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Aβ-Aggregation-Generated Blue Autofluorescence Illuminates Senile Plaques as well as Complex Blood and Vascular Pathologies in Alzheimer’s Disease

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Neuroscience Bulletin 2024年第8期40卷 1115-1126页

作者： Hualin Fu Jilong Li Chunlei Zhang Peng Du Guo Gao Qiqi Ge xinping Guan Daxiang Cui Institute of Nano Biomedicine and Engineering School of Sensing Science and EngineeringSchool of Electronic Information and Electrical EngineeringShanghai Jiao Tong UniversityShanghai 200240China Institute of Marine Equipment Shanghai Jiao Tong UniversityShanghai 200240China National Center for Translational medicine Shanghai Jiao Tong UniversityShanghai 200240China Department of Colorectal Surgery School of MedicineXinhua HospitalShanghai Jiao Tong UniversityShanghai 200092China Department of Automation Shanghai Jiao Tong UniversityShanghai 200240China The Key Laboratory of System Control and Information Processing Ministry of EducationShanghai 200240China

Senile plaque blue autofluorescence was discovered around 40 years ago,however,its impact on Alzheimer’s disease(AD)pathology has not been fully *** analyzed senile plaques with immunohistochemistry and fluorescence imaging on AD brain sections and also Aβ aggregation in *** DAPI or Hoechst staining,the nuclear blue fluorescence could only be correctly assigned after subtracting the blue plaque *** flower-like structures wrapping dense-core blue fluorescence formed by cathepsin D staining could not be considered central-nucleated neurons with defective lysosomes since there was no nuclear staining in the plaque core when the blue autofluorescence was *** Aβ self-oligomers and Aβ/hemoglobin heterocomplexes generated blue *** Aβ amyloid blue autofluorescence not only labels senile plaques but also illustrates red cell aggregation,hemolysis,cerebral amyloid angiopathy,vascular plaques,vascular adhesions,and *** summary,we conclude that Aβ-aggregation-generated blue autofluorescence is an excellent multi-amyloidosis marker in Alzheimer’s disease.

关键词： Senile plaque Blue autofluorescence Aβ Amyloid aggregation Hemoglobin Cathepsin D.Microaneurysm Alzheimer's disease

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Multi-omics integration reveals potential stage-specific druggable targets in T-cell acute lymphoblastic leukemia

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Genes & Diseases 2024年第5期11卷 374-389页

作者： Zijun Yan Jie xia Ziyang Cao Hongyang Zhang Jinxia Wang Tienan Feng Yi Shu Lin Zou Clinical Research Unit Shanghai Children’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200062China Institute of Pediatric Infection Immunityand Critical Care MedicineShanghai Jiao Tong University School of MedicineShanghai 200062China Center for Clinical Molecular Laboratory medicine of Children’s hospital of Chongqing Medical university Chongqing 400014China Clinical Research Institute Shanghai Jiao Tong University School of MedicineShanghai 200025China Bioinformatics and BioMedical Bigdata Mining Laboratory School of Big HealthGuizhou Medical UniversityGuiyangGuizhou 554300China

T-cell acute lymphoblastic leukemia(T-ALL),a heterogeneous hematological malignancy,is caused by the developmental arrest of normal T-cell *** development of targeted therapeutic regimens is impeded by poor knowledge of the stage-specific aberrances in this *** this study,we performed multi-omics integration analysis,which included mRNA expression,chromatin accessibility,and gene-dependency database analyses,to identify potential stage-specific druggable targets and repositioned drugs for this *** multi-omics integration helped identify 29 potential pathological genes for *** genes exhibited tissue-specific expression profiles and were enriched in the cell cycle,hematopoietic stem cell differentiation,and the AMPK signaling *** these,four known druggable targets(CDK6,TUBA1A,TUBB,and TYMS)showed dysregulated and stage-specific expression in malignant T cells and may serve as stage-specific targets in *** TUBA1A expression level was higher in the early T cell precursor(ETP)-ALL cells,while TUBB and TYMS were mainly highly expressed in malignant T cells arrested at the CD4 and CD8 double-positive or single-positive ***6 exhibited a U-shaped expression pattern in malignant T cells along the naıve to maturation ***,mebendazole and gemcitabine,which target TUBA1A and TYMS,respectively,exerted stage-specific inhibitory effects on T-ALL cell lines,indicating their potential stage-specific antileukemic role in ***,our findings might aid in identifying potential stage-specific druggable targets and are promising for achieving more precise therapeutic strategies for T-ALL.

关键词： Multi-omics Stage-specific druggable targets Targeted therapeutic strategies T-cell acute lymphoblastic leukemia Drug repositioning

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A Transformer-Assisted Cascade Learning Network for Choroidal Vessel Segmentation

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Journal of Computer Science & Technology 2024年第2期39卷 286-304页

作者：温阳吴依林毕磊石武祯刘潇骁许毓鹏许迅曹文明冯大淦 Guangdong Provincial Key Laboratory of Intelligent Information Processing School of Electronics and Information EngineeringShenzhen UniversityShenzhen 518060China Institute of Translational medicine Shanghai Jiao Tong UniversityShanghai 200240China Department of Ophthalmology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China school of Information Technologies The University of SydneySydney 2006Australia

As a highly vascular eye part,the choroid is crucial in various eye disease ***,limited research has focused on the inner structure of the choroid due to the challenges in obtaining sufficient accurate label data,particularly for the choroidal ***,the existing direct choroidal vessel segmentation methods for the intelligent diagnosis of vascular assisted ophthalmic diseases are still unsatisfactory due to noise data,while the synergistic segmentation methods compromise vessel segmentation performance for the choroid layer segmentation *** cascaded structures grapple with error propagation during *** address these challenges,we propose a cascade learning segmentation method for the inner vessel structures of the choroid in this ***,we propose TransformerAssisted Cascade Learning Network(TACLNet)for choroidal vessel segmentation,which comprises a two-stage training strategy:pre-training for choroid layer segmentation and joint training for choroid layer and choroidal vessel *** also enhance the skip connection structures by introducing a multi-scale subtraction connection module designated as MSC,capturing differential and detailed information ***,we implement an auxiliary Transformer branch named ATB to integrate global features into the segmentation *** results exhibit that our method achieves the state-of-the-art performance for choroidal vessel ***,we further validate the significant superiority of the proposed method for retinal fluid segmentation in optical coherence tomography(OCT)scans on a publicly available *** these fully prove that our TACLNet contributes to the advancement of choroidal vessel segmentation and is of great significance for ophthalmic research and clinical application.

关键词： choroidal vessel segmentation optical coherence tomography(OCT) Transformer-assisted cascade learning retinal fluid segmentation multi-scale feature extraction

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Development and Characterization of Novel FAP-Targeted Theranostic Pairs: A Bench-to-Bedside Study

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Research 2024年第3期2023卷 473-485页

作者： Wei Huang Yizhen Pang Qiufang Liu Chenyi Liang Shuxian An Qianyun Wu You Zhang Gang Huang Haojun Chen Jianjun Liu Weijun Wei Department of Nuclear medicine Institute of Clinical Nuclear MedicineRenj HospitalSchool of Medicine Shanghai Jiao Tong UniversityShanghai 200127China Department of Nuclear medicine and Minnan PET Center Xiamen Cancer CenterXiamen Key Laboratory of Radiation OncologyThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361003China Department of Nuclear medicine Fudan University Shanghai Cancer CenterFudan UniversityShanghai 200032China

Fibroblast activation protein (FAP) is among the most popular targets in nuclear medicine imaging and cancer theranostics. Several small-molecule moieties (FAPI-04, FAPI-46, etc.) are used for developing FAP-targeted theranostic agents. Nonetheless, the circulation time of FAP inhibitors is relatively short, resulting in rapid clearance via kidneys, low tumor uptake, and associated unsatisfactory treatment efficacy. To address the existing drawbacks, we engineered 3 peptides named FD1, FD2, and FD3 with different circulation times through solid-phase peptide synthesis. All the 3 reported peptides bind to human and murine FAP with single-digit nanomolar affinity measured by surface plasmon resonance. The diagnostic and therapeutic potential of the agents labeled with 68Ga and 177Lu was assessed in several tumor models exhibiting different levels of FAP expression. While radiolabeled FD1 was rapidly excreted from kidneys, radiolabeled FD2/FD3 have significantly prolonged circulation, increased tumor uptake, and decreased kidney accumulation. Our findings indicated that [68Ga]Ga-DOTA-FD1 positron emission tomography (PET) effectively detected FAP dynamics, whereas [177Lu]Lu-DOTA-FD2 and [177Lu]Lu-DOTA-FD3 exhibited remarkable therapeutic efficacy in FAP-overexpressing tumor models, including pancreatic cancer cell models characterized by abundant stroma. Moreover, a pilot translational investigation demonstrated that [68Ga]Ga-DOTA-FD1 had the capability to identify both primary and metastatic tumors with precision and distinction. In summary, we developed [68Ga]Ga-DOTA-FD1 for same-day PET imaging of FAP dynamics and [177Lu]Lu-DOTA-FD2 and [177Lu]Lu-DOTA-FD3 for effective radioligand therapy of FAP-overexpressing tumors.

关键词： DOTA expressing labeled

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Finger-actuated wireless-charging wearable multifunctional sweatsensing system for levodopa and vitamin C

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Nano Research 2024年第4期17卷 3096-3106页

作者： Qihong Ning Shaoqing Feng Qingwen Sun Ruoyao Yu Tangan Li Hao Xu Daxiang Cui Kan Wang school of Sensing Science and Engineering School of Electronic Information and Electrical EngineeringShanghai Jiao Tong UniversityKey Laboratory of Thin Film and Microfabrication Technology(Ministry of Education)Shanghai 200240China Department of Plastic and Reconstructive Surgery Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China school of Naval Architecture Ocean&Civil EngineeringShanghai Jiao Tong UniversityShanghai 200240China

Efficient portable wearable sweat sensors allow the long-term monitoring of changes in the status of biomarkers in sweat,which can be useful in diagnosis,medication,and nutritional *** this study,we designed and tested a wireless,battery-free,flexible,self-pumping sweat-sensing system that simultaneously tracks levodopa and vitamin C levels in human sweat and detects body *** system includes a microfluidic chip with a self-driven pump and anti-reflux valve,a flexible wireless circuit board,and a purpose-designed smartphone *** microfluidic chip is used for the efficient collection of sweat and the drainage of excess *** dual electrochemical sensing electrodes in the chip are modified with functional materials and appropriate enzymatic reagents,achieving excellent selectivity and *** sensitivities of the levodopa sensor and the vitamin C sensor are 0.0073 and 0.0018μA·μM^(-1),respectively,and the detection correlation coefficients of both exceed *** sensors have a wide linear detection range of 0–100 and 0–1000μM,respectively,and low detection limits of 0.28 and 17.9μM,*** flexible wireless circuit board is equipped with the functions of wireless charging,electrical signal capture and processing,and wireless *** data recorded from each sensor are displayed on a smartphone via a self-developed app.A series of experimental results confirmed the reliability of the sweat-sensing system in noninvasively monitoring important biomarkers in the human body and its potential utility in the comprehensive assessment of biological health.

关键词： self-pumping microfluidic channel wireless charging wearable sensor health monitoring

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Dexmedetomidine ameliorates diabetic intestinal injury by promoting the polarization of M2 macrophages through the MMP23B pathway

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World Journal of Diabetes 2024年第9期15卷 1962-1978页

作者： Man Lu xiao-Wen Guo Fang-Fang Zhang Dan-Hong Wu Di xie Feng-Qin Luo Department of Anesthesiology The First Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Traditional Chinese Medicine)Hangzhou 310006Zhejiang ProvinceChina Department of Emergency Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China

BACKGROUND Diabetes is often associated with gastrointestinal dysfunctions,which can lead to ***(DEX)is a commonly used sedative in perioperative diabetic patients and may affect gastrointestinal *** To investigate whether sedative doses of DEX alleviate diabetes-caused intestinal *** Sedation/anesthesia scores and vital signs of streptozotocin(STZ)-induced diabetic mice under DEX sedation were *** mice were divided into saline and DEX *** injecting sedatives intraperitoneally,tight junctions(TJs)and apoptotic levels were evaluated 24 hours later to assess the intestinal barrier *** role of DEX was validated using Villin-MMP23B flox/flox mice with intestinal epithelial *** vitro,high glucose and hyperosmolarity were used to culture Caco-2 monolayer cells with STZ *** techniques were used to monitor the barrier and mitochondrial *** MMP23B protein levels in the intestinal tissue of STZ-induced diabetic mice were significantly higher than those in the intestinal tissue of control mice,with the DEX group displaying decreased MMP23B ***-mediated TJ disruption,increased intestinal mucosal permeability,and systemic inflammation in wild-type mice might be reversed by *** Caco-2 cells,MMP23B was associated with increased reactive oxygen species accumulation,mitochondrial membrane potential depolarization,and TJ *** DEX reduces MMP23B,which may potentially contribute to STZ-induced intestinal barrier dysfunction,affecting TJ modification through mitochondrial dysfunction.

关键词： Diabetes Dexmedetomidine Intestinal barrier Piezo1 Tight junctions

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Multi-omics analysis of human tendon adhesion reveals that ACKR1-regulated macrophage migration is involved in regeneration

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Bone Research 2024年第2期12卷 390-406页

作者： xinshu Zhang Yao xiao Bo Hu Yanhao Li Shaoyang Zhang Jian Tian Shuo Wang Zaijin Tao xinqi Zeng Ning-Ning Liu Baojie Li Shen Liu Department of Orthopaedics Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine600 Yishan RdShanghai 200233PR China Section of Spine Surgery Department of OrthopaedicsChangzheng HospitalNaval Medical UniversityShanghai 200003PR China Bio-X Institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric DisordersMinistry of EducationShanghai Jiao Tong UniversityShanghai 200241PR China Department of Orthopaedics Wuxi Ninth People’s Hospital Affiliated to Soochow UniversityWuxi 214062PR China State Key Laboratory of Systems medicine for Cancer Center for Single-Cell OmicsSchool of Public HealthShanghai Jiao Tong University School of MedicineShanghai 200025China

Tendon adhesion is a common complication after tendon injury with the development of accumulated fibrotic tissues without effective anti-fibrotic therapies,resulting in severe *** are widely recognized as a fibrotic trigger during peritendinous adhesion ***,different clusters of macrophages have various functions and receive multiple regulation,which are both still *** our current study,multi-omics analysis including single-cell RNA sequencing and proteomics was performed on both human and mouse tendon adhesion tissue at different stages after tendon *** transcriptomes of over 74000 human single cells were *** results,we found that SPP1^(+)macrophages,RGCC^(+)endothelial cells,ACKR1^(+)endothelial cells and ADAM12^(+)fibroblasts participated in tendon adhesion ***,despite specific fibrotic clusters in tendon adhesion,FOLR2^(+)macrophages were identified as an antifibrotic cluster by in vitro experiments using human ***,ACKR1 was verified to regulate FOLR2^(+)macrophages migration at the injured peritendinous site by transplantation of bone marrow from Lysm-Cre;R26R^(tdTomato) mice to lethally irradiated Ackr1^(-/-)mice(Ackr1^(-/-)chimeras;deficient in ACKR1)and control mice(WT chimeras).Compared with WT chimeras,the decline of FOLR2^(+)macrophages was also observed,indicating that ACKR1 was specifically involved in FOLR2^(+)macrophages *** together,our study not only characterized the fibrosis microenvironment landscape of tendon adhesion by multi-omics analysis,but also uncovered a novel antifibrotic cluster of macrophages and their *** results provide potential therapeutic targets against human tendon adhesion.

关键词： tendon analysis landscape

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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 *** 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 *** 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)*** 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 *** 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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Cross-sectional network analysis of plasma proteins/metabolites correlated with pathogenesis and therapeutic response in acute promyelocytic leukemia

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Frontiers of medicine 2024年第2期18卷 327-343页

作者： Niu Qiao Yizhu Lyu Feng Liu Yuliang Zhang xiaolin Ma xiaojing Lin Junyu Wang Yinyin xie Ruihong Zhang Jing Qiao Hongming Zhu Li Chen Hai Fang tong Yin Zhu Chen Qiang Tian Saijuan Chen Shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine at ShanghaiRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200025China Department of Hematology Second Hospital of Dalian Medical UniversityDalian116021China

The treatment of PML/RARA+acute promyelocytic leukemia(APL)with all-trans-retinoic acid and arsenic trioxide(ATRA/ATO)has been recognized as a model for translational medicine *** an altered microenvironment is a general cancer hallmark,how APL blasts shape their plasma composition is poorly ***,we reported a cross-sectional correlation network to interpret multilayered datasets on clinical parameters,proteomes,and metabolomes of paired plasma samples from patients with APL before or after ATRA/ATO induction *** study revealed the two prominent features of the APL plasma,suggesting a possible involvement of APL blasts in modulating plasma *** was characterized by altered secretory protein and metabolite profiles correlating with heightened proliferation and energy consumption in APL blasts,and the other featured APL plasma-enriched proteins or enzymes catalyzing plasma-altered metabolites that were potential trans-regulatory targets of PML/***,results indicated heightened interferon-gamma signaling characterizing a tumor-suppressing function of the immune system at the first hematological complete remission stage,which likely resulted from therapy-induced cell death or senescence and ensuing supraphysiological levels of intracellular ***,our work sheds new light on the pathophysiology and treatment of APL and provides an information-rich reference data cohort for the exploratory and translational study of leukemia microenvironment.

关键词： acute promyelocytic leukemia plasma proteomics plasma metabolomics cross-sectional correlation network pathogenesis treatment

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Superplastic Tension Behavior of Dissimilar TC4/SP700 Laminate through Diffusion Bonding

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Acta Metallurgica Sinica(English Letters) 2024年第2期37卷 353-363页

作者： Qianwen Zhang Tianle Li Yanbin Han Wei Zheng xifeng Li Jianjun Wu school of Mechanical Engineering Northwestern Polytechnical UniversityXi’an710072China AVIC xi’an Aircraft Industry Group Company Ltd Xi’an710089China Institute of Forming Technology and Equipment School of Materials Science and EngineeringShanghai Jiao Tong UniversityShanghai200030China

Superplastic forming is a practical method to manufacture complex-shaped parts of titanium alloys with large *** parts of dissimilar titanium alloys fabricated by superplastic forming can achieve excellent performance by combining the advantages of *** work displays the superplastic tension behavior and microstructural evolution of dissimilar TC4/SP700 laminate prepared by the diffusion bonding *** titanium alloys can achieve metallurgical bonding at parameters of 800℃/1 h/5 *** for dynamic recrystallization and grain growth behaviors upon superplastic tension,stress-induced phase transformation plays an important role inαtoβphase transformation apart from the elevated *** superplastic deformation can be attributed to the grain boundary sliding accommodated multiplex motion of *** addition,the retained strengths of all dissimilar TC4/SP700 laminates after superplastic deformation with different strain rates and temperatures range from 807 to 890 MPa.

关键词： TC4/SP700 laminate Diffusion bonding Microstructure Superplastic tension Strength

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