Measuring the absolute protein expression quantity for a specific promoter is necessary in the fields of both molecular biology and synthetic biology.The strength of a promoter is traditionally characterized by measur...Measuring the absolute protein expression quantity for a specific promoter is necessary in the fields of both molecular biology and synthetic biology.The strength of a promoter is traditionally characterized by measuring the fluorescent intensity of the fluorescent protein downstream of the promoter.Until now,measurement of the absolute protein expression quantity for a promoter,however,has been unsuccessful in synthetic biology.The fact that the protein coding sequence influences the expression level for different proteins,and the inconvenience of measuring the absolute protein expression level,present a challenge to absolute quantitative measurement.Here,we introduce a new method that combines the insulator RiboJ with the standard fluorescence curve in order to measure the absolute protein expression quantity quickly;this method has been validated by modeling verification.Using this method,we successfully measured nine constitutive promoters in the Anderson promoter family.Our method provides data with higher accuracy for pathway design and is a straightforward way to standardize the strength of different promoters.展开更多
Background:Erosive esophagitis(EE)is a gastroesophageal reflux disease characterized by mucosal breaks in the esophagus.Proton pump inhibitors are widely used as maintenance therapy for EE,but many patients still rela...Background:Erosive esophagitis(EE)is a gastroesophageal reflux disease characterized by mucosal breaks in the esophagus.Proton pump inhibitors are widely used as maintenance therapy for EE,but many patients still relapse.In this trial,we evaluated the noninferiority of vonoprazan vs.lansoprazole as maintenance therapy in patients with healed EE.Methods:We performed a double-blind,double-dummy,multicenter,phase 3 clinical trial among non-Japanese Asian adults with endoscopically confirmed healed EE from April 2015 to February 2019.Patients from China,South Korea,and Malaysia were randomized to vonoprazan 10 mg or 20 mg once daily or lansoprazole 15 mg once daily for 24 weeks.The primary endpoint was endoscopically confirmed EE recurrence rate over 24 weeks with a noninferiority margin of 10%using a two-sided 95%confidence interval(CI).Treatment-emergent adverse events(TEAEs)were recorded.Results:Among 703 patients,EE recurrence was observed in 24/181(13.3%)and 21/171(12.3%)patients receiving vonoprazan 10 mg or 20 mg,respectively,and 47/184(25.5%)patients receiving lansoprazole(differences:-12.3%[95%CI,-20.3%to-4.3%]and-13.3%[95%CI,-21.3%to-5.3%],respectively),meeting the primary endpoint of noninferiority to lansoprazole in preventing EE recurrence at 24 weeks.Evidence of superiority(upper bound of 95%CI<0%)was also observed.At 12 weeks,endoscopically confirmed EE recurrence was observed in 5/18,2/20,and 7/20 of patients receiving vonoprazan 10 mg,vonoprazan 20 mg,and lansoprazole,respectively.TEAEs were experienced by 66.8%(157/235),69.0%(156/226),and 65.3%(158/242)of patients receiving vonoprazan 10 mg,vonoprazan 20 mg,and lansoprazole,respectively.The most common TEAE was upper respiratory tract infection in 12.8%(30/235)and 12.8%(29/226)patients in vonoprazan 10 mg and 20 mg groups,respectively and 8.7%(21/242)patients in lansoprazole group.Conclusion:Vonoprazan maintenance therapy was well-tolerated and noninferior to lansoprazole for preventing EE recurrence in Asian patients with healed EE.Trial Registration:https://clinicaltrials.gov;NCT02388737.展开更多
基金Fundamental Research Funds for Central Universities to Yunzi Luo,the National Natural Science Foundation of China(81502966)the China Innovation and Entrepreneurship Training Program for Undergraduates(201710611744).
文摘Measuring the absolute protein expression quantity for a specific promoter is necessary in the fields of both molecular biology and synthetic biology.The strength of a promoter is traditionally characterized by measuring the fluorescent intensity of the fluorescent protein downstream of the promoter.Until now,measurement of the absolute protein expression quantity for a promoter,however,has been unsuccessful in synthetic biology.The fact that the protein coding sequence influences the expression level for different proteins,and the inconvenience of measuring the absolute protein expression level,present a challenge to absolute quantitative measurement.Here,we introduce a new method that combines the insulator RiboJ with the standard fluorescence curve in order to measure the absolute protein expression quantity quickly;this method has been validated by modeling verification.Using this method,we successfully measured nine constitutive promoters in the Anderson promoter family.Our method provides data with higher accuracy for pathway design and is a straightforward way to standardize the strength of different promoters.
文摘Background:Erosive esophagitis(EE)is a gastroesophageal reflux disease characterized by mucosal breaks in the esophagus.Proton pump inhibitors are widely used as maintenance therapy for EE,but many patients still relapse.In this trial,we evaluated the noninferiority of vonoprazan vs.lansoprazole as maintenance therapy in patients with healed EE.Methods:We performed a double-blind,double-dummy,multicenter,phase 3 clinical trial among non-Japanese Asian adults with endoscopically confirmed healed EE from April 2015 to February 2019.Patients from China,South Korea,and Malaysia were randomized to vonoprazan 10 mg or 20 mg once daily or lansoprazole 15 mg once daily for 24 weeks.The primary endpoint was endoscopically confirmed EE recurrence rate over 24 weeks with a noninferiority margin of 10%using a two-sided 95%confidence interval(CI).Treatment-emergent adverse events(TEAEs)were recorded.Results:Among 703 patients,EE recurrence was observed in 24/181(13.3%)and 21/171(12.3%)patients receiving vonoprazan 10 mg or 20 mg,respectively,and 47/184(25.5%)patients receiving lansoprazole(differences:-12.3%[95%CI,-20.3%to-4.3%]and-13.3%[95%CI,-21.3%to-5.3%],respectively),meeting the primary endpoint of noninferiority to lansoprazole in preventing EE recurrence at 24 weeks.Evidence of superiority(upper bound of 95%CI<0%)was also observed.At 12 weeks,endoscopically confirmed EE recurrence was observed in 5/18,2/20,and 7/20 of patients receiving vonoprazan 10 mg,vonoprazan 20 mg,and lansoprazole,respectively.TEAEs were experienced by 66.8%(157/235),69.0%(156/226),and 65.3%(158/242)of patients receiving vonoprazan 10 mg,vonoprazan 20 mg,and lansoprazole,respectively.The most common TEAE was upper respiratory tract infection in 12.8%(30/235)and 12.8%(29/226)patients in vonoprazan 10 mg and 20 mg groups,respectively and 8.7%(21/242)patients in lansoprazole group.Conclusion:Vonoprazan maintenance therapy was well-tolerated and noninferior to lansoprazole for preventing EE recurrence in Asian patients with healed EE.Trial Registration:https://clinicaltrials.gov;NCT02388737.