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Emerging evidence indicates that microRNAs (miRNAs) have important roles in regulating osteogenic differentiation and bone formation. Thus far, no study has established the pathophysiological role for miRNAs identified in human osteoporotic bone specimens. Here we found that elevated miR-214 levels correlated with a lower degree of bone formation in bone specimens from aged patients with fractures. We also found that osteoblast-specific manipulation of miR-214 levels by miR-214 antagomir treatment in miR-214 transgenic, ovariectomized, or hindlimb-unloaded mice revealed an inhibitory role of miR-214 in regulating bone formation. Further, in vitro osteoblast activity and matrix mineralization were promoted by antagomir-214 and decreased by agomir-214, and miR-214 directly targeted ATF4 to inhibit osteoblast activity. These data suggest that miR-214 has a crucial role in suppressing bone formation and that miR-214 inhibition in osteoblasts may be a potential anabolic strategy for ameliorating osteoporosis.

Three novel copolymers containing alternating 1,4-bis(phenylethenyl)benzene, 1,4-bis(phenylethenyl)-2,5dimethoxybenzene or 1,5-bis(phenylethenyl)naphthalene chromophores and crown ether (CE) spacers within the polymer backbone were synthesized by the Wittig polycondensation reaction. These copolymers exhibit good thermal stability (decomposition temperature around 380-411 uC). Photoluminescence (PL) and electroluminescence (EL) color can be easily tuned in these copolymers by simply changing the structure of the chromophores. Excimer emission is responsible for the changes in the PL spectra on going from solution to the thin films. Typical light-emitting electrochemical cell (LEC) behavior is observed in the EL devices with these copolymers as both electronic and ionic conductors. The turn-on voltage for emission is at 13.9 V, in forward bias, and at 24.4 V, under reverse bias. Efficient LECs with low turn-on voltages can be demonstrated upon addition of poly(ethylene oxide) (PEO) into the active layers. CE spacers in these copolymers contribute to the increasing ionic conductivity and the improvement in the morphology of the active layers. The d.c. response and a.c. impedance behaviors of the LECs with PEO were investigated, and the results indicate the operation of these LECs corresponds to the electrochemical doping mechanism.

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The polymer light-emitting electrochemical cells (LECs) were fabricated with MEH-PPV as the luminescent polymer and the ionic liquid of imidazolium salts as the supporting electrolyte. The imidazolium salts utilized include various 1-methyl-3-alkylimidazolium salts with the alkyl substituents of butyl (bmim), dodecyl (dmim), tetradecyl (tmim), or hexadecyl (hmim) and the anions of PF 6or BF 4 -, which possess different melting points from room temperature for [bmim + ][PF 6 -] to 83 °C for [hmim + ][PF 6 -]. The electroluminescent (EL) properties and the electronic structure of the LECs were characterized by current-voltage (I-V), light intensity-voltage (L-V), and ac impedance measurements. It was found that the phase compatibility between the conjugated polymer and the ionic liquid determines the performance of the light-emitting devices, and the concentration of the ionic liquid and the ionic conductivity of the polymer blend films also play an important role. The imidazolium salts investigated in this work are suitable for fabricating the LECs except for [bmim + ][PF 6 -] which encounters phase separation problem with MEH-PPV. The LEC doped by [dmim + ][BF 4 -] shows an EL external quantum efficiency of 0.2% at 4 V, which is comparable with that of the traditional LEC with PEO/Li + salt as the polymer electrolyte. Room-temperature frozen p-i-n junction LEC was realized on the LECs based on MEH-PPV doped by [tmim + ][PF 6 -] and [hmim + ][PF 6 -] with the higher melting point. The frozen-junction LEC shows fast response, wide operating voltage window exceed 10 V and high EL performance. The external quantum efficiency of the LEC/[hmim + ][PF 6 -] achieved 1.4% at 10 V. The electrochemical doping mechanism of the LECs was confirmed by the ac impedance measurement of the devices. The ionic liquids are very stable and insensitive to humidity, which could enable the fabrication and characterization of the LEC outside a drybox.

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Owing to their narrow bright emission band, broad size-tunable emission wavelength, superior photostability, and excellent flexible-substrate compatibility, light-emitting diodes based on quantum dots (QD-LEDs) are currently under intensive research and development for multiple consumer applications including flat-panel displays and flat lighting. However, their commercialization is still precluded by the slow development to date of efficient QD-LEDs as even the highest reported efficiency of 2.0% cannot favorably compete with their organic counterparts. Here, we report QD-LEDs with a record high efficiency (approximately 4%), high brightness (approximately 6580 cd/m(2)), low turn-on voltage (approximately 2.6 V), and significantly improved color purity by simply using deoxyribonucleic acid (DNA) complexed with cetyltrimetylammonium (CTMA) (DNA-CTMA) as a combined hole transporting and electron-blocking layer (HTL/EBL). This, together with controlled thermal decomposition of ligand molecules from the QD shell, represents a novel combined, but simple and very effective, approach toward the development of highly efficient QD-LEDs with a high color purity.

Background-Sustained cardiac pressure overload-induced hypertrophy and pathological remodeling frequently leads to heart failure. Casein kinase-2 interacting protein-1 (CKIP-1) has been identified to be an important regulator of cell proliferation, differentiation, and apoptosis. However, the physiological role of CKIP-1 in the heart is unknown. Methods and Results-The results of echocardiography and histology demonstrate that CKIP-1-deficient mice exhibit spontaneous cardiac hypertrophy with aging and hypersensitivity to pressure overload-induced pathological cardiac hypertrophy, as well. Transgenic mice with cardiac-specific overexpression of CKIP-1 showed resistance to cardiac hypertrophy in response to pressure overload. The results of GST pull-down and coimmunoprecipitation assays showed the interaction between CKIP-1 and histone deacetylase 4 (HDAC4), through which they synergistically inhibited transcriptional activity of myocyte-specific enhancer factor 2C. By directly interacting with the catalytic subunit of phosphatase 2A, CKIP-1 overexpression enhanced the binding of catalytic subunit of phosphatase-2A to HDAC4 and promoted HDAC4 dephosphorylation. Conclusions-CKIP-1 was found to be an inhibitor of cardiac hypertrophy by upregulating the dephosphorylation of HDAC4 through the recruitment of protein phosphatase 2A. These results demonstrated a unique function of CKIP-1, by which it suppresses cardiac hypertrophy through its capacity to regulate HDAC4 dephosphorylation and fetal cardiac genes expression. (Circulation. 2012;126:3028-3040.)Key Words: hypertrophy Ⅲ molecular biology Ⅲ cardiomyopathy Ⅲ heart failure D espite recent treatment advances, heart failure continues to impose a substantial healthcare burden. One of the major risk factors for developing heart failure is preexisting cardiac hypertrophy resulting from pathological stimuli, such as long-standing hypertension or myocardial infarction. 1,2 Among the intracellular signaling pathways involved in the regulation of cardiac hypertrophy, class II histone deacetylases (HDACs) act as signal-responsive repressors by inhibiting the activity of myocyte-specific enhancer factor 2C (MEF2C) in the nucleus. [3][4][5] Dynamic nucleocytoplasmic shuttling has been proposed as one of the most fundamental mechanisms regulating the function of class II HDACs. 4,6,7 Phosphorylation of class II HDACs at specific serine residues after hypertrophic stimulation induces its interaction with 14-3-3, through which the class II HDACs are exported to the cytosol, where they can no longer suppress target transcription factors. 4,8 -10 In the heart, nuclear export of class II HDACs directly elicits activation of myocyte enhancer factor-2 (MEF2), which is a master positive regulator of cardiac hypertrophy. Serine/threonine protein phosphatase 2A (PP2A) could interact with and dephosphorylate HDAC4, thus reinforcing its nuclear accumulation. 11,12 However, little is known about the regulation of HDAC4 dephosphorylation in response to extracellular stimuli leading to car...