Alzheimer's disease (AD) is a neurodegenerative disorder characterized by extracellular senile plaques and intracellular neurofibrillary tangles in the brain. Amyloid-β peptides (Aβ) are considered to play a critical role in the onset and progression of AD. Apigenin (4',5,7-trihydroxyflavone) is a pharmacologically active agent. Even though some evidence suggests that it has potential neuroprotective effects, no preexisting study has reported any therapeutic effects of apigenin in AD models. In the present study, we examined the effects of apigenin on cognitive function in APP/PS1 double transgenic AD mice and explored its mechanism(s) of action. Three-month oral treatment with apigenin rescued learning deficits and relieved memory retention in APP/PS1 mice. Apigenin also showed effects affecting APP processing and preventing Aβ burden due to the down-regulation of BACE1 and β-CTF levels, the relief of Aβ deposition, and the decrease of insoluble Aβ levels. Moreover, apigenin exhibited superoxide anion scavenging effects and improved antioxidative enzyme activity of superoxide dismutase and glutathione peroxidase. In addition, apigenin restored neurotrophic ERK/CREB/BDNF pathway in the cerebral cortex. In conclusion, apigenin may ameliorate AD-associated learning and memory impairment through relieving Aβ burden, suppressing amyloidogenic process, inhibiting oxidative stress, and restoring ERK/CREB/BDNF pathway. Therefore, apigenin appears to represent an alternative medication for the prevention and/or therapy of AD.

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Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) play important roles in initiation and development of human diseases. However, the mechanism of ceRNA regulated by lncRNA in myocardial infarction (MI) remained unclear. In this study, we performed a multi-step computational method to construct dysregulated lncRNA-mRNA networks for MI occurrence (DLMN_MI_OC) and recurrence (DLMN_MI_Re) based on “ceRNA hypothesis”. We systematically integrated lncRNA and mRNA expression profiles and miRNA-target regulatory interactions. The constructed DLMN_MI_OC and DLMN_MI_Re both exhibited biological network characteristics, and functional analysis demonstrated that the networks were specific for MI. Additionally, we identified some lncRNA-mRNA ceRNA modules involved in MI occurrence and recurrence. Finally, two new panel biomarkers defined by four lncRNAs (RP1-239B22.5, AC135048.13, RP11-4O1.2, RP11-285F7.2) from DLMN_MI_OC and three lncRNAs (RP11-363E7.4, CTA-29F11.1, RP5-894A10.6) from DLMN_MI_Re with high classification performance were, respectively, identified in distinguishing controls from patients, and patients with recurrent events from those without recurrent events. This study will provide us new insight into ceRNA-mediated regulatory mechanisms involved in MI occurrence and recurrence, and facilitate the discovery of candidate diagnostic and prognosis biomarkers for MI.

We report the fabrication and characterization of the solar-blind AlGaN avalanche photodiodes grown by metal-organic chemical vapor deposition on c-plane sapphire substrate. The fabricated devices with 100 μm diameter active area exhibit a peak responsivity of 79.8 mA/W at 270 nm and zero bias, corresponding to an external quantum efficiency of 37%. Multiplication gains as high as more than 2500 were obtained in these devices.

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Injection current, and temperature, dependences of the electroluminescence (EL) spectrum from green InGaN/GaN multiple quantum well (MQW)-based light-emitting diodes (LED) grown on a Si substrate, are investigated over a wide range of injection currents (0.5 µA-350 mA) and temperatures (6-350 K). The results show that an increasing temperature can result in the change of injection current-dependent behavior of the EL spectrum in initial current range. That is, with increasing the injection current in the low current range, the emission process of the MQWs is dominated by filling effect of low-energetic localized states at the low temperature range of around 6 K, and by Coulomb screening of the quantum confinement Stark effect followed by a filling effect of the higher levels of the low-energetic localized states at the intermediate temperature range of around 160 K. However, when the temperature is further raised to the higher temperature range of around 350 K, the emission process of the MQWs in the low current range is dominated by carrier-scattering effect followed by non-radiative recombination process. The aforementioned current-dependent behaviors of the EL spectrum are mainly attributed to the strong localized effect of the green LED, as confirmed by the anomalous temperature dependence of the EL spectrum measured at the low injection current of 5 µA. In addition, the injection current dependence of external quantum efficiency at different temperatures shows that, with increasing temperature from 6 to 350 K, in addition to the enhanced non-radiative recombination, electron overflow becomes more significant, especially in the higher temperature range above 300 K.

Two InGaN/GaN multiple quantum well (MQW)-based blue light emitting diodes (LEDs) emitting photons at approximately the same wavelength, with different indium contents and well widths, are prepared, and the temperature-dependences of their electroluminescence (EL) spectra at different fixed injection currents are investigated. The results show that, compared with sample B with its lower indium content and larger well width, sample A with its higher indium content and smaller well width, has a stronger carrier localization effect and higher external quantum efficiency (EQE) at the lower fixed currents; however, upon increasing the injection current, both the localization effect and EQE for sample A decrease at a faster rate. The former is mainly attributed to the deeper potential levels due to the larger indium fluctuations originating from the higher indium content, and to the smaller well width-induced stronger carrier quantum-confine effect (QCE); the latter is mainly attributed to the more significant growing in the electron leakage and/or electron overflow originating from the smaller well width and larger lattice mismatch-induced stronger piezoelectric field, and to the more significant reduction in carrier localization effect originating from the smaller well width-induced smaller density of high-energy localized states.

Objective— Endothelin-1 is a potent vasoconstrictor derived from vascular endothelium. Elevated endothelin-1 levels are observed in a host of cardiovascular pathologies including cardiomyopathy. The epigenetic mechanism responsible for endothelin-1 induction in these pathological processes remains elusive. Approach and Results— We report here that induction of endothelin-1 expression in endothelial cells by angiotensin II (Ang II) was accompanied by the accumulation of histone H3K4 trimethylation, a preeminent histone modification for transcriptional activation, on the endothelin-1 promoter. In the meantime, Ang II stimulated the expression and the occupancy of Suv, Ez, and Trithorax domain 1 (SET1), a mammalian histone H3K4 trimethyltransferase, on the endothelin-1 promoter, both in vitro and in vivo. SET1 was recruited to the endothelin-1 promoter by activating protein 1 (c-Jun/c-Fos) and synergized with activating protein 1 to activate endothelin-1 transcription in response to Ang II treatment. Knockdown of SET1 in endothelial cells blocked Ang II–induced endothelin-1 synthesis and abrogated hypertrophy of cultured cardiomyocyte. Finally, endothelial-specific depletion of SET1 in mice attenuated Ang II–induced pathological hypertrophy and cardiac fibrosis. Conclusions— Our data suggest that SET1 epigenetically activates endothelin-1 transcription in endothelial cells, thereby contributing to Ang II–induced cardiac hypertrophy. As such, screening of small-molecule compound that inhibits SET1 activity will likely offer a new therapeutic solution to the treatment of cardiomyopathy.