Farnesoid X receptor (FXR) has become a particularly attractive target for the discovery of drugs for the treatment of liver and metabolic diseases. Obeticholic acid (INT-747), a FXR agonist, has ...advanced into clinical phase III trials in patients with nonalcoholic steatohepatitis (NASH), but adverse effects (e.g., pruritus, LDL increase) were observed. Pruritus might be induced by Takeda G-protein-coupled receptor 5 (TGR5, GPBAR1), and there are chances to develop FXR agonists with higher selectivity over TGR5. In this letter, novel bile acids bearing different modifications on ring A and side chain of INT-747 are reported and discussed. Our results indicated that the side chain of INT-747 is amenable to a variety of chemical modifications with good FXR potency in vitro. Especially, compound 18 not only showed promising FXR potency and excellent pharmacokinetic properties, but also proved superior pharmacological efficacy in the HFD + CCl4 model.
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The rare and expensive D‐talose was conveniently synthesized from readily available D‐galactose in four steps with an overall yield of 58%. The key step was the inversion of equatorial 2‐OH of ...galactose to the axial one by SN2 reaction under the modified Lattrell‐Dax reaction conditions.
D‐Talose was synthesized from D‐galactose in four steps with an overall yield of 58%. The key step was the inversion of equatorial 2‐OH of galactose to the axial one by SN2 reaction.
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Simultaneous electroanalysis of isoniazid and uric acid (UA) was achieved at a poly(sulfosalicylic acid) (PSA) and carboxylated graphene (CG)-modified glassy carbon electrode (GCE). The CG ...cast-coated on the GCE was cathodically reduced to form electroreduced CG (ERCG), while the PSA was electrochemically synthesized on the ERCG/GCE. Electrochemical quartz crystal microbalance was used to investigate the electrodeposition processes. The surface morphologies and electrochemical properties of the PSA/ERCG/GCE were studied by scanning electron microscopy, cyclic voltammetry (CV) and electrochemical impedance spectroscopy. The electrochemical behaviors of isoniazid and UA at PSA/ERCG/GCE were investigated by CV and differential pulse voltammetry (DPV), giving well defined and well separated oxidation peaks of isoniazid and UA. The PSA/ERCG/GCE exhibited notably enhanced electro-oxidation signals of isoniazid and UA in NH3-NH4Cl buffer solution (pH 9.0), as compared with bare GCE and PSA/GCE. Under optimum conditions, the DPV peak currents at PSA/ERCG/GCE responded linearly to isoniazid concentration from 0.05 to 15μM and to UA concentration from 0.02 to 15μM, with limits of detection of 12nM for both isoniazid and UA, which is an improvement compared to many other reported techniques. The PSA/ERCG/GCE was successfully applied to the simultaneous determination of isoniazid and UA in urine substrate samples.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
High-performance liquid chromatography (HPLC) with gradient elution was coupled to a glassy carbon electrode (GCE)-based wall-jet/thin-layer electrochemical detector (ECD) for the simultaneous ...analysis of isoniazid (isonicotinyl hydrazide, INH) and rifampicin (RIF). The simultaneous HPLC-ECD analysis of INH and RIF was performed using a reversed phase C18 column (150 mm 4.6 mm, 5 mu m) using a gradient elution program at a flow rate of 1.0 mL min super(-1), and an HPLC-Ultraviolet (UV) detector at a wavelength of 268 nm and the HPLC-ECD at a working potential of 0.9 V vs.SCE were used. Linear calibration plots for INH and RIF were obtained in the range of 0.01-100 mu M for INH and RIF. Our wall-jet/thin-layer ECD gave limits of detection (LODs) of 0.3 and 0.5 nM (S/N= 3) for INH and RIF, respectively, which are lower than those obtained with the UV detector and a commercial ECD. Our method was successfully applied for the simultaneous determination of INH and RIF in an antitubercolosis drug and urine substrate samples.
A carboxylated graphene (CG) modified glassy carbon electrode (GCE) was prepared by cast-coating a CG solution on a GCE surface, for quantitative analysis of nicotine based on cyclic voltammetry ...after potentiostatic enrichment of nicotine at −1.1 V for 240 s in 0.1 M KH 2 PO 4 –Na 2 HPO 4 buffer solution (pH 7.0). At this enrichment potential, partially electroreduced CG (ERCG) was obtained, as characterized by Fourier transform infrared spectroscopy, Raman spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscopy and electrochemistry techniques. The oxidation peak current of nicotine at the ERCG/GCE after a semi-derivative treatment responded linearly to nicotine concentration from 2 to 5 μM and from 5 to 60 μM, with a limit of detection of 0.1 μM. The ERCG/GCE gave analytical performance superior to that at a bare GCE, and the semi-derivative treatment notably improved the signal resolution. The ERCG/GCE was used to determine nicotine in real tobacco samples, with recoveries over 95%.
A carboxylated graphene (CG) modified glassy carbon electrode (GCE) was prepared by cast-coating a CG solution on a GCE surface, for quantitative analysis of nicotine based on cyclic voltammetry ...after potentiostatic enrichment of nicotine at −1.1 V for 240 s in 0.1 M KH
2
PO
4
-Na
2
HPO
4
buffer solution (pH 7.0). At this enrichment potential, partially electroreduced CG (ERCG) was obtained, as characterized by Fourier transform infrared spectroscopy, Raman spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscopy and electrochemistry techniques. The oxidation peak current of nicotine at the ERCG/GCE after a semi-derivative treatment responded linearly to nicotine concentration from 2 to 5 μM and from 5 to 60 μM, with a limit of detection of 0.1 μM. The ERCG/GCE gave analytical performance superior to that at a bare GCE, and the semi-derivative treatment notably improved the signal resolution. The ERCG/GCE was used to determine nicotine in real tobacco samples, with recoveries over 95%.
Nicotine is determined at a glassy carbon electrode modified with partially electroreduced carboxylated graphene by cyclic voltammetry and semi-derivative treatment after enrichment at −1.1 V in 0.1 M pH 7.0 phosphate buffer solution.
A series of glycosphingolipids with 1,2-trans-glycosidic linkages were synthesized in the presence of neighboring group participation using trichloroacetimidates as glycosyl donors and an ...azido-sphingosine as the glycosyl acceptor. During the preparation of the target compounds, it was found that the α-L-arabinopyranosyl unit in target 7e and intermediates 7b-7d existed in the
1
C
4
conformation and that the β-L-fucopyranosyl unit in 10e adopted the
4
C
1
conformation.
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Most electronic devices exploit the electric charge of electrons, but it is also possible to build devices that rely on other properties of electrons. Spintronic devices, for example, make use of the ...spin of electrons. Valleytronics is a more recent development that relies on the fact that the conduction bands of some materials have two or more minima at equal energies but at different positions in momentum space. To make a valleytronic device it is necessary to control the number of electrons in these valleys, thereby producing a valley polarization. Single-layer MoS(2) is a promising material for valleytronics because both the conduction and valence band edges have two energy-degenerate valleys at the corners of the first Brillouin zone. Here, we demonstrate that optical pumping with circularly polarized light can achieve a valley polarization of 30% in pristine monolayer MoS(2). Our results, and similar results by Mak et al., demonstrate the viability of optical valley control and valley-based electronic and optoelectronic applications in MoS(2) monolayers.
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Nitrogen-vacancy (NV) centers in diamond are attractive as quantum sensors owing to their superb coherence under ambient conditions. However, the NV center spin resonances are relatively insensitive ...to some important parameters such as temperature and pressure. Here we design and experimentally demonstrate a hybrid nanothermometer composed of NV centers and a magnetic nanoparticle (MNP), in which the temperature sensitivity is enhanced by the critical magnetization of the MNP near the ferromagnetic-paramagnetic transition temperature. The temperature susceptibility of the NV center spin resonance reaches14MHz/K, nearly 200 times larger than that of bare NV centers. The sensitivity of a hybrid nanothermometer composed of aCu1−xNixMNP and a nanodiamond is measured to be11mK/Hzunder ambient conditions. The working range of the hybrid thermometer can be designed from cryogenic temperature to about 600 K by tuning the chemical composition of theCu1−xNixMNP. We demonstrate in situ detection of the magnetic phase transition of a single magnetic nanoparticle using the hybrid nanothermometer. This hybrid nanothermometer provides a novel approach to studying a broad range of thermal processes at nanoscales such as nanoplasmonics, heat-stimulated subcellular processes, and thermodynamics of nanosystems.
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