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Endothelial phosphodiesterase 4B inactivation ameliorates endothelial-to-mesenchymal transition and pulmonary hypertension

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1726-1741页

作者： Yanjiang Xing Yangfeng Hou Tianfei Fan Ran Gao Xiaohang Feng bolun li Junling Pang Wenjun Guo Ting Shu Jinqiu li Jie Yang Qilong Mao Ya Luo Xianmei Qi Peiran Yang Chaoyang liang Hongmei Zhao Wenhui Chen Jing Wang Chen Wang State Key Laboratory of Respiratory Health and Multimorbidity Institute of Basic Medical SciencesChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100005China Department of Lung Transplantation National Center for Respiratory MedicineNational Clinical Research Center for Respiratory DiseasesChina–Japan Friendship HospitalInstitute of Respiratory MedicineChinese Academy of Medical SciencesBeijing 100029China Haihe Laboratory of Cell Ecosystem Chinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin 300051China The State Key Laboratory of Complex Severeand Rare DiseasesInstitute of Basic Medical SciencesChinese Academy of Medical SciencesDepartment of PathophysiologyPeking Union Medical CollegeBeijing 100005China Department of Pharmacy West China HospitalSichuan UniversityChengdu 610044China

Pulmonary hypertension (PH) is a fatal disorder characterized by pulmonary vascular remodeling and obstruction. The phosphodiesterase 4 (PDE4) family hydrolyzes cyclic AMP (cAMP) and is comprised of four subtypes (PDE4A–D). Previous studies have shown the beneficial effects of pan-PDE4 inhibitors in rodent PH;however, this class of drugs is associated with side effects owing to the broad inhibition of all four PDE4 isozymes. Here, we demonstrate that PDE4B is the predominant PDE isozyme in lungs and that it was upregulated in rodent and human PH lung tissues. We also confirmed that PDE4B is mainly expressed in the lung endothelial cells (ECs). Evaluation of PH in Pde4b wild type and knockout mice confirmed that Pde4b is important for the vascular remodeling associated with PH. In vivo EC lineage tracing demonstrated that Pde4b induces PH development by driving endothelial-to-mesenchymal transition (EndMT), and mechanistic studies showed that Pde4b regulates EndMT by antagonizing the cAMP-dependent PKA–CREB–BMPRII axis. Finally, treating PH rats with a PDE4B-specific inhibitor validated that PDE4B inhibition has a significant pharmacological effect in the alleviation of PH. Collectively, our findings indicate a critical role for PDE4B in EndMT and PH, prompting further studies of PDE4B-specific inhibitors as a therapeutic strategy for PH.

关键词： Phosphodiesterase 4B Pulmonary hypertension Endothelial-to-mesenchymal transition

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Natural Disaster Risk Monitoring for Immovable Cultural Relics Based on Digital Twin

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Journal of Geodesy and Geoinformation Science 2024年第1期7卷 90-104页

作者： li bolun DONG Youqiang QIAO Yunfei HOU Miaole WEN Caihuan The International Joint Laboratory of Safety and Energy Conservation for Ancient Buildings Beijing University of Civil Engineering and ArchitectureBeijing 102616China China Cultural Heritage Information and Consulting Center Beijing 100029China Hebei Institute of Geological Surveying and Mapping Langfang 065000China

Natural disaster risk monitoring is an important task for disaster prevention and reduction.In the case of immovable cultural relics,however,the feedback mechanism,risk factors,monitoring logic,and monitoring indicators of natural disaster risk monitoring are complex.How to achieve intelligent perception and monitoring of natural disaster risk for immovable cultural relics has always been a focus and a challenge for researchers.Based on the analysis of the concepts and issues related to the natural disaster risk of immovable cultural relics,this paper proposes a framework for natural disaster risk monitoring for immovable cultural relics based on the digital twin.This framework focuses on risk monitoring,including the physical entities of natural disaster risk for immovable cultural relics,monitoring indicators,and virtual entity construction.A platform for monitoring the natural disaster risk of immovable cultural relics is proposed.Using the Puzhou Ancient City Site as a test bed,the proposed concept can be used for monitoring the natural disaster risk of immovable cultural relics at different scales.

关键词： immovable cultural relics natural disaster risk digital twin risk monitoring

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Development of a new index for automated mapping of ratoon rice areas using time-series normalized difference vegetation index imagery

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Pedosphere 2022年第4期32卷 576-587页

作者： bolun li Shaobing PENG Runping SHEN Zong-liang YANG Xiaoyuan YAN Xiaofeng li Rongrong li Chengye li Guangbin ZHANG School of Geographical Sciences Nanjing University of Information Science and TechnologyNanjing 210044China College of Plant Science and Technology Huazhong Agricultural UniversityWuhan 430070China Jackson School of Geosciences The University of Texas at AustinAustinUSA Institute of Soil Science Chinese Academy of SciencesNanjing 210008China Northeast Institute of Geography and Agroecology Chinese Academy of SciencesChangchun 130102China

Over recent decades, the global demand for food has continued to grow, owing to population growth and the loss of arable land. Rice ratooning offers new opportunities for increasing rice production and has received renewed interest because of the minimal additional labor input required for its adoption. Regular, regional-scale monitoring of the spatial patterns of both traditional and ratoon rice cropping systems provides essential information for agricultural resource management and food security studies. However, the similar phenological characteristics of traditional double rice and ratoon rice cropping systems make it challenging to accurately classify these cropping practices based on satellite observations alone. In this study, we first proposed an improved phenology-based rice cropping area detection algorithm using moderate resolution imaging spectroradiometer (MODIS) normalized difference vegetation index (NDVI) imagery. A new index, ratoon rice index, was then developed to automatically delineate ratoon rice cropping areas with the aid of a base map of rice in Hubei Province, China. The accuracy assessment using ground truth data showed that our approach could map both traditional and ratoon rice cropping areas with high user accuracy (91.25% and 91.43%, respectively). The MODIS-retrieved rice cropping areas were validated using annual agricultural census data, and coefficient of determination (R2) values of 0.60 and 0.41 were recorded for traditional and ratoon rice cropping systems, respectively. The total area of ratoon rice was estimated to be 1 283.6 km2, 5.0% of the total rice cropping area, in Hubei Province in 2016. These demonstrated the feasibility of extracting the spatial patterns of both traditional and ratoon rice cropping systems solely from time-series NDVI and field survey data and strides made in facilitating the timely and routine monitoring of traditional and ratoon rice distribution at subnational level. Given sufficient historical satellite and phenology records, the proposed algor

关键词： cropping area estimationcross correlogram moderate resolution imaging spectroradiometer(MODIS) ratoon rice index spectral matching

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Nanostructured MXene-based materials for boosting hydrogen sorption properties of Mg/MgH_(2)

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Materials Reports(Energy) 2024年第1期4卷 58-68页

作者： Yingyan Zhao bolun Wang li Ren Yinghui li Xi lin Qiuyu Zhang Zhigang Hu Jianxin Zou National Engineering Research Center of light Alloys Net Forming&State Key Laboratory of Metal Matrix Composites Shanghai Jiao Tong UniversityShanghai200240PR China Shanghai Engineering Research Center of Mg Materials and Applications&School of Materials Science and Engineering Shanghai Jiao Tong UniversityShanghai200240PR China Shanghai Key Laboratory of Hydrogen Science&Center of Hydrogen Science Shanghai Jiao Tong UniversityShanghai200240PR China

Hydrogen holds the advantages of high energy density,great natural abundance and zero emission,making it suitable for large scale and long term energy storage,while its safe and efficient storage is still challenging.Among various solid state hydrogen storage materials,MgH_(2) is promising for industrial applications due to its high gravimetric and volumetric hydrogen densities and the abundance of Mg on earth.However,the practical application of MgH_(2) has been limited by its stable thermodynamics and slow hydrogen desorption kinetics.Nanocatalysis is considered as a promising approach for improving the hydrogen storage performance of MgH_(2) and bringing it closer to the requirements of commercial applications.It is worth mentioning that the recently emerging two-dimensional material,MXene,has showcased exceptional catalytic abilities in modifying the hydrogen storage properties of MgH_(2).Besides,MXene possesses a high surface area,excellent chemical/physical stability,and negatively charged terminating groups,making it an ideal support for the"nanoconfinement"of MgH_(2) or highly active catalysts.Herein,we endeavor to provide a comprehensive overview of recent investigations on MXene-based catalysts and MXene supports for improving the hydrogen sorption properties of Mg/MgH_(2).The mechanisms of hydrogen sorption involved in Mg-MXene based composites are highlighted with special emphases on thermodynamics,kinetics,and catalytic behaviors.The aim of this work is to provide a comprehensive and objective review of researches on the development of high-performance catalysts/supports to improve hydrogen storage performances of Mg/MgH_(2) and to identify the opportunities and challenges for future applications.

关键词： Magnesium-based hydride MXene Catalytic modification Nano-confinement Hydrogen storage performance

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Estimating rice paddy areas in China using multi-temporal cloud-free normalized difference vegetation index (NDVI) imagery based on change detection

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Pedosphere 2020年第6期30卷 734-746页

作者： bolun li Chaopu TI Xiaoyuan YAN State Key Laboratory of Soil and Sustainable Agriculture Institute of Soil ScienceChinese Academy of SciencesNanjing 210008China University of Chinese Academy of Sciences Beijing 100049China

The spatial pattern of rice paddies is an essential parameter used for studies of greenhouse gas emissions,agricultural resource management,and environmental monitoring.On large spatial scales,previous studies have usually mapped rice paddies using a single vegetation index product based on a traditional classification method,or a combined analysis of various vegetation and water indices derived from the moderate resolution imaging spectroradiometer(MODIS)satellite data.However,different indices increase the computational cost and constrain the satellite data sources,and traditional classification methods(e.g.,maximum likelihood classification)may be time-consuming and difficult to carry out over a large area like China.In this study,we designed an auto-thresholding and single vegetation index(normalized difference vegetation index(NDVI))-based procedure to estimate the spatial distribution of rice paddies in China.The MOD09Q1 product,which was available at MODIS’s highest spatial resolution(250 m),was taken as the input source.An auto-threshold function was also introduced into the change detection process to distinguish rice paddies from other croplands.Our MODIS-derived maps were validated with ground surveys and then compared with China national statistical data of rice paddy areas.The results indicated that the best classification result was achieved for plain regions,and that the accuracy declined for hilly regions,where the complex landscape could lead to an underestimation of the rice paddy area.A comparison between the modeled results and other analyses using 500-m MODIS data suggests that rice paddies may be identified routinely using a single vegetation index with finer resolution on large spatial scales.

关键词： HANTS algorithm moderate resolution imaging spectroradiometer(MODIS) land surface water index Otsu’s algorithm rice cultivation

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Gefitinib and fostamatinib target EGFR and SYK to attenuate silicosis:a multi-omics study with drug exploration

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Signal Transduction and Targeted Therapy 2022年第6期7卷 2066-2078页

作者： Mingyao Wang Zhe Zhang Jiangfeng liu Meiyue Song Tiantian Zhang Yiling Chen Huiyuan Hu Peiran Yang bolun li Xiaomin Song Junling Pang Yanjiang Xing Zhujie Cao Wenjun Guo Hao Yang Jing Wang Juntao Yang Chen Wang State Key Laboratory of Medical Molecular Biology Institute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijing 100005China Laboratory of Stem Cell and Tissue Engineering Orthopedic Research InstituteState Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan University and Collaborative Innovation Center of BiotherapyChengdu 610041China Department of Pulmonary and Critical Care Medicine The First Hospital of Shanxi Medical UniversityTaiyuan 030001China NHC Key Laboratory of Pneumoconiosis Taiyuan 030001China Shanxi Province Key Laboratory of Respiratory Disease Taiyuan 030001China Department of Pulmonary and Critical Care Medicine Center of Respiratory MedicineChina-Japan Friendship HospitalBeijing 100029China Department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Xi’an Jiao tong UniversityXi’an 710061China Key Lab of Transplant Engineering and Immunology MOHRegenerative Medical Research CenterWest China HospitalSichuan UniversityChengdu 610041China

Silicosis is the most prevalent and fatal occupational disease with no effective therapeutics,and currently used drugs cannot reverse the disease progress.Worse still,there are still challenges to be addressed to fully decipher the intricated pathogenesis.Thus,specifying the essential mechanisms and targets in silicosis progression then exploring anti-silicosis pharmacuticals are desperately needed.In this work,multi-omics atlas was constructed to depict the pivotal abnormalities of silicosis and develop targeted agents.By utilizing an unbiased and time-resolved analysis of the transcriptome,proteome and phosphoproteome of a silicosis mouse model,we have verified the significant differences in transcript,protein,kinase activity and signaling pathway level during silicosis progression,in which the importance of essential biological processes such as macrophage activation,chemotaxis,immune cell recruitment and chronic inflammation were emphasized.Notably,the phosphorylation of EGFR(p-EGFR)and SYK(pSYK)were identified as potential therapeutic targets in the progression of silicosis.To inhibit and validate these targets,we tested fostamatinib(targeting SYK)and Gefitinib(targeting EGFR),and both drugs effectively ameliorated pulmonary dysfunction and inhibited the progression of inflammation and fibrosis.Overall,our drug discovery with multi-omics approach provides novel and viable therapeutic strategies for the treatment of silicosis.

关键词： silicosis SYK drugs

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基于使用者自建策略应用程序的护士信息学能力培训

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护理学杂志 2024年第6期39卷 22-26页

作者：蔡真真陈媛李开新张博论厦门大学附属心血管病医院护理部福建厦门361006 阳明交通大学生物医学资讯所

目的探讨基于使用者自建策略的应用程序培训对提升护士信息学能力的效果。方法成立培训指导小组,基于使用者自建策略,利用编程工具对33名护士进行应用程序设计课程培训。采用护士信息胜任力量表、课程学习评价问卷和信息专案产出评估... 详细信息

目的探讨基于使用者自建策略的应用程序培训对提升护士信息学能力的效果。方法成立培训指导小组,基于使用者自建策略,利用编程工具对33名护士进行应用程序设计课程培训。采用护士信息胜任力量表、课程学习评价问卷和信息专案产出评估培训成效。结果培训后,护士的计算机能力、信息能力及信息胜任力总分显著提升(均P<0.05)。课程满意度总分(81.48±12.91)分,在课程内容、知识、态度和专案管理方面的满意度均分为中上水平。9个护士小组共设计编写出9个信息应用程序专案。结论护士可以通过应用程序设计课程培养信息思维,提升信息学能力,并取得较好的课程满意度。

关键词：护士使用者自建程序设计课程信息胜任力计算机能力信息能力课程满意度护士培训

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聚碳酸酯挤压形变力学行为有限元模拟

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材料工程 2024年第3期52卷 90-99页

作者：王博伦王韬霍钟祺孙琦伟李茂源张云陈宇宏颜悦中国航发北京航空材料研究院北京100095 北京市先进运载系统结构透明件工程技术研究中心北京100095 华中科技大学材料成形与模具技术国家重点实验室武汉430074

采用有限元方法研究了聚碳酸酯在中应变率下挤压形变的力学行为。基于DSGZ本构模型,开展聚碳酸酯圆柱单轴压缩形变有限元模拟,对比模拟与实验结果,计算模型预测准确度,分析材料压缩形变后的多物理场分布,验证模型对压缩力学响应预测的... 详细信息

采用有限元方法研究了聚碳酸酯在中应变率下挤压形变的力学行为。基于DSGZ本构模型,开展聚碳酸酯圆柱单轴压缩形变有限元模拟,对比模拟与实验结果,计算模型预测准确度,分析材料压缩形变后的多物理场分布,验证模型对压缩力学响应预测的有效性。模拟聚碳酸酯平板在侧向受限挤压模式下的固态形变,获得了制件的力学演变规律。结果显示,单轴压缩模拟与实验应力-应变曲线吻合度高,DSGZ模型可较为准确地预测压缩弹-塑性形变过程中的应力-应变关系。在圆柱单轴压缩形变与平板挤压形变模拟中,材料整体变形均匀,应力响应温度变化比响应应变率变化更敏感。模拟结果有效地反映了聚碳酸酯挤压形变力学特性,可成为聚碳酸酯挤压形变工程实现的重要依据,为材料强化及其在飞机座舱透明件中的应用提供有力支持。

关键词：聚碳酸酯挤压形变本构模型有限元

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一株具有插入和缺失突变特征鸭腺病毒B2毒株的分离鉴定

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福建农业学报 2024年第2期39卷 125-130页

作者：郭博伦李雅汝郑欣江丹丹曾丽陈少莺马燕梅陈仕龙福建农林大学动物科学学院/福建省-尼泊尔畜禽重大疫病防控联合实验室福建福州350002 福建省农业科学院畜牧兽医研究所福建福州350013 福建省畜禽疫病防治工程技术研究中心福建福州350013

【目的】对一份疑似鸭腺病毒B2(Duck adenovirus B2,DAdV B2)感染的番鸭白肝病的病例进行确诊,并对分离株进行测序,为福建省DAdV B2流行病学研究提供参考。【方法】开展病料PCR检测,并进行病毒的分离鉴定、全基因二代测序,利用MegAlign... 详细信息

【目的】对一份疑似鸭腺病毒B2(Duck adenovirus B2,DAdV B2)感染的番鸭白肝病的病例进行确诊,并对分离株进行测序,为福建省DAdV B2流行病学研究提供参考。【方法】开展病料PCR检测,并进行病毒的分离鉴定、全基因二代测序,利用MegAlign和SnapGene软件对测序结果进行同源性及遗传进化分析,再进行动物回归试验,确定对雏番鸭的致病性。【结果】病料样本检测为DAdV B2阳性,并成功分离到一株DAdV B2毒株,命名为DAdV B2/BG48。该分离株感染鸡肝癌细胞(LMH)后细胞变大变圆、最后死亡崩解,形成特征性细胞病变;感染MDEF后细胞由长梭形变为圆形并聚集,细胞间出现空隙。测序结果表明,BG48基因组在pX基因区域中有3 bp的插入,在ORF19B基因区域有33 bp的插入,在ORF64和ORF67基因区域的交界处有42 bp的缺失,ORF67基因起始密码子往后第133位碱基为G,没有突变为终止密码子,其他编码基因与CH-GD-12-2014、实验室之前鉴定的BG27和BG18无特征性差异。动物回归试验显示,2日龄的番鸭对DAdV B2分离株BG48易感,致病率为50%,死亡率为0,发病鸭可见与自然感染病鸭相似的临床症状和病理变化。【结论】成功从番鸭白肝病病例中分离鉴定1株DAdV B2突变株BG48,BG48具有多位点插入和缺失特征,提示DAdV B2毒株容易突变,临床流行毒株复杂。本结果为DAdV B2的分子流行病学调查和遗传进化研究提供了参考。

关键词：番鸭白肝病鸭腺病毒B2 分离鉴定插入和缺失 ORF67

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不同碳源对E.adhaerens产维生素B_(12)发酵代谢动力学分析

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华东理工大学学报（自然科学版） 2024年第1期50卷 80-87页

作者：陈欣怡栗波赵杜娟汪博伦郭华楠付丽刘爱军杨辉王泽建广西大学生命科学与技术学院南宁530004 华东理工大学生物反应器工程国家重点实验室上海200237 浙江工业大学杭州310014 河北欣港药业有限公司石家庄051530

考察了Ensifer adhaerens(E.adhaerens)在不同碳源(麦芽糖、蔗糖、葡萄糖和果糖)条件下的生理代谢特性,并利用Logistic和Luedeking-Piret模型分析了黏着剑菌发酵过程生长动力学及产物合成动力学特性变化。结果表明,蔗糖能够显著促进E.ad... 详细信息

考察了Ensifer adhaerens(E.adhaerens)在不同碳源(麦芽糖、蔗糖、葡萄糖和果糖)条件下的生理代谢特性,并利用Logistic和Luedeking-Piret模型分析了黏着剑菌发酵过程生长动力学及产物合成动力学特性变化。结果表明,蔗糖能够显著促进E.adhaerens的生长和合成代谢,补料批培养条件下发酵单位分别比葡萄糖、麦芽糖、果糖组高出53%、40%、103%;发酵代谢动力学分析表明,不同碳源条件下,E.adhaerens生产维生素B_(12)(VB_(12))呈现部分生长偶联型;蔗糖为最优碳源,最大比生长速率和最高发酵单位分别为0.054 h^(-1)和115 mg/L。E.adhaerens发酵过程中,蔗糖能够被逐渐分解为葡萄糖和果糖,维持合适的葡萄糖生成速率,用于提供足够的能量和前体用于菌体生长和VB_(12)合成,有效缓解了高质量浓度葡萄糖对菌体生长和产物合成的抑制。

关键词： E.adhaerens VB_(12) 碳源发酵代谢动力学

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