The kagome metal FeGe provides a rich platform for understanding the mechanisms behind competing orders,as it exhibits charge order(CO)emerging deep within the antiferromagnetic phase.To investigate the intrinsic orig...The kagome metal FeGe provides a rich platform for understanding the mechanisms behind competing orders,as it exhibits charge order(CO)emerging deep within the antiferromagnetic phase.To investigate the intrinsic origin of this behavior,we examine the evolution of the low-energy electronic structure across the phase transition in annealed FeGe samples using angleresolved photoemission spectroscopy.We find no evidence supporting a conventional nesting mechanism,such as Fermi surface nesting or van Hove singularities.However,we observe two notable changes in the band structure:an electron-like band around the K point and another around the A point,both shifting upward in energy when CO forms.These findings are consistent with our density-functional theory calculations,which suggest that the charge order in FeGe is primarily driven by magnetic energy savings due to a lattice distortion involving Ge1-dimerization.Our results provide photoemission evidence supporting this novel mechanism for CO formation in FeGe,in contrast to the conventional nesting-driven mechanisms.展开更多
The role of ethylene as an initial signaling molecule in waterlogging stress is well-established.However,the complex molecular mechanisms underlying ethylene biosynthesis and its functional significance in chrysanthem...The role of ethylene as an initial signaling molecule in waterlogging stress is well-established.However,the complex molecular mechanisms underlying ethylene biosynthesis and its functional significance in chrysanthemums under waterlogging conditions have remained unclear.In this study,we observed an increase in the expression of 1-aminocyclopropane-1-carboxylate synthase 6(CmACS6),which encodes a key enzyme responsible for ethylene biosynthesis,in response to waterlogging.This elevation increases ethylene production,induces leaf chlorosis,and enhances the chrysanthemum’s sensitivity to waterlogging stress.Moreover,our analysis of upstream regulators revealed that the expression of CmACS6,in response to waterlogging,is directly upregulated by CmHRE2-like(Hypoxia Responsive ERF-like,CmHRE2L),an ethylene response factor.Notably,CmHRE2-L binds directly to the GCClike motif in the promoter region of CmACS6.Genetic validation assays demonstrated that CmHRE2L was induced by waterlogging and contributed to ethylene production,consequently reducing waterlogging tolerance in a partially CmACS6-dependent manner.This study identified the regulatory module involving CmHRE2L and CmACS6,which governs ethylene biosynthesis in response to waterlogging stress.展开更多
With the rapid advancements in large language model technology and the emergence of bioinformatics-specific language models(BioLMs),there is a growing need for a comprehensive analysis of the current landscape,computa...With the rapid advancements in large language model technology and the emergence of bioinformatics-specific language models(BioLMs),there is a growing need for a comprehensive analysis of the current landscape,computational characteristics,and diverse applications.This survey aims to address this need by providing a thorough review of BioLMs,focusing on their evolution,classification,and distinguishing features,alongside a detailed examination of training methodologies,datasets,and evaluation frameworks.We explore the wide-ranging applications of BioLMs in critical areas such as disease diagnosis,drug discovery,and vaccine development,highlighting their impact and transformative potential in bioinformatics.We identify key challenges and limitations inherent in BioLMs,including data privacy and security concerns,interpretability issues,biases in training data and model outputs,and domain adaptation complexities.Finally,we high-light emerging trends and future directions,offering valuable insights to guide researchers and clinicians toward advancing BioLMs for increasingly sophisticated biological and clinical applications.展开更多
Derived from the bacterial adaptive immune system,CRISPR technology has revolutionized conventional genetic engineering methods and unprecedentedly facilitated strain engineering.In this review,we outline the fundamen...Derived from the bacterial adaptive immune system,CRISPR technology has revolutionized conventional genetic engineering methods and unprecedentedly facilitated strain engineering.In this review,we outline the fundamental CRISPR tools that have been employed for strain optimization.These tools include CRISPR editing,CRISPR interference,CRISPR activation and protein imaging.To further characterize the CRISPR technology,we present current applications of these tools in microbial systems,including model-and non-model industrial microorganisms.Specially,we point out the major challenges of the CRISPR tools when utilized for multiplex genome editing and sophisticated expression regulation.To address these challenges,we came up with strategies that place emphasis on the amelioration of DNA repair efficiency through CRISPR-Cas9-assisted recombineering.Lastly,multiple promising research directions were proposed,mainly focusing on CRISPR-based construction of microbial ecosystems toward high production of desired chemicals.展开更多
Scanning tunneling microscopy/spectroscopy is applied herein to study the pristine and potassium(K)-doped single-layer pquaterphenyl(P4P) films grown on the Au(111) substrate at the molecular level. Abundant complex s...Scanning tunneling microscopy/spectroscopy is applied herein to study the pristine and potassium(K)-doped single-layer pquaterphenyl(P4P) films grown on the Au(111) substrate at the molecular level. Abundant complex structural and electronic phases are induced by various K doping. The Fermi-level pinning effect is observed at a low doping level. On the contrary,K3P4P exhibits intriguing versatile phases and properties because charge carriers are effectively doped in. For example, two kinds of molecular vibration modes with energies below 100 meV are observed, indicating a possible strong electron-phonon coupling. The splitting of the lowest unoccupied molecular orbital state in K3P4P illustrates an electronic correlation effect, and its strength varies for four different K3P4P phases with different structures. In addition, the appearance of a Kondo resonance on the molecular vacancy/impurity implies a local molecular magnetic moment. Our results demonstrate that the complex electronic properties of an alkali metal-doped P4P/Au film stem from the existence of many competing interactions, such as electronelectron correlations and electron-vibration coupling, which can be effectively tuned via variable carrier doping and molecular structure. Our work also opens new routes toward engineering novel molecular devices and creating new electronic phases in strongly correlated molecular materials.展开更多
Herein, we show that a self-assembled phase of potassium(K)-doped single-layer para-sexiphenyl(PSP) film on a gold substrate is an excellent platform for studying the two-impurity Kondo model. On K-doped PSP molecules...Herein, we show that a self-assembled phase of potassium(K)-doped single-layer para-sexiphenyl(PSP) film on a gold substrate is an excellent platform for studying the two-impurity Kondo model. On K-doped PSP molecules well separated from others, we observe a Kondo resonance peak close to EFwith a Kondo temperature of 30 K. The Kondo resonance peak splits when another K-doped PSP molecule is present in the vicinity, and the splitting gradually increases with the decrease in intermolecular distance without signs of phase transition. Our data demonstrate how a Kondo singlet state gradually evolves into an antiferromagnetic singlet state due to the competition between Kondo screening and antiferromagnetic Ruderman-Kittel-Kasuya-Yosida coupling,as described in the two-impurity Kondo model. Intriguingly, the antiferromagnetic singlet is quickly destroyed on increasing temperature and transforms back to a Kondo singlet below the Kondo temperature. Our data provide a comprehensive picture and quantitative constraints on related theories and calculations of the two-impurity Kondo model.展开更多
Background:Human immunodeficiency virus type 1(HIV-1)remains a persistent global health challenge.Therefore,a continuous exploration of novel therapeutic strategies is essential.A comprehensive understanding of how HI...Background:Human immunodeficiency virus type 1(HIV-1)remains a persistent global health challenge.Therefore,a continuous exploration of novel therapeutic strategies is essential.A comprehensive understanding of how HIV-1 utilizes the cellular metabolism machinery for replication can provide insights into new therapeutic approaches.Methods:In this study,we performed a flux balance analysis using a genome-scale metabolic model(GEM)integrated with an HIV-1 viral biomass objective function to identify potential targets for anti–HIV-1 interventions.We generated a GEM by integrating an HIV-1 production reaction into CD4+T cells and optimized for both host and virus optimal states as objective functions to depict metabolic profiles of cells in the status for optimal host biomass maintenance or for optimal HIV-1 virion production.Differential analysis was used to predict biochemical reactions altered optimal for HIV-1 production.In addition,we conducted in silico simulations involving gene and reaction knock-outs to identify potential anti–HIV-1 targets,which were subsequently validated by human phytohemagglutinin(PHA)blasts infected with HIV-1.Results:Differential analysis identified several altered biochemical reactions,including increased lysine uptake and oxidative phosphorylation(OXPHOS)activities in the virus optima compared with the host optima.In silico gene and reaction knock-out simulations revealed de novo pyrimidine synthesis,and OXPHOS could serve as potential anti–HIV-1 metabolic targets.In vitro assay confirmed that targeting OXPHOS using metformin could suppress the replication of HIV-1 by 56.6%(385.4±67.5 pg/mL in the metformintreated group vs.888.4±32.3 pg/mL in the control group,P<0.001).Conclusion:Our integrated host-virus genome-scale metabolic study provides insights on potential targets(OXPHOS)for anti-HIV therapies.展开更多
Coumarin and its derivatives,presenting in many organisms(plants,fungi,and bacteria),are critical metabolites composed of fused benzene andα-pyrone rings.With unique biological and chemical properties,coumarin deriva...Coumarin and its derivatives,presenting in many organisms(plants,fungi,and bacteria),are critical metabolites composed of fused benzene andα-pyrone rings.With unique biological and chemical properties,coumarin derivatives possess great technological potential in the agrochemicals,pharmaceuticals,food,and cosmetic industries.The increasing demand for coumarin derivatives accelerates the research in biological and chemical synthesis to provide stable and scalable sources of coumarins.However,the complex structures and unknown pathways have limited the progress in the biosynthesis of coumarin derivatives.Here,we summarize recent developments and provide a detailed analysis of coumarin derivative biosynthetic pathways in different organisms.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.12174362,11888101,11790312,92065202,12474142,and 12174365)the Innovation Program for Quantum Science and Technology(Grant No.2021ZD0302803)the New Cornerstone Science Foundation.Part of this research used Beamline 03U of the Shanghai Synchrotron Radiation Facility,which is supported by the ME2 project from the National Natural Science Foundation of China(Grant No.11227902).
文摘The kagome metal FeGe provides a rich platform for understanding the mechanisms behind competing orders,as it exhibits charge order(CO)emerging deep within the antiferromagnetic phase.To investigate the intrinsic origin of this behavior,we examine the evolution of the low-energy electronic structure across the phase transition in annealed FeGe samples using angleresolved photoemission spectroscopy.We find no evidence supporting a conventional nesting mechanism,such as Fermi surface nesting or van Hove singularities.However,we observe two notable changes in the band structure:an electron-like band around the K point and another around the A point,both shifting upward in energy when CO forms.These findings are consistent with our density-functional theory calculations,which suggest that the charge order in FeGe is primarily driven by magnetic energy savings due to a lattice distortion involving Ge1-dimerization.Our results provide photoemission evidence supporting this novel mechanism for CO formation in FeGe,in contrast to the conventional nesting-driven mechanisms.
基金funded by the National Key Research and Development Program of China(2023YFD2300900)the National Natural Science Foundation of China(32102421)+4 种基金Natural Science Foundation of Jiangsu Province(BK20210395)the"JBGS"Project of Seed Industry Revitalization in Jiangsu Province(JBGS[2021]020)China Agriculture Research System(CARS-23-A18)the earmarked fund for Jiangsu Agricultural Industry Technology System,the Fundamental Research Funds for the Central Universities(QTPY2023002,KYT2023006)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘The role of ethylene as an initial signaling molecule in waterlogging stress is well-established.However,the complex molecular mechanisms underlying ethylene biosynthesis and its functional significance in chrysanthemums under waterlogging conditions have remained unclear.In this study,we observed an increase in the expression of 1-aminocyclopropane-1-carboxylate synthase 6(CmACS6),which encodes a key enzyme responsible for ethylene biosynthesis,in response to waterlogging.This elevation increases ethylene production,induces leaf chlorosis,and enhances the chrysanthemum’s sensitivity to waterlogging stress.Moreover,our analysis of upstream regulators revealed that the expression of CmACS6,in response to waterlogging,is directly upregulated by CmHRE2-like(Hypoxia Responsive ERF-like,CmHRE2L),an ethylene response factor.Notably,CmHRE2-L binds directly to the GCClike motif in the promoter region of CmACS6.Genetic validation assays demonstrated that CmHRE2L was induced by waterlogging and contributed to ethylene production,consequently reducing waterlogging tolerance in a partially CmACS6-dependent manner.This study identified the regulatory module involving CmHRE2L and CmACS6,which governs ethylene biosynthesis in response to waterlogging stress.
文摘With the rapid advancements in large language model technology and the emergence of bioinformatics-specific language models(BioLMs),there is a growing need for a comprehensive analysis of the current landscape,computational characteristics,and diverse applications.This survey aims to address this need by providing a thorough review of BioLMs,focusing on their evolution,classification,and distinguishing features,alongside a detailed examination of training methodologies,datasets,and evaluation frameworks.We explore the wide-ranging applications of BioLMs in critical areas such as disease diagnosis,drug discovery,and vaccine development,highlighting their impact and transformative potential in bioinformatics.We identify key challenges and limitations inherent in BioLMs,including data privacy and security concerns,interpretability issues,biases in training data and model outputs,and domain adaptation complexities.Finally,we high-light emerging trends and future directions,offering valuable insights to guide researchers and clinicians toward advancing BioLMs for increasingly sophisticated biological and clinical applications.
基金This work was supported by grants from National Natural Science Foundation of China(No.21276014,21476011)National High Technology Research and Development Program(863 Program)(No.2015AA021003)+1 种基金Fundamental Research Funds for the Central Universities(YS1407)111 project(B13005).
文摘Derived from the bacterial adaptive immune system,CRISPR technology has revolutionized conventional genetic engineering methods and unprecedentedly facilitated strain engineering.In this review,we outline the fundamental CRISPR tools that have been employed for strain optimization.These tools include CRISPR editing,CRISPR interference,CRISPR activation and protein imaging.To further characterize the CRISPR technology,we present current applications of these tools in microbial systems,including model-and non-model industrial microorganisms.Specially,we point out the major challenges of the CRISPR tools when utilized for multiplex genome editing and sophisticated expression regulation.To address these challenges,we came up with strategies that place emphasis on the amelioration of DNA repair efficiency through CRISPR-Cas9-assisted recombineering.Lastly,multiple promising research directions were proposed,mainly focusing on CRISPR-based construction of microbial ecosystems toward high production of desired chemicals.
基金supported by the National Natural Science Foundation of China(Grant No.11774060)the National Key R&D Program of the MOST of China(Grant Nos.2016YFA0300200,2017YFA0303004,2017YFA0303104,2016YFA0302300,and 2017YFA0303003)+2 种基金the National Basic Research Program of China(Grant No.2015CB921700)the Science Challenge Project(Grant No.TZ2016004)the Shanghai Education Development Foundation and Shanghai Municipal Education Commission(Chenguang Program)。
文摘Scanning tunneling microscopy/spectroscopy is applied herein to study the pristine and potassium(K)-doped single-layer pquaterphenyl(P4P) films grown on the Au(111) substrate at the molecular level. Abundant complex structural and electronic phases are induced by various K doping. The Fermi-level pinning effect is observed at a low doping level. On the contrary,K3P4P exhibits intriguing versatile phases and properties because charge carriers are effectively doped in. For example, two kinds of molecular vibration modes with energies below 100 meV are observed, indicating a possible strong electron-phonon coupling. The splitting of the lowest unoccupied molecular orbital state in K3P4P illustrates an electronic correlation effect, and its strength varies for four different K3P4P phases with different structures. In addition, the appearance of a Kondo resonance on the molecular vacancy/impurity implies a local molecular magnetic moment. Our results demonstrate that the complex electronic properties of an alkali metal-doped P4P/Au film stem from the existence of many competing interactions, such as electronelectron correlations and electron-vibration coupling, which can be effectively tuned via variable carrier doping and molecular structure. Our work also opens new routes toward engineering novel molecular devices and creating new electronic phases in strongly correlated molecular materials.
基金supported by the National Key R&D Program of China(Grant Nos.2017YFA0303004,and 2017YFA0303104)the National Natural Science Foundation of China(Grant No.11774060)+2 种基金the Science Challenge Project(Grant No.TZ2016004)the Shanghai Education Development Foundation and Shanghai Municipal Education Commission(Chenguang Program)the Shanghai Municipal Science and Technology Major Project(Grant No.2019SHZDZX01)。
文摘Herein, we show that a self-assembled phase of potassium(K)-doped single-layer para-sexiphenyl(PSP) film on a gold substrate is an excellent platform for studying the two-impurity Kondo model. On K-doped PSP molecules well separated from others, we observe a Kondo resonance peak close to EFwith a Kondo temperature of 30 K. The Kondo resonance peak splits when another K-doped PSP molecule is present in the vicinity, and the splitting gradually increases with the decrease in intermolecular distance without signs of phase transition. Our data demonstrate how a Kondo singlet state gradually evolves into an antiferromagnetic singlet state due to the competition between Kondo screening and antiferromagnetic Ruderman-Kittel-Kasuya-Yosida coupling,as described in the two-impurity Kondo model. Intriguingly, the antiferromagnetic singlet is quickly destroyed on increasing temperature and transforms back to a Kondo singlet below the Kondo temperature. Our data provide a comprehensive picture and quantitative constraints on related theories and calculations of the two-impurity Kondo model.
基金the National Natural Science Foundation of China(82071784)the Fundamental Research Funds for the Central Universities(2042022dx0003 and PTPP2023002)+1 种基金the Key Research and Development Project of Hubei Province(2020BCA069)the Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University(ZNJC202007).
文摘Background:Human immunodeficiency virus type 1(HIV-1)remains a persistent global health challenge.Therefore,a continuous exploration of novel therapeutic strategies is essential.A comprehensive understanding of how HIV-1 utilizes the cellular metabolism machinery for replication can provide insights into new therapeutic approaches.Methods:In this study,we performed a flux balance analysis using a genome-scale metabolic model(GEM)integrated with an HIV-1 viral biomass objective function to identify potential targets for anti–HIV-1 interventions.We generated a GEM by integrating an HIV-1 production reaction into CD4+T cells and optimized for both host and virus optimal states as objective functions to depict metabolic profiles of cells in the status for optimal host biomass maintenance or for optimal HIV-1 virion production.Differential analysis was used to predict biochemical reactions altered optimal for HIV-1 production.In addition,we conducted in silico simulations involving gene and reaction knock-outs to identify potential anti–HIV-1 targets,which were subsequently validated by human phytohemagglutinin(PHA)blasts infected with HIV-1.Results:Differential analysis identified several altered biochemical reactions,including increased lysine uptake and oxidative phosphorylation(OXPHOS)activities in the virus optima compared with the host optima.In silico gene and reaction knock-out simulations revealed de novo pyrimidine synthesis,and OXPHOS could serve as potential anti–HIV-1 metabolic targets.In vitro assay confirmed that targeting OXPHOS using metformin could suppress the replication of HIV-1 by 56.6%(385.4±67.5 pg/mL in the metformintreated group vs.888.4±32.3 pg/mL in the control group,P<0.001).Conclusion:Our integrated host-virus genome-scale metabolic study provides insights on potential targets(OXPHOS)for anti-HIV therapies.
基金supported by the National Institute of General Medical Sciences of the National Institutes of Health under award number R35GM128620the support from the College of Engineering,The University of Georgia,Athens
文摘Coumarin and its derivatives,presenting in many organisms(plants,fungi,and bacteria),are critical metabolites composed of fused benzene andα-pyrone rings.With unique biological and chemical properties,coumarin derivatives possess great technological potential in the agrochemicals,pharmaceuticals,food,and cosmetic industries.The increasing demand for coumarin derivatives accelerates the research in biological and chemical synthesis to provide stable and scalable sources of coumarins.However,the complex structures and unknown pathways have limited the progress in the biosynthesis of coumarin derivatives.Here,we summarize recent developments and provide a detailed analysis of coumarin derivative biosynthetic pathways in different organisms.
