Bibenzyls,a kind of important plant polyphenols,have attracted growing attention for their broad and remarkable pharmacological activities.However,due to the low abundance in nature,uncontrollable and environmentally ...Bibenzyls,a kind of important plant polyphenols,have attracted growing attention for their broad and remarkable pharmacological activities.However,due to the low abundance in nature,uncontrollable and environmentally unfriendly chemical synthesis processes,these compounds are not readily accessible.Herein,one high-yield bibenzyl backbone-producing Escherichia coli strain was constructed by using a highly active and substrate-promiscuous bibenzyl synthase identified from Dendrobium officinale in combination with starter and extender biosynthetic enzymes.Three types of efficiently postmodifying modular strains were engineered by employing methyltransferases,prenyltransferase,and glycosyltransferase with high activity and substrate tolerance together with their corresponding donor biosynthetic modules.Structurally different bibenzyl derivatives were tandemly and/or divergently synthesized by co-culture engineering in various combination modes.Especially,a prenylated bibenzyl derivative(12)was found to be an antioxidant that exhibited potent neuroprotective activity in the cellular and rat models of ischemia stroke.RNA-seq,quantitative RT-PCR,and Western-blot analysis demonstrated that 12 could up-regulate the expression level of an apoptosis-inducing factor,mitochondria associated 3(Aifm3),suggesting that Aifm3 might be a new target in ischemic stroke therapy.This study provides a flexible plug-and-play strategy for the easy-to-implement synthesis of structurally diverse bibenzyls through a modular co-culture engineering pipeline for drug discovery.展开更多
This paper is concerned with distributed containment maneuvering of second-order Multi-Input Multi-Output(MIMO)multi-agent systems with non-periodic communication and actuation.The agent is subject to unmatched nonlin...This paper is concerned with distributed containment maneuvering of second-order Multi-Input Multi-Output(MIMO)multi-agent systems with non-periodic communication and actuation.The agent is subject to unmatched nonlinear dynamics and external disturbances.Event-triggered containment maneuvering control methods is developed based on a modular design.Specifically,an estimator module is constructed based on neural networks and the nonperiodic obtained follower information through event-triggered communication.Next,a controller module is designed by using the identified information from the estimator module and a third-order linear tracking differentiator.An event-triggered mechanism is introduced for updating the actuator.Then,a path update law is designed based on the non-periodic leader information through event-triggered communication.The closed-loop system cascaded by the estimation subsystem and control subsystem is proved to be input-to-state stable,and Zeno behavior is excluded in the control process.The proposed method is capable of reducing the consumption of communication and actuation.A simulation example is provided to substantiate the effectiveness of the proposed event-triggered control method for distributed containment maneuvering of second-order MIMO multi-agent systems.展开更多
The rapid expansion of enterprises makes product collaborative design （PCD） a critical issue under the distributed heterogeneous environment, but as the collaborative task of large-scale network becomes more complic...The rapid expansion of enterprises makes product collaborative design （PCD） a critical issue under the distributed heterogeneous environment, but as the collaborative task of large-scale network becomes more complicated, neither unified task decomposition and allocation methodology nor Agent-based network management platform can satisfy the increasing demands. In this paper, to meet requirements of PCD for distributed product development, a collaborative design mechanism based on the thought of modularity and the Agent technology is presented. First, the top-down 4-tier process model based on task-oriented modular and Agent is constructed for PCD after analyzing the mapping relationships between requirements and functions in the collaborative design. Second, on basis of sub-task decomposition for PCD based on a mixed method, the mathematic model of task-oriented modular based on multi-objective optimization is established to maximize the module cohesion degree and minimize the module coupling degree, while considering the module executable degree as a restriction. The mathematic model is optimized and simulated by the modified PSO, and the decomposed modules are obtained. Finally, the Agent structure model for collaborative design is put forward, and the optimism matching Agents are selected by using similarity algorithm to implement different task-modules by the integrated reasoning and decision-making mechanism with the behavioral model of collaborative design Agents. With the results of experimental studies for automobile collaborative design, the feasibility and efficiency of this methodology of task-oriented modular and Agent-based collaborative design in the distributed heterogeneous environment are verified. On this basis, an integrative automobile collaborative R＆D platform is developed. This research provides an effective platform for automobile manufacturing enterprises to achieve PCD, and helps to promote product numeralization collaborative R＆D and management development.展开更多
基金supported by the National Key Research and Development Program of China(2020YFA0908000)CAMS Innovation fund for Medical Sciences(CIFMS-2021-I2M1-028 and CIFMS-2021-I2M-1-029,China)Beijing Key Laboratory of non-Clinical Drug Metabolism and PK/PD Study(Z141102004414062,China)。
文摘Bibenzyls,a kind of important plant polyphenols,have attracted growing attention for their broad and remarkable pharmacological activities.However,due to the low abundance in nature,uncontrollable and environmentally unfriendly chemical synthesis processes,these compounds are not readily accessible.Herein,one high-yield bibenzyl backbone-producing Escherichia coli strain was constructed by using a highly active and substrate-promiscuous bibenzyl synthase identified from Dendrobium officinale in combination with starter and extender biosynthetic enzymes.Three types of efficiently postmodifying modular strains were engineered by employing methyltransferases,prenyltransferase,and glycosyltransferase with high activity and substrate tolerance together with their corresponding donor biosynthetic modules.Structurally different bibenzyl derivatives were tandemly and/or divergently synthesized by co-culture engineering in various combination modes.Especially,a prenylated bibenzyl derivative(12)was found to be an antioxidant that exhibited potent neuroprotective activity in the cellular and rat models of ischemia stroke.RNA-seq,quantitative RT-PCR,and Western-blot analysis demonstrated that 12 could up-regulate the expression level of an apoptosis-inducing factor,mitochondria associated 3(Aifm3),suggesting that Aifm3 might be a new target in ischemic stroke therapy.This study provides a flexible plug-and-play strategy for the easy-to-implement synthesis of structurally diverse bibenzyls through a modular co-culture engineering pipeline for drug discovery.
基金supported in part by the National Natural Science Foundation of China(Nos.61673081,51979020,51909021,51939001)in part by Science and Technology Fund for Distinguished Young Scholars of Dalian(No.2018RJ08)+5 种基金in part by the Stable Supporting Fund of Science and Technology on Underwater Vehicle Technology(No.JCKYS2019604SXJQR-01)in part by the Supporting Program for High-level Talent in Transportation Department(No.2018-030)in part by the National Key Research and Development Program of China(No.2016YFC0301500)in part by the Fundamental Research Funds for the Central Universities(Nos.3132019319,3132020101,3132020102)in part by China Postdoctoral Science Foundation(No.2019M650086)the Training Program for Doctoral Innovative Talents of DLMU(No.CXXM2019BS001)。
文摘This paper is concerned with distributed containment maneuvering of second-order Multi-Input Multi-Output(MIMO)multi-agent systems with non-periodic communication and actuation.The agent is subject to unmatched nonlinear dynamics and external disturbances.Event-triggered containment maneuvering control methods is developed based on a modular design.Specifically,an estimator module is constructed based on neural networks and the nonperiodic obtained follower information through event-triggered communication.Next,a controller module is designed by using the identified information from the estimator module and a third-order linear tracking differentiator.An event-triggered mechanism is introduced for updating the actuator.Then,a path update law is designed based on the non-periodic leader information through event-triggered communication.The closed-loop system cascaded by the estimation subsystem and control subsystem is proved to be input-to-state stable,and Zeno behavior is excluded in the control process.The proposed method is capable of reducing the consumption of communication and actuation.A simulation example is provided to substantiate the effectiveness of the proposed event-triggered control method for distributed containment maneuvering of second-order MIMO multi-agent systems.
基金Supported by National Science and Technology Major Project of China(Grant No.2009ZX04014-103)PhD Programs Foundation of Ministry of Education of China(Grant No.20100072110038)+1 种基金National Natural Science Foundation of China(Grant Nos.61075064,61034004,61005090)Program for New Century Excellent Talents in University of Ministry of Education of China(Grant No.NECT-10-0633)
文摘The rapid expansion of enterprises makes product collaborative design （PCD） a critical issue under the distributed heterogeneous environment, but as the collaborative task of large-scale network becomes more complicated, neither unified task decomposition and allocation methodology nor Agent-based network management platform can satisfy the increasing demands. In this paper, to meet requirements of PCD for distributed product development, a collaborative design mechanism based on the thought of modularity and the Agent technology is presented. First, the top-down 4-tier process model based on task-oriented modular and Agent is constructed for PCD after analyzing the mapping relationships between requirements and functions in the collaborative design. Second, on basis of sub-task decomposition for PCD based on a mixed method, the mathematic model of task-oriented modular based on multi-objective optimization is established to maximize the module cohesion degree and minimize the module coupling degree, while considering the module executable degree as a restriction. The mathematic model is optimized and simulated by the modified PSO, and the decomposed modules are obtained. Finally, the Agent structure model for collaborative design is put forward, and the optimism matching Agents are selected by using similarity algorithm to implement different task-modules by the integrated reasoning and decision-making mechanism with the behavioral model of collaborative design Agents. With the results of experimental studies for automobile collaborative design, the feasibility and efficiency of this methodology of task-oriented modular and Agent-based collaborative design in the distributed heterogeneous environment are verified. On this basis, an integrative automobile collaborative R＆D platform is developed. This research provides an effective platform for automobile manufacturing enterprises to achieve PCD, and helps to promote product numeralization collaborative R＆D and management development.
