Objective Our study aimed to conduct genomic characterization of Salmonella strains carrying the blaNDM-1 gene in the intestinal tract of healthy individuals.The objectives were to underscore the importance of genomic...Objective Our study aimed to conduct genomic characterization of Salmonella strains carrying the blaNDM-1 gene in the intestinal tract of healthy individuals.The objectives were to underscore the importance of genomic surveillance for drug resistance in both commensal and pathogenic bacteria among healthy populations,and to establish protocols for regulating drug resistance plasmids based on the completion of a comprehensive map of drug resistance plasmid genomes.Methods We performed antimicrobial susceptibility testing and employed second-and third-generation sequencing techniques to analyze Salmonella strains harboring the blaNDM-1 gene,to surveil drug-resistant bacteria in the intestines of healthy subjects.Sequence comparison was conducted using both core-and pan-genome approaches.Concurrently,conjugation experiments were carried out to assess the efficiency of plasmid transfer.Results We isolated a carbapenem-resistant Salmonella enterica serovar Typhimurium strain from a healthy food worker in China.This strain harbored an IncHI2/IncHI2A plasmid carrying blaNDM-1 along with multiple antibiotic resistance genes(ARGs).Our findings highlight the potential for asymptomatic carriers to facilitate the transmission of ARGs.Pan-genomic analysis revealed that blaNDM-1-positive plasmids could traverse bacterial species barriers,facilitating cross-host transmission.Conclusion This study marks the first detection of blaNDM-1 in Salmonella strains isolated from healthy individuals.We underscore the risk associated with the transmission of conjugative hybrid plasmids carrying blaNDM-1,which have the potential to be harbored and transmitted among healthy individuals.Enhanced surveillance of drug-resistant pathogens and plasmids in the intestinal microbiota of healthy individuals could provide insights into the risk of ARG transmission and pathways for population-wide dissemination via ARG transfer factors.展开更多
The present study induced in vitro-cultured passage 4 bone marrow-derived mesenchymal stem cells to differentiate into neural-like cells with a mixture of alkaloid, polysaccharide, aglycone, glycoside, essential oils,...The present study induced in vitro-cultured passage 4 bone marrow-derived mesenchymal stem cells to differentiate into neural-like cells with a mixture of alkaloid, polysaccharide, aglycone, glycoside, essential oils, and effective components of Buyang Huanwu decoction （active principle region of decoction for invigorating yang for recuperation）. After 28 days, nestin and neuron-specific enolase were expressed in the cytoplasm. Reverse transcription-PCR and western blot analyses showed that nestin and neuron-specific enolase mRNA and protein expression was greater in the active principle region group compared with the original formula group. Results demonstrated that the active principle region of Buyang Huanwu decoction induced greater differentiation of rat bone marrow-derived mesenchymal stem cells into neural-like cells in vitro than the original Buyang Huanwu decoction formula.展开更多
Salmonella enterica serovar 4,[5],12:i:-(S.4,[5],12:i:-)is a monophasic variant of Salmonella enterica serovar Typhimurium that has emerged as a global serovar causing public health concern.To date,the epidemiology an...Salmonella enterica serovar 4,[5],12:i:-(S.4,[5],12:i:-)is a monophasic variant of Salmonella enterica serovar Typhimurium that has emerged as a global serovar causing public health concern.To date,the epidemiology and genomic characterization of this pathogen in China have not been well described.We investigated the prevalence,antimicrobial resistance(AMR)phenotypes,and population genomics of sequence type 34(ST34)S.4,[5],12:i:-among cases of human salmonellosis in Henan Province,China.A total of 100 ST34 S.4,[5],12:i:-isolates were studied from 2008 to 2017 and found mostly resistant to ampicillin(AMP),streptomycin(STR),sulfonamides(SUL),and tetracycline(TET)(ASSu T).Bayesian phylogenetic analysis demonstrated that isolates identified in China were mostly related to the European lineage and evolved into two major clades with different resistance genes and plasmid profiles.Notably,clade 1 showed a significantly higher rate of mutations in gyr A and plasmid-mediated quinolone resistance genes.The carrying of the resistance-containing region(encoding R-type ASSu T),including bla(conferring resistance to AMP),str AB(STR),sul2(SUL),and tet(B)(TET)inserted into the flj BA operon,was responsible for most of the monophasic variants in clade 2.Inc HI2 plasmids were the dominant multi-drug resistance mobile genetic elements accounting for the transmission of acquired resistance genes in this serovar,and these were more prevalent in clade 1.Our findings highlighted the increasing prevalence of multi-drug resistant S.4,[5],12:i:-in China,along with the differential characteristics of resistance gene acquisition among various lineages.Based on our data,control measures are required to address the spread of this zoonotic pathogen.Further owing to its potential origin in food-producing animals,a"One Health"approach,should be implemented to support surveillance whilst informing interventional strategies.展开更多
An advanced precooled airbreathing engine with a closed Brayton cycle is a promising solution for high-speed propulsion,of which the Synergetic Air Breathing Rocket Engine(SABRE)is a representative configuration.The p...An advanced precooled airbreathing engine with a closed Brayton cycle is a promising solution for high-speed propulsion,of which the Synergetic Air Breathing Rocket Engine(SABRE)is a representative configuration.The performance of the latest SABRE-4 cycle was analyzed in this paper.Firstly,a relatively complete engine performance model that considers the characteristics of turbomachinery and heat exchangers was developed.Then,Sobol’global sensitivity analysis of key performance parameters was carried out to identify the most influential design variables.Optimal specific impulses under different target specific thrusts were obtained by particle swarm optimization,of which the thermodynamic parameters corresponding to a specific thrust of 1.12 kN·s·kg^(-1)and a specific impulse of 3163 s were chosen as the design values.Four different control laws were analyzed in contrast,and the charge control method had the strongest ability of thrust regulation as well as maintaining a favorable specific impulse performance.Finally,working characteristics under the charge control and over a typical flight envelope were calculated,in which the average value of the maximum specific impulse was as high as 5315 s.This study would help to deepen the understanding of SABRE-4 thermodynamic characteristics and other precooled airbreathing engine cycles with similar layouts.展开更多
Uncertainty impact of random geometric variations on the aerodynamic performance of low-pressure turbine blades is considerable,which is further amplified by the current ultra-high-lift design trend for weight reducti...Uncertainty impact of random geometric variations on the aerodynamic performance of low-pressure turbine blades is considerable,which is further amplified by the current ultra-high-lift design trend for weight reduction.Therefore,this uncertainty impact on ultra-highly loaded blades under extreme operational conditions near the margins with potential large-scale open separation is focused on in this study.It is demonstrated that this impact is significant,unfavourable,and nonlinear,which is clearly severer under extreme conditions.In addition to the overall attenuation and notable scattering of specific performance,the operational margins with open separation are also notably scattered with great risk of significant reduction.This scattering and nonlinearity are dominated by the variations in leading-edge thickness.The thinning of leading edge triggers local transition,enhancing downstream friction and reducing resistance to open separation,which is further exacerbated by operational deterioration.However,the opposite thickening yields less benefit,implying nonlinearity.This unfavourable impact highlights the need for robust aerodynamic design,where both a safer operational condition and a more robust blade are indispensable,i.e.,a compromise among performance,weight,and robustness.Besides the necessary limitation of loading levels,a mid-loaded design is recommended to reduce adverse pressure gradients in both the leading edge and rear region of the suction side,which helps to decrease the susceptibility of the transition and open separation to random perturbations.Similar improvements can also be achieved by appropriately thickening the leading edge.展开更多
Two decades have passed since the first bacterial whole-genome sequencing, which provides new opportunity for microbial genome. Consequently, considerable genetic diversity encoded by bacterial genomes and among the s...Two decades have passed since the first bacterial whole-genome sequencing, which provides new opportunity for microbial genome. Consequently, considerable genetic diversity encoded by bacterial genomes and among the strains in the same species has been revealed. In recent years, genome sequencing techniques and bioinformatics have developed rapidly, which has resulted in transformation and expedited the application of strategy and methodology for bacterial genome comparison used in dissection of infectious disease epidemics. Bacterial whole-genome sequencing and bioinformatic computing allow genotyping to satisfy the requirements of epidemiological study in disease control. In this review, we outline the significance and summarize the roles of bacterial genome sequencing in the context of bacterial disease control and prevention. We discuss the applications of bacterial genome sequencing in outbreak detection, source tracing, transmission mode discovery, and new epidemic clone identification. Wide applications of genome sequencing and data sharing in infectious disease surveillance networks will considerably promote outbreak detection and early warning to prevent the dissemination of bacterial diseases.展开更多
Inevitable geometric variations significantly affect the performance of turbines or even that of entire engines;thus,it is necessary to determine their actual characteristics and accurately estimate their impact on pe...Inevitable geometric variations significantly affect the performance of turbines or even that of entire engines;thus,it is necessary to determine their actual characteristics and accurately estimate their impact on performance.In this study,based on 1781 measured profiles of a typical turbine blade,the statistical characteristics of the geometric variations and the uncertainty impact are analyzed,and some commonly used uncertainty modelling methods based on Principal-Component Analysis(PCA)are verified.The geometric variations are found to be evident,asymmetric,and non-uniform,and the non-normality of the random distributions is non-negligible.The performance is notably affected,which is manifested as an overall offset,a notable scattering,and significant deterioration in several extreme cases.Additionally,it is demonstrated that the PCA reconstruction model is effective in characterizing major uncertainty characteristics of the geometric variations and their impact on the performance with almost the first 10 PCA modes.Based on a reasonable profile error and mean geometric deviation,the Gaussian assumption and stochasticprocess-based model are also found to be effective in predicting the mean values and standard deviations of the performance variations.However,they fail to predict the probability of some extreme cases with high loss.Finally,a Chi-square-based correction model is proposed to compensate for this deficiency.The present work can provide a useful reference for uncertainty analysis of the impact of geometric variations,and the corresponding uncertainty design of turbine blades.展开更多
Identifying antimicrobial resistant(AMR) bacteria in metagenomics samples is essential for public health and food safety. Next-generation sequencing(NGS) technology has provided a powerful tool in identifying the gene...Identifying antimicrobial resistant(AMR) bacteria in metagenomics samples is essential for public health and food safety. Next-generation sequencing(NGS) technology has provided a powerful tool in identifying the genetic variation and constructing the correlations between genotype and phenotype in humans and other species. However, for complex bacterial samples, there lacks a powerful bioinformatic tool to identify genetic polymorphisms or copy number variations(CNVs) for given genes. Here we provide a Bayesian framework for genotype estimation for mixtures of multiple bacteria, named as Genetic Polymorphisms Assignments(GPA). Simulation results showed that GPA has reduced the false discovery rate(FDR) and mean absolute error(MAE) in CNV and single nucleotide variant(SNV) identification. This framework was validated by whole-genome sequencing and Pool-seq data from Klebsiella pneumoniae with multiple bacteria mixture models, and showed the high accuracy in the allele fraction detections of CNVs and SNVs in AMR genes between two populations. The quantitative study on the changes of AMR genes fraction between two samples showed a good consistency with the AMR pattern observed in the individual strains. Also, the framework together with the genome annotation and population comparison tools has been integrated into an application, which could provide a complete solution for AMR gene identification and quantification in unculturable clinical samples. The GPA package is available at https://github.com/IID-DTH/GPA-package.展开更多
基金supported by the National Key Research and Development Program of China(2022YFC2303900)the major projects of the National Natural Science Foundation of China(22193064)the Science Foundation(2022SKLID303)of the State Key Laboratory of Infectious Disease Prevention and Control,China。
文摘Objective Our study aimed to conduct genomic characterization of Salmonella strains carrying the blaNDM-1 gene in the intestinal tract of healthy individuals.The objectives were to underscore the importance of genomic surveillance for drug resistance in both commensal and pathogenic bacteria among healthy populations,and to establish protocols for regulating drug resistance plasmids based on the completion of a comprehensive map of drug resistance plasmid genomes.Methods We performed antimicrobial susceptibility testing and employed second-and third-generation sequencing techniques to analyze Salmonella strains harboring the blaNDM-1 gene,to surveil drug-resistant bacteria in the intestines of healthy subjects.Sequence comparison was conducted using both core-and pan-genome approaches.Concurrently,conjugation experiments were carried out to assess the efficiency of plasmid transfer.Results We isolated a carbapenem-resistant Salmonella enterica serovar Typhimurium strain from a healthy food worker in China.This strain harbored an IncHI2/IncHI2A plasmid carrying blaNDM-1 along with multiple antibiotic resistance genes(ARGs).Our findings highlight the potential for asymptomatic carriers to facilitate the transmission of ARGs.Pan-genomic analysis revealed that blaNDM-1-positive plasmids could traverse bacterial species barriers,facilitating cross-host transmission.Conclusion This study marks the first detection of blaNDM-1 in Salmonella strains isolated from healthy individuals.We underscore the risk associated with the transmission of conjugative hybrid plasmids carrying blaNDM-1,which have the potential to be harbored and transmitted among healthy individuals.Enhanced surveillance of drug-resistant pathogens and plasmids in the intestinal microbiota of healthy individuals could provide insights into the risk of ARG transmission and pathways for population-wide dissemination via ARG transfer factors.
基金supported by the Natural Science Foundation of Anhui Province (Role of substance P in electroacupuncture for focal brain ischemia in rats), No. 050431003the National Natural Science Foundation of China (Target point and signal transduction pathway of Yangxin Tongmai active principle region for BMSCs), No. 81102595
文摘The present study induced in vitro-cultured passage 4 bone marrow-derived mesenchymal stem cells to differentiate into neural-like cells with a mixture of alkaloid, polysaccharide, aglycone, glycoside, essential oils, and effective components of Buyang Huanwu decoction （active principle region of decoction for invigorating yang for recuperation）. After 28 days, nestin and neuron-specific enolase were expressed in the cytoplasm. Reverse transcription-PCR and western blot analyses showed that nestin and neuron-specific enolase mRNA and protein expression was greater in the active principle region group compared with the original formula group. Results demonstrated that the active principle region of Buyang Huanwu decoction induced greater differentiation of rat bone marrow-derived mesenchymal stem cells into neural-like cells in vitro than the original Buyang Huanwu decoction formula.
基金supported by grants from the National Natural Science Foundation of China(31871899 and 31930110)Henan Medical Science and Technology Research Plan(LHGJ20200128)。
文摘Salmonella enterica serovar 4,[5],12:i:-(S.4,[5],12:i:-)is a monophasic variant of Salmonella enterica serovar Typhimurium that has emerged as a global serovar causing public health concern.To date,the epidemiology and genomic characterization of this pathogen in China have not been well described.We investigated the prevalence,antimicrobial resistance(AMR)phenotypes,and population genomics of sequence type 34(ST34)S.4,[5],12:i:-among cases of human salmonellosis in Henan Province,China.A total of 100 ST34 S.4,[5],12:i:-isolates were studied from 2008 to 2017 and found mostly resistant to ampicillin(AMP),streptomycin(STR),sulfonamides(SUL),and tetracycline(TET)(ASSu T).Bayesian phylogenetic analysis demonstrated that isolates identified in China were mostly related to the European lineage and evolved into two major clades with different resistance genes and plasmid profiles.Notably,clade 1 showed a significantly higher rate of mutations in gyr A and plasmid-mediated quinolone resistance genes.The carrying of the resistance-containing region(encoding R-type ASSu T),including bla(conferring resistance to AMP),str AB(STR),sul2(SUL),and tet(B)(TET)inserted into the flj BA operon,was responsible for most of the monophasic variants in clade 2.Inc HI2 plasmids were the dominant multi-drug resistance mobile genetic elements accounting for the transmission of acquired resistance genes in this serovar,and these were more prevalent in clade 1.Our findings highlighted the increasing prevalence of multi-drug resistant S.4,[5],12:i:-in China,along with the differential characteristics of resistance gene acquisition among various lineages.Based on our data,control measures are required to address the spread of this zoonotic pathogen.Further owing to its potential origin in food-producing animals,a"One Health"approach,should be implemented to support surveillance whilst informing interventional strategies.
基金supported by the Project of National Key Laboratory of Science and Technology on Aero-engine and Aerothermodynamics at Beihang University,China(No.2022-JCJQ-LB-062-0204).
文摘An advanced precooled airbreathing engine with a closed Brayton cycle is a promising solution for high-speed propulsion,of which the Synergetic Air Breathing Rocket Engine(SABRE)is a representative configuration.The performance of the latest SABRE-4 cycle was analyzed in this paper.Firstly,a relatively complete engine performance model that considers the characteristics of turbomachinery and heat exchangers was developed.Then,Sobol’global sensitivity analysis of key performance parameters was carried out to identify the most influential design variables.Optimal specific impulses under different target specific thrusts were obtained by particle swarm optimization,of which the thermodynamic parameters corresponding to a specific thrust of 1.12 kN·s·kg^(-1)and a specific impulse of 3163 s were chosen as the design values.Four different control laws were analyzed in contrast,and the charge control method had the strongest ability of thrust regulation as well as maintaining a favorable specific impulse performance.Finally,working characteristics under the charge control and over a typical flight envelope were calculated,in which the average value of the maximum specific impulse was as high as 5315 s.This study would help to deepen the understanding of SABRE-4 thermodynamic characteristics and other precooled airbreathing engine cycles with similar layouts.
基金This study was supported by the National Science and Technology Major Project,China(No.J2019-II-0012-0032),which is gratefully acknowledged.
文摘Uncertainty impact of random geometric variations on the aerodynamic performance of low-pressure turbine blades is considerable,which is further amplified by the current ultra-high-lift design trend for weight reduction.Therefore,this uncertainty impact on ultra-highly loaded blades under extreme operational conditions near the margins with potential large-scale open separation is focused on in this study.It is demonstrated that this impact is significant,unfavourable,and nonlinear,which is clearly severer under extreme conditions.In addition to the overall attenuation and notable scattering of specific performance,the operational margins with open separation are also notably scattered with great risk of significant reduction.This scattering and nonlinearity are dominated by the variations in leading-edge thickness.The thinning of leading edge triggers local transition,enhancing downstream friction and reducing resistance to open separation,which is further exacerbated by operational deterioration.However,the opposite thickening yields less benefit,implying nonlinearity.This unfavourable impact highlights the need for robust aerodynamic design,where both a safer operational condition and a more robust blade are indispensable,i.e.,a compromise among performance,weight,and robustness.Besides the necessary limitation of loading levels,a mid-loaded design is recommended to reduce adverse pressure gradients in both the leading edge and rear region of the suction side,which helps to decrease the susceptibility of the transition and open separation to random perturbations.Similar improvements can also be achieved by appropriately thickening the leading edge.
文摘Two decades have passed since the first bacterial whole-genome sequencing, which provides new opportunity for microbial genome. Consequently, considerable genetic diversity encoded by bacterial genomes and among the strains in the same species has been revealed. In recent years, genome sequencing techniques and bioinformatics have developed rapidly, which has resulted in transformation and expedited the application of strategy and methodology for bacterial genome comparison used in dissection of infectious disease epidemics. Bacterial whole-genome sequencing and bioinformatic computing allow genotyping to satisfy the requirements of epidemiological study in disease control. In this review, we outline the significance and summarize the roles of bacterial genome sequencing in the context of bacterial disease control and prevention. We discuss the applications of bacterial genome sequencing in outbreak detection, source tracing, transmission mode discovery, and new epidemic clone identification. Wide applications of genome sequencing and data sharing in infectious disease surveillance networks will considerably promote outbreak detection and early warning to prevent the dissemination of bacterial diseases.
基金supported by the National Science and Technology Major Project, China (No. J2019-II-0012-0032)
文摘Inevitable geometric variations significantly affect the performance of turbines or even that of entire engines;thus,it is necessary to determine their actual characteristics and accurately estimate their impact on performance.In this study,based on 1781 measured profiles of a typical turbine blade,the statistical characteristics of the geometric variations and the uncertainty impact are analyzed,and some commonly used uncertainty modelling methods based on Principal-Component Analysis(PCA)are verified.The geometric variations are found to be evident,asymmetric,and non-uniform,and the non-normality of the random distributions is non-negligible.The performance is notably affected,which is manifested as an overall offset,a notable scattering,and significant deterioration in several extreme cases.Additionally,it is demonstrated that the PCA reconstruction model is effective in characterizing major uncertainty characteristics of the geometric variations and their impact on the performance with almost the first 10 PCA modes.Based on a reasonable profile error and mean geometric deviation,the Gaussian assumption and stochasticprocess-based model are also found to be effective in predicting the mean values and standard deviations of the performance variations.However,they fail to predict the probability of some extreme cases with high loss.Finally,a Chi-square-based correction model is proposed to compensate for this deficiency.The present work can provide a useful reference for uncertainty analysis of the impact of geometric variations,and the corresponding uncertainty design of turbine blades.
基金supported by the Beijing Municipal Science & Technology Commission (Grant No. Z161100000516021)the National Key R&D Program of China (Grant No. 2016YFC1200804)the National Natural Science Foundation of China (Grant Nos. 81571956 and 81702038)
文摘Identifying antimicrobial resistant(AMR) bacteria in metagenomics samples is essential for public health and food safety. Next-generation sequencing(NGS) technology has provided a powerful tool in identifying the genetic variation and constructing the correlations between genotype and phenotype in humans and other species. However, for complex bacterial samples, there lacks a powerful bioinformatic tool to identify genetic polymorphisms or copy number variations(CNVs) for given genes. Here we provide a Bayesian framework for genotype estimation for mixtures of multiple bacteria, named as Genetic Polymorphisms Assignments(GPA). Simulation results showed that GPA has reduced the false discovery rate(FDR) and mean absolute error(MAE) in CNV and single nucleotide variant(SNV) identification. This framework was validated by whole-genome sequencing and Pool-seq data from Klebsiella pneumoniae with multiple bacteria mixture models, and showed the high accuracy in the allele fraction detections of CNVs and SNVs in AMR genes between two populations. The quantitative study on the changes of AMR genes fraction between two samples showed a good consistency with the AMR pattern observed in the individual strains. Also, the framework together with the genome annotation and population comparison tools has been integrated into an application, which could provide a complete solution for AMR gene identification and quantification in unculturable clinical samples. The GPA package is available at https://github.com/IID-DTH/GPA-package.
