Objective:To analyze the characteristics,dynamic changes,and outcomes of the first imaging manifestations of 3 patients with severe COVID-19 in our hospital.Methods:Computed tomography(CT)findings of 3 patients with s...Objective:To analyze the characteristics,dynamic changes,and outcomes of the first imaging manifestations of 3 patients with severe COVID-19 in our hospital.Methods:Computed tomography(CT)findings of 3 patients with severe COVID-19 who tested positive by the nucleic acid test in our hospital were selected,mainly focusing on the morphology,distribution characteristics,and dynamic changes of the first CT findings.Results:3 patients with severe pneumonia were older,with one aged 80.The first chest CT examination for all 3 patients differed.Imaging showed a leafy distribution of consolidation,primarily affecting the lower lobes of both lungs and extending subpleurally.A grid-like pattern was observed,along with changes in the consolidation and air bronchogram.These changes had slower absorption,especially in patients with underlying diseases.Conclusion:CT manifestations of severe COVID-19 have specific characteristics and the analysis of their characteristics and dynamic changes provide valuable insights for clinical treatment.展开更多
Cell-free synthetic biology system organizes multiple enzymes(parts)from different sources to implement unnatural catalytic functions.Highly adaption between the catalytic parts is crucial for building up efficient ar...Cell-free synthetic biology system organizes multiple enzymes(parts)from different sources to implement unnatural catalytic functions.Highly adaption between the catalytic parts is crucial for building up efficient artificial biosynthetic systems.Protein engineering is a powerful technology to tailor various enzymatic properties including catalytic efficiency,substrate specificity,temperature adaptation and even achieve new catalytic functions.However,altering enzymatic pH optimum still remains a challenging task.In this study,we proposed a novel sequence homolog-based protein engineering strategy for shifting the enzymatic pH optimum based on statistical analyses of sequence-function relationship data of enzyme family.By two statistical procedures,artificial neural networks(ANNs)and least absolute shrinkage and selection operator(Lasso),five amino acids in GH11 xylanase family were identified to be related to the evolution of enzymatic pH optimum.Site-directed mutagenesis of a thermophilic xylanase from Caldicellulosiruptor bescii revealed that four out of five mutations could alter the enzymatic pH optima toward acidic condition without compromising the catalytic activity and thermostability.Combination of the positive mutants resulted in the best mutant M31 that decreased its pH optimum for 1.5 units and showed increased catalytic activity at pH<5.0 compared to the wild-type enzyme.Structure analysis revealed that all the mutations are distant from the active center,which may be difficult to be identified by conventional rational design strategy.Interestingly,the four mutation sites are clustered at a certain region of the enzyme,suggesting a potential“hot zone”for regulating the pH optima of xylanases.This study provides an efficient method of modulating enzymatic pH optima based on statistical sequence analyses,which can facilitate the design and optimization of suitable catalytic parts for the construction of complicated cell-free synthetic biology systems.展开更多
基金Qinghai Provincial Health Commission Medical and Health Science and Technology Project Guiding Topics“Analysis of Dynamic Changes in Chest Imaging of New Coronavirus Pneumonia in Qinghai Province”(2022-wjzdx-63)。
文摘Objective:To analyze the characteristics,dynamic changes,and outcomes of the first imaging manifestations of 3 patients with severe COVID-19 in our hospital.Methods:Computed tomography(CT)findings of 3 patients with severe COVID-19 who tested positive by the nucleic acid test in our hospital were selected,mainly focusing on the morphology,distribution characteristics,and dynamic changes of the first CT findings.Results:3 patients with severe pneumonia were older,with one aged 80.The first chest CT examination for all 3 patients differed.Imaging showed a leafy distribution of consolidation,primarily affecting the lower lobes of both lungs and extending subpleurally.A grid-like pattern was observed,along with changes in the consolidation and air bronchogram.These changes had slower absorption,especially in patients with underlying diseases.Conclusion:CT manifestations of severe COVID-19 have specific characteristics and the analysis of their characteristics and dynamic changes provide valuable insights for clinical treatment.
基金National High Technology Research and Development Program of China(863 Program,2013AA102801)the National Basic Research Program of China(973 Program,2012CB721000)Natural Science Foundation of China(Grant No.31470788,11371142).
文摘Cell-free synthetic biology system organizes multiple enzymes(parts)from different sources to implement unnatural catalytic functions.Highly adaption between the catalytic parts is crucial for building up efficient artificial biosynthetic systems.Protein engineering is a powerful technology to tailor various enzymatic properties including catalytic efficiency,substrate specificity,temperature adaptation and even achieve new catalytic functions.However,altering enzymatic pH optimum still remains a challenging task.In this study,we proposed a novel sequence homolog-based protein engineering strategy for shifting the enzymatic pH optimum based on statistical analyses of sequence-function relationship data of enzyme family.By two statistical procedures,artificial neural networks(ANNs)and least absolute shrinkage and selection operator(Lasso),five amino acids in GH11 xylanase family were identified to be related to the evolution of enzymatic pH optimum.Site-directed mutagenesis of a thermophilic xylanase from Caldicellulosiruptor bescii revealed that four out of five mutations could alter the enzymatic pH optima toward acidic condition without compromising the catalytic activity and thermostability.Combination of the positive mutants resulted in the best mutant M31 that decreased its pH optimum for 1.5 units and showed increased catalytic activity at pH<5.0 compared to the wild-type enzyme.Structure analysis revealed that all the mutations are distant from the active center,which may be difficult to be identified by conventional rational design strategy.Interestingly,the four mutation sites are clustered at a certain region of the enzyme,suggesting a potential“hot zone”for regulating the pH optima of xylanases.This study provides an efficient method of modulating enzymatic pH optima based on statistical sequence analyses,which can facilitate the design and optimization of suitable catalytic parts for the construction of complicated cell-free synthetic biology systems.
基金supported by the National Natural Science Foundation of China (31801094 to C.L. and 31771416 to X.L.)the Key Research Program of the Chinese Academy of Sciences (KFZD-SW-220-1 to X.L.)+3 种基金CAS “Light of West China” Program (to X.L.)the National Natural Science Foundation of China (31900417 to G.L.)the National Key Basic Research Program of China (2014CB542006 to C.L.)China Postdoctoral Science Foundation (2019M653162 to G.L.)。
