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Wireless sequential dual light delivery for programmed PDT in vivo

Light(science & Applications) 2024年第6期13卷 1047-1061页

作者： Jiayi Liu Bowen sun Wenkai Li Han-Joon Kim shu Uin Gan john s.ho Juwita Norasmara Bte Rahmat Yong Zhang Department of Oncology The Second Xiangya HospitalCentral South UniversityChangshaHunan410011China Department of Biomedical Engineering College of Design and EngineeringNational University of SingaporeSingapore117585Singapore Department of Mechanical Engineering College of Design and EngineeringNational University of SingaporeSingapore117576Singapore Department of Electrical and Computer Engineering College of Design and EngineeringNational University of SingaporeSingapore117583Singapore Department of Medical IT Convergence Engineering Kumoh National Institute of TechnologyGumi39253Republic of Korea Department of surgery Yong Loo Lin School of MedicineNational University of SingaporeSingapore119228Singapore The N.1 Institute for Health National University of SingaporeSingapore117456Singapore Institute for Health Innovation and Technology National University of SingaporeSingapore119276Singapore Department of Biomedical Engineering College of EngineeringCity University of Hong KongKowloonHong Kong SARChina

Using photodynamic therapy(PDT)to treat deep-seated cancers is limited due to inefficient delivery of photosensitizers and low tissue penetration of *** nanocarriers are widely used for photosensitizer delivery,while the self-quenching of the encapsulated photosensitizers would impair the PDT ***,the generated short-lived reactive oxygen spieces(ROs)can hardly diffuse out of nanocarriers,resulting in low PDT ***,a smart nanocarrier system which can be degraded by light,followed by photosensitizer activation can potentially overcome these limitations and enhance the PDT efficacy.A light-sensitive polymer nanocarrier encapsulating photosensitizer(RB-M)was *** implantable wireless dual wavelength microLED device which delivers the two light wavelengths sequentially was developed to programmatically control the release and activation of the loaded *** transmitter coils with matching resonant frequencies allow activation of the connected LEDs to emit different wavelengths *** irradiation time,dose,and RB-M concentration were determined using an agent-based digital simulation *** vitro and in vivo validation experiments in an orthotopic rat liver hepatocellular carcinoma disease model confirmed that the nanocarrier rupture and sequential low dose light irradiation strategy resulted in successful PDT at reduced photosensitizer and irradiation dose,which is a clinically significant event that enhances treatment safety.

关键词： PDT overcome hardly

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A shared Neural Node for Multiple Innate Behaviors in Drosophila

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Neuroscience Bulletin 2018年第6期34卷 1103-1104页

作者： Margaret s.ho s.hool of Life science and Technology ShanghaiTech University

The nervous system orchestrates diverse behaviors such as reproduction, sleep, feeding, and aggression, and selects a single behavior for execution at any given time. This requires neural mechanisms for behavioral selection sensitive to both internal physiological states and external environmental conditions. For example, hungry animals

关键词： In A shared Neural Node for Multiple Innate Behaviors in Drosophila

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Neurodevelopment and degeneration

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Neuroscience Bulletin 2014年第4期30卷 539-541页

作者： Margaret s.ho Department of Anatomy and Neurobiology School of MedicineTongji University

Over the past decades, continuous effort has been made to resolve unsettled matters in the emerging scene of neuronal development. Despite the rapid progress, neuroscientists remain fascinated by the intricate networks of signaling pathways and molecules conserved among species. Fundamental questions such as progenitor cell specification, compartmentalized cellular tactics, and the identification of factors involved in orchestrating the progression of development are being actively pursued. Furthermore, reversing the effects of development, neurodegeneration symbolizes an opposite force in limiting growth and has been linked to a variety of diseases. To date, a tremendous amount of work from the research community has conceptualized the central image of how nervous systems develop and are equipped to modulate animal functions, albeit with mysterious gaps in the picture that remain to be filled.

关键词： Neurodevelopment degeneration equipped

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The autophagy protein Atg9 functions in glia and contributes to parkinsonian symptoms in a Drosophila model of Parkinson’s disease

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Neural Regeneration Research 2024年第5期19卷 1150-1155页

作者： shuanglong Yi Linfang Wang Margaret s.ho shiping Zhang s.hool of Life science and Technology ShanghaiTech UniversityShanghaiChina College of Life sciences University of Chinese Academy of SciencesBeijingChina

Parkinson’s disease is a progressive neurodegenerative disease characterized by motor deficits,dopaminergic neuron loss,and brain accumulation ofα-synuclein aggregates called Lewy *** in protein degradation pathways,such as autophagy,has been demonstrated in neurons as a critical mechanism for eliminating protein aggregates in Parkinson’s ***,it is less well understood how protein aggregates are eliminated in glia,the other cell type in the *** the present study,we show that autophagy-related gene 9(Atg9),the only transmembrane protein in the autophagy machinery,is highly expressed in Drosophila glia from adult *** from immunostaining and live cell imaging analysis reveal that a portion of Atg9 localizes to the trans-Golgi network,autophagosomes,and lysosomes in ***9 is persistently in contact with these *** glial atg9 reduces the number of omegasomes and autophagosomes,and impairs autophagic substrate *** suggests that glial Atg9 participates in the early steps of autophagy,and hence the control of autophagic ***,loss of glial atg9 induces parkinsonian symptoms in Drosophila including progressive loss of dopaminergic neurons,locomotion deficits,and glial *** findings identify a functional role of Atg9 in glial autophagy and establish a potential link between glial autophagy and Parkinson’s *** results may provide new insights on the underlying mechanism of Parkinson’s disease.

关键词： Atg9 autophagy glia Parkinson’s disease

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Analysis of Glial Distribution in Drosophila Adult Brains

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Neuroscience Bulletin 2016年第2期32卷 162-170页

作者： Jiayao Ou Zongbao Gao Li song Margaret s.ho Research Center for Translational Medicine Shanghai East Hospital Tongji University School of Medicine Key Laboratory of Arrhythmias of the Ministry of Education of China Shanghai East Hospital Tongji University School of Medicine Department of Anatomy and Neurobiology Tongji University School of Medicine

Neurons and glia are the two major cell types in the nervous system and work closely with each other to program neuronal interplay. Traditionally, neurons are thought to be the major cells that actively regulate processes like synapse formation, plasticity, and behavioral output. Glia, on the other hand, serve a more supporting role. To date, accumulating evidence has suggested that glia are active participants in virtually every aspect of neuronal function. Despite this, fundamental features of how glia interact with neurons, and their spatial relationships, remain elusive. Here, we describe the glial cell population in Drosophila adult brains. Glial cells extend and tightly associate their processes with major structures such as the mushroom body（MB）, ellipsoid body（EB）,and antennal lobe（AL） in the brain. Glial cells are distributed in a more concentrated manner in the MB. Furthermore, subsets of glia exhibit distinctive association patterns around different neuronal structures. Whereas processes extended by astrocyte-like glia and ensheathing glia wrap around the MB and infiltrate into the EB and AL, cortex glia stay where cell bodies of neurons are and remain outside of the synaptic regions structured by EB or AL.

关键词： Glia Drosophila Mushroom body

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Brain delivering RNA-based therapeutic strategies by targeting mTOR pathway for axon regeneration after central nervous system injury

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Neural Regeneration Research 2022年第10期17卷 2157-2165页

作者： Ming-Xi Li Jing-Wen Weng Eric s.ho shing Fung Chow Chi Kwan Tsang Clinical Neuroscience Institute The First Affiliated Hospital of Jinan UniversityGuangzhouGuangdong ProvinceChina Department of Pharmacology and Pharmacy Li Ka Shing Faculty of MedicineUniversity of Hong KongHong Kong Special Administrative RegionChina Department of Biology and Department of Computer science Lafayette CollegeEastonPAUSA

Injuries to the central nervous system(CNs)such as stroke,brain,and spinal cord trauma often result in permanent disabilities because adult CNs neurons only exhibit limited axon *** brain has a surprising intrinsic capability of recovering itself after ***,the hostile extrinsic microenvironment significantly hinders axon *** advances have indicated that the inactivation of intrinsic regenerative pathways plays a pivotal role in the failure of most adult CNs neuronal ***,substantial evidence has convincingly demonstrated that the mechanistic target of rapamycin(mTOR)signaling is one of the most crucial intrinsic regenerative pathways that drive axonal regeneration and sprouting in various CNs *** this review,we will discuss the recent findings and highlight the critical roles of mTOR pathway in axon regeneration in different types of CNs ***,we will demonstrate that the reactivation of this regenerative pathway can be achieved by blocking the key mTOR signaling components such as phosphatase and tensin homolog(PTEN).Given that multiple mTOR signaling components are endogenous inhibitory factors of this pathway,we will discuss the promising potential of RNA-based therapeutics which are particularly suitable for this purpose,and the fact that they have attracted substantial attention recently after the success of coronavirus disease 2019 *** specifically tackle the blood-brain barrier issue,we will review the current technology to deliver these RNA therapeutics into the brain with a focus on nanoparticle *** will propose the clinical application of these RNA-mediated therapies in combination with the brain-targeted drug delivery approach against mTOR signaling components as an effective and feasible therapeutic strategy aiming to enhance axonal regeneration for functional recovery after CNs injury.

关键词： axon sprouting axon regeneration brain targeted drug delivery CNs injury ischemic stroke mTOR nanoparticle neural circuit reconstruction PTEN RNA-based therapeutics

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Glial cells in neuronal development:recent advances and insights from Drosophila melanogaster

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Neuroscience Bulletin 2014年第4期30卷 584-594页

作者： Jiayao Ou Yijing He Xi Xiao Tian-Ming Yu Changyan Chen Zongbao Gao Margaret s.ho Department of Anatomy and Neurobiology School of MedicineTongji University s.hool of Life sciences Tongji University

Gila outnumber neurons and are the most abundant cell type in the nervous system. Whereas neurons are the major carriers, transducers, and processors of information, glial cells, once considered mainly to play a passive supporting role, are now recognized for their active contributions to almost every aspect of nervous system development. Recently, insights from the invertebrate organism Drosophila melanogaster have advanced our knowledge of glial cell biology. In particular, findings on neuron-glia interactions via intrinsic and extrinsic mechanisms have shed light on the importance of gtia during different stages of neuronal development. Here, we summarize recent advances in understanding the functions of Drosophila glia, which resemble their mammalian counterparts in morphology and function, neural stem-cell conversion, synapse formation, and developmental axon pruning. These discoveries reinforce the idea that glia are substantial players in the developing nervous system and further advance the understanding of mechanisms leading to neurodegeneration.

关键词： glia neuronal development Gcm neurodegeneration neural stem cell synapse formation axon pruning

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sCIENCE AND PACKAGING APPLICATION OF METAL/POLYMER INTERFACEs

SCIENCE AND PACKAGING APPLICATION OF METAL/POLYMER INTERFACE...

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The second International Conference on solid state and Integrated Circuit Technology

作者： PAUL s.ho IBM Research Division T.J.Watson Research Center Box 218Yorktown HeightsNY 10598

＜正＞The drive for performance and density in VLsI microelectronics imposes stringent demands on the interconnect structures of semiconductor devices as well as for *** necessitates the development of complex multilaycrcd interconnect structures with challenging requirements in materials and *** current trend in packaging development is to integrate polymer layers as wiring layers together with glass or ceramic substrate to make optimum use of these two types of *** such structures,an important reliability concern is the mechanical integrity during operation and *** problem has been investigated by studying the chemistry and adhesion at the metal-polymer interface. Results will be summarized.

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Targeting TrkB–PsD-95 coupling to mitigate neurological disorders

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Neural Regeneration Research 2025年第3期20卷 715-724页

作者： Xin Yang Yu-Wen Alvin Huang john Marshall Department of Molecular Biology Cell Biology and BiochemistryBrown UniversityProvidenceRIUSA Department of Neurology Warren Alpert Medical School of Brown UniversityProvidenceRIUSA Center for Translational Neuroscience Robert J.and Nancy D.Carney Institute for Brain Science and Brown Institute for Translational ScienceBrown UniversityProvidenceRIUSA

Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and *** activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term ***,the association of postsynaptic density protein-95 with TrkB enhances phos.holipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term *** this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and *** with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 *** TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific *** TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

关键词： Angelman syndrome autism brain-derived neurotrophic factor depression neurodegenerative disorder neurodevelopmental disorder postsynaptic density protein-95 synaptic plasticity TrkB

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Neuroglial Crosstalk by Mitochondria

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Neuroscience Bulletin 2017年第1期33卷 111-112页

作者： Margaret s. ho Research Center for Translational Medicine Shanghai East Hospital No. 150/imo Road Shanghai 200120 China Key Laboratory of Arrhythmias of the Ministry of Education of China Shanghai East Hospital No. 150 Jimo RoadShanghai 200120 China Department of Anatomy and Neurobiology Tongji University School of Medicine 1239 Siping RoadShanghai 200092 China

Glia-neuron interaction is an integral part of signaling networks in the brain. Abundant evidence has suggested a pivotal role for glia in neuronal survival and activity [1-3], yet the mechanisms that lead to neuroglial crosstalk have not been well elucidated, nor has the diverse function of the exchange and transfer for materials between the two types of cells. Intriguingly, glia have been demonstrated as the recipients of axonal mitochondria from retinal ganglion cells [4]. This transcellular degradation of mitochondria provides an excellent example of how glia and neurons communicate, and prompts us to reconsider the importance and implications of how dysfunctional neuroglial crosstalk might underlie possible causes of brain diseases.

关键词： ADPR CD Neuroglial Crosstalk by Mitochondria

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