Ultra‐Narrowband Blue Multi‐Resonance Thermally Activated Delayed Fluorescence Materials

Ultra-narrowband blue multi-resonance-induced thermally activated delayed fluorescence (MR-TADF) materials (V-DABNA and V-DABNA-F), consisting of three DABNA subunits possessing phenyl or 2, 6-difluorophenyl substituents on the peripheral nitrogen atoms are synthesized by one-shot triple borylation. Benefiting from the inductive effect of fluorine atoms, the emission maximum of V-DABNA-F (464 nm) is blueshifted from that of the parent V-DABNA (481 nm), while maintaining a small full width at half maximum (FWHM, 16 nm) and a high rate constant for reverse intersystem crossing (6.5 × 10⁵ s⁻¹). The organic light-emitting diodes (OLEDs) using V-DABNA and V-DABNA-F as emitters are fabricated by vapor deposition and exhibit blue emission at 483 and 468 nm with small FWHMs of 17 and 15 nm, corresponding to Commission Internationale d’Éclairage coordinates of (0.09, 0.27) and (0.12, 0.10), respectively. Both devices achieve high external quantum efficiencies of 26.2% and 26.6% at the maximum with minimum efficiency roll-offs of 0.9% and 3.2%, respectively, even at 1000 cd m⁻², which are record-setting values for blue MR-TADF OLEDs

Angiotensin II and III suppress food intake via angiotensin AT2 receptor and prostaglandin EP4 receptor in mice

AbstractIntracerebroventricularly administered angiotensin (Ang) II and III dose-dependently suppressed food intake in mice and their anorexigenic activities were inhibited by AT2 receptor-selective antagonist. Ang II did not suppress food intake in AT2 receptor-knockout mice, while it did significantly in wild-type and AT1 receptor-knockout mice. The suppression of food intake in AT1 receptor-knockout mice was smaller than that in wild-type. The anorexigenic activities of Ang II and III were also blocked by a selective antagonist for prostaglandin EP4 receptor. Taken together, centrally administered Ang II and III may decrease food intake through AT2 receptor with partial involvement of AT1 receptor, followed by EP4 receptor activation, which is a novel pathway regulating food intake

Serum Fragmented Cytokeratin 18 Levels Reflect the Histologic Activity Score of Nonalcoholic Fatty Liver Disease More Accurately Than Serum Alanine Aminotransferase Levels

Background and Goals: Reliable noninvasive biomarkers to assess the histologic activity of nonalcoholic fatty liver disease (NAFLD) have not been established. As the frequency of Mallory bodies is known to be closely associated with the disease severity, we hypothesized that serum levels of Mallory body-related proteins were correlated with NAFLD histologic activity and evaluated this possibility. Study: Serum levels of total and fragmented cytokeratin (CK) 18, heat shock protein (Hsp) 70, Hsp90 alpha, ubiquitin + 1, and p38 alpha at the time of liver biopsy were measured in 118 NAFLD patients and their association with histologic findings and NAFLD histologic activity score (NAS) was investigated. Results: Serum levels of both forms of CK18 and Hsp90 alpha were markedly higher in patients having nonalcoholic steatohepatitis (NASH) compared with non-NASH ones. Both forms of CK18 significantly correlated with degree of steatosis, lobular inflammation, and ballooning, and showed stronger positive correlations with NAS than serum aspartate and alanine aminotransferase (AST and ALT). Multiple regression analysis further revealed that fragmented CK18 and AST were effective predictors of NAS, with the former being the more definitive of the two (P < 0.001 vs. 0.005). In 20 NAFLD patients who received a follow-up biopsy, changes in fragmented CK18 levels, but not AST or ALT levels, closely paralleled those in NAS. Conclusions: These results establish the usefulness of fragmented CK18 measurement for assessing and monitoring the histologic activity of NAFLD.ArticleJOURNAL OF CLINICAL GASTROENTEROLOGY. 44(6):440-447 (2010)journal articl

Guideline for Hereditary Angioedema (HAE) 2010 by the Japanese Association for Complement Research - Secondary Publication

ABSTRACTThis guideline was provided by the Japanese Association for Complement Research targeting clinicians for making an accurate diagnosis of hereditary angioedema (HAE), and for prompt treatment of the HAE patient in Japan. This is a 2010 year version and will be updated according to any pertinent medical advancements

Histidine Hydrogen-Deuterium Exchange Mass Spectrometry for Probing the Microenvironment of Histidine Residues in Dihydrofolate Reductase

Histidine Hydrogen-Deuterium Exchange Mass Spectrometry (His-HDX-MS) determines the HDX rates at the imidazole C(2)-hydrogen of histidine residues. This method provides not only the HDX rates but also the pK(a) values of histidine imidazole rings. His-HDX-MS was used to probe the microenvironment of histidine residues of E. coli dihydrofolate reductase (DHFR), an enzyme proposed to undergo multiple conformational changes during catalysis.Using His-HDX-MS, the pK(a) values and the half-lives (t(1/2)) of HDX reactions of five histidine residues of apo-DHFR, DHFR in complex with methotrexate (DHFR-MTX), DHFR in complex with MTX and NADPH (DHFR-MTX-NADPH), and DHFR in complex with folate and NADP+ (DHFR-folate-NADP+) were determined. The results showed that the two parameters (pK(a) and t(1/2)) are sensitive to the changes of the microenvironment around the histidine residues. Although four of the five histidine residues are located far from the active site, ligand binding affected their pK(a), t(1/2) or both. This is consistent with previous observations of ligand binding-induced distal conformational changes on DHFR. Most of the observed pK(a) and t(1/2) changes could be rationalized using the X-ray structures of apo-DHFR, DHFR-MTX-NADPH, and DHFR-folate-NADP+. The availability of the neutron diffraction structure of DHFR-MTX enabled us to compare the protonation states of histidine imidazole rings.Our results demonstrate the usefulness of His-HDX-MS in probing the microenvironments of histidine residues within proteins