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Photochromic 1,2-bis(5-carboxy-3-methyl-2-thienyl)hexafluorocyclopentene and its dimethyl ester incorporated in human serum albumin (HSA) showed highly enantioselective photochromic ring-closing reactions upon 366 nm light irradiation. The absolute stereochemistry of the major ring-closed form of the dicarboxylic acid at the newly formed sp3 carbon atoms was determined to be (S,S) by the process of docking simulation of the diarylethene molecule and HSA followed by molecular dynamics calculations and comparison of the measured and calculated CD spectra. Esterification of the major closed form of the diacid gave the minor closed form of the diester. The absolute stereochemistry of the major diester was thus determined to be (R,R).

The design and control of self-assembling biomaterials have significantly attracted attention over the last decades because of their broad ranges of applications. Here, we introduce the self-assemb...

Background and Objectives Topiroxostat, a selective xanthine oxidoreductase inhibitor, is used for the management of hyperuricemic patients with or without gout in Japan. Accumulating evidence has demonstrated the efficacy of topiroxostat for the treatment of hyperuricemia with or without gout. However, the safety and efficacy of topiroxostat in the clinical setting remain unclear, and there is little large-scale clinical evidence. We conducted a post-marketing observational study over 54 weeks. Patients and Methods Patients were centrally enrolled, and case report forms of 4491 patients were collected between April 2014 and March 2019 from 825 medical sites. Results Overall, 4329 patients were assessed for safety and 4253 patients for effectiveness. The overall incidence of adverse drug reactions was 6.95%, and the incidence rates of adverse drug reactions of gouty arthritis, hepatic dysfunction, and skin disorders, which are of special interest in this study, were 0.79%, 1.73%, and 0.95%, respectively. No case of serious gouty arthritis was observed. Serum urate levels decreased stably over time and showed a significant reduction rate at 54 weeks (21.19% ± 22.07%) and on the final visit (19.91% ± 23.35%) compared to the baseline. The rates for subjects who achieved serum uric acid levels ≤ 6.0 mg/dL at 18 and 54 weeks after administration were 43.80% and 48.28%, respectively. Conclusions This study suggests that there is no particular concern about adverse drug reactions or the efficacy of topiroxostat for hyperuricemic patients with or without gout in a post-marketing setting in Japan. Electronic supplementary material The online version of this article (10.1007/s40261-020-00941-3) contains supplementary material, which is available to authorized users.

Significance X-ray crystallographic analyses of mitochondrial cytochrome c oxidase (CcO) have been based on its dimeric form. Recent cryo-electron microscopy structures revealed that CcO exists in its monomeric form in the respiratory supercomplex. This study, using amphipol-stabilized CcO, shows that the activity of monomer is higher than that of the dimer. The crystal structure of monomer determined here shows that the local structure of one of the proton transfer pathways differs from that in the dimer. The crystal structure also shows that cardiolipins are located at the interface region in the supercomplex. Taken together, these results suggest that CcO in the monomeric state, dimeric state, and supercomplex state depending on cardiolipins are involved in regulation of respiratory electron transport., Cytochrome c oxidase (CcO), a membrane enzyme in the respiratory chain, catalyzes oxygen reduction by coupling electron and proton transfer through the enzyme with a proton pump across the membrane. In all crystals reported to date, bovine CcO exists as a dimer with the same intermonomer contacts, whereas CcOs and related enzymes from prokaryotes exist as monomers. Recent structural analyses of the mitochondrial respiratory supercomplex revealed that CcO monomer associates with complex I and complex III, indicating that the monomeric state is functionally important. In this study, we prepared monomeric and dimeric bovine CcO, stabilized using amphipol, and showed that the monomer had high activity. In addition, using a newly synthesized detergent, we determined the oxidized and reduced structures of monomer with resolutions of 1.85 and 1.95 Å, respectively. Structural comparison of the monomer and dimer revealed that a hydrogen bond network of water molecules is formed at the entry surface of the proton transfer pathway, termed the K-pathway, in monomeric CcO, whereas this network is altered in dimeric CcO. Based on these results, we propose that the monomer is the activated form, whereas the dimer can be regarded as a physiological standby form in the mitochondrial membrane. We also determined phospholipid structures based on electron density together with the anomalous scattering effect of phosphorus atoms. Two cardiolipins are found at the interface region of the supercomplex. We discuss formation of the monomeric CcO, dimeric CcO, and supercomplex, as well as their role in regulation of CcO activity.

Ohkubo Y., Nakagawa T., Endo K., et al. "Influence of air contamination during heat-assisted plasma treatment on adhesion properties of polytetrafluoroethylene (PTFE)", RSC Advances, 9(40), 22900, 2019. https://doi.org/10.1039/c9ra01789e., Plasma surface treatment is typically not effective on fluoropolymers containing polytetrafluoroethylene (PTFE). It is reported that heat-assisted plasma (HAP) treatment at high temperatures (above 200 °C) under atmospheric pressure helium (He) plasma improves the adhesion properties of PTFE. In this study, we investigated the influence of the air concentration during HAP treatment on the adhesion properties of PTFE. Air concentration was controlled via ambient air inflow amount, in other words, base pressure. The PTFE samples HAP-treated in different air concentrations were thermally compressed with an unvulcanized isobutylene-isoprene rubber (IIR). Then, the PTFE/IIR adhesion strength was measured via T-peel test. We show that, when PTFE was HAP-treated in 0.01% air, its PTFE/IIR adhesion strength was over 2 N mm-1; the IIR underwent cohesion failure. However, the PTFE/IIR adhesion strength drastically decreased in the presence of air contamination. The relationships between air concentration during HAP treatment, adhesion properties of PTFE, surface chemical composition, surface morphology, and surface hardness were investigated and discussed.

A thermoresponsive fluorophore based on a photochromic diarylethene possessing donor and acceptor moieties in close proximity to each other has been synthesized. The fluorophore exhibits dual fluorescence, where photoresponsive turn-off switching as well as a thermoresponsive relative intensity change are observed.

In this review, the chirality and stereoselectivity in photochromic reactions are broadly discussed. Stereoselectivity is categorized into the two main areas of enantioselectivity and diastereoselectivity. Enantioselective photochromism was discussed according to the methods of generating chirality, that is: (1) optical resolution of chiral and racemic compounds, (2) spontaneous separation of racemic compounds during crystallization, (3) chiral template-assisted photochromic reactions to preferentially generate an enantiomer or cause chirality-based events, and (4) the generation of a non-racemic mixture of the photoisomers by irradiation of circularly polarized light to the racemic starting photoisomer. Diastereoselective photochromism was discussed for each family of photochromic reactions, namely, (1) fulgides, (2) diarylethenes, (3) spiro-compounds, (4) azobenzenes, and (5) organometallic complexes. Chirality-related reactions in overcrowded alkenes are discussed in a separate chapter. These include: (1) the discovery of the light-driven molecular motor, (2) the first generation of light-driven molecular motors with unidirectional rotation, which have two chiral carbon atoms in a molecule, (3) the second generation of light-driven molecular motors with unidirectional rotation, which have a single chiral carbon atom in a molecule. Finally, two distinctive novel photochromic systems are introduced in which the reactions proceed stereoselectively, although their enantio- or diastereoselectivity during photochromic reactions have yet to be examined.

A spiro-functionalized photochromic diarylethene derivative showed multi-colour fluorescence modulation with a photon-quantitative photocyclization reactivity and high thermal stability.

We previously reported a cell-based toxicity assay using sandwich-cultured hepatocytes in combination with a titrated amount of human bile acid (BA) species. In this assay, test compound-induced inhibition of BA efflux from sandwich-cultured hepatocytes leads to BA-dependent cell toxicity (BAtox, i.e., cell death due to the accumulation of BAs). Using this assay, we investigated whether 1-aminobenzotriazole (1-ABT; a nonselective cytochrome P450 inhibitor) enhanced or suppressed test compound-induced BAtox. There was a tendency that BAtox of many compounds was enhanced by 1-ABT in human hepatocytes; in contrast, such a tendency was not observed in rat hepatocytes. In particular, 1-ABT tended to enhance BAtox of several compounds (clopidogrel, ticlopidine, everolimus, etc.) in human, whereas 1-ABT tended to enhance BAtox of only ticlopidine in rat. These results indicate that this system can be used to evaluate BAtox while taking into account drug metabolism and the existence of an interspecies difference in the effect of 1-ABT treatment on BAtox.

Troglitazone and pioglitazone were developed as thiazolidinedione-type antidiabetes drugs, but only troglitazone was withdrawn from the markets due to severe liver injury. As both troglitazone and its sulfate metabolite are strong inhibitors of the bile salt export pump (BSEP), troglitazone-induced bile acid (BA) retention is thought to be one of the underlying mechanisms of liver injury. However, pioglitazone is also a strong BSEP inhibitor, indicating other mechanisms may also be involved in troglitazone-induced BA retention. Although retention of hydrophobic BAs (eg, chenodeoxycholic acid [CDCA]: a nonamidated BA) is known to cause hepatocyte injury, little is known about the hepatic conversion of nonamidated, hydrophobic BA species into less toxic hydrophilic BAs (eg, glycochenodeoxycholic acid: amidated BA) as a mechanism of drug-induced liver injury. In this study, we, therefore, investigated the effects of troglitazone and pioglitazone on BA amidation and the role of amidated BAs in troglitazone-associated BA-mediated hepatotoxicity. We also evaluated the intracellular BA composition of human hepatocytes treated with nonamidated BA species (CDCA or deoxycholic acid [DCA]) in the presence of troglitazone or pioglitazone. Amidation of CDCA and DCA was significantly inhibited by troglitazone (IC50: 5 and 3 µmol/l, respectively), but not pioglitazone. Moreover, treatment with troglitazone led to the retention of CDCA and DCA and decrease of glycine-amidation in hepatocytes. From these results, we suggest that troglitazone-induced liver injury might be caused by the accumulation of nonamidated BAs in hepatocytes due to inhibition of BA amidation.

This study aimed to investigate the applicability of the Oie-Tozer model to predict human distribution volume (Vd) in the central compartment (V1 ), Vd at steady state (Vdss ), and Vd at beta phase (Vdβ ) based on animal Vd. Twenty compounds that have a human V1 /Vdss of 0.053-0.66 were selected from the literature. After intravenous administration of the compounds at 0.1 mg/kg to rats, dogs, and monkeys, plasma concentrations were determined, and pharmacokinetic parameters were obtained by one/two-compartmental analyses. The human V1 , Vdss , and Vdβ were predicted from animal Vd using the Oie-Tozer model, and the predictability was compared with that using proportionality and simple allometry. The Oie-Tozer model was the most reliable method for the overall prediction of Vd and applicable for accurately predicting human V1 , Vdss , and Vdβ (89%, 85%, and 68% of the compounds within a 3-fold error, respectively) when data of monkey for V1 and data of three animal species for Vdss and Vdβ were used. Additionally, the predicted human Vd with the two-compartment model was applicable for predicting pharmacokinetic profiles/parameters in humans after intravenous administration of 18 compounds [except for valproic acid (monophasic elimination profile) and chlorpromazine (deviation: Vdss < V1 )]. The prediction was more accurate than that using the predicted Vdss with the one-compartment model (e.g., underestimation of maximum plasma concentrations: 2 vs 8 compounds within a 3-fold error, respectively). In summary, the Oie-Tozer model was applicable for predicting human V1 , Vdss , and Vdβ , and their predicted Vd with the two-compartment model can lead to accurate pharmacokinetic prediction of compounds that show biphasic elimination.

An on/off switching for charge-transfer interactions between the side chains of a diarylethene based on photochromic reactions has been proved by the disappearance and appearance of an additional fluorescence band.

The metabolism and pharmacokinetics of DSP-0565 [2-(2'-fluoro[1,1'-biphenyl]-2-yl)acetamide], an antiepileptic drug candidate, was investigated in rats, dogs, and humans. In human hepatocytes, [14 C]DSP-0565 was primarily metabolized via amide bond hydrolysis to (2'-fluoro[1,1'-biphenyl]-2-yl)acetic acid (M8), while in rat and dog hepatocytes, it was primarily metabolized via both hydrolysis to M8 and hydroxylation at the benzene ring or the benzyl site to oxidized metabolites. After single oral administration of [14 C]DSP-0565 to rats and dogs, the major radioactivity fraction was recovered in the urine (71-72% of dose) with a much smaller fraction recovered in feces (23-25% of dose). As primary metabolites in their excreta, M8, oxidized metabolites, and glucuronide of DSP-0565 were detected. The contribution of metabolic pathways was estimated from metabolite profiles in their excreta: the major metabolic pathway was oxidation (57-62%) and the next highest was the hydrolysis pathway (23-33%). These results suggest that there are marked species differences in the metabolic pathways of DSP-0565 between humans and animals. Finally, DSP-0565 human oral clearance (CL/F) was predicted using in vitro-in vivo extrapolation (IVIVE) with/without animal scaling factors (SF, in vivo intrinsic clearance/in vitro intrinsic clearance). The SF improved the underestimation of IVIVE (fold error = 0.22), but the prediction was overestimated (fold error = 2.4-3.3). In contrast, the use of SF for hydrolysis pathway was the most accurate for the prediction (fold error = 1.0-1.4). Our findings suggest that understanding of species differences in metabolic pathways between humans and animals is important for predicting human metabolic clearance when using animal SF.

Amodiaquine (AQ) treatment is associated with a high incidence of idiosyncratic drug-induced liver injury (IDILI) and agranulocytosis. Evidence suggests that AQ-induced IDILI is immune mediated. A significant impediment to mechanistic studies of IDILI is the lack of valid animal models. This study reports the first animal model of IDILI with characteristics similar to mild IDILI in humans. Treatment of female C57BL/6 mice with AQ led to liver injury with delayed onset, which resolved despite continued treatment. Covalent binding of AQ was detected in the liver, which was greater in female than in male mice, and higher in the liver than in other organs. Covalent binding in the liver was maximal by Day 3, which did not explain the delayed onset of alanine aminotransferase (ALT) elevation. However, coincident with the elevated serum ALT, infiltration of liver and splenic mononuclear cells and activation of CD8 T-cells within the liver were identified. By Week 7, when ALT levels had returned close to normal, down-regulation of several inflammatory cytokines and up-regulation of PD-1 on T-cells suggested induction of immune tolerance. Treatment of Rag1(-/-) mice with AQ resulted in higher ALT activities than C57BL/6 mice, which suggested that the adaptive immune response was responsible for immune tolerance. In contrast, depletion of NK cells significantly attenuated the increase in ALT, which implied a role for NK cells in mild AQ-induced IDILI. This is the first example of a delayed-onset animal model of IDILI that appears to be immune-mediated.

Highly efficient deep-blue thermally activated delayed fluorescence (TADF) is observed from a charge-transfer compound bis[4-(3,6-dimethoxycarbazole)phenyl]sulfone (DMOC-DPS). In comparison with the previously reported carbazole/sulfone derivative with tert-butyl substituents on the carbazole donors, DMOC-DPS exhibits a much shorter excited-state lifetime in both an aromatic solution and an organic thin film, because the change of the substituent on the donor affects the molecular energy levels of the first singlet (S1) and triplet (T1) excited states in different ways, decreasing the energy gap between S1 and T1 (ΔEST). An organic light emitting diode (OLED) based on DMOC-DPS achieves a maximum external electroluminescence quantum efficiency (EQE) of 14.5% and reduced efficiency roll-off, with Commission Internationale de L'Eclairage (CIE) coordinates of (0.16, 0.16), owing to efficient exciton harvesting that occurs through triplet-to-singlet up-conversion.

1. Prediction of human pharmacokinetics might be made more precise by using species with similar metabolic activities to humans. We had previously reported the species differences in intestinal and hepatic metabolic activities of 43 cytochrome P450 (CYP) substrates between cynomolgus monkeys and humans. However, the species differences between humans and rats or dogs had not yet been determined using comparable data sets with sufficient number of compounds. 2. Here, we investigated metabolic stabilities in intestinal and liver microsomes obtained from rats, dogs and humans using 43 substrates of human CYP1A2, CYP2J2, CYP2C, CYP2D6 and CYP3A. 3. Hepatic intrinsic clearance (CLint) values for most compounds in dogs were comparable to those in humans (within 10-fold), whereas in rats, those for the human CYP2D6 substrates were much higher and showed low correlation with humans. In dog intestine, as with human intestine, CLint values for almost all human CYP1A2, CYP2C, CYP2D6 substrates were not determined because they were very low. Intestinal CLint values for human CYP3A substrates in rats and dogs appeared to be lower for most of the compounds and showed moderate correlation with those in humans. 4. In conclusion, dogs showed the most similar metabolic activity to humans.

The number of new drug candidates that are cleared via non-cytochrome P450 (P450) enzymes has increased. However, unlike oxidation by P450, the roles of reductive enzymes are less understood. The metabolism in intestine is especially not well known. The purposes of this study were to investigate the significance of reductive metabolism in human intestine, and to establish a quantitative prediction method of intestinal first-pass metabolism by cytosolic reductive enzymes, using haloperidol, mebendazole, and ziprasidone. First, we estimated the metabolic activities for these compounds in intestine and liver using subcellular fractions. Metabolic activities were detected in human intestinal cytosol (HIC) for all three compounds, and the intrinsic clearance values were higher than those in human liver cytosol for haloperidol and mebendazole. These metabolic activities in HIC were NADPH- and/or NADH-dependent. Furthermore, the metabolic activities for all three compounds in HIC were largely inhibited by menadione, which has been used as a carbonyl reductase (CBR)-selective chemical inhibitor. Therefore, considering subcellular location, cofactor requirement, and chemical inhibition, these compounds might be metabolized by CBRs in human intestine. Subsequently, we tried to quantitatively predict intestinal availability (F(g)) for these compounds using human intestinal S9 (HIS9). Our prediction model using apparent permeability of parallel artificial membrane permeability assay and metabolic activities in HIS9 could predict F(g) in humans for the three compounds well. In conclusion, CBRs might have higher metabolic activities in human intestine than in human liver. Furthermore, our prediction method of human F(g) using HIS9 is applicable to substrates of cytosolic reductive enzymes.

Upon visible light irradiation, a thermally reversible photochromic acid generator merocyanine dye gives a proton to the dimethylamino group of a non-photochromic diarylethene in acetonitrile. The protonation rendered the non-photochromic diarylethene photochromic. Thus, the thermally irreversible photochromic nature of the diarylethene is activated without any physical contact or addition of any compound but only by photoirradiation to the merocyanine dye.

Isoniazid (INH) is associated with serious liver injury and autoimmunity. Classic studies in rats indicated that a reactive metabolite of acetylhydrazine is responsible for the covalent binding and toxicity of INH. Studies in rabbits suggested that hydrazine might be the toxic species. However, these models involved acute toxicity with high doses of INH, and INH-induced liver injury in humans has very different features than such animal models. In this study, we demonstrated that a reactive metabolite of INH itself can covalently bind in the liver of mice and also to human liver microsomes. Covalent binding also occurred in rats, but it was much less than that in mice. We were able to trap the reactive metabolite of INH with N-α-acetyl-l-lysine in incubations with human liver microsomes. This suggests that the reactive intermediate of INH that leads to covalent binding is a diazohydroxide rather than a radical or carbocation because those reactive metabolites would be too reactive to trap in this way. Treatment of mice or rats with INH for up to 5 weeks did not produce severe liver injury. The alanine transaminase assay (ALT) is inhibited by INH, and other assays such as glutamate and sorbitol dehydrogenase (SDH) were better biomarkers of INH-induced liver injury. High doses of INH (200 and 400 mg/kg/day) for one week produced steatosis in rats and an increase in SDH, which suggests that it can cause mitochondrial injury. However, steatosis was not observed when INH was given at lower doses for longer periods of time to either mice or rats. We propose that covalent binding of the parent drug can contribute to INH-induced hepatotoxicity and autoimmunity. We also propose that these are immune-mediated reactions, and there are clinical data to support these hypotheses.

Make your OLED fluorescent: an aromatic molecule based on a spiro-acridine derivative was designed, and its photoluminescence and electroluminescence were characterized. By combining the donor and acceptor moieties a small energy gap between the lowest singlet and triplet states was achieved. This design leads to an organic light-emitting diode (OLED) that rivals phosphorescent devices regarding exciton generation efficiency.

To simulate irradiation assisted stress corrosion cracking (IASCC) behavior by in-pile experiments, it is necessary to irradiate specimens up to a neutron fluence that is higher than the IASCC threshold fluence. Pre-irradiated specimens must be relocated from pre-irradiation capsules to in-pile capsules. Hence, a remote welding machine has been developed. And the integrity of capsule housing for a long term irradiation was evaluated by tensile tests in air and slow strain rate tests in water. Two type specimens were prepared. Specimens were obtained from the outer tubes of capsule irradiated to 1.0–3.9 × 10 26 n/m 2 ( E > 1 MeV). And specimens were irradiated in a leaky capsule to 0.03–1.0 × 10 26 n/m 2 . Elongation more than 15% in tensile test at 423 K was confirmed and no IGSCC fraction was shown in SSRT at 423 K which was estimated as temperature at the outer tubes of the capsule under irradiation.

Characteristic triboluminescence from a lanthanide coordination polymer with a non-centrosymmetric structure is reported. The lanthanide coordination polymer is composed of luminescent EuIII ions and bidentate phosphane oxides, poly[3,3′-bis(diphenylphosphoryl)-2,2′-bipyridine][tris(hexafluoroacetylacetonate)]europium (poly-Eu-BIPYPO) crystals. The coordination geometry of poly-Eu-BIPYPO is categorized as an asymmetric eight-coordinate square antiprism (8-SAP). The space group of the crystal is also classified as the non-centrosymmetric Cc, which is suitable for piezoelectricity and triboluminescence. The photoluminescence quantum yield of poly-Eu-BIPYPO crystals excited at 380 nm is found to be 61 %. Triboluminescence of the lanthanide coordination polymer is observed upon breaking, even at ambient temperature and in daylight. The remarkable triboluminescence phenomenon and geometrical structure of lanthanide coordination polymer are demonstrated.

A series of diaryl acenaphthylenes has been synthesized, and their photochromic properties are studied both in solution and in the crystalline state. 2,4-Dimethyl-5-phenylthiophene derivative 1a showed no photochromic reaction, while 2-methyl-5-phenylthiophene derivative 2a and 5-methyl-2-phenylthiazol derivative 3a showed reversible photochromism in solution. Fluorescence spectrum of compound 3a changed upon photoirradiation. In the single-crystal state, compound 3a showed no photochromic reaction possibly because of π–π and CH/S inter-molecular interactions. The photocyclization quantum yield of 3a was determined to be as low as 0.7%. The closed-isomer 3b showed relatively high thermal stability by the rigidity of acenaphtylene.

Near-infrared (NIR) luminescent Yb(III) complexes composed of low-vibrational frequency (LVF) fluorinated acetylacetonate and phosphine oxide ligands are reported. Their structures are determined u...

A spiro compound DPAA-AF combining an electron-accepting diazafluorene unit and an electron-donating bis(diphenylamino)acridane unit has been synthesized and used as an emitter in organic light-emi...

Photo-responsive molecules have been studied extensively because of their light irradiation abilities that enable modulation of certain physical and chemical properties in emerging molecular electronic and photonic devices. For advanced photonic applications, photochromic metal complexes that have photochromic units as the photo-responsive ligand are highly desirable, as they allow improvement of the photochromic properties and their photo-switching functionality. This article focuses on recent progress in luminescent metal complexes with photochromic units. Luminescence-switching properties of photochromic metal complexes depend on characteristic electronic transitions. The electronic transitions of photochromic metal complexes can be divided into three categories: (1) π–π* transition of the ligand, (2) metal to ligand charge transfer (MLCT) in transition-metal complex, and (3) f – f transition in lanthanide complex. Luminescence modulation using various metal complexes with photochromic units has been studied extensively in recent years, and various applications for future molecular switching devices are expected in the field of advanced photonics. Based on the literature and our studies on luminescent metal complexes with photochromic units, we report on the recent progress of luminescent metal complexes with photochromic units.

It has been reported that the incidence of ureteral injury during laparoscopic surgery is higher than during laparotomy. Accordingly, we investigated the usefulness and safety of ureteral illuminating catheters during gynecological surgery. Two patients underwent laparoscopic assisted vaginal hysterectomy and laparoscopic hysterectomy with the use of ureteral illuminating catheters. After introduction of the laparoscope, the catheters were clearly seen within the ureters through the pelvic peritoneum, facilitating dissection of the ureters and control of periureteric bleeding. Regarding the complications of ureteral illuminating catheters, lumbar backache was noted postoperatively in one patient, but it resolved after one day. No other complications were found. This method can be applied for training in laparoscopy at teaching hospitals, as well as in technically challenging cases where identification of the ureters is likely to be difficult, e.g. patients with severe pelvic adhesions, severe endometriosis, and malignant tumours. To assess the safety of ureteral illuminating catheters, we will investigate more cases in the future.

Novel EuIII complexes with bidentate phosphine oxide ligands containing a bipyridine framework, i.e., [3,3′-bis(diphenylphosphoryl)-2,2′-bipyridine]tris(hexafluoroacetylacetonato)europium(III) ([Eu(hfa)3(BIPYPO)]) and [3,3′-bis(diphenylphosphoryl)-6,6′-dimethyl-2,2′-bipyridine]tris(hexafluoroacetylacetonato)europium(III) ([Eu(hfa)3(Me-BIPYPO)]), were synthesized for lanthanide-based sensor materials having high emission quantum yields and effective chemosensing properties. The emission quantum yields of [Eu(hfa)3(BIPYPO)] and [Eu(hfa)3(Me-BIPYPO)] were 71 and 73%, respectively. Metal-ion sensing properties of the EuIII complexes were also studied by measuring the emission spectra of EuIII complexes in the presence of ZnII or CuII ions. The metal-ion sensing and the photophysical properties of luminescent EuIII complexes with a bidentate phosphine oxide containing 2,2′-bipyridine framework are demonstrated for the first time.

Structures and photophysical properties of f-block metal complexes with tandem-connected tridentate phosphane oxide ligands, {bis[o-(diphenylphosphoryl)phenyl]phenylphosphane oxide}tris(hexafluoroacetylacetonato)europium(III) [Eu(hfa)3(DPPPO)], {bis[o-(diphenylphosphoryl)pyridyl]phenylphosphane oxide}tris(hexafluoroacetylacetonato)europium(III) [Eu(hfa)3(DPPYPO)] and {bis[o-(diphenylphosphoryl)benzothienyl]phenylphosphane oxide}tris(hexafluoroacetylacetonato)europium(III) [Eu(hfa)3(DPBTPO)], are reported. The coordination geometries of Eu(hfa)3(DPPPO) and Eu(hfa)3(DPBTPO) provide characteristic distorted, capped square antiprism structures with nine-coordinate oxygen atoms. The emission properties related to the electric transition are characterized by the emission spectra, the emission quantum yields, the emission lifetimes, and the radiative and non-radiative rate constants. EuIII complexes with tridentate phosphane oxide ligands offer relatively high emission quantum yields (> 60 % in [D6]acetone) due to their low-symmetric and low-frequency vibrational structures. The electric dipole transition intensities in the emission spectra depend on the chemical structures of tridentate phosphane oxides. The characteristic photophysical properties of polyhedral f-block metal complexes, nine-coordinate EuIII complexes with tridentate phosphane oxide, are demonstrated for the first time.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Luminescence properties and their photoinduced control of the electric dipole transitions of a Eu(III) complex that has photochromic triangle terarylenes ligands, tris(hexafluoroacetylacetonato)bis[4,5-bis(5-methyl-2-phenylthiazol-4-yl)-2-phenylthiazole]europium(III) (Eu(hfa)3(THIA)2), were studied. Fairly high photochromic reactivity of the ligand between the open-ring and closed-ring forms were found to be maintained even in the complex, and reversible color change could be observed many times. The photocyclization and the cycloreversion quantum yields of the Eu(hfa)3(THIA)2 were found to be 37% and 3.4%, respectively. The thermal stability of the closed-ring form of THIA ligand is significantly improved in the Eu(III) complex. The (5)D0-(7)F2 transition intensity of the Eu(III) complex with open-ring form ligands (Eu(hfa)3(THIA)2-O) is larger than that of the Eu(III) complex with closed-ring form ligands (Eu(hfa)3(THIA)2-C). The radiative rate constants of Eu(hfa)3(THIA)2-O and Eu(hfa)3(THIA)2-C are estimated to be 1.7 x 10(2) and 1.5 x 10(2) s(-1), respectively. The reversible control of the emission properties of the Eu(III) complex by the photochromic reactions is demonstrated for the first time.

Triangle terarylene derivatives based on the 4,5-diarylthiazole structure have been synthesized and their photochromic properties have been studied both in solution and in the crystalline state. The thiazolyl-substituted terarylenes displayed reversible photochromism in solution, with photocyclization quantum yields as high as 60 %, while a 4,5-dithienylthiazole derivative underwent photochromic reaction even in the single-crystal state, although a 4,5-dithiazolylthiazole (terthiazole) showed no photochromic reaction in the crystalline phase. The difference in photochromic reactivity between the 4,5-dithienylthiazole and the 4,5-dithiazolylthiazole was found by X-ray crystallographic analyses to originate from conformational differences in the crystalline state. The thermal cycloreversion activation energies in the solution phase were measured for thiazolyl-substituted terarylenes and for a corresponding terthiophene derivative. The activation energy for the transition from photogenerated closed-ring isomer to open-ring isomer increased with the number of substitutions of thiazole unit for thiophene. The lower aromatic stabilization energy of thiazole in relation to that of thiophene was considered to be responsible for the thermal stability of the closed-ring isomers of thiazolyl-substituted terarylenes.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Our work reveals a high dependence on charge-transfer (CT) amounts for the optimal Hartree-Fock percentage in the exchange-correlation functional of time-dependent density functional theory (TD-DFT) and the error of a vertical transition energy calculated by a given functional. Using these relations, the zero-zero transition energies of the first singlet and first triplet excited states of various CT compounds are accurately reproduced. (3)CT and locally excited triplet ((3)LE) states are well distinguished and calculated independently.

Currently, organic light-emitting diodes (OLEDs) have reached the stage of commercialization, and there has been an intense drive to use them in various applications from small- and medium-sized mobile devices to illumination equipment and large television screens. In particular, room-temperature phosphorescent materials have become core OLED components as alternatives to conventionally used fluorescent materials because devices made with phosphorescent materials exhibit excellent light-emitting performance with internal electroluminescence efficiencies (η int) of nearly 100 %. However, phosphorescent materials have several intrinsic problems, such as being limited to metal–organic compounds containing rare metals, for example, Ir, Pt, Au, and Os, and difficulty in realizing stable blue light emission. As a result, researchers have attempted to develop new materials for use as emissive dopants in OLEDs that overcome these limitations. In this chapter, first we briefly review the progress of OLED materials and device architectures mainly based on fluorescent (first-generation) and phosphorescent (second-generation) emitters. Then, we discuss third-generation OLEDs that use a new light-emitting mechanism called thermally activated delayed fluorescence (TADF). Recently, highly efficient TADF, which had been difficult to realize with conventional molecular design, has been achieved by very sophisticated molecular structures, allowing access to the unlimited freedom of molecular design using carbon-based materials. This has led to the production of ultimate OLEDs that are made of common organic compounds without precious metals and can convert electricity to light at η int of nearly 100 %.

Efficient thermally activated delayed fluorescence was observed from a spiro-anthracenone derivative (ACRSA). An organic light-emitting diode containing ACRSA exhibited blue-greenish electroluminescence with a maximum external quantum efficiency of 16.5%.

背景:子宮頸部粘表皮癌は, 1997年版の子宮頸癌取扱規約では項目が削除され, 腺扁平上皮癌の範疇に含まれるまれな腫瘍である. 今回, 特徴的な子宮頸部粘表皮癌の細胞像を呈した1例を経験したので報告する.症例:54歳. 集団検診時に, 子宮頸部細胞診陽性のため, 近医を受診した. 子宮頸部細胞診はclass V (扁平上皮癌), 子宮頸部組織診で腺扁平上皮癌と診断され, 7月上旬に当院紹介受診となった. 診察所見で, 子宮頸部に長径20mmの腫瘍を認めたため, 精査治療目的で入院となった.1998年7月中旬, 当院に入院. MRI断層撮影で子宮頸部後唇に30×20×23mmの限局した腫瘍が認められた. 集塊を構成する細胞は, 細胞質がやや豊富で厚く扁平上皮様形態を示す細胞と細胞質内に粘液を有し核偏在性を呈する腺系細胞が混在して認められた. 子宮頸膣部の細胞診所見は, 血性背景の中に, 腫瘍細胞が平面的な小集塊として出現. 子宮頸癌Ib1期と診断され, 7月下旬に手術を施行した. 病理組織学的所見は, 非角化型扁平上皮癌の胞巣と粘表皮癌の胞巣があり, 両者の間の移行像が認められた. 粘表皮癌の胞巣部分では, 組織構築および癌細胞の細胞質は扁平上皮癌の性格を示し, それらに混じって細胞質内に粘液を豊富に含んだ癌細胞が認められた.結論:子宮頸部原発の粘表皮癌は, 腺扁平上皮癌の範疇に含まれるが, そのなかで, 他の腺扁平上皮癌に比較して, 細胞病理学的に特徴的な像を示し, かつ, 臨床的にリンパ節転移頻度が比較的高いために, 細胞診による病変推定が必要であると考えられた.

Background: The prognostic significance of positive peritoneal cytology in endometrial cancer remains unsettled. We previously classified malignant cell clusters on peritoneal smears into two morphologic types and found that those with irregular edges, so-called “scalloped clusters”, were associated with peritoneal seeding or a poor clinical outcome. We have also reported on the use of postoperative peritoneal washings to investigate residual malignant cells in the peritoneal cavity.Case: A 56-year-old woman underwent surgery for endometrial cancer (grade 1 endometrioid adenocarcinoma). At operation, positive peritoneal cytology was found without obvious peritoneal seeding, so a tube for cytologic studies was inserted when closing the abdomen. Washings were obtained via the tube at 7 days and 14 days after surgery, and both sets of washings were also positive for malignant cells. All three peritoneal smears showed scalloped clusters. These findings strongly suggested the presence of occult metastasis in the peritoneal cavity that had been overlooked at operation. Despite adjuvant therapy, the patient developed intraperitonal recurrence 8 months after surgery.Conclusion: Postoperative peritoneal washings and morphologic analysis of positive peritoneal smears are useful to determine the malignant potential of endometrial cancer with positive peritoneal cytology.

We present an optical telemetry system using a small implantable transmitter which is both powered and given a carrier wave by transcutaneous near-infrared laser irradiation. The transmitter transcutaneously sends a phase-modulated signal to the receiver by the use of a near-infrared light-emitting diode. The received signal is demodulated with a lock-in amplifier. The operation of the transmitter is stable as long as it is irradiated with enough power. In the irradiation intensity range of 3.2–19 mW/cm2, the variation in the receiver output was only 3% for a baseband signal of 3.0 V, in peak-to-peak amplitude. Using the present system, we have succeeded in optical transmission through chicken several millimeters thick.

Thermoelectrics is a challenging issue for modern and future energy conversion and recovery technology. Carbon nanotubes are promising active thermoelectic materials owing to their narrow bandgap energy and high charge carrier mobility, and they can be integrated into flexible thermoelectrics that can recover any waste heat. We here report air-stable n-type single walled carbon nanotubes with a variety of weak electron donors in the range of HOMO level between ca. -4.4 eV and ca. -5.6 eV, in which partial uphill electron injection from the dopant to the conduction band of single walled carbon nanotubes is dominant. We display flexible films of the doped single walled carbon nanotubes possessing significantly large thermoelectric effect, which is applicable to flexible ambient thermoelectric modules.

Leiomyomatosis peritonealis disseminata (LPD) is an extremely rare condition, which is characterized by the presence of multiple peritoneal and subperitoneal nodules composed of bland smooth muscle cells. Albeit extremely rare, coexistence of endometriosis within LPD lesions has also reported. Herein, we report the seventh documented case of LPD coexisting with endometriosis within the same lesions and review the pathogenesis of this lesion. A 42-year-old Japanese female presented with an abdominal tumor. Computed tomography revealed a tumorous lesion in the right ovary and multiple small nodules in the abdominal cavity. Under a clinical diagnosis of ovarian cancer with peritoneal dissemination, resection of these lesions was performed. Histopathological study of the disseminated peritoneal nodules revealed proliferation of interlacing bundles of spindle cells with eosinophilic cytoplasm and bland cigar-shaped nuclei. Mitotic figures were hardly seen. The peritoneal nodules of the rectum had cystic cavities within the spindle cell bundles, and endometrial glands and stroma were present around the cystic cavities and spindle cells. The resected tissues of the ovary and cecum showed the same histopathological features. Accordingly, a diagnosis of LPD with endometriosis within the same lesions was made. A possible origin of LPD is thought to be the submesothelial multipotential stem cells, also referred to as the secondary müllerian system. The presence of endometrial tissues within LPD lesions, as seen in the present case, also support this hypothesis because endometrial tissues are also derived from the müllerian system.

Considerable progress in organic light-emitting diodes (OLEDs) has triggered intensive effort to develop efficient solid-state electroluminescent (EL) materials over the past two decades. Among the many classes of materials being investigated, transition metal complexes are highly attractive because phosphorescent OLEDs containing Ir (III), Pt (II) and Os (II) complexes exhibit very high external quantum efficiencies (ηext). This is because such complexes effectively harvest triplet excitons, so their efficiencies are four times higher than that of conventional fluorescent OLEDs. However, phosphorescent OLEDs containing transition metal-based compounds are rather expensive and unsustainable because they contain rare metals. While OLEDs containing Cu (I) complexes that exhibit high ηext comparable to those with transition metal complexes have been examined as an alternative, the relatively low reliability and high driving voltage of such OLED are fundamental problems. Therefore, a novel way to realize high EL efficiency is required. Although fluorescent OLEDs have been assumed to show limited efficiency because of the branching ratio of singlet and triplet excitons of 1:3, the most recent fluorescence-based OLEDs have overcome this limitation using triplet-triplet annihilation and thermally activated delayed fluorescence (TADF) [1-2]. In particular, we have developed promising blue and green TADF materials [3-4]. However, the design of efficient orange or red emitters is inherently difficult because the photoluminescence (PL) quantum efficiency tends to decrease as the emission wavelength increases according to the energy gap law.

A case of hepatocellular carcinoma complicating biliary cirrhosis caused by biliary atresia is reported. The patient had persistent severe jaundice with hepatosplenomegaly. A liver tumor was suspected because of the elevated serum alpha-fetoprotein and was shown by ultrasonography at 6 years of age. The tumor was treated with percutaneous ethanol injection therapy (PEIT). Nine months after initiation of PEIT, the patient died of massive bleeding from a metastatic tumor.