Triggering receptor expressed on myeloid cells 2 (TREM2) is known to be involved in the anti-inflammatory response and osteoclast development. However, the role of TREM2 in adipogenesis or obesity ...has not yet been defined. The effect of TREM2 on adipogenesis and obesity was investigated in TREM2 transgenic (TG) mice on a high-fat diet (HFD). To block TREM2 signaling, a neutralizing fusion protein specific for TREM2 (TREM2-Ig) was used. TG mice were much more obese than wild-type mice after feeding with an HFD, independent of the quantity of food intake. These HFD-fed TG mice manifested adipocyte hypertrophy, glucose and insulin resistance, and hepatic steatosis. The expression of adipogenic regulator genes, such as peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α, was markedly increased in HFD-fed TG mice. Additionally, HFD-fed TG mice exhibited decreased Wnt10b expression and increased GSK-3β (glycogen synthase kinase-3β)-mediated β-catenin phosphorylation. In contrast, the blockade of TREM2 signaling using TREM2-Ig resulted in the inhibition of adipocyte differentiation in vitro and a reduction in body weight in vivo by downregulating the expression of adipogenic regulators. Our data demonstrate that TREM2 promotes adipogenesis and diet-induced obesity by upregulating adipogenic regulators in conjunction with inhibiting the Wnt10b/β-catenin signaling pathway.
Understanding the dielectric breakdown voltage of coatings inside plasma equipment is important for improving the reliability of semiconductor processes. Measurements of breakdown voltage can vary ...owing to many factors, but the measurement itself has not yet been studied systematically. In this paper, we designed two type tools to measure the breakdown voltage. We decided to use a one-electrode method with a 20 mm2 electrode and chose to apply the voltage at 15 V/s to minimise measurement error. We used these tools to systematically evaluate the breakdown voltages of different coatings deposited using various methods. Coatings deposited using suspension plasma spraying had a higher breakdown voltage than coatings deposited using atmospheric plasma spraying, because suspension plasma spraying films can be deposited at high density, minimizing electrical stress. As the fluorine content in the coating increased, it is widely used for material of excellent etching resistance in fluorine plasma etching. However, dielectric breakdown voltage decreased with increasing fluorine content, which could affect process reliability.
The histamine H4 receptor (H4R), a member of the G-protein coupled receptor family, has been considered as a potential therapeutic target for treating atopic dermatitis (AD). A large number of H4R ...antagonists have been disclosed, but no efficient agents controlling both pruritus and inflammation in AD have been developed yet. Here, we have discovered a novel class of orally available H4R antagonists showing strong anti-itching and anti-inflammation activity as well as excellent selectivity against off-targets. A pharmacophore-based virtual screening system constructed in-house successfully identified initial hit compound 9, and the subsequent homology model-guided optimization efficiently led us to discover pyrido2,3-etetrazolo1,5-apyrazine analogue 48 as a novel chemotype of a potent and highly selective H4R antagonist. Importantly, orally administered compound 48 exhibits remarkable efficacy on antipruritus and anti-inflammation with a favorable pharmacokinetic (PK) profile in several mouse models of AD. Thus, these data strongly suggest that our compound 48 is a promising clinical candidate for treatment of AD.
A reliability assessment was performed to predict the lifetime of an anodic aluminum oxide film coated on equipment used in plasma etching processes. An anodic aluminum-oxide-coated part was exposed ...to an argon plasma, and its weight loss was monitored. This plasma test was conducted at four different pressure levels (125, 150, 200, and 250 mTorr). The failure distribution data obtained for each pressure level were found to indicate the same failure mechanism. Subsequently, an inverse power model was the best fit model for describing the relationship between the applied pressure and the lifetime of a part. The failure of the anodic aluminum oxide film caused by long-term exposure to plasma is, thus, shown to be closely linked to a decrease in the weight of the film.
Abstract Bacterial β-(1,3)-glucan has more advantages in terms of cost, yield and efficiency than that derived from mushrooms, plants, yeasts and fungi. We have previously developed a novel and ...high-yield β-(1,3)-glucan produced by Agrobacterium sp. R259. This study aimed to elucidate the functional mechanism and therapeutic efficacy of bacterial β-(1,3)-glucan in dextran sulfate sodium (DSS)-induced inflammatory bowel disease (IBD).Mice were orally pretreated with bacterial β-(1,3)-glucan at daily doses of 2.5 or 5 mg/kg for 2 weeks. After 6 days of DSS treatment, clinical assessment of IBD severity and expression of pro-inflammatory cytokines were evaluated. In vivo cell proliferation was examined by immunohistochemistry using Ki-67 and ER-TR7 antibodies. The frequency of regulatory T cells (Tregs) was analyzed by flow cytometry. Natural killer (NK) activity and IgA level were evaluated using NK cytotoxicity assay and ELISA.The deterioration of body weight gain, colonic architecture, disease score and histological score was recovered in DSS-induced IBD mice when pretreated with bacterial β-(1,3)-glucan. The recruitment of macrophages and the gene expression of proinflammatory cytokines, such as IL-1β, IL-6 and IL-17A/F, were markedly decreased in the colon of β-(1,3)-glucan-pretreated mice. β-(1,3)-Glucan induced the recovery of Tregs in terms of their frequency in DSS-induced IBD mice. Intriguingly, β-(1,3)-glucan reversed the functional defects of NK cells and excessive IgA production in DSS-induced IBD mice.We conclude that bacterial β-(1,3)-glucan prevented the progression of DSS-induced IBD by recovering the reduction of Tregs, functional defect of NK cells and excessive IgA production.
A phytochemical investigation of the whole plants of Adonis multiflora Nishikawa & Koki Ito. resulted in the isolation and identification of two new cardenolides--adonioside A (1) and adonioside B ...(6)--as well as four known cardenolides: tupichinolide (2) oleandrine (3), cryptostigmin II (4), and cymarin (5). Their structures were elucidated on the basis of NMR, MS, and IR spectroscopic analyses. Compounds 1, 2, 5, and 6 showed significant cytotoxicity against six human cancer cell lines (HCT-116, HepG2, HeLa, SK-OV-3, and SK-MEL-5, and SK-BR-3).
We investigated the heat loss of the metal wire to the gases in the free molecular region, whose pressure is below 10−3 Pa. The heat transfer characteristics at the interface between the metal ...surface and the gases are only accessible when the conductional heat loss along the wire is comparable to or less than 100 nW/K. Unfortunately, such an infinitesimal heat flow is not controllable from typical metal wire. For this reason, we have synthesized a new material, metal-carbon hybrid wire (MCHW). In the free molecular flow region, the resistance of MCHW is inversely proportional to the pressure (P), R∼1/P, regardless of gas species, which contradicts the gas-dependent heat loss theory. At a pressure <1 × 10−4 Pa, we observe a deviation from reciprocal linearity attributed to a growing radiational heat loss. Our results realize the thermal conductive sensing of the pressure below 10−5 Pa, which has been unprecedented.
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Accelerated Degradation Test (ADT) is a test conducted under extreme stress conditions to accelerate degradation. In the plasma etching process, the life time of the anodic film deteriorates due to ...fatigue cracking, wear, and erosion arising from ion bombardment and radical reaction. However, ADT has yet to be studied in relation to plasma stress. A fault tree analysis are performed on plasma corrosion. The failure criterion of the corrosion is an increase in number of contamination particles. Since contamination particles are produced by an increase in by-products caused by corrosion, they can also be traced to the reduced mass of the oxide film. CF4, Ar, and O2 gas are used for the plasma corrosion test, and the acceleration factors are set as the pressure of the gases and the input power for plasma. This study proposes an efficient ADT design for the reliability analysis of anodic films under the plasma etching process.
In this study, we analyzed the photocurrent generation mechanism (PGM) of a heterostructure comprising n-type ReS2 and p-type two-dimensional (2D) Te. The PGM of the integrated structure was not ...solely driven by the photovoltaic effect, which is attributed to the built-in potential invoked by the bandgap mismatch and Fermi level difference. The PGM was manipulated and dramatically varied as the source-drain bias (Vds) and backgate bias (Vgs) were modulated. Under the control of Vds and Vgs, the dominant photocurrent generation in our heterostructure was attributed to photovoltaic (PV), photothermoelectric (PTE) effects, and their combinations PV+PTE. In addition, the photocurrent hotspot varied depending on the bias conditions. Our results provide new insights into the possibility to adapt the PGM of a conventional photovoltaic system, which can contribute to the development of multimodal detection of the incident light, extend the spectral detection range, and facilitate the design of photodetectors and energy-harvesting devices with enhanced performance.
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•New multimodal approach in interpreting photocurrent generation mechanisms.•Drain-source and backgate bias controlled photocurrent generation mechanisms.•Adaptive control of photovoltaic (PV), photothermoelectric (PTE), and PV+PTE in ReS2-2D Te heterostructure.•New insight into designs of unprecedented optical sensors, photodetectors, and energy-harvesting devices.
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