BACKGROUND: Corticosteroids remain the most effective therapy available for asthma. They have widespread effects on asthmatic airway inflammation. However, little is known about the effects of corticosteroids on the p...BACKGROUND: Corticosteroids remain the most effective therapy available for asthma. They have widespread effects on asthmatic airway inflammation. However, little is known about the effects of corticosteroids on the production of bone marrow inflammatory cells in asthma. This study observed the effects of glucocorticoid and cysteinyl leukotriene 1 receptor antagonist on CD34+ hematopoietic cells, so as to explore the possible effectiveness of a bone marrow-targeted anti-inflammatory strategy. METHODS: Balb/c mice were sensitized and challenged with ovalbumin (OVA) to establish an asthmatic model. For two consecutive weeks, asthmatic mice were challenged with OVA while being given either prednisone, montelukast, prednisone plus montelukast, or sterile saline solution. The mice were killed 24 hours after the last challenge with OVA, and bronchoalveolar lavage fluid (BALF), peripheral blood, and bone marrow were collected. Eosinophils in peripheral blood and BALF, and nucleated cells in BALF, peripheral blood, and bone marrow were counted. The percentages of CD34+ cells, CD4+ T lymphocytes and CD8+ T lymphocytes among nucleated cells in peripheral blood and bone marrow were counted by flow cytometry. Immunocytochemistry and in situ hybridization were employed to detect expression of CD34 and interleukin (IL)-5Ralpha mRNA (CD34+ IL-5Ralpha mRNA+ cells) among bone marrow hematopoietic cells. RESULTS: Compared with the sterile saline solution group, the number of eosinophils in BALF and peripheral blood, CD34+ cells in peripheral blood and bone marrow, and CD34+ IL-5Ralpha mRNA+ cells in bone marrow of mice from the prednisone and prednisone plus montelukast groups were significantly lower (P展开更多
Herein,we disclose a novel copper-catalyzed C(sp)-H aryl amination of terminal alkynes with anthranils,enabling the rapid generation of highly reactive secondary N-aryl ynamines for the modular synthesis of structural...Herein,we disclose a novel copper-catalyzed C(sp)-H aryl amination of terminal alkynes with anthranils,enabling the rapid generation of highly reactive secondary N-aryl ynamines for the modular synthesis of structurally diverse C2-substituted quinolines and 2-quinolinones.The in-situ formed carbonyl-ynamines are prone to tautomerize to carbonyl-ketenimines,which can efficiently react with a series of nucleophiles,including amines,alcohols,phenols,thiols,thiophenols,active-methylene compounds,and even water to produce various quinoline derivatives with the generation of H_(2)O as a sole and green byproduct.This method also unlocks a practical route to create various quinoline-fused heterocycles and can be successfully applied to the late-stage modification of complex molecules and the concise synthesis of bioactive targets.Mechanistic studies reveal a coppercatalyzed inner-sphere nitrene transfer process by using anthranils as novel aryl nitrene precursors.展开更多
Employing triflic anhydride/2-fluoropyridine as an activation system, the coupling reactions of secondary N-aryl amides with terminal alkynes yielded substituted quinolines in moderate to excellent yields. The reactio...Employing triflic anhydride/2-fluoropyridine as an activation system, the coupling reactions of secondary N-aryl amides with terminal alkynes yielded substituted quinolines in moderate to excellent yields. The reaction tolerated both electron-donating and electron-withdrawing groups at the benzamide moiety. Electron-rich aryl acetylenes served as excellent coupling partners, and aliphatic terminal alkynes such as cyclopropyl and conjugate vinyl acetylenes could also be used as reaction partners. By means of 2 D NMR techniques(heteronuclear multiple bond correlation(HMBC), heteronuclear single quantum correlation(HSQC)),nitrilium ions were probed as reactive intermediates which are in contrast with that suggested by Movassaghi on the basis of in situ IR monitoring experiments. On the basis of these results, a plausible mechanism for the formation of quinolines was suggested.展开更多
Reusable acidic nickel oxide nanoparticles have been synthesized,characterized and applied as a catalyst to convert 2-aminoaryl ketones and β-ketoesters/ketones into the corresponding quinolines in good yields with h...Reusable acidic nickel oxide nanoparticles have been synthesized,characterized and applied as a catalyst to convert 2-aminoaryl ketones and β-ketoesters/ketones into the corresponding quinolines in good yields with high selectivity.This could serve as a simple and convenient procedure for the Friedlander annulations.展开更多
基金ThisprojectwassupportedbytheNationalNaturalScienceFoundationofChina (No 3 9770 3 40 )
文摘BACKGROUND: Corticosteroids remain the most effective therapy available for asthma. They have widespread effects on asthmatic airway inflammation. However, little is known about the effects of corticosteroids on the production of bone marrow inflammatory cells in asthma. This study observed the effects of glucocorticoid and cysteinyl leukotriene 1 receptor antagonist on CD34+ hematopoietic cells, so as to explore the possible effectiveness of a bone marrow-targeted anti-inflammatory strategy. METHODS: Balb/c mice were sensitized and challenged with ovalbumin (OVA) to establish an asthmatic model. For two consecutive weeks, asthmatic mice were challenged with OVA while being given either prednisone, montelukast, prednisone plus montelukast, or sterile saline solution. The mice were killed 24 hours after the last challenge with OVA, and bronchoalveolar lavage fluid (BALF), peripheral blood, and bone marrow were collected. Eosinophils in peripheral blood and BALF, and nucleated cells in BALF, peripheral blood, and bone marrow were counted. The percentages of CD34+ cells, CD4+ T lymphocytes and CD8+ T lymphocytes among nucleated cells in peripheral blood and bone marrow were counted by flow cytometry. Immunocytochemistry and in situ hybridization were employed to detect expression of CD34 and interleukin (IL)-5Ralpha mRNA (CD34+ IL-5Ralpha mRNA+ cells) among bone marrow hematopoietic cells. RESULTS: Compared with the sterile saline solution group, the number of eosinophils in BALF and peripheral blood, CD34+ cells in peripheral blood and bone marrow, and CD34+ IL-5Ralpha mRNA+ cells in bone marrow of mice from the prednisone and prednisone plus montelukast groups were significantly lower (P
基金supported by the National Natural Science Foundation of China (22271065,22271314)the Guangzhou Basic and Applied Research (202201010396)。
文摘Herein,we disclose a novel copper-catalyzed C(sp)-H aryl amination of terminal alkynes with anthranils,enabling the rapid generation of highly reactive secondary N-aryl ynamines for the modular synthesis of structurally diverse C2-substituted quinolines and 2-quinolinones.The in-situ formed carbonyl-ynamines are prone to tautomerize to carbonyl-ketenimines,which can efficiently react with a series of nucleophiles,including amines,alcohols,phenols,thiols,thiophenols,active-methylene compounds,and even water to produce various quinoline derivatives with the generation of H_(2)O as a sole and green byproduct.This method also unlocks a practical route to create various quinoline-fused heterocycles and can be successfully applied to the late-stage modification of complex molecules and the concise synthesis of bioactive targets.Mechanistic studies reveal a coppercatalyzed inner-sphere nitrene transfer process by using anthranils as novel aryl nitrene precursors.
基金supported by the National Key R&D Program of China (2017YFA0207302)the National Natural Science Foundation of China (21332007, 21672176)+1 种基金the Natural Science Foundation of Fujian Province, China (2017J01021)the Program for Changjiang Scholars and Innovative Research Team in University of Ministry of Education, China
文摘Employing triflic anhydride/2-fluoropyridine as an activation system, the coupling reactions of secondary N-aryl amides with terminal alkynes yielded substituted quinolines in moderate to excellent yields. The reaction tolerated both electron-donating and electron-withdrawing groups at the benzamide moiety. Electron-rich aryl acetylenes served as excellent coupling partners, and aliphatic terminal alkynes such as cyclopropyl and conjugate vinyl acetylenes could also be used as reaction partners. By means of 2 D NMR techniques(heteronuclear multiple bond correlation(HMBC), heteronuclear single quantum correlation(HSQC)),nitrilium ions were probed as reactive intermediates which are in contrast with that suggested by Movassaghi on the basis of in situ IR monitoring experiments. On the basis of these results, a plausible mechanism for the formation of quinolines was suggested.
基金the VIT University for providing the generous support to carry out this work
文摘Reusable acidic nickel oxide nanoparticles have been synthesized,characterized and applied as a catalyst to convert 2-aminoaryl ketones and β-ketoesters/ketones into the corresponding quinolines in good yields with high selectivity.This could serve as a simple and convenient procedure for the Friedlander annulations.
