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SWIR FluorescenceImaging In Vivo Monitoring and Evaluating Implanted M2 Macrophages in Skeletal Muscle Regeneration

Engineering 2024年第2期33卷 283-294页

作者： Mo chen Yuzhou chen Sijia Feng Shixian Dong Luyi Sun Huizhu Li Fuchun chen Nguyen Thi Kim Thanh Yunxia Li shiyi chen You Wang Jun chen Sports Medicine Institute of Fudan University Department of Sports MedicineHuashan HospitalFudan UniversityShanghai 200040China Department of Bone and Joint Surgery Department of OrthopedicsRenji HospitalSchool of MedicineShanghai Jiaotong UniversityShanghai 200127China Department of Anatomy and Physiology School of MedicineShanghai Jiao Tong UniversityShanghai 200025China Key Laboratory of Infrared System Detection&Imaging Technology Shanghai Institute of Technical PhysicsChinese Academy of SciencesShanghai 200083China Biophysics Group Department of Physics and AstronomyUniversity College LondonLondon WC1E 6BTUK Healthcare Biomagnetic and Nanomaterials Laboratories University College LondonLondon W1S 4BSUK

Skeletal muscle has a robust regeneration ability that is impaired by severe injury,disease,and aging.resulting in a decline in skeletal muscle function.Therefore,improving skeletal muscle regeneration is a key challenge in treating skeletal muscle-related disorders.Owing to their significant role in tissue regeneration,implantation of M2 macrophages(M2MФ)has great potential for improving skeletal muscle regeneration.Here,we present a short-wave infrared(SWIR)fluorescence imaging technique to obtain more in vivo information for an in-depth evaluation of the skeletal muscle regeneration effect after M2MФtransplantation.SWIR fluorescence imaging was employed to track implanted M2MФin the injured skeletal muscle of mouse models.It is found that the implanted M2MФaccumulated at the injury site for two weeks.Then,SWIR fluorescence imaging of blood vessels showed that M2MФimplantation could improve the relative perfusion ratio on day 5(1.09±0.09 vs 0.85±0.05;p=0.01)and day 9(1.38±0.16 vs 0.95±0.03;p=0.01)post-injury,as well as augment the degree of skeletal muscle regencration on day 13 post-injury.Finally,multiple linear regression analyses determined that post-injury time and relative perfusion ratio could be used as predictive indicators to evaluate skeletal muscle regeneration.These results provide more in vivo details about M2MФin skeletal muscle regeneration and confirm that M2MФcould promote angiogenesis and improve the degree of skeletal muscle repair,which will guide the research and development of M2MФimplantation to improve skeletal muscle regeneration.

关键词： In vivo Short-wave infrared Skeletal muscle Macrophage Regeneration

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Single-base editing in IGF2 improves meat production and intramuscular fat deposition in Liang Guang Small Spotted pigs

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Journal of Animal Science and Biotechnology 2024年第1期15卷 108-126页

作者： Tianqi Duo Xiaohong Liu Delin Mo Yu Bian Shufang Cai Min Wang Ruiqiang Li Qi Zhu Xian Tong Ziyun Liang Weilun Jiang shiyi chen Yaosheng chen Zuyong He State Key Laboratory of Biocontrol School of Life SciencesSun Yat-Sen UniversityGuangzhou 510275GuangdongChina Department of Pharmacology(the State‑Province Key Laboratories of Biomedicine‑Pharmaceutics of China Key Laboratory of Cardiovascular ResearchMinistry of Education)College of PharmacyHarbin Medical UniversityHarbin 150081China Hunan Provincial Key Laboratory for Genetic Improvement of Domestic Animal College of Animal Science and TechnologyHunan Agricultural UniversityChangsha 410128China

Background Chinese indigenous pigs are popular with consumers for their juiciness,flavour and meat quality,but they have lower meat production.Insulin-like growth factor 2(IGF2) is a maternally imprinted growth factor that promotes skeletal muscle growth by regulating cell proliferation and differentiation.A single nucleotide polymorphism(SNP) within intron 3 of porcine IGF2 disrupts a binding site for the repressor,zinc finger BED-type containing 6(ZBED6),leading to up-regulation of IGF2 and causing major effects on muscle growth,heart size,and backfat thickness.This favorable mutation is common in Western commercial pig populations,but absent in most Chinese indigenous pig breeds.To improve meat production of Chinese indigenous pigs,we used cytosine base editor 3(CBE3)to introduce IGF2 intron3-C3071T mutation into porcine embryonic fibroblasts(PEFs) isolated from a male Liang Guang Small Spotted pig(LGSS),and single-cell clones harboring the desired mutation were selected for somatic cell nuclear transfer(SCNT) to generate the founder line of IGF2^(T/T) pigs.Results We found the heterozygous progeny IGF2^(C/T) pigs exhibited enhanced expression of IGF2,increased lean meat by 18%-36%,enlarged loin muscle area by 3%-17%,improved intramuscular fat(IMF) content by 18%-39%,marbling score by 0.75-1,meat color score by 0.53-1.25,and reduced backfat thickness by 5%-16%.The enhanced accumulation of intramuscular fat in IGF2^(C/T) pigs was identified to be regulated by the PI3K-AKT/AMPK pathway,which activated SREBP1 to promote adipogenesis.Conclusions We demonstrated the introduction of IGF2-intron3-C3071T in Chinese LGSS can improve both meat production and quality,and first identified the regulation of IMF deposition by IGF2 through SREBP1 via the PI3KAKT/AMPK signaling pathways.Our study provides a further understanding of the biological functions of IGF2and an example for improving porcine economic traits through precise base editing.

关键词： CBE3 IGF2 Intramuscular fat Meat production PI3K-AKT/AMPK ZBED6

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Antibody Levels and Infection Status of Pertussis in the Population under Pertussis Resurgence in Guangxi in 2018:A Cross-Sectional Survey

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Biomedical and Environmental Sciences 2024年第6期37卷 628-638页

作者： Liang Liang Qiuyun Deng Lili Deng Jinghang Wei shiyi chen Yizhi Wei Yuyan Ma Yue Qin and Wei Liu Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention Nanning 530028GuangxiChina

Objective Pertussis cases have increased markedly since 2018 in Guangxi.The aim of this study was to evaluate antibody levels and the infection status of pertussis in the resident population.Method A total of 10,215 serum samples from residents were collected from August-November 2018 and tested for anti-pertussis IgG and toxin IgG using the enzyme-linked immunosorbent assay(ELISA).Results Of the collected samples,1,833(17.94%)tested positive for anti-pertussis IgG,with the median concentration of 16.06 IU/mL.Antibody level<10 IU/mL accounted for more than 60%in children under 4 years of age,but declined with age,whereas the percentages of the other three levels(10-40,40-50,and≥50 IU/mL)increased almost with age(P<0.001).Moreover,7,924 samples were selected for anti-pertussis toxin IgG,of which 653(8.24%)tested positive(≥40 IU/mL)with the median concentration of 5.89 IU/mL,and 204 participants(2.56%)had recent pertussis infection(≥100 IU/mL).Among the different age groups,the highest rates of positivity and recent infection were observed at 11-20 years of age,the lowest positivity rate at 5 years of age,and the lowest recent infection rate at 4 years of age(P<0.001,P=0.005,respectively).Conclusion The survey results showed that all age groups in Guangxi lacked immunity against pertussis,which was one of the main factors contributing to the resurgence of pertussis in 2018.In addition,the prevalence of pertussis is relatively high in Guangxi,and its incidence is seriously underestimated,especially in adolescents and adults.

关键词： Pertussis resurgence Anti-pertussis IgG Anti-pertussis toxin IgG Antibody level Infection status

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In vivo real-time monitoring delayed administration of M2 macrophages to enhance healing of tendon by NIR-II fluorescence imaging

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Nano Research 2024年第5期17卷 4379-4390页

作者： Yuzhou chen Mo chen chengxuan Yu Huizhu Li Liman Sai Nguyen T.K.Thanh Yueming Wang Yan Wo Jian Zhang Xing Yang Evgenii L.Guryev Andrei V.Zvyagin Hao De Min Tang shiyi chen Yunxia Li Yuefeng Hao Sijia Feng Jun chen Sports Medicine Institute of Fudan University Department of Sports MedicineHuashan HospitalFudan UniversityShanghai 200040China Department of Orthopedic Surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Department of Bone and Joint Surgery Department of OrthopedicsRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200001China Department of Physics Shanghai Normal UniversityShanghai 200234China Biophysics Group Department of Physics and AstronomyUniversity College LondonLondon WC1E 6BTUK UCL Healthcare Biomagnetic and Nanomaterials Laboratories London W1S 4BSUK Department of Anatomy and Physiology School of MedicineShanghai Jiao Tong UniversityShanghai 200025China Department of Orthopedics Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou 215500China Institute of Biology and Biomedicine Lobachevsky State University of Nizhny NovgorodNizhny Novgorod 603950Russia Mathematical Institute University of OxfordOxford OX26GGUK Institute of Natural Sciences School of MathematicsShanghai Jiao Tong UniversityShanghai 200240China

The administration time is a critical but long-neglected point in cell therapy based on macrophages because the incorrect time of macrophage administration could result in diverse outcomes regarding the same macrophage therapy.In this work,the second near-infrared(NIR-II)fluorescence imaging in vivo tracking of M2 macrophages during a pro-healing therapy in the mice model of rotator cuff injury revealed that the behavior of administrated macrophages was influenced by the timing of their administration.The delayed cell therapy(DCT)group had a longer retention time of injected M2 macrophages in the repairing tissue than that in the immediate cell therapy(ICT)group.Both Keller-Segel model and histological analysis further demonstrated that DCT altered the chemotaxis of M2 macrophages and improved the healing outcome of the repaired structure in comparison with ICT.Our results offer a possible explanation of previous conflicting results on reparative cell therapy and provoke reconsideration of the timing of these therapies.

关键词： macrophage cell therapy NIR-II in vivo imaging delayed therapy tendon healing

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Impacts of Nutlin-3a and exercise on murine double minute 2-enriched glioma treatment

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Neural Regeneration Research 2025年第4期20卷 1135-1152页

作者： Yisheng chen Zhongcheng Fan Zhiwen Luo Xueran Kang Renwen Wan Fangqi Li Weiwei Lin Zhihua Han Beijie Qi Jinrong Lin Yaying Sun Jiebin Huang Yuzhen Xu shiyi chen Department of Sport Medicine Huashan HospitalFudan UniversityShanghaiChina Department of Orthopedic Surgery Hainan Province Clinical Medical CenterHaikou Affiliated Hospital of Central South University Xiangya School of MedicineHaikouHainan ProvinceChina Department of Basic Medicine Shanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Neurosurgery Second Affiliated Hospital of Zhejiang University School of MedicineZhejiang UniversityHangzhouZhejiang ProvinceChina Department of Orthopedics Shanghai General HospitalSchool of Medicine Shanghai Jiao Tong UniversityShanghaiChina Department of Infectious Diseases Children’s Hospital of Fudan UniversityNational Children’s Medical CenterShanghaiChina Department of Rehabilitation The Second Affiliated Hospital of Shandong First Medical UniversityTaianShandong ProvinceChina

Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural regeneration.The role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of SUMOylation.We used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other cancers.We demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by nutlin-3.This underscores the intricate relationship between natural compounds such as nutlin-3 and immune regulation.Using comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma progression.We also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic simulation.Nutlin-3a inhibited glioma cell proliferation and activated the p53 pathway.Its efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or exercise.Experiments using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway regulation.Notably,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing cells.These results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma management.Our research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.

关键词： exercise and SUMO-related gene signatures(ESLRS) glioblastoma management low-grade glioma natural bioactives neural regeneration physical exercise

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Predictive value of T cell receptor repertoire profiling for immunosuppressive therapy in severe aplastic anemia

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Genes & Diseases 2024年第1期11卷 95-98页

作者： Cunte chen Yuling Zhang Dongpei Lu Zelong Zhang Jun Yang Xiaowei chen Ming Zhou Wenjian Mo Caixia Wang Qinghua Cai Yumiao Li Ruiqing Zhou Shilin Xu Wei Zhou Tingfen Deng shiyi Pan Yanli Xu Shunqing Wang Yuping Zhang Department of Hematology Guangzhou First People's HospitalSouth China University of TechnologyGuangzhouGuangdong 510180China Guangzhou Junruikang Biotechnology Co. LtdGuangzhouGuangdong 510700China

Increasing evidence supports the hypothesis of autologous immune attack in severe aplastic anemia(SAA):the predominant role of activated cytotoxic T cells(CTL)expressing-interferon in inhibiting the growth of bone marrow(BM)cells,putative autoantigens,and oligoclonal expansion of CD8+T cells.1 For SAA patients,the definitive therapies are immunosuppressive therapy(IST)or hematopoietic stem transplantation(HSCT).

关键词： anemia aplastic interferon

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Recent progress in the study of transition in the hypersonic boundary layer

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National Science Review 2019年第1期6卷 155-170页

作者： Cunbiao Lee shiyi chen State Key Laboratory for Turbulence and Complex Systems Advanced Aero Engine Collaborative Innovation Center Peking University

Turbulence is a universal form of fluid motion. It is the key issue in fluid mechanics. Very recently, it has become a bottleneck in some key engineering research of national importance, such as aeronautics,astronautics and navigation. Developed turbulence and the onset of turbulence, i.e. transition, are two interrelated parts of turbulence. The hypersonic boundary-layer transition is a strategic focus in the fluid mechanics community. This article reviews recent developments in the study of the hypersonic boundary-layer transition, research facilities and experimental techniques. The hypersonic quiet wind tunnel is introduced as a necessary device to obtain real flight data in near space. Near-wall measurement techniques, such as temperature-sensitive paint, near-wall particle image velocimetry and Rayleigh-scattering visualization, are shown. The most important issues in the recent development of the transition in the hypersonic boundary layer are addressed. The instability and nonlinear interaction of different instability modes are discussed. The recent contributions from China, especially at Peking University, are also introduced.

关键词： hypersonic boundary layer transition quiet wind tunnel

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Anthropogenic monoterpenes aggravating ozone pollution

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National Science Review 2022年第9期9卷 178-185页

作者： Haichao Wang Xuefei Ma Zhaofeng Tan Hongli Wang Xiaorui chen shiyi chen Yaqin Gao Ying Liu Yuhan Liu Xinping Yang Bin Yuan Limin Zeng cheng Huang Keding Lu Yuanhang Zhang State Key Joint Laboratory of Environmental Simulation and Pollution Control State Environmental Protection Key Laboratory of Atmospheric Ozone Pollution ControlCollege of Environmental Sciences and Engineering Peking University School of Atmospheric Sciences Sun Yat-sen University Guangdong Provincial Observation and Research Station for Climate Environment and Air Quality Change in the Pearl River Estuary Key Laboratory of Tropical Atmosphere–Ocean System Ministry of Education Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai) Institute of Energy and Climate Research IEK-8:TroposphereForschungszentrum Jülich Gmb H State Environmental Protection Key Laboratory of Formation and Prevention of the Urban Air Complex Shanghai Academy of Environmental Sciences Institute for Environmental and Climate Research Jinan University

Monoterpenes have been known to have a critical influence on air quality and climate change through their impact on the formation of fine particles.Here we present field evidence that monoterpene oxidations largely enhanced local ozone production in a regional site in eastern China.The observed monoterpene was most likely from biomass burning rather than biogenic emissions,as indicated by the high correlation with CO at night-time,and the observed ratio of these two species was consistent with previously determined values from biomass burning experiments.Fast monoterpene oxidations were determined experimentally based on direct radical measurements,leading to a daily ozone enhancement of 4-18 parts per billion by volume(ppb),which was 6%-16% of the total ozone production,depending on the speciation of monoterpenes.It demonstrates that the previously overlo oked anthropogenic monoterpenes make an important contribution to 03 production in eastern China.The role could possibly be important at similar locations across China and other parts of the world that are characterized by massive emissions,especially where there are high NOxlevels.Our results highlight that anthropogenic monoterpenes should be taken into account when proceeding with the coordinated mitigation of O3and particulate matter pollution.

关键词： anthropogenic emissions biomass burning monoterpenes ozone pollution radical chemistry

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Transport of particles in an atmospheric turbulent boundary layer

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Acta Mechanica Sinica 2005年第3期21卷 235-242页

作者： Xiongping Luo shiyi chen National Key Laboratory for Turbulence Research Peking University Beijing 100871 China Department of Mechanical Engineering Johns Hopkins University Baltimore MD 21218 USA

A program incorporating the parallel code of large eddy simulation （LES） and particle transportation model is developed to simulate the motion of particles in an atmospheric turbulent boundary layer （ATBL）. A model of particles of 100-micrometer order coupling with large scale ATBL is proposed. Two typical cases are studied, one focuses on the evolution of particle profile in the ATBL and the landing displacement of particles, whereas the other on the motion of particle stream.

关键词： Transport of particles Large eddy simulation Atmospheric turbulent boundary layer

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Macrophage LMO7 deficiency facilitates inflammatory injury via metabolic-epigenetic reprogramming

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Acta Pharmaceutica Sinica B 2023年第12期13卷 4785-4800页

作者： Shixin Duan Xinyi Lou shiyi chen Hongchao Jiang Dongxin chen Rui Yin Mengkai Li Yuseng Gou Wenjuan Zhao Lei Sun Feng Qian Shanghai Frontiers Science Center of Drug Target Identification and Delivery National Key Laboratory of Innovative ImmunotherapyEngineering Research Center of Cell&Therapeutic AntibodyMinistry of EducationSchool of PharmacyShanghai Jiao Tong UniversityShanghai 200240China

Inflammatory bowel disease(IBD)is a formidable disease due to its complex pathogenesis.Macrophages,as a major immune cell population in IBD,are crucial for gut homeostasis.However,it is still unveiled how macrophages modulate IBD.Here,we found that LIM domain only 7(LMO7)was downregulated in pro-inflammatory macrophages,and that LMO7 directly degraded 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3(PFKFB3)through K48-mediated ubiquitination in macrophages.As an enzyme that regulates glycolysis,PFKFB3 degradation led to the glycolytic process inhibition in macrophages,which in turn inhibited macrophage activation and ultimately attenuated murine colitis.Moreover,we demonstrated that PFKFB3 was required for histone demethylase Jumonji domaincontaining protein 3(JMJD3)expression,thereby inhibiting the protein level of trimethylation of histone H3 on lysine 27(H3K27me3).Overall,our results indicated the LMO7/PFKFB3/JMJD3 axis is essential for modulating macrophage function and IBD pathogenesis.Targeting LMO7 or macrophage metabolism could potentially be an effective strategy for treating inflammatory diseases.

关键词： Inflammatory bowel disease Macrophage LMO7 Ubiquitination PFKFB3 JMJD3

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