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We aimed to test the hypothesis that selenoprotein P (SELENOP), a hepatokine involved in the development of both insulin resistance and impaired insulin production in mice, is related to future onset of hyperglycemia in humans. 76 healthy non-pregnant human subjects without diabetes underwent oral glucose tolerance test (OGTT) at baseline and 4-years follow-up. Nine subjects developed either impaired glucose tolerance or type 2 diabetes at follow-up. At baseline, SELENOP concentrations correlated negatively with insulinogenic index, but not with homeostasis model assessment-estimated insulin resistance (HOMA-IR). Multivariate analysis showed that baseline SELENOP predicted fasting plasma glucose at follow-up independently of the other parameters. The receiver operating characteristic (ROC) curve analysis showed that baseline concentrations of serum SELENOP, but not of selenium, were a reliable test to predict future onset of glucose intolerance. In conclusion, elevation of circulating SELENOP, but not of circulating selenium, was positively and independently associated with future onset of glucose intolerance in a general Japanese population.

Background We introduce a new assay method to measure the concentration of fecal calprotectin that can be applied in exclusive analyzers. The assay method uses gold colloidal reagents. In addition, we report performance evaluation results for the new method and the results of comparisons with enzyme-linked immunosorbent assay (ELISA) methods. Methods We evaluated the new method by linearity tests and within-run tests. In addition, we collected specimens from patients with a definitive diagnosis of inflammatory bowel disease (n = 566) and examined them using the new method. The results were compared with those from 2 commercially available ELISA kits. Results In the linearity tests, the correlation coefficients between the measured values and the theoretical values were 0.9980–0.9990. In the within-run tests, the CVs were 3.4–4.3%. The correlation coefficients for our method and the 2 ELISA kits showed high correlations of 0.945 and 0.942. Conclusions Our assay is capable of measuring calprotectin concentrations in feces, and has a similar performance to commercially available ELISA methods. Our method is an automated assay system, which is an easier, cheaper, and quicker measurement method than conventional ELISA kits. Therefore, our assay is suitable for daily clinical use.

Continuous tuning of the backbone conformation and interchain distance of a π-conjugated polymer is an essential prerequisite to unveil the inherent electrical and optical features of organic electronics. To this end, applying pressure in a hydrostatic medium or diamond anvil cell is a facile approach without the need for side-chain synthetic engineering. We report the development of high-pressure, time-resolved microwave conductivity (HP-TRMC) and evaluation of transient photoconductivity in the regioregular poly(3-hexylthiophene) (P3HT) film and its bulk heterojunction blend with methanofullerene (PCBM). X-ray diffraction experiments under high pressure were performed to detail the pressure dependence of π-stacking and interlamellar distances in P3HT crystallites and PCBM aggregates. The HP-TRMC results were further correlated with high-pressure Raman spectroscopy and density functional theory calculation. The increased HP-TRMC conductivity of P3HT under pressure was found to be relevant to the planarity of the backbone conformation and intramolecular hole mobility. The effects of pressure on the backbone planarity are estimated to be ∼0.3 kJ mol(-1) based on the compressibility derived from the X-ray diffraction under high pressure, suggesting the high enough energy to cause modulation of the planarity in terms of the Landau-de Gennes free energy of isolated P3HT chains as 0.23 kJ mol(-1). In contrast, the P3HT:PCBM blend showed a simple decrease in photoconductivity irrespective of the identical compressive behavior of P3HT. A mechanistic insight into the interplay of intra- and intermolecular mobilities is a key to tailoring the dynamic π-figuration associated with electrical properties, which may lead to the use of HP-TRMC for exploring divergent π-conjugated materials at the desired molecular arrangement and conformation.

Background Selenoprotein P (SeP), a selenium-rich extracellular glycoprotein, is the primary selenoprotein in the plasma. SeP plays an important role in the maintenance of selenium levels in the peripheral tissues. We developed a new sol particle homogeneous immunoassay (SPIA) for measuring full-length SeP (FL-SeP) levels in the human serum. Methods We used colloidal gold particles coated with two types of anti-SeP monoclonal antibodies, one recognizing the N-terminal side domain of SeP and the other recognizing the C-terminal side domain. Results The assay range was 0.2–9 mg/l, and the linearity was excellent. The within-day and between-day coefficients of variation ranged from 0.73% to 2.24% and 0.45% to 1.11%, respectively. Serum samples (n = 200) were examined using the newly developed assay system (employing a Model 7070 Hitachi automatic clinical analyzer) and the conventional enzyme-linked immunosorbent assay. These two methods were compared using the Passing–Bablok regression analysis; the resulting regression equation and correlation coefficient were y = 0.940x + 0.165 and r = 0.954, respectively. Conclusions Our new SPIA assay is a fully automated homogeneous immunoassay that can be used in conjunction with various commercial analyzers. The assay was sensitive, precise, and suitable for clinical measurement of the FL-SeP in the human serum.

A silacyclophane molecule with two disilanyl pillars and two oligoarylene units was synthesized. The molecule was packed in a single crystal with a new motif interfusing π-stack and herringbone packing structures. The hole transporting ability of the solid was revealed by using the flash-photolysis time-resolved microwave conductivity method. The molecular structure, albeit a singly-bonded arylene macrocycle, was rigidified by the unique packing array, which favorably contributed to the hole transporting ability of the solid via the small reorganization energy through the charge transport.

Exercise has numerous health-promoting effects in humans; however, individual responsiveness to exercise with regard to endurance or metabolic health differs markedly. This 'exercise resistance' is considered to be congenital, with no evident acquired causative factors. Here we show that the anti-oxidative hepatokine selenoprotein P (SeP) causes exercise resistance through its muscle receptor low-density lipoprotein receptor-related protein 1 (LRP1). SeP-deficient mice showed a 'super-endurance' phenotype after exercise training, as well as enhanced reactive oxygen species (ROS) production, AMP-activated protein kinase (AMPK) phosphorylation and peroxisome proliferative activated receptor γ coactivator (Ppargc)-1α (also known as PGC-1α; encoded by Ppargc1a) expression in skeletal muscle. Supplementation with the anti-oxidant N-acetylcysteine (NAC) reduced ROS production and the endurance capacity in SeP-deficient mice. SeP treatment impaired hydrogen-peroxide-induced adaptations through LRP1 in cultured myotubes and suppressed exercise-induced AMPK phosphorylation and Ppargc1a gene expression in mouse skeletal muscle-effects which were blunted in mice with a muscle-specific LRP1 deficiency. Furthermore, we found that increased amounts of circulating SeP predicted the ineffectiveness of training on endurance capacity in humans. Our study suggests that inhibitors of the SeP-LRP1 axis may function as exercise-enhancing drugs to treat diseases associated with a sedentary lifestyle.

New donor–acceptor-type copolymers comprised of benzobisthiazole (BBTz) as a weak donor rather than acceptor are proposed. This approach can simultaneously lead to deepening the HOMO and LUMO of the polymers with moderate energy offset against fullerene derivatives in bulk heterojunction organic photovoltaics. As a proof-of-concept, BBTz-based random copolymers conjugated with typical electron acceptors: thienopyrroledione (TPD) and benzothiadiazole (BT) based on density functional theory calculations are synthesized. Laser-flash and Xe-flash time-resolved microwave conductivity (TRMC) evaluations of polymer:[6,6]-phenyl C61 butyric acid methyl ester (PCBM) blends are conducted to screen the feasibility of the copolymers, leading to optimization of processing conditions for photovoltaic device application. According to the TMRC results, alternating BBTz-BT copolymers are designed, exhibiting extended photoabsorption up to ca. 750 nm, deep HOMO (–5.5 to –5.7 eV), good miscibility with PCBM, and inherent crystalline nature. Moreover, the maximized PCE of 3.8%, the top-class among BBTz-based polymers reported so far, is realized in an inverted cell using TiOx and MoOx as the buffer layers. This study opens up opportunities to create low-bandgap polymers with deep HOMO, and shows how the device-less TRMC evaluation is of help for decision-making on judicious molecular design.

Group V secretory phospholipase A2 (sPLA2-V) hydrolyzes phosphatidylcholine in low-density lipoprotein (LDL) to increase lysophosphatidylcholine (LPC) content. Because in human umbilical vein endothelial cells (HUVEC), tumor necrosis factor alpha (TNFα)-induced sPLA2-V expression, and LPC content in LDL and monocyte chemoattractant protein-1 mRNA were enhanced by incubation of LDL with TNFα-stimulated HUVEC, we investigated whether an angiotensin II receptor type 1 blocker, telmisartan, or an antioxidant drug, N-acetylcysteine (NAC), suppressed TNFα-induced sPLA2-V expression. Telmisartan or NAC administered before and during TNFα stimulation diminished the increase of sPLA2-V mRNA in HUVEC and reduced TNFα-induced sPLA2-V protein at 3 days after TNFα stimulation. Angiotensin II did not induce sPLA2-V mRNA, and a peroxisome proliferator-activated receptor-γ antagonist, GW3335, did not influence the inhibitory effect of telmisartan on TNFα-induced sPLA2-V mRNA. At 3 days after TNFα stimulation, 30 μM telmisartan or 20 mM NAC administered before and during TNFα stimulation prevented the enhancement of LPC content in LDL and monocyte chemoattractant protein-1 mRNA by LDL incubation with TNFα-stimulated HUVEC. A 2-month treatment with telmisartan in 29 hypertensive type 2 diabetic patients significantly reduced LPC content in circulating LDL. Telmisartan's suppressive effect on TNFα-induced sPLA2-V expression may have beneficial effects in preventing proatherogenic changes of LDL.

A copper-promoted annulative direct coupling of o-alkynylaniline derivatives with 1,3,4-oxadiazoles for the synthesis of C3-azolylindoles has been developed. The copper-based system provides a new protocol for the dehydrogenative construction of indole­–oxadiazole conjugations from nonhalogenated and nonmetalated starting materials.

The cross-dimerization of diphenylacetylene with trimethylsilylacetylene via C¯H bond cleavage in the presence of a catalytic amount of bis(cyclooctadiene)nickel [Ni(cod) 2 ] together with a pyridine-based ligand efficiently proceeds to give the corresponding enyne compound with good yield. In contrast, their 1:2 cross-trimerization leading to a dienyne derivative takes place selectively using a triarylphosphine ligand. The regioselective cross-dimerization of some unsymmetrical internal arylalkynes with terminal silylacetylenes is also accomplished using the pyridine ligand.

The direct alkynylation reaction of 1,3,4-oxadiazoles with alkynyl bromides efficiently proceeds in the presence of a copper catalyst at room temperature to create the corresponding heteroaryl-alkynyl linkage in good yields. This direct coupling provides a rapid and convergent access to oxadiazole core pi-conjugated systems.

Curved π-conjugated molecules with closed and three-dimensional (3D) structures, such as fullerenes and carbon nanotubes, have been the subject of intensive research due to their potential applications in molecular electronics. However, basic molecular skeletons of 3D molecules are limited because of the lack of a rational and selective synthetic method by organic synthesis. Here we report the synthesis of a 3D π-conjugated molecule based on the platinum-mediated assembly of four molecules of a stannylated trisubstituted benzene derivative forming a hexanuclear platinum complex with an octahedral shape, from which reductive elimination of platinum gave the target molecule. As many supramolecular transition metal-ligand complexes with 3D cages and polyhedral structures have been synthesized by self-assembly of ligands and metals, the current assembly/reductive elimination strategy could provide a variety of new 3D π-conjugated molecules with different structures and topologies, which are challenging to obtain using conventional synthetic methods.

o-Alkynylanilines bearing a suitable leaving group (generally o-fluorobenzoyl) at the nitrogen are coupled with oxadiazoles to produce N-unsubstituted indoles directly.

In 1969, McCully (1) observed that increased plasma homocysteine (Hcy) was linked with vascular disease. Subsequent studies demonstrated that even mild hyperhomocysteinemia is an independent risk factor for cardiovascular, cerebrovascular, and peripheral vascular disease (2)(3)(4)(5)(6)(7)(8). Increased plasma Hcy is associated with a thermolabile variant of 5,10-methylenetetrahydrofolate reductase, smoking, lack of exercise, and excessive use of alcohol and coffee. Plasma or serum total Hcy (tHcy) concentrations are most commonly measured by HPLC (9), which is time- consuming and expensive, and by immunochemical (10)(11)(12) or enzymatic (13) methods, which may not be applicable to all colorimetric-based clinical chemistry analyzers. The thiol group of Hcy allows it to form a disulfide bond with other thiol-containing molecules, such as Hcy itself, cysteine, and the cysteine residue of plasma proteins. Biologic fluids may often contain both reduced and oxidized species of Hcy, and the sum of all the forms of Hcy is usually called total Hcy (tHcy) (14). Most clinical studies concerning Hcy have relied on the measurement of tHcy. An initial chemical reduction step of the sample is inevitable in the tHcy assay. Because reducing agents can interfere with the oxidation of redox indicators, such as Trinder’s reagents and derivatives of methylene blue generally used in diagnostic reagents, methods for tHcy that use these indicators have not been developed. The present method is a new enzymatic colorimetric assay for tHcy in biologic samples. The principle is as follows. In the first step, samples are reduced by dithiothreitol …

Direct cross coupling reaction of azoles, e.g. (I) and (IV), with terminal alkynes is smoothly achieved using a Ni(II)—bipyridine catalyst under oxygen.

The direct alkynylation reaction of 1,3,4-oxadiazoles with alkynyl bromides efficiently proceeds in the presence of a copper catalyst at room temperature to create the corresponding heteroaryl−alkynyl linkage in good yields. This direct coupling provides a rapid and convergent access to oxadiazole core π-conjugated systems.

The direct C-H alkynylation of azoles with terminal alkynes proceeds efficiently under a nickel/O(2) catalytic system. On the other hand, a copper/air catalyst enables the coupling of polyfluoroarenes with terminal alkynes. These catalyses provide new accesses to arylacetylenes through the formal direct Sonogashira coupling.

The direct C−H alkynylation of azoles with alkynyl bromides proceeds efficiently in the presence of a nickel-based catalyst system. The reaction enables the introduction of various alkynyl groups bearing aryl, alkenyl, alkyl, and silyl substituents to the azole cores. In some cases, addition of a catalytic amount of CuI is observed to accelerate the direct coupling dramatically.

The cross-addition of terminal silylacetylenes to γ-arylated propargyl amines occurs efficiently via C−H cleavage by using either a nickel or rhodium catalyst. Taking advantage of the catalyst-cont...

Pt/CeO(2)-ZrO(2)-Bi(2)O(3)/gamma-Al(2)O(3) (Pt/CZB/Al(2)O(3)) catalysts for the catalytic combustion of toluene, which is one of the volatile organic compounds (VOCs), were prepared by the wet impregnation method in the presence of polyvinyl pyrrolidone (PVP). X-ray powder diffraction, transmission electron microscopy, and BET specific surface area measurement using N(2) adsorption have been used to characterize the catalysts. The catalytic test was conducted from room temperature in a flow of 900 ppm of toluene in air and gas hourly space velocity (GHSV) of 8000 h(-1). The catalytic activity was evaluated in terms of C(7)H(8) conversion and the gas composition after the reaction was analyzed using two gas chromatographs with a flame ionization detector (FID) and a thermal conductivity detector (TCD). The Pt/CZB/Al(2)O(3) catalysts are specific for the total toluene oxidation and CO and any toluene-derivative compounds were not detected as by-products. The specific surface area of the catalysts was increased by the addition of PVP in the preparation process. By the optimization of the amount of platinum, complete oxidation of toluene was realized at a temperature as low as 120 degrees C on a 7 wt%Pt/16 wt%Ce(0.64)Zr(0.15)Bi(0.21)O(1.895)/gamma-Al(2)O(3) catalyst.

The cross-addition of terminal silylacetylenes to gamma-arylated propargyl amines occurs efficiently via C-H cleavage by using either a nickel or rhodium catalyst. Taking advantage of the catalyst-controlled switching of regioselectivity in the reaction, both the 2- and 3-alkynylallylamines are readily accessible from the same starting materials.

The cross-dimerization of diphenylacetylene with trimethylsilylacetylene via C¯H bond cleavage in the presence of a catalytic amount of bis(cyclooctadiene)nickel [Ni(cod) 2 ] together with a pyridine-based ligand efficiently proceeds to give the corresponding enyne compound with good yield. In contrast, their 1:2 cross-trimerization leading to a dienyne derivative takes place selectively using a triarylphosphine ligand. The regioselective cross-dimerization of some unsymmetrical internal arylalkynes with terminal silylacetylenes is also accomplished using the pyridine ligand.

Aims We studied the relations of lysophosphatidylcholine (lyso-PC) in LDL with serum lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ), paraoxonase and homocysteine thiolactonase (HTLase) activities in patients with type 2 diabetes mellitus. Methods Lyso-PC was measured by electrospray ionization-liquid chromatography/mass spectrometry. Paraoxonase and HTLase activities were measured with paraoxon and γ-thiobutyrolactone as substrates, respectively. Results Serum HTLase and paraoxonase activities were significantly suppressed in diabetic patients ( n = 96) compared with control ( n = 25), whereas serum Lp-PLA 2 did not differ in control and diabetic patients. Lyso-PC contents in LDL correlated with serum Lp-PLA 2 activity positively and with serum HTLase activity negatively. Stepwise regression analysis revealed that serum Lp-PLA 2 and HTLase activities independently contributed to lyso-PC contents in LDL. In patients with diabetic nephropathy, lyso-PC contents in LDL were increased with reduced serum HTLase and paraoxonase activities compared with control, while serum Lp-PLA 2 activity did not differ. On the other hand, 3-month treatment with simvastatin reduced both lyso-PC contents in LDL and serum Lp-PLA 2 activity in hypercholesterolemic diabetic patients, while serum HTLase or paraoxonase activities did not change. Conclusions Increased lyso-PC contents in LDL were associated with the suppressed HTLase activity, and serum Lp-PLA 2 and HTLase activities may be related to lyso-PC in type 2 diabetic patients.

A series of polyunsaturated fatty acid anilides were synthesized and evaluated as ACAT inhibitors. Compound 24 had potent inhibitory activity against microsomal ACAT derived from U937, HepG2 and Caco-2 cell lines. Therefore, it might be expected to act as an antiarteriosclerotic and hypocholesterolemic agent. Interestingly, the ACAT inhibitory potency of 24 varied significantly depending on the source of the enzyme.