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Nucleotide-binding domain,leucine-rich repeat,and pyrin domaincontaining protein 3 inflammasome:From action mechanism to therapeutic target in clinical trials

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World Journal of Gastrointestinal Oncology 2025年第2期17卷 6-16页

作者： Chun-Ye Zhang Shuai Liu Yu-xiang sui Ming Yang Bond Life Sciences Center University of MissouriColumbiaMO 65212United States The First Affiliated Hospital Zhejiang UniversityHangzhou 310006Zhejiang ProvinceChina School of Life Science Shanxi Normal UniversityLinfen 041004Shanxi ProvinceChina Department of Surgery University of ConnecticutSchool of MedicineFarmingtonCT 06030United States

The nucleotide-binding domain,leucine-rich repeat,and pyrin domain-containing protein 3(NLRP3)inflammasome is a critical modulator in inflammatory *** and mutation of NLRP3 can cause severe inflammation in diseases such as chronic infantile neurologic cutaneous and articular syndrome,Muckle-Wells syndrome,and familial cold autoinflammatory syndrome *** date,a great effort has been made to decode the underlying mechanisms of NLRP3 *** priming and activation of NLRP3 drive the maturation and release of active interleukin(IL)-18 and IL-1βto cause inflammation and pyroptosis,which can significantly trigger many diseases including inflammatory diseases,immune disorders,metabolic diseases,and neurodegenerative *** investigation of NLRP3 as a therapeutic target for disease treatment is a hot topic in both preclinical studies and clinical *** potent NLRP3 inhibitors and downstream IL-1 inhibitors attracts wide-spectrum attention in both research and pharmaceutical *** this minireview,we first updated the molecular mechanisms involved in NLRP3 inflammasome activation and the associated downstream signaling *** then reviewed the molecular and cellular pathways of NLRP3 in many diseases,including obesity,diabetes,and other metabolic *** addition,we briefly reviewed the roles of NLRP3 in cancer growth and relative immune checkpoint ***,clinical trials with treatments targeting NLRP3 and its downstream signaling pathways were summarized.

关键词： Nucleotide-binding domain,leucine-rich repeat,and pyrin domain-containing protein 3 Metabolic disease Inflammation Cancer Immunotherapy Clinical trial

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Advances and prospects in biomimetic multilayered scaffolds for articular cartilage regeneration

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Regenerative Biomaterials 2020年第6期7卷 527-542页

作者： Liwei Fu Zhen Yang Cangjian Gao Hao Li Zhiguo Yuan Fuxin Wang xiang sui Shuyun Liu Quanyi Guo School of Medicine Nankai UniversityNo.94 Weijin RoadNankai DistrictTianjin 300071China Beijing Key Lab of Regenerative Medicine in Orthopedics Key Laboratory of Musculoskeletal Trauma and War Injuries PLAInstitute of OrthopedicsThe First Medical CenterChinese PLA General HospitalNo.28 Fuxing RoadHaidian DistrictBeijing 100853China Department of Bone and Joint Surgery Renji HospitalSchool of MedicineShanghai Jiaotong UniversityNo.160 Pujian RoadPudong New DistrictShanghai 200127China

Due to the sophisticated hierarchical structure and limited reparability of articular cartilage(AC),the ideal regeneration of AC defects has been a major challenge in the field of regenerative *** defects progress,they often extend from the cartilage layer to the subchondral bone and ultimately lead to *** engineering techniques bring new hope for AC *** meet the regenerative requirements of the heterogeneous and layered structure of native AC tissue,a substantial number of multilayered biomimetic scaffolds have been *** multilayered scaffolds should generate zone-specific functional tissue similar to native AC *** review focuses on the current status of multilayered scaffolds developed for AC defect repair,including design strategies based on the degree of defect severity and the zone-specific characteristics of AC tissue,the selection and composition of biomaterials,and techniques for design and *** challenges and future perspectives of biomimetic multilayered scaffold strategies for AC regeneration are also discussed.

关键词： biomimetic multilayered scaffold articular cartilage regeneration tissue engineering osteochondral

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A quantitative method for storm surge vulnerability assessment – a case study of Weihai city

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International Journal of Digital Earth 2017年第5期10卷 539-559页

作者： Jin Liu Jian-Hua Gong Jian-Ming Liang Yi Li Lin-Chong Kang Li-Li Song sui-xiang Shi State Key Laboratory of Remote Sensing Science Institute of Remote Sensing and Digital EarthChinese Academy of SciencesBeijingPeople’s Republic of China National Marine Data and Information Service TianjinPeople’s Republic of China University of Chinese Academy of Sciences BeijingPeople’s Republic of China

In traditional vulnerability assessments,a synthetic index method is usually used to select all types of social and economic indexes so that more aspects can be covered;however,the requisite social and economic data are not always available or are not highly relevant to the studied geographical space,which makes it difficult to conduct quantitative *** this paper,a spatial value density assessment method was developed to improve the hazard of place ***,a three-dimensional(3D)model of a coastal city was obtained using oblique airborne photogrammetry and image-based 3D reconstruction and then,architecture footprints were employed to extract the geometric information of each individual ***,a vulnerability assessment system was established to quantitatively account for the aggregate economic value of a selected set of urban surface *** geographic information system(GIS)techniques,the aggregate value of these urban features within each geographic unit can be accurately calculated to quantify the exposure and vulnerability of coastal cities to storm surge.A vulnerability assessment was conducted using Weihai city as an *** study shows that vulnerability assessment accuracy was greatly improved by downscaling the assessment granularity from county-level administrative districts to a 1-km grid.

关键词： Storm surge vulnerability assessment oblique photogrammetry 3D-GIS Weihai city

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Advancing drug delivery to articular cartilage:From single to multiple strategies

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Acta Pharmaceutica Sinica B 2023年第10期13卷 4127-4148页

作者： Tianyuan Zhao Xu Li Hao Li Haoyuan Deng Jianwei Li Zhen Yang Songlin He Shuangpeng Jiang xiang sui Quanyi Guo Shuyun Liu Institute of Orthopedics The First Medical CenterChinese PLA General HospitalBeijing Key Lab of Regenerative Medicine in OrthopedicsKey Laboratory of Musculoskeletal Trauma&War Injuries PLABeijing 100853China School of Medicine Nankai UniversityTianjin 300071China Musculoskeletal Research Laboratory Department of Orthopedics&TraumatologyThe Chinese University of Hong Kong999077Hong KongChina Arthritis Clinic&Research Center Peking University People’s HospitalPeking UniversityBeijing 100044China Department of Joint Surgery Beijing Shijitan HospitalCapital Medical UniversityBeijing 100038China

Articular cartilage(AC) injuries often lead to cartilage degeneration and may ultimately result in osteoarthritis(OA) due to the limited self-repair ability. To date, numerous intra-articular delivery systems carrying various therapeutic agents have been developed to improve therapeutic localization and retention, optimize controlled drug release profiles and target different pathological processes. Due to the complex and multifactorial characteristics of cartilage injury pathology and heterogeneity of the cartilage structure deposited within a dense matrix, delivery systems loaded with a single therapeutic agent are hindered from reaching multiple targets in a spatiotemporal matched manner and thus fail to mimic the natural processes of biosynthesis, compromising the goal of full cartilage regeneration. Emerging evidence highlights the importance of sequential delivery strategies targeting multiple pathological processes. In this review, we first summarize the current status and progress achieved in single-drug delivery strategies for the treatment of AC diseases. Subsequently, we focus mainly on advances in multiple drug delivery applications, including sequential release formulations targeting various pathological processes, synergistic targeting of the same pathological process, the spatial distribution in multiple tissues, and heterogeneous regeneration. We hope that this review will inspire the rational design of intraarticular drug delivery systems(DDSs) in the future.

关键词： Drug delivery systems Articular cartilage Cartilage injury Osteoarthritis Cartilage regeneration Multiple drug delivery strategy Biomaterials Therapeutic factors

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Tetrahedral framework nucleic acids enhance the chondrogenic potential of human umbilical cord mesenchymal stem cells via the PI3K/AKT axis

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Regenerative Biomaterials 2023年第1期10卷 1552-1565页

作者： Liwei Fu Pinxue Li Jiang Wu Yazhe Zheng Chao Ning Zhiyao Liao Xun Yuan Zhengang Ding Zhichao Zhang xiang sui Sirong Shi Shuyun Liu Quanyi Guo School of Medicine Nankai UniversityTianjin 300071People’s Republic of China Institute of Orthopedics Chinese PLA General HospitalBeijing Key Laboratory of Regenerative Medicine in OrthopedicsKey Laboratory of Musculoskeletal Trauma&War Injuries PLABeijing 100853People’s Republic of China Guizhou Medical University GuiyangGuizhou 550004People’s Republic of China State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu 610041People’s Republic of China

The field of regenerative medicine faces a notable challenge in terms of the regeneration of articular *** proper treatment,it can lead to *** on the research findings,human umbilical cord mesenchymal stem cells(hUMSCs)are considered an excellent choice for regenerating ***,there is still a lack of suitable biomaterials to control their ability to self-renew and *** address this issue,in this study using tetrahedral framework nucleic acids(tFNAs)as a new method in an in vitro culture setting to manage the behaviour of hUMSCs was ***,the influence of tFNAs on hUMSC proliferation,migration and chondrogenic differentiation was explored by combining bioinformatics *** addition,a variety of molecular biology techniques have been used to investigate deep molecular *** results demonstrated that tFNAs can affect the transcriptome and multiple signalling pathways of hUMSCs,among which the PI3K/Akt pathway is significantly ***,tFNAs can regulate the expression levels of multiple proteins(GSK3β,RhoA and mTOR)downstream of the PI3K-Akt axis to further enhance cell proliferation,migration and hUMSC chondrogenic *** provide new insight into enhancing the chondrogenic potential of hUMSCs,which exhibits promising potential for future utilization within the domains of AC regeneration and clinical treatment.

关键词： tFNAs articular cartilage hUMSCs chondrogenic differentiation

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Joint Analysis Method for Major Genes Controlling Multiple Correlated Quantitative Traits

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Agricultural Sciences in China 2006年第3期5卷 179-187页

作者： XIAO Jing WANG Xue-feng HU Zhi-qiu TANG Zai-xiang sui Jiong-ming LI Xin XU Chen-wu Jiangsu Provincial Key Laboratory of Crop Genetics and Physiology Yangzhou University Yangzhou 225009 P.R.China

Based on the major gene and polygene mixed inheritance model for multiple correlated quantitative traits, the authors proposed a new joint segregation analysis method of major gene controlling multiple correlated quantitative traits, which include major gene detection and its effect and variation estimation. The effect and variation of major gene are estimated by the maximum likelihood method implemented via expectation-maximization （EM） algorithm. Major gene is tested with the likelihood ratio （LR） test statistic. Extensive simulation studies showed that joint analysis not only increases the statistical power of major gene detection but also improves the precision and accuracy of major gene effect estimates. An example of the plant height and the number of tiller of F2 population in rice cross Duonieai x Zhonghua 11 was used in the illustration. The results indicated that the genetic difference of these two traits in this cross refers to only one pleiotropic major gene. The additive effect and dominance effect of the major gene are estimated as -21.3 and 40.6 cm on plant height, and 22.7 and -25.3 on number of tiller, respectively. The major gene shows overdominance for plant height and close to complete dominance for number of tillers.

关键词： multiple correlated quantitative traits major gene joint segregation analysis maximum likelihood estimation,EM algorithm

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A novel mesenchymal stem cell-targeting dual-miRNA delivery system based on aptamer-functionalized tetrahedral framework nucleic acids:Application to endogenous regeneration of articular cartilage

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Bioactive Materials 2024年第10期40卷 634-648页

作者： Liwei Fu Jiang Wu Pinxue Li Yazhe Zheng Zhichao Zhang Xun Yuan Zhengang Ding Chao Ning xiang sui Shuyun Liu Sirong Shi Quanyi Guo Yunfeng Lin School of Medicine Nankai UniversityTianjin300071People’s Republic of China Institute of Orthopedics The First Medical CenterChinese PLA General HospitalBeijing Key Lab of Regenerative Medicine in OrthopedicsKey Laboratory of Musculoskeletal Trauma&War Injuries PLANo.28 Fuxing RoadHaidian DistrictBeijingPeople’s Republic of China Department of Orthopedics The Fourth Medical CenterChinese PLA General HospitalBeijingPeople’s Republic of China National Clinical Research Center for Orthopedics Sports Medicine&RehabilitationBeijingPeople’s Republic of China State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu610041People’s Republic of China Guizhou Medical University Guiyang550004Guizhou ProvincePeople’s Republic of China

Articular cartilage injury(ACI)remains one of the key challenges in regenerative medicine,as current treatment strategies do not result in ideal regeneration of hyaline-like *** endogenous repair via micro-RNAs(miRNAs)shows promise as a regenerative ***-140 and miRNA-455 are two key and promising candidates for regulating the chondrogenic differentiation of mesenchymal stem cells(MSCs).In this study,we innovatively synthesized a multifunctional tetrahedral framework in which a nucleic acid(tFNA)-based targeting miRNA codelivery system,named A-T-M,was *** tFNAs as vehicles,miR-140 and miR-455 were connected to and modified on tFNAs,while Apt19S(a DNA aptamer targeting MSCs)was directly integrated into the *** relevant results showed that A-T-M efficiently delivered miR-140 and miR-455 into MSCs and subsequently regulated MSC chondrogenic differentiation through corresponding ***,a synergistic effect between miR-140 and miR-455 was ***,A-T-M successfully enhanced the endogenous repair capacity of articular cartilage in vivo and effectively inhibited hypertrophic chondrocyte formation.A-T-M provides a new perspective and strategy for the regeneration of articular cartilage,showing strong clinical application value in the future treatment of ACI.

关键词： Tetrahedral framework nucleic acids miRNAs co-delivery Targeting system Articular cartilage endogenous regeneration Mesenchymal stem cells

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紫外导数分光光度法直接同时测定炼油厂污水中的石油类和苯酚

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石油化工 2000年第1期29卷 46-48页

作者：王林隋向云石油大学炼制系山东东营257062

研究了用二阶导数紫外分光光度法直接同时测定炼油厂污水中的石油类和苯酚的最佳条件。用非离子表面活性剂和助表面活性剂将标准油制成微乳液，使整个测定均在水相进行。利用零交技术消除了主要干扰，使测定方法简单、快速，且不造成二... 详细信息

研究了用二阶导数紫外分光光度法直接同时测定炼油厂污水中的石油类和苯酚的最佳条件。用非离子表面活性剂和助表面活性剂将标准油制成微乳液，使整个测定均在水相进行。利用零交技术消除了主要干扰，使测定方法简单、快速，且不造成二次污染。本方法的石油类和苯酚的线性范围均为０～８ μｇ／ｍｌ。加标回收率：石油类为９０％～１０９％；苯酚为９０％～１０２％。

关键词：分光光度法炼油厂污水石油类苯酚水质监测

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人工智能技术与劳动者就业环境改善

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经济问题 2022年第10期 73-82页

作者：隋想哈尔滨商业大学金融学院黑龙江哈尔滨150028

人工智能技术是未来产业技术的重要发展方向,人工智能技术将对改善劳动者就业环境,加强就业工作,稳定就业局势产生重要作用。以2011—2019年城市层面数据为样本,探究人工智能技术对劳动者就业环境的影响。研究发现,人工智能技术的应用... 详细信息

人工智能技术是未来产业技术的重要发展方向,人工智能技术将对改善劳动者就业环境,加强就业工作,稳定就业局势产生重要作用。以2011—2019年城市层面数据为样本,探究人工智能技术对劳动者就业环境的影响。研究发现,人工智能技术的应用显著改善了劳动者的就业环境;城镇化水平提升与劳动要素收入增加是人工智能技术作用于就业环境的传导路径;城市地理位置、行政级别与智能设施水平是影响人工智能技术作用发挥的关键。整体来看,在东部及东北地区、普通城市、智能设施水平较高的城市,人工智能技术对就业环境的改善作用更为明显;进一步研究发现,人工智能技术的就业环境提升效应存在维度差异,其对保障环境的促进作用更为明显而对市场环境的影响不显著;从长期来看,人工智能技术依然会对就业环境产生激励作用,且这一作用可能比短期更强。

关键词：人工智能技术就业环境城镇化水平劳动要素收入

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Enhancement of acellular cartilage matrix scaffold by Wharton’s jelly mesenchymal stem cell-derived exosomes to promote osteochondral regeneration

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Bioactive Materials 2021年第9期6卷 2711-2728页

作者： Shuangpeng Jiang Guangzhao Tian Zhen Yang xiang Gao Fuxin Wang Juntan Li Zhuang Tian Bo Huang Fu Wei Xinyu Sang Liuqi Shao Jian Zhou Zhenyong Wang Shuyun Liu xiang sui Quanyi Guo Weimin Guo Xu Li Department of Orthopedics The First Hospital of China Medical University155 Nanjing North StreetHeping DistrictShenyang110001Liaoning ProvinceChina Institute of Orthopedics The First Medical CenterChinese PLA General HospitalBeijing Key Lab of Regenerative Medicine in OrthopedicsKey Laboratory of Musculoskeletal Trauma and War Injuries PLANo.28 Fuxing RoadHaidian DistrictBeijing100853China School of Medicine Nankai UniversityTianjin300071China

Articular cartilage defect repair is a problem that has long plagued *** mesenchymal stem cells(MSCs)have the potential to regenerate articular cartilage,they also have many *** studies have found that MSC-derived exosomes(MSC-Exos)play an important role in tissue *** purpose of this study was to verify whether MSC-Exos can enhance the reparative effect of the acellular cartilage extracellular matrix(ACECM)scaffold and to explore the underlying *** results of in vitro experiments show that human umbilical cord Wharton’s jelly MSC-Exos(hWJMSC-Exos)can promote the migration and proliferation of bone marrow-derived MSCs(BMSCs)and the proliferation of *** also found that hWJMSC-Exos can promote the polarization of macrophages toward the M2 *** results of a rabbit knee osteochondral defect repair model confirmed that hWJMSC-Exos can enhance the effect of the ACECM scaffold and promote osteochondral *** demonstrated that hWJMSC-Exos can regulate the microenvironment of the articular cavity using a rat knee joint osteochondral defect *** effect was mainly manifested in promoting the polarization of macrophages toward the M2 phenotype and inhibiting the inflammatory response,which may be a promoting factor for osteochondral *** addition,microRNA(miRNA)sequencing confirmed that hWJMSC-Exos contain many miRNAs that can promote the regeneration of hyaline *** further clarified the role of hWJMSC-Exos in osteochondral regeneration through target gene prediction and pathway enrichment *** summary,this study confirms that hWJMSC-Exos can enhance the effect of the ACECM scaffold and promote osteochondral regeneration.

关键词： Articular cartilage Regeneration Tissue engineering Mesenchymal stem cells Exosomes

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