Over one-third of 700,000 military personnel who served in the first Gulf War(GW)suffer from an assortment of symptoms,including cognitive and memory problems,musculoskeletal pain,gastrointestinal discomfort,fatigue,a...Over one-third of 700,000 military personnel who served in the first Gulf War(GW)suffer from an assortment of symptoms,including cognitive and memory problems,musculoskeletal pain,gastrointestinal discomfort,fatigue,and respiratory issues[1,2].The precise etiology of Gulf War illness(GWI)is unclear.However,epidemiological and preclinical studies imply that exposures to the prophylactic drug pyridostigmine bromide,insecticides,pesticides,smoke from oil well fires,and interaction between these exposures and war-related stress underlie this illness[2].As per the Kansas case definition,GWI is a chronic multi-symptom illness displaying one moderately severe and/or multiple symptoms of any severity in at least 3 of 6 symptom domains(fatigue,pain,neurological/cognitive/mood,skin,gastrointestinal,respiratory)[1,2].While the exact pathophysiological changes underlying GWI have not been identified,alterations in immune regulation and dysregulation of the redox balance have been observed in GWI,resulting in chronic systemic inflammation and neuroinflammation[2].展开更多
Photothermal and photodynamic therapies(PTT/PDT)hold promise for localized tumor treatment,yet their full potential is hampered by limitations such as the hypoxic tumor microenvironment and inadequate systemic immune ...Photothermal and photodynamic therapies(PTT/PDT)hold promise for localized tumor treatment,yet their full potential is hampered by limitations such as the hypoxic tumor microenvironment and inadequate systemic immune activation.Addressing these challenges,we present a novel near-infrared(NIR)-triggered RNS nanoreactor(PBNO-Ce6)to amplify the photodynamic and photothermal therapy efficacy against triple-negative breast cancer(TNBC).The designed PBNOCe6 combines sodium nitroprusside-doped Prussian Blue nanoparticles with Chlorin e6 to enable on-site RNS production through NIR-induced concurrent NO release and ROS generation.This not only enhances tumor cell eradication but also potentiates local and systemic antitumor immune responses,protecting mice from tumor rechallenge.Our in vivo evaluations revealed that treatment with PBNO-Ce6 leads to a remarkable 2.7-fold increase in cytotoxic T lymphocytes and a 62%decrease in regulatory T cells in comparison to the control PB-Ce6(Prussian Blue nanoparticles loaded with Chlorin e6),marking a substantial improvement over traditional PTT/PDT.As such,the PBNO-Ce6 nanoreactor represents a transformative approach for improving outcomes in TNBC and potentially other malignancies affected by similar barriers.展开更多
With the rise of probiotics fermentation in food industry,fermented foods have attracted worldwide attention.In this study,protective effects of Rosa roxburghii&edible fungus fermentation broth(REFB)on immune func...With the rise of probiotics fermentation in food industry,fermented foods have attracted worldwide attention.In this study,protective effects of Rosa roxburghii&edible fungus fermentation broth(REFB)on immune function and gut health in Cyclophosphamide induced immunosuppressed mice were investigated.Results showed that REFB could improve the immune organ index,and promote the proliferation and differentiation of splenic T lymphocytes.In addition,it attenuated intestinal mucosal damage and improved intestinal cellular immunity.REFB administration also up-regulated the expression of IL-4,INF-γ,TNF-α,T-bet and GATA-3 mRNA in small intestine.Furthermore,administration of REFB modulated gut microbiota composition and increased the relative abundance of beneficial genus,such as Bacteroides.It also increased the production of fecal short-chain fatty acids.These indicate that REFB has the potential to improve immunity,alleviate intestinal injury and regulate gut microbiota in immunosuppressed mice.展开更多
Accumulating evidence indicates that antibiotic exposure may lead to impaired vaccine responses1-4;however,the mechanisms underlying this association remain poorly understood.Here we prospectively followed 191 healthy...Accumulating evidence indicates that antibiotic exposure may lead to impaired vaccine responses1-4;however,the mechanisms underlying this association remain poorly understood.Here we prospectively followed 191 healthy,vaginally born,term infants from birth to 15 months,using a systems vaccinology approach to assess the effects of antibiotic exposure on immune responses to vaccination.Exposure to direct neonatal but not intrapartum antibiotics was associated with significantly lower antibody titres against various polysaccharides in the 13-valent pneumococcal conjugate vaccine and the Haemophilus influenzae type b polyribosylribitol phosphate and diphtheria toxoid antigens in the combined 6-in-1 Infanrix Hexa vaccine at 7 months of age.Blood from infants exposed to neonatal antibiotics had an inflammatory transcriptional profile before vaccination;in addition,faecal metagenomics showed reduced abundance of Bifidobacterium species in these infants at the time of vaccination,which was correlated with reduced vaccine antibody titres 6 months later.In preclinical models,responses to the 13-valent pneumococcal conjugate vaccine were strongly dependent on an intact microbiota but could be restored in germ-free mice by administering a consortium of Bifidobacterium species or a probiotic already widely used in neonatal units.Our data suggest that microbiota-targeted interventions could mitigate the detrimental effects of early-life antibiotics on vaccine immunogenicity.展开更多
Objective Venous thromboembolism is a highly prevalent condition after polytrauma,and recognized as an important factor contributing to poor prognosis.The aim of this study was to investigate the risk factors for lowe...Objective Venous thromboembolism is a highly prevalent condition after polytrauma,and recognized as an important factor contributing to poor prognosis.The aim of this study was to investigate the risk factors for lower extremity deep venous thrombosis(LEDVT)in a severely traumatized population and to evaluate their predictive value for LEDVT.Methods This was a retrospective,single-center observational study.All subjects were severely traumatized patients who were admitted to the Traumatic Intensive Care Unit from January 2021 to May 2024.Based on Doppler ultrasound findings of both lower extremities from the time of injury to 30 days post-injury,patients who developed LEDVT were enrolled in the LEDVT group,and those who did not develop LEDVT were enrolled in the NLEDVT group.Demographic,clinical,and laboratory data were collected upon admission.Multivariable logistic regression analysis was performed to identify risk factors for LEDVT.Receiver operating characteristic(ROC)curve was used to evaluate the overall fit of the final model.Results There were 56 patients enrolled in the LEDVT group and 81 patients in the NLEDVT group.Age,Aggregate Index of Systemic Inflammation(AISI),Systemic Inflammation Response Index(SIRI),ICU length of stay,and albumin were identified as independent risk factors for LEDVT(all P<0.05).The area under their ROC curves were 0.604,0.657,0.694,0.668,and 0.405,respectively.Combined model for early clinical prediction of LEDVT in severely traumatized patients by age,SIRI,AISI,and albumin resulted in an area under the ROC curve of 0.805(95%CI:0.73-0.88,SE=0.037).Conclusion The combination of age,SIRI,AISI,and albumin has a predictive value for LEDVT in severely traumatized patients.展开更多
We investigate the stochastic responses of a tumor–immune system competition model with environmental noise and periodic treatment. Firstly, a mathematical model describing the interaction between tumor cells and imm...We investigate the stochastic responses of a tumor–immune system competition model with environmental noise and periodic treatment. Firstly, a mathematical model describing the interaction between tumor cells and immune system under external fluctuations and periodic treatment is established based on the stochastic differential equation. Then, sufficient conditions for extinction and persistence of the tumor cells are derived by constructing Lyapunov functions and Ito＇s formula. Finally, numerical simulations are introduced to illustrate and verify the results. The results of this work provide the theoretical basis for designing more effective and precise therapeutic strategies to eliminate cancer cells, especially for combining the immunotherapy and the traditional tools.展开更多
This article proposes a diffused hepatitis B virus （HBV） model with CTL immune response and nonlinear incidence for the control of viral infections. By means of different Lyapunov functions, the global asymptotical ...This article proposes a diffused hepatitis B virus （HBV） model with CTL immune response and nonlinear incidence for the control of viral infections. By means of different Lyapunov functions, the global asymptotical properties of the viral-free equilibrium and immune-free equilibrium of the model are obtained. Global stability of the positive equilibrium of the model is also considered. The results show that the free diffusion of the virus has no effect on the global stability of such HBV infection problem with Neumann homogeneous boundary conditions.展开更多
BACKGROUND： Sepsis and secondary multiple organ failure in critically ill patients are the major cause of death, but the pathogenesis of sepsis is not clear, especially the dysfunction of the immune system. In this p...BACKGROUND： Sepsis and secondary multiple organ failure in critically ill patients are the major cause of death, but the pathogenesis of sepsis is not clear, especially the dysfunction of the immune system. In this paper, we review the response and regulation of the immune system and the functions of a variety of inflammatory mediators in sepsis. DATA SOURCES Studies were identified by searching MEDLINE and PubMed for articles using the keywords ＂sepsis＂, ＂immune response＂, and ＂inflammatory mediator＂ up to October 2010. Additional papers were identified by a manual search of the references from the key articles.RESULTS： This systematic review was conducted of： 1） the immune response; 2） immune regulation; 3） inflammatory mediators; 4） high-mobility group box 1 protein; 5） the complement system; and 6） the autonomic nervous system. There are no therapeutic approaches available for sepsis that target inflammatory response; the mortality of sepsis has not been significantly reduced. Sepsis is complex and dynamic, and it has a group of heterogeneous syndromes.CONCLUSIONS： Since different patients with sepsis have different etiology, susceptibility, and responses, treatment should be prescribed individually.展开更多
In this paper,dynamics analysis of a delayed HIV infection model with CTL immune response and antibody immune response is investigated.The model involves the concentrations of uninfected cells,infected cells,free viru...In this paper,dynamics analysis of a delayed HIV infection model with CTL immune response and antibody immune response is investigated.The model involves the concentrations of uninfected cells,infected cells,free virus,CTL response cells,and antibody antibody response cells.There are three delays in the model:the intracellular delay,virus replication delay and the antibody delay.The basic reproductive number of viral infection,the antibody immune reproductive number,the CTL immune reproductive number,the CTL immune competitive reproductive number and the antibody immune competitive reproductive number are derived.By means of Lyapunov functionals and LaSalle’s invariance principle,sufficient conditions for the stability of each equilibrium is established.The results show that the intracellular delay and virus replication delay do not impact upon the stability of each equilibrium,but when the antibody delay is positive,Hopf bifurcation at the antibody response and the interior equilibrium will exist by using the antibody delay as a bifurcation parameter.Numerical simulations are carried out to justify the analytical results.展开更多
This paper considers a model of cell-to-cell spread of HIV-I with CTL immune response. By using a discrete delay to model the intracellular delay, it is shown that the uninfected equilibrium is globally asymptotical s...This paper considers a model of cell-to-cell spread of HIV-I with CTL immune response. By using a discrete delay to model the intracellular delay, it is shown that the uninfected equilibrium is globally asymptotical stable in some conditions and the sufficient condition to ensure the stability of the infected equilibrium does not change would be enlarged by Sturm sequence. Numerical simulations are presented to illustrate the results.展开更多
Combining the advantages of a genetic algorithm and an artificial immune system, a novel genetic algorithm named immune genetic algorithm based on quasi secondary response （IGA QSR） is proposed. IGA QSR employs a da...Combining the advantages of a genetic algorithm and an artificial immune system, a novel genetic algorithm named immune genetic algorithm based on quasi secondary response （IGA QSR） is proposed. IGA QSR employs a database to simulate the standard secondary response and the quasi secondary response. Elitist strategy, automatic extinction, clonal propagation, diversity guarantee, and selection based on comprehensive fitness are also used in the process of IGA QSR. Theoretical analysis, numerical examples of three benchmark mathematical optimization problems and a trave ling salesman problem all demonstrate that IGA-QSR is more effective not only on convergence speed but also on convergence probability than a simple genetic algorithm with the elitist strategy （ SGA ES）. Besides, IGA QSR allows the designers to stop and restart the optimization process freely with out losing the best results that have already been obtained. These properties make IGA QSR be a fea sible, effective and robust search algorithm for complex engineering problems.展开更多
In this paper, a virus infection model with standard incidence rate and delayed CTL immune response is investigated. By analyzing corresponding characteristic equations,the local stability of each of feasible equilibr...In this paper, a virus infection model with standard incidence rate and delayed CTL immune response is investigated. By analyzing corresponding characteristic equations,the local stability of each of feasible equilibria and the existence of Hopf bifurcations at the CTL-activated infection equilibrium are established, respectively. By means of comparison arguments, it is verified that the infection-free equilibrium is globally asymptotically stable if the basic reproduction ratio is less than unity. By using suitable Lyapunov functional and LaSalle's invariance principle, it is shown that the CTL-inactivated infection equilibrium of the system is globally asymptotically stable if the immune response reproduction ratio is less than unity and the basic reproduction ratio is greater than unity. Numerical simulations are carried out to illustrate the theoretical result.展开更多
To investigate the humoral immune response induced by HCV core DNA vaccine in mice and to furnish evidence for HCV DNA vaccine for humans. Methods: HCV core DNA vaccine (pcDNA3. 1HCVcore) was constructed by inserting ...To investigate the humoral immune response induced by HCV core DNA vaccine in mice and to furnish evidence for HCV DNA vaccine for humans. Methods: HCV core DNA vaccine (pcDNA3. 1HCVcore) was constructed by inserting the full-length cDNA of HCV core gene into an eukaryotic expression vector pcDNA3. 1. Balb/c mice were injected intramuscularly with the recombinant construct and serum anti-HCV core antibody was screened by ELISA. Lysate of NIH3T3 cells trans feeted with pcDNA3. 1 core was analyzed by Western-blot and the anti--HCV core antibody positive murine sera were used as specific antibodies to detect the expression of the vaccine. Results: ELISA detection revealed that 3 out of the 10 vaccinated mice produced HCV antibodies. Western-blot analysis showed that the anti--HCV core antibodies could detect HCV core protein expressed by NIH3T3 cells. Conclusion:HCV core DNA vaccine is able to induce specific antibodies in mice.展开更多
With improvements in personnel and vehicular body armor,robust casualty evacuation capabilities,and damage control resuscitation strategies,more combat casualties are surviving to reach higher levels of care throughou...With improvements in personnel and vehicular body armor,robust casualty evacuation capabilities,and damage control resuscitation strategies,more combat casualties are surviving to reach higher levels of care throughout the casualty evacuation system.As such,medical centers are becoming more accustomed to managing the deleterious late consequences of combat trauma related to the dysregulation of the immune system.In this review,we aim to highlight these late consequences and identify areas for future research and therapeutic strategies.Trauma leads to the dysregulation of both the innate and adaptive immune responses,which places the injured at risk for several late consequences,including delayed wound healing,late onset sepsis and infection,multi-organ dysfunction syndrome,and acute respiratory distress syndrome,which are significant for their association with the increased morbidity and mortality of wounded personnel.The mechanisms by which these consequences develop are complex but include an imbalance of the immune system leading to robust inflammatory responses,triggered by the presence of damage associated molecules and other immune-modifying agents following trauma.Treatment strategies to improve outcomes have been difficult to develop as the immunophenotype of injured personnel following trauma is variable,fluid and difficult to determine.As more information regarding the triggers that lead to immune dysfunction following trauma is elucidated,it may be possible to identify the immunophenotype of injured personnel and provide targeted treatments to reduce the late consequences of trauma,which are known to lead to significant morbidity and mortality.展开更多
基金Department of Defense(W81XWH-17-1-0447 and W81XWH1910548 to AKS)Texas A&M University School of Medicine。
文摘Over one-third of 700,000 military personnel who served in the first Gulf War(GW)suffer from an assortment of symptoms,including cognitive and memory problems,musculoskeletal pain,gastrointestinal discomfort,fatigue,and respiratory issues[1,2].The precise etiology of Gulf War illness(GWI)is unclear.However,epidemiological and preclinical studies imply that exposures to the prophylactic drug pyridostigmine bromide,insecticides,pesticides,smoke from oil well fires,and interaction between these exposures and war-related stress underlie this illness[2].As per the Kansas case definition,GWI is a chronic multi-symptom illness displaying one moderately severe and/or multiple symptoms of any severity in at least 3 of 6 symptom domains(fatigue,pain,neurological/cognitive/mood,skin,gastrointestinal,respiratory)[1,2].While the exact pathophysiological changes underlying GWI have not been identified,alterations in immune regulation and dysregulation of the redox balance have been observed in GWI,resulting in chronic systemic inflammation and neuroinflammation[2].
基金the financial support from the National Natural Science Foundation of China (No. 82372019, 82022034, 82173327)Jiangsu Province Natural Science Foundation of China (BK20200032)Double First Class Foundation of China Pharmaceutical University(CPUQNJC22_03)
文摘Photothermal and photodynamic therapies(PTT/PDT)hold promise for localized tumor treatment,yet their full potential is hampered by limitations such as the hypoxic tumor microenvironment and inadequate systemic immune activation.Addressing these challenges,we present a novel near-infrared(NIR)-triggered RNS nanoreactor(PBNO-Ce6)to amplify the photodynamic and photothermal therapy efficacy against triple-negative breast cancer(TNBC).The designed PBNOCe6 combines sodium nitroprusside-doped Prussian Blue nanoparticles with Chlorin e6 to enable on-site RNS production through NIR-induced concurrent NO release and ROS generation.This not only enhances tumor cell eradication but also potentiates local and systemic antitumor immune responses,protecting mice from tumor rechallenge.Our in vivo evaluations revealed that treatment with PBNO-Ce6 leads to a remarkable 2.7-fold increase in cytotoxic T lymphocytes and a 62%decrease in regulatory T cells in comparison to the control PB-Ce6(Prussian Blue nanoparticles loaded with Chlorin e6),marking a substantial improvement over traditional PTT/PDT.As such,the PBNO-Ce6 nanoreactor represents a transformative approach for improving outcomes in TNBC and potentially other malignancies affected by similar barriers.
基金The financial supports from the Key Program of the National Natural Science Foundation of China(32130082)Jiangxi High Level Talent Cultivation Project(20204BCJ24006)+1 种基金Project of State Key Laboratory of Food Science and Technology(SKLF-ZZA-201911)Central Government Guide Local Special Fund Project for Scientific and Technological Development of Jiangxi Province(20212ZDD02008)。
文摘With the rise of probiotics fermentation in food industry,fermented foods have attracted worldwide attention.In this study,protective effects of Rosa roxburghii&edible fungus fermentation broth(REFB)on immune function and gut health in Cyclophosphamide induced immunosuppressed mice were investigated.Results showed that REFB could improve the immune organ index,and promote the proliferation and differentiation of splenic T lymphocytes.In addition,it attenuated intestinal mucosal damage and improved intestinal cellular immunity.REFB administration also up-regulated the expression of IL-4,INF-γ,TNF-α,T-bet and GATA-3 mRNA in small intestine.Furthermore,administration of REFB modulated gut microbiota composition and increased the relative abundance of beneficial genus,such as Bacteroides.It also increased the production of fecal short-chain fatty acids.These indicate that REFB has the potential to improve immunity,alleviate intestinal injury and regulate gut microbiota in immunosuppressed mice.
文摘Accumulating evidence indicates that antibiotic exposure may lead to impaired vaccine responses1-4;however,the mechanisms underlying this association remain poorly understood.Here we prospectively followed 191 healthy,vaginally born,term infants from birth to 15 months,using a systems vaccinology approach to assess the effects of antibiotic exposure on immune responses to vaccination.Exposure to direct neonatal but not intrapartum antibiotics was associated with significantly lower antibody titres against various polysaccharides in the 13-valent pneumococcal conjugate vaccine and the Haemophilus influenzae type b polyribosylribitol phosphate and diphtheria toxoid antigens in the combined 6-in-1 Infanrix Hexa vaccine at 7 months of age.Blood from infants exposed to neonatal antibiotics had an inflammatory transcriptional profile before vaccination;in addition,faecal metagenomics showed reduced abundance of Bifidobacterium species in these infants at the time of vaccination,which was correlated with reduced vaccine antibody titres 6 months later.In preclinical models,responses to the 13-valent pneumococcal conjugate vaccine were strongly dependent on an intact microbiota but could be restored in germ-free mice by administering a consortium of Bifidobacterium species or a probiotic already widely used in neonatal units.Our data suggest that microbiota-targeted interventions could mitigate the detrimental effects of early-life antibiotics on vaccine immunogenicity.
基金Basic Research Spe-cial Project of Suzhou Science and Technology Bureau(SSD2024050).
文摘Objective Venous thromboembolism is a highly prevalent condition after polytrauma,and recognized as an important factor contributing to poor prognosis.The aim of this study was to investigate the risk factors for lower extremity deep venous thrombosis(LEDVT)in a severely traumatized population and to evaluate their predictive value for LEDVT.Methods This was a retrospective,single-center observational study.All subjects were severely traumatized patients who were admitted to the Traumatic Intensive Care Unit from January 2021 to May 2024.Based on Doppler ultrasound findings of both lower extremities from the time of injury to 30 days post-injury,patients who developed LEDVT were enrolled in the LEDVT group,and those who did not develop LEDVT were enrolled in the NLEDVT group.Demographic,clinical,and laboratory data were collected upon admission.Multivariable logistic regression analysis was performed to identify risk factors for LEDVT.Receiver operating characteristic(ROC)curve was used to evaluate the overall fit of the final model.Results There were 56 patients enrolled in the LEDVT group and 81 patients in the NLEDVT group.Age,Aggregate Index of Systemic Inflammation(AISI),Systemic Inflammation Response Index(SIRI),ICU length of stay,and albumin were identified as independent risk factors for LEDVT(all P<0.05).The area under their ROC curves were 0.604,0.657,0.694,0.668,and 0.405,respectively.Combined model for early clinical prediction of LEDVT in severely traumatized patients by age,SIRI,AISI,and albumin resulted in an area under the ROC curve of 0.805(95%CI:0.73-0.88,SE=0.037).Conclusion The combination of age,SIRI,AISI,and albumin has a predictive value for LEDVT in severely traumatized patients.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11402157 and 11571009)Shanxi Scholarship Council of China(Grant No.2015-032)+1 种基金Technological Innovation Programs of Higher Education Institutions in Shanxi,China(Grant No.2015121)Applied Basic Research Programs of Shanxi Province,China(Grant No.2016021013)
文摘We investigate the stochastic responses of a tumor–immune system competition model with environmental noise and periodic treatment. Firstly, a mathematical model describing the interaction between tumor cells and immune system under external fluctuations and periodic treatment is established based on the stochastic differential equation. Then, sufficient conditions for extinction and persistence of the tumor cells are derived by constructing Lyapunov functions and Ito＇s formula. Finally, numerical simulations are introduced to illustrate and verify the results. The results of this work provide the theoretical basis for designing more effective and precise therapeutic strategies to eliminate cancer cells, especially for combining the immunotherapy and the traditional tools.
基金supported by the National Natural Science Foundation of China(10971166,10901131)the National High Technology Research and Development Program of China(863 Program,2009AA01A135)the Natural Science Foundation of Xinjiang Province(2010211B04)
文摘This article proposes a diffused hepatitis B virus （HBV） model with CTL immune response and nonlinear incidence for the control of viral infections. By means of different Lyapunov functions, the global asymptotical properties of the viral-free equilibrium and immune-free equilibrium of the model are obtained. Global stability of the positive equilibrium of the model is also considered. The results show that the free diffusion of the virus has no effect on the global stability of such HBV infection problem with Neumann homogeneous boundary conditions.
文摘BACKGROUND： Sepsis and secondary multiple organ failure in critically ill patients are the major cause of death, but the pathogenesis of sepsis is not clear, especially the dysfunction of the immune system. In this paper, we review the response and regulation of the immune system and the functions of a variety of inflammatory mediators in sepsis. DATA SOURCES Studies were identified by searching MEDLINE and PubMed for articles using the keywords ＂sepsis＂, ＂immune response＂, and ＂inflammatory mediator＂ up to October 2010. Additional papers were identified by a manual search of the references from the key articles.RESULTS： This systematic review was conducted of： 1） the immune response; 2） immune regulation; 3） inflammatory mediators; 4） high-mobility group box 1 protein; 5） the complement system; and 6） the autonomic nervous system. There are no therapeutic approaches available for sepsis that target inflammatory response; the mortality of sepsis has not been significantly reduced. Sepsis is complex and dynamic, and it has a group of heterogeneous syndromes.CONCLUSIONS： Since different patients with sepsis have different etiology, susceptibility, and responses, treatment should be prescribed individually.
基金The work was supported by NSF of China(11201002)Natural Science Foundation of Universities in Anhui Province(KJ2017A815).
文摘In this paper,dynamics analysis of a delayed HIV infection model with CTL immune response and antibody immune response is investigated.The model involves the concentrations of uninfected cells,infected cells,free virus,CTL response cells,and antibody antibody response cells.There are three delays in the model:the intracellular delay,virus replication delay and the antibody delay.The basic reproductive number of viral infection,the antibody immune reproductive number,the CTL immune reproductive number,the CTL immune competitive reproductive number and the antibody immune competitive reproductive number are derived.By means of Lyapunov functionals and LaSalle’s invariance principle,sufficient conditions for the stability of each equilibrium is established.The results show that the intracellular delay and virus replication delay do not impact upon the stability of each equilibrium,but when the antibody delay is positive,Hopf bifurcation at the antibody response and the interior equilibrium will exist by using the antibody delay as a bifurcation parameter.Numerical simulations are carried out to justify the analytical results.
基金Supposed by the National Science Fund of China(10571143)
文摘This paper considers a model of cell-to-cell spread of HIV-I with CTL immune response. By using a discrete delay to model the intracellular delay, it is shown that the uninfected equilibrium is globally asymptotical stable in some conditions and the sufficient condition to ensure the stability of the infected equilibrium does not change would be enlarged by Sturm sequence. Numerical simulations are presented to illustrate the results.
基金Supported by the National Science Foundation for Post-doctoral Scientists of China(20090460216)the National Defense Fundamental Research Foundation of China(B222006060)
文摘Combining the advantages of a genetic algorithm and an artificial immune system, a novel genetic algorithm named immune genetic algorithm based on quasi secondary response （IGA QSR） is proposed. IGA QSR employs a database to simulate the standard secondary response and the quasi secondary response. Elitist strategy, automatic extinction, clonal propagation, diversity guarantee, and selection based on comprehensive fitness are also used in the process of IGA QSR. Theoretical analysis, numerical examples of three benchmark mathematical optimization problems and a trave ling salesman problem all demonstrate that IGA-QSR is more effective not only on convergence speed but also on convergence probability than a simple genetic algorithm with the elitist strategy （ SGA ES）. Besides, IGA QSR allows the designers to stop and restart the optimization process freely with out losing the best results that have already been obtained. These properties make IGA QSR be a fea sible, effective and robust search algorithm for complex engineering problems.
基金Supported by the NNSF of China(11371368,11071254)Supported by the NSF of Hebei Province(A2014506015)Supported by the NSF for Young Scientists of Hebei Province(A2013506012)
文摘In this paper, a virus infection model with standard incidence rate and delayed CTL immune response is investigated. By analyzing corresponding characteristic equations,the local stability of each of feasible equilibria and the existence of Hopf bifurcations at the CTL-activated infection equilibrium are established, respectively. By means of comparison arguments, it is verified that the infection-free equilibrium is globally asymptotically stable if the basic reproduction ratio is less than unity. By using suitable Lyapunov functional and LaSalle's invariance principle, it is shown that the CTL-inactivated infection equilibrium of the system is globally asymptotically stable if the immune response reproduction ratio is less than unity and the basic reproduction ratio is greater than unity. Numerical simulations are carried out to illustrate the theoretical result.
文摘To investigate the humoral immune response induced by HCV core DNA vaccine in mice and to furnish evidence for HCV DNA vaccine for humans. Methods: HCV core DNA vaccine (pcDNA3. 1HCVcore) was constructed by inserting the full-length cDNA of HCV core gene into an eukaryotic expression vector pcDNA3. 1. Balb/c mice were injected intramuscularly with the recombinant construct and serum anti-HCV core antibody was screened by ELISA. Lysate of NIH3T3 cells trans feeted with pcDNA3. 1 core was analyzed by Western-blot and the anti--HCV core antibody positive murine sera were used as specific antibodies to detect the expression of the vaccine. Results: ELISA detection revealed that 3 out of the 10 vaccinated mice produced HCV antibodies. Western-blot analysis showed that the anti--HCV core antibodies could detect HCV core protein expressed by NIH3T3 cells. Conclusion:HCV core DNA vaccine is able to induce specific antibodies in mice.
基金RJS was supported by National Institutes of Health grants,K08-GM117367.
文摘With improvements in personnel and vehicular body armor,robust casualty evacuation capabilities,and damage control resuscitation strategies,more combat casualties are surviving to reach higher levels of care throughout the casualty evacuation system.As such,medical centers are becoming more accustomed to managing the deleterious late consequences of combat trauma related to the dysregulation of the immune system.In this review,we aim to highlight these late consequences and identify areas for future research and therapeutic strategies.Trauma leads to the dysregulation of both the innate and adaptive immune responses,which places the injured at risk for several late consequences,including delayed wound healing,late onset sepsis and infection,multi-organ dysfunction syndrome,and acute respiratory distress syndrome,which are significant for their association with the increased morbidity and mortality of wounded personnel.The mechanisms by which these consequences develop are complex but include an imbalance of the immune system leading to robust inflammatory responses,triggered by the presence of damage associated molecules and other immune-modifying agents following trauma.Treatment strategies to improve outcomes have been difficult to develop as the immunophenotype of injured personnel following trauma is variable,fluid and difficult to determine.As more information regarding the triggers that lead to immune dysfunction following trauma is elucidated,it may be possible to identify the immunophenotype of injured personnel and provide targeted treatments to reduce the late consequences of trauma,which are known to lead to significant morbidity and mortality.
