Contrary to the adult central nervous system,the peripheral nervous system has an intrinsic ability to regenerate that relies on the expression of regenerationassociated genes,such as some kinesin family members.Kines...Contrary to the adult central nervous system,the peripheral nervous system has an intrinsic ability to regenerate that relies on the expression of regenerationassociated genes,such as some kinesin family members.Kinesins contribute to nerve regeneration through the transport of specific cargo,such as proteins and membrane components,from the cell body towards the axon periphery.We show here that KIF4A,associated with neurodevelopmental disorders and previously believed to be only expressed during development,is also expressed in the adult vertebrate nervous system and up-regulated in injured peripheral nervous system cells.KIF4A is detected both in the cell bodies and regrowing axons of injured neurons,consistent with its function as an axonal transporter of cargoes such asβ1-integrin and L1CAM.Our study further demonstrates that KIF4A levels are greatly increased in Schwann cells from injured distal nerve stumps,particularly at a time when they are reprogrammed into an essential proliferative repair phenotype.Moreover,Kif4a m RNA levels were approximately~6-fold higher in proliferative cultured Schwann cells compared with non-proliferative ones.A hypothesized function for Kif4a in Schwann cell proliferation was further confirmed by Kif4a knockdown,as this significantly reduced Schwann cell proliferation in vitro.Our findings show that KIF4A is expressed in adult vertebrate nervous systems and is up-regulated following peripheral injury.The timing of KIF4A up-regulation,its location during regeneration,and its proliferative role,all suggest a dual role for this protein in neuroregeneration that is worth exploring in the future.展开更多
Neuroimmunology is emerging as a pivotal field,shedding light on the intricate dialogues between the central nervous system(CNS)and the immune system.This exploration is particularly significant in understanding micro...Neuroimmunology is emerging as a pivotal field,shedding light on the intricate dialogues between the central nervous system(CNS)and the immune system.This exploration is particularly significant in understanding microglia,the CNS’s innate immune cells,beyond the conventional conflation of“neuroinflammation”and“microglial activation.”This conflation has clouded the true complexity of these processes,potentially stalling scientific progress and the development of new therapies.We challenge the long-standing perspectives that have oversimplified these interactions,advocating for a deeper exploration of the dynamic relationship between neuroinflammation and microglial activation.By dissecting specific molecular pathways,we aim to illuminate their elaborate roles in neuroinflammatory responses,especially in the context of Alzheimer’s disease(AD).Here,neuroinflammation is not merely a passive observer or a direct antagonist but a complex agent in the disease’s progression.This article calls for a significant paradigm shift towards an integrative,multi-omics approach to neuroimmunology.Adopting such a comprehensive framework is crucial for advancing our understanding of neuroinflammatory conditions and paving the way for targeted therapeutic strategies for brain diseases.展开更多
Early diagnosis and accurate boundary delineation are the key steps of tumor precision medicine.Circulating tumor cells(CTCs)detection of liquid biopsy can provide abundant information for early diagnosis of cancer.Hi...Early diagnosis and accurate boundary delineation are the key steps of tumor precision medicine.Circulating tumor cells(CTCs)detection of liquid biopsy can provide abundant information for early diagnosis of cancer.High detection specificity and good enrichment features are two key factors for CTCs accurate identification in peripheral blood sample.For this purpose,iron oxide(IO)-based surface-enhanced Raman scattering(SERS)bioprobes with good biocompatibility,high detection sensitivity,remarkable detection specificity,and good enrichment efficiency,were developed for detecting different types of CTCs.Magnetic SERS bioprobes combined with programmed death ligand-1(PD-L1)antibody are regarded as an effective way to boost the targeting ability and detection specificity,benefiting for accurately capturing and identifying rare CTCs.Four types of CTCs with different PD-L1 expression were accurately distinguished among white blood cells via high-resolution SERS mapping images and stable Raman signals.Subsequently,CTCs blood samples obtained from the triple negative breast cancer patients were also successfully recognized compared to that of health people,indicating IO@AR@PDA-a PD-L1 SERS bioprobe possessed great potential for CTCs detection in liquid biopsy.Additionally,IO-based bioprobe exhibited excellent dual-modal imaging abilities of high-resolution SERS imaging mode and microimaging magnetic resonance imaging mode.These two highly complementary imaging modes endowed IO-based bioprobes unrivalled capacity in tumor boundary differentiation,supporting tumor accurate resection and precise surgery.To our best knowledge,this is the first time that biocompatible IO-based SERS bioprobes without noble metal element were reported not only for CTCs accurate detection,but also for precise tumor boundary delineation,showing great advantages in tumor diagnosis and treatment.展开更多
基金supported by the Portuguese Foundation for Science and Technology(FCT),Centro 2020 and Portugol2020 and the EU FEDER program,via the project GoBack to SIV(PTDC/CVT-CVT/32261/2017,CENTRO-01-0145-FEDER-032261)the doctoral grants of PDC(SFRH/BD/139974/2018)and BMS(2020.06525.BD and DOI 10.54499/2020.06525.BD)+5 种基金the post-doctoral grant to JPF(SFRH/BPD/113359/2015-program-contract described in paragraphs 4,5,6 of art.23 of Law no.100157/2016,of August 29,as amended by Law no.57/2017 of July 2019),the project PTDC/MED-NEU/1677/2021 to JBRthe Institute of Biomedicine iBiMED(UIDB/04501/2020 and DOI 10.54499/UIDB/04501/2020,UIDP/04501/2020 and DOI 10.54499/UIDP/04501/2020)its LiM Bioimaging Facility-a PPBI node(POCI-01-0145-FEDER-022122)supported by the Research Commission of the Medical Faculty of the Heinrich-Heine-University(HHU)Düsseldorf,of the Biologisch-Medizinisches Forschungszentrum(BMFZ)of HHUfinanced by the Spanish"Plan Nacional de Investigacion Cientifica,Desarrollo e Innovacion Tecnologica,Ministerio de Economia y Competitividad(Instituto de Salud CarlosⅢ)",co-financed by the European Union(FEDER program),(grant FIS P/20/00318 and FIS P23/00337 to VC)grant CPP2021-009070 to VC by the"Proyectos de colaboracion publico-privada,Plan de Investigacion Cientifica,Tecnica y de inovacion 2021-2023,Ministerio de Ciencia e Innovacion,Union Europea,Agencia Estatal de Investigacion,Espana"。
文摘Contrary to the adult central nervous system,the peripheral nervous system has an intrinsic ability to regenerate that relies on the expression of regenerationassociated genes,such as some kinesin family members.Kinesins contribute to nerve regeneration through the transport of specific cargo,such as proteins and membrane components,from the cell body towards the axon periphery.We show here that KIF4A,associated with neurodevelopmental disorders and previously believed to be only expressed during development,is also expressed in the adult vertebrate nervous system and up-regulated in injured peripheral nervous system cells.KIF4A is detected both in the cell bodies and regrowing axons of injured neurons,consistent with its function as an axonal transporter of cargoes such asβ1-integrin and L1CAM.Our study further demonstrates that KIF4A levels are greatly increased in Schwann cells from injured distal nerve stumps,particularly at a time when they are reprogrammed into an essential proliferative repair phenotype.Moreover,Kif4a m RNA levels were approximately~6-fold higher in proliferative cultured Schwann cells compared with non-proliferative ones.A hypothesized function for Kif4a in Schwann cell proliferation was further confirmed by Kif4a knockdown,as this significantly reduced Schwann cell proliferation in vitro.Our findings show that KIF4A is expressed in adult vertebrate nervous systems and is up-regulated following peripheral injury.The timing of KIF4A up-regulation,its location during regeneration,and its proliferative role,all suggest a dual role for this protein in neuroregeneration that is worth exploring in the future.
基金funded by Portuguese funds through FCT——Funda??o para a Ciência e a Tecnologia/Ministério da Ciência,Tecnologia e Ensino Superior in the framework of the project PTDC/MEDNEU/1677/2021(to JBR)。
文摘Neuroimmunology is emerging as a pivotal field,shedding light on the intricate dialogues between the central nervous system(CNS)and the immune system.This exploration is particularly significant in understanding microglia,the CNS’s innate immune cells,beyond the conventional conflation of“neuroinflammation”and“microglial activation.”This conflation has clouded the true complexity of these processes,potentially stalling scientific progress and the development of new therapies.We challenge the long-standing perspectives that have oversimplified these interactions,advocating for a deeper exploration of the dynamic relationship between neuroinflammation and microglial activation.By dissecting specific molecular pathways,we aim to illuminate their elaborate roles in neuroinflammatory responses,especially in the context of Alzheimer’s disease(AD).Here,neuroinflammation is not merely a passive observer or a direct antagonist but a complex agent in the disease’s progression.This article calls for a significant paradigm shift towards an integrative,multi-omics approach to neuroimmunology.Adopting such a comprehensive framework is crucial for advancing our understanding of neuroinflammatory conditions and paving the way for targeted therapeutic strategies for brain diseases.
基金supported by the funding from National Natural Science Foundation of China(Nos.32025021,12374390,31971292,82072032,82202274)Ningbo 3315 Innovative Teams Program(No.2019A-14-C)+6 种基金The member of Youth Innovation Promotion Association Foundation of CAS(No.2023310)Key Scientific and Technological Special Project of Ningbo City(Nos.2023Z209,2020Z189)National Key R&D Program of China(No.2019YFA0405603)Provincial Natural Science Foundation of Zhejiang(Nos.LQ23H180007,LQ23H180003)Zhejiang Province Science and Technology Plan of Traditional Chinese Medicine(No.2021KY085)Zhejiang Provincial Traditional Chinese Medicine Foundation(No.2021ZB04)the Major Medical and Health Science and Technology Project of Zhejiang Province(No.WKJ-ZJ-2002)。
文摘Early diagnosis and accurate boundary delineation are the key steps of tumor precision medicine.Circulating tumor cells(CTCs)detection of liquid biopsy can provide abundant information for early diagnosis of cancer.High detection specificity and good enrichment features are two key factors for CTCs accurate identification in peripheral blood sample.For this purpose,iron oxide(IO)-based surface-enhanced Raman scattering(SERS)bioprobes with good biocompatibility,high detection sensitivity,remarkable detection specificity,and good enrichment efficiency,were developed for detecting different types of CTCs.Magnetic SERS bioprobes combined with programmed death ligand-1(PD-L1)antibody are regarded as an effective way to boost the targeting ability and detection specificity,benefiting for accurately capturing and identifying rare CTCs.Four types of CTCs with different PD-L1 expression were accurately distinguished among white blood cells via high-resolution SERS mapping images and stable Raman signals.Subsequently,CTCs blood samples obtained from the triple negative breast cancer patients were also successfully recognized compared to that of health people,indicating IO@AR@PDA-a PD-L1 SERS bioprobe possessed great potential for CTCs detection in liquid biopsy.Additionally,IO-based bioprobe exhibited excellent dual-modal imaging abilities of high-resolution SERS imaging mode and microimaging magnetic resonance imaging mode.These two highly complementary imaging modes endowed IO-based bioprobes unrivalled capacity in tumor boundary differentiation,supporting tumor accurate resection and precise surgery.To our best knowledge,this is the first time that biocompatible IO-based SERS bioprobes without noble metal element were reported not only for CTCs accurate detection,but also for precise tumor boundary delineation,showing great advantages in tumor diagnosis and treatment.
