NYGGF4, an obesity-related gene, is proposed to be involved in the development of insulin resistance. Skeletal muscle is a primary target organ for insulin and NYGGF4 showed a relatively high ...expression level in skeletal muscle. Therefore, this study aimed to explore the effect of NYGGF4 on insulin sensitivity of skeletal muscle cells. RNA interference (RNAi) was adopted to silence NYGGF4 expression in mice C2C12 skeletal myocytes. A remarkably increased insulin-stimulated glucose uptake and GLUT4 translocation was observed in NYGGF4 silencing C2C12 cells. Importantly, the enhanced glucose uptake induced by NYGGF4 silencing could be abrogated by the PI3K inhibitor LY294002. In addition, the crucial molecules involved in PI3K insulin signaling pathway were detected by western blotting. The results showed that NYGGF4 knockdown dramatically activate the insulin-stimulated phosphorylation of IRS-1 and AKT. Taken together, these data demonstrate that NYGGF4 knockdown increases glucose transport in myocytes by activation of the IRS-1/PI3K/AKT insulin pathway.
To support pharmacokinetic studies of ginsenosides, a novel method to quantitatively analyze ginsenoside Rg3 (Rg3), its prosapogenin ginsenoside Rh2 (Rh2) and aglycone 20(S)-protopanaxadiol (ppd) in ...rat plasma was developed and validated. The method was based on gradient separation of ginsenosides present in rat plasma using high performance liquid chromatography (HPLC), followed by detection with electrospray ionization(ESI) mass spectrometry (MS) in negative ion mode with the mobile phase additive, ammonium chloride (500 microM). Differentiation of ginsenosides was achieved through simultaneous detection of the M(+)Cl(-) adduct of ginsenoside Rg3 and M(+)Cl(-) adducts of its deglycosylated metabolites Rh2 and ppd, and other ions after solid phase extraction (SPE). The /specific ions monitored were m/z 819.50 for Rg3, m/z 657.35 for Rh2, m/z 495.40 for ppd and m/z 799.55 for the internal standard (digitoxin). The mean recoveries for Rg3, Rh2 and ppd were 77.85, 82.65 and 98.33%, respectively using 0.1 ml plasma for extraction. The lower limits of quantification were 10.0, 2.0 and 8.0 ng/ml (equivalent to 0.1, 0.02 and 0.08 ng in each 10 microl injection onto the HPLC column) for Rg3, Rh2 and ppd, respectively. The method has been demonstrated to be highly sensitive and accurate for the determination of Rg3 and its metabolites in rat plasma.
Weather factors have long been considered as key sources for regional heterogeneity of influenza seasonal patterns. As influenza peaks coincide with both high and low temperature in subtropical ...cities, weather factors may nonlinearly or interactively affect influenza activity. This study aims to assess the nonlinear and interactive effects of weather factors with influenza activity and compare the responses of influenza epidemic to weather factors in two subtropical regions of southern China (Shanghai and Hong Kong) and one temperate province of Canada (British Columbia). Weekly data on influenza activity and weather factors (i.e., mean temperature and relative humidity (RH)) were obtained from pertinent government departments for the three regions. Absolute humidity (AH) was measured by vapor pressure (VP), which could be converted from temperature and RH. Generalized additive models were used to assess the exposure-response relationship between weather factors and influenza virus activity. Interactions of weather factors were further assessed by bivariate response models and stratification analyses. The exposure-response curves of temperature and VP, but not RH, were consistent among three regions/cities. Bivariate response model revealed a significant interactive effect between temperature (or VP) and RH (
P
< 0.05). Influenza peaked at low temperature or high temperature with high RH. Temperature and VP are important weather factors in developing a universal model to explain seasonal outbreaks of influenza. However, further research is needed to assess the association between weather factors and influenza activity in a wider context of social and environmental conditions.
Objective To determine whether the novel avian influenza H7N9 virus can transmit from person to person and its efficiency. Design Epidemiological investigations conducted after a family cluster of ...two patients with avian H7N9 in March 2013. Setting Wuxi, Eastern China. Participants Two patients, their close contacts, and relevant environments. Samples from the patients and environments were collected and tested by real time reverse transcriptase-polymerase chain reaction (rRT-PCR), viral culture, and haemagglutination inhibition assay. Any contacts who became ill had samples tested for avian H7N9 by rRT-PCR. Paired serum samples were obtained from contacts for serological testing by haemagglutination inhibition assays. Main outcomes measures Clinical data, history of exposure before the onset of illnesses, and results of laboratory testing of pathogens and further analysis of sequences and phylogenetic tree to isolated strains. Results The index patient became ill five to six days after his last exposure to poultry. The second patient, his daughter aged 32, who provided unprotected bedside care in the hospital, had no known exposure to poultry. She developed symptoms six days after her last contact with her father. Two strains were isolated successfully from the two patients. Genome sequence and analyses of phylogenetic trees showed that both viruses were almost genetically identical. Forty three close contacts of both patients were identified. One had mild illness but had negative results for avian H7N9 by rRT-PCR. All 43 close contacts tested negative for haemagglutination inhibition antibodies specific for avian H7N9. Conclusions The infection of the daughter probably resulted from contact with her father (the index patient) during unprotected exposure, suggesting that in this cluster the virus was able to transmit from person to person. The transmissibility was limited and non-sustainable.
The photodissociation experiments of A2M+and G2M+ complexes at 266nm show that the loss of one nucleobase is the predominant channel for M=Cu and Ag, while the loss of AAu or GAu is the major channel ...for M=Au.
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•All of A2M+ and G2M+ cations are planar structures in nucleobase-M+-nucleobase style, containing a nearly linear N–M+–N bond.•The dissociation channels depend on the types of nucleobases and metal ions.•The loss of one nucleobase (adenine or guanine) molecule are the predominant channels for M=Cu and Ag.•The loss of AAu or GAu are the major channels for M=Au.
To understand the interactions between nucleobases and coinage metal cations, we conducted combined photodissociation and density functional theory studies on A2M+ and G2M+ (A=adenine, G=guanine, M=Cu, Ag, and Au) cations. The nucleobase-metal complexes were produced by laser ablation and detected by a reflectron time-of-flight mass spectrometer. The mass peaks of A2M+ and G2M+ cations have high intensities in the mass spectra of AnM+ and GnM+ complexes, indicating that these cations have relatively high stabilities. They were mass-selected and then photodissociated by 266nm photons. Their photodissociation spectra clearly show that the loss of adenine or guanine is the predominant channel for these complexes. The density functional theory calculations show that A2M+ and G2M+ complexes prefer planar structures with the metal cations interacting with the N atoms in the carbon-nitrogen rings of adenine and guanine. The calculated bond dissociation energies of different dissociation channels are in good agreement with the experimental observed fragment ions.
The incorporation of pentagon‐heptagon pairs into helical nanographenes lacks a facile synthetic route, and the impact of these pairs on chiroptical properties remains unclear. In this study, a ...method for the stepwise construction of pentagon‐heptagon pairs in helical nanographenes by the dehydrogenation of 6helicene units was developed. Three helical nanographenes containing pentagon‐heptagon pairs were synthesized and characterized using this approach. A wide variation in the molecular geometries and photophysical properties of these helical nanographenes was observed, with changes in the helical length of these structures and the introduction of the pentagon‐heptagon pairs. The embedded pentagon‐heptagon pairs reduced the oxidation potential of the synthesized helical nanographenes. The high isomerization energy barriers enabled the chiral resolution of the helicene enantiomers. Chiroptical investigations revealed remarkably enhanced circularly polarized luminescence and luminescence dissymmetry factors with an increasing number of the pentagon‐heptagon pairs.
The controlled dehydrogenation of 6helicene units provides a facile and feasible method for the synthesis of helical nanographenes containing pentagon‐heptagon pairs. The presence of pentagon‐heptagon pairs has proven to be quite effective in modulating the electrochemical and photophysical properties of the resulting nanographenes, including enhanced circularly polarized luminescence.
The ecological risk posed by tritium (T) and carbon-14 (C-14) discharge from nuclear accidents has gained attention. This study evaluated the toxic impact of T and C-14 (at a concentration of 37 ...kBq/L for 15 days) on the cyanobacteria (Synechococcus elongatus). The results showed that the assimilation efficiency of cyanobacteria was significantly higher for C-14 than T, and the intracellular C-14 activity reached 30.62–40.58 kBq/kg. T and C-14 exposure had no significant effect on cell proliferation but impacted photosynthesis and respiration. T exposure increased the content of Ca, Mg, Na, P, K, and Mn, while C-14 exposure primarily affected trace element absorption in cyanobacteria. 31, 27, and 58 different metabolites (DEMs) were identified under T, C-14, and combined exposure conditions. These DEMs were enriched in the amino acid biosynthesis pathway, and nitrogen assimilation was one of the crucial pathways affected by T and C-14 exposure. The absorption of mineral elements by cyanobacteria was influenced by the variation in metabolites in the ABC transporter pathway caused by T and C-14 exposure. Our findings provide insights into the metabolic response of cyanobacteria to T and C-14 exposure and will help to guide the ecological risk evaluation of nuclear accidents.
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•T and C-14 had an impact on photosynthesis and respiration of cyanobacteria.•T and C-14 exposure affected trace elements absorption in cyanobacteria.•T and C-14 exposure alters metabolites in amino acid and ABC transporter pathways.•Variants of ABC transporter pathway affect cyanobacteria's ability to absorb mineral elements.
Background Despite the proven benefits of clopidogrel combined aspirin therapy for coronary artery disease （CAD）, CAD patients with metabolic syndrome （MS） still tend to have coronary thrombotic ...events. We aimed to investigate the influence of metabolic risk factors on the efficacy of clopidogrel treatment in patients with CAD undergoing percutaneous coronary intervention （PCI）. Methods Cohorts of 168 MS and 168 non-MS subjects with CAD identified by coronary angiography （CAG） were enrolled in our study. MS was defined by modified Adult Treatment Panel Ⅲ criteria. All subjects had taken 100 mg aspirin and 75 mg clopidogrel daily for more than 1 month, and administered loading doses of 600 mg clopidogrel and 300 mg aspirin before PCI. Blood samples were taken 24 h after the loading doses of clopidogrel and aspirin. Platelet aggregation was measured using light transmittance aggregometry （LTA） and thrombelastography （TEG）. Clopidogrel resistance was defined as more than 50% adenosine diphosphate （ADP） induced platelet aggregation as measured by TEG. Re- sults Platelet aggregation inhibition rate by ADP was significantly lower in patients with MS as measured both by TEG （55% ＋ 31% vs. 68% ± 32%; P 〈 0.001） and LTA （29% ± 23% vs. 42% ± 29%; P 〈 0.001）. In the multivariate analysis, elderly OR （95% CI）： 1.483 （1.047±.248）; P = 0.002, obesity OR （95% CI）： 3.608 （1.241-10.488）; P = 0.018, high fasting plasma glucose level OR （95% CI）： 2.717 （1.176±.277）; P = 0.019 and hyperuricemia OR （95% CI）： 2.583 （1.095-6.094）; P = 0.030 were all statistically risk factors for clopido- grel resistance. CAD patients with diabetes and obesity were more likely to have clopidogrel resistance than the CAD patients without dia- betes and obesity 75% （61/81） vs. 43% （67/156）; P 〈 0.001. Conclusions CAD patients with MS appeared to have poorer antiplatelet response to clopidogrel compared to those without MS. Obesity, diabetes and hyperuricemia were all significantly associated with clopido- grel resistance.
Premise of research. In advanced ferns that possess an egg envelope and a fertilization pore, a sac that persistently blocks the fertilization pore is considered a barrier for preventing polyspermy. ...However, for those ferns with no egg envelope and fertilization pore, the cytological mechanism for preventing polyspermy is still unclear. In this investigation, the main cytological processes during fertilization and zygote formation of the primitive fern Osmunda japonica are observed, and a novel cytological mechanism for preventing polyspermy is described.
Methodology. The fertilization process was observed under stereomicroscope, and the fertilization time was recorded. The selected plants were fixed with glutaraldehyde and osmic acid and embedded in pure Spurr’s resin. Specimens were first thick-sectioned and then thin-sectioned for LM and TEM observations.
Pivotal results. The observations showed that only one spermatozoid penetrates into the egg at the center in the upper surface of the mature egg. The egg immediately shrinks as the spermatozoid enters into the cytoplasm of the egg. The volume of the fertilized egg decreases remarkably, and simultaneously, a large vesicle forms above the fertilized egg. This vesicle can block other spermatozoids approaching the egg. During nuclear fusion, the male cytoskeleton defines a spatial framework, within which the male chromatin progressively fuses with the egg nucleus. The male organelles, including the microtubular ribbon, multilayered structure, flagella, and male mitochondria, are finally digested in the zygotic cytoplasm. A functional zygote is then formed at the venter of the archegonium.
Conclusions. In the primitive fern O. japonica, the large vesicle, formed during fertilization above the egg, can block other spermatozoids approaching the egg, which is considered to be a novel cytological mechanism for preventing polyspermy.
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