Two graphs are defined to be adjointly equivalent if and only if their complements are chromatically equivalent. Using the properties of the adjoint polynomials and the fourth character R4（G）, the adjoint equivalenc...Two graphs are defined to be adjointly equivalent if and only if their complements are chromatically equivalent. Using the properties of the adjoint polynomials and the fourth character R4（G）, the adjoint equivalence class of graph Bn-8,l,4 is determined. According to the relations between adjoint polynomial and chromatic polynomial, we also simultaneously determine the chromatic equivalence class of Bn-8,l,4 that is the complement of Bn-8,l,4.展开更多
The atom-bond connectivity（ABC） index of a graph G, introduced by Estrada,Torres, Rodr′？guez and Gutman in 1998, is defined as the sum of the weights√1/di＋1/dj-2/didj of all edges vivj of G, where di denotes th...The atom-bond connectivity（ABC） index of a graph G, introduced by Estrada,Torres, Rodr′？guez and Gutman in 1998, is defined as the sum of the weights√1/di＋1/dj-2/didj of all edges vivj of G, where di denotes the degree of the vertex vi in G. In this paper, we give an upper bound of the ABC index of a two-tree G with n vertices, that is, ABC（G） ≤（2n- 4）√2/2＋√2n-4/n-1. We also determine the two-trees with the maximum and the second maximum ABC index.展开更多
In order to improve the accuracy of wireless network positioning,the triangulation method of wireless network positioning technology is proposed,which is based on the linear least square fitting method.It makes the ob...In order to improve the accuracy of wireless network positioning,the triangulation method of wireless network positioning technology is proposed,which is based on the linear least square fitting method.It makes the observed value and the fitting value very close,effectively solves the problem of significant contradiction between the fitting result and the observed value in the principle of least square method,and can realize the accurate measurement of geographic information by wireless network positioning technology.展开更多
Based on the analysis of the advantages and disadvantages of GPS positioning system in practical application,this paper proposes the combination of wireless network positioning technology and GPS positioning system to...Based on the analysis of the advantages and disadvantages of GPS positioning system in practical application,this paper proposes the combination of wireless network positioning technology and GPS positioning system to overcome the low accuracy of GPS positioning system in the case of occlusion.This paper introduces in detail the principle of the application of wireless network positioning technology based on GPS positioning system in geographic information measurement,and illustrates its practical application in production by taking coal mine positioning as an example.展开更多
Reactive oxygen species(ROS)plays critical roles in modulating plant growth and stress response and its homeostasis is fine tuned using multiple peroxidases.H_(2)O_(2),a major kind of ROS,is removed rapidly and direct...Reactive oxygen species(ROS)plays critical roles in modulating plant growth and stress response and its homeostasis is fine tuned using multiple peroxidases.H_(2)O_(2),a major kind of ROS,is removed rapidly and directly using three catalases,CAT1,CAT2,and CAT3,in Arabidopsis.Although the activity regulations of catalases have been well studied,their degradation pathway is less clear.Here,we report that CAT2 and CAT3 protein abundance was partially controlled using the 26S proteasome.To further identify candidate proteins that modulate the stability of CAT2,we performed yeast-two-hybrid screening and recovered several clones encoding a protein with RING and vWA domains,CIRP1(CAT2Interacting RING Protein 1).Drought and oxidative stress downregulated CIRP1 transcripts.CIRP1 harbored E3 ubiquitination activity and accelerated the degradation of CAT2 and CAT3 by direct interaction and ubiquitination.The cirp1 mutants exhibited stronger drought and oxidative stress tolerance,which was opposite to the cat2 and cat3 mutants.Genetic analysis revealed that CIRP1 acts upstream of CAT2 and CAT3 to negatively regulate drought and oxidative stress tolerance.The increased drought and oxidative stress tolerance of the cirp1mutants was due to enhanced catalase(CAT)activities and alleviated ROS levels.Our data revealed that the CIRP1-CAT2/CAT3 module plays a vital role in alleviating ROS levels and balancing growth and stress responses in Arabidopsis.展开更多
Phenylethylisoquinoline alkaloids(PIAs)are medicinally important natural products derived from the 1-phenyl-ethylisoquinoline precursor.Heterologous production of the PIAs remains challenging due to the incomplete elu...Phenylethylisoquinoline alkaloids(PIAs)are medicinally important natural products derived from the 1-phenyl-ethylisoquinoline precursor.Heterologous production of the PIAs remains challenging due to the incomplete elucidation of biosynthetic pathway and the lack of proper microbial cell factory designed for precursor enhancement.In this work,an artificial pathway composed of eight enzymes from different species was estab-lished for de novo 1-phenylethylisoquinoline biosynthesis in engineered Escherichia coli.The yield of the inter-mediate 4-hydroxydihydrocinnamaldehyde was optimized through screening various NADP^(+)-dependent 2-alkenal reductases,cofactor regeneration and the site-directed mutagenesis of key residues in ChAER1.Subse-quently,incorporation of the modified dopamine pathway into an endogenous reductase-deficient E.coli with high tyrosine yield boosted the production of 1-phenylethylisoquinoline,reaching 402.58 mg/L in a 5L fermenter.Our work lays a foundation for the future large-scale production of high value-added 1-phenylethy-lisoquinolinerelated alkaloids.展开更多
Squalene,a lipophilic triterpene with multifaceted bioactivities,faces bioproduction bottlenecks in microbial hosts due to inefficient biosynthetic pathways and limited storage capacity.Here,we address these challenge...Squalene,a lipophilic triterpene with multifaceted bioactivities,faces bioproduction bottlenecks in microbial hosts due to inefficient biosynthetic pathways and limited storage capacity.Here,we address these challenges through systems metabolic engineering integrating redox-balanced 3-hydroxy-3-methyl glutaryl coenzyme A reductase(HMGR)variants and membrane lipid remodeling.By developing a hybrid HMGRs system combining NADPH-dependent and NADH-preferred enzymes,squalene production reached 852.06±28.95 mg/L with balanced cofactor utilization.Subsequent engineering of membrane morphology and lipid metabolism generated lipid-enriched elongated cells,through the overexpression of dgs,murG and plsC,boosting squalene production to 970.86±55.67 mg/L.Implementation of delayed induction strategies coupled with 10%dodecane overlay as an in situ recovery system achieved a final squalene titer of 1267.01 mg/L in a 3 L bioreactor.Mechanistic studies revealed fatty acid(FA)and phosphatidylethanolamine(PE)as key reservoirs for squalene in E.coli,with dgs overexpression specifically promoting cellular elongation.This article provides comprehensive insights into engineering strategies and mechanistic perspectives,establishing a universal framework for hydrophobic metabolite biomanufacturing in prokaryotic hosts.展开更多
Drug-target interaction(DTI)is a widely explored topic in the field of bioinformatics and plays a pivotal role in drug discovery.However,the traditional bio-experimental process of drug-target interaction identificati...Drug-target interaction(DTI)is a widely explored topic in the field of bioinformatics and plays a pivotal role in drug discovery.However,the traditional bio-experimental process of drug-target interaction identification requires a large investment of time and labor.To address this challenge,graph neural network(GNN)approaches in deep learning are becoming a prominent trend in the field of DTI research,which is characterized by multimodal processing of data,feature learning and interpretability in DTI.Nevertheless,some methods are still limited by homogeneous graphs and single features.To address the problems,we mechanistically analyze graph convolutional neural networks(GCNs)and graph attentional neural networks(GATs)to propose a new model for the prediction of drug-target interactions using graph neural networks named BiTGNN[Bidirectional Transformer(Bi-Transformer)-graph neural network].The method first establishes drug-target pairs through the pseudo-position specificity scoring matrix(PsePSSM)and drug fingerprint data,and constructs a heterogeneous network by utilizing the relationship between the drug and the target.Then,the computational extraction of drug and target attributes is performed using GCNs and GATs for the purpose of model information flow extension and graph information enhancement.We collect interaction data using the proposed Bi-Transformer architecture,in which we design a bidirectional cross-attention mechanism for calculating the effects of drugtarget interactions for realistic biological interaction simulations.Finally,a feed-forward neural network is used to obtain the feature matrices of the drug and the target,and DTI prediction is performed by fusing the two feature matrices.The Enzyme,Ion Channel(IC),G Protein-coupled Receptor(GPCR)and Nuclear Receptor(NR)datasets are used in the experiments,and compared with several existing mainstream models,our model outperforms in Area Under the ROC Curve(AUC),Specificity,Accuracy and the metric Area Under the Precision-Recall Curve(AUPR).展开更多
The ent-kaurenoids(e.g.,oridonin and enmein)from the Isodon genus(Lamiaceae)are one class of diterpenoids with rich structural diversity and intriguing pharmaceutical activity.In contrast to the well-established gibbe...The ent-kaurenoids(e.g.,oridonin and enmein)from the Isodon genus(Lamiaceae)are one class of diterpenoids with rich structural diversity and intriguing pharmaceutical activity.In contrast to the well-established gibberellin pathway,oxidative modifications diversifying the ent-kaurene skeleton in Isodon have remained undetermined for half a century.Here we report a chromosome-level genome assembly of I.rubescens,a well-recognized oridonin producer long favored by Asian people as a traditional herb with antitumor effects.The shoot apex was confirmed to be the actual region actively producing ent-kaurene diterpenoids.Through comparative genomics and phylogenetic analyses,we discovered a cluster of tandem-duplicated CYP706V oxygenase-encoding genes located on an ancient genomic block widely distributed in eudicots,whereas almost exclusively emerged in Isodon plants.In the shoot apex,IrCYP706V2 and IrCYP706V7 oxidized the ent-kaurene core in the initial stage of oridonin biosynthesis.Loss of CYP706Vs in other Lamiaceae plants offered an explanation for the specific kaurenoid production in Isodon plants.Moreover,we found that the Isodon genomes encode multiple diterpenoid synthases that are potentially involved in generating diterpenoid diversity.These findings provided new insights into the evolution of the lineage-specific diterpenoid pathway and laid a foundation for improving production of bioactive ent-kaurene-type diterpenoids by molecular breeding and synthetic biology approaches.展开更多
基金Supported by the National Natural Science Foundation of China(Grant No.11161037)the Science Found of Qinghai Province(Grant No.2011-z-907)
文摘Two graphs are defined to be adjointly equivalent if and only if their complements are chromatically equivalent. Using the properties of the adjoint polynomials and the fourth character R4（G）, the adjoint equivalence class of graph Bn-8,l,4 is determined. According to the relations between adjoint polynomial and chromatic polynomial, we also simultaneously determine the chromatic equivalence class of Bn-8,l,4 that is the complement of Bn-8,l,4.
基金Supported by the National Natural Science Foundation of China(Grant Nos.6116400561440005+6 种基金11161037)the Program for Changjiang Scholars and Innovative Research Team in Universities(Grant No.IRT-15R40)Key Laboratory of Tibetan Information Processing of Ministry of Education of Chinathe Research Fund for the Chunhui Program of Ministry of Education of China(Grant No.Z2014022)the Nature Science Foundation of Qinghai Province(Grant Nos.2013-Z-Y172014-ZJ-9072014-ZJ-721)
文摘The atom-bond connectivity（ABC） index of a graph G, introduced by Estrada,Torres, Rodr′？guez and Gutman in 1998, is defined as the sum of the weights√1/di＋1/dj-2/didj of all edges vivj of G, where di denotes the degree of the vertex vi in G. In this paper, we give an upper bound of the ABC index of a two-tree G with n vertices, that is, ABC（G） ≤（2n- 4）√2/2＋√2n-4/n-1. We also determine the two-trees with the maximum and the second maximum ABC index.
文摘In order to improve the accuracy of wireless network positioning,the triangulation method of wireless network positioning technology is proposed,which is based on the linear least square fitting method.It makes the observed value and the fitting value very close,effectively solves the problem of significant contradiction between the fitting result and the observed value in the principle of least square method,and can realize the accurate measurement of geographic information by wireless network positioning technology.
基金supported by the Key R&D and transformation Projects in Qinghai,China(2019-GX-170).
文摘Based on the analysis of the advantages and disadvantages of GPS positioning system in practical application,this paper proposes the combination of wireless network positioning technology and GPS positioning system to overcome the low accuracy of GPS positioning system in the case of occlusion.This paper introduces in detail the principle of the application of wireless network positioning technology based on GPS positioning system in geographic information measurement,and illustrates its practical application in production by taking coal mine positioning as an example.
基金supported by grants from the National Natural Science Foundation of China(32170304 and 32070340)the Natural Science Foundation of Guangdong Province(2022A1515012572)。
文摘Reactive oxygen species(ROS)plays critical roles in modulating plant growth and stress response and its homeostasis is fine tuned using multiple peroxidases.H_(2)O_(2),a major kind of ROS,is removed rapidly and directly using three catalases,CAT1,CAT2,and CAT3,in Arabidopsis.Although the activity regulations of catalases have been well studied,their degradation pathway is less clear.Here,we report that CAT2 and CAT3 protein abundance was partially controlled using the 26S proteasome.To further identify candidate proteins that modulate the stability of CAT2,we performed yeast-two-hybrid screening and recovered several clones encoding a protein with RING and vWA domains,CIRP1(CAT2Interacting RING Protein 1).Drought and oxidative stress downregulated CIRP1 transcripts.CIRP1 harbored E3 ubiquitination activity and accelerated the degradation of CAT2 and CAT3 by direct interaction and ubiquitination.The cirp1 mutants exhibited stronger drought and oxidative stress tolerance,which was opposite to the cat2 and cat3 mutants.Genetic analysis revealed that CIRP1 acts upstream of CAT2 and CAT3 to negatively regulate drought and oxidative stress tolerance.The increased drought and oxidative stress tolerance of the cirp1mutants was due to enhanced catalase(CAT)activities and alleviated ROS levels.Our data revealed that the CIRP1-CAT2/CAT3 module plays a vital role in alleviating ROS levels and balancing growth and stress responses in Arabidopsis.
基金the National Key R&D Program of China(2020YFA0907900,2018YFA0900600,2024YFA1700126)the National Natural Science Foundation of China(32070328)+4 种基金Derivative Bank of Chinese Biological Resources(KFJ-BRP-009-002)the Chinese Academy of Sciences Collaborative Innovation project(CNXT001)the Key Laboratory of Plant Carbon Capture,Chinese Academy of Sciencesthe Key Laboratory of Plant Design,Chinese Academy of Sciencesthe Foundation of Youth Innovation Promotion Association of the Chinese Academy of Sciences.
文摘Phenylethylisoquinoline alkaloids(PIAs)are medicinally important natural products derived from the 1-phenyl-ethylisoquinoline precursor.Heterologous production of the PIAs remains challenging due to the incomplete elucidation of biosynthetic pathway and the lack of proper microbial cell factory designed for precursor enhancement.In this work,an artificial pathway composed of eight enzymes from different species was estab-lished for de novo 1-phenylethylisoquinoline biosynthesis in engineered Escherichia coli.The yield of the inter-mediate 4-hydroxydihydrocinnamaldehyde was optimized through screening various NADP^(+)-dependent 2-alkenal reductases,cofactor regeneration and the site-directed mutagenesis of key residues in ChAER1.Subse-quently,incorporation of the modified dopamine pathway into an endogenous reductase-deficient E.coli with high tyrosine yield boosted the production of 1-phenylethylisoquinoline,reaching 402.58 mg/L in a 5L fermenter.Our work lays a foundation for the future large-scale production of high value-added 1-phenylethy-lisoquinolinerelated alkaloids.
基金supported by the National Key R&D Program of China(No.2024YFA0919900)the Key Laboratory of Shanghai To-bacco Group Cigarette Smoke(No.K2023-1-044P)+2 种基金the State Key Laboratory of Plant Trait Designthe Key Laboratory of Plant Carbon Capture,Chinese Academy of Sciencesthe Shanghai Municipal Science and Technology Major Project.
文摘Squalene,a lipophilic triterpene with multifaceted bioactivities,faces bioproduction bottlenecks in microbial hosts due to inefficient biosynthetic pathways and limited storage capacity.Here,we address these challenges through systems metabolic engineering integrating redox-balanced 3-hydroxy-3-methyl glutaryl coenzyme A reductase(HMGR)variants and membrane lipid remodeling.By developing a hybrid HMGRs system combining NADPH-dependent and NADH-preferred enzymes,squalene production reached 852.06±28.95 mg/L with balanced cofactor utilization.Subsequent engineering of membrane morphology and lipid metabolism generated lipid-enriched elongated cells,through the overexpression of dgs,murG and plsC,boosting squalene production to 970.86±55.67 mg/L.Implementation of delayed induction strategies coupled with 10%dodecane overlay as an in situ recovery system achieved a final squalene titer of 1267.01 mg/L in a 3 L bioreactor.Mechanistic studies revealed fatty acid(FA)and phosphatidylethanolamine(PE)as key reservoirs for squalene in E.coli,with dgs overexpression specifically promoting cellular elongation.This article provides comprehensive insights into engineering strategies and mechanistic perspectives,establishing a universal framework for hydrophobic metabolite biomanufacturing in prokaryotic hosts.
基金supported by the National Key R&D Program of China under the Project No.2021YFB2802300National Natural Science Foundation of China under the Grant Nos.12271362 and 12061059.
文摘Drug-target interaction(DTI)is a widely explored topic in the field of bioinformatics and plays a pivotal role in drug discovery.However,the traditional bio-experimental process of drug-target interaction identification requires a large investment of time and labor.To address this challenge,graph neural network(GNN)approaches in deep learning are becoming a prominent trend in the field of DTI research,which is characterized by multimodal processing of data,feature learning and interpretability in DTI.Nevertheless,some methods are still limited by homogeneous graphs and single features.To address the problems,we mechanistically analyze graph convolutional neural networks(GCNs)and graph attentional neural networks(GATs)to propose a new model for the prediction of drug-target interactions using graph neural networks named BiTGNN[Bidirectional Transformer(Bi-Transformer)-graph neural network].The method first establishes drug-target pairs through the pseudo-position specificity scoring matrix(PsePSSM)and drug fingerprint data,and constructs a heterogeneous network by utilizing the relationship between the drug and the target.Then,the computational extraction of drug and target attributes is performed using GCNs and GATs for the purpose of model information flow extension and graph information enhancement.We collect interaction data using the proposed Bi-Transformer architecture,in which we design a bidirectional cross-attention mechanism for calculating the effects of drugtarget interactions for realistic biological interaction simulations.Finally,a feed-forward neural network is used to obtain the feature matrices of the drug and the target,and DTI prediction is performed by fusing the two feature matrices.The Enzyme,Ion Channel(IC),G Protein-coupled Receptor(GPCR)and Nuclear Receptor(NR)datasets are used in the experiments,and compared with several existing mainstream models,our model outperforms in Area Under the ROC Curve(AUC),Specificity,Accuracy and the metric Area Under the Precision-Recall Curve(AUPR).
基金funded by the National Key R&D Program of China(2018YFA0900600)the National Natural Science Foundation of China(32070328,22077129,and 41876084),the Program of Shanghai Academic Research Leader(20XD1404400)+2 种基金the Strategic Priority Research Program“Molecular Mechanism of Plant Growth and Development”of CAS(XDB27020202)the Construction of the Registry and Database of Bioparts for Synthetic Biology of the Chinese Academy of Sciences(ZSYS-016),the International Partnership Program of the Chinese Academy of Sciences(153D31KYSB20170121),Derivative Bank of Chinese Biological Resources(KFJ-BRP-009-002)the National Key Laboratory of Plant Molecular Genetics,SIPPE,CAS.Y.S.is supported by the Foundation of Youth Innovation Promotion Association of the Chinese Academy of Sciences.
文摘The ent-kaurenoids(e.g.,oridonin and enmein)from the Isodon genus(Lamiaceae)are one class of diterpenoids with rich structural diversity and intriguing pharmaceutical activity.In contrast to the well-established gibberellin pathway,oxidative modifications diversifying the ent-kaurene skeleton in Isodon have remained undetermined for half a century.Here we report a chromosome-level genome assembly of I.rubescens,a well-recognized oridonin producer long favored by Asian people as a traditional herb with antitumor effects.The shoot apex was confirmed to be the actual region actively producing ent-kaurene diterpenoids.Through comparative genomics and phylogenetic analyses,we discovered a cluster of tandem-duplicated CYP706V oxygenase-encoding genes located on an ancient genomic block widely distributed in eudicots,whereas almost exclusively emerged in Isodon plants.In the shoot apex,IrCYP706V2 and IrCYP706V7 oxidized the ent-kaurene core in the initial stage of oridonin biosynthesis.Loss of CYP706Vs in other Lamiaceae plants offered an explanation for the specific kaurenoid production in Isodon plants.Moreover,we found that the Isodon genomes encode multiple diterpenoid synthases that are potentially involved in generating diterpenoid diversity.These findings provided new insights into the evolution of the lineage-specific diterpenoid pathway and laid a foundation for improving production of bioactive ent-kaurene-type diterpenoids by molecular breeding and synthetic biology approaches.
