A security issue with multi-sensor unmanned aerial vehicle(UAV)cyber physical systems(CPS)from the viewpoint of a false data injection(FDI)attacker is investigated in this paper.The FDI attacker can employ attacks on ...A security issue with multi-sensor unmanned aerial vehicle(UAV)cyber physical systems(CPS)from the viewpoint of a false data injection(FDI)attacker is investigated in this paper.The FDI attacker can employ attacks on feedback and feed-forward channels simultaneously with limited resource.The attacker aims at degrading the UAV CPS's estimation performance to the max while keeping stealthiness characterized by the Kullback-Leibler(K-L)divergence.The attacker is resource limited which can only attack part of sensors,and the attacked sensor as well as specific forms of attack signals at each instant should be considered by the attacker.Also,the sensor selection principle is investigated with respect to time invariant attack covariances.Additionally,the optimal switching attack strategies in regard to time variant attack covariances are modeled as a multi-agent Markov decision process(MDP)with hybrid discrete-continuous action space.Then,the multi-agent MDP is solved by utilizing the deep Multi-agent parameterized Q-networks(MAPQN)method.Ultimately,a quadrotor near hover system is used to validate the effectiveness of the results in the simulation section.展开更多
Spastic cerebral palsy is generally considered to result from cerebral cortical or pyramidal tract damage. Here, we precisely targeted the left pyramidal tract of 2-month-old Sprague-Dawley rats placed on a stereotaxi...Spastic cerebral palsy is generally considered to result from cerebral cortical or pyramidal tract damage. Here, we precisely targeted the left pyramidal tract of 2-month-old Sprague-Dawley rats placed on a stereotaxic instrument under intraperitoneal anesthesia. Based on the rat brain stereotaxic map, a 1-mm hole was made 10 mm posterior to bregma and 0.8 mm left of sagittal suture. A microsyringe was inserted perpendicularly to the surface of the brain to a depth of 9.7 mm, and 15 wL of ethanol was slowly injected to establish a rat model of spastic cerebral palsy. After modeling, the rats appeared to have necrotic voids in the pyramidal tract and exhibited typical signs and symptoms of flexion spasms that lasted for a long period of time. These findings indicate that this is an effective and easy method of establishing a rat model of spastic cerebral palsy with good reproducibility. Ethanol as a chemical ablation agent specifically and thoroughly damages the py- ramidal tract, and therefore, the animals display flexion spasms, which are a typical symptom of the disease.展开更多
The study was conducted to evaluate the safety of Flunixin meglumine injection on target animal dogs, and to provide a scientific basis for the dose selec- tion of clinical application. A total of 24 healthy Springer ...The study was conducted to evaluate the safety of Flunixin meglumine injection on target animal dogs, and to provide a scientific basis for the dose selec- tion of clinical application. A total of 24 healthy Springer Spaniels were randomly divided into four groups. Intramuscular injection of Flunixin meglumine was carried out to test group dogs with the doses of 2 rag/kg, 6 rag/kg, 10 mg/kg for 5 days, respectively. The injected doses were one times, three times and five times as the recommended clinical dose. Intramuscular injection of water was carried out to control group dogs for 5 days. Clinical symptom was observed after the injection, and the blood was collected at different times （before, during and after the injection） to conduct blood routine examination and blood biochemical indexes measurement. Post-mortem examination and histopathological examination were carried out after the test. The results indicated that test dogs showed normal spirit, with no death and no other adverse reactions. Part values of blood routine examination indexes and blood biochemical indexes in test groups showed significant differences between pre-administration and post-administration, but basically fluctuated within the reference range. Autopsy results showed no obvious pathological changes. Histological examination showed the viscera and tissues （liver, heart, spleen, lung, kidney） in high dose group and control group showed no abnormality and pathological changes. The results indicated that Flunixin meglumine injection with the dose of 2 - 10 rag/kg had a minimal effect on physiological and biochemical indexes of dog blood.展开更多
Background:To predict the effective targets of Kang’ai injection and analyze the pharmacological mechanism for the treatment of breast cancer based on the method of network pharmacology.Methods:The Traditional Chines...Background:To predict the effective targets of Kang’ai injection and analyze the pharmacological mechanism for the treatment of breast cancer based on the method of network pharmacology.Methods:The Traditional Chinese Medicine Systems Pharmacology database was used to predict the effective components of the Chinese patent medicine Kang’ai injection,and GeneCards database,Online Mendelian Inheritance in Man database and the Therapeutic Target Database were used to predict the therapeutic targets of breast cancer.Cytoscape 3.7.2 was used to construct active ingredient-disease-target network.String database and Cytoscape 3.7.2 software were used to draw the protein-protein interaction network and obtain the core target.Bioconductor and R language were used to analyze the effective action target for gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis.Results:There were 42 effective active ingredients in the Chinese patent medicine Kang’ai injection,which acted on 105 targets,and it had 32 components that acted on 96 targets associated with breast cancer.The target regulates various biological processes such as inflammation,angiogenesis,apoptosis and cell proliferation,and regulates pathways such as PI3K-Akt signaling pathway,MAPK signaling pathway,AGE-RAGE signaling pathway in diabetic complications and thyroid hormone signaling pathway through gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis.Conclusion:The treatment of breast cancer with the Chinese patent medicine Kang’ai injection is a complex mechanism process with multiple targets,multiple pathways,and multiple choices,which provides a theoretical basis for the further extraction of effective components in the treatment of breast cancer.展开更多
Aiming at the effective realization of particle filter for maneuvering target tracking in multi-sensor measurements,a novel multi-sensor multiple model particle filtering algorithm with correlated noises is proposed.C...Aiming at the effective realization of particle filter for maneuvering target tracking in multi-sensor measurements,a novel multi-sensor multiple model particle filtering algorithm with correlated noises is proposed.Combined with the kinetic evolution equation of target state,a multi-sensor multiple model particle filter is firstly constructed,which is also used as the basic framework of a new algorithm.In the new algorithm,in order to weaken the adverse influence from random measurement noises in the measuring process of particle weight,a weight optimization strategy is introduced to improve the reliability and stability of particle weight.In addition,considering the correlated noise existing in the practical engineering,a decoupling method of correlated noise is given by the rearrangement and transformation of the state transition equation and measurement equation.Since the weight optimization strategy and noise decoupling method adopt respectively the center fusion structure and the off-line way,it improves the adverse effect effectively on computational complexity for increasing state dimension and sensor number.Finally,the theoretical analysis and experimental results show the feasibility and efficiency of the proposed algorithm.展开更多
As a computer-assisted approach, molecular docking has been universally applied in drug research and development and plays an important role in the investigation and evaluation of herbal medicines. Herein, the method ...As a computer-assisted approach, molecular docking has been universally applied in drug research and development and plays an important role in the investigation and evaluation of herbal medicines. Herein, the method was used to estimate the pharmacodynamics of Mai-Luo-Ning injection, a traditional Chinese compound herbal prescription. Through investigating the interactions between several important proteins in cardiovascular system and characteristic components of the formula, its effect on cardiovascular protection was evaluated. Results showed the differences in the interactions between each component and the selected target proteins and revealed the possible mechanisms for synergistic effects of various characteristic components on cardiovascular protection. The study provided scientific evidence supporting the mechanistic study of the interactions among multi-components and targets, offering a general approach to investigating the pharmacodynamics of complicated materials in compound herbal prescriptions.展开更多
In recent years, macromolecules such as antibodies, peptides,and nucleic acids have captured a significant share of the pharmaceutical market. Compared to small-molecule drugs, macromolecules exhibit superior target s...In recent years, macromolecules such as antibodies, peptides,and nucleic acids have captured a significant share of the pharmaceutical market. Compared to small-molecule drugs, macromolecules exhibit superior target specificity due to their structural complexity and precise biological mechanisms, including antigen-antibody recognition, ligand-receptor interactions,and complementary base pairing [1,2]. These properties enhance their safety profile and reduce toxicity. However, the oral absorption of macromolecules is particularly challenging due to their large molecular weight and complex spatial conformation [3].展开更多
Previously, we developed a novel siRNA transfer method to the liver by sequential intravenous injection of poly-L-glutamic acid (PGA) and cationic liposome/siRNA complex (cationic lipoplex). In this study, we examined...Previously, we developed a novel siRNA transfer method to the liver by sequential intravenous injection of poly-L-glutamic acid (PGA) and cationic liposome/siRNA complex (cationic lipoplex). In this study, we examined the effects of the charge ratio (+/-) of cationic liposome/siRNA, molecular weight of PGA and cationic lipid of cationic liposome on the biodistribution of siRNA after sequential injection of PGA plus cationic lipoplex. When 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)/cholesterol (Chol) lipoplex was intravenously injected into mice, the accumulation of siRNA was mainly observed in the lungs. In contrast, when DOTAP/Chol lipoplex was intravenously injected at 1 min after intravenous injection of PGA, siRNA was largely accumulated in the liver. The charge ratio (+/-) of DOTAP/Chol liposome/siRNA did not affect the biodistribution of siRNA after sequential injection. As regards the molecular weight of PGA, the accumulation of siRNA was observed mainly in the liver after the sequential injection of PGA of 20.5, 38, 64 or 200 kDa plus DOTAP/Chol lipoplex. Furthermore, to examine the effect of cationic lipid of cationic liposome on the biodistribution of siRNA, we prepared other cationic liposomes composed of 1,2-di-O-octadecenyl-3-trimethylammonium propane chloride (DOTMA)/Chol, dimethyldioctade-cylammonium bromide (DDAB)/Chol and O,O’-ditetradecanoyl-N-(α-trimethylammonioacetyl)di-ethanolamine chloride (DC-6-14)/Chol. For the cationic liposomes, the accumulation of siRNA was observed mainly in the liver when their cationic lipoplexes were sequentially injected after injection of PGA into mice. From these findings, sequential injection of PGA plus cationic lipoplex could deliver siRNA efficiently into the liver regardless of the charge ratio (+/-) of lipoplex, lengths of PGA and cationic lipid of liposome.展开更多
AIM To compare the effects of intravenous routeand peritoneal route on liver targeted uptake andexpression of plasmid delivered by galactose-terminal glyco-poly-L-lysine(G-PLL).METHODS The plasmid pTM/MMP-1 which coul...AIM To compare the effects of intravenous routeand peritoneal route on liver targeted uptake andexpression of plasmid delivered by galactose-terminal glyco-poly-L-lysine(G-PLL).METHODS The plasmid pTM/MMP-1 which couldbe expressed in eukaryotic cells was bound to G-PLL,and was then transferred into Wistar rats byintravenous and intraperitoneal injection.Theexpression and distribution of the plasmid wereobserved at different time periods by in situhybridization and immunohistochemistry.RESULTS The plasmid could be expressedsignificantly within 24 h after being transferred invivo by both intravenous and intraperitonealroutes.One week later the expression began todecrease,and could still be observed three weekslater.Although both the intravenous andintraperitoneal route could target-specificallydeliver the plasmid to the liver,the effect of theformer was better as compared to that of the latter.CONCLUSION Intravenous route is better for livertargeted uptake and expression of G-PLL-boundplasmids than the peritoneal route.展开更多
文摘A security issue with multi-sensor unmanned aerial vehicle(UAV)cyber physical systems(CPS)from the viewpoint of a false data injection(FDI)attacker is investigated in this paper.The FDI attacker can employ attacks on feedback and feed-forward channels simultaneously with limited resource.The attacker aims at degrading the UAV CPS's estimation performance to the max while keeping stealthiness characterized by the Kullback-Leibler(K-L)divergence.The attacker is resource limited which can only attack part of sensors,and the attacked sensor as well as specific forms of attack signals at each instant should be considered by the attacker.Also,the sensor selection principle is investigated with respect to time invariant attack covariances.Additionally,the optimal switching attack strategies in regard to time variant attack covariances are modeled as a multi-agent Markov decision process(MDP)with hybrid discrete-continuous action space.Then,the multi-agent MDP is solved by utilizing the deep Multi-agent parameterized Q-networks(MAPQN)method.Ultimately,a quadrotor near hover system is used to validate the effectiveness of the results in the simulation section.
文摘Spastic cerebral palsy is generally considered to result from cerebral cortical or pyramidal tract damage. Here, we precisely targeted the left pyramidal tract of 2-month-old Sprague-Dawley rats placed on a stereotaxic instrument under intraperitoneal anesthesia. Based on the rat brain stereotaxic map, a 1-mm hole was made 10 mm posterior to bregma and 0.8 mm left of sagittal suture. A microsyringe was inserted perpendicularly to the surface of the brain to a depth of 9.7 mm, and 15 wL of ethanol was slowly injected to establish a rat model of spastic cerebral palsy. After modeling, the rats appeared to have necrotic voids in the pyramidal tract and exhibited typical signs and symptoms of flexion spasms that lasted for a long period of time. These findings indicate that this is an effective and easy method of establishing a rat model of spastic cerebral palsy with good reproducibility. Ethanol as a chemical ablation agent specifically and thoroughly damages the py- ramidal tract, and therefore, the animals display flexion spasms, which are a typical symptom of the disease.
文摘The study was conducted to evaluate the safety of Flunixin meglumine injection on target animal dogs, and to provide a scientific basis for the dose selec- tion of clinical application. A total of 24 healthy Springer Spaniels were randomly divided into four groups. Intramuscular injection of Flunixin meglumine was carried out to test group dogs with the doses of 2 rag/kg, 6 rag/kg, 10 mg/kg for 5 days, respectively. The injected doses were one times, three times and five times as the recommended clinical dose. Intramuscular injection of water was carried out to control group dogs for 5 days. Clinical symptom was observed after the injection, and the blood was collected at different times （before, during and after the injection） to conduct blood routine examination and blood biochemical indexes measurement. Post-mortem examination and histopathological examination were carried out after the test. The results indicated that test dogs showed normal spirit, with no death and no other adverse reactions. Part values of blood routine examination indexes and blood biochemical indexes in test groups showed significant differences between pre-administration and post-administration, but basically fluctuated within the reference range. Autopsy results showed no obvious pathological changes. Histological examination showed the viscera and tissues （liver, heart, spleen, lung, kidney） in high dose group and control group showed no abnormality and pathological changes. The results indicated that Flunixin meglumine injection with the dose of 2 - 10 rag/kg had a minimal effect on physiological and biochemical indexes of dog blood.
基金This research was funded by Science and Technology Program of Guangzhou(Nos.201803010051).
文摘Background:To predict the effective targets of Kang’ai injection and analyze the pharmacological mechanism for the treatment of breast cancer based on the method of network pharmacology.Methods:The Traditional Chinese Medicine Systems Pharmacology database was used to predict the effective components of the Chinese patent medicine Kang’ai injection,and GeneCards database,Online Mendelian Inheritance in Man database and the Therapeutic Target Database were used to predict the therapeutic targets of breast cancer.Cytoscape 3.7.2 was used to construct active ingredient-disease-target network.String database and Cytoscape 3.7.2 software were used to draw the protein-protein interaction network and obtain the core target.Bioconductor and R language were used to analyze the effective action target for gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis.Results:There were 42 effective active ingredients in the Chinese patent medicine Kang’ai injection,which acted on 105 targets,and it had 32 components that acted on 96 targets associated with breast cancer.The target regulates various biological processes such as inflammation,angiogenesis,apoptosis and cell proliferation,and regulates pathways such as PI3K-Akt signaling pathway,MAPK signaling pathway,AGE-RAGE signaling pathway in diabetic complications and thyroid hormone signaling pathway through gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis.Conclusion:The treatment of breast cancer with the Chinese patent medicine Kang’ai injection is a complex mechanism process with multiple targets,multiple pathways,and multiple choices,which provides a theoretical basis for the further extraction of effective components in the treatment of breast cancer.
基金Supported by the National Natural Science Foundation of China(No.61300214)the National Natural Science Foundation of Henan Province(No.132300410148)+1 种基金the Post-doctoral Science Foundation of China(No.2014M551999)the Funding Scheme of Young Key Teacher ofHenan Province Universities(No.2013GGJS-026)
文摘Aiming at the effective realization of particle filter for maneuvering target tracking in multi-sensor measurements,a novel multi-sensor multiple model particle filtering algorithm with correlated noises is proposed.Combined with the kinetic evolution equation of target state,a multi-sensor multiple model particle filter is firstly constructed,which is also used as the basic framework of a new algorithm.In the new algorithm,in order to weaken the adverse influence from random measurement noises in the measuring process of particle weight,a weight optimization strategy is introduced to improve the reliability and stability of particle weight.In addition,considering the correlated noise existing in the practical engineering,a decoupling method of correlated noise is given by the rearrangement and transformation of the state transition equation and measurement equation.Since the weight optimization strategy and noise decoupling method adopt respectively the center fusion structure and the off-line way,it improves the adverse effect effectively on computational complexity for increasing state dimension and sensor number.Finally,the theoretical analysis and experimental results show the feasibility and efficiency of the proposed algorithm.
基金financially supported by Natural Science Foundation of Jiangsu province(Nos.BK2011065 and BK2012026)Jiangsu Province Key Lab of Drug Metabolism and Pharmacokinetics(No.BM2012012)+3 种基金National Basic Research Program of China("973 Program"No.2011 CB505300-03)Foundation for the Author of National Excellent Doctoral Dissertation of China(No.200979)the Program for New Century Excellent Talents in University(No.NCET-09-0770)
文摘As a computer-assisted approach, molecular docking has been universally applied in drug research and development and plays an important role in the investigation and evaluation of herbal medicines. Herein, the method was used to estimate the pharmacodynamics of Mai-Luo-Ning injection, a traditional Chinese compound herbal prescription. Through investigating the interactions between several important proteins in cardiovascular system and characteristic components of the formula, its effect on cardiovascular protection was evaluated. Results showed the differences in the interactions between each component and the selected target proteins and revealed the possible mechanisms for synergistic effects of various characteristic components on cardiovascular protection. The study provided scientific evidence supporting the mechanistic study of the interactions among multi-components and targets, offering a general approach to investigating the pharmacodynamics of complicated materials in compound herbal prescriptions.
基金supported by the National Key Research and Development Program of China (2020YFA0908200)the National Natural Science Foundation of China (32271383)。
文摘In recent years, macromolecules such as antibodies, peptides,and nucleic acids have captured a significant share of the pharmaceutical market. Compared to small-molecule drugs, macromolecules exhibit superior target specificity due to their structural complexity and precise biological mechanisms, including antigen-antibody recognition, ligand-receptor interactions,and complementary base pairing [1,2]. These properties enhance their safety profile and reduce toxicity. However, the oral absorption of macromolecules is particularly challenging due to their large molecular weight and complex spatial conformation [3].
文摘Previously, we developed a novel siRNA transfer method to the liver by sequential intravenous injection of poly-L-glutamic acid (PGA) and cationic liposome/siRNA complex (cationic lipoplex). In this study, we examined the effects of the charge ratio (+/-) of cationic liposome/siRNA, molecular weight of PGA and cationic lipid of cationic liposome on the biodistribution of siRNA after sequential injection of PGA plus cationic lipoplex. When 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)/cholesterol (Chol) lipoplex was intravenously injected into mice, the accumulation of siRNA was mainly observed in the lungs. In contrast, when DOTAP/Chol lipoplex was intravenously injected at 1 min after intravenous injection of PGA, siRNA was largely accumulated in the liver. The charge ratio (+/-) of DOTAP/Chol liposome/siRNA did not affect the biodistribution of siRNA after sequential injection. As regards the molecular weight of PGA, the accumulation of siRNA was observed mainly in the liver after the sequential injection of PGA of 20.5, 38, 64 or 200 kDa plus DOTAP/Chol lipoplex. Furthermore, to examine the effect of cationic lipid of cationic liposome on the biodistribution of siRNA, we prepared other cationic liposomes composed of 1,2-di-O-octadecenyl-3-trimethylammonium propane chloride (DOTMA)/Chol, dimethyldioctade-cylammonium bromide (DDAB)/Chol and O,O’-ditetradecanoyl-N-(α-trimethylammonioacetyl)di-ethanolamine chloride (DC-6-14)/Chol. For the cationic liposomes, the accumulation of siRNA was observed mainly in the liver when their cationic lipoplexes were sequentially injected after injection of PGA into mice. From these findings, sequential injection of PGA plus cationic lipoplex could deliver siRNA efficiently into the liver regardless of the charge ratio (+/-) of lipoplex, lengths of PGA and cationic lipid of liposome.
基金National Natural Science Foundation of China(№39570336).
文摘AIM To compare the effects of intravenous routeand peritoneal route on liver targeted uptake andexpression of plasmid delivered by galactose-terminal glyco-poly-L-lysine(G-PLL).METHODS The plasmid pTM/MMP-1 which couldbe expressed in eukaryotic cells was bound to G-PLL,and was then transferred into Wistar rats byintravenous and intraperitoneal injection.Theexpression and distribution of the plasmid wereobserved at different time periods by in situhybridization and immunohistochemistry.RESULTS The plasmid could be expressedsignificantly within 24 h after being transferred invivo by both intravenous and intraperitonealroutes.One week later the expression began todecrease,and could still be observed three weekslater.Although both the intravenous andintraperitoneal route could target-specificallydeliver the plasmid to the liver,the effect of theformer was better as compared to that of the latter.CONCLUSION Intravenous route is better for livertargeted uptake and expression of G-PLL-boundplasmids than the peritoneal route.
