Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism rem...Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.展开更多
Neuromyelitis optica spectrum disorder-related optic neuritis involves various cellular responses to inflammation and degeneration.In most patients,the primary mechanism underlying neuromyelitis optica spectrum disord...Neuromyelitis optica spectrum disorder-related optic neuritis involves various cellular responses to inflammation and degeneration.In most patients,the primary mechanism underlying neuromyelitis optica spectrum disorder-related optic neuritis is the interaction of aquaporin-4 antibodies with the aquaporin-4 protein present on astrocytes within posterior optic nerve.This binding subsequently initiates a cascade of events leading to secondary demyelination of the optic nerve,ultimately culminating in optic nerve degeneration.Earlier studies on this disorder primarily used systemic-induced animal models,which often require prior activation of a systemic immune response.This can result in primary demyelination of the optic nerve,complicating the interpretation of experimental results.Such methodologies hinder the ability to isolate immune responses triggered by specific antibodies.Additionally,the lack of a detailed profile of disease progression over time limits our capacity to identify potential intervention windows.Therefore,constructing a targeted optic neuritis animal model induced by specific antibodies and elucidate the disease progression arecrucial for exploring the mechanisms underlying neuromyelitis optica spectrum disorder-related optic neuritis.In this study,specific antibodies against aquaporin-4 were precisely injected into the retrobulbar optic nerve of mice to induce a targeted inflammatory response in the posterior optic nerve,resulting in a more representative mouse model of neuromyelitis optica spectrum disorder-related optic neuritis than current models.The progression of the disease was then dynamically observed from both histological and functional perspectives over the course of 1 month following the induction of inflammation.By the first week,astrocytes were damaged,as evidenced by the loss of aquaporin-4 and glial fibrillary acidic protein,the activation of microglia,and the upregulation of microglia-related cytokines,including tumor necrosis factor,interleukin-6,interleukin-1β,C-X-C motif ligand 10,and brain-derived neurotrophic factor.Starting from the second week,there were signs of optic nerve demyelination and significant damage to axonal fibers and retinal ganglion cell bodies.Visual-evoked potentials and dark adaptation threshold responses in electroretinogram both indicated dysfunction in the visual pathway and retina,while optical coherence tomography revealed thinning of the retinal nerve fiber layer in live mice.In summary,in this study we conducted a dynamic exploration of the occurrence and progression of neuromyelitis optica spectrum disorder-related optic neuritis triggered by specific antibodies.Our results show pathological changes at various stages and correlate histological and molecular alterations with in vivo structural and functional deterioration.The findings from this study lay an important foundation for further research on neuromyelitis optica spectrum disorder-related optic neuritis.展开更多
A set of uniaxial tensile creep tests at different pre-deformations, aging temperatures and stress levels were carried out for Al-Li-S4 alloy, and the creep behavior and the effects of pre-deformation on mechanical pr...A set of uniaxial tensile creep tests at different pre-deformations, aging temperatures and stress levels were carried out for Al-Li-S4 alloy, and the creep behavior and the effects of pre-deformation on mechanical properties and microstructures were determined under basic thermodynamics conditions of aging forming. The results show that pre-deformation shortens the time of primary creep and raises the second steady-state creep rate. Then, the total creep strain is greater, but in the range of test parameters it is still smaller than that without pre-deformation. In addition, transmission electron microscopy（TEM） observation shows that pre-deformation promotes the formation of T1 phase and θ′ phase and makes them distribute more dispersively, while inhibits the generation of δ′ phase, which leads to the improvement of mechanical properties of the alloy. A unified constitutive model reflecting the effects of aging mechanism, stress levels and different pre-deformations was established. The fitting results agree with the experimental data well.展开更多
Numerical control（NC） warm bending is a proven strategy to form the large diameter thin-walled（LDTW） Ti-6 Al-4 V tubes, which are typical light-weight and high-performance structural components urgently required i...Numerical control（NC） warm bending is a proven strategy to form the large diameter thin-walled（LDTW） Ti-6 Al-4 V tubes, which are typical light-weight and high-performance structural components urgently required in many industries. In virtue of unveiling the thermo-mechanical coupled deformation behaviors, uniaxial tensile tests were conducted on Ti-6 Al-4 V tube within wide ranges of temperatures（25-600 ℃） and strain rates（0.00067-0.1 s～（-1））. Moreover, a modified Johnson-Cook（JC） model is proposed with a consideration of nonlinear strain rate hardening and the interaction between strain hardening and thermal softening. Resultantly, the present model gives more accurate predictions for flow stress over the entire deformation ranges and the maximum error decreases by about 90%. By employing proposed model to NC warm bending, preferable precision is obtained in predicting forming defects including fracture, wrinkling and over thinning. The present work lays foundation for the forming limit prediction and process optimization in NC warm bending of LDTW Ti-6 Al-4 V tubes.展开更多
The mathematical model of 4He quantum interferometer gyroscope is presented. The model includes the driven equation, the current equation and the position equation. Therefore, it can sufficiently describe the gyro- sc...The mathematical model of 4He quantum interferometer gyroscope is presented. The model includes the driven equation, the current equation and the position equation. Therefore, it can sufficiently describe the gyro- scope system. The driven equation shows the thermally driven gyroscope can work for a long time but the pres- sure driven one cannot. From the current equation, the superfluid currents passing through the weak link contain the AC currents which show the rotation flux, and other currents caused by drive. As shown in the position equa- tion, the displacement of diaphragm is the only detectable parameter in the gyroscope system. The model is tested by the simulations based on experimental parameters, and can be used to research performance of the gyroscope and analyse the gyroscope error.展开更多
Production o f aromatics from lignin has attracted much attention. Because of the coexistence of C-O and C-C bonds and their complex combinations in the lignin macromolecular network, a plausible roadmap for de...Production o f aromatics from lignin has attracted much attention. Because of the coexistence of C-O and C-C bonds and their complex combinations in the lignin macromolecular network, a plausible roadmap for developing a lignin catalytic decomposition process could be developed by exploring the transformation mechanisms of various model compounds. Herein, decomposition of a lignin model compound, 2-phenoxyacetophenone （2-PAP）, was investigated over several ce-sium-exchanged polyoxometalate （Cs-POM） catalysts. Decomposition of 2-PAP can follow two dif-ferent mechanisms： an active hydrogen transfer mechanism or an oxonium cation mechanism. The mechanism for most reactions depends on the competition between the acidity and redox proper-ties of the catalysts. The catalysts of POMs perform the following functions： promoting active hy-drogen liberated from ethanol and causing formation of and then temporarily stabilizing oxonium cations from 2-PAP. The use of Cs-PMo, which with strong redox ability, enhances hydrogen libera-tion and promotes liberated hydrogen transfer to the reaction intermediates. As a consequence, complete conversion of 2-PAP （〉99%） with excellent selectivities to the desired products （98.6% for phenol and 91.1% for acetophenone） can be achieved.展开更多
文摘Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.
基金The study was partially supported by the General Research Fund(GRF)from the Research Grants Council(RGC)of the Hong Kong Special Administrative Region,China,No.15103522(to ST)the Internal Research Grant from the Hong Kong Polytechnic University 2021-23,No.P0035512(to ST)and P0035375(to HHLC)+1 种基金the Innovation and Technology Commission of the Hong Kong Special Administrative Region(ITC InnoHK CEVR Project)The Hong Kong Polytechnics University Research Center for Sharp Vision,No.P0039595.
文摘Neuromyelitis optica spectrum disorder-related optic neuritis involves various cellular responses to inflammation and degeneration.In most patients,the primary mechanism underlying neuromyelitis optica spectrum disorder-related optic neuritis is the interaction of aquaporin-4 antibodies with the aquaporin-4 protein present on astrocytes within posterior optic nerve.This binding subsequently initiates a cascade of events leading to secondary demyelination of the optic nerve,ultimately culminating in optic nerve degeneration.Earlier studies on this disorder primarily used systemic-induced animal models,which often require prior activation of a systemic immune response.This can result in primary demyelination of the optic nerve,complicating the interpretation of experimental results.Such methodologies hinder the ability to isolate immune responses triggered by specific antibodies.Additionally,the lack of a detailed profile of disease progression over time limits our capacity to identify potential intervention windows.Therefore,constructing a targeted optic neuritis animal model induced by specific antibodies and elucidate the disease progression arecrucial for exploring the mechanisms underlying neuromyelitis optica spectrum disorder-related optic neuritis.In this study,specific antibodies against aquaporin-4 were precisely injected into the retrobulbar optic nerve of mice to induce a targeted inflammatory response in the posterior optic nerve,resulting in a more representative mouse model of neuromyelitis optica spectrum disorder-related optic neuritis than current models.The progression of the disease was then dynamically observed from both histological and functional perspectives over the course of 1 month following the induction of inflammation.By the first week,astrocytes were damaged,as evidenced by the loss of aquaporin-4 and glial fibrillary acidic protein,the activation of microglia,and the upregulation of microglia-related cytokines,including tumor necrosis factor,interleukin-6,interleukin-1β,C-X-C motif ligand 10,and brain-derived neurotrophic factor.Starting from the second week,there were signs of optic nerve demyelination and significant damage to axonal fibers and retinal ganglion cell bodies.Visual-evoked potentials and dark adaptation threshold responses in electroretinogram both indicated dysfunction in the visual pathway and retina,while optical coherence tomography revealed thinning of the retinal nerve fiber layer in live mice.In summary,in this study we conducted a dynamic exploration of the occurrence and progression of neuromyelitis optica spectrum disorder-related optic neuritis triggered by specific antibodies.Our results show pathological changes at various stages and correlate histological and molecular alterations with in vivo structural and functional deterioration.The findings from this study lay an important foundation for further research on neuromyelitis optica spectrum disorder-related optic neuritis.
基金Project(2014CB046602)supported by the National Basic Research Program of ChinaProject(51235010)supported by the National Natural Science Foundation of China
文摘A set of uniaxial tensile creep tests at different pre-deformations, aging temperatures and stress levels were carried out for Al-Li-S4 alloy, and the creep behavior and the effects of pre-deformation on mechanical properties and microstructures were determined under basic thermodynamics conditions of aging forming. The results show that pre-deformation shortens the time of primary creep and raises the second steady-state creep rate. Then, the total creep strain is greater, but in the range of test parameters it is still smaller than that without pre-deformation. In addition, transmission electron microscopy（TEM） observation shows that pre-deformation promotes the formation of T1 phase and θ′ phase and makes them distribute more dispersively, while inhibits the generation of δ′ phase, which leads to the improvement of mechanical properties of the alloy. A unified constitutive model reflecting the effects of aging mechanism, stress levels and different pre-deformations was established. The fitting results agree with the experimental data well.
基金Projects(50905144,51275415)supported by the National Natural Science Foundation of ChinaProject supported by the Program for New Century Excellent Talents in University,China+1 种基金Project(3102014KYJD001)supported by Fundamental Research Funds for the Central Universities,ChinaProject(B08040)supported by Program of Introducing Talents of Discipline to Universities("111"Project),China
文摘Numerical control（NC） warm bending is a proven strategy to form the large diameter thin-walled（LDTW） Ti-6 Al-4 V tubes, which are typical light-weight and high-performance structural components urgently required in many industries. In virtue of unveiling the thermo-mechanical coupled deformation behaviors, uniaxial tensile tests were conducted on Ti-6 Al-4 V tube within wide ranges of temperatures（25-600 ℃） and strain rates（0.00067-0.1 s～（-1））. Moreover, a modified Johnson-Cook（JC） model is proposed with a consideration of nonlinear strain rate hardening and the interaction between strain hardening and thermal softening. Resultantly, the present model gives more accurate predictions for flow stress over the entire deformation ranges and the maximum error decreases by about 90%. By employing proposed model to NC warm bending, preferable precision is obtained in predicting forming defects including fracture, wrinkling and over thinning. The present work lays foundation for the forming limit prediction and process optimization in NC warm bending of LDTW Ti-6 Al-4 V tubes.
基金Supported by the National Natural Science Foundation of China(61074162)the Ph.D.Program Foundation of Ministry of Education of China(200802870011)~~
文摘The mathematical model of 4He quantum interferometer gyroscope is presented. The model includes the driven equation, the current equation and the position equation. Therefore, it can sufficiently describe the gyro- scope system. The driven equation shows the thermally driven gyroscope can work for a long time but the pres- sure driven one cannot. From the current equation, the superfluid currents passing through the weak link contain the AC currents which show the rotation flux, and other currents caused by drive. As shown in the position equa- tion, the displacement of diaphragm is the only detectable parameter in the gyroscope system. The model is tested by the simulations based on experimental parameters, and can be used to research performance of the gyroscope and analyse the gyroscope error.
基金supported by the National Key Basic Research Program of China(973 program,2013CB934101)National Natural Science Foundation of China(21433002,21573046)+1 种基金China Postdoctoral Science Foundation(2016M601492)International Science and Technology Cooperation Projects of Guangxi(15104001-5)~~
文摘Production o f aromatics from lignin has attracted much attention. Because of the coexistence of C-O and C-C bonds and their complex combinations in the lignin macromolecular network, a plausible roadmap for developing a lignin catalytic decomposition process could be developed by exploring the transformation mechanisms of various model compounds. Herein, decomposition of a lignin model compound, 2-phenoxyacetophenone （2-PAP）, was investigated over several ce-sium-exchanged polyoxometalate （Cs-POM） catalysts. Decomposition of 2-PAP can follow two dif-ferent mechanisms： an active hydrogen transfer mechanism or an oxonium cation mechanism. The mechanism for most reactions depends on the competition between the acidity and redox proper-ties of the catalysts. The catalysts of POMs perform the following functions： promoting active hy-drogen liberated from ethanol and causing formation of and then temporarily stabilizing oxonium cations from 2-PAP. The use of Cs-PMo, which with strong redox ability, enhances hydrogen libera-tion and promotes liberated hydrogen transfer to the reaction intermediates. As a consequence, complete conversion of 2-PAP （〉99%） with excellent selectivities to the desired products （98.6% for phenol and 91.1% for acetophenone） can be achieved.
