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
α_(1)-Adrenergic receptor(AR)blockers can be effective for the treatment of benign prostatic hyperplasia/lower urinary tract symptoms(BPH/LUTS),their usage is limited by cardiovascular-related side effects that are c...α_(1)-Adrenergic receptor(AR)blockers can be effective for the treatment of benign prostatic hyperplasia/lower urinary tract symptoms(BPH/LUTS),their usage is limited by cardiovascular-related side effects that are caused by the subtype nonselective nature or low selectivity of many current drugs.We previously reported that phenylpiperazine analogues with amide and propane linker were moderateα_(1D/1A)adrenoceptor antagonists and exhibited better anti-BPH effect than lead compound naftopidil(NAF)in vivo,however,with modestα_(1D/1A)-subtype selectivity.Herein,we replaced propane moiety with2-hydroxypropanol linker and synthesized twenty-seven racemic derivatives with modified aromatic and hetero aromatic groups.Of these new compounds,quinoline surrogate 17 exhibited extremely weak antagonistic affinity onα_(1B)in both cell-based calcium assay and tissue-based functional assay,so that elicited significantα_(1A/1B)andα_(1D/1B)selectivity.Intriguingly,the R enantiomer of 17 preferentially displayed superior anti-BPH effect in rat model compared with S-17,supporting ligand regulates the receptor in a highly stereospecific manner.Finally,the computer-aided modelling research was also performed in order to deeply understand the unique binding mode of R-17 in complex withα_(1A)and the subtype receptor selectivity for R-17 was also rationalized in this study.Taken together,our work enriched the diversity of phenylpiperazines for the treatment of BPH/LUTS,and provided a basis for discovery ofα_(1D/1A)-selective ligands.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
We estimate tree heights using polarimetric interferometric synthetic aperture radar(PolInSAR)data constructed by the dual-polarization(dual-pol)SAR data and random volume over the ground(RVoG)model.Considering the Se...We estimate tree heights using polarimetric interferometric synthetic aperture radar(PolInSAR)data constructed by the dual-polarization(dual-pol)SAR data and random volume over the ground(RVoG)model.Considering the Sentinel-1 SAR dual-pol(SVV,vertically transmitted and vertically received and SVH,vertically transmitted and horizontally received)configuration,one notes that S_(HH),the horizontally transmitted and horizontally received scattering element,is unavailable.The S_(HH)data were constructed using the SVH data,and polarimetric SAR(PolSAR)data were obtained.The proposed approach was first verified in simulation with satisfactory results.It was next applied to construct PolInSAR data by a pair of dual-pol Sentinel-1A data at Duke Forest,North Carolina,USA.According to local observations and forest descriptions,the range of estimated tree heights was overall reasonable.Comparing the heights with the ICESat-2 tree heights at 23 sampling locations,relative errors of 5 points were within±30%.Errors of 8 points ranged from 30%to 40%,but errors of the remaining 10 points were>40%.The results should be encouraged as error reduction is possible.For instance,the construction of PolSAR data should not be limited to using SVH,and a combination of SVH and SVV should be explored.Also,an ensemble of tree heights derived from multiple PolInSAR data can be considered since tree heights do not vary much with time frame in months or one season.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
In the R&D phase of Gravity-1(YL-1), a multi-domain modeling and simulation technology based on Modelica language was introduced, which was a recent attempt in the practice of modeling and simulation method for la...In the R&D phase of Gravity-1(YL-1), a multi-domain modeling and simulation technology based on Modelica language was introduced, which was a recent attempt in the practice of modeling and simulation method for launch vehicles in China. It realizes a complex coupling model within a unified model for different domains, so that technologists can work on one model. It ensured the success of YL-1 first launch mission, supports rapid iteration, full validation, and tight design collaboration.展开更多
目的研究以专科护士为主导的“1+1+X”协同管理模式对稳定型心绞痛患者病情、自我管理能力的影响。方法方便选取2021年3月—2023年3月聊城市第二人民医院心血管内科收治的86例稳定型心绞痛患者为研究对象,根据不同护理方法分为常规组和...目的研究以专科护士为主导的“1+1+X”协同管理模式对稳定型心绞痛患者病情、自我管理能力的影响。方法方便选取2021年3月—2023年3月聊城市第二人民医院心血管内科收治的86例稳定型心绞痛患者为研究对象,根据不同护理方法分为常规组和协同管理组,各43例。常规组采用常规护理,协同管理组采用以专科护士为主导的“1+1+X”协同管理模式护理,两组均持续护理1个月。观察对比两组患者护理前后生活质量[健康调查简表(MOS Item Short Form Health Survey,SF-36)]、焦虑抑郁心理状况、自我管理能力[冠心病自我管理行为量表(Coronary Artery Disease Self-management Scale,CSMS)]。结果护理后,协同管理组SF-36量表评分高于常规组,差异有统计学意义(P<0.05);协同管理组焦虑自评量表(38.18±3.52)分、抑郁自评量表(39.21±3.24)分均优于常规组的(43.23±3.61)分、(45.03±3.69)分,差异有统计学意义(t=6.568、7.772,P均<0.05);协同管理组CSMS评分高于常规组,差异有统计学意义(P均<0.05)。结论以专科护士为主导的“1+1+X”协同管理模式应用于稳定型心绞痛患者护理可有效提升生活质量,改善不良心理状态,提高自我管理能力。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
The gray renewal GM (1,1) landslide prediction model was established by improving the gray model. Based on the established model, the author has made prediction of landslide deformation to the Xiangjiapo landslide and...The gray renewal GM (1,1) landslide prediction model was established by improving the gray model. Based on the established model, the author has made prediction of landslide deformation to the Xiangjiapo landslide and the Lianziya dangerous rock body. The results show that the gray renewal GM (1,1) model can supplement the new information in time and remove the old information which reduces the meaning of the information because of time lapse. Therefore, the model is closer to reality.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.
基金supported by Natural Science Foundation of Guangdong Province(Nos.2021A1515010101,2021A1515011372,2023A1515011895)National Natural Science Foundation of China(Nos.21807017,82273759,32371529)Guangzhou Medical University Scientific Research Capacity Improvement Project(No.02-410-2405104)。
文摘α_(1)-Adrenergic receptor(AR)blockers can be effective for the treatment of benign prostatic hyperplasia/lower urinary tract symptoms(BPH/LUTS),their usage is limited by cardiovascular-related side effects that are caused by the subtype nonselective nature or low selectivity of many current drugs.We previously reported that phenylpiperazine analogues with amide and propane linker were moderateα_(1D/1A)adrenoceptor antagonists and exhibited better anti-BPH effect than lead compound naftopidil(NAF)in vivo,however,with modestα_(1D/1A)-subtype selectivity.Herein,we replaced propane moiety with2-hydroxypropanol linker and synthesized twenty-seven racemic derivatives with modified aromatic and hetero aromatic groups.Of these new compounds,quinoline surrogate 17 exhibited extremely weak antagonistic affinity onα_(1B)in both cell-based calcium assay and tissue-based functional assay,so that elicited significantα_(1A/1B)andα_(1D/1B)selectivity.Intriguingly,the R enantiomer of 17 preferentially displayed superior anti-BPH effect in rat model compared with S-17,supporting ligand regulates the receptor in a highly stereospecific manner.Finally,the computer-aided modelling research was also performed in order to deeply understand the unique binding mode of R-17 in complex withα_(1A)and the subtype receptor selectivity for R-17 was also rationalized in this study.Taken together,our work enriched the diversity of phenylpiperazines for the treatment of BPH/LUTS,and provided a basis for discovery ofα_(1D/1A)-selective ligands.
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We estimate tree heights using polarimetric interferometric synthetic aperture radar(PolInSAR)data constructed by the dual-polarization(dual-pol)SAR data and random volume over the ground(RVoG)model.Considering the Sentinel-1 SAR dual-pol(SVV,vertically transmitted and vertically received and SVH,vertically transmitted and horizontally received)configuration,one notes that S_(HH),the horizontally transmitted and horizontally received scattering element,is unavailable.The S_(HH)data were constructed using the SVH data,and polarimetric SAR(PolSAR)data were obtained.The proposed approach was first verified in simulation with satisfactory results.It was next applied to construct PolInSAR data by a pair of dual-pol Sentinel-1A data at Duke Forest,North Carolina,USA.According to local observations and forest descriptions,the range of estimated tree heights was overall reasonable.Comparing the heights with the ICESat-2 tree heights at 23 sampling locations,relative errors of 5 points were within±30%.Errors of 8 points ranged from 30%to 40%,but errors of the remaining 10 points were>40%.The results should be encouraged as error reduction is possible.For instance,the construction of PolSAR data should not be limited to using SVH,and a combination of SVH and SVV should be explored.Also,an ensemble of tree heights derived from multiple PolInSAR data can be considered since tree heights do not vary much with time frame in months or one season.
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. .
文摘In the R&D phase of Gravity-1(YL-1), a multi-domain modeling and simulation technology based on Modelica language was introduced, which was a recent attempt in the practice of modeling and simulation method for launch vehicles in China. It realizes a complex coupling model within a unified model for different domains, so that technologists can work on one model. It ensured the success of YL-1 first launch mission, supports rapid iteration, full validation, and tight design collaboration.
文摘目的研究以专科护士为主导的“1+1+X”协同管理模式对稳定型心绞痛患者病情、自我管理能力的影响。方法方便选取2021年3月—2023年3月聊城市第二人民医院心血管内科收治的86例稳定型心绞痛患者为研究对象,根据不同护理方法分为常规组和协同管理组,各43例。常规组采用常规护理,协同管理组采用以专科护士为主导的“1+1+X”协同管理模式护理,两组均持续护理1个月。观察对比两组患者护理前后生活质量[健康调查简表(MOS Item Short Form Health Survey,SF-36)]、焦虑抑郁心理状况、自我管理能力[冠心病自我管理行为量表(Coronary Artery Disease Self-management Scale,CSMS)]。结果护理后,协同管理组SF-36量表评分高于常规组,差异有统计学意义(P<0.05);协同管理组焦虑自评量表(38.18±3.52)分、抑郁自评量表(39.21±3.24)分均优于常规组的(43.23±3.61)分、(45.03±3.69)分,差异有统计学意义(t=6.568、7.772,P均<0.05);协同管理组CSMS评分高于常规组,差异有统计学意义(P均<0.05)。结论以专科护士为主导的“1+1+X”协同管理模式应用于稳定型心绞痛患者护理可有效提升生活质量,改善不良心理状态,提高自我管理能力。
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The gray renewal GM (1,1) landslide prediction model was established by improving the gray model. Based on the established model, the author has made prediction of landslide deformation to the Xiangjiapo landslide and the Lianziya dangerous rock body. The results show that the gray renewal GM (1,1) model can supplement the new information in time and remove the old information which reduces the meaning of the information because of time lapse. Therefore, the model is closer to reality.
