Antibiotics played an important role in controlling the development of enteric infection. However, the emergence of antibiotic resistance and gut dysbiosis led to a growing interest in the use of ...natural antimicrobial agents as alternatives for therapy and disinfection. Chitosan is a nontoxic natural antimicrobial polymer and is approved by GRAS (Generally Recognized as Safe by the United States Food and Drug Administration). Chitosan and chitosan derivatives can kill microbes by neutralizing negative charges on the microbial surface. Besides, chemical modifications give chitosan derivatives better water solubility and antimicrobial property. This review gives an overview of the preparation of chitosan, its derivatives, and the conjugates with other polymers and nanoparticles with better antimicrobial properties, explains the direct and indirect mechanisms of action of chitosan, and summarizes current treatment for enteric infections as well as the role of chitosan and chitosan derivatives in the antimicrobial agents in enteric infections. Finally, we suggested future directions for further research to improve the treatment of enteric infections and to develop more useful chitosan derivatives and conjugates.
Ischemic stroke presents a significant threat to human health due to its high disability rate and mortality. Currently, the clinical treatment drug, rt-PA, has a narrow therapeutic window and carries ...a high risk of bleeding. There is an urgent need to find new effective therapeutic drugs for ischemic stroke. Icariin (ICA), a key ingredient in the traditional Chinese medicine Epimedium, undergoes metabolism in vivo to produce Icaritin (ICT). While ICA has been reported to inhibit neuronal apoptosis after cerebral ischemia-reperfusion (I/R), yet its underlying mechanism remains unclear.BACKGROUNDIschemic stroke presents a significant threat to human health due to its high disability rate and mortality. Currently, the clinical treatment drug, rt-PA, has a narrow therapeutic window and carries a high risk of bleeding. There is an urgent need to find new effective therapeutic drugs for ischemic stroke. Icariin (ICA), a key ingredient in the traditional Chinese medicine Epimedium, undergoes metabolism in vivo to produce Icaritin (ICT). While ICA has been reported to inhibit neuronal apoptosis after cerebral ischemia-reperfusion (I/R), yet its underlying mechanism remains unclear.PC-12 cells were treated with 200 µM H2O2 for 8 h to establish a vitro model of oxidative damage. After administration of ICT, cell viability was detected by Thiazolyl blue tetrazolium Bromide (MTT) assay, reactive oxygen species (ROS) and apoptosis level, mPTP status and mitochondrial membrane potential (MMP) were detected by flow cytometry and immunofluorescence. Apoptosis and mitochondrial permeability transition pore (mPTP) related proteins were assessed by Western blotting. Middle cerebral artery occlusion (MCAO) model was used to establish I/R injury in vivo. After the treatment of ICA, the neurological function was scored by ZeaLonga socres; the infarct volume was observed by 2,3,5-Triphenyltetrazolium chloride (TTC) staining; HE and Nissl staining were used to detect the pathological state of the ischemic cortex; the expression changes of mPTP and apoptosis related proteins were detected by Western blotting.METHODSPC-12 cells were treated with 200 µM H2O2 for 8 h to establish a vitro model of oxidative damage. After administration of ICT, cell viability was detected by Thiazolyl blue tetrazolium Bromide (MTT) assay, reactive oxygen species (ROS) and apoptosis level, mPTP status and mitochondrial membrane potential (MMP) were detected by flow cytometry and immunofluorescence. Apoptosis and mitochondrial permeability transition pore (mPTP) related proteins were assessed by Western blotting. Middle cerebral artery occlusion (MCAO) model was used to establish I/R injury in vivo. After the treatment of ICA, the neurological function was scored by ZeaLonga socres; the infarct volume was observed by 2,3,5-Triphenyltetrazolium chloride (TTC) staining; HE and Nissl staining were used to detect the pathological state of the ischemic cortex; the expression changes of mPTP and apoptosis related proteins were detected by Western blotting.In vitro: ICT effectively improved H2O2-induced oxidative injury through decreasing the ROS level, inhibiting mPTP opening and apoptosis. In addition, the protective effects of ICT were not enhanced when it was co-treated with mPTP inhibitor Cyclosporin A (CsA), but reversed when combined with mPTP activator Lonidamine (LND). In vivo: Rats after MCAO shown cortical infarct volume of 32-40%, severe neurological impairment, while mPTP opening and apoptosis were obviously increased. Those damage caused was improved by the administration of ICA and CsA.RESULTSIn vitro: ICT effectively improved H2O2-induced oxidative injury through decreasing the ROS level, inhibiting mPTP opening and apoptosis. In addition, the protective effects of ICT were not enhanced when it was co-treated with mPTP inhibitor Cyclosporin A (CsA), but reversed when combined with mPTP activator Lonidamine (LND). In vivo: Rats after MCAO shown cortical infarct volume of 32-40%, severe neurological impairment, while mPTP opening and apoptosis were obviously increased. Those damage caused was improved by the administration of ICA and CsA.ICA improves cerebral ischemia-reperfusion injury by inhibiting mPTP opening, making it a potential candidate drug for the treatment of ischemic stroke.CONCLUSIONSICA improves cerebral ischemia-reperfusion injury by inhibiting mPTP opening, making it a potential candidate drug for the treatment of ischemic stroke.
UDGb belongs to family 5 of the uracil DNA glycosylase (UDG) superfamily. Here, we report that family 5 UDGb from Thermus thermophilus HB8 is not only a uracil DNA glycosyase acting on G/U, T/U, C/U, ...and A/U base pairs, but also a hypoxanthine DNA glycosylase acting on G/I, T/I, and A/I base pairs and a xanthine DNA glycosylase acting on all double-stranded and single-stranded xanthine-containing DNA. Analysis of potentials of mean force indicates that the tendency of hypoxanthine base flipping follows the order of G/I > T/I, A/I > C/I, matching the trend of hypoxanthine DNA glycosylase activity observed in vitro. Genetic analysis indicates that family 5 UDGb can also act as an enzyme to remove uracil incorporated into DNA through the existence of dUTP in the nucleotide pool. Mutational analysis coupled with molecular modeling and molecular dynamics analysis reveals that although hydrogen bonding to O2 of uracil underlies the UDG activity in a dissociative fashion, Tth UDGb relies on multiple catalytic residues to facilitate its excision of hypoxanthine and xanthine. This study underscores the structural and functional diversity in the UDG superfamily.
Background: Uracil DNA glycosylases are DNA repair enzymes involved in the removal of base damage.
Results: Family 5 UDGb is a uracil, hypoxanthine, and xanthine DNA glycosylase.
Conclusion: Family 5 UDGb adapts multiple catalytic amino acids for the excision of pyrimidine and purine deaminated DNA bases.
Significance: Family 5 UDGb exemplifies functional diversity in enzyme superfamilies.
The relationship between states (status of a system) and modes (capabilities of a system) used to describe system requirements is often poorly defined. The unclear relationship could make systems of ...interest out of control because of the out of boundaries of the systems caused by the newly added modes. Formally modeling and verifying requirements can clarify the relationship, making the system safer. To this end, an innovative approach to analyzing requirements is proposed. The MoSt language (a Domain Specific Language implemented on the Xtext framework) is firstly designed for requirements modeling and a model validator is realized to check requirements statically. A code generator is then provided to realize the automatic model transformation from the MoSt model to a NuSMV model, laying the foundation for the dynamic checks of requirements through symbolic model checking. Next, a NuSMV runner is designed to connect the NuSMV with the validator to automate the whole dynamic checks. The grammar, the model validator, the code generator, and the NuSMV runner are finally integrated into a publicly available Eclipse-based tool. Two case studies have been employed to illustrate the feasibility of our approach. For each case study, we injected 14 errors. The results show that the static and dynamic checks can successfully detect all the errors.
•A novel autonomous system framework for aircraft maintenance is proposed.•The framework integrates System Engineering and Agent-Based Modeling and Simulation.•A variety of maintenance processes are ...considered.•First time a significant exploration of real-world maintenance data is performed.•Maintenance cost and service level are evaluated in the experiments.
Operational support is a key issue for aircraft maintenance, which aims to improve operational efficiency and reduce operating costs under the premise of ensuring flight safety. Although many works have emerged to achieve this aim, they mostly address the concept of maintenance systems, the relationship between stakeholders and the loop of maintenance information separately. Hence, the cooperation between stakeholders could be impeded especially when urgent decisions should be made, relying on historical data and real-time data. In this paper, we propose an innovative design of an autonomous system supporting the automatic decision-making for maintenance scheduling. The design starts from the proposition of the analysis framework, to concept formulation of the system, to information transitional level interface, and ends with an instance of system module interactions. The underlying architecture illustrates the high-level fusion of technical and business drives; optimizes strategies and plans with regard to maintenance costs, service level and reliability. An agent-based simulation system is developed as a proof to illustrate the feasibility of the system principle and algorithms. Furthermore, the simulation experiment analyzing the impact of maintenance sequence strategies on maintenance costs and service level has demonstrated the algorithm functionality and the feasibility of the proposed approach.
The concept of Digital Twin (DT) seems promising to improve the management of patient pathways in Emergency Departments (EDs). This article proposes an agent-based architecture of a DT designed for ...that purpose. The core of this DT is its Information System (IS), which is regularly synchronised on the IS of the Physical Twin (PT). The agents model the ED’s resources (equipment and staff) and patients in the DT and update this information in the DT’s IS. This article shows how such a DT may operate in three modes: (0) “Digital Shadow” to monitor the ED’s current state in real time, (1) “Synchronised DT” to monitor the ED’s current and future states according to a predictive simulation, and (2) “Exploratory DT” in order to perform Monte Carlo simulations of various future states. Mode (1) is the main contribution. This proposition is illustrated in a simulation of the ED in order to demonstrate the capabilities.
This paper addresses the problem of resource scheduling of emergency departments in an uncertain environment. An innovative approach based on Agent-Based Simulation (ABS) and Discrete Event ...Simulation (DES) is proposed. To do so, this paper first proposes a framework integrating ABS and DES. Subsequently, we provide a detailed description of the DES and ABS parts of the model of the ED. Five combinations of strategies - namely, "FIFO+Random" (
FIFO: the queue of patients operates in FIFO; Random: the patients are randomly assigned to doctors), "FIFO+Centralised", "Random+Centralised" ("Centralised" implies the assignment of the most appropriate doctor to a patient is only determined by the Platform agent via optimising all the resources), "Random+Random" and "Autonomous" - are implemented to schedule the resources of the ED. Finally, experiments analyse the efficiency of the five combinations of strategies on the duration of patients' stay. The results show that "FIFO+Centralised" outperforms others regarding the average for the duration of patients' stay without hospitalisation: 3.75% of the time has been saved; "Random+Centralised" outperforms others regarding the average for the duration of patients' stay with hospitalisation: 0.57% of the time has been saved.
Model checking is an effective way to verify behaviours of an agent-based simulation system. Three behaviours are analysed: operational, control, and global behaviours. Global behaviours of a system ...emerge from operational behaviours of local components regulated by control behaviours of the system. The previous works principally focus on verifying the system from the operational point of view (operational behaviour). The satisfaction of the global behaviour of the system conforming to the control behaviour has not been investigated. Thus, in this paper, we propose a more complete approach for verifying global and operational behaviours of systems. To do so, these three behaviours are firstly formalized by automata-based techniques. The meta-transformation between automata theories and Kripke structure is then provided, in order to illustrate the feasibility for the model transformation between the agent-based simulation model and Kripke structure-based model. Then, a mapping between the models is proposed. Subsequently, the global behaviour of the system is verified by the properties extracted from the control behaviour and the operational behaviour is checked by general system performance properties (e.g. safety, deadlock freedom). Finally, a case study on the simulation system for aircraft maintenance has been carried out. A counterexample of signals sending between Flight agent and Plane agent has been produced by NuSMV model checker. Modifications for the NuSMV model and agent-based simulation model have been performed. The experiment results show that 9% out of 19% of flights have been changed to be serviceable.
This paper addresses the problem of Fault Classification and Prediction (FCP) without sufficient data in aircraft maintenance. An innovative approach based on Agent-Based Simulation System (ABSS) and ...the Fuzzy-Rough Nearest Neighbour (FRNN) method is proposed. To do so, a framework for integrating the FRNN approach into ABSS is firstly provided. The concept and architecture models of FRNN-ABSS are then used to describe the FRNN-ABSS system. Subsequently, random and sequence strategies are designed for the FCP of the engine. An algorithm for integrating the FRNN method into ABSS is also developed to automate FCP. Finally, the experiments analysing the impact of different strategies on maintenance costs and service level have been conducted. The results show that the approach proposed has achieved success for random and sequence strategies: 9.3% and 2.5% of maintenance costs have been saved; 4.17% and 12.5% of delayed flights have been changed into on-time flights.
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