By analyzing the observed phenomena and the data collected in the study, a multi-compartment linear circulation model for targeting drug delivery system was developed and the function formulas of the drug concentratio...By analyzing the observed phenomena and the data collected in the study, a multi-compartment linear circulation model for targeting drug delivery system was developed and the function formulas of the drug concentration-time in blood and target organ by computing were figured out. The drug concentration-time curve for target organ can be plotted with reference to the data of drug concentration in blood according to the model. The pharmacokinetic parameters of the drug in target organ could also be obtained. The practicability of the model was further checked by the curves of drug concentration-time in blood and target organ(liver) of liver-targeting nanoparticles in animal tests. Based on the liver drug concentration-time curves calculated by the function formula of the drug in target organ, the pharmacokinetic behavior of the drug in target organ(liver) was analyzed by statistical moment, and its pharmacokinetic parameters in liver were obtained. It is suggested that the (relative targeting index( can be used for quantitative evaluation of the targeting drug delivery systems.展开更多
The multi-compartment electric vehicle routing problem(EVRP)with soft time window and multiple charging types(MCEVRP-STW&MCT)is studied,in which electric multi-compartment vehicles that are environmentally friendl...The multi-compartment electric vehicle routing problem(EVRP)with soft time window and multiple charging types(MCEVRP-STW&MCT)is studied,in which electric multi-compartment vehicles that are environmentally friendly but need to be recharged in course of transport process,are employed.A mathematical model for this optimization problem is established with the objective of minimizing the function composed of vehicle cost,distribution cost,time window penalty cost and charging service cost.To solve the problem,an estimation of the distribution algorithm based on Lévy flight(EDA-LF)is proposed to perform a local search at each iteration to prevent the algorithm from falling into local optimum.Experimental results demonstrate that the EDA-LF algorithm can find better solutions and has stronger robustness than the basic EDA algorithm.In addition,when comparing with existing algorithms,the result shows that the EDA-LF can often get better solutions in a relatively short time when solving medium and large-scale instances.Further experiments show that using electric multi-compartment vehicles to deliver incompatible products can produce better results than using traditional fuel vehicles.展开更多
Objective:To evaluate the formulation of multi-compartmental transdermal patches for simultaneous delivery of multiple drugs:aceclofenac and serratiopeptidase.Methods:The patch was prepared by simple solvent casting m...Objective:To evaluate the formulation of multi-compartmental transdermal patches for simultaneous delivery of multiple drugs:aceclofenac and serratiopeptidase.Methods:The patch was prepared by simple solvent casting method using hydroxy propyl methyl celluloseK100Mas matrix forming agent and dimethyl sulphoxide as permeation enhancer.The prepared transdermal patch was evaluated by physiochemical parameters andin-vitro diffusion studies.Results:The multi-compartmental transdermal patch showed sustained drug release over the period of 12 h.Conclusions:Multicompartmental transdermal patches shows better bioavailability,therapeutic efficacy and very economic as compared with other dosage forms.展开更多
Deep reinforcement learning(DRL)achieves success through the representational capabilities of deep neural networks(DNNs).Compared to DNNs,spiking neural networks(SNNs),known for their binary spike information processi...Deep reinforcement learning(DRL)achieves success through the representational capabilities of deep neural networks(DNNs).Compared to DNNs,spiking neural networks(SNNs),known for their binary spike information processing,exhibit more biological characteristics.However,the challenge of using SNNs to simulate more biologically characteristic neuronal dynamics to optimize decision-making tasks remains,directly related to the information integration and transmission in SNNs.Inspired by the advanced computational power of dendrites in biological neurons,we propose a multi-dendrite spiking neuron(MDSN)model based on Multi-compartment spiking neurons(MCN),expanding dendrite types from two to multiple and deriving the analytical solution of somatic membrane potential.We apply the MDSN to deep distributional reinforcement learning to enhance its performance in executing complex decisionmaking tasks.The proposed model can effectively and adaptively integrate and transmit meaningful information from different sources.Our model uses a bioinspired event-enhanced dendrite structure to emphasize features.Meanwhile,by utilizing dynamic membrane potential thresholds,it adaptively maintains the homeostasis of MDSN.Extensive experiments on Atari games show that the proposed model outperforms some state-of-the-art spiking distributional RL models by a significant margin.展开更多
A novel fluorinated triblock copolymer incorporating 2-ethylhexyl methacrylate （EHMA）, tert-butyl methacrylate （tBMA） and 1H,1H,2H,2H-perfluorodecyl acrylate （FA） （PEHMA-b-PtBMA-b-PFA） was first synthesized us...A novel fluorinated triblock copolymer incorporating 2-ethylhexyl methacrylate （EHMA）, tert-butyl methacrylate （tBMA） and 1H,1H,2H,2H-perfluorodecyl acrylate （FA） （PEHMA-b-PtBMA-b-PFA） was first synthesized using three successive reversible addition fragmentation chain transfer （RAFT） polymerization and the subsequent hydrolyzing at acidic condition. The as-fabricated triblock copolymer exhibited an interesting morphology evolution from the multi-compartment rod-like structure to spherical structure along with the addition of a selective solution. At the same time, a visible phase separation domain could be seen in the core area due to the existence of fluorocarbon segments. Furthermore, the self- assembly behavior of the triphilic copolymer at different pH was also verified by transmission electron microscopy, as well as the dynamic light scattering. These stimuli-responsive multi-compartment nanostructures may have potential applications in drug delivery.展开更多
Rapid plant immune responses in the appropriate cells are needed for effective defense against pathogens.Although transcriptome analysis is often used to describe overall immune responses,collection of transcriptome d...Rapid plant immune responses in the appropriate cells are needed for effective defense against pathogens.Although transcriptome analysis is often used to describe overall immune responses,collection of transcriptome data with sufficient resolution in both space and time is challenging.We reanalyzed public Arabidopsis time-course transcriptome data obtained after low-dose inoculation with a Pseudomonas syringae strain expressing the effector AvrRpt2,which induces effector-triggered immunity in Arabidopsis.Double-peak time-course patterns are prevalent among thousands of upregulated genes.We implemented a multicompartment modeling approach to decompose the double-peak pattern into two single-peak patterns for each gene.The decomposed peaks reveal an“echoing”pattern:the peak times of the first and second peaks correlate well across most upregulated genes.We demonstrated that the two peaks likely represent responses of two distinct cell populations that respond either cell autonomously or indirectly to AvrRpt2.Thus,the peak decomposition has extracted spatial information from the time-course data.The echoing pattern also indicates a conserved transcriptome response with different initiation times between the two cell populations despite different elicitor types.A gene set highly overlapping with the conserved gene set is also upregulated with similar kinetics during pattern-triggered immunity.Activation of a WRKY network via different entry-point WRKYs can explain the similar but not identical transcriptome responses elicited by different elicitor types.We discuss potential benefits of the properties of the WRKY activation network as an immune signaling network in light of pressure from rapidly evolving pathogens.展开更多
Organ-on-a-chip(OOC)is now becoming a potential alternative to the classical preclinical animal models,which reconstitutes in vitro the basic function of specifc human tissues/organs and dynamically simulates physiolo...Organ-on-a-chip(OOC)is now becoming a potential alternative to the classical preclinical animal models,which reconstitutes in vitro the basic function of specifc human tissues/organs and dynamically simulates physiological or pathological activities in tissue and organ level.Despite of the much progress achieved so far,there is still an urgent need to explore new biomaterials to construct a reliable and efcient tissue-tissue interface and a general fabrication strategy to expand from single-organ OOC to multi-organ OOC in an easy manner.In this paper,we propose a novel strategy to prepare doublecompartment organ-on-a-chip(DC-OOC)using electrospun poly(l-lactic acid)/collagen I(PLLA/Col I)nanofber membrane as tissue-tissue interface.The unique features of PLLA/Col I nanofber membrane like excellent biocompatibility,strong afnity to multiple cells,adjustable orientation,controllable thickness and porosity endow the tissue-tissue interface with excellent semi-permeability,appropriate mechanical support,inducible cell orientation,good cell adhesion and proliferation.The integration of 3D printing technology during the fabrication process enables precise size control of the tissue-tissue interface and stable bonding with microfuidic channels.More importantly,our fabrication strategy and OOC confguration makes it easy to extend from DC-OOC to multi-compartment organ-on-a-chip(MC-OOC).To show its possible application,in vitro jaundice disease model is established by constructing blood vessel/skin/liver/lung organ-on-a-chip via MC-OOC.The downward trends of the cell viability after perfusion of bilirubin,the variation in cell sensitivity to bilirubin for diferent type of cells and recovery of cell viability after blue light therapy prove the feasibility of this jaundice disease model.We believe this general strategy of constructing tissue-tissue interface and multi-organ OOC can be used for many other in vitro physiological and pathological models.展开更多
文摘By analyzing the observed phenomena and the data collected in the study, a multi-compartment linear circulation model for targeting drug delivery system was developed and the function formulas of the drug concentration-time in blood and target organ by computing were figured out. The drug concentration-time curve for target organ can be plotted with reference to the data of drug concentration in blood according to the model. The pharmacokinetic parameters of the drug in target organ could also be obtained. The practicability of the model was further checked by the curves of drug concentration-time in blood and target organ(liver) of liver-targeting nanoparticles in animal tests. Based on the liver drug concentration-time curves calculated by the function formula of the drug in target organ, the pharmacokinetic behavior of the drug in target organ(liver) was analyzed by statistical moment, and its pharmacokinetic parameters in liver were obtained. It is suggested that the (relative targeting index( can be used for quantitative evaluation of the targeting drug delivery systems.
基金supported by the National Natural Science Foundation of China(71571076)the National Key R&D Program for the 13th-Five-Year-Plan of China(2018YFF0300301).
文摘The multi-compartment electric vehicle routing problem(EVRP)with soft time window and multiple charging types(MCEVRP-STW&MCT)is studied,in which electric multi-compartment vehicles that are environmentally friendly but need to be recharged in course of transport process,are employed.A mathematical model for this optimization problem is established with the objective of minimizing the function composed of vehicle cost,distribution cost,time window penalty cost and charging service cost.To solve the problem,an estimation of the distribution algorithm based on Lévy flight(EDA-LF)is proposed to perform a local search at each iteration to prevent the algorithm from falling into local optimum.Experimental results demonstrate that the EDA-LF algorithm can find better solutions and has stronger robustness than the basic EDA algorithm.In addition,when comparing with existing algorithms,the result shows that the EDA-LF can often get better solutions in a relatively short time when solving medium and large-scale instances.Further experiments show that using electric multi-compartment vehicles to deliver incompatible products can produce better results than using traditional fuel vehicles.
文摘Objective:To evaluate the formulation of multi-compartmental transdermal patches for simultaneous delivery of multiple drugs:aceclofenac and serratiopeptidase.Methods:The patch was prepared by simple solvent casting method using hydroxy propyl methyl celluloseK100Mas matrix forming agent and dimethyl sulphoxide as permeation enhancer.The prepared transdermal patch was evaluated by physiochemical parameters andin-vitro diffusion studies.Results:The multi-compartmental transdermal patch showed sustained drug release over the period of 12 h.Conclusions:Multicompartmental transdermal patches shows better bioavailability,therapeutic efficacy and very economic as compared with other dosage forms.
基金supported by the National Natural Science Foundation of China(62236002,62303009,62206001,52305001,62102387,62206005)the University Synergy Innovation Program of Anhui Province(GXXT-2022-041)the China Postdoctoral Science Foundation(2023M740013)
文摘Deep reinforcement learning(DRL)achieves success through the representational capabilities of deep neural networks(DNNs).Compared to DNNs,spiking neural networks(SNNs),known for their binary spike information processing,exhibit more biological characteristics.However,the challenge of using SNNs to simulate more biologically characteristic neuronal dynamics to optimize decision-making tasks remains,directly related to the information integration and transmission in SNNs.Inspired by the advanced computational power of dendrites in biological neurons,we propose a multi-dendrite spiking neuron(MDSN)model based on Multi-compartment spiking neurons(MCN),expanding dendrite types from two to multiple and deriving the analytical solution of somatic membrane potential.We apply the MDSN to deep distributional reinforcement learning to enhance its performance in executing complex decisionmaking tasks.The proposed model can effectively and adaptively integrate and transmit meaningful information from different sources.Our model uses a bioinspired event-enhanced dendrite structure to emphasize features.Meanwhile,by utilizing dynamic membrane potential thresholds,it adaptively maintains the homeostasis of MDSN.Extensive experiments on Atari games show that the proposed model outperforms some state-of-the-art spiking distributional RL models by a significant margin.
基金financially supported by the National Natural Science Foundation of China(Nos.51622301 and 51573046)Fundamental Research Funds for the Central Universities(Nos.B14018,WD1616010 and 222201717001)
文摘A novel fluorinated triblock copolymer incorporating 2-ethylhexyl methacrylate （EHMA）, tert-butyl methacrylate （tBMA） and 1H,1H,2H,2H-perfluorodecyl acrylate （FA） （PEHMA-b-PtBMA-b-PFA） was first synthesized using three successive reversible addition fragmentation chain transfer （RAFT） polymerization and the subsequent hydrolyzing at acidic condition. The as-fabricated triblock copolymer exhibited an interesting morphology evolution from the multi-compartment rod-like structure to spherical structure along with the addition of a selective solution. At the same time, a visible phase separation domain could be seen in the core area due to the existence of fluorocarbon segments. Furthermore, the self- assembly behavior of the triphilic copolymer at different pH was also verified by transmission electron microscopy, as well as the dynamic light scattering. These stimuli-responsive multi-compartment nanostructures may have potential applications in drug delivery.
基金supported by grants from the National Science Foundation(grant nos.MCB-0918908 and MCB-1518058 to F.K.and C.L.M.and IOS1645460 to F.K.)a grant from the United States Department of Agriculture-National Institute of Food and Agriculture to F.K.(grant no.2020-67013-31187)a grant from Ajinomoto Co.,Inc.to F.K.We thank the Minnesota Supercomputing Institute for their computing resources.We thank Tatsuya Nobori for information on the gene symbols in his snRNA-seq data.
文摘Rapid plant immune responses in the appropriate cells are needed for effective defense against pathogens.Although transcriptome analysis is often used to describe overall immune responses,collection of transcriptome data with sufficient resolution in both space and time is challenging.We reanalyzed public Arabidopsis time-course transcriptome data obtained after low-dose inoculation with a Pseudomonas syringae strain expressing the effector AvrRpt2,which induces effector-triggered immunity in Arabidopsis.Double-peak time-course patterns are prevalent among thousands of upregulated genes.We implemented a multicompartment modeling approach to decompose the double-peak pattern into two single-peak patterns for each gene.The decomposed peaks reveal an“echoing”pattern:the peak times of the first and second peaks correlate well across most upregulated genes.We demonstrated that the two peaks likely represent responses of two distinct cell populations that respond either cell autonomously or indirectly to AvrRpt2.Thus,the peak decomposition has extracted spatial information from the time-course data.The echoing pattern also indicates a conserved transcriptome response with different initiation times between the two cell populations despite different elicitor types.A gene set highly overlapping with the conserved gene set is also upregulated with similar kinetics during pattern-triggered immunity.Activation of a WRKY network via different entry-point WRKYs can explain the similar but not identical transcriptome responses elicited by different elicitor types.We discuss potential benefits of the properties of the WRKY activation network as an immune signaling network in light of pressure from rapidly evolving pathogens.
基金Human foreskin fbroblasts(HFFs)were gifted from Prof.Xiaoling Fu’s group(School of Biomedical Science and Engineering,South China University of Technology).Human Liver Cells(LO2)were donated by Prof.Yuyou Duan’s group(School of Medicine,South China University of Technology).Lung cancer cells(PC-9)were obtained from Guangdong Provincial People’s Hospital.This research was fnancially sponsored by the National Natural Science Foundation of China(Grant No.51873071,32071321,51873069)the National Key R&D Program of China(2018YFC1106300).
文摘Organ-on-a-chip(OOC)is now becoming a potential alternative to the classical preclinical animal models,which reconstitutes in vitro the basic function of specifc human tissues/organs and dynamically simulates physiological or pathological activities in tissue and organ level.Despite of the much progress achieved so far,there is still an urgent need to explore new biomaterials to construct a reliable and efcient tissue-tissue interface and a general fabrication strategy to expand from single-organ OOC to multi-organ OOC in an easy manner.In this paper,we propose a novel strategy to prepare doublecompartment organ-on-a-chip(DC-OOC)using electrospun poly(l-lactic acid)/collagen I(PLLA/Col I)nanofber membrane as tissue-tissue interface.The unique features of PLLA/Col I nanofber membrane like excellent biocompatibility,strong afnity to multiple cells,adjustable orientation,controllable thickness and porosity endow the tissue-tissue interface with excellent semi-permeability,appropriate mechanical support,inducible cell orientation,good cell adhesion and proliferation.The integration of 3D printing technology during the fabrication process enables precise size control of the tissue-tissue interface and stable bonding with microfuidic channels.More importantly,our fabrication strategy and OOC confguration makes it easy to extend from DC-OOC to multi-compartment organ-on-a-chip(MC-OOC).To show its possible application,in vitro jaundice disease model is established by constructing blood vessel/skin/liver/lung organ-on-a-chip via MC-OOC.The downward trends of the cell viability after perfusion of bilirubin,the variation in cell sensitivity to bilirubin for diferent type of cells and recovery of cell viability after blue light therapy prove the feasibility of this jaundice disease model.We believe this general strategy of constructing tissue-tissue interface and multi-organ OOC can be used for many other in vitro physiological and pathological models.
