Obstructive sleep apnea (OSA) is associated with nonalcoholic fatty liver disease (NAFLD), and causes chronic intermittent hypoxia (CIH) during sleep. Inflammation is associated with the development of metabolic complications induced by CIH. Research suggests that innate immune mechanisms are involved in the pro-inflammatory pathways of liver fibrosis. The purpose of this study was to investigate whether innate immune responses induce liver fibrosis, and to evaluate mechanisms underlying hepatic inflammation related to CIH in a murine diet-induced obesity (DIO) model. Inflammatory and oxidative stress markers, TLR4, MyD88, Toll/interleukin-1-receptor-domain-containing adaptor-inducing interferon-β (TRIF), I-κB, NF-κB, p38 MAPK, c-JNK, and ERK activation, were measured in the serum and liver. As a result, α1(I)-collagen mRNA was significantly higher in DIO mice exposed to CIH than in the control groups. CIH mice exhibited liver fibrosis and significantly higher protein expression of TLR4, MyD88, phosphorylated (phospho-) I-κB, and phospho-ERK1/2 activation in the liver, and higher expression of NF-κB than that in the controls. TRIF, p38 MAPK, and JNK activation did not differ significantly between groups. We conclude that CIH in DIO mice leads to liver fibrosis via TLR4/MyD88/MAPK/NF-kB signaling pathways.

The potential application of an antiangiogenetic laser for the treatment of melasma specially accompanied by pronounced telangiectasia in Asian skin is a possible treatment option.

Summary The ε4 allele of APOE -encoding apolipoprotein (ApoE) is one of the strongest genetic risk factors for Alzheimer’s disease (AD). One of the overarching questions is whether and how this astrocyte-enriched risk factor initiates AD-associated pathology in neurons such as amyloid-β (Aβ) accumulation. Here, we generate neurons and astrocytes from isogenic human induced pluripotent stem cells (hiPSCs) carrying either APOE ε3 or APOE ε4 allele and investigate the effect of astrocytic ApoE4 on neuronal Aβ production. Secretory factors in conditioned media from ApoE4 astrocytes significantly increased amyloid precursor protein (APP) levels and Aβ secretion in neurons. We further found that increased cholesterol secretion from ApoE4 astrocytes was necessary and sufficient to induce the formation of lipid rafts that potentially provide a physical platform for APP localization and facilitate its processing. Our study reveals the contribution of ApoE4 astrocytes to amyloidosis in neurons by expanding lipid rafts and facilitating Aβ production through an oversupply of cholesterol.

This pilot study showed that a 1,550-nm fractional erbium-glass laser might induce hair growth, but more intensive studies are required to clarify the clinical applications of this treatment.

Faint z ∼ 5 quasars with M 1450 ∼ −23 mag are known to be potentially important contributors to the ultraviolet ionizing background in the postreionization era. However, their number density has not been well determined, making it difficult to assess their role in the early ionization of the intergalactic medium (IGM). In this work, we present the updated results of our z ∼ 5 quasar survey using the Infrared Medium-deep Survey (IMS), a near-infrared imaging survey covering an area of 85 deg2. From our spectroscopic observations with the Gemini Multi-Object Spectrograph on the Gemini-South 8 m telescope, we discovered eight new quasars at z ∼ 5 with  −26.1 ≤ M 1450 ≤ −23.3. Combining our IMS faint quasars (M 1450 > −27 mag) with the brighter Sloan Digital Sky Survey quasars (M 1450 < −27 mag), we derive the z ∼ 5 quasar luminosity function (QLF) without any fixed parameters down to the magnitude limit of M 1450 = −23 mag. We find that the faint-end slope of the QLF is very flat ( ), with a characteristic luminosity of mag. The number density of z ∼ 5 quasars from the QLF gives an ionizing emissivity at 912 Å of ϵ 912 = (3.7–7.1) × 1023 erg s−1 Hz−1 Mpc−3 and an ionizing photon density of Mpc−3 s−1. These results imply that quasars are responsible for only 10%–20% (up to 50% even in the extreme case) of the photons required to completely ionize the IGM at z ∼ 5, disfavoring the idea that quasars alone could have ionized the IGM at z ∼ 5.