Balancing hydrogen adsorption/desorption by orbital modulation for efficient hydrogen evolution catalysis

Hydrogen adsorption/desorption behavior plays a key role in hydrogen evolution reaction (HER) catalysis. The HER reaction rate is a trade-off between hydrogen adsorption and desorption on the catalyst surface. Herein, we report the rational balancing of hydrogen adsorption/desorption by orbital modulation using introduced environmental electronegative carbon/nitrogen (C/N) atoms. Theoretical calculations reveal that the empty d orbitals of iridium (Ir) sites can be reduced by interactions between the environmental electronegative C/N and Ir atoms. This balances the hydrogen adsorption/ desorption around the Ir sites, accelerating the related HER process. Remarkably, by anchoring a small amount of Ir nanoparticles (7.16 wt%) in nitrogenated carbon matrixes, the resulting catalyst exhibits significantly enhanced HER performance. This includs the smallest reported overpotential at 10 mA cm(-2) (4.5 mV), the highest mass activity at 10 mV (1.12 A mg(Ir)(-1)) and turnover frequency at 25 mV (4.21 H2 s(-1)) by far, outperforming Ir nanoparticles and commercial Pt/C

The novel adipokine progranulin counteracts IL-1 and TLR4-driven inflammatory response in human and murine chondrocytes via TNFR1

Progranulin (PGRN) is a recently identified adipokine that is supposed to have anti-inflammatory actions. The proinflammatory cytokine interleukin-1? (IL1?) stimulates several mediators of cartilage degradation. Toll like receptor-4 (TLR4) can bind to various damage-associated molecular patterns, leading to inflammatory condition. So far, no data exist of PGRN effects in inflammatory conditions induced by IL1? or lipopolysaccharide (LPS). Here, we investigated the anti-inflammatory potential of PGRN in IL1?- or LPS-induced inflammatory responses of chondrocytes. Human osteoarthritic chondrocytes and ATDC-5 cells were treated with PGRN in presence or not of IL1? or LPS. First, we showed that recombinant PGRN had no effects on cell viability. We present evidence that PGRN expression was increased during the differentiation of ATDC-5 cell line. Moreover, PGRN mRNA and protein expression is increased in cartilage, synovial and infrapatellar fat pad tissue samples from OA patients. PGRN mRNA levels are upregulated under TNF? and IL1? stimulation. Our data showed that PGRN is able to significantly counteract the IL1?-induced expression of NOS2, COX2, MMP13 and VCAM-1. LPS-induced expression of NOS2 is also decreased by PGRN. These effects are mediated, at least in part, through TNFR1. Taken together, our results suggest that PGRN has a clear antiinflammatory function

Shugoshin1 May Play Important Roles in Separation of Homologous Chromosomes and Sister Chromatids during Mouse Oocyte Meiosis

Background: Homologous chromosomes separate in meiosis I and sister chromatids separate in meiosis II, generating haploid gametes. To address the question why sister chromatids do not separate in meiosis I, we explored the roles of Shogoshin1 (Sgo1) in chromosome separation during oocyte meiosis. Methodology/Principal Findings: Sgo1 function was evaluated by exogenous overexpression to enhance its roles and RNAi to suppress its roles during two meioses of mouse oocytes. Immunocytochemistry and chromosome spread were used to evaluate phenotypes. The exogenous Sgo1 overexpression kept homologous chromosomes and sister chromatids not to separate in meiosis I and meiosis II, respectively, while the Sgo1 RNAi promoted premature separation of sister chromatids. Conclusions: Our results reveal that prevention of premature separation of sister chromatids in meiosis I requires th

Interaction and efficacy of Keigai-rengyo-to extract and acupuncture in male patients with acne vulgaris: A study protocol for a randomized controlled pilot trial

<p>Abstract</p> <p>Background</p> <p>In consideration of patients seeking to use traditional Chinese medicine, an evidence-based potentiality for safe and effective use of herbal medicine and acupuncture in treatment of acne vulgaris has been suggested. However, despite common use of a combination of herbal medicine and acupuncture in clinical practice, the current level of evidence is insufficient to draw a conclusion for an interaction and efficacy of herbal medicine and acupuncture. Therefore, considering these methodological flaws, this study was designed to assess the interaction and efficacy of an available herbal medicine, Keigai-rengyo-to extract (KRTE), and acupuncture for treatment of acne using the 2 × 2 factorial design and the feasibility of a large clinical trial.</p> <p>Methods/Design</p> <p>A randomized, assessor single blinded, 2 × 2 factorial pilot trial will be conducted. Forty four participants with acne vulgaris will be randomized into one of four groups: waiting list group (WL), KRTE only group (KO), acupuncture only group (AO), and KRTE and acupuncture combined treatment group (KA). After randomization, a total of 8 sessions of acupuncture treatment will be performed twice a week in the AO- and KA groups, respectively. Patients in the KO- and KA groups will be prescribed KRTE 3 times a day at a dose of 7.4 g after meals for 4 weeks. The following outcome measurements will be used in examination of subjects: the mean percentage change and the count change of inflammatory and non-inflammatory acne lesions, the Skindex 29, visual analogue scale (VAS) and investigator global assessment (IGA) from baseline to the end of the trial.</p> <p>Trial Registration</p> <p>The trial is registered with the Clinical Research Information Service (CRiS), Republic of Korea: KCT0000071.</p

STING couples with PI3K to regulate actin reorganization during BCR activation

The adaptor protein, STING (stimulator of interferon genes), has been rarely studied in adaptive immunity. We used Sting KO mice and a patient's mutated STING cells to study the effect of STING deficiency on B cell development, differentiation, and BCR signaling. We found that STING deficiency promotes the differentiation of marginal zone B cells. STING is involved in BCR activation and negatively regulates the activation of CD1 9 and Btk but positively regulates the activation of SHIP. The activation of WASP and accumulation of F-actin were enhanced in Sting KO B cells upon BCR stimulation. Mechanistically, STING uses PI3K mediated by the CD19-Btk axis as a central hub for controlling the actin remodeling that, in turn, offers feedback to BCR signaling. Overall, our study provides a mechanism of how STING regulates BCR signaling via feedback from actin reorganization, which contributes to positive regulation of STING on the humoral immune response

Peripheral nervous system manifestations in a Sandhoff disease mouse model: nerve conduction, myelin structure, lipid analysis

<p>Abstract</p> <p>Background</p> <p>Sandhoff disease is an inherited lysosomal storage disease caused by a mutation in the gene for the β-subunit (<it>Hexb </it>gene) of β-hexosaminidase A (αβ) and B (ββ). The β-subunit together with the GM2 activator protein catabolize ganglioside GM2. This enzyme deficiency results in GM2 accumulation primarily in the central nervous system. To investigate how abnormal GM2 catabolism affects the peripheral nervous system in a mouse model of Sandhoff disease (<it>Hexb-/-</it>), we examined the electrophysiology of dissected sciatic nerves, structure of central and peripheral myelin, and lipid composition of the peripheral nervous system.</p> <p>Results</p> <p>We detected no significant difference in signal impulse conduction velocity or any consistent change in the frequency-dependent conduction slowing and failure between freshly dissected sciatic nerves from the <it>Hexb</it>+/- and <it>Hexb</it>-/- mice. The low-angle x-ray diffraction patterns from freshly dissected sciatic and optic nerves of <it>Hexb</it>+/- and <it>Hexb</it>-/- mice showed normal myelin periods; however, <it>Hexb</it>-/- mice displayed a ~10% decrease in the relative amount of compact optic nerve myelin, which is consistent with the previously established reduction in myelin-enriched lipids (cerebrosides and sulfatides) in brains of <it>Hexb-/- </it>mice. Finally, analysis of lipid composition revealed that GM2 content was present in the sciatic nerve of the <it>Hexb</it>-/- mice (undetectable in <it>Hexb</it>+/-).</p> <p>Conclusion</p> <p>Our findings demonstrate the absence of significant functional, structural, or compositional abnormalities in the peripheral nervous system of the murine model for Sandhoff disease, but do show the potential value of integrating multiple techniques to evaluate myelin structure and function in nervous system disorders.</p

Profound Effect of Profiling Platform and Normalization Strategy on Detection of Differentially Expressed MicroRNAs – A Comparative Study

Adequate normalization minimizes the effects of systematic technical variations and is a prerequisite for getting meaningful biological changes. However, there is inconsistency about miRNA normalization performances and recommendations. Thus, we investigated the impact of seven different normalization methods (reference gene index, global geometric mean, quantile, invariant selection, loess, loessM, and generalized procrustes analysis) on intra- and inter-platform performance of two distinct and commonly used miRNA profiling platforms.We included data from miRNA profiling analyses derived from a hybridization-based platform (Agilent Technologies) and an RT-qPCR platform (Applied Biosystems). Furthermore, we validated a subset of miRNAs by individual RT-qPCR assays. Our analyses incorporated data from the effect of differentiation and tumor necrosis factor alpha treatment on primary human skeletal muscle cells and a murine skeletal muscle cell line. Distinct normalization methods differed in their impact on (i) standard deviations, (ii) the area under the receiver operating characteristic (ROC) curve, (iii) the similarity of differential expression. Loess, loessM, and quantile analysis were most effective in minimizing standard deviations on the Agilent and TLDA platform. Moreover, loess, loessM, invariant selection and generalized procrustes analysis increased the area under the ROC curve, a measure for the statistical performance of a test. The Jaccard index revealed that inter-platform concordance of differential expression tended to be increased by loess, loessM, quantile, and GPA normalization of AGL and TLDA data as well as RGI normalization of TLDA data.We recommend the application of loess, or loessM, and GPA normalization for miRNA Agilent arrays and qPCR cards as these normalization approaches showed to (i) effectively reduce standard deviations, (ii) increase sensitivity and accuracy of differential miRNA expression detection as well as (iii) increase inter-platform concordance. Results showed the successful adoption of loessM and generalized procrustes analysis to one-color miRNA profiling experiments

MicroRNA Profiling during Cardiomyocyte-Specific Differentiation of Murine Embryonic Stem Cells Based on Two Different miRNA Array Platforms

MicroRNA (miRNA) plays a critical role in a wide variety of biological processes. Profiling miRNA expression during differentiation of embryonic stem cells will help to understand the regulation pathway of differentiation, which in turn may elucidate disease mechanisms. The identified miRNAs could then serve as a new group of possible therapeutic targets. In the present paper, miRNA expression profiles were determined during cardiomyocyte-specific differentiation and maturation of murine embryonic stem (ES) cells. For this purpose a homogeneous cardiomyocyte population was generated from a transgenic murine ES cell line. Two high throughput array platforms (Affymetrix and Febit) were used for miRNA profiling in order to compare the effect of the platforms on miRNA profiling as well as to increase the validity of target miRNA identification. Four time points (i.e. day 0, day 12, day 19 and day 26) were chosen for the miRNA profiling study, which corresponded to different stages during cardiomyocyte-specific differentiation and maturation. Fifty platform and pre-processing method-independent miRNAs were identified as being regulated during the differentiation and maturation processes. The identification of these miRNAs is an important step for characterizing and understanding the events involved in cardiomyocyte-specific differentiation of ES cells and may also highlight candidate target molecules for therapeutic purposes

Assessment of dietary intake among pregnant women in a rural area of western China

<p>Abstract</p> <p>Background</p> <p>Adequate maternal nutrient intake during pregnancy is important to ensure satisfactory birth outcomes. There are no data available on the usual dietary intake among pregnant women in rural China. The present study describes and evaluates the dietary intake in a cohort of pregnant women living in two counties of rural Shaanxi, western China.</p> <p>Methods</p> <p>1420 pregnant women were recruited from a trial that examined the effects of micronutrient supplementation on birth outcomes. Dietary information was collected at the end of their trimester or after delivery with an interviewed-administrated semi-quantitative food frequency questionnaire (FFQ). Nutrients intake was calculated from the FFQ and compared to the Estimated Average Requirements (EAR). The EAR cut-offs based on the Chinese Nutrition Society Dietary Reference Intakes (DRIs) were used to assess the prevalence of inadequate dietary intakes of energy, protein, calcium, zinc, riboflavin, vitamin C and folate. Mann-Whitney U and Kruskal Wallis tests were used to compare nutrient intakes across subgroups.</p> <p>Results</p> <p>The mean nutrient intakes assessed by the FFQ was similar to those reported in the 2002 Chinese National Nutrition and Health Survey from women living in rural areas except for low intakes of protein, fat, iron and zinc. Of the participants, 54% were at risk of inadequate intake of energy. There were high proportions of pregnant women who did not have adequate intakes of folate (97%) and zinc (91%). Using the "probability approach", 64% of subjects had an inadequate consumption of iron.</p> <p>Conclusion</p> <p>These results reveal that the majority of pregnant women in these two counties had low intakes of nutrients that are essential for pregnancy such as iron and folate.</p> <p>Trial registration</p> <p>ISRCTN08850194.</p