The polymerase chain reaction is one of the most useful technical ad- vance and inventions in modern molecular biology. Developed in 1983 by Kary Mullis, PCR is now a common and indispensable technique used in medical...The polymerase chain reaction is one of the most useful technical ad- vance and inventions in modern molecular biology. Developed in 1983 by Kary Mullis, PCR is now a common and indispensable technique used in medical and bi- ology research labs for a variety of applications. A large number of articles relat- ed to PCR are available on the internet and other places. People know well about the basic principle and are very familiar with the procedures of the PCR. But, some details were neglected on the numbers of the target sequence and other DNA strands number after 30 to 35 cycles of the PCR. In most papers, the number of newly synthesized DNA strands including target DNA and non target DNA is am- biguous and even wrong. In this paper, highlights were given to the theoretical number of target DNA number in details and the exact number of the target DNA number can be concluded by analysis.展开更多
The global antibiotic resistance crisis necessitates urgent solutions.One innovative approach involves potentiating antibiotics and non-antibiotic drugs with adjuvants or boosters.A major drawback of these membrane-ac...The global antibiotic resistance crisis necessitates urgent solutions.One innovative approach involves potentiating antibiotics and non-antibiotic drugs with adjuvants or boosters.A major drawback of these membrane-active boosters is their limited biocompatibility,as they struggle to differentiate between prokaryotic and eukaryotic membranes.This study reports the chemical biology investigation of a dual-action oligoamidine(OA1)booster with a glutathione-triggered decomposition mechanism.OA1,when combined with other antimicrobial molecules,exhibits a triple-targeting mechanism including cell membrane disruption,DNA targeting,and intracellular enzyme inhibition.This multi-targeting mechanism not only enhances the in vitro and in vivo eradication of antibiotic-resistant“ESKAPE”pathogens,but also suppresses the development of bacterial resistance.Furthermore,OA1 maintains its activity in bacterial cells by creating an oxidative environment,while it quickly decomposes in mammalian cells due to high glutathione levels.These mechanistic insights and design principles may provide a feasible approach to develop novel antimicrobial agents and effective anti-resistance combination therapies.展开更多
文摘The polymerase chain reaction is one of the most useful technical ad- vance and inventions in modern molecular biology. Developed in 1983 by Kary Mullis, PCR is now a common and indispensable technique used in medical and bi- ology research labs for a variety of applications. A large number of articles relat- ed to PCR are available on the internet and other places. People know well about the basic principle and are very familiar with the procedures of the PCR. But, some details were neglected on the numbers of the target sequence and other DNA strands number after 30 to 35 cycles of the PCR. In most papers, the number of newly synthesized DNA strands including target DNA and non target DNA is am- biguous and even wrong. In this paper, highlights were given to the theoretical number of target DNA number in details and the exact number of the target DNA number can be concluded by analysis.
基金supported by the National Key Research and Development Program of China(2023YFD1800100 to Feng X and Bai Y)the National Natural Science Foundation of China(22177031 to Feng X,92163127 to Bai Y,82102415 to Wan M,and 82304277 to Zhang C)+4 种基金the Natural Science Foundation of Hunan Province(2024JJ4007 and 2024RC3078 to Feng X,2022RC1107 and 2024JJ2010 to Bai Y)the Natural Science Foundation of Changsha(kq2208050 to Zhang C)the Health and Medical Research Fund(HMRF),Hong Kong SAR(22210412to Wong WL)the Independent Research Project of the College of Advanced Interdisciplinary Studies of NUDT(22-ZZKY-03 to Pu H)the Project of Hunan Provincial Key Laboratory of Anti-Resistance Microbial Drugs(2023TP1013)。
文摘The global antibiotic resistance crisis necessitates urgent solutions.One innovative approach involves potentiating antibiotics and non-antibiotic drugs with adjuvants or boosters.A major drawback of these membrane-active boosters is their limited biocompatibility,as they struggle to differentiate between prokaryotic and eukaryotic membranes.This study reports the chemical biology investigation of a dual-action oligoamidine(OA1)booster with a glutathione-triggered decomposition mechanism.OA1,when combined with other antimicrobial molecules,exhibits a triple-targeting mechanism including cell membrane disruption,DNA targeting,and intracellular enzyme inhibition.This multi-targeting mechanism not only enhances the in vitro and in vivo eradication of antibiotic-resistant“ESKAPE”pathogens,but also suppresses the development of bacterial resistance.Furthermore,OA1 maintains its activity in bacterial cells by creating an oxidative environment,while it quickly decomposes in mammalian cells due to high glutathione levels.These mechanistic insights and design principles may provide a feasible approach to develop novel antimicrobial agents and effective anti-resistance combination therapies.
