for high‐efficiency phosphorescent organic light‐emitting devices (PhOLEDs), many studies have been conducted on the development of bipolar host materials. A ...series of imidazolyl‐phenylcarbazole‐based host materials, i. e., im‐CzP, im‐CzPCz, im‐CzPtBu, and im‐OCzP, were synthesized to obtain high‐efficiency green and red‐emitting PhOLEDs. With im‐OCzP as the host, satisfactory peak efficiencies of 22.2 (77.0 cd A−1 and 93.1 lm W−1) and 14.1 % (9.0 cd A−1 and 10.1 lm W−1) could be obtained, respectively. To further improve the performance of the devices, an electron transport material, bis‐4,6‐(3,5‐di‐3‐pyridylphenyl)‐2‐methylpyrimidine (B3PyMPM) was selected to construct a co‐hosted system. The efficiency of im‐OCzP combined with B3PyMPM forming co‐hosts could also achieve high values of 23.0 (80.0 cd A−1 and 98.8 lm W−1) and 16.5 % (10.2 cd A−1 and 13.4 lm W−1) for green and red PhOLEDs, respectively. These results exhibited that the proposed bipolar hosts have great flexibility in adjusting the carrier balance of EML in OLEDs, demonstrating their ingenious design and high potential.
A series of imidazolyl‐phenylcarbazole‐based host materials, i. e., im‐CzP, im‐CzPCz, im‐CzPtBu, and im‐OCzP, were synthesized to obtain high‐efficiency green and red‐emitting PhOLEDs. An electron transport material, bis‐4,6‐(3,5‐di‐3‐pyridylphenyl)‐2‐methylpyrimidine (B3PyMPM) was selected to construct a co‐hosted system. The efficiency of im‐OCzP combined with B3PyMPM forming co‐hosts could also achieve high values of 23.0 (80.0 cd A−1 and 98.8 lm W−1) and 16.5 % (10.2 cd A−1 and 13.4 lm W−1) for green and red PhOLEDs, respectively.
Highly ordered nanostructured organic/inorganic hybrids offer chemical tunability, novel functionalities and enhanced performance over their individual components. Hybrids of complementary p-type ...organic and n-type inorganic components have attracted interest in optoelectronics, where high-efficiency devices with minimal cost are desired. We demonstrate here self-assembly of a lamellar hybrid containing periodic and alternating 1-nm-thick sheets of polycrystalline ZnO separated by 2-3 nm layers of conjugated molecules, directly onto an electrode. Initially the electrodeposited inorganic is Zn(OH)(2), but pi-pi interactions among conjugated molecules stabilize synergistically the periodic nanostructure as it converts to ZnO at 150 degrees C. As photoconductors, normalized detectivities (D(*)) greater than 2x10(10) Jones, photocurrent gains of 120 at 1.2 V microm(-1) and dynamic ranges greater than 60 dB are observed on selective excitation of the organic. These are among the highest values measured for organic, hybrid and amorphous silicon, making them technologically competitive as low-power, wavelength-tunable, flexible and environmentally benign photoconductors.
In response to cold exposure, placental mammals maintain body temperature by increasing sympathetic nerve activity in brown adipose tissue (BAT). Triggering of β-adrenergic receptors on brown ...adipocytes stimulates thermogenesis via induction of the cAMP/PKA pathway. Although cAMP response element-binding protein (CREB) and its coactivators—the cAMP-regulated transcriptional coactivators (CRTCs)—mediate transcriptional effects of cAMP in most tissues, other transcription factors such as ATF2 appear critical for induction of thermogenic genes by cAMP in BAT. Brown adipocytes arise from Myf5-positive mesenchymal cells under the control of PRDM16, a coactivator that concurrently represses differentiation along the skeletal muscle lineage. Here, we show that the CREB coactivator CRTC3 is part of an inhibitory feedback pathway that antagonizes PRDM16-dependent differentiation. Mice with a knockout of CRTC3 in BAT (BKO) have increased cold tolerance and reduced adiposity, whereas mice overexpressing constitutively active CRTC3 in adipose tissue are more cold sensitive and have greater fat mass. CRTC3 reduced sympathetic nerve activity in BAT by up-regulating the expression of miR-206, a microRNA that promotes differentiation along the myogenic lineage and that we show here decreases the expression of VEGFA and neurotrophins critical for BAT innervation and vascularization. Sympathetic nerve activity to BAT was enhanced in BKO mice, leading to increases in catecholamine signaling that stimulated energy expenditure. As reexpression of miR-206 in BAT from BKO mice reversed the salutary effects of CRTC3 depletion on cold tolerance, our studies suggest that small-molecule inhibitors against this coactivator may provide therapeutic benefit to overweight individuals.
Under fasting conditions, increases in circulating glucagon maintain glucose balance by promoting hepatic gluconeogenesis. Triggering of the cAMP pathway stimulates gluconeogenic gene expression ...through the PKA-mediated phosphorylation of the cAMP response element binding (CREB) protein and via the dephosphorylation of the latent cytoplasmic CREB regulated transcriptional coactivator 2 (CRTC2). CREB and CRTC2 activities are increased in insulin resistance, in which they promote hyperglycemia because of constitutive induction of the gluconeogenic program. The extent to which CREB and CRTC2 are coordinately up-regulated in response to glucagon, however, remains unclear. Here we show that, following its activation, CRTC2 enhances CREB phosphorylation through an association with the protein arginine methyltransferase 5 (PRMT5). In turn, PRMT5 was found to stimulate CREB phosphorylation via increases in histone H3 Arg2 methylation that enhanced chromatin accessibility at gluconeogenic promoters. Because depletion of PRMT5 lowers hepatic glucose production and gluconeogenic gene expression, these results demonstrate how a chromatin-modifying enzyme regulates a metabolic program through epigenetic changes that impact the phosphorylation of a transcription factor in response to hormonal stimuli.
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