In vitro metabolism of corydaline in human liver microsomes and hepatocytes using liquid chromatography-ion trap mass spectrometry

Corydaline is a pharmacologically active isoquinoline alkaloid isolated from Corydalis tubers. It exhibits the antiacetylcholinesterase, antiallergic, antinociceptive, and gastric emptying activities. The purposes of this study were to establish in vitro metabolic pathways of corydaline in human liver microsomes and hepatocytes by identification of their metabolites using liquid chromatography-ion trap mass spectrometry. Human liver microsomal incubation of corydaline in the presence of an NADPH-generating system resulted in the formation of nine metabolites, namely, four O-desmethylcorydaline [M1 (yuanhunine), M2 (9-O-desmethylcorydaline), M3 (isocorybulbine), and M4 (corybulbine)], three di-O-desmethylcorydaline [M5 (9,10-di-O-desmethylcorydaline), M6 (2,10-di-O-desmethylcorydaline), and M7 (3,10-di-O-desmethylcorydaline)], M8 (hydroxyyuanhunine), and M9 (hydroxycorydaline). Incubation of corydaline in human hepatocytes produced four metabolites including M1, M5, M6, and M9. O-Demethylation and hydroxylation were the major metabolic pathways for the metabolism of corydaline in human liver microsomes and hepatocytes.     

Oxygen excess nonstoichiometry and thermodynamic quantities of La2NiO4?+?δ

The oxygen excess nonstoichiometry of La₂NiO_4 + δ is measured as a function of temperature and oxygen partial pressure (pO₂) by coulometric titration method. A positive deviation from the ideal dilution solution behavior is exhibited, and the partial molar thermodynamic quantities of La₂NiO_4 + δ are calculated from the Gibbs–Helmholtz equation for regular solution by introducing the activity coefficient of the charge carriers. The activity coefficient of holes is successfully calculated by using the Joyce–Dixon approximation of the Fermi–Dirac integral. The effective mass of holes ( m_\texth^* m_{\text{h}}^{{*}} ) is 1.27–1.29 times the rest mass (m _h), which indicate the action of band-like conduction and allow the effect of the small degree of polaron hopping to be ignored. The activity coefficient of holes calculated against the oxygen nonstoichiometry clearly illustrates the early positive deviation of the activity coefficient of holes from unit, leading to g_{\texth ^·} \gamma_{{{\text{h}}^{ \bullet }}}  ≈ 14 at δ ≈ 0.08, which is quite close to the literature value of g_{\texth ^·} \gamma_{{{\text{h}}^{ \bullet }}}  ≈ 10 at δ ≈ 0.08. All the evaluated thermodynamic quantities are in good agreement with the experimental literature values.     

Biomolecular theorem proving on a chip: a novel microfluidic solution to a classical logic problem

Biomolecules inside a microfluidic system can be used to solve computational problems, such as theorem proving, which is an important class of logical reasoning problems. In this article, the Boolean variables (literals) were represented using single-stranded DNA molecules, and theorem proving was performed by the hybridization and ligation of these variables into a double-stranded "solution" DNA. Then, a novel sequential reaction mixing method in a microfluidic chip was designed to solve a theorem proving problem, where a reaction loop and three additional chambers were integrated and controlled by pneumatic valves. DNA hybridization, ligation, toehold-mediated DNA strand displacement, exonuclease I digestion, and fluorescence detection of the double-stranded DNA were sequentially performed using this platform. Depending on the computational result, detection of the correct answer was demonstrated based on the presence of a fluorescence signal. This result is the first demonstration that microfluidics can be used to facilitate DNA-based logical inference.     

Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow

Development of an in vitro living cell-based model of the intestine that mimics the mechanical, structural, absorptive, transport and pathophysiological properties of the human gut along with its crucial microbial symbionts could accelerate pharmaceutical development, and potentially replace animal testing. Here, we describe a biomimetic 'human gut-on-a-chip' microdevice composed of two microfluidic channels separated by a porous flexible membrane coated with extracellular matrix (ECM) and lined by human intestinal epithelial (Caco-2) cells that mimics the complex structure and physiology of living intestine. The gut microenvironment is recreated by flowing fluid at a low rate (30 μL h(-1)) producing low shear stress (0.02 dyne cm(-2)) over the microchannels, and by exerting cyclic strain (10%; 0.15 Hz) that mimics physiological peristaltic motions. Under these conditions, a columnar epithelium develops that polarizes rapidly, spontaneously grows into folds that recapitulate the structure of intestinal villi, and forms a high integrity barrier to small molecules that better mimics whole intestine than cells in cultured in static Transwell models. In addition, a normal intestinal microbe (Lactobacillus rhamnosus GG) can be successfully co-cultured for extended periods (>1 week) on the luminal surface of the cultured epithelium without compromising epithelial cell viability, and this actually improves barrier function as previously observed in humans. Thus, this gut-on-a-chip recapitulates multiple dynamic physical and functional features of human intestine that are critical for its function within a controlled microfluidic environment that is amenable for transport, absorption, and toxicity studies, and hence it should have great value for drug testing as well as development of novel intestinal disease models.     

Highly luminescent InP/GaP/ZnS nanocrystals and their application to white light-emitting diodes

Highly stable and luminescent InP/GaP/ZnS QDs with a maximum quantum yield of 85% were synthesized by in situ method. The GaP shell rendered passivation of the surface and removed the traps. TCSPC data showed an evidence for the GaP shell. InP/GaP/ZnS QDs show better stability than InP/ZnS. We studied the optical properties of white QD-LEDs corresponding to various QD concentrations. Among various concentrations, the white QD-LEDs with 0.5 mL of QDs exhibited a luminous efficiency of 54.71 lm/W, Ra of 80.56, and CCT of 7864 K.     

Pendant polymer:amino-β-cyclodextrin:siRNA guest:host nanoparticles as efficient vectors for gene silencing

A novel siRNA delivery vector has been developed, based on the self-assembly of monosubstituted cationic β-CD derivatives with a poly(vinyl alcohol)MW27kD (PVA) main-chain polymer bearing poly(ethylene glycol)MW2000 (PEG) and acid-labile cholesterol-modified (Chol) grafts through an acid-sensitive benzylidene acetal linkage. These components were investigated for their ability to form nanoparticles with siRNA using two different assembly schemes, involving either precomplexation of the pendant Chol-PVA-PEG polymer with the cationic β-CD derivatives before siRNA condensation or siRNA condensation with the cationic β-CD derivatives prior to addition of Chol-PVA-PEG to engage host:guest complexation. The pendant polymer:amino-β-CD:siRNA complexes were shown to form nanoparticles in the size range of 120-170 nm, with a slightly negative zeta potential. Cell viability studies in CHO-GFP cells shows that these materials have 10(3)-fold lower cytotoxicities than 25 kD bPEI, while maintaining gene-silencing efficiencies that are comparable to those of benchmark transfection reagents such as bPEI and Lipofectamine 2000. These results suggest that the degradable Chol-PVA-PEG polymer is able to self-assemble in the presence of siRNA and cationic-β-CD to form nanoparticles that are an effective and low-toxicity vehicle for delivering siRNA cargo to target cells.     

Simple replacement reaction for the preparation of ternary Fe(1-x)PtRu(x) nanocrystals with superior catalytic activity in methanol oxidation reaction

The finding of new metal alloyed nanocrystals (NCs) with high catalytic activity and low cost to replace PtRu NCs is a critical step toward the commercialization of fuel cells. In this work, a simple cation replacement reaction was utilized to synthesize a new type of ternary Fe(1-x)PtRu(x) NCs from binary FePt NCs. The detailed structural transformation from binary FePt NCs to ternary Fe(1-x)PtRu(x) NCs was analyzed by X-ray absorption spectroscopy (XAS). Ternary Fe(35)Pt(40)Ru(25), Fe(31)Pt(40)Ru(29), and Fe(17)Pt(40)Ru(43) NCs exhibit superior catalytic ability to withstand CO poisoning in methanol oxidation reaction (MOR) than do binary NCs (FePt and J-M PtRu). Also, the Fe(31)Pt(40)Ru(29) NCs had the highest alloying extent and the lowest onset potential among the ternary NCs. Furthermore, the origin for the superior CO resistance of ternary Fe(1-x)PtRu(x) NCs was investigated by determining the adsorption energy of CO on the NCs' surfaces and the charge transfer from Fe/Ru to Pt using a simulation based on density functional theory. The simulation results suggested that by introducing a new metal into binary PtRu/PtFe NCs, the anti-CO poisoning ability of ternary Fe(1-x)PtRu(x) NCs was greatly enhanced because the bonding of CO-Pt on the NCs' surface was weakened. Overall, our experimental and simulation results have indicated a simple route for the discovery of new metal alloyed catalysts with superior anti-CO poisoning ability and low usage of Pt and Ru for fuel cell applications.     

A photocatalyst-enzyme coupled artificial photosynthesis system for solar energy in production of formic acid from CO2

The photocatalyst-enzyme coupled system for artificial photosynthesis process is one of the most promising methods of solar energy conversion for the synthesis of organic chemicals or fuel. Here we report the synthesis of a novel graphene-based visible light active photocatalyst which covalently bonded the chromophore, such as multianthraquinone substituted porphyrin with the chemically converted graphene as a photocatalyst of the artificial photosynthesis system for an efficient photosynthetic production of formic acid from CO(2). The results not only show a benchmark example of the graphene-based material used as a photocatalyst in general artificial photosynthesis but also the benchmark example of the selective production system of solar chemicals/solar fuel directly from CO(2).     

Paired pulse voltammetry for differentiating complex analytes

Although fast-scan cyclic voltammetry (FSCV) has contributed to important advances in neuroscience research, the technique is encumbered by significant analytical challenges. Confounding factors such as pH change and transient effects at the microelectrode surface make it difficult to discern the analytes represented by complex voltammograms. Here we introduce paired-pulse voltammetry (PPV), that mitigates the confounding factors and simplifies the analytical task. PPV consists of a selected binary waveform with a specific time gap between each of its two comprising pulses, such that each binary wave is repeated, while holding the electrode at a negative potential between the waves. This allows two simultaneous yet very different voltammograms (primary and secondary) to be obtained, each corresponding to the two pulses in the binary waveform. PPV was evaluated in the flow cell to characterize three different analytes, (dopamine, adenosine, and pH changes). The peak oxidation current decreased by approximately 50%, 80%, and 4% for dopamine, adenosine, and pH, in the secondary voltammogram compared with the primary voltammogram, respectively. Thus, the influence of pH changes could be virtually eliminated using the difference between the primary and secondary voltammograms in the PPV technique, which discriminates analytes on the basis of their adsorption characteristics to the carbon fiber electrode. These results demonstrate that PPV can be effectively used for differentiating complex analytes.