Generation of Healthy Mice from Gene-Corrected Disease-Specific Induced Pluripotent Stem Cells

Using the murine model of tyrosinemia type 1 (fumarylacetoacetate hydrolase [FAH] deficiency; FAH−/− mice) as a paradigm for orphan disorders, such as hereditary metabolic liver diseases, we evaluated fibroblast-derived FAH−/−-induced pluripotent stem cells (iPS cells) as targets for gene correction in combination with the tetraploid embryo complementation method. First, after characterizing the FAH−/− iPS cell lines, we aggregated FAH−/−-iPS cells with tetraploid embryos and obtained entirely FAH−/−-iPS cell–derived mice that were viable and exhibited the phenotype of the founding FAH−/− mice. Then, we transduced FAH cDNA into the FAH−/−-iPS cells using a third-generation lentiviral vector to generate gene-corrected iPS cells. We could not detect any chromosomal alterations in these cells by high-resolution array CGH analysis, and after their aggregation with tetraploid embryos, we obtained fully iPS cell–derived healthy mice with an astonishing high efficiency for full-term development of up to 63.3%. The gene correction was validated functionally by the long-term survival and expansion of FAH-positive cells of these mice after withdrawal of the rescuing drug NTBC (2-(2-nitro-4-fluoromethylbenzoyl)-1,3-cyclohexanedione). Furthermore, our results demonstrate that both a liver-specific promoter (transthyretin, TTR)-driven FAH transgene and a strong viral promoter (from spleen focus-forming virus, SFFV)-driven FAH transgene rescued the FAH-deficiency phenotypes in the mice derived from the respective gene-corrected iPS cells. In conclusion, our data demonstrate that a lentiviral gene repair strategy does not abrogate the full pluripotent potential of fibroblast-derived iPS cells, and genetic manipulation of iPS cells in combination with tetraploid embryo aggregation provides a practical and rapid approach to evaluate the efficacy of gene correction of human diseases in mouse models

Accruals quality, underwriter reputation, and corporate bond underpricing: Evidence from China

This study examines the relationship between accruals quality and the underpricing of corporate bonds in China and how underwriter reputation affects this relationship. We find that (1) accruals quality is negatively associated with the magnitude of bond underpricing and (2) the impact of low accruals quality on underpricing is partially offset by hiring reputable underwriters. A path analysis shows that approximately 11% of the effect of accruals quality on underpricing is attributable to the indirect path through reputable underwriters, suggesting that accruals quality is more effective than reputable underwriters in lowering bond underpricing. These findings are significant for initial bond offerings, but not for secondary bond offerings. We also find that low accruals quality is associated with more restrictive non-price contract terms such as greater collateral requirements and stricter covenants

Response Surface Methodology for the Optimization of Ultrasound-Assisted Extraction of Tetrodotoxin from the Liver of <i>Takifugu pseudommus</i>

Tetrodotoxin (TTX) is a marine biotoxin that has high scientific value. However, the lack of efficient TTX extraction and preparation methods has led to a scarcity of TTX samples for clinical application. In this study, TTX from the liver of Takifugu pseudommus was ultrasound-assisted extracted with acidified organic solvents. The extraction process was analyzed and optimized by single factor method and response surface methodology (RSM). The optimal extraction conditions predicted by a response surface model were as follows: liquid:material ratio, 2.8:1; extraction temperature, 60 &#176;C; extraction time, 23.3 min. Under these conditions, the extraction of TTX had a yield of 89.65%, and the results were further verified by experimental extraction, and analyzed by ultra performance liquid chromatography&#8315;tandem mass spectrometry (UPLC&#8315;MS/MS). It was found that the extracts of T. pseudommus liver contained TTX and its four analogues at certain proportions (TTX: 10.4%; 5,6,11-trideoxyTTX: 83.3%; 5,11-dideoxyTTX:2.4%; 4,9-anhydro TTX:2.6%; 5-deoxyTTX:1.3%). This study demonstrates a stable and efficient extraction process of TTX from pufferfish liver, which can be helpful for further research and analysis, as well as the utilization of TTX from pufferfish

Nitrogen doped carbon quantum dots mediated silver phosphate/bismuth vanadate Z-scheme photocatalyst for enhanced antibiotic degradation

A novel nitrogen doped carbon quantum dots (N-CQDs) mediated Ag3PO4/BiVO4 Z-scheme photocatalyst was synthesized through a solvothermal-precipitation method. The as-prepared photocatalysts were comprehensive characterized by X-ray diffraction, X-ray photo-electron spectroscopy, scanning electron microscopy, transmission electron micrograph, UV-vis diffuse reflection spectroscopy, vis photoluminescence and electron spin resonance analysis. The photocatalytic performances of as-prepared photocatalysts were used for degradation of tetracycline (TC) under visible-light illumination. Results exhibited the increased photocatalytic efficiency of BiVO4/N-CQDs/Ag3PO4-10 (Ag3PO4 with the mass ratio of BiVO4/N-CQDs/Ag3PO4 = 10%) to photodegrade TC is up to 88.9% in 30 min and 59.8% mineralization in 90 min. The degradation reaction coefficient (k) is about 6.00, 2.78 and 1.80 times higher than that of BiVO4, N-CQDs/BiVO4 and Ag3PO4/BiVO4, respectively. The excellent photocatalytic performance of the Z-scheme BiVO4/N-CQDs/Ag3PO4 was attributed to the construction of Z-scheme system, increased light harvesting capacity and improved molecular oxygen activation ability. Moreover, the photocatalytic activity of BiVO4/N-CQDs/Ag3PO4 remained 79.9% after five cycling runs, indicating the high stability and reusability of the as-prepared photocatalyst. Additionally, a possible photocatalytic mechanism of the novel Z-scheme BiVO4/N-CQDs/Ag3PO4 was proposed

Contrast enhancement of spectral domain optical coherence tomography using spectrum correction

We report a spectrum correction method to enhance the image contrast of spectral domain optical coherence tomography (SD-OCT). Our method treats SD-OCT signals as the product of harmonic signals backscattered from a sample comprising a series of discrete reflectors and a window corresponding to the light source spectrum. The method restores the magnitude of the main lobe of the axial point spread function (PSF) by estimating the magnitudes of the backscattered harmonic signals and strengthens OCT signals using these estimated values. Experimental results acquired from fresh rat corneas and fixed human aortic atherosclerosis tissues show that our method provides clearer microstructural information than the conventional methods by improving the contrast to noise ratios (CNRs) by 1.4779 dB and 3.2595 dB, respectively. This improved image quality is obtained without any hardware change, making our method a cost-effective alternative to compete with hardware advances.NRF (Natl Research Foundation, S’pore)MOE (Min. of Education, S’pore)NMRC (Natl Medical Research Council, S’pore)Accepted versio

Enhanced coking resistance of Ni cermet anodes for solid oxide fuel cells based on methane on-cell reforming by a redox-stable double-perovskite Sr2MoFeO6-δ

Carbon deposition on a Ni-based anode is troublesome for the direct power generation from methane-based fuels using solid oxide fuel cell. In this paper, a redox-stable double-perovskite SrMoFeO (SMFO) is applied as an independent on-cell reforming catalyst over a Ni-YSZ anode to improve coking resistance. The morphology, catalytic activity and electrochemical performance for wet methane/coal-bed gas (CBG) are investigated. A Ni-YSZ anode supported cell with SMFO generates a high power output of 1.77\ua0W·cm and exhibits favorable stability operated on wet CH at 800°C. Post-mortem micro-structural analyses of cells indicate the cell operated on CBG shows coking probably due to the heavy carbon compounds in CBG

A strategy to reduce the impact of tar on a Ni ‐ YSZ anode of solid oxide fuel cells

High-temperature raw coke oven gas (COG) is a promising fuel for use in solid oxide fuel cells (SOFCs) because it is rich in both hydrogen (55%-60%) and methane (23%-27%). However, the tar present in COG limits its ability to directly generate power using state-of-art SOFCs because the presence of tar limits the cell's performance and stability. In this work, a strategy is presented in the attempt to reduce the influence of tar on SOFCs by applying a La Sr MnO catalyst as a protective layer for the cell. The results showed that 44-g Nm toluene had a profoundly negative effect on the performance of a conventional cell, which showed severely reduced performance after only 1.4 hours of exposure to toluene-contaminated hydrogen. In contrast, the catalyst-modified cell showed good stability for at least 110 hours under the same conditions. This work provides a promising route to directly utilize raw COG as an SOFC fuel that is also suitable for biosyngas

A steel slag–derived Boudouard reaction catalyst for improved performance of direct carbon solid oxide fuel cells

Solid oxide fuel cells (SOFCs) can directly utilize solid carbon as fuel by integrating with the reverse Boudouard reaction in the anode chamber. Efficiency of the Boudouard gasification of solid carbon fuel is one of the crucial factors influencing the performance of direct carbon SOFCs (DC-SOFCs). In this paper, a novel Boudouard reaction catalyst derived from steel slag was first introduced into DC-SOFCs for improving the electrochemical performance. The catalytic activity of the steel slag was activated using the molten alkali method to decompose the inert mineral phases of the raw material. The steel slag–derived catalyst was loaded on the activated charcoal by a wet ball milling method. This kind of catalyst can match up to the readily available solid carbon fuels in cost. Promoted by this highly active Boudouard reaction catalyst, the initial Boudouard gasification temperature of the carbon fuel decreased by 99°C, and the producing rate of carbon monoxide doubled. Furthermore, the power outputs of the fuel cells increased from 91 to 159 mW cm, and the fuel utilization increased from 17.10% to 46.43% at 825°C. This study demonstrates that the steel slag–derived catalyst is a promising material for the performance improvement of DC-SOFCs and may make a valuable contribution to their commercial application

Preparation of thin electrolyte film via dry pressing/heating/ quenching/calcining for electrolyte-supported SOFCs

The development of technologies used to prepare thin electrolyte films will stimulate the application of electrolyte supported SOFCs since thin electrolyte films typically have low ohmic resistances and good electrochemical performance. This paper presents a novel method for the preparation of thin electrolyte films for yttria-stabilized zirconia (YSZ)-supported solid oxide fuel cells (SOFCs) via dry pressing/heating/quenching/calcining. The thicknesses of the as-prepared YSZ films were as low as 78 mu m, which is significantly thinner than those prepared using a traditional method (greater than 200 mu m) via dry pressing/calcining/polishing. More importantly, the preparation process was quicker. Using this novel method, a YSZ-supported cell with a configuration of (La0.6Sr0.4)(0.9)Co0.8Fe0.2O3-delta (LSCF)-Ce0.8Sm0.2O2-delta(SDC)/SDC/YSZ/SDC/Ba0.5Sr0.5Co0.8Fe0.2O3-delta(BSCF)-SDC was fabricated and tested. The results showed promising electrochemical performance and a peak power density of 0.64 W cm(-2) at 850 degrees C was obtained, which was much higher than the cell fabricated using the traditional method (0.29 W cm(-2)). The ohmic resistance (R-O) at 850 degrees C is 0.19 Omega cm(2), which is much lower than that of the cell fabricated using the traditional method (0.33 Omega cm(2)) at an identical temperature. The modified method described in this work is shown to be a promising technique to prepare thin electrolyte films for high-performance, electrolyte-supported SOFCs