Background:This study aimed to construct and characterize a humanized influenza mouse model expressing hST6GAL1.Methods:Humanized fragments,consisting of the endothelial cell-specific K18 promoter,human ST6GAL1-encodi...Background:This study aimed to construct and characterize a humanized influenza mouse model expressing hST6GAL1.Methods:Humanized fragments,consisting of the endothelial cell-specific K18 promoter,human ST6GAL1-encoding gene,and luciferase gene,were microinjected into the fertilized eggs of mice.The manipulated embryos were transferred into the oviducts of pseudopregnant female mice.The offspring were identified using PCR.Mice exhibiting elevated expression of the hST6GAL1 gene were selectively bred for propagation,and in vivo analysis was performed for screening.Expression of the humanized gene was tested by performing immunohistochemical(IHC)analysis.Hematologic and biochemical analyses using the whole blood and serum of humanized hST6GAL1 mice were performed.Results:Successful integration of the human ST6GAL1 gene into the mouse genome led to the overexpression of human SiaT ST6GAL1.Seven mice were identified as carrying copies of the humanized gene,and the in vivo analysis indicated that hST6GAL1gene expression in positive mice mirrored influenza virus infection characteristics.The IHC results revealed that hST6GAL1 was expressed in the lungs of humanized mice.Moreover,the hematologic and biochemical parameters of the positive mice were within the normal range.Conclusion:A humanized influenza mouse model expressing the hST6GAL1 gene was successfully established and characterized.展开更多
This research aims to optimize the utilization of long-term sea level data from the TOPEX/Poseidon,Jason1,Jason2,and Jason3 altimetry missions for tidal modeling.We generate a time series of along-track observations a...This research aims to optimize the utilization of long-term sea level data from the TOPEX/Poseidon,Jason1,Jason2,and Jason3 altimetry missions for tidal modeling.We generate a time series of along-track observations and apply a developed method to produce tidal models with specific tidal constituents for each location.Our tidal modeling methodology follows an iterative process:partitioning sea surface height(SSH)observations into analysis/training and prediction/validation parts and ultimately identi-fying the set of tidal constituents that provide the best predictions at each time series location.The study focuses on developing 1256 time series along the altimetry tracks over the Baltic Sea,each with its own set of tidal constituents.Verification of the developed tidal models against the sSH observations within the prediction/validation part reveals mean absolute error(MAE)values ranging from 0.0334 m to 0.1349 m,with an average MAE of 0.089 m.The same validation process is conducted on the FES2014 and EOT20 global tidal models,demonstrating that our tidal model,referred to as BT23(short for Baltic Tide 2023),outperforms both models with an average MAE improvement of 0.0417 m and 0.0346 m,respectively.In addition to providing details on the development of the time series and the tidal modeling procedure,we offer the 1256 along-track time series and their associated tidal models as supplementary materials.We encourage the satellite altimetry community to utilize these resources for further research and applications.展开更多
Atmospheric models are physical equations based on the ideal gas law. Applied to the atmosphere, this law yields equations for water, vapor (gas), ice, air, humidity, dryness, fire, and heat, thus defining the model o...Atmospheric models are physical equations based on the ideal gas law. Applied to the atmosphere, this law yields equations for water, vapor (gas), ice, air, humidity, dryness, fire, and heat, thus defining the model of key atmospheric parameters. The distribution of these parameters across the entire planet Earth is the origin of the formation of the climatic cycle, which is a normal climatic variation. To do this, the Earth is divided into eight (8) parts according to the number of key parameters to be defined in a physical representation of the model. Following this distribution, numerical models calculate the constants for the formation of water, vapor, ice, dryness, thermal energy (fire), heat, air, and humidity. These models vary in complexity depending on the indirect trigonometric direction and simplicity in the sum of neighboring models. Note that the constants obtained from the equations yield 275.156˚K (2.006˚C) for water, 273.1596˚K (0.00963˚C) for vapor, 273.1633˚K (0.0133˚C) for ice, 0.00365 in/s for atmospheric dryness, 1.996 in<sup>2</sup>/s for humidity, 2.993 in<sup>2</sup>/s for air, 1 J for thermal energy of fire, and 0.9963 J for heat. In summary, this study aims to define the main parameters and natural phenomena contributing to the modification of planetary climate. .展开更多
Parkinson’s disease(PD)relates to defective mitochondrial quality control in the dopaminergic motor network.Genetic studies have revealed that PINK1 and Parkin mutations are indicative of a heightened propensity to P...Parkinson’s disease(PD)relates to defective mitochondrial quality control in the dopaminergic motor network.Genetic studies have revealed that PINK1 and Parkin mutations are indicative of a heightened propensity to PD onset,pinpointing mitophagy and inflammation as the culprit pathways involved in neuronal loss in the substantia nigra(SNpc).In a reciprocal manner,LRRK2 functions in the regulation of basal flux and inflammatory responses responsible for PINK1/Parkin-dependent mitophagy activation.Pharmacological intervention in these diseasemodifying pathways may facilitate the development of novel PD therapeutics,despite the current lack of an established drug evaluation model.As such,we reviewed the feasibility of employing the versatile global Pink1knockout(KO)rat model as a self-sufficient,spontaneous PD model for investigating both disease etiology and drug pharmacology.These rats retain clinical features encompassing basal mitophagic flux changes with PD progression.We demonstrate the versatility of this PD rat model based on the incorporation of additional experimental insults to recapitulate the proinflammatory responses observed in PD patients.展开更多
Lie symmetry analysis is applied to a(3+1)-dimensional Virasoro integrable model and the corresponding similarity reduction equations are obtained with the different infinitesimal generators.Invariant solutions with a...Lie symmetry analysis is applied to a(3+1)-dimensional Virasoro integrable model and the corresponding similarity reduction equations are obtained with the different infinitesimal generators.Invariant solutions with arbitrary functions for the(3+1)-dimensional Virasoro integrable model,including the interaction solution between a kink and a soliton,the lump-type solution and periodic solutions,have been studied analytically and graphically.展开更多
The impulse waves induced by large-reservoir landslides can be characterized by a low Froude number.However,systematic research on predictive models specifically targeting the initial primary wave is lacking.Taking th...The impulse waves induced by large-reservoir landslides can be characterized by a low Froude number.However,systematic research on predictive models specifically targeting the initial primary wave is lacking.Taking the Shuipingzi 1#landslide that occurred in the Baihetan Reservoir area of the Jinsha River in China as an engineering example,this study established a large-scale physical model(with dimensions of 30 m×29 m×3.5 m at a scale of 1:150)and conducted scaled experiments on 3D landslide-induced impulse waves.During the process in which a sliding mass displaced and compressed a body of water to generate waves,the maximum initial wave amplitude was found to be positively correlated with the sliding velocity and the volume of the landslide.With the increase in the water depth,the wave amplitude initially increased and then decreased.The duration of pressure exertion by the sliding mass at its maximum velocity directly correlated with an elevated wave amplitude.Based on the theories of low-amplitude waves and energy conservation,while considering the energy conversion efficiency,a predictive model for the initial wave amplitude was derived.This model could fit and validate the functions of wavelength and wave velocity.The accuracy of the initial wave amplitude was verified using physical experiment data,with a prediction accuracy for the maximum initial wave amplitude reaching 90%.The conversion efficiency(η)directly determined the accuracy of the estimation formula.Under clear conditions for landslide-induced impulse wave generation,estimating the value ofηthrough analogy cases was feasible.This study has derived the landslide-induced impulse waves amplitude prediction formula from the standpoints of wave theory and energy conservation,with greater consideration given to the intrinsic characteristics in the formation process of landslide-induced impulse waves,thereby enhancing the applicability and extensibility of the formula.This can facilitate the development of empirical estimation methods for landslide-induced impulse waves toward universality.展开更多
Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein functio...Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein function or structure,understanding their genetic basis is crucial for accurate diagnosis and targeted therapies.To investigate the underlying pathogenesis of these conditions,researchers often use non-mammalian model organisms,such as Drosophila(fruit flies),which is valued for their genetic manipulability,cost-efficiency,and preservation of genes and biological functions across evolutionary time.Genetic tools available in Drosophila,including CRISPR-Cas9,offer a means to manipulate gene expression,allowing for a deep exploration of the genetic underpinnings of rare neurological diseases.Drosophila boasts a versatile genetic toolkit,rapid generation turnover,and ease of large-scale experimentation,making it an invaluable resource for identifying potential drug candidates.Researchers can expose flies carrying disease-associated mutations to various compounds,rapidly pinpointing promising therapeutic agents for further investigation in mammalian models and,ultimately,clinical trials.In this comprehensive review,we explore rare neurological diseases where fly research has significantly contributed to our understanding of their genetic basis,pathophysiology,and potential therapeutic implications.We discuss rare diseases associated with both neuron-expressed and glial-expressed genes.Specific cases include mutations in CDK19 resulting in epilepsy and developmental delay,mutations in TIAM1 leading to a neurodevelopmental disorder with seizures and language delay,and mutations in IRF2BPL causing seizures,a neurodevelopmental disorder with regression,loss of speech,and abnormal movements.And we explore mutations in EMC1 related to cerebellar atrophy,visual impairment,psychomotor retardation,and gain-of-function mutations in ACOX1 causing Mitchell syndrome.Loss-of-function mutations in ACOX1 result in ACOX1 deficiency,characterized by very-long-chain fatty acid accumulation and glial degeneration.Notably,this review highlights how modeling these diseases in Drosophila has provided valuable insights into their pathophysiology,offering a platform for the rapid identification of potential therapeutic interventions.Rare neurological diseases involve a wide range of expression systems,and sometimes common phenotypes can be found among different genes that cause abnormalities in neurons or glia.Furthermore,mutations within the same gene may result in varying functional outcomes,such as complete loss of function,partial loss of function,or gain-of-function mutations.The phenotypes observed in patients can differ significantly,underscoring the complexity of these conditions.In conclusion,Drosophila represents an indispensable and cost-effective tool for investigating rare neurological diseases.By facilitating the modeling of these conditions,Drosophila contributes to a deeper understanding of their genetic basis,pathophysiology,and potential therapies.This approach accelerates the discovery of promising drug candidates,ultimately benefiting patients affected by these complex and understudied diseases.展开更多
Background: Diabetes education is crucial in empowering persons with Type 1 diabetes (T1DM) and their families to properly manage the condition by providing comprehensive knowledge, tools, and support. It boosts one’...Background: Diabetes education is crucial in empowering persons with Type 1 diabetes (T1DM) and their families to properly manage the condition by providing comprehensive knowledge, tools, and support. It boosts one’s belief in their ability to succeed, encourages following medical advice, and adds to the general enhancement of health. Objective: This study is to investigate the effectiveness of diabetes education in empowering individuals with Type 1 Diabetes Mellitus (T1DM) and their families to effectively manage the condition. Furthermore, it strives to improve nursing care for families whose children have been diagnosed with Type 1 Diabetes Mellitus (T1DM). Design: This research study investigates the efficacy of diabetes education in empowering individuals with Type 1 Diabetes Mellitus (T1DM) and their families to effectively handle the condition. Materials and Methods: A systematic search was conducted between the years 2000 and 2022, utilizing the Medline and Google Scholar databases. The purpose of the search was to uncover relevant papers pertaining to diabetes education, management of Type 1 Diabetes Mellitus (T1DM), nurse care, and empowerment. The search focused on peer-reviewed research, clinical trials, and scholarly articles that evaluated the efficacy of diabetes education in empowering individuals and families. Results: Diabetes education is crucial for understanding and controlling T1DM. It includes personalized sessions, webinars, group classes, and clinics that provide customized therapies. Comprehensive education enhances glycemic control and family dynamics. Nevertheless, the implementation of diabetes education for families requires specific standards, especially in the field of nursing. Conclusion: Diabetes education is essential for effectively managing Type 1 Diabetes Mellitus (T1DM), providing patients and families with crucial knowledge, resources, and confidence. It encourages independence in-home care and provides explicit guidelines for diabetic nurses to improve nursing care.展开更多
基金National Key Research and Development Program of China,Grant/Award Number:2021YFC2301403 and 2022YFF0711000。
文摘Background:This study aimed to construct and characterize a humanized influenza mouse model expressing hST6GAL1.Methods:Humanized fragments,consisting of the endothelial cell-specific K18 promoter,human ST6GAL1-encoding gene,and luciferase gene,were microinjected into the fertilized eggs of mice.The manipulated embryos were transferred into the oviducts of pseudopregnant female mice.The offspring were identified using PCR.Mice exhibiting elevated expression of the hST6GAL1 gene were selectively bred for propagation,and in vivo analysis was performed for screening.Expression of the humanized gene was tested by performing immunohistochemical(IHC)analysis.Hematologic and biochemical analyses using the whole blood and serum of humanized hST6GAL1 mice were performed.Results:Successful integration of the human ST6GAL1 gene into the mouse genome led to the overexpression of human SiaT ST6GAL1.Seven mice were identified as carrying copies of the humanized gene,and the in vivo analysis indicated that hST6GAL1gene expression in positive mice mirrored influenza virus infection characteristics.The IHC results revealed that hST6GAL1 was expressed in the lungs of humanized mice.Moreover,the hematologic and biochemical parameters of the positive mice were within the normal range.Conclusion:A humanized influenza mouse model expressing the hST6GAL1 gene was successfully established and characterized.
文摘This research aims to optimize the utilization of long-term sea level data from the TOPEX/Poseidon,Jason1,Jason2,and Jason3 altimetry missions for tidal modeling.We generate a time series of along-track observations and apply a developed method to produce tidal models with specific tidal constituents for each location.Our tidal modeling methodology follows an iterative process:partitioning sea surface height(SSH)observations into analysis/training and prediction/validation parts and ultimately identi-fying the set of tidal constituents that provide the best predictions at each time series location.The study focuses on developing 1256 time series along the altimetry tracks over the Baltic Sea,each with its own set of tidal constituents.Verification of the developed tidal models against the sSH observations within the prediction/validation part reveals mean absolute error(MAE)values ranging from 0.0334 m to 0.1349 m,with an average MAE of 0.089 m.The same validation process is conducted on the FES2014 and EOT20 global tidal models,demonstrating that our tidal model,referred to as BT23(short for Baltic Tide 2023),outperforms both models with an average MAE improvement of 0.0417 m and 0.0346 m,respectively.In addition to providing details on the development of the time series and the tidal modeling procedure,we offer the 1256 along-track time series and their associated tidal models as supplementary materials.We encourage the satellite altimetry community to utilize these resources for further research and applications.
文摘Atmospheric models are physical equations based on the ideal gas law. Applied to the atmosphere, this law yields equations for water, vapor (gas), ice, air, humidity, dryness, fire, and heat, thus defining the model of key atmospheric parameters. The distribution of these parameters across the entire planet Earth is the origin of the formation of the climatic cycle, which is a normal climatic variation. To do this, the Earth is divided into eight (8) parts according to the number of key parameters to be defined in a physical representation of the model. Following this distribution, numerical models calculate the constants for the formation of water, vapor, ice, dryness, thermal energy (fire), heat, air, and humidity. These models vary in complexity depending on the indirect trigonometric direction and simplicity in the sum of neighboring models. Note that the constants obtained from the equations yield 275.156˚K (2.006˚C) for water, 273.1596˚K (0.00963˚C) for vapor, 273.1633˚K (0.0133˚C) for ice, 0.00365 in/s for atmospheric dryness, 1.996 in<sup>2</sup>/s for humidity, 2.993 in<sup>2</sup>/s for air, 1 J for thermal energy of fire, and 0.9963 J for heat. In summary, this study aims to define the main parameters and natural phenomena contributing to the modification of planetary climate. .
基金supported by the KIZ-CUHK Joint Lab of Bioresources and Molecular Research of Common Diseases(4750378)the VC Discretionary Fund provided to the Hong Kong Branch of Chinese Academy of Science Center for Excellence in Animal Evolution and Genetics(Acc 8601011)partially by the State Key Laboratory CUHKJinan MOE Key Laboratory for Regenerative medicine(2622009)。
文摘Parkinson’s disease(PD)relates to defective mitochondrial quality control in the dopaminergic motor network.Genetic studies have revealed that PINK1 and Parkin mutations are indicative of a heightened propensity to PD onset,pinpointing mitophagy and inflammation as the culprit pathways involved in neuronal loss in the substantia nigra(SNpc).In a reciprocal manner,LRRK2 functions in the regulation of basal flux and inflammatory responses responsible for PINK1/Parkin-dependent mitophagy activation.Pharmacological intervention in these diseasemodifying pathways may facilitate the development of novel PD therapeutics,despite the current lack of an established drug evaluation model.As such,we reviewed the feasibility of employing the versatile global Pink1knockout(KO)rat model as a self-sufficient,spontaneous PD model for investigating both disease etiology and drug pharmacology.These rats retain clinical features encompassing basal mitophagic flux changes with PD progression.We demonstrate the versatility of this PD rat model based on the incorporation of additional experimental insults to recapitulate the proinflammatory responses observed in PD patients.
文摘Lie symmetry analysis is applied to a(3+1)-dimensional Virasoro integrable model and the corresponding similarity reduction equations are obtained with the different infinitesimal generators.Invariant solutions with arbitrary functions for the(3+1)-dimensional Virasoro integrable model,including the interaction solution between a kink and a soliton,the lump-type solution and periodic solutions,have been studied analytically and graphically.
基金The authors would like thank LI Renjiang and HU Bin from the China Three Gorges Corporation for providing many valuable suggestions for the establishment of the physical models.This work was supported by the National Natural Science Foundation of China(No.U23A2045)the China Three Gorges Corporation(YM(BHT)/(22)022)the Scientific Research Project of Chongqing Municipal Bureau of Planning and Natural Resources(Evaluation and Reinforcement Technology of Surge Disaster Caused by High and Steep Dangerous Rocks in Chongqing Reservoir Area of the Three Gorges Project,KJ-2023046).
文摘The impulse waves induced by large-reservoir landslides can be characterized by a low Froude number.However,systematic research on predictive models specifically targeting the initial primary wave is lacking.Taking the Shuipingzi 1#landslide that occurred in the Baihetan Reservoir area of the Jinsha River in China as an engineering example,this study established a large-scale physical model(with dimensions of 30 m×29 m×3.5 m at a scale of 1:150)and conducted scaled experiments on 3D landslide-induced impulse waves.During the process in which a sliding mass displaced and compressed a body of water to generate waves,the maximum initial wave amplitude was found to be positively correlated with the sliding velocity and the volume of the landslide.With the increase in the water depth,the wave amplitude initially increased and then decreased.The duration of pressure exertion by the sliding mass at its maximum velocity directly correlated with an elevated wave amplitude.Based on the theories of low-amplitude waves and energy conservation,while considering the energy conversion efficiency,a predictive model for the initial wave amplitude was derived.This model could fit and validate the functions of wavelength and wave velocity.The accuracy of the initial wave amplitude was verified using physical experiment data,with a prediction accuracy for the maximum initial wave amplitude reaching 90%.The conversion efficiency(η)directly determined the accuracy of the estimation formula.Under clear conditions for landslide-induced impulse wave generation,estimating the value ofηthrough analogy cases was feasible.This study has derived the landslide-induced impulse waves amplitude prediction formula from the standpoints of wave theory and energy conservation,with greater consideration given to the intrinsic characteristics in the formation process of landslide-induced impulse waves,thereby enhancing the applicability and extensibility of the formula.This can facilitate the development of empirical estimation methods for landslide-induced impulse waves toward universality.
基金supported by Warren Alpert Foundation and Houston Methodist Academic Institute Laboratory Operating Fund(to HLC).
文摘Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein function or structure,understanding their genetic basis is crucial for accurate diagnosis and targeted therapies.To investigate the underlying pathogenesis of these conditions,researchers often use non-mammalian model organisms,such as Drosophila(fruit flies),which is valued for their genetic manipulability,cost-efficiency,and preservation of genes and biological functions across evolutionary time.Genetic tools available in Drosophila,including CRISPR-Cas9,offer a means to manipulate gene expression,allowing for a deep exploration of the genetic underpinnings of rare neurological diseases.Drosophila boasts a versatile genetic toolkit,rapid generation turnover,and ease of large-scale experimentation,making it an invaluable resource for identifying potential drug candidates.Researchers can expose flies carrying disease-associated mutations to various compounds,rapidly pinpointing promising therapeutic agents for further investigation in mammalian models and,ultimately,clinical trials.In this comprehensive review,we explore rare neurological diseases where fly research has significantly contributed to our understanding of their genetic basis,pathophysiology,and potential therapeutic implications.We discuss rare diseases associated with both neuron-expressed and glial-expressed genes.Specific cases include mutations in CDK19 resulting in epilepsy and developmental delay,mutations in TIAM1 leading to a neurodevelopmental disorder with seizures and language delay,and mutations in IRF2BPL causing seizures,a neurodevelopmental disorder with regression,loss of speech,and abnormal movements.And we explore mutations in EMC1 related to cerebellar atrophy,visual impairment,psychomotor retardation,and gain-of-function mutations in ACOX1 causing Mitchell syndrome.Loss-of-function mutations in ACOX1 result in ACOX1 deficiency,characterized by very-long-chain fatty acid accumulation and glial degeneration.Notably,this review highlights how modeling these diseases in Drosophila has provided valuable insights into their pathophysiology,offering a platform for the rapid identification of potential therapeutic interventions.Rare neurological diseases involve a wide range of expression systems,and sometimes common phenotypes can be found among different genes that cause abnormalities in neurons or glia.Furthermore,mutations within the same gene may result in varying functional outcomes,such as complete loss of function,partial loss of function,or gain-of-function mutations.The phenotypes observed in patients can differ significantly,underscoring the complexity of these conditions.In conclusion,Drosophila represents an indispensable and cost-effective tool for investigating rare neurological diseases.By facilitating the modeling of these conditions,Drosophila contributes to a deeper understanding of their genetic basis,pathophysiology,and potential therapies.This approach accelerates the discovery of promising drug candidates,ultimately benefiting patients affected by these complex and understudied diseases.
文摘Background: Diabetes education is crucial in empowering persons with Type 1 diabetes (T1DM) and their families to properly manage the condition by providing comprehensive knowledge, tools, and support. It boosts one’s belief in their ability to succeed, encourages following medical advice, and adds to the general enhancement of health. Objective: This study is to investigate the effectiveness of diabetes education in empowering individuals with Type 1 Diabetes Mellitus (T1DM) and their families to effectively manage the condition. Furthermore, it strives to improve nursing care for families whose children have been diagnosed with Type 1 Diabetes Mellitus (T1DM). Design: This research study investigates the efficacy of diabetes education in empowering individuals with Type 1 Diabetes Mellitus (T1DM) and their families to effectively handle the condition. Materials and Methods: A systematic search was conducted between the years 2000 and 2022, utilizing the Medline and Google Scholar databases. The purpose of the search was to uncover relevant papers pertaining to diabetes education, management of Type 1 Diabetes Mellitus (T1DM), nurse care, and empowerment. The search focused on peer-reviewed research, clinical trials, and scholarly articles that evaluated the efficacy of diabetes education in empowering individuals and families. Results: Diabetes education is crucial for understanding and controlling T1DM. It includes personalized sessions, webinars, group classes, and clinics that provide customized therapies. Comprehensive education enhances glycemic control and family dynamics. Nevertheless, the implementation of diabetes education for families requires specific standards, especially in the field of nursing. Conclusion: Diabetes education is essential for effectively managing Type 1 Diabetes Mellitus (T1DM), providing patients and families with crucial knowledge, resources, and confidence. It encourages independence in-home care and provides explicit guidelines for diabetic nurses to improve nursing care.
