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A K~+-sensitive AND-gate dual-mode probe for simultaneous tumor imaging and malignancy identification

National Science Review 2022年第7期9卷 127-136页

作者： Qiyue Wang Fangyuan Li Zeyu Liang Hongwei Liao Bo Zhang Peihua Lin Xun Liu Shen Hu Jiyoung Lee Daishun Ling Institute of Pharmaceutics Hangzhou Institute of Innovative MedicineCollege of Pharmaceutical Sciences Zhejiang University World Laureates Association (WLA) Laboratories frontiers Science center for Transformative Molecules School of Chemistry and Chemical EngineeringNational Center for Translational Medicine Shanghai Jiao Tong University Department of Obstetrics The Second Affiliated Hospital of Zhejiang University School of Medicine

Although molecular imaging probes have the potential to non-invasively diagnose a tumor,imaging probes that can detect a tumor and simultaneously identify tumor malignancy remain ***,we demonstrate a potassium ion(K+) sensitive dual-mode nanoprobe(KDMN) for non-invasive tumor imaging and malignancy identification,which operates via a cascaded ’AND’ logic gate controlled by inputs of magnetic resonance imaging(MRI) and fluorescence imaging(FI) *** encapsulate commercial K~+ indicators into the hollow cavities of magnetic mesoporous silica nanoparticles,which are subsequently coated with a K+-selective membrane that exclusively permits the passage of K+while excluding other *** KDMN can readily accumulate in tumors and enhance the MRI contrast after systemic *** information of the tumor lesion is thus accessible via MRI and forms the first layer of the ’AND’ ***,the KDMN selectively captures K+and prevents interference from other cations,triggering a K~+-activated FI signal as the second layer of the ’AND’ gate in the case of a malignant tumor with a high extracellular K~+*** dual-mode imaging approach effectively eliminates false positive or negative diagnostic results and allows for non-invasive imaging of tumor malignancy with high sensitivity and accuracy.

关键词： dual-mode imaging probe fluorescence imaging MRI tumor malignancy identification potassium ion

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Memory Trace for Fear Extinction:Fragile yet Reinforceable

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Neuroscience Bulletin 2024年第6期40卷 777-794页

作者： Ying Liu Shuai Ye Xin-Ni Li Wei-Guang Li Department of Rehabilitation medicine State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain ScienceHuashan HospitalInstitute for Translational Brain ResearchFudan UniversityShanghai200032China

Fear extinction is a biological process in which learned fear behavior diminishes without anticipated reinforcement,allowing the organism to re-adapt to ever-changing *** on the behavioral hypothesis that extinction is new learning and forms an extinction memory,this new memory is more readily forgettable than the original fear *** brain’s cellular and synaptic traces underpinning this inherently fragile yet reinforceable extinction memory remain *** questions are about the whereabouts of the engram neurons that emerged during extinction learning and how they constitute a dynamically evolving functional construct that works in concert to store and express the extinction *** this review,we discuss recent advances in the engram circuits and their neural connectivity plasticity for fear extinction,aiming to establish a conceptual framework for understanding the dynamic competition between fear and extinction memories in adaptive control of conditioned fear responses.

关键词： Fear extinction memory Memory trace Fear relapse Medial prefrontal cortex Basolateral amygdala Ventral hippocampus Insular cortex Synaptic adaptations

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Hyperlanins A and B, Two Highly Rearranged Meroterpenoids from Hypericum lancasteri

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Chinese Journal of Chemistry 2024年第18期42卷 2180-2186页

作者： Jin-Qiu You Yun-Qi Jin Meng-Yu Li Bo-Chao Zhang Xin-Yu Sun Chun-Yong Ding Jing-Ya Li Ai-Jun Hou shanghai frontiers Science center of Drug Target Identification and Delivery School of Pharmaceutical SciencesShanghai Jiao Tong UniversityShanghai200240China National Key Laboratory of Innovative Immunotherapy Shanghai Jiao Tong UniversityShanghai 200240China shanghai Jiao Tong University School of medicine Shanghai 200025China shanghai Institute of Materia Medica Chinese Academy of SciencesShanghai 201203China

Hyperlanins A(1)and B(2),two highly rearranged polycyclic polyprenylated acylphloroglucinol(PPAP)-related meroterpenoids based on different new carbon skeletons,were isolated from Hypericum *** 1 incorporates an unprecedented 5/6/7/5 ring system featuring a 3,13-dioxatetracyclo[9.***.1.12.5.01.8]pentadecane *** 2 possesses a unique compact 6/6/5/6/6/5/6 ring system with a caged tetracyclo[6.***.1.13.8.05,11]dodecane *** structures were established by spectroscopic data,X-ray diffraction,and computational *** compounds showed anti-inflammatory activity in *** 1 and 2 could decrease the lipopolysaccharide(LPS)-/nigericin-induced IL-1βrelease in THP-1 *** compounds also showed inhibition in hypoxia-inducible factor-1α(HIF-1αa)pathway luciferase reporter assay.

关键词： Natural products Hypericum lancasteri Meroterpenoids Structureelucidation Inflammation

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A biomimetic nanoplatform for customized photothermal therapy of HNSCC evaluated on patient-derived xenograft models

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International Journal of Oral Science 2023年第1期15卷 87-98页

作者： Qi Wu Lan Chen Xiaojuan Huang Jiayi Lin Jiamin Gao Guizhu Yang Yaping Wu Chong Wang Xindan Kang Yanli Yao Yujue Wang Mengzhu Xue Xin Luan Xin Chen Zhiyuan Zhang Shuyang Sun Department of Oral and Maxillofacial-Head&Neck Oncology Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of Medicine/College of StomatologyShanghai Jiao Tong University/National Center for Stomatology/National Clinical Research Center for Oral Diseases/Shanghai Key Laboratory of Stomatology/Shanghai Research Institute of StomatologyShanghaiChina shanghai frontiers Science center for Chinese medicine Chemical Biology Institute of Interdisciplinary Integrative Medicine ResearchShanghai University of Traditional Chinese MedicineShanghaiChina School of Chemical Engineering and Technology Shaanxi Key Laboratory of Energy Chemical Process IntensificationInstitute of Polymer Science in Chemical EngineeringXi’an Jiao Tong UniversityXi’anChina

Cancer cell membrane(CCM)derived nanotechnology functionalizes nanoparticles(NPs)to recognize homologous cells,exhibiting translational potential in accurate tumor ***,these nanoplatforms are majorly generated from fixed cell lines and are typically evaluated in cell line-derived subcutaneous-xenografts(CDX),ignoring the tumor heterogeneity and differentiation from inter-and intra-individuals and microenvironments between heterotopic-and orthotopic-tumors,limiting the therapeutic efficiency of such ***,various biomimetic nanoplatforms(CCM-modified gold@Carbon,i.e.,Au@C-CCM)were fabricated by coating CCMs of head and neck squamous cell carcinoma(HNSCC)cell lines and patient-derived cells on the surface of Au@C *** generated Au@C-CCMs were evaluated on corresponding CDX,tongue orthotopic xenograft(TOX),immunecompetent primary and distant tumor models,and patient-derived xenograft(PDX)*** Au@C-CCM generates a photothermal conversion efficiency up to 44.2% for primary HNSCC therapy and induced immunotherapy to inhibit metastasis via photothermal therapy-induced immunogenic cell *** homologous CCM endowed the nanoplatforms with optimal targeting properties for the highest therapeutic efficiency,far above those with mismatched CCMs,resulting in distinct tumor ablation and tumor growth inhibition in all four *** work reinforces the feasibility of biomimetic NPs combining modular designed CMs and functional cores for customized treatment of HNSCC,can be further extended to other malignant tumors therapy.

关键词： xenograft patient custom

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Highly efficient discovery of the covalent Mpro inhibitors from crude Pu-erh tea by integrating biochemical and chemoproteomic approaches

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Food Science and Human Wellness 2024年

作者： Guang-Hao Zhu Ya-Ni Zhang Sheng-Lan Qi Jian-Rong Xu Yuan Xiong Zhao-Qin Zhang Xi-Xiang Chen Yuan-Yuan Xie Xiao-Qing Guan Wei-Dong Zhang Wei Liu Guang-Bo Ge shanghai frontiers Science center of TCM Chemical Biology， Institute of Interdisciplinary Integrative medicine Research， shanghai University of Traditional Chinese medicine Shuguang Hospital Affiliated to shanghai University of Traditional Chinese medicine

The main proteases (Mpros) are hydrolases playing essential roles in the replication of β-coronaviruses including SARS-CoV-2. Herein， a highly efficient strategy was developed for discovering the Mproinactivators from crude plant extract integrating target-based biochemical assay and chemoproteomic approaches. Firstly， Pu-erh tea was found to potently suppress SARS-CoV-2 Mproin a time-dependent manner. Next， global chemical analysis coupling with peptide-modification profiling were used to identify the cysteine-modified constituents in Pu-erh tea. The results suggested that seven constituents in Pu-erh tea could modify SARS-CoV-2 Mpro， which turned out that epigallocatechin， gallocatechin and gallic acid were the most efficacious Mproinactivators. Further investigations demonstrated that epigallocatechin and gallocatechin could inactivate SARS-CoV-2 Mprovia blocking the formation of the homodimers. Collectively， this work proposed a novel and practical strategy for highly efficient discovery of time-dependent inhibitors of SARS-CoV-2 Mprofrom plant extracts， while three constituents in Pu-erh tea have emerged as robust SARS-CoV-2 Mproinactivators.

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Novel heterozygous USH1C mutation impacts hair cell mechanotransduction and causes progressive hearing loss

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Science Bulletin 2024年第2期69卷 167-172页

作者： Yanyan Jia Gaogan Jia Luo Guo Nan Song Yu-Meng Wang Luoying Jiang Yilai Shu Yan Chen Shujia Zhu Huawei Li Wenyan Li ENT Institute and Otorhinolaryngology Department of Eye&ENT Hospital State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceFudan UniversityShanghai 200031China Institutes of Biomedical Sciences Fudan UniversityShanghai 200032China NHC Key Laboratory of Hearing medicine(Fudan University) Shanghai 200031China The Institutes of Brain Science and the Collaborative Innovation center for Brain Science Fudan UniversityShanghai 200032China shanghai center for Brain Science and Brain-Inspired Intelligence Technology Shanghai 201210China Institute of Neuroscience State Key Laboratory of NeuroscienceCAS Center for Excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesShanghai 200031China Department of Cardiology and Institute for Developmental and Regenerative Cardiovascular MedicineXinhua Hospital Affiliated to Shanghai Jiaotong University School of MedicineShanghai 200092China

Hearing loss is one of the most common sensory disorders worldwide,affecting approximately 466 million people,including 34 million children[1].Genetic mutations accounts for approximately 60%of inherited hearing loss cases[2,3].These genetic changes result in a wide variety of clinical manifestations,ranging from nonsyndromic hearing loss(NSHL)to over 400 syndromes involving hearing loss and from mild adult-onset hearing loss to profound congenital deafness,covering the entire spectrum of Mendelian inheritance.

关键词： mec hearing approximate

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Pro-senescence neddylation inhibitor combined with a senescence activated β-galactosidase prodrug to selectively target cancer cells

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Signal Transduction and Targeted Therapy 2022年第10期7卷 3645-3648页

作者： Shuaishuai Ni Qian Liu Xin Chen Lele Ding Lili Cai Fei Mao Donglei Shi Robert M.Hoffman Jian Li Lijun Jia Cancer Institute Longhua HospitalShanghai University of Traditional Chinese Medicine200032 ShanghaiChina State Key Laboratory of Bioreactor Engineering Shanghai Frontiers Science Center of Optogenetic Techniques for Cell MetabolismFrontiers Science Center for Materiobiology and Dynamic ChemistryShanghai Key Laboratory of New Drug DesignSchool of PharmacyEast China University of Science and Technology200037 ShanghaiChina Department of Surgery University of CaliforniaSan DiegoCAUSA

Dear Editor,Targeting senescence therapy is a promising anticancer strategy by arresting the cell-cycle and inducing cellular ***,senescent cells can promote malignancy and drug resistance.1,2 Thus,with the induction of senescence emerged as a viable therapeutic concept,it is important to consider how to eliminate those senescent cancer cells.

关键词： viable cancer eliminate

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Head-to-head comparison of plasma and PET imaging ATN markers in subjects with cognitive complaints

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Translational Neurodegeneration 2023年第1期12卷 428-442页

作者： Jiaying Lu Xiaoxi Ma Huiwei Zhang Zhenxu Xiao Ming Li Jie Wu Zizhao Ju Li Chen Li Zheng Jingjie Ge Xiaoniu Liang Weiqi Bao Ping Wu Ding Ding Tzu-Chen Yen Yihui Guan Chuantao Zuo Qianhua Zhao 无 Department of Nuclear medicine and PET center Huashan HospitalFudan UniversityShanghaiChina National Clinical Research center for Aging and medicine and National center for Neurological Disorders Huashan Hos-pitalFudan UniversityShanghaiChina Department of Neurology Huashan HospitalFudan UniversityShanghaiChina Department of Ultrasound Huashan HospitalFudan UniversityShanghaiChina APRINOIA Therapeu-tics Co. LtdSuzhouChina Human Phenome Institute Fudan UniversityShanghaiChina MOE frontiers center for Brain Science Fudan UniversityShanghaiChina on behalf of the shanghai Memory Study(SMS)

Background Gaining more information about the reciprocal associations between different biomarkers within the ATN(Amyloid/Tau/Neurodegeneration)framework across the Alzheimer’s disease(AD)spectrum is clinically *** aimed to conduct a comprehensive head-to-head comparison of plasma and positron emission tomography(PET)ATN biomarkers in subjects with cognitive *** A hospital-based cohort of subjects with cognitive complaints with a concurrent blood draw and ATN PET imaging(18F-florbetapir for A,18F-Florzolotau for T,and 18F-fluorodeoxyglucose[18F-FDG]for N)was enrolled(n=137).Theβ-amyloid(Aβ)status(positive versus negative)and the severity of cognitive impairment served as the main outcome measures for assessing biomarker *** Plasma phosphorylated tau 181(p-tau181)level was found to be associated with PET imaging of ATN biomarkers in the entire *** p-tau181 level and PET standardized uptake value ratios of AT biomarkers showed a similarly excellent diagnostic performance for distinguishing between Aβ+and Aβ−*** increased tau burden and glucose hypometabolism were significantly associated with the severity of cognitive impairment in Aβ+***,glucose hypometabolism-along with elevated plasma neurofilament light chain level-was related to more severe cognitive impairment in Aβ−*** Plasma p-tau181,as well as 18F-florbetapir and 18F-Florzolotau PET imaging can be considered as interchangeable biomarkers in the assessment of Aβstatus in symptomatic stages of AD.18F-Florzolotau and 18F-FDG PET imaging could serve as biomarkers for the severity of cognitive *** findings have implications for establishing a roadmap to identifying the most suitable ATN biomarkers for clinical use.

关键词： ATN biomarkers PET imaging Plasma Clinical severity

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Neuronal and synaptic adaptations underlying the benefits of deep brain stimulation for Parkinson’s disease

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Translational Neurodegeneration 2023年第1期12卷 90-110页

作者： Wenying Xu Jie Wang Xin-Ni Li Jingxue Liang Lu Song Yi Wu Zhenguo Liu Bomin Sun Wei-Guang Li Department of Rehabilitation medicine Huashan HospitalInstitute for Translational Brain ResearchState Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain ScienceFudan UniversityShanghai 200032China Department of Neurosurgery Center for Functional NeurosurgeryRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Department of Neurology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Ministry of Education-shanghai Key Laboratory for Children’s Environmental Health Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China

Deep brain stimulation(DBS)is a well-established and effective treatment for patients with advanced Parkinson’s disease(PD),yet its underlying mechanisms remain ***,primarily conducted in animal models,provides a unique approach that allows cell type-and projection-specific modulation that mirrors the frequency-dependent stimulus effects of ***-DBS research in animal models plays a pivotal role in unraveling the neuronal and synaptic adaptations that contribute to the efficacy of DBS in PD ***-induced neuronal responses rely on a complex interplay between the distributions of presynaptic inputs,frequency-dependent synaptic depression,and the intrinsic excitability of postsynaptic *** orchestration leads to conversion of firing patterns,enabling both antidromic and orthodromic modulation of neural *** these mechanisms is vital for decoding position-and programming-dependent effects of ***,patterned stimulation is emerging as a promising strategy yielding long-lasting therapeutic *** on the neuronal and synaptic adaptations to DBS may pave the way for the development of more enduring and precise modulation *** technologies,such as adaptive DBS or directional electrodes,can also be integrated for circuit-specific *** insights hold the potential to greatly improve the effectiveness of DBS and advance PD treatment to new levels.

关键词： Parkinson’s disease Deep brain stimulation Optogenetics Opto-DBS Synaptic adaptation Orthodromic effects Antidromic effects Long-lasting therapeutic effects

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Recent advances in nanomedicines for the treatment of ischemic stroke

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Acta Pharmaceutica Sinica B 2021年第7期11卷 1767-1788页

作者： Chao Li Tao Sun Chen Jiang Key Laboratory of Smart Drug Delivery Ministry of EducationState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceDepartment of PharmaceuticsSchool of PharmacyResearch Center on Aging and MedicineFudan UniversityShanghai 201203China

Ischemic stroke is a cerebrovascular disease normally caused by interrupted blood supply to the *** would initiate the cascade reaction consisted of multiple biochemical events in the damaged areas of the brain,where the ischemic cascade eventually leads to cell death and brain *** researches focusing on different stages of the cascade reaction have been conducted with the aim of curing ischemic ***,traditional treatment methods based on antithrombotic therapy and neuroprotective therapy are greatly limited for their poor safety and treatment *** provides new possibilities for treating stroke as they could improve the pharmacokinetic behavior of drugs in vivo,achieve effective drug accumulation at the target site,enhance the therapeutic effect and meanwhile reduce the side *** this review,we comprehensively describe the pathophysiology of stroke,traditional treatment strategies and emerging nanomedicines,summarize the barriers and methods for transporting nanomedicine to the lesions,and illustrate the latest progress of nanomedicine in treating ischemic stroke,with a view to providing a new feasible path for the treatment of cerebral ischemia.

关键词： Stroke Ischemic cascade Reperfusion Neuroprotectant Thrombolytics Nanomedicine Blood-brain barrier

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