Emerging research underscores the pivotal role of the gut-immune-brain axis,a dynamic bidirectional communication system involving intricate interactions between the gut microbiota,immune responses,and the central ner...Emerging research underscores the pivotal role of the gut-immune-brain axis,a dynamic bidirectional communication system involving intricate interactions between the gut microbiota,immune responses,and the central nervous system.Gut microbes and their metabolites have profound effects on immune and neurological homeostasis,influencing the development and function of multiple physiological systems.Disruption of the composition of the gut microbiota and barrier integrity has been implicated in various neurological and psychiatric disorders,including autism spectrum disorder,Alzheimer's disease,Parkinson's disease,depression,and anxiety.Most insights into these host-microbiota interactions come from preclinical models,revealing both the complexity and potential therapeutic opportunities of the gut-brain communication pathways.This review synthesizes the current understanding of these intricate interactions,exploring how microbiota-driven modulation of the gut and brain barriers,immune signaling,and neuronal pathways,such as those through the vagus nerve,contributes to health and disease.We further explore therapeutic implications,including personalized precision microbiota interventions,microbiome-derived biomarkers,and barrierstrengthening strategies.Advancing this field offers transformative potential for developing innovative,personalized therapies tailored to individual microbiomes and immune profiles,ultimately redefining clinical approaches to neurological and immunemediated diseases.展开更多
Ultra-thin crystalline silicon stands as a cornerstone material in the foundation of modern micro and nano electronics.Despite the proliferation of various materials including oxide-based,polymer-based,carbon-based,an...Ultra-thin crystalline silicon stands as a cornerstone material in the foundation of modern micro and nano electronics.Despite the proliferation of various materials including oxide-based,polymer-based,carbon-based,and two-dimensional(2D)materials,crystal silicon continues to maintain its stronghold,owing to its superior functionality,scalability,stability,reliability,and uniformity.Nonetheless,the inherent rigidity of the bulk silicon leads to incompatibility with soft tissues,hindering the utilization amid biomedical applications.Because of such issues,decades of research have enabled successful utilization of various techniques to precisely control the thickness and morphology of silicon layers at the scale of several nanometres.This review provides a comprehensive exploration on the features of ultra-thin single crystalline silicon as a semiconducting material,and its role especially among the frontier of advanced bioelectronics.Key processes that enable the transition of rigid silicon to flexible form factors are exhibited,in accordance with their chronological sequence.The inspected stages span both prior and subsequent to transferring the silicon membrane,categorized respectively as on-wafer manufacturing and rigid-to-soft integration.Extensive guidelines to unlock the full potential of flexible electronics are provided through ordered analysis of each manufacturing procedure,the latest findings of biomedical applications,along with practical perspectives for researchers and manufacturers.展开更多
AIM： To cost-effectively express the 23-ku pE2, the most promising subunit vaccine encoded by the E2 fragment comprising of the 3＇-portion of hepatitis E virus （HEV） open reading frame 2 （ORF2） in plastids of to...AIM： To cost-effectively express the 23-ku pE2, the most promising subunit vaccine encoded by the E2 fragment comprising of the 3＇-portion of hepatitis E virus （HEV） open reading frame 2 （ORF2） in plastids of tobacco （Nicotiana tabacum cv. SR1）, to investigate the transgene expression and pE2 accumulation in plastids, and to evaluate the antigenic effect of the plastid-derived pE2 in mice. METHODS： Plastid-targeting vector pRB94-E2 containing the E2 fragment driven by rice psbA promoter was constructed. Upon delivery into tobacco plastids, this construct could initiate homologous recombination in psaB-trnfM and trnG-psbC fragments in plastid genome, and result in transgene inserted between the two fragments. The pRB94-E2 was delivered with a biolistic particle bombardment method, and the plastid-transformed plants were obtained following the regeneration of the bombarded leaf tissues on a spectinomycin-supplemented medium. Transplastomic status of the regenerated plants was confirmed by PCR and Southern blot analysis, transgene expression was investigated by Northern blot analysis, and accumulation of pE2 was measured by ELISA. Furthermore, protein extracts were used to immunize mice, and the presence of the pE2-reactive antibodies in serum samples of the immunized mice was studied by ELISA. RESULTS： Transplastomic lines confirmed by PCR and Southern blot analysis could actively transcribe the E2 mRNA. The pE2 polypeptide was accumulated to a level as high as 13.27 μg/g fresh leaves. The pE2 could stimulate the immunized mice to generate pE2-specific antibodies. CONCLUSION： HEV-E2 fragment can be inserted into the plastid genome and the recombinant pE2 antigen derived is antigenic in mice. Hence, plastids may be a novel source for cost-effective production of HEV vaccines.展开更多
Lung cancer remains the leading cause of cancer death in 2024,with∼80%being non-small cell lung cancer(NSCLC).Anaplastic lymphoma kinase(ALK)rearrangements occur in∼5%of NSCLC cases,typically treated with ALK inhibi...Lung cancer remains the leading cause of cancer death in 2024,with∼80%being non-small cell lung cancer(NSCLC).Anaplastic lymphoma kinase(ALK)rearrangements occur in∼5%of NSCLC cases,typically treated with ALK inhibitors,though resistance often develops[1].Immunotherapy has been explored for advanced or resistant ALK-positive NSCLC,but immune checkpoint blockade(ICB)treatments have shown limited clinical benefits[1].展开更多
Neuroregeneration and remyelination rarely occur in the adult mammalian brain and spinal cord following central nervous system(CNS)injury.The glial scar has been proposed as a major contributor to this failure in the ...Neuroregeneration and remyelination rarely occur in the adult mammalian brain and spinal cord following central nervous system(CNS)injury.The glial scar has been proposed as a major contributor to this failure in the regenerative process.However,its underlying molecular and cellular mechanisms remain unclear.Here,we report that monoamine oxidase B(MAOB)-dependent excessiveγ-aminobutyric acid(GABA)release from reactive astrocytes suppresses the CNS repair system by reducing brain‒derived neurotrophic factor(BDNF)and tropomyosin receptor kinase B(TrkB)expression in severe spinal cord injury(SCI)animal models.Genetic deletion of MAOB in a mouse SCI model promotes both functional and tissue recovery.Notably,the selective MAOB inhibitor,KDS2010,facilitates recovery and regeneration by disinhibiting the BDNF-TrkB axis in a rat SCI model.Its dose-dependent effects were further validated in a monkey SCI model.Moreover,KDS2010 demonstrated a tolerable safety profile and doseproportional pharmacokinetics in healthy humans during a phase 1 clinical trial.This pathway therefore represents a pivotal target for overcoming the intrinsic barriers to CNS repair after injury.Our findings identify the astrocytic MAOB‒GABA axis as a crucial molecular and cellular brake on the CNS repair system following SCI and highlight the translational potential of KDS2010 as a promising therapeutic candidate for SCI treatment.展开更多
Optogenetics enables precise,cell-specific control of neural activity,surpassing traditional electrical stimulation methods that indiscriminately activate nearby cells,making it crucial for rehabilitation,neurological...Optogenetics enables precise,cell-specific control of neural activity,surpassing traditional electrical stimulation methods that indiscriminately activate nearby cells,making it crucial for rehabilitation,neurological disorder treatment,and understanding neural circuits.Among light sources for delivering light to genetically modified cells,bio-implants integrated with Light Emitting Diodes(LEDs)have recently been the focus of extensive research due to their advantage of enabling local photogeneration.Unlike laser-based systems,which require tethered setups that hinder behavioral experiments,μ-LED-based devices allow for wireless operation,facilitating more natural movement in subjects.Furthermore,μ-LED arrays can be designed with higher spatial resolution compared to waveguide-coupled external light sources,enabling more precise control over neural activity.This paper presents design rules for implantable flexible optogenetic devices based onμ-LED,tailored to the unique anatomical and functional requirements of various regions of the nervous system.Integration of recent advancements in devices withμ-LEDs(e.g.wireless systems,optofluidic systems,multifunctionality,and closed-loop systems)enhances behavioral experiments and deepens understanding of complex neural functions in the brain,spinal cord,autonomic nervous system,and somatic nervous system.The combination of optogenetics with advanced bio-implantable devices offers promising avenues in medical science,providing more effective tools for neuromodulation research and clinical applications.展开更多
Understanding the interaction mechanisms of engineered nanomaterials(ENMs)with plant membranes is crucial for their effective use in various applications.While passive transport of smaller ENMs is well-documented,the ...Understanding the interaction mechanisms of engineered nanomaterials(ENMs)with plant membranes is crucial for their effective use in various applications.While passive transport of smaller ENMs is well-documented,the mechanisms underlying active transport of larger ENMs remain poorly understood.This study systematically investigates the active transport and subcellular distribution of ENMs(100-1000 nm)within protoplasts using optical ratiometric silica pH sensors for localization.Highly monodispersed ratiometric pH sensors,based on silica particles modified with fluorescein-5-isothiocyanate(FITC)and cyanine3 NHS ester(CY3)dyes,were employed to elucidate internalization mechanisms.Protoplasts from Nicotiana tabacum L.leaves successfully internalized the sensors.3D segmentation of protoplasts revealed distinct pH gradients,indicating vacuole accumulation.Colocalization analysis and cellular compartments staining further confirmed sensor distribution.High-throughput imaging flow cytometry showed efficient internalization rates,which decreased after cell wall regeneration.Notably,inhibition experiments with the salicylic acid(SA)and Tyrphostin A23(TyrA23)inhibitors confirmed clathrin-mediated endocytosis in particle uptake.This study establishes rational design principles for controlling active ENM uptake and subcellular localization via optical pH sensing in protoplasts.The findings enhance our understanding of plant cell trafficking mechanisms and hold promise for targeted delivery and applications in plant biology research.展开更多
Guard cells are specialized cells forming stomatal pores at the leaf surface for gas exchanges between the plant and the atmosphere. Stomata have been shown to playan important role in plant defense as a part of the i...Guard cells are specialized cells forming stomatal pores at the leaf surface for gas exchanges between the plant and the atmosphere. Stomata have been shown to playan important role in plant defense as a part of the innate immune response. Plants actively close their stomata upon contact with microbes, thereby preventing pathogen entry into the leaves and the subsequent colonization of host tissues. In this review, we present current knowledge of molecular mechanisms and signaling pathways implicated in stomatal defenses, with particular emphasis on plant-bacteria interactions. Stomatal defense responses begin from the perception of pathogen-associated molecular patterns （PAMPs） and activate a signaling cascade involving the production of secondary messengers such as reactive oxygen species, nitric oxide, and calcium for the regulation of plasma membrane ion channels. The analyses on downstream molecular mechanisms implicated in PAMP-triggered stomatal closure have revealed extensive interplays among the components regulating hormonal signaling pathways. We also discuss the strategies deployed by pathogenic bacteria to counteract stomatal immunity through the example of the phytotoxin coronatine.展开更多
In 2012,a novel coronavirus,initially named as human coronavirus EMC(HCoV-EMC) but recently renamed as Middle East respiratory syndrome human coronavirus(MERS-CoV),was identified in patients who suffered severe acute ...In 2012,a novel coronavirus,initially named as human coronavirus EMC(HCoV-EMC) but recently renamed as Middle East respiratory syndrome human coronavirus(MERS-CoV),was identified in patients who suffered severe acute respiratory infection and subsequent renal failure that resulted in death.Ongoing epidemiological investigations together with retrospective studies have found 61 laboratory-confirmed cases of infection with this novel coronavirus,including 34 deaths to date.This novel coronavirus is culturable and two complete genome sequences are now available.Furthermore,molecular detection and indirect immunofluorescence assay have been developed.The present paper summarises the limited recent advances of this novel human coronavirus,including its discovery,genomic characterisation and detection.展开更多
基金supported by grants from the National Research Foundation of Korea funded by the Korea Ministry of Science and ICT(MSIT):L.C.and H.-K.K.were supported by RS-2024-00361620,RS-2019-NR040072,RS-2025-00561456,and RS2024-00438443.S.-H.I was supported by RS-2024-00345575.We would like to thank MID(Medical Illustration&Design),a member of the Medical Research Support Services of Yonsei University College of Medicine,for providing excellent support with medical illustrations.
文摘Emerging research underscores the pivotal role of the gut-immune-brain axis,a dynamic bidirectional communication system involving intricate interactions between the gut microbiota,immune responses,and the central nervous system.Gut microbes and their metabolites have profound effects on immune and neurological homeostasis,influencing the development and function of multiple physiological systems.Disruption of the composition of the gut microbiota and barrier integrity has been implicated in various neurological and psychiatric disorders,including autism spectrum disorder,Alzheimer's disease,Parkinson's disease,depression,and anxiety.Most insights into these host-microbiota interactions come from preclinical models,revealing both the complexity and potential therapeutic opportunities of the gut-brain communication pathways.This review synthesizes the current understanding of these intricate interactions,exploring how microbiota-driven modulation of the gut and brain barriers,immune signaling,and neuronal pathways,such as those through the vagus nerve,contributes to health and disease.We further explore therapeutic implications,including personalized precision microbiota interventions,microbiome-derived biomarkers,and barrierstrengthening strategies.Advancing this field offers transformative potential for developing innovative,personalized therapies tailored to individual microbiomes and immune profiles,ultimately redefining clinical approaches to neurological and immunemediated diseases.
基金support received from National Research Foundation of Korea (NRF) Grant funded by the Korea government (MSIT)(RS-2024-00353768)the National Research Foundation of Korea (NRF) Grant funded by the Korea government (MSIT)(RS-2025-02217919)+1 种基金funded by the Yonsei Fellowshipfunded by Lee Youn Jae and the KIST Institutional Program Project No.2E31603-22-140 (KJY).
文摘Ultra-thin crystalline silicon stands as a cornerstone material in the foundation of modern micro and nano electronics.Despite the proliferation of various materials including oxide-based,polymer-based,carbon-based,and two-dimensional(2D)materials,crystal silicon continues to maintain its stronghold,owing to its superior functionality,scalability,stability,reliability,and uniformity.Nonetheless,the inherent rigidity of the bulk silicon leads to incompatibility with soft tissues,hindering the utilization amid biomedical applications.Because of such issues,decades of research have enabled successful utilization of various techniques to precisely control the thickness and morphology of silicon layers at the scale of several nanometres.This review provides a comprehensive exploration on the features of ultra-thin single crystalline silicon as a semiconducting material,and its role especially among the frontier of advanced bioelectronics.Key processes that enable the transition of rigid silicon to flexible form factors are exhibited,in accordance with their chronological sequence.The inspected stages span both prior and subsequent to transferring the silicon membrane,categorized respectively as on-wafer manufacturing and rigid-to-soft integration.Extensive guidelines to unlock the full potential of flexible electronics are provided through ordered analysis of each manufacturing procedure,the latest findings of biomedical applications,along with practical perspectives for researchers and manufacturers.
基金Supported by a grant from the Hong Kong Research Grant Council, No. 7342/03M to YX Zhou and E Lam
文摘AIM： To cost-effectively express the 23-ku pE2, the most promising subunit vaccine encoded by the E2 fragment comprising of the 3＇-portion of hepatitis E virus （HEV） open reading frame 2 （ORF2） in plastids of tobacco （Nicotiana tabacum cv. SR1）, to investigate the transgene expression and pE2 accumulation in plastids, and to evaluate the antigenic effect of the plastid-derived pE2 in mice. METHODS： Plastid-targeting vector pRB94-E2 containing the E2 fragment driven by rice psbA promoter was constructed. Upon delivery into tobacco plastids, this construct could initiate homologous recombination in psaB-trnfM and trnG-psbC fragments in plastid genome, and result in transgene inserted between the two fragments. The pRB94-E2 was delivered with a biolistic particle bombardment method, and the plastid-transformed plants were obtained following the regeneration of the bombarded leaf tissues on a spectinomycin-supplemented medium. Transplastomic status of the regenerated plants was confirmed by PCR and Southern blot analysis, transgene expression was investigated by Northern blot analysis, and accumulation of pE2 was measured by ELISA. Furthermore, protein extracts were used to immunize mice, and the presence of the pE2-reactive antibodies in serum samples of the immunized mice was studied by ELISA. RESULTS： Transplastomic lines confirmed by PCR and Southern blot analysis could actively transcribe the E2 mRNA. The pE2 polypeptide was accumulated to a level as high as 13.27 μg/g fresh leaves. The pE2 could stimulate the immunized mice to generate pE2-specific antibodies. CONCLUSION： HEV-E2 fragment can be inserted into the plastid genome and the recombinant pE2 antigen derived is antigenic in mice. Hence, plastids may be a novel source for cost-effective production of HEV vaccines.
基金supported by the Bio&Medical Technology Development Program of the National Research Foundation funded by the Ministry of Science and ICT(2021R1A2C2094629 and 2017M3A9E9072669 to Hye Ryun Kim,and 2018R1A5A2025079,2022M3A9F3016364,and 2022R1A2C1092062 to Insuk Lee)supported in part by Brain Korea 21(BK21)FOUR program+1 种基金supported by the Technology Innovation Program(20022947)funded by the Ministry of Trade Industry&Energy(MOTIE,Korea)supported by the Yonsei Fellow Program,funded by Lee Youn Jae.
文摘Lung cancer remains the leading cause of cancer death in 2024,with∼80%being non-small cell lung cancer(NSCLC).Anaplastic lymphoma kinase(ALK)rearrangements occur in∼5%of NSCLC cases,typically treated with ALK inhibitors,though resistance often develops[1].Immunotherapy has been explored for advanced or resistant ALK-positive NSCLC,but immune checkpoint blockade(ICB)treatments have shown limited clinical benefits[1].
基金supported by a faculty research grant from Yonsei University College of Medicine(6-2018-0161)the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(RS-2024-00341308)+1 种基金the Center for Cognition and Sociality from Institute for Basic Science(IBS)(IBS-R001-D2)and NeuroBiogen Co.,LTD.
文摘Neuroregeneration and remyelination rarely occur in the adult mammalian brain and spinal cord following central nervous system(CNS)injury.The glial scar has been proposed as a major contributor to this failure in the regenerative process.However,its underlying molecular and cellular mechanisms remain unclear.Here,we report that monoamine oxidase B(MAOB)-dependent excessiveγ-aminobutyric acid(GABA)release from reactive astrocytes suppresses the CNS repair system by reducing brain‒derived neurotrophic factor(BDNF)and tropomyosin receptor kinase B(TrkB)expression in severe spinal cord injury(SCI)animal models.Genetic deletion of MAOB in a mouse SCI model promotes both functional and tissue recovery.Notably,the selective MAOB inhibitor,KDS2010,facilitates recovery and regeneration by disinhibiting the BDNF-TrkB axis in a rat SCI model.Its dose-dependent effects were further validated in a monkey SCI model.Moreover,KDS2010 demonstrated a tolerable safety profile and doseproportional pharmacokinetics in healthy humans during a phase 1 clinical trial.This pathway therefore represents a pivotal target for overcoming the intrinsic barriers to CNS repair after injury.Our findings identify the astrocytic MAOB‒GABA axis as a crucial molecular and cellular brake on the CNS repair system following SCI and highlight the translational potential of KDS2010 as a promising therapeutic candidate for SCI treatment.
基金support received from the National Research Foundation of Korea(Grant Nos.RS-2024-00353768 and RS-2024-00400874)supported by the Yonsei Fellowship,funded by Lee Youn Jae+1 种基金supported by the WISH Center at Georgia Tech Institute for Matter and Systemssupported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(RS-2024-00464654).
文摘Optogenetics enables precise,cell-specific control of neural activity,surpassing traditional electrical stimulation methods that indiscriminately activate nearby cells,making it crucial for rehabilitation,neurological disorder treatment,and understanding neural circuits.Among light sources for delivering light to genetically modified cells,bio-implants integrated with Light Emitting Diodes(LEDs)have recently been the focus of extensive research due to their advantage of enabling local photogeneration.Unlike laser-based systems,which require tethered setups that hinder behavioral experiments,μ-LED-based devices allow for wireless operation,facilitating more natural movement in subjects.Furthermore,μ-LED arrays can be designed with higher spatial resolution compared to waveguide-coupled external light sources,enabling more precise control over neural activity.This paper presents design rules for implantable flexible optogenetic devices based onμ-LED,tailored to the unique anatomical and functional requirements of various regions of the nervous system.Integration of recent advancements in devices withμ-LEDs(e.g.wireless systems,optofluidic systems,multifunctionality,and closed-loop systems)enhances behavioral experiments and deepens understanding of complex neural functions in the brain,spinal cord,autonomic nervous system,and somatic nervous system.The combination of optogenetics with advanced bio-implantable devices offers promising avenues in medical science,providing more effective tools for neuromodulation research and clinical applications.
基金supported by the European Research Council(ERC)under the European Union’s Horizon 2020 research and innovation program ERC Starting Grant“INTERCELLMED”(Nr.759959)the Associazione Italiana per la Ricerca contro il Cancro(AIRC)(MFAG-2019,Nr.22902)+4 种基金the PRIN 2022(Nr.2022CRFNCP_PE11_PRIN2022 and PRIN 2022-SAPPHIRE(CUP 2022MWK7Y7)funded by European Union-Next Generation EU,the“Tecnopolo per la medicina di precisione”(TecnoMed Puglia)-Regione Puglia:DGR n.2117 of 21/11/2018,CUP B84I18000540002)the Italian Ministry of Research(MUR)in the framework of the National Recovery and Resilience Plan(NRRP),“NFFA-DI”Grant(CUP B53C22004310006)“I-PHOQS”Grant(CUP B53C22001750006)under the complementary actions to the NRRP funded by NextGenerationEU,“Fit4MedRob”Grant(PNC0000007,CUP B53C22006960001).
文摘Understanding the interaction mechanisms of engineered nanomaterials(ENMs)with plant membranes is crucial for their effective use in various applications.While passive transport of smaller ENMs is well-documented,the mechanisms underlying active transport of larger ENMs remain poorly understood.This study systematically investigates the active transport and subcellular distribution of ENMs(100-1000 nm)within protoplasts using optical ratiometric silica pH sensors for localization.Highly monodispersed ratiometric pH sensors,based on silica particles modified with fluorescein-5-isothiocyanate(FITC)and cyanine3 NHS ester(CY3)dyes,were employed to elucidate internalization mechanisms.Protoplasts from Nicotiana tabacum L.leaves successfully internalized the sensors.3D segmentation of protoplasts revealed distinct pH gradients,indicating vacuole accumulation.Colocalization analysis and cellular compartments staining further confirmed sensor distribution.High-throughput imaging flow cytometry showed efficient internalization rates,which decreased after cell wall regeneration.Notably,inhibition experiments with the salicylic acid(SA)and Tyrphostin A23(TyrA23)inhibitors confirmed clathrin-mediated endocytosis in particle uptake.This study establishes rational design principles for controlling active ENM uptake and subcellular localization via optical pH sensing in protoplasts.The findings enhance our understanding of plant cell trafficking mechanisms and hold promise for targeted delivery and applications in plant biology research.
文摘Guard cells are specialized cells forming stomatal pores at the leaf surface for gas exchanges between the plant and the atmosphere. Stomata have been shown to playan important role in plant defense as a part of the innate immune response. Plants actively close their stomata upon contact with microbes, thereby preventing pathogen entry into the leaves and the subsequent colonization of host tissues. In this review, we present current knowledge of molecular mechanisms and signaling pathways implicated in stomatal defenses, with particular emphasis on plant-bacteria interactions. Stomatal defense responses begin from the perception of pathogen-associated molecular patterns （PAMPs） and activate a signaling cascade involving the production of secondary messengers such as reactive oxygen species, nitric oxide, and calcium for the regulation of plasma membrane ion channels. The analyses on downstream molecular mechanisms implicated in PAMP-triggered stomatal closure have revealed extensive interplays among the components regulating hormonal signaling pathways. We also discuss the strategies deployed by pathogenic bacteria to counteract stomatal immunity through the example of the phytotoxin coronatine.
基金supported by grants from the National Basic Research Program of China (2011CB504704)the State Megaproject for Infectious Disease Research of China (2011ZX10004-001)
文摘In 2012,a novel coronavirus,initially named as human coronavirus EMC(HCoV-EMC) but recently renamed as Middle East respiratory syndrome human coronavirus(MERS-CoV),was identified in patients who suffered severe acute respiratory infection and subsequent renal failure that resulted in death.Ongoing epidemiological investigations together with retrospective studies have found 61 laboratory-confirmed cases of infection with this novel coronavirus,including 34 deaths to date.This novel coronavirus is culturable and two complete genome sequences are now available.Furthermore,molecular detection and indirect immunofluorescence assay have been developed.The present paper summarises the limited recent advances of this novel human coronavirus,including its discovery,genomic characterisation and detection.
