Alkylation of benzene with carbon dioxide and hydrogen to produce toluene and xylene could increase the added-value of surplus benzene as well as relieve environmental problems like green-house effect.In this work,the...Alkylation of benzene with carbon dioxide and hydrogen to produce toluene and xylene could increase the added-value of surplus benzene as well as relieve environmental problems like green-house effect.In this work,the alkylation benzene with carbon dioxide and hydrogen reaction was proceeded by using the mixture of zinc-zirconium oxide and HZSM-5 as bifunctional catalyst.The equivalent of Zn/Zr=1 displays the best catalytic performance at 425℃ and 3.0 MPa,and benzene conversion reaches 42.9%with a selectivity of 90%towards toluene and xylene.Moreover,the carbon dioxide conversion achieves 23.3%and the carbon monoxide selectivity is lower than 35%,indicating that more than 50%carbon dioxide has been effectively incorporated into the target product,which is the best result as far as we know.Combined with characterizations,it indicated that the Zn and Zr formed a solid solution under specific conditions(Zn/Zr=1).The as-formed solid solution not only possesses a high surface area but also provides a large amount of oxygen vacancies.Additionally,the bifunctional catalyst has excellent stabilities that could keep operating without deactivation for at least 80 h.This work provides promising industrial applications for the upgrading of aromatics.展开更多
Bicyclol is a synthetic drug for hepatoprotection in clinic since 2004. Preliminary clinical observations suggest that bicyclol might be active against hepatitis C virus(HCV) with unknown mechanism. Here, we showed th...Bicyclol is a synthetic drug for hepatoprotection in clinic since 2004. Preliminary clinical observations suggest that bicyclol might be active against hepatitis C virus(HCV) with unknown mechanism. Here, we showed that bicyclol significantly inhibited HCV replication in vitro and in hepatitis C patients. Using bicyclol as a probe, we identified glycolipid transfer protein(GLTP) to be a novel restrictive factor for HCV replication. The GLTP preferentially bound host vesicle-associated membrane protein-associated protein-A(VAP-A) in competition with the HCV NS5 A, causing an interruption of the complex formation between VAP-A and HCV NS5 A. As the formation of VAP-A/NS5 A complex is essential for viral RNA replication, up-regulation of GLTP by bicyclol reduced the level of VAP-A/NS5 A complex and thus inhibited HCV replication. Bicyclol also exhibited an inhibition on HCV variants resistant to direct-acting antiviral agents(DAAs) with an efficacy identical to that on wild type HCV. In combination with bicyclol, DAAs inhibited HCV replication in a synergistic fashion. GLTP appears to be a newly discovered host restrictive factor for HCV replication, Up-regulation of GLTP causes spontaneous restriction of HCV replication.展开更多
In antiviral therapy of hepatitis B virus(HBV)infection,drug resistance remains a huge obstacle to the long-term effectiveness of nucleoside/tide analogs(NAs).Primary resistance mutation(rtM204V)contributes to lamivud...In antiviral therapy of hepatitis B virus(HBV)infection,drug resistance remains a huge obstacle to the long-term effectiveness of nucleoside/tide analogs(NAs).Primary resistance mutation(rtM204V)contributes to lamivudine(LAM)-resistance,and compensatory mutations(rtL180M and rtV173L)restore viral fitness and increase replication efficiency.The evaluation of new anti-viral agents against drug-resistant HBV is limited by the lack of available small-animal models.We established LAM-resistance HBV replication mice models based on clinical LAM-resistant HBV mutants.Double(rtM204VþrtL180M)or triple(rtM204VþrtL180MþrtV173L)lamivudine-resistant mutations were introduced into HBV expression vector,followed by hydrodynamic injection into tail vein of NOD/SCID mice.Viremia was detected on days 5,9,13 and 17 and liver HBV DNA was detected on day 17 after injection.The serum and liver HBV DNA levels in LAM-resistant model carrying triple mutations are the highest among the models.Two NAs,LAM and entecavir(ETV),were used to test the availability of the models.LAM and ETV inhibited viral replication on wild-type model.LAM was no longer effective on LAM-resistant models,but ETV retains a strong activity.Therefore,these models can be used to evaluate anti-viral agents against lamivudine-resistance,affording new opportunities to establish other drug-resistant HBV small-animal models.展开更多
基金sponsored financially by the National Natural Science Foundation of China (Grant No.21776076)the Fundamental Research Funds for the Central Universities (Grant No.JKA01211710).
文摘Alkylation of benzene with carbon dioxide and hydrogen to produce toluene and xylene could increase the added-value of surplus benzene as well as relieve environmental problems like green-house effect.In this work,the alkylation benzene with carbon dioxide and hydrogen reaction was proceeded by using the mixture of zinc-zirconium oxide and HZSM-5 as bifunctional catalyst.The equivalent of Zn/Zr=1 displays the best catalytic performance at 425℃ and 3.0 MPa,and benzene conversion reaches 42.9%with a selectivity of 90%towards toluene and xylene.Moreover,the carbon dioxide conversion achieves 23.3%and the carbon monoxide selectivity is lower than 35%,indicating that more than 50%carbon dioxide has been effectively incorporated into the target product,which is the best result as far as we know.Combined with characterizations,it indicated that the Zn and Zr formed a solid solution under specific conditions(Zn/Zr=1).The as-formed solid solution not only possesses a high surface area but also provides a large amount of oxygen vacancies.Additionally,the bifunctional catalyst has excellent stabilities that could keep operating without deactivation for at least 80 h.This work provides promising industrial applications for the upgrading of aromatics.
基金supported by the National Natural Science Foundation of China(81321004,81621064,Jiandong Jiang81322050,Zonggen Peng)+2 种基金National Mega-Project for “R&D for Innovative drugs”,Ministry of Science and Technology,China(2012ZX09301-002-001,Jiandong Jiang,2018ZX09711001-003-010,Zonggen Peng)Ministry of Education,China(NCET-12-0072,Zonggen Peng)CAMS Innovation Fund for Medical Sciences,China(CIFMS)(2017-I2M-3-012,Zonggen Peng)
文摘Bicyclol is a synthetic drug for hepatoprotection in clinic since 2004. Preliminary clinical observations suggest that bicyclol might be active against hepatitis C virus(HCV) with unknown mechanism. Here, we showed that bicyclol significantly inhibited HCV replication in vitro and in hepatitis C patients. Using bicyclol as a probe, we identified glycolipid transfer protein(GLTP) to be a novel restrictive factor for HCV replication. The GLTP preferentially bound host vesicle-associated membrane protein-associated protein-A(VAP-A) in competition with the HCV NS5 A, causing an interruption of the complex formation between VAP-A and HCV NS5 A. As the formation of VAP-A/NS5 A complex is essential for viral RNA replication, up-regulation of GLTP by bicyclol reduced the level of VAP-A/NS5 A complex and thus inhibited HCV replication. Bicyclol also exhibited an inhibition on HCV variants resistant to direct-acting antiviral agents(DAAs) with an efficacy identical to that on wild type HCV. In combination with bicyclol, DAAs inhibited HCV replication in a synergistic fashion. GLTP appears to be a newly discovered host restrictive factor for HCV replication, Up-regulation of GLTP causes spontaneous restriction of HCV replication.
基金This work was supported by the Basic Scientific Research Program of Materia Medica,CAMS(2013ZD05)State Mega Programs(2012ZX09301002-003/006)+1 种基金the Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study(BZ0150)973 Project(2012CB911103).
文摘In antiviral therapy of hepatitis B virus(HBV)infection,drug resistance remains a huge obstacle to the long-term effectiveness of nucleoside/tide analogs(NAs).Primary resistance mutation(rtM204V)contributes to lamivudine(LAM)-resistance,and compensatory mutations(rtL180M and rtV173L)restore viral fitness and increase replication efficiency.The evaluation of new anti-viral agents against drug-resistant HBV is limited by the lack of available small-animal models.We established LAM-resistance HBV replication mice models based on clinical LAM-resistant HBV mutants.Double(rtM204VþrtL180M)or triple(rtM204VþrtL180MþrtV173L)lamivudine-resistant mutations were introduced into HBV expression vector,followed by hydrodynamic injection into tail vein of NOD/SCID mice.Viremia was detected on days 5,9,13 and 17 and liver HBV DNA was detected on day 17 after injection.The serum and liver HBV DNA levels in LAM-resistant model carrying triple mutations are the highest among the models.Two NAs,LAM and entecavir(ETV),were used to test the availability of the models.LAM and ETV inhibited viral replication on wild-type model.LAM was no longer effective on LAM-resistant models,but ETV retains a strong activity.Therefore,these models can be used to evaluate anti-viral agents against lamivudine-resistance,affording new opportunities to establish other drug-resistant HBV small-animal models.
