Le developpement de nouveaux donneurs d’oxyde nitrique (NO) dans le traitement chronique des maladies cardiovasculaires necessite l’etude de leur biodisponibilite apres administration par voie orale. Les S-nitrosothiols (RSNOs) apparaissent d’interessants candidats medicaments pour ce faire, et l’etude de leur permeabilite intestinale est une premiere etape indispensable. Il est necessaire de disposer d’une methodologie analytique suffisamment sensible et selective, en particulier permettant de differencier entre la production endogene de NO, l’apport alimentaire en ions nitrites et nitrate et le medicament lui-meme. Nos travaux de these ont consiste a utiliser le S-nitrosoglutathion (GSNO) comme modele apres son marquage par l’isotope stable 15 de l’azote (15N). La derivation du 15NO libere par deux methodes conventionnelles (methode de Griess conduisant a la formation d’un adduit azoique ; reaction avec le 2,3-diaminonaphtalene (DAN) formant l’adduit 2,3-naphtotriazole (NAT)) et l’etude de la fragmentation en spectrometrie de masse tandem (MS/MS) des deux adduits correspondants ont mene a selectionner la derivation par le DAN comme etant la plus sensible. Une transition originale resultant de la fragmentation du NAT en mode Higher-energy Collisional Dissociation (HCD) au lieu du mode conventionnel Collisionally Induced Dissociation (CID) a ete mise en evidence ; elle permet d’atteindre une limite de quantification de 5 nM (soit 20 fois plus basse que celle offerte par la fluorescence). La methode LC-MS/MS a ete validee et appliquee a l’etude de la permeabilite intestinale du GS15NO par deux modeles : l’un in vitro (monocouche de cellules epitheliales type Caco-2), l’autre ex vivo (intestin de rat isole (ileum) dans une chambre de Ussing). Les valeurs de permeabilite apparente calculees a partir des concentrations des metabolites du GS15NO (ions nitrites, nitrates et RSNOs) le classent comme un medicament de permeabilite intermediaire. En outre, des etudes sur les mecanismes de denitrosation du GSNO ont ete menees sur intestin isole, demontrant en particulier le role d’enzymes telles que la γ-glutamyltransferase et la protein disulfide isomerase
Lobothorax typus Bleeker, 1857, is recorded for the first time from Chinese waters. The species is redescribed, and the taxonomy, known hosts, and distributional data are discussed. A brief diagnosis of the genus is given.
Hepatocellular carcinoma (HCC) is a highly malignant disease that currently lacks effective treatment. Epidemiological studies have suggested the preventive role of raw garlic intake in different tumors, such as HCC. Although diallyl sulfide (DAS), the main component of garlic extracts, has been reported to inhibit the growth of HCC cells, the underlying mechanism remains elusive. This study aimed to investigate the inhibitory effect of DAS on the growth of HepG2 and Huh7 hepatocellular carcinoma cells and its underlying mechanism. HepG2 and Huh7 cells were treated with DAS and nude mice were intrahepatically injected with human HCC HepG2 cells and maintained with or without DAS administration for 28 days. MTS and clonogenic assays revealed that DAS inhibited the growth and clonogenicity of HepG2 and Huh7 hepatocellular carcinoma cells. Furthermore, DAS inhibited the growth of xenograft tumors accompanied by a decreased rate of pathological karyomitosis as observed by H&E staining. The expression levels of estrogen receptor-α36 (ER-α36) and epidermal growth factor receptor (EGFR) in HepG2 and Huh7 cells and in xenograft tumors derived from HepG2 cells after DAS treatment were detected by immunohistochemistry and western blotting. We found that DAS disrupted the positive regulatory loop between ER-α36 and EGFR, and decreased the phosphorylation of AKT at Ser 473 both in vivo and in vitro. DAS also induced cell apoptosis, as evidenced by Hoechst and TUNEL staining. Western blotting revealed activation of caspase3, increased BAX and decreased Bcl-2 expression. However, the ER-α36 expression knockdown attenuated DAS-induced ERK and AKT phosphorylation in HCC cells. DAS was also able to inhibit ER-α36-mediated activation of the MAPK/ERK signaling induced by estrogen. Thus, our results indicate that ER-α36 signaling is involved in DAS-induced inhibition of HCC cell growth both in vitro and in vivo.
<p>Understanding the spatial distribution and controlling factors of soil organic carbon (SOC) at different scales is essential for an accurate estimation of soil organic carbon stocks. Furthermore, this understanding is vital for evaluating the impact of soil management on both soil quality and climate change. This study was conducted in a Loess revegetated small watershed and the effects of the topography and vegetation factors on the content and distribution of SOC at different soil depths were evaluated. Soil profiles (0-200 cm; n = 122) were sampled that represent six vegetation types (i.e., natural mixed forests, artificial mixed forests, artificial forests with a single tree species, shrubbery, and grassland) and four topographic factors (i.e., elevation, slope gradient, slope position, and slope aspect). The following results were obtained: (1) The mean SOC of the 200 cm soil profile ranged from 2.34 g kg-1 to 5.70 g kg-1, decreasing with increasing soil depth. (2) The interactions between vegetation type and topography and soil depth significantly impacted SOC (P < 0.05). Significant differences in the SOC content (P < 0.05) were also found for slope gradient, slope position, slope aspect, and elevation for 0-200cm, 0-160cm, 0-120 cm and 0-200 cm, respectively. (3) The relative contribution of topographic factors to the SOC content exceeded that of vegetation type in entire soil profile. Topography was the dominant factor controlling the spatial distribution of SOC in the studied small watershed. Therefore, topographic factors should be considered more than vegetation types for an accurate estimation of SOC storage in a revegetated small watershed. This is particularly important for the complicated topography of the loess-gully region.</p>
Message-based debugging facilities for Web or Grid Services are separated from an infrastructure of source level debugging and can work in a self-identifying and coexisting mode within a normal services container. In this paper, we discuss problems for services debugging and approaches we take. We present the operational model and context inspection of message-based debugging facilities. The facilities are able to trace service behaviors, dump debugging information, and manage states and behavioral breakpoints of debugged services. This model supports a mechanism of multi-user and multi-site service debugging without requiring programmers or developers to one by one duplicate full scenarios in multiple servers.
Aegilops tauschii Coss. is known as a noxious grass weed seriously affecting wheat quality and yield. To investigate its present occurrence in wheat fields and the potential genetic diversity of the grass weed in China, a filed survey covering major wheat production regions was conducted during 2017–2019. Seeds of different Ae. tauschii populations collected from the survey were analyzed with Simple Sequence Repeats (SSRs) technique. Results showed that Ae. tauschii was occurring in each of the provinces surveyed with varied occurrence frequency ranging from 0.91% in Sichuan Province to 92.85% in Henan Provinces. Eighty alleles with size ranging from 98 bp to 277 bp were detected from the 192 collected Ae. tauschii populations with 17 SSR markers. Ae. tauschii, in this study, exhibited a moderately high level of genetic diversity, high differentiation, deficient heterozygosity and limited gene flow. Compared with other provinces, Hubei populations possessed relatively low genetic diversity. Dendrogram analysis showed that genetic distance did not seem to be related to geographic distribution. Additionally, STRUCTURE analysis suggested that Ae. tauschii populations in wheat fields of China can be divided into three groups, which was further supported by cluster analysis. Among the three groups, solely 7% of the total variation was detected, whereas the majority variation (67%) occurred among different populations within same group. Undoubtedly, such information will help us to better understand population relationships and spread of Ae. tauschii in China and will provide a new perspective for its integrated management.
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