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Discovery of Trametinib as an orchestrator for cytoskeletal vimentin remodeling

Journal of Molecular Cell biology 2024年第3期16卷 24-34页

作者： Shuangshuang Zhao Zhifang Li Qian Zhang Yue Zhang Jiali Zhang Gaofeng Fan Xiaobao Cao Yaming Jiu Unit of Cell biology and imaging Study of Pathogen Host Interaction The Center for MicrobesDevelopment and HealthKey Laboratory of Molecular Virology and ImmunologyShanghai Institute of Immunity and InfectionChinese Academy of SciencesShanghai 200031China Guangzhou National Laboratory Guangzhou 510005China University of Chinese Academy of Sciences Beĳing 100049China School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China

The dynamic remodeling of the cytoskeletal network of vimentin intermediate filaments supports various cellular functions,including cell morphology,elasticity,migration,organelle localization,and resistance against mechanical or pathological *** available chemicals targeting vimentin predominantly induce network reorganization and shrinkage around the *** tools for long-term manipulation of vimentin network dispersion in living cells are still lacking,limiting in-depth studies on vimentin function and potential therapeutic ***,we verified that a commercially available small molecule,trametinib,is capable of inducing spatial spreading of the cellular vimentin network without affecting its transcriptional or Translational *** evidence confirmed its low cytotoxicity and similar effects on different cell ***,Trametinib has no impact on the other two cytoskeletal systems,actin filaments and the microtubule ***,Trametinib regulates vimentin network dispersion rapidly and efficiently,with effects persisting for up to 48 h after drug *** also ruled out the possibility that Trametinib directly affects the phosphorylation level of *** summary,we identified an unprecedented regulator Trametinib,which is capable of spreading the vimentin network toward the cell periphery,and thus complemented the existing repertoire of vimentin remodeling drugs in the field of cytoskeletal research.

关键词： vimentin intermediate filaments cytoskeleton small molecule network reorganization

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Neuropathological characteristics of abnormal white matter functional signaling in adolescents with major depression

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World Journal of Psychiatry 2024年第2期14卷 276-286页

作者： Xin-Lin Huang Ju Gao Yong-Ming Wang Feng Zhu Jing Qin Qian-Nan Yao Xiao-Bin Zhang Hong-Yan Sun imaging and Nuclear Medicine Jiamusi UniversityJiamusi 154000Heilongjiang ProvinceChina Department of Psychiatry The Affiliated Guangji Hospital of Soochow UniversitySuzhou 215137Jiangsu ProvinceChina School of biology&Basic Medical Sciences Medical College of Soochow UniversitySuzhou 215137Jiangsu ProvinceChina Department of Radiology Shanghai Anting HospitalShanghai 20000China Department of Radiology The Affiliated Guangji Hospital of Soochow UniversitySuzhou 215137Jiangsu ProvinceChina

BACKGROUND Major depression disorder(MDD)constitutes a significant mental health *** surveys indicate that the lifetime prevalence of depression in adolescents is much higher than that in adults,with a corresponding increased risk of *** studying brain dysfunction associated with MDD in adolescents,research on brain white matter(WM)is *** researchers even mistakenly regard the signals generated by the WM as noise *** fact,studies have shown that WM exhibits similar blood oxygen level-dependent signal *** alterations in WM signals and their relationship with disease severity in adolescents with MDD remain *** To explore potential abnormalities in WM functional signals in adolescents with *** This study involved 48 adolescent patients with MDD and 31 healthy controls(HC).All participants were assessed using the Patient Health Questionnaire-9 Scale and the mini international neuropsychiatric interview(MINI)suicide *** addition,a Siemens Skyra 3.0T magnetic resonance scanner was used to obtain the subjects'image *** DPABI software was utilized to calculate the WM signal of the fractional amplitude of low frequency fluctuations(fALFF)and regional homogeneity,followed by a two-sample t-test between the MDD and HC *** component analysis(ICA)was also used to evaluate the WM functional ***’s correlation was performed to assess the relationship between statistical test results and clinical *** Compared to HC,individuals with MDD demonstrated a decrease in the fALFF of WM in the corpus callosum body,left posterior limb of the internal capsule,right superior corona radiata,and bilateral posterior corona radiata[P<0.001,family-wise error(FWE)voxel correction].The regional homogeneity of WM increased in the right posterior limb of internal capsule and left superior corona radiata,and decreased in the left superior longitudinal fasciculus(P<0.001,FWE voxel corre

关键词： White matter Regional homogeneity The fractional amplitude of low-frequency fluctuations Independent component analysis Adolescents Major depression disorders

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Activatable photoacoustic bioprobe for visual detection of aging in vivo

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Chinese Chemical Letters 2024年第4期35卷 324-329页

作者： Zihong Li Jie Cheng Ping Huang Guoliang Wu Weiying Lin Institute of Optical Materials and Chemical biology Guangxi Key Laboratory of Electrochemical Energy MaterialsSchool of Chemistry and Chemical EngineeringGuangxi UniversityNanning 530004China

Aging is a natural physiological process with various challenges, related to the loss of homeostasis within the organism, which is not a disease, but a significantly strong risk factor for multiple diseases, including myocardial infarction, stroke, some age-related cancers, macular degeneration, osteoarthritis, neurodegeneration, and many others. In the body, the main manifestation of aging is cellular aging, which exists within tissues and has a local or global impact on tissue function. However, the lack of effective aging detection tools has always been an issue that cannot be ignored in the field of aging research. Therefore,it is necessary to construct a non-invasive tool for in vivo detection of aging. Here, we show that the photoacoustic probe(LGAL), which has peak excitation and emission wavelengths in the near-infrared optical window, binds in vivo and at high contrast to the hallmark of aging, and allows for the microscopic imaging of aging through the intact mice. Firstly, this tool LGAL has been successfully applied to detect senescence in cells, displaying stronger photoacoustic signals than normal cells. Then, by using the photoacoustic probe, the blood vessels and tissues inside the mice can be visualized. Young and elderly mice exhibit varying intensities of photoacoustic signals, marking the first time a probe has been used to explore the aging of blood vessels and tissues inside the mice. Finally, we monitored the changes in the degree of aging during tumor treatment under photoacoustic(PA) imaging for the first time. As the treatment time increased, the degree of aging of the tumor gradually deepened. We expect the powerful tool could be a noninvasive and powerful tool for the study of aging biology.

关键词： Near-infrared Photoacoustic Aging Senescence Tumor Sa-β-gal

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Evaluating the tumor stratification with a lysosomal pH sensitive-probe by fluorescence lifetime imaging

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Chinese Chemical Letters 2024年第3期35卷 262-267页

作者： Jun Yan Xing Liang Qian Zhang Luolin Wang Weiying Lin Guangxi Key Laboratory of Electrochemical Energy Materials Institute of Optical Materials and Chemical BiologySchool of Chemistry and Chemical EngineeringGuangxi UniversityNanning 530004China

Owing to the anaerobic metabolism in the tumor,abundant acidic metabolites are produced and accumulated in the ***,the cells in different tumor layers are directly linked to the pH ***,due to the lack of robust tools,the high-efficient evaluation of the acidic micro-environment of tumor stratification faces the challenge of accurate *** designed a new pH sensitive fluorescent lifetime probe target to *** we expected,the fluorescence lifetime of PLN possesses a good linear fit to the pH value,which could detect the pH change at a single lysosome level in real time,and then evaluate the different acidity of tumor *** probe PLN is successfully used to evaluate the tumor stratification by fluorescence lifetime imaging microscopy(FLIM)for the first time,which is of great significance in the preoperative diagnosis of clinical tumor treatment or evaluation of drug delivery effect.

关键词： FLIM pH Fluorescence imaging Lysosome Tumor imaging

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通过单分子荧光显微成像解析活细胞内的生物分子动态

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Science Bulletin 2024年第12期69卷 1823-1828页

作者：高兆帅李茜樊春海侯尚国 School of Chemistry and Chemical Engineering New Cornerstone Science LaboratoryFrontiers Science Center for Transformative MoleculesNational Center for Translational MedicineShanghai Jiao Tong UniversityShanghai 200240China Institute of systems and Physical biology Shenzhen Bay LaboratoryShenzhen 518055China

The live-cell biomolecular dynamics refers to the rapid movement,interacting with their surroundings,and the transformation of biomolecules within living *** understanding of biomolecular dynamics in their native state may reveal fundamental molecular mechanisms of cell function and disease formation[1].Also,understanding the disease associated biomolecular dynamics can assist in disease diagnosis and therapy.

关键词：单分子荧光生物分子显微成像

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The First-in-Human Whole-Body Dynamic Pharmacokinetics Study of Aptamer

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Research 2024年第1期2023卷 119-130页

作者： Ding Ding Haitao Zhao Dali Wei Qinglai Yang Cai Yang Ruowen Wang Yumei Chen Lianghua Li Shuxian An Qian Xia Gang Huang Jianjun Liu Zeyu Xiao Weihong Tan Institute of Molecular Medicine(IMM) Renji HospitalState Key Laboratory of Oncogenes and Related GenesShanghai Jiao Tong University School of Medicineand College of Chemistry and Chemical EngineeringShanghai Jiao Tong UniversityShanghai 200240China Department of Nuclear Medicine Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China Center for Molecular imaging Probes Cancer Research InstituteUniversity of South ChinaHengyangHunan 421001China The Key Laboratory of Zhejiang Province for Aptamers and Theranostics Zhejiang Cancer HospitalHangzhou Institute of Medicine(HIM)Chinese Academy of SciencesHangzhouZhejiang 310022China Molecular Science and Biomedicine Laboratory(MBL) State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of Chemistry and Chemical EngineeringHunan UniversityChangshaHunan 410082China Shanghai Key Laboratory of Molecular imaging Shanghai University of Medicine and Health SciencesShanghai 201318China Department of Pharmacology and Chemical biology Shanghai Jiao Tong University School of MedicineShanghai200127China

Serving as targeting ligands,aptamers have shown promise in precision ***,the lack of knowledge of the biosafety and metabolism patterns in the human body largely impeded aptamers’clinical *** bridge this gap,here we report the first-in-human pharmacokinetics study of protein tyrosine kinase 7 targeted SGC8 aptamer via in vivo PET tracking of gallium-68(^(68)Ga)radiolabeled *** specificity and binding affinity of a radiolabeled aptamer,named ^(68)Ga[Ga]-NOTA-SGC8,were maintained as proven in *** preclinical biosafety and biodistribution evaluation confirmed that aptamers have no biotoxicity,potential mutation risks,or genotoxicity at high dosage(40 mg/kg).Based on this result,a first-in-human clinical trial was approved and carried out to evaluate the circulation and metabolism profiles,as well as biosafety,of the radiolabeled SGC8 aptamer in the human *** advantage of the cutting-edge total-body PET,the aptamers’distribution pattern in the human body was acquired in a dynamic fashion.

关键词： metabolism dosage Whole

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IMAGGS: a radiogenomic framework for identifying multi-way associations in breast cancer subtypes

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Journal of Genetics and Genomics 2024年第4期51卷 443-453页

作者： Shuyu Liang Sicheng Xu Shichong Zhou Cai Chang Zhiming Shao Yuanyuan Wang Sheng Chen Yunxia Huang Yi Guo Department of Electronic Engineering School of Information Science and TechnologyFudan UniversityShanghai 200433China The Key Laboratory of Medical imaging Computing and Computer Assisted Intervention(MICCAI)of Shanghai Shanghai 200032China Shanghai Key Laboratory of Metabolic Remodeling and Health Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200433China Department of Ultrasound Fudan University Shanghai Cancer CenterDepartment of OncologyShanghai Medical CollegeFudan UniversityShanghai 200032China Department of Breast Surgery Fudan University Shanghai Cancer CenterDepartment of OncologyShanghai Medical CollegeFudan UniversityShanghai 200032China

Investigating correlations between radiomic and genomic profiling in breast cancer(BC)molecular subtypes is crucial for understanding disease mechanisms and providing personalized *** present a well-designed radiogenomic framework image–gene–gene set(IMAGGS),which detects multi-way associations in BC subtypes by integrating radiomic and genomic *** dataset consists of 721 patients,each of whom has 12 ultrasound(US)images captured from different angles and gene mutation *** better characterize tumor traits,12 multi-angle US images are fused using two distinct ***,we analyze complex many-to-many associations between phenotypic and genotypic features using a machine learning algorithm,deviating from the prevalent one-to-one relationship pattern observed in previous *** radiomic and genomic features are screened using these *** addition,gene set enrichment analysis is performed to investigate the joint effects of gene sets and delve deeper into the biological functions of BC *** further validate the feasibility of IMAGGS in a glioblastoma multiforme dataset to demonstrate the scalability of IMAGGS across different modalities and *** together,IMAGGS provides a comprehensive characterization for diseases by associating imaging,genes,and gene sets,paving the way for biological interpretation of radiomics and development of targeted therapy.

关键词： IMAGGS Radiogenomic framework "lmage-gene-geneset"associations Molecular subtypes Breast cancer

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Dual-objective two-photon microscope for volumetric imaging of dense scattering biological samples by bidirectional excitation and collection

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Photonics Research 2024年第6期12卷 1351-1361页

作者： MUYUE ZHAI JING YU YANHUI HU HANG YU BEICHEN XIE YI YU DAWEI LI AIMIN WANG HEPING CHENG National Biomedical imaging Center College of Future TechnologyPeking UniversityBeijing 100871China Research Unit of Mitochondria in Brain Diseases Chinese Academy of Medical SciencesPKU-Nanjing Institute of Translational MedicineNanjing 211500China Beijing Transcend Vivoscope Biotech Beijing 100085China College of Engineering Peking UniversityBeijing 100871China Academy for Advanced Interdisciplinary Studies Peking UniversityBeijing 100871China Center for Quantitative biology Peking UniversityBeijing 100871China School of Electronics Peking UniversityBeijing 100871China State Key Laboratory of Advanced Optical Communication System and Networks Peking UniversityBeijing 100871China

Full view observation throughout entire specimens over a prolonged period is crucial when exploring the physiological functions and system-level ***-photon microscopy(MPM)has been widely employed for such purposes owing to its deep penetration ***,the current MPM struggles with balancing the imaging depth and quality while avoiding photodamage for the exponential increasement of excitation power with the imaging ***,we present a dual-objective two-photon microscope(Duo-2P),characterized by bidirectional two-photon excitation and fluorescence collection,for long-duration volumetric imaging of dense scattering ***-2P effectively doubles the imaging depth,reduces the total excitation energy by an order of magnitude for samples with a thickness five times the scattering length,and enhances the signal-to-noise ratio up to 1.4 *** these advantages,we acquired volumetric images of a 380-μm suprachiasmatic nucleus slice for continuous 4-h recording at a rate of 1.67 s/volume,visualized the calcium activities over 4000 neurons,and uncovered their state-switching *** conclude that Duo-2P provides an elegant and powerful means to overcome the fundamental depth limit while mitigating photodamages for deep tissue volumetric imaging.

关键词： excitation overcome exponential

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Self-assembled amphiphilic NIR-Ⅱ emissive nano-micelles for imaging-guided photothermal therapy of colorectal cancer

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Science China Chemistry 2024年第8期67卷 2767-2774页

作者： Axin He Fangfang Xia Da Han Qinglai Yang Weihong Tan Institute of Molecular Medicine(IMM) Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200240China Center for Molecular imaging Probe Hunan Province Key Laboratory of Cancer Cellular and Molecular PathologyCancer Research InstituteHengyang Medical SchoolUniversity of South ChinaHengyang 421001China The Key Laboratory of Zhejiang Province for Aptamers and Theranostics Zhejiang Cancer Hospital Hangzhou Institute of Medicine(HIM)Chinese Academy of SciencesHangzhou 310022China Molecular Science and Biomedicine Laboratory(MBL) State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of Chemistry and Chemical EngineeringCollege of BiologyAptamer Engineering Center of Hunan ProvinceHunan UniversityChangsha 410082China

Colorectal cancer(CRC) is one of the major causes of cancer-related mortality worldwide. Most near-infrared(NIR) agents used in clinical CRC treatment are at NIR-I(700–900 nm) window, which has limitations on deep tissue, and fluorescent probes in the second NIR(1,000–1,700 nm) allow high-resolution bioimaging with deep tissue penetration. However, existing NIR-II fluorophores used in clinical are still rare. Herein, based on shielding-donor-acceptor-donor-shielding(S-D-A-D-S) scaffold, we developed an organic small-molecule fluorophore IR-BTGP with NIR-II emission for imaging-guided photothermal therapy(PTT) in CRC mice model. Amphiphilic IR-BTGP can be self-assembled into spherical nano-micelles, which presents reliable water solubility and photothermal conversion efficiency(30.2%). In vitro experiments indicate that cancer cells treated with IRBTGP were significantly killed upon 808 nm light irradiation. Furthermore, in vivo NIR-II fluorescence imaging confirms that IR-BTGP accumulates in the tumor region. Remarkably, a significant tumor inhibition rate(78.5%) was observed in tumorbearing mice when treated with IR-BTGP plus 808 nm irradiation. Therefore, this work shows that IR-BTGP holds great promise as an NIR-II fluorescence imaging-guided PTT platform for CRC in the future.

关键词： photothermal therapy(PTT) second near-infrared(NIR-Ⅱ)imaging organic molecule

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Building Expertise on FAIR Through Evolving Bring Your Own Data(BYOD) Workshops: Describing the Data, Software, and Management-focused Approaches and Their Evolution

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Data Intelligence 2024年第2期6卷 429-456页

作者： César H.Bernabé Lieze Thielemans Rajaram Kaliyaperumal Claudio Carta Shuxin Zhang Celia W.G.van Gelder Nirupama Benis Luiz Olavo Bonino da Silva Santos Ronald Cornet Bruna dos Santos Vieira Nawel Lalout Ines Henriques Alberto Camara Ballesteros Kees Burger Martijn G.Kersloot Friederike Ehrhart Esther van Enckevort Chris T.Evelo Alasdair J.G.Gray Marc Hanauer Kristina Hettne Joep de Ligt Arnaldo Pereira Nuria Queralt-Rosinach Erik Schultes Domenica Taruscio Andra Waagmeester Mark D.Wilkinson Egon L.Willighagen Mascha Jansen Barend Mons Marco Roos Annika Jacobsen Biosemantics Group Department of Human GeneticsLeiden University Medical CentreLeidenThe Netherlands NIHR Academic Fellow in General Practice University College London and The Royal Free NHS Foundation Trust National centre for Rare Diseases Istituto Superiore di SanitaRomeItaly Department of Medical Informatics Amsterdam UMC location University of AmsterdamMeibergdreef 9AmsterdamThe Netherlands Amsterdam Public Health Methodology&Digital HealthAmsterdamThe Netherlands Health-Rl UtrechtThe Netherlands Semantics Services and Cybersecurity groupUniversity of TwenteEnschedeThe Netherlands Department of Medical imaging Radboud Institute for Health SciencesRadboud University Medical CenterNijmegenThe Netherlands Department of Medical BioSciences Radboud University Medical CenterNijmegenThe Netherlands The Duchenne Parent Project VeneendaalThe Netherlands Departamento de Biotecnologia-Biologia Vegetal Escuela Tecnica Superior de Ingenieria AgronomicaAlimentaria y de BiosistemasCentro de Biotecnologia y Genomica de PlantasUniversidad Politecnica de Madrid(UPM)-Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria-CSIC(INIA-CSIC).Campus MontegancedoPozuelo de Alarcon(Madrid)Spain Castor AmsterdamThe Netherlands Department of Bioinformatics-BiGCaT Maastricht UniversityMaastrichtThe Netherlands University Medical Center Groningen University of GroningenGroningenThe Netherlands Maastricht centre for systems biology(MaCSBio) Maastricht UniversityMaastrichtThe Netherlands Department of Computer Science Heriot-Watt UniversityEdinburghUK INSERM US14-OrphanetPlateforme Maladies RaresParisFrance centre for Digital Scholarship Leiden University LibrariesThe Netherlands Center for Molecular Medicine Cancer Genomics NetherlandsDepartment of GeneticsUniversity Medical Center UtrechtUniversity UtrechtThe Netherlands University of Aveiro DETI/IEETAAveiroPortugal GO FAIR Foundation LeidenThe Netherlands The Leiden Academic Center for Drug Research LeidenThe Netherlands Micel

Since 2014,"Bring Your Own Data"workshops(BYODs)have been organised to inform people about the process and benefits of making resources Findable,Accessible,Interoperable,and Reusable(FAIR,and the FAIRification process).The BYOD workshops'content and format differ depending on their goal,context,and the background and needs of ***-focused BYODs educate domain experts on how to make their data FAIR to find new answers to research ***-focused BYODs promote the benefits of making data FAIR and instruct project managers and policy-makers on the characteristics of FAIRification ***-focused BYODs gather software developers and experts on FAIR to implement or improve software resources that are used to support ***,these BYODs intend to foster collaboration between different types of stakeholders involved in data management,curation,and reuse(*** experts,trainers,developers,data owners,data analysts,FAIR experts).The BYODs also serve as an opportunity to learn what kind of support for FAIRification is needed from different communities and to develop teaching materials based on practical examples and *** this paper,we detail the three different structures of the BYODs and describe examples of early BYODs related to plant breeding data,and rare disease registries and biobanks,which have shaped the structure of the *** discuss the latest insights into making BYODs more productive by leveraging our almost ten years of training experience in these workshops,including successes and encountered ***,we examine how the participants'feedback has motivated the research on FAIR,including the development of workflows and software.

关键词： FAIR FAIRification FAIR expertise Bring Your Own Data Workshop BYOD

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