CRISPR (clustered regularly interspaced short palindromic repeats)‐Cas (CRISPR associated protein) systems serve as the adaptive immune system by which prokaryotes defend themselves against phages. It has also been d...CRISPR (clustered regularly interspaced short palindromic repeats)‐Cas (CRISPR associated protein) systems serve as the adaptive immune system by which prokaryotes defend themselves against phages. It has also been developed into a series of powerful gene‐editing tools. As the natural inhibitors of CRISPR‐Cas systems, anti‐CRISPRs (Acrs) can be used as the “off‐switch” for CRISPR‐Cas systems to limit the off‐target effects caused by Cas9. Since the discovery of CRISPR‐Cas systems, much research has focused on the identification, mechanisms and applications of Acrs. In light of the rapid development and scientific significance of this field, this review summarizes the history and research status of Acrs, and considers future applications.展开更多
Thermus thermophilus is an attractive species in the bioindustry due to its valuable natural products,abundant thermophilic enzymes,and promising fermentation capacities.However,efficient and versatile genome editing ...Thermus thermophilus is an attractive species in the bioindustry due to its valuable natural products,abundant thermophilic enzymes,and promising fermentation capacities.However,efficient and versatile genome editing tools are not available for this species.In this study,we developed an efficient genome editing tool for T.thermophilus HB27 based on its endogenous type IB,I-C,and III-A/B CRISPR-Cas systems.First,we systematically characterized the DNA interference capabilities of the different types of the native CRISPR-Cas systems in T.thermophilus HB27.We found that genomic manipulations such as gene deletion,mutation,and in situ tagging could be easily implemented by a series of genome-editing plasmids carrying an artificial self-targeting mini-CRISPR and a donor DNA responsible for the recombinant recovery.We also compared the genome editing efficiency of different CRISPR-Cas systems and the editing plasmids with donor DNAs of different lengths.Additionally,we developed a reporter gene system for T.thermophilus based on a heat-stableβ-galactosidase gene TTP0042,and constructed an engineered strain with a high production capacity of superoxide dismutases by genome modification.展开更多
The discovery and utilization of RNA-guided surveillance complexes,such as CRISPR-Cas9,for sequencespecific DNA or RNA cleavage,has revolutionised the process of gene modification or knockdown.To optimise the use of t...The discovery and utilization of RNA-guided surveillance complexes,such as CRISPR-Cas9,for sequencespecific DNA or RNA cleavage,has revolutionised the process of gene modification or knockdown.To optimise the use of this technology,an exploratory race has ensued to discover or develop new RNA-guided endonucleases with the most flexible sequence targeting requirements,coupled with high cleavage efficacy and specificity.Here we review the constraints of existing gene editing and assess the merits of exploiting the diversity of CRISPR-Cas effectors as a methodology for surmounting these limitations.展开更多
This paper provides an overview of conventional geothermal systems and unconventional geothermal developments as a common reference is needed for discussions between energy professionals. Conventional geothermal syste...This paper provides an overview of conventional geothermal systems and unconventional geothermal developments as a common reference is needed for discussions between energy professionals. Conventional geothermal systems have the heat, permeability and fluid, requiring only drilling down to °C, normal heat flow or decaying radiogenic granite as heat sources, and used in district heating. Medium-temperature (MT) 100°C - 190°C, and high-temperature (HT) 190°C - 374°C resources are mostly at plate boundaries, with volcanic intrusive heat source, used mostly for electricity generation. Single well capacities are °C - 500°C) and a range of depths (1 m to 20 Km), but lack permeability or fluid, thus requiring stimulations for heat extraction by conduction. HVAC is 1 - 2 m deep and shallow geothermal down to 500 m in wells, both capturing °C, with °C are either advanced by geothermal developers at <7 Km depth (Enhanced Geothermal Systems (EGS), drilling below brittle-ductile transition zones and under geothermal fields), or by the Oil & Gas industry (Advanced Geothermal Systems, heat recovery from hydrocarbon wells or reservoirs, Superhot Rock Geothermal, and millimeter-wave drilling down to 20 Km). Their primary aim is electricity generation, relying on closed-loops, but EGS uses fractures for heat exchange with earthquake risks during fracking. Unconventional approaches could be everywhere, with shallow geothermal already functional. The deeper and hotter unconventional alternatives are still experimental, overcoming costs and technological challenges to become fully commercial. Meanwhile, the conventional geothermal resources remain the most proven opportunities for investments and development.展开更多
This paper introduces a systems theory-driven framework to integration artificial intelligence(AI)into traditional Chinese medicine(TCM)research,enhancing the understanding of TCM’s holistic material basis while adhe...This paper introduces a systems theory-driven framework to integration artificial intelligence(AI)into traditional Chinese medicine(TCM)research,enhancing the understanding of TCM’s holistic material basis while adhering to evidence-based principles.Utilizing the System Function Decoding Model(SFDM),the research progresses through define,quantify,infer,and validate phases to systematically explore TCM’s material basis.It employs a dual analytical approach that combines top-down,systems theory-guided perspectives with bottom-up,elements-structure-function methodologies,provides comprehensive insights into TCM’s holistic material basis.Moreover,the research examines AI’s role in quantitative assessment and predictive analysis of TCM’s material components,proposing two specific AIdriven technical applications.This interdisciplinary effort underscores AI’s potential to enhance our understanding of TCM’s holistic material basis and establishes a foundation for future research at the intersection of traditional wisdom and modern technology.展开更多
Powered by advanced information technology,more and more complex systems are exhibiting characteristics of the cyber-physical-social systems(CPSS).In this context,computational experiments method has emerged as a nove...Powered by advanced information technology,more and more complex systems are exhibiting characteristics of the cyber-physical-social systems(CPSS).In this context,computational experiments method has emerged as a novel approach for the design,analysis,management,control,and integration of CPSS,which can realize the causal analysis of complex systems by means of“algorithmization”of“counterfactuals”.However,because CPSS involve human and social factors(e.g.,autonomy,initiative,and sociality),it is difficult for traditional design of experiment(DOE)methods to achieve the generative explanation of system emergence.To address this challenge,this paper proposes an integrated approach to the design of computational experiments,incorporating three key modules:1)Descriptive module:Determining the influencing factors and response variables of the system by means of the modeling of an artificial society;2)Interpretative module:Selecting factorial experimental design solution to identify the relationship between influencing factors and macro phenomena;3)Predictive module:Building a meta-model that is equivalent to artificial society to explore its operating laws.Finally,a case study of crowd-sourcing platforms is presented to illustrate the application process and effectiveness of the proposed approach,which can reveal the social impact of algorithmic behavior on“rider race”.展开更多
基金Strategic Priority Research Programs of the Chinese Academy of Sciences,Grant/Award Number:XDA19050301National Natural Science Foundation of China,Grant/Award Number:31601189,81572433 and 81772646+1 种基金Biological Resources Program from Chinese Academy of Sciencesthe Young Elite Scientist Sponsorship Program by CAST,Grant/Award Number:2018QNRC001
文摘CRISPR (clustered regularly interspaced short palindromic repeats)‐Cas (CRISPR associated protein) systems serve as the adaptive immune system by which prokaryotes defend themselves against phages. It has also been developed into a series of powerful gene‐editing tools. As the natural inhibitors of CRISPR‐Cas systems, anti‐CRISPRs (Acrs) can be used as the “off‐switch” for CRISPR‐Cas systems to limit the off‐target effects caused by Cas9. Since the discovery of CRISPR‐Cas systems, much research has focused on the identification, mechanisms and applications of Acrs. In light of the rapid development and scientific significance of this field, this review summarizes the history and research status of Acrs, and considers future applications.
基金the National Natural Science Foundation of China(32170096)the Fundamental Research Funds for the Central Universities(2662022S KPY001)Cooperation Fund of Huazhong Agricultural University-Agricultural Genomics Institute at Shenzhen(CAAS)(SZYJY2021002).
文摘Thermus thermophilus is an attractive species in the bioindustry due to its valuable natural products,abundant thermophilic enzymes,and promising fermentation capacities.However,efficient and versatile genome editing tools are not available for this species.In this study,we developed an efficient genome editing tool for T.thermophilus HB27 based on its endogenous type IB,I-C,and III-A/B CRISPR-Cas systems.First,we systematically characterized the DNA interference capabilities of the different types of the native CRISPR-Cas systems in T.thermophilus HB27.We found that genomic manipulations such as gene deletion,mutation,and in situ tagging could be easily implemented by a series of genome-editing plasmids carrying an artificial self-targeting mini-CRISPR and a donor DNA responsible for the recombinant recovery.We also compared the genome editing efficiency of different CRISPR-Cas systems and the editing plasmids with donor DNAs of different lengths.Additionally,we developed a reporter gene system for T.thermophilus based on a heat-stableβ-galactosidase gene TTP0042,and constructed an engineered strain with a high production capacity of superoxide dismutases by genome modification.
基金the National Health and Medical Research Council of Australia(Grant No.APP1143008)the Australian Research Council(Grant No.DP180101494)the National Natural Science Foundation of China(Grant No.81772214).
文摘The discovery and utilization of RNA-guided surveillance complexes,such as CRISPR-Cas9,for sequencespecific DNA or RNA cleavage,has revolutionised the process of gene modification or knockdown.To optimise the use of this technology,an exploratory race has ensued to discover or develop new RNA-guided endonucleases with the most flexible sequence targeting requirements,coupled with high cleavage efficacy and specificity.Here we review the constraints of existing gene editing and assess the merits of exploiting the diversity of CRISPR-Cas effectors as a methodology for surmounting these limitations.
文摘This paper provides an overview of conventional geothermal systems and unconventional geothermal developments as a common reference is needed for discussions between energy professionals. Conventional geothermal systems have the heat, permeability and fluid, requiring only drilling down to °C, normal heat flow or decaying radiogenic granite as heat sources, and used in district heating. Medium-temperature (MT) 100°C - 190°C, and high-temperature (HT) 190°C - 374°C resources are mostly at plate boundaries, with volcanic intrusive heat source, used mostly for electricity generation. Single well capacities are °C - 500°C) and a range of depths (1 m to 20 Km), but lack permeability or fluid, thus requiring stimulations for heat extraction by conduction. HVAC is 1 - 2 m deep and shallow geothermal down to 500 m in wells, both capturing °C, with °C are either advanced by geothermal developers at <7 Km depth (Enhanced Geothermal Systems (EGS), drilling below brittle-ductile transition zones and under geothermal fields), or by the Oil & Gas industry (Advanced Geothermal Systems, heat recovery from hydrocarbon wells or reservoirs, Superhot Rock Geothermal, and millimeter-wave drilling down to 20 Km). Their primary aim is electricity generation, relying on closed-loops, but EGS uses fractures for heat exchange with earthquake risks during fracking. Unconventional approaches could be everywhere, with shallow geothermal already functional. The deeper and hotter unconventional alternatives are still experimental, overcoming costs and technological challenges to become fully commercial. Meanwhile, the conventional geothermal resources remain the most proven opportunities for investments and development.
基金supported by the National Natural Science Foundation of China(82230117).
文摘This paper introduces a systems theory-driven framework to integration artificial intelligence(AI)into traditional Chinese medicine(TCM)research,enhancing the understanding of TCM’s holistic material basis while adhering to evidence-based principles.Utilizing the System Function Decoding Model(SFDM),the research progresses through define,quantify,infer,and validate phases to systematically explore TCM’s material basis.It employs a dual analytical approach that combines top-down,systems theory-guided perspectives with bottom-up,elements-structure-function methodologies,provides comprehensive insights into TCM’s holistic material basis.Moreover,the research examines AI’s role in quantitative assessment and predictive analysis of TCM’s material components,proposing two specific AIdriven technical applications.This interdisciplinary effort underscores AI’s potential to enhance our understanding of TCM’s holistic material basis and establishes a foundation for future research at the intersection of traditional wisdom and modern technology.
基金the National Key Research and Development Program of China(2021YFF0900800)the National Natural Science Foundation of China(61972276,62206116,62032016)+2 种基金the New Liberal Arts Reform and Practice Project of National Ministry of Education(2021170002)the Open Research Fund of the State Key Laboratory for Management and Control of Complex Systems(20210101)Tianjin University Talent Innovation Reward Program for Literature and Science Graduate Student(C1-2022-010)。
文摘Powered by advanced information technology,more and more complex systems are exhibiting characteristics of the cyber-physical-social systems(CPSS).In this context,computational experiments method has emerged as a novel approach for the design,analysis,management,control,and integration of CPSS,which can realize the causal analysis of complex systems by means of“algorithmization”of“counterfactuals”.However,because CPSS involve human and social factors(e.g.,autonomy,initiative,and sociality),it is difficult for traditional design of experiment(DOE)methods to achieve the generative explanation of system emergence.To address this challenge,this paper proposes an integrated approach to the design of computational experiments,incorporating three key modules:1)Descriptive module:Determining the influencing factors and response variables of the system by means of the modeling of an artificial society;2)Interpretative module:Selecting factorial experimental design solution to identify the relationship between influencing factors and macro phenomena;3)Predictive module:Building a meta-model that is equivalent to artificial society to explore its operating laws.Finally,a case study of crowd-sourcing platforms is presented to illustrate the application process and effectiveness of the proposed approach,which can reveal the social impact of algorithmic behavior on“rider race”.
