Background:In recent decades,the global incidence of dengue fever has been stead-ily increasing,with continuous geographical expansion.Researchers have successfully modeled most clinical symptoms of human dengue fever...Background:In recent decades,the global incidence of dengue fever has been stead-ily increasing,with continuous geographical expansion.Researchers have successfully modeled most clinical symptoms of human dengue fever using interferon type I(IFN-I)or combined IFN-I/II receptor knockout mice infected with dengue virus(DENV).However,this model requires further optimization to better support related studies.Methods:This study aimed to establish a stable dengue infection model by evaluating the effects of different genetic backgrounds and injection routes on DENV infection in interferon receptor knockout mice.We first infected various strains of interferon receptor-deficient mice with DENV and compared their susceptibility based on clini-cal symptoms,viremia levels,organ indices,histopathological findings,and vascular leakage markers.Subsequently,we selected the most susceptible strain to further investigate the impact of different injection methods on infection outcomes.Results:We found that BALB/c background mice with type 1 interferon recep-tor knockout(IFNAR)had the most obvious symptoms.Subsequently,we selected IFNAR−/−BALB/c mice to further explore the effects of different injection methods on dengue virus infection.The results showed that the intraperitoneal injection group had the most severe clinical symptoms,the longest duration of viremia,and the most obvious degree of organ damage.Conclusion:Through systematic screening and optimization,we established a robust animal model of dengue virus infection via intraperitoneal injection in IFNAR−/−BALB/c mice.This model offers a valuable tool for future dengue research.展开更多
Alzheimer’s disease is initially thought to be caused by age-associated accumulation of plaques,in recent years,research has increasingly associated Alzheimer’s disease with lysosomal storage and metabolic disorders...Alzheimer’s disease is initially thought to be caused by age-associated accumulation of plaques,in recent years,research has increasingly associated Alzheimer’s disease with lysosomal storage and metabolic disorders,and the explanation of its pathogenesis has shifted from amyloid and tau accumulation to oxidative stress and impaired lipid and glucose metabolism aggravated by hypoxic conditions.However,the underlying mechanisms linking those cellular processes and conditions to disease progression have yet to be defined.Here,we applied a disease similarity approach to identify unknown molecular targets of Alzheimer’s disease by using transcriptomic data from congenital diseases known to increase Alzheimer’s disease risk,namely Down syndrome,Niemann-Pick type C disease,and mucopolysaccharidoses I.We uncovered common pathways,hub genes,and miRNAs across in vitro and in vivo models of these diseases as potential molecular targets for neuroprotection and amelioration of Alzheimer’s disease pathology,many of which have never been associated with Alzheimer’s disease.We then investigated common molecular alterations in brain samples from a Niemann-Pick type C disease mouse model by juxtaposing them with brain samples of both human and mouse models of Alzheimer’s disease.Detailed phenotypic,molecular,chronological,and biological aging analyses revealed that the Npc1tm(I1061T)Dso mouse model can serve as a potential short-lived in vivo model for brain aging and Alzheimer’s disease research.This research represents the first comprehensive approach to congenital disease association with neurodegeneration and a new perspective on Alzheimer’s disease research while highlighting shortcomings and lack of correlation in diverse in vitro models.Considering the lack of an Alzheimer’s disease mouse model that recapitulates the physiological hallmarks of brain aging,the short-lived Npc1^(tm(I1061T)Dso) mouse model can further accelerate the research in these fields and offer a unique model for understanding the molecular mechanisms of Alzheimer’s disease from a perspective of accelerated brain aging.展开更多
Based on the data of daily precipitation in Lianyungang area from 1951 to 2012 and various climate signal data from the National Climate Center website and the NOAA website,a model for predicting whether the number of...Based on the data of daily precipitation in Lianyungang area from 1951 to 2012 and various climate signal data from the National Climate Center website and the NOAA website,a model for predicting whether the number of rainstorm days in summer in Lianyungang area is large was established by the classical C5. 0 decision tree algorithm. The data samples in 48 years( accounting for about 80% of total number of samples)was as the training set of a model,and the training accuracy rate of the model was 95. 83%. The data samples in the remaining 14 years( accounting for about 20% of total number of samples) were used as the test set of the model to test the model,and the test accuracy of the model was 85. 71%. The results showed that the prediction model of number of rainstorm days in summer constructed by C5. 0 algorithm had high accuracy and was easy to explain. Moreover,it is convenient for meteorological staff to use directly. At the same time,this study provides a new idea for short-term climate prediction of number of rainstorm days in summer.展开更多
Bacckground:Based on the 3C model,this study explores the current situation of HPV vaccine hesitancy among women of childbearing age and the factors influencing vaccine hesitancy.Methods:Based on the free cervical can...Bacckground:Based on the 3C model,this study explores the current situation of HPV vaccine hesitancy among women of childbearing age and the factors influencing vaccine hesitancy.Methods:Based on the free cervical cancer screening project in Baoan District,this study designed a questionnaire under the framework of vaccine hesitation 3C theory and carried out a self-filling electronic questionnaire survey among women of childbearing age.Results:The rate of HPV vaccination awareness among women of childbearing age in Bao’an District was 93.25%.HPV vaccine acceptance reached 71.55%,and 24.59%of the survey respondents experienced HPV vaccine hesitation,a high percentage of whom were hesitant.The influencing factors of HPV vaccine hesitation among women of childbearing age were perceived necessity of HPV vaccination(0.482),no one around them receiving the HPV vaccine(0.411),perception of the price of the vaccine(0.354),degree of trust in the safety of the vaccine(0.223),and degree of concern about the HPV vaccine(0.153).Conclusion:The 3C model can be used for the study of HPV vaccine hesitancy.Strengthening the publicity of HPV vaccination and improving women’s knowledge of the HPV vaccine can reduce their hesitation toward HPV vaccination.展开更多
With the widespread application of large language models(LLMs)in natural language processing and code generation,traditional High-Level Language Programming courses are facing unprecedented challenges and opportunitie...With the widespread application of large language models(LLMs)in natural language processing and code generation,traditional High-Level Language Programming courses are facing unprecedented challenges and opportunities.As a core programming language for computer science majors,C language remains irreplaceable due to its foundational nature and engineering adaptability.This paper,based on the rapid development of large model technologies,proposes a systematic reform design for C language teaching,focusing on teaching objectives,content structure,teaching methods,and evaluation systems.The article suggests a teaching framework centered on“human-computer collaborative programming,”integrating prompt training,AI-assisted debugging,and code generation analysis,aiming to enhance students’problem modeling ability,programming expression skills,and AI collaboration literacy.展开更多
Background:The precise insertion of large DNA fragments(>3–5 kb)remains one of the key obstacles in establishment of genetically modified murine models.Methods:A 21 kb large DNA fragment containing three tandemly ...Background:The precise insertion of large DNA fragments(>3–5 kb)remains one of the key obstacles in establishment of genetically modified murine models.Methods:A 21 kb large DNA fragment containing three tandemly linked copies of the human HRAS gene was inserted into the genome of C57BL/6J mouse,generating a mouse model designated as KI.C57-ras(or named NF-h HRAS).Whole-genome sequencing and Sanger sequencing were utilized to it confirm precise insertion and copy number.The stability of transgene expression among different generations was verified from multiple aspects using by digital PCR,western blot and DNA sequencing.To assess tumor susceptibility in the mouse model,N-Nitroso-N-methylurea(MNU)was administered at a dosage of 75 mg/kg.Histopathological examinations were conducted using hematoxylin and eosin(H&E)staining.Results:The HRAS DNA fragment was inserted into mouse chromosome 15E1 site,locating between 80623202 bp and 80625020 bp.NF-h HRAS mice exhibited stable inheritance and displayed consistent phenotypes across individuals.Moreover,this mouse model exhibited a high susceptibility to carcinogens.Upon administration of MNU the earliest mortality onset was earlier than that of wild-type littermates(day 65 vs.day 78 for male and day 56 vs.day 84 for female).Notably,100%of the NF-h HRAS transgenic mice developed tumors,with approximately 84%of male NF-h HRAS mice exhibiting specific tumor types,such as squamous cell carcinoma or squamous cell papilloma,which was consistent with the previously reported carcinogenic rasH2 mouse model.The types of tumors and the target organs exhibited diversity in NFh HRAS mice,while the spontaneous tumor incidence remained low(1/50).Conclusions:The NF-h HRAS mice demonstrated excellent genetic stability,a reproducible phenotype,and high susceptibility to carcinogens,indicating their potential utility in non-clinical safety evaluations of drugs as per the S1B guidelines issued by the ICH(The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use).展开更多
使用医疗信息系统的数据进行睡眠呼吸暂停低通气综合征(OSAHS)预测和分析过程中,存在不平衡数据问题。为此,在现有临床研究的基础上,提出了一种基于ROSE(Random Over Sampling Examples)和C5.0算法的初筛模型。利用收集到的人体测量学...使用医疗信息系统的数据进行睡眠呼吸暂停低通气综合征(OSAHS)预测和分析过程中,存在不平衡数据问题。为此,在现有临床研究的基础上,提出了一种基于ROSE(Random Over Sampling Examples)和C5.0算法的初筛模型。利用收集到的人体测量学指标数据,通过数据预处理,删除异常值并填补缺失值。然后采用ROSE算法对数据进行平衡,利用C5.0分类器对平衡后的数据构建筛查模型,通过十则交叉验证的方法检验模型的筛查效果。实验结果表明,使用该模型进行打鼾患者的OSAHS筛查,可以有效地提高筛查效率。展开更多
基金Guangdong Province Medical Research Fund Project,Grant/Award Number:B2024112The Scientific Research Special Project of the Joint Construction Project of High-level Hospitals between Guangzhou University of Chinese Medicine and the Scientific Research Fund Project,Grant/Award Number:GZYZS2024G09+2 种基金Special Project of the Research Platform of Guangdong Provincial Department of Traditional Chinese Medicine,Grant/Award Number:20254040the Project of the Incubation Program for the Science and Technology Development of Chinese Medicine Guangdong Laboratory/Hengqin Laboratory,Grant/Award Number:HQL2024PZ043Guangdong Province Natural Science Foundation-Guangzhou-South China Joint Youth Fund Project,Grant/Award Number:2023A1515110849。
文摘Background:In recent decades,the global incidence of dengue fever has been stead-ily increasing,with continuous geographical expansion.Researchers have successfully modeled most clinical symptoms of human dengue fever using interferon type I(IFN-I)or combined IFN-I/II receptor knockout mice infected with dengue virus(DENV).However,this model requires further optimization to better support related studies.Methods:This study aimed to establish a stable dengue infection model by evaluating the effects of different genetic backgrounds and injection routes on DENV infection in interferon receptor knockout mice.We first infected various strains of interferon receptor-deficient mice with DENV and compared their susceptibility based on clini-cal symptoms,viremia levels,organ indices,histopathological findings,and vascular leakage markers.Subsequently,we selected the most susceptible strain to further investigate the impact of different injection methods on infection outcomes.Results:We found that BALB/c background mice with type 1 interferon recep-tor knockout(IFNAR)had the most obvious symptoms.Subsequently,we selected IFNAR−/−BALB/c mice to further explore the effects of different injection methods on dengue virus infection.The results showed that the intraperitoneal injection group had the most severe clinical symptoms,the longest duration of viremia,and the most obvious degree of organ damage.Conclusion:Through systematic screening and optimization,we established a robust animal model of dengue virus infection via intraperitoneal injection in IFNAR−/−BALB/c mice.This model offers a valuable tool for future dengue research.
基金supported by the NIA/NIH(1K01AG060040).Studies performed by JN were funded by the NICHD/NIH(5R00HD096117)Microscopy Core Facility supported,in part,with funding from NIH-NCI Cancer Center Support Grant P30 CA016059.
文摘Alzheimer’s disease is initially thought to be caused by age-associated accumulation of plaques,in recent years,research has increasingly associated Alzheimer’s disease with lysosomal storage and metabolic disorders,and the explanation of its pathogenesis has shifted from amyloid and tau accumulation to oxidative stress and impaired lipid and glucose metabolism aggravated by hypoxic conditions.However,the underlying mechanisms linking those cellular processes and conditions to disease progression have yet to be defined.Here,we applied a disease similarity approach to identify unknown molecular targets of Alzheimer’s disease by using transcriptomic data from congenital diseases known to increase Alzheimer’s disease risk,namely Down syndrome,Niemann-Pick type C disease,and mucopolysaccharidoses I.We uncovered common pathways,hub genes,and miRNAs across in vitro and in vivo models of these diseases as potential molecular targets for neuroprotection and amelioration of Alzheimer’s disease pathology,many of which have never been associated with Alzheimer’s disease.We then investigated common molecular alterations in brain samples from a Niemann-Pick type C disease mouse model by juxtaposing them with brain samples of both human and mouse models of Alzheimer’s disease.Detailed phenotypic,molecular,chronological,and biological aging analyses revealed that the Npc1tm(I1061T)Dso mouse model can serve as a potential short-lived in vivo model for brain aging and Alzheimer’s disease research.This research represents the first comprehensive approach to congenital disease association with neurodegeneration and a new perspective on Alzheimer’s disease research while highlighting shortcomings and lack of correlation in diverse in vitro models.Considering the lack of an Alzheimer’s disease mouse model that recapitulates the physiological hallmarks of brain aging,the short-lived Npc1^(tm(I1061T)Dso) mouse model can further accelerate the research in these fields and offer a unique model for understanding the molecular mechanisms of Alzheimer’s disease from a perspective of accelerated brain aging.
基金Support by Meteorological Open Research Foundation for the Huaihe River Basin(HRM201602)Foundation for Young Scholars of Jiangsu Meteorological Bureau(Q201708,KQ201802)+2 种基金Science and Technology Innovation Team Foundation for Marine Meteorological Forecast Technology of Lianyungang Meteorological BureauKey Technology R&D Program Project of Lianyungang City(SH1634)Special Project for Forecasters of Jiangsu Meteorological Bureau(JSYBY201811,JSYBY201812,JSYBY201810)
文摘Based on the data of daily precipitation in Lianyungang area from 1951 to 2012 and various climate signal data from the National Climate Center website and the NOAA website,a model for predicting whether the number of rainstorm days in summer in Lianyungang area is large was established by the classical C5. 0 decision tree algorithm. The data samples in 48 years( accounting for about 80% of total number of samples)was as the training set of a model,and the training accuracy rate of the model was 95. 83%. The data samples in the remaining 14 years( accounting for about 20% of total number of samples) were used as the test set of the model to test the model,and the test accuracy of the model was 85. 71%. The results showed that the prediction model of number of rainstorm days in summer constructed by C5. 0 algorithm had high accuracy and was easy to explain. Moreover,it is convenient for meteorological staff to use directly. At the same time,this study provides a new idea for short-term climate prediction of number of rainstorm days in summer.
基金District of Medical and Health Research Project(2023JD212)Shenzhen Bao’an District of Traditional Chinese Medicine Clinical Research Project(2023ZYYLCZX-12)+2 种基金Shenzhen“Medical and Health Three Projects”Project Grant(SZZYSM 202106003)Weifang Health Committee Scientific Research Project(wfwsjk-2023-170)Shenzhen Pingshan District of Health System Research Project(2024334).
文摘Bacckground:Based on the 3C model,this study explores the current situation of HPV vaccine hesitancy among women of childbearing age and the factors influencing vaccine hesitancy.Methods:Based on the free cervical cancer screening project in Baoan District,this study designed a questionnaire under the framework of vaccine hesitation 3C theory and carried out a self-filling electronic questionnaire survey among women of childbearing age.Results:The rate of HPV vaccination awareness among women of childbearing age in Bao’an District was 93.25%.HPV vaccine acceptance reached 71.55%,and 24.59%of the survey respondents experienced HPV vaccine hesitation,a high percentage of whom were hesitant.The influencing factors of HPV vaccine hesitation among women of childbearing age were perceived necessity of HPV vaccination(0.482),no one around them receiving the HPV vaccine(0.411),perception of the price of the vaccine(0.354),degree of trust in the safety of the vaccine(0.223),and degree of concern about the HPV vaccine(0.153).Conclusion:The 3C model can be used for the study of HPV vaccine hesitancy.Strengthening the publicity of HPV vaccination and improving women’s knowledge of the HPV vaccine can reduce their hesitation toward HPV vaccination.
基金Education and Teaching Research Project of Beijing University of Technology(ER2024KCB08)。
文摘With the widespread application of large language models(LLMs)in natural language processing and code generation,traditional High-Level Language Programming courses are facing unprecedented challenges and opportunities.As a core programming language for computer science majors,C language remains irreplaceable due to its foundational nature and engineering adaptability.This paper,based on the rapid development of large model technologies,proposes a systematic reform design for C language teaching,focusing on teaching objectives,content structure,teaching methods,and evaluation systems.The article suggests a teaching framework centered on“human-computer collaborative programming,”integrating prompt training,AI-assisted debugging,and code generation analysis,aiming to enhance students’problem modeling ability,programming expression skills,and AI collaboration literacy.
基金National Key R&D Program of China,Grant/Award Number:2023YFC3402000National Institutes for Food and Drug Control,State Key Laboratory of Drug Regulatory Science,Grant/Award Number:2023SKLDRS0124。
文摘Background:The precise insertion of large DNA fragments(>3–5 kb)remains one of the key obstacles in establishment of genetically modified murine models.Methods:A 21 kb large DNA fragment containing three tandemly linked copies of the human HRAS gene was inserted into the genome of C57BL/6J mouse,generating a mouse model designated as KI.C57-ras(or named NF-h HRAS).Whole-genome sequencing and Sanger sequencing were utilized to it confirm precise insertion and copy number.The stability of transgene expression among different generations was verified from multiple aspects using by digital PCR,western blot and DNA sequencing.To assess tumor susceptibility in the mouse model,N-Nitroso-N-methylurea(MNU)was administered at a dosage of 75 mg/kg.Histopathological examinations were conducted using hematoxylin and eosin(H&E)staining.Results:The HRAS DNA fragment was inserted into mouse chromosome 15E1 site,locating between 80623202 bp and 80625020 bp.NF-h HRAS mice exhibited stable inheritance and displayed consistent phenotypes across individuals.Moreover,this mouse model exhibited a high susceptibility to carcinogens.Upon administration of MNU the earliest mortality onset was earlier than that of wild-type littermates(day 65 vs.day 78 for male and day 56 vs.day 84 for female).Notably,100%of the NF-h HRAS transgenic mice developed tumors,with approximately 84%of male NF-h HRAS mice exhibiting specific tumor types,such as squamous cell carcinoma or squamous cell papilloma,which was consistent with the previously reported carcinogenic rasH2 mouse model.The types of tumors and the target organs exhibited diversity in NFh HRAS mice,while the spontaneous tumor incidence remained low(1/50).Conclusions:The NF-h HRAS mice demonstrated excellent genetic stability,a reproducible phenotype,and high susceptibility to carcinogens,indicating their potential utility in non-clinical safety evaluations of drugs as per the S1B guidelines issued by the ICH(The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use).
文摘使用医疗信息系统的数据进行睡眠呼吸暂停低通气综合征(OSAHS)预测和分析过程中,存在不平衡数据问题。为此,在现有临床研究的基础上,提出了一种基于ROSE(Random Over Sampling Examples)和C5.0算法的初筛模型。利用收集到的人体测量学指标数据,通过数据预处理,删除异常值并填补缺失值。然后采用ROSE算法对数据进行平衡,利用C5.0分类器对平衡后的数据构建筛查模型,通过十则交叉验证的方法检验模型的筛查效果。实验结果表明,使用该模型进行打鼾患者的OSAHS筛查,可以有效地提高筛查效率。
