旨在构建尘螨诱导的特应性皮炎(atopic dermatitis, AD)小鼠模型和哮喘小鼠模型。本研究利用3种主要尘螨螨种(屋尘螨、粉尘螨、热带无爪螨)的主要变应原Der p 1、Der f 1、Blo t 5等比混合,分别诱导AD小鼠模型和哮喘小鼠模型,并通过皮...旨在构建尘螨诱导的特应性皮炎(atopic dermatitis, AD)小鼠模型和哮喘小鼠模型。本研究利用3种主要尘螨螨种(屋尘螨、粉尘螨、热带无爪螨)的主要变应原Der p 1、Der f 1、Blo t 5等比混合,分别诱导AD小鼠模型和哮喘小鼠模型,并通过皮肤及肺组织的相关炎症细胞因子水平(IFN-γ、IL-4、IL-10、IL-17A)、血清总IgE水平等指标对AD小鼠的过敏程度进行评估;通过IgE水平、耳朵点刺试验、肺部组织苏木精-伊红染色(hematoxylin-eosin staining, HE)等指标评估哮喘小鼠模型。结果表明,AD模型中致敏区域皮肤出现破损后结痂现象,皮肤及肺组织中细胞因子水平的变化表明小鼠体内反应偏向Th2反应,IgE水平较正常组显著升高;哮喘模型组小鼠血清总IgE水平显著升高,变应原激发后模型小鼠体温下降明显,且90 min后仍未恢复初始温度,耳朵点刺试验中,抗原的攻击使模型组小鼠耳朵染料渗漏增加,肺组织HE染色显示模型组小鼠炎症细胞浸润增加。本研究成功诱导尘螨AD小鼠模型和尘螨哮喘小鼠模型。展开更多
旨在预防猫、犬诱导的过敏反应,本研究将猫主要变应原Fel d 1与犬主要变应原Can f 1融合原核表达,纯化制备了rFel d 1-Can f 1融合变应原。将层状双氢氧化物(layered double hydroxides,LDH)与rFel d 1-Can f 1混合,制备LDH-rFel d 1-Ca...旨在预防猫、犬诱导的过敏反应,本研究将猫主要变应原Fel d 1与犬主要变应原Can f 1融合原核表达,纯化制备了rFel d 1-Can f 1融合变应原。将层状双氢氧化物(layered double hydroxides,LDH)与rFel d 1-Can f 1混合,制备LDH-rFel d 1-Can f 1,皮下注射法免疫BALB/c小鼠,随后利用rFel d 1-Can f 1融合变应原诱导过敏小鼠模型,通过检测小鼠应激性过敏反应的体温变化、耳朵点刺试验、肺部组织切片HE染色、血清IgE水平等指标评价LDH-rFel d 1-Can f 1对猫犬诱发过敏反应的预防效果。研究表明,LDH与rFel d 1-Can f 1质量比为7∶1时,LDH可以完全吸附rFel d 1-Can f 1融合蛋白。LDH-rFel d 1-Can f 1可以有效缓解应激性过敏反应引起的小鼠体温下降,显著减少过敏导致的染料渗透面积。肺部组织切片HE染色结果显示,LDH-rFel d 1-Can f 1可以缓解过敏引起的炎症细胞浸润。此外,LDH-rFel d 1-Can f 1免疫后可以诱导小鼠产生较高水平IgG,这为开发抑制宠物猫犬诱发过敏反应的疫苗奠定基础。展开更多
为构建可靠、稳定的过敏性哮喘小鼠模型,选取12只5周龄雌性BALB/c小鼠,随机分为模型组和对照组,每组6只。模型组每只小鼠腹腔注射100μL的1 g·L^(-1)猫、犬融合变应原Fel d 1-Can f 1/氢氧化铝复合物致敏,并经气管注入100μL的1 g&...为构建可靠、稳定的过敏性哮喘小鼠模型,选取12只5周龄雌性BALB/c小鼠,随机分为模型组和对照组,每组6只。模型组每只小鼠腹腔注射100μL的1 g·L^(-1)猫、犬融合变应原Fel d 1-Can f 1/氢氧化铝复合物致敏,并经气管注入100μL的1 g·L^(-1)猫、犬融合变应原Fel d 1-Can f 1激发,对照组给予等体积PBS(pH=7.4)。检测血清特异性IgE水平、气道反应性水平、变应原诱发应激性过敏反应、耳朵点刺试验、肺部组织炎症浸润程度、肺部组织多黏液杯状细胞数和胶原纤维沉积程度等多个指标,以判断过敏性哮喘模型是否构建成功。结果表明,与对照组相比,经Fel d 1-Can f 1诱导的小鼠血清特异性IgE水平显著上升,气道反应性显著增高,变应原诱发体温下降明显,耳朵染料渗漏面积增大,渗漏净强度显著增强,肺部炎症浸润显著增加,多黏液杯状细胞数增加,胶原纤维沉积程度加重。综上所述,本研究成功构建过敏性哮喘小鼠模型,可为猫、犬过敏防治型疫苗的开发及评价提供模型条件。展开更多
With the rapid growth of global air traffic,flight delays are increasingly serious.Convective weather is one of the influential causes for flight delays,which has affected the sustainable development of civil aviation...With the rapid growth of global air traffic,flight delays are increasingly serious.Convective weather is one of the influential causes for flight delays,which has affected the sustainable development of civil aviation industry and became a social problem.If it can be predicted that whether a weather-related flight diverts,participants in air traffic activities can coordinate the scheduling,and flight delays can be reduced greatly.In this paper,the weather avoidance prediction model(WAPM)is proposed to find the relationship between weather and flight trajectories,and predict whether a future flight diverts based on historical flight data.First,given the large amount of weather data,the principal component analysis is used to reduce the ten dimensional weather indicators to extract 90%information.Second,the support vector machine is adopted to predict whether the flight diverts by determining the hyperparameters c and γ of the radial basis function.Finally,the performance of the proposed model is evaluated by prediction accuracy,precision,recall and F1,and compared with the methods of the k nearest neighbor(kNN),the logistic regression(LR),the random forest(RF)and the deep neural networks(DNNs).WAPM’s accuracy is 5.22%,2.63%,2.26%and 1.03%greater than those of kNN,LR,RF and DNNs,respectively;WAPM’s precision is 6.79%,5.19%,4.37%and 3.21%greater than those of kNN,LR,RF and DNNs,respectively;WAPM’s recall is 4.05%,1.05%,0.04%greater than those of kNN,LR,and RF,respectively,and 1.38%lower than that of the DNNs;and F1 of WAPM is 5.28%,1.69%,1.98%and 0.68%greater than those of kNN,LR,RF and DNNs,respectively.展开更多
目的 采用“分子对接-分子动力学-体外药理学”研究方法筛选并优化阻断程序性细胞死亡蛋白1/程序性细胞死亡配体1(programmed cell death protein 1/programmed death-ligand 1, PD-1/PD-L1)结合,获得具有较高抗肿瘤活性的多肽小分子化...目的 采用“分子对接-分子动力学-体外药理学”研究方法筛选并优化阻断程序性细胞死亡蛋白1/程序性细胞死亡配体1(programmed cell death protein 1/programmed death-ligand 1, PD-1/PD-L1)结合,获得具有较高抗肿瘤活性的多肽小分子化合物。方法 利用本团队构建的5肽化合物数据库,以及从蛋白质数据库(protein data bank, PDB)中下载的PD-L1蛋白质三维结构数据,采用Molecular Operating Environment软件进行柔性分子对接得到多肽化合物;对其中GWVI/WSA(generalized Born volume integral/weighted surface area)自由能变化值(ΔG)排名最高的化合物分子进行分子动力学计算分析,包括配体重原子位置变动的均方根偏差(root mean square error, RMSD)以及相互作用能[为兰纳-琼斯势能(Lennard-Jones potential)与库伦势能(Coulombic energy)之和]。通过均相时间分辨荧光(homogeneous time-resolved fluorescence, HTRF)技术分析配体化合物对PD-1/PD-L1相互结合的阻断作用,建立Jurkat T淋巴细胞与黑色素瘤B16-F10细胞的共培养体系,探索化合物配体对T细胞杀伤肿瘤作用的影响以及对共培养上清液中IL-2分泌水平的影响。结果 在筛选的多肽化合物中,RGGHA与RGGHH与PD-L1的结合更为稳定,其中RGGHA与PD-L1存在多种相互作用力,与PD-1竞争性结合PD-L1的Asp122、Try123、Lys124等位点阻断PD-1/PD-L1信号转导。HTRF实验表明,RGGHA对PD-1和PD-L1结合抑制率为58.38%,RGGHH为42.73%。此外,在共培养体系中,RGGHA与RGGHH能够显著增加IL-2的分泌水平,提高T细胞对于肿瘤细胞的杀伤能力,激活肿瘤免疫微环境。结论 研究发现多肽化合物RGGHA与RGGHH可以有效阻断PD-1/PD-L1相互作用,重新激活有利于抗癌的免疫反应,可以将其作为先导化合物用于新药研发。展开更多
文摘旨在构建尘螨诱导的特应性皮炎(atopic dermatitis, AD)小鼠模型和哮喘小鼠模型。本研究利用3种主要尘螨螨种(屋尘螨、粉尘螨、热带无爪螨)的主要变应原Der p 1、Der f 1、Blo t 5等比混合,分别诱导AD小鼠模型和哮喘小鼠模型,并通过皮肤及肺组织的相关炎症细胞因子水平(IFN-γ、IL-4、IL-10、IL-17A)、血清总IgE水平等指标对AD小鼠的过敏程度进行评估;通过IgE水平、耳朵点刺试验、肺部组织苏木精-伊红染色(hematoxylin-eosin staining, HE)等指标评估哮喘小鼠模型。结果表明,AD模型中致敏区域皮肤出现破损后结痂现象,皮肤及肺组织中细胞因子水平的变化表明小鼠体内反应偏向Th2反应,IgE水平较正常组显著升高;哮喘模型组小鼠血清总IgE水平显著升高,变应原激发后模型小鼠体温下降明显,且90 min后仍未恢复初始温度,耳朵点刺试验中,抗原的攻击使模型组小鼠耳朵染料渗漏增加,肺组织HE染色显示模型组小鼠炎症细胞浸润增加。本研究成功诱导尘螨AD小鼠模型和尘螨哮喘小鼠模型。
文摘旨在预防猫、犬诱导的过敏反应,本研究将猫主要变应原Fel d 1与犬主要变应原Can f 1融合原核表达,纯化制备了rFel d 1-Can f 1融合变应原。将层状双氢氧化物(layered double hydroxides,LDH)与rFel d 1-Can f 1混合,制备LDH-rFel d 1-Can f 1,皮下注射法免疫BALB/c小鼠,随后利用rFel d 1-Can f 1融合变应原诱导过敏小鼠模型,通过检测小鼠应激性过敏反应的体温变化、耳朵点刺试验、肺部组织切片HE染色、血清IgE水平等指标评价LDH-rFel d 1-Can f 1对猫犬诱发过敏反应的预防效果。研究表明,LDH与rFel d 1-Can f 1质量比为7∶1时,LDH可以完全吸附rFel d 1-Can f 1融合蛋白。LDH-rFel d 1-Can f 1可以有效缓解应激性过敏反应引起的小鼠体温下降,显著减少过敏导致的染料渗透面积。肺部组织切片HE染色结果显示,LDH-rFel d 1-Can f 1可以缓解过敏引起的炎症细胞浸润。此外,LDH-rFel d 1-Can f 1免疫后可以诱导小鼠产生较高水平IgG,这为开发抑制宠物猫犬诱发过敏反应的疫苗奠定基础。
文摘为构建可靠、稳定的过敏性哮喘小鼠模型,选取12只5周龄雌性BALB/c小鼠,随机分为模型组和对照组,每组6只。模型组每只小鼠腹腔注射100μL的1 g·L^(-1)猫、犬融合变应原Fel d 1-Can f 1/氢氧化铝复合物致敏,并经气管注入100μL的1 g·L^(-1)猫、犬融合变应原Fel d 1-Can f 1激发,对照组给予等体积PBS(pH=7.4)。检测血清特异性IgE水平、气道反应性水平、变应原诱发应激性过敏反应、耳朵点刺试验、肺部组织炎症浸润程度、肺部组织多黏液杯状细胞数和胶原纤维沉积程度等多个指标,以判断过敏性哮喘模型是否构建成功。结果表明,与对照组相比,经Fel d 1-Can f 1诱导的小鼠血清特异性IgE水平显著上升,气道反应性显著增高,变应原诱发体温下降明显,耳朵染料渗漏面积增大,渗漏净强度显著增强,肺部炎症浸润显著增加,多黏液杯状细胞数增加,胶原纤维沉积程度加重。综上所述,本研究成功构建过敏性哮喘小鼠模型,可为猫、犬过敏防治型疫苗的开发及评价提供模型条件。
基金supported by Nanjing University of Aeronautics and Astronautics Graduate Innovation Base(Laboratory)Open Fund(No.kfjj20200710).
文摘With the rapid growth of global air traffic,flight delays are increasingly serious.Convective weather is one of the influential causes for flight delays,which has affected the sustainable development of civil aviation industry and became a social problem.If it can be predicted that whether a weather-related flight diverts,participants in air traffic activities can coordinate the scheduling,and flight delays can be reduced greatly.In this paper,the weather avoidance prediction model(WAPM)is proposed to find the relationship between weather and flight trajectories,and predict whether a future flight diverts based on historical flight data.First,given the large amount of weather data,the principal component analysis is used to reduce the ten dimensional weather indicators to extract 90%information.Second,the support vector machine is adopted to predict whether the flight diverts by determining the hyperparameters c and γ of the radial basis function.Finally,the performance of the proposed model is evaluated by prediction accuracy,precision,recall and F1,and compared with the methods of the k nearest neighbor(kNN),the logistic regression(LR),the random forest(RF)and the deep neural networks(DNNs).WAPM’s accuracy is 5.22%,2.63%,2.26%and 1.03%greater than those of kNN,LR,RF and DNNs,respectively;WAPM’s precision is 6.79%,5.19%,4.37%and 3.21%greater than those of kNN,LR,RF and DNNs,respectively;WAPM’s recall is 4.05%,1.05%,0.04%greater than those of kNN,LR,and RF,respectively,and 1.38%lower than that of the DNNs;and F1 of WAPM is 5.28%,1.69%,1.98%and 0.68%greater than those of kNN,LR,RF and DNNs,respectively.
