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Reactive glial cells are hallmarks of brain injury. However, whether these cells contribute to secondary inflammatory pathology and neurological deficits remains poorly understood. Lipocalin-2 (LCN2) has inflammatory and neurotoxic effects in various disease models; however, its pathogenic role in traumatic brain injury remains unknown. The aim of the present study was to investigate the expression of LCN2 and its role in neuroinflammation following brain injury. LCN2 expression was high in the mouse brain after controlled cortical impact (CCI) and photothrombotic stroke (PTS) injury. Brain levels of LCN2 mRNA and protein were also significantly higher in patients with chronic traumatic encephalopathy (CTE) than in normal subjects. RT-PCR and immunofluorescence analyses revealed that astrocytes were the major cellular source of LCN2 in the injured brain. Lcn2 deficiency or intracisternal injection of an LCN2 neutralizing antibody reduced CCI- and PTS-induced brain lesions, behavioral deficits, and neuroinflammation. Mechanistically, in cultured glial cells, recombinant LCN2 protein enhanced scratch injury-induced proinflammatory cytokine gene expression and inhibited Gdnf gene expression, whereas Lcn2 deficiency exerted opposite effects. Together, our results from CTE patients, rodent brain injury models, and cultured glial cells suggest that LCN2 mediates secondary damage response to traumatic and ischemic brain injury by promoting neuroinflammation and suppressing the expression of neurotropic factors.

Dual-frequency unidirectional reflectionlessness is investigated in a quantum system consisting of a two-level and a V-type three-level quantum dots coupled to a plasmonic waveguide based on electromagnetically induced transparency-like effect. The results show that the dual-frequency unidirectional reflectionlessness can be obtained by appropriately adjusting the phase shift between two quantum dots, decay rates of quantum dots, and coupling strengths between quantum dots and plasmonic waveguide. Moreover, the dual-frequency low unidirectional reflection can be manipulated in the wide ranges of decay rates and coupling strengths.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, featuring social communication deficit and repetitive/restricted behaviors as common symptoms. Its prevalence has continuously increased, but, till now, there are no therapeutic approaches to relieve the core symptoms, particularly social deficit. In previous studies, abnormal function of the glutamatergic neural system has been proposed as a critical mediator and therapeutic target of ASD-associated symptoms. Here, we investigated the possible roles of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) in autism symptoms using two well-known autistic animal models, Cntnap2 knockout (KO) mice and in utero valproic acid-exposed ICR (VPA) mice. We found that Cntnap2 KO mice displayed decreased glutamate receptor expression and transmission. Contrarily, VPA mice exhibited increased glutamate receptor expression and transmission. Next, we investigated whether AMPAR modulators (positive-allosteric-modulator for Cntnap2 KO mice and antagonist for VPA mice) can improve autistic symptoms by normalizing the aberrant excitatory transmission in the respective animal models. Interestingly, the AMPAR modulation specifically ameliorated social deficits in both animal models. These results indicated that AMPAR-derived excitatory neural transmission changes can affect normal social behavior. To validate this, we injected an AMPAR agonist or antagonist in control ICR mice and, interestingly, these treatments impaired only the social behavior, without affecting the repetitive and hyperactive behaviors. Collectively, these results provide insight into the role of AMPARs in the underlying pathophysiological mechanisms of ASD, and demonstrate that modulation of AMPAR can be a potential target for the treatment of social behavior deficits associated with ASD.

Six cultivars of kiwifruits grown in Korea, including Actinidia eriantha ‘Bidan’, A. arguta ‘Chiak’, A. arguta ‘Darae No. 2’, A. chinensis ‘Haegeum’, A. chinensis ‘Haehyang’, and A. arguta × A. deliciosa ‘Mansoo’, were harvested at various maturity stages to test whether kiwifruit maturity has an influence on antioxidant capacity or total phenolic and flavonoid contents. Kiwifruit extracts were isolated using absolute methanol and then 80% (v·v-1) aqueous methanol during homogenization. ‘Bidan’, collected at the second harvest stage, contained the greatest amount of total phenolics (775.3 mg gallic acid equivalents·100 g-1 fresh weight) and had the highest antioxidant capacity [816.5, 633.2, and 2,662.7 mg vitamin C equivalents·100 g-1 fresh weight for 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) scavenging, 1,1-diphenyl-2-picrylhydrazyl scavenging, and oxygen radical absorbance capacity assays, respectively] among cultivars tested, while ‘Haehyang’, collected at the first harvest, contained the greatest amount of total flavonoids (13.1 mg catechin equivalents·100 g-1 fresh weight). Kiwifruit cultivar and genotype influenced antioxidant capacity, as well as total phenolic and flavonoid contents. No trend, however, was observed in total phenolic and flavonoid contents, and in the antioxidant capacity with respect to maturity stage. Antioxidant capacity had a higher linear correlation coefficient with total phenolic contents than with total flavonoid contents. The results above suggest that kiwifruits at various maturity stages are a valuable source of phenolics and antioxidants for industrial application and consumer health benefit.

A marine bacterium, NMD7(T), was isolated from seawater of the East China Sea. The cells were found to be aerobic, Gram-stain negative, non-motile rods. Growth of strain NMD7(T) could be observed in the medium without Na(+). Flexirubin-type pigments were observed to be produced. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain NMD7(T) is an authentic member of the Cytophaga-Flavobacterium-Bacteroides phylum, forming a monophyletic clade as retrieved in neighbor-joining, maximum-likelihood and maximum-parsimony phylogenetic trees, and is closely related to Formosa spongicola A2(T) (96.0 %). The predominant respiratory quinone was determined to be MK-6. Major cellular fatty acids were identified as iso-C15:0, iso-C15:1 G and iso-C17:0 3-OH. The main polar lipids were found to consist of phosphatidylethanolamine, one aminophospholipid, three aminolipids and five unidentified lipids. Based on phenotypic, chemotaxonomic and phylogenetic characteristics, it is proposed that strain NMD7(T) be classified as representing a new genus, Feifantangia gen. nov. and a new species, Feifantangia zhejiangensis sp. nov. The type strain is NMD7(T) (=KCTC 42445T =MCCC 1K00458T).

We intended to elucidate the mechanism of the molecular weight (Mw) threshold (i.e., 200 +/- 50) for appreciable hepatobiliary excretion of quaternary ammonium compounds (QACs) in rats.We measured the effect of ion-pair complexation of QACs with taurodeoxycholate (TDC), an endogenous anionic bile salt, on the apparent partition coefficients (APC) of QACs between n-octanol and phosphate buffer, and the inhibition of organic cation transporter1 (OCT1)- and P-glycoprotein (P-gp)-mediated transport of representative substrates.By measuring the APC, we demonstrated that there is a Mw threshold of 200 +/- 50 in the ion-pair complexation of QACs with an endogenous bile salt, TDC. We also demonstrated, by measuring the inhibition of relevant transports, that a Mw threshold of 200 +/- 50 exists for the binding of QACs to canalicular P-gp, but not for sinusoidal OCT1. The Mw threshold values for ion-pair formation and P-gp binding were identical and consistent with the reported Mw threshold value for appreciable biliary excretion of QACs in rats.Mw-dependent binding of QACs to canalicular P-gp contributes in part to the mechanism of the Mw threshold of 200 +/- 50. The formation of lipophilic ion-pair complexes with bile salts, followed by stronger binding to canalicular P-gp, appears to accelerate biliary excretion of QACs with a high Mw.

The antiplatelet effects of a novel guanidine derivative, KR-32570 ([5-(2-methoxy-5-chlorophenyl) furan-2-ylcarbonyl]guanidine), were investigated with an emphasis on the mechanisms underlying its inhibition of collagen-induced platelet aggregation. KR-32570 significantly inhibited the aggregation of washed rabbit platelets induced by collagen (10 microg/mL), thrombin (0.05 U/mL), arachidonic acid (100 microM), a thromboxane (TX) A2 mimetic agent U46619 (9,11-dideoxy-9,11-methanoepoxy-prostaglandin F2, 1 microM) and a Ca2+ ATPase inhibitor thapsigargin (0.5 microM) (IC50 values: 13.8 +/- 1.8, 26.3 +/- 1.2, 8.5 +/- 0.9, 4.3 +/- 1.7 and 49.8 +/- 1.4 microM, respectively). KR-32570 inhibited the collagen-induced liberation of [3H]arachidonic acid from the platelets in a concentration dependent manner with complete inhibition being observed at 50 microM. The TXA2 synthase assay showed that KR-32570 also inhibited the conversion of the substrate PGH2 to TXB2 at all concentrations. Furthermore, KR-32570 significantly inhibited the [Ca2+]i mobilization induced by collagen at 50 microM, which is the concentration that completely inhibits platelet aggregation. KR-32570 also decreased the level of collagen (10 microg/mL)-induced secretion of serotonin from the dense-granule contents of platelets, and inhibited the NHE-1-mediated rabbit platelet swelling induced by intracellular acidification. These results suggest that the antiplatelet activity of KR-32570 against collagen-induced platelet aggregation is mediated mainly by inhibiting the release of arachidonic acid, TXA2 synthase, the mobilization of cytosolic Ca2+ and NHE-1.

The abnormal proliferation of aortic vascular smooth muscle cells (VSMCs) plays a central role in the pathogenesis of atherosclerosis and restenosis after angioplasty and possibly also in the development of hypertension. The present study was designed to examine the inhibitory effects and the mechanism of luteolin 7-glucoside (L7G) on the platelet-derived growth factor (PDGF)-BB-induced proliferation of VSMCs. L7G significantly inhibited the PDGF-BB-induced proliferation and the DNA synthesis of the VSMCs in a concentration-dependent manner. Pre-incubation of the VSMCs with L7G significantly inhibited the PDGF-BB-induced extracellular signal-regulated kinase 1/2 (ERK1/2), Akt and the phospholipase C (PLC)-gamma1 activation. However, L7G had almost no affect on the phosphorylation of PDGF-beta receptor tyrosine kinase, which was induced by PDGF-BB. These results suggest that L7G inhibits the PDGF-BB-induced proliferation of VSMCs via the blocking of PLC-gamma1, Akt, and ERK1/2 phosphorylation.

The effect of dc electric field upon the spatial variation of microstructure during the sintering of BaTiO3 in a N2 atmosphere was investigated. When BaTiO3 specimens were heat-treated in a N2 atmosphere at 1350 ∘C under an electric field, grain growth was enhanced at the positive-biased region for a 0.5 mol% Nb-doped specimen, while it was promoted at the negative-biased region for a 3.0 mol% Nb-doped specimen. The grain growth behavior at both the positive and negative-biased region was similar for a 1.0 mol% Nb-doped specimen. The results have been explained mainly in terms of the boundary potential, which varies with the donor concentration, and the oxygen partial pressure of the surrounding atmosphere.

Falcarindiol (FAD) is a natural polyyne with various beneficial biological activities. We show here that FAD preferentially kills colon cancer cells but not normal colon epithelial cells. Furthermore, FAD inhibits tumor growth in a xenograft tumor model and exhibits strong synergistic killing of cancer cells with 5-fluorouracil, an approved cancer chemotherapeutic drug. We demonstrate that FAD-induced cell death is mediated by induction of endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR). Decreasing the level of ER stress, either by overexpressing the ER chaperone protein glucose-regulated protein 78 (GRP78) or by knockout of components of the UPR pathway, reduces FAD-induced apoptosis. In contrast, increasing the level of ER stress by knocking down GRP78 potentiates FAD-induced apoptosis. Finally, FAD-induced ER stress and apoptosis is correlated with the accumulation of ubiquitinated proteins, suggesting that FAD functions at least in part by interfering with proteasome function, leading to the accumulation of unfolded protein and induction of ER stress. Consistent with this, inhibition of protein synthesis by cycloheximide significantly decreases the accumulation of ubiquitinated proteins and blocks FAD-induced ER stress and cell death. Taken together, our study shows that FAD is a potential new anticancer agent that exerts its activity through inducing ER stress and apoptosis.