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Atherosclerosis caused major morbidity and mortality worldwide. Molecules possessing lipid-lowering and/or anti-inflammatory properties are potential druggable targets against atherosclerosis. We examined the anti-atherosclerotic effects of fluorescent gold nanoclusters (FANC), which were dihydrolipoic acid (DHLA)-capped 2-nm gold nanoparticles. We evaluated the 8-week effects of FANC in Western-type diet-fed ApoE-deficient mice by either continuous intraperitoneal delivery (20 μM, 50 μl weekly) or via drinking water (300 nM). FANC reduced aortic atheroma burden, serum total cholesterol, and oxidative stress markers malondialdehyde and 4-hydroxynonenal levels. FANC attenuated hepatic lipid deposit, with changed expression of lipid homeostasis-related genes HMGCR, SREBP, PCSK9, and LDLR in a pattern similar to mice treated with ezetimibe. FANC also inhibited intestinal cholesterol absorption, resembling the action of ezetimibe. The lipid-lowering and anti-atherosclerotic effects of FANC reappeared in Western-type diet-fed LDLr-deficient mice. FANC bound insulin receptor β (IRβ) via DHLA, leading to AKT activation. However, unlike insulin, which also bound IRβ to activate AKT to induce HO-1, activation of AKT by FANC was independent of HO-1 expression in human aortic endothelial cells (HAECs). Alternatively, FANC up-regulated NRF2, interfered the binding of KEAP1 to NRF2, and promoted KEAP1 degradation to free NRF2 for nuclear entry to induce HO-1 that suppressed the expression of ICAM-1 and VCAM-1. Consistently, FANC suppressed ox-LDL-induced enhanced attachment of THP-derived macrophages onto HAECs. In macrophages, FANC up-regulated ABCA1, and reversed ox-LDL-induced suppression of cholesterol efflux. FANC effected in vitro at nano moles. In conclusion, our findings showed novel actions and multiple mechanisms of FANC worked coherently against atherosclerosis.

Today, more and more Greater Chinese students are motivated to study in Western universities more specifically French universities. This makes France one of the fourth most popular destination for international students. Using pragmatics and social-cultural constructivist perspectives, this article aims at improving the adaptation of the Greater Chinese students benefiting from a French-Greater Chinese university exchange. The method employed in this study was descriptive qualitative research based on interviews and online surveys with Greater Chinese students for two academic years before they went to France and while staying there. The results at the end of which we made some suggestions for academic purposes took place prior to these exchanges. Furthermore, we focus on what seems the most important to us, meaning adaptation to French university pedagogical methods. Thus, the article proposed a presentation of the characteristics, the main obstacles faced and the appropriate advice for the elaboration of the syllabus. To summarize, the paper proposes reflections in the sense of designing FFL preparatory syllabi specific to study programs. By listing the real encountered problems and suggesting means to overcome them, we think this can be helpful to FFL teachers and students involved. Implications for teachers, researchers and learners are highlighted. Keywords: FFL, academic competences, university pedagogical methods, lectures, FSP (French for Specific Purposes)

This paper explores factors that influenced the quality of stay of Chinese-speaking mobile students in France, as the living experience abroad is one of the most-cited difficulties for international students. For practicality, we sieve through previous researches to identify 20 factors (grouped into 4 Dimensions: Personal Dimension Teacher's Effectiveness Dimension, Campus Environment Dimension, and Daily Environment Dimension), which most likely correlated with the quality of the stay of mobile Chinese-speaking students in France. We adopt the DANP (DEMATEL-based ANP) model, i.e., combining the Decision Making and Trial Evaluation Laboratory (DEMATEL) method and the Analysis Network Process (ANP), to construct the Influential Network Relation Maps, identifying the hierarchical structure among the factors and the dimensions. We find that the "Teacher's Effectiveness" is the most influential dimension to the other 3 dimension. Our research can provide more insights on the French educational system improvement, and help define a more effective policy strategy focus.

The selective genotyping approach, where only individuals from the high and low extremes of the trait distribution are selected for genotyping and the remaining individuals are not genotyped, has been known as a cost-saving strategy to reduce genotyping work and can still maintain nearly equivalent efficiency to complete genotyping in QTL mapping. We propose a novel and simple statistical method based on the normal mixture model for selective genotyping when both genotyped and ungenotyped individuals are fitted in the model for QTL analysis. Compared to the existing methods, the main feature of our model is that we first provide a simple way for obtaining the distribution of QTL genotypes for the ungenotyped individuals and then use it, rather than the population distribution of QTL genotypes as in the existing methods, to fit the ungenotyped individuals in model construction. Another feature is that the proposed method is developed on the basis of a multiple-QTL model and has a simple estimation procedure similar to that for complete genotyping. As a result, the proposed method has the ability to provide better QTL resolution, analyze QTL epistasis, and tackle multiple QTL problem under selective genotyping. In addition, a truncated normal mixture model based on a multiple-QTL model is developed when only the genotyped individuals are considered in the analysis, so that the two different types of models can be compared and investigated in selective genotyping. The issue in determining threshold values for selective genotyping in QTL mapping is also discussed. Simulation studies are performed to evaluate the proposed methods, compare the different models, and study the QTL mapping properties in selective genotyping. The results show that the proposed method can provide greater QTL detection power and facilitate QTL mapping for selective genotyping. Also, selective genotyping using larger genotyping proportions may provide roughly equivalent power to complete genotyping and that using smaller genotyping proportions has difficulties doing so. The R code of our proposed method is available on http://www.stat.sinica.edu.tw/chkao/. [ABSTRACT FROM AUTHOR]

Two approaches are proposed for constructing one- and two-sided confidence limits for conformance proportions in a normal variance components model. One approach is based on the concepts of a generalized pivotal quantity, and the other is developed using the modified large-sample method for estimating linear combinations of variance components. The performance of the proposed methods is evaluated through detailed simulation studies. The results reveal that the empirical coverage probabilities for both methods are close to the claimed values and hence their performance is judged to be satisfactory. Nonetheless, the modified large-sample-based method might be recommended in practical applications due to its slightly better performance and computational ease. The framework established in this article can be applied to conformance proportion questions arising in arbitrary balanced mixed linear-model situations. The methods are illustrated using three real datasets. Finally, a bootstrap calibration approach is adopted to have empirical coverage probabilities sufficiently close to the nominal level for the proposed methods. [ABSTRACT FROM AUTHOR]

Cytokine and antiangiogenic gene therapies have proved effective in implanted hepatocellular carcinoma (HCC) models in which small tumor burdens were established in small rodents. These models, however. may not reflect human HCCs, which are frequently detected at a stage when tumors are large and multifocal. In addition. .HCC in patients is often associated with viral hepatitis. To in- vestigate the effectiveness of a mixture type of gene therapy strategy on large tumor burdens, we used the woodchuck model in which woodchuck hepatitis virus-induced HCC5 are large and multifocal, simulating the conditions in humans. Adenoviruses en- coding antiangiogenic factors (pigment epithelium-derived factor and endostatin) or cytokines (GM-CSF and IL-12) were delivered via the hepatic artery separately or in combination into woodchuck livers bearing HCC5. Our results showed that the mixture type of strategy, which contained two cytokines and two antiangiogenic factors, had better antitumor effects on large tumors as compared with monotherapy either with antiangiogenic or cytokine genes. The immunotherapy recruited significant levels of CD3 T cells that infiltrated the tumors, whereas the antiangiogenesis-based ther- apy significantly reduced tumor vasculature. The mixture type of gene therapy achieved both effects. In addition, it induced high levels of natural killer cells and apoptotic cells and reduced the levels of immunosuppressive effectors in the tumor regions. Hence, antiangiogenic therapy may provide the advantage of reducing immune tolerance in large tumors, making them more vulnerable to the immune reactions. Our study implies that in the future, the combination therapy may prove effective for the treatment of patients with advanced HCC. [ABSTRACT FROM AUTHOR]

Abstract The therapeutic effects of ultrasonic microbubble transfection (UMT)-based vascular endothelial growth factor 165 (VEGF165) gene delivery on young and senescent endothelial progenitor cells (EPCs) were investigated. By UMT, plasmid DNA (pDNA) can be delivered into both young EPCs and senescent EPCs. In the UMT groups, higher pDNA-derived protein expression was found in senescent EPCs than in young EPCs. Consistent with this finding, a higher intracellular level of pDNA copy number was detected in senescent EPCs, with a peak at the 2-h time point post UMT. Ultrasonic microbubble delivery with or without VEGF improved the angiogenic properties, including the proliferation and/or migration activities, of senescent EPCs. Supernatants from young and senescent EPCs subjected to UMT-mediated VEGF transfection enhanced the proliferation and migration of human aortic endothelial cells (HAECs), and the supernatant of senescent EPCs enhanced proliferation more strongly than the supernatant from young EPCs. In the UMT groups, the stronger enhancing effect of the supernatant from senescent cells on HAEC proliferation was consistent with the higher intracellular VEGF pDNA copy number and level of protein production per cell in the supernatant from senescent cells in comparison to the supernatant from young EPCs. Given that limitations for cell therapies are the inadequate number of transplanted cells and/or insufficient cell angiogenesis, these findings provide a foundation for enhancing the therapeutic angiogenic effect of cell therapy with senescent EPCs in ischaemic cardiovascular diseases.