Jumonji domain-containing 6(JMJD6)is a candidate gene associated with tumorigenesis,and JMJD6 overexpression predicts poor differentiation and unfavorable survival in some cancers.However,there are no studies reportin...Jumonji domain-containing 6(JMJD6)is a candidate gene associated with tumorigenesis,and JMJD6 overexpression predicts poor differentiation and unfavorable survival in some cancers.However,there are no studies reporting the expression of JMJD6 in ovarian cancer,and no JMJD6 inhibitors have been developed and applied to targeted cancer therapy research.In the present study,we found that the high expression of JMJD6 in ovarian cancer was correlated with poor prognosis in ovarian cancer.A potential inhibitor(SKLB325)was designed based on the crystal structure of the jmjC domain of JMJD6.This molecule significantly suppressed proliferation and induced apoptosis in a dose-dependent manner in SKOV3 cell lines as detected by CCK-8 cell proliferation assays and flow cytometry.A Matrigel endothelial tube formation assay showed that SKLB325 inhibited capillary tube organization and migration in HUVECs in vitro.We also observed that JMJD6 colocalized with p53 protein in the nucleus,with mRNA and protein expression of p53 as well as its downstream effectors significantly increasing both in vitro and in intraperitoneal tumor tissues treated with SKLB325.In addition,SKLB325 significantly reduced the intraperitoneal tumor weight and markedly prolonged the survival of tumor-bearing mice.Taken together,our findings suggest that JMJD6 may be a marker of poor prognosis in ovarian cancer and that SKLB325 may be a potential candidate drug for the treatment of ovarian cancer.展开更多
Based on Hamiltonian energy theory, this paper proposes a robust nonlinear controller for the wind turbine with doubly fed induction generator （DFIG）, such that the closed-loop system can achieve its stability. Furt...Based on Hamiltonian energy theory, this paper proposes a robust nonlinear controller for the wind turbine with doubly fed induction generator （DFIG）, such that the closed-loop system can achieve its stability. Furthermore, in the presence of disturbances, the closed-loop system is finite-gain L2 stable by the Hamiltonian controller. The Hamiltonian energy approach provides us a physical insight and gives a new way to the controller design. The simulation results illustrate that the proposed method is effective and has its advantage.展开更多
Brewers who create hop-forward styles such as American-style India Pale Ales typically add hops toward the end of or after wort boiling to avoid aroma volatilization and thereby impart strong hopderived aromas.However...Brewers who create hop-forward styles such as American-style India Pale Ales typically add hops toward the end of or after wort boiling to avoid aroma volatilization and thereby impart strong hopderived aromas.However,previous studies have demonstrated that despite the volatilization effects of boiling wort,hops that are added early in the kettle boil can contribute to hop aroma.Nonvolatile hopderived precursors,specifically glycosides,may survive the boiling process and become hydrolyzed to release volatile aglycones capable of contributing to aroma.To investigate the contribution of these different hop fractions to the aroma of kettle-hopped beers,12 single-hopped pilot-scale(3 hL)beers were brewed using pellet,supercritical CO2 extract,and spent hop fractions of Citra,Simcoe,Centennial,or Cascade cultivars.Pellet,extract,and spent additions consisted of a single hop add让ion 5 min into a 60 min boil.Volatile analysis of beers was perfonned using stir-bar sorptive extraction and quantified using gas chromatographymass spectrometry.Beers were analyzed for the common terpenoid compoundsα-pinene,β-pinene,3-myrcene,limonene,linalool,E,β-caryophyllene,α-humulene,andα-terpineol.In addition,beers were evaluated using descriptive sensory analysis.The descriptive sensory data identified significant differences among the cultivar and hop product treatments.The spent hop treatments produced beers that had a noticeable hop aroma,which suggests that the water-soluble components left behind in the spent hops may contribute to hop aroma in beer.The intensity and nature of the hop aroma in the spent treatments were hop variety specific.However,the contributions of water-soluble components found in spent hops to increased aroma intensity in beer were small,especially compared with the pellet and extract treatments.展开更多
基金This work is supported by the National Key Research and Development Program of China(No.2016YFA0201402)the National Major Scientific and Technological Special Project for“Significant New Drugs Development”(No.2018ZX09733001)the Natural Science Foundation of China(No.81602492).
文摘Jumonji domain-containing 6(JMJD6)is a candidate gene associated with tumorigenesis,and JMJD6 overexpression predicts poor differentiation and unfavorable survival in some cancers.However,there are no studies reporting the expression of JMJD6 in ovarian cancer,and no JMJD6 inhibitors have been developed and applied to targeted cancer therapy research.In the present study,we found that the high expression of JMJD6 in ovarian cancer was correlated with poor prognosis in ovarian cancer.A potential inhibitor(SKLB325)was designed based on the crystal structure of the jmjC domain of JMJD6.This molecule significantly suppressed proliferation and induced apoptosis in a dose-dependent manner in SKOV3 cell lines as detected by CCK-8 cell proliferation assays and flow cytometry.A Matrigel endothelial tube formation assay showed that SKLB325 inhibited capillary tube organization and migration in HUVECs in vitro.We also observed that JMJD6 colocalized with p53 protein in the nucleus,with mRNA and protein expression of p53 as well as its downstream effectors significantly increasing both in vitro and in intraperitoneal tumor tissues treated with SKLB325.In addition,SKLB325 significantly reduced the intraperitoneal tumor weight and markedly prolonged the survival of tumor-bearing mice.Taken together,our findings suggest that JMJD6 may be a marker of poor prognosis in ovarian cancer and that SKLB325 may be a potential candidate drug for the treatment of ovarian cancer.
基金supported by the National Natural Science Foundation of China(No.51007019)the Priority Academic Program Development of Jiangsu Higher Education Institutions(Coastal Development Conservancy)
文摘Based on Hamiltonian energy theory, this paper proposes a robust nonlinear controller for the wind turbine with doubly fed induction generator （DFIG）, such that the closed-loop system can achieve its stability. Furthermore, in the presence of disturbances, the closed-loop system is finite-gain L2 stable by the Hamiltonian controller. The Hamiltonian energy approach provides us a physical insight and gives a new way to the controller design. The simulation results illustrate that the proposed method is effective and has its advantage.
文摘Brewers who create hop-forward styles such as American-style India Pale Ales typically add hops toward the end of or after wort boiling to avoid aroma volatilization and thereby impart strong hopderived aromas.However,previous studies have demonstrated that despite the volatilization effects of boiling wort,hops that are added early in the kettle boil can contribute to hop aroma.Nonvolatile hopderived precursors,specifically glycosides,may survive the boiling process and become hydrolyzed to release volatile aglycones capable of contributing to aroma.To investigate the contribution of these different hop fractions to the aroma of kettle-hopped beers,12 single-hopped pilot-scale(3 hL)beers were brewed using pellet,supercritical CO2 extract,and spent hop fractions of Citra,Simcoe,Centennial,or Cascade cultivars.Pellet,extract,and spent additions consisted of a single hop add让ion 5 min into a 60 min boil.Volatile analysis of beers was perfonned using stir-bar sorptive extraction and quantified using gas chromatographymass spectrometry.Beers were analyzed for the common terpenoid compoundsα-pinene,β-pinene,3-myrcene,limonene,linalool,E,β-caryophyllene,α-humulene,andα-terpineol.In addition,beers were evaluated using descriptive sensory analysis.The descriptive sensory data identified significant differences among the cultivar and hop product treatments.The spent hop treatments produced beers that had a noticeable hop aroma,which suggests that the water-soluble components left behind in the spent hops may contribute to hop aroma in beer.The intensity and nature of the hop aroma in the spent treatments were hop variety specific.However,the contributions of water-soluble components found in spent hops to increased aroma intensity in beer were small,especially compared with the pellet and extract treatments.
