As the control center of organisms, the brain remains little understood due to its complexity. Taking advantage of imaging methods, scientists have found an accessible approach to unraveling the mystery of neuroscienc...As the control center of organisms, the brain remains little understood due to its complexity. Taking advantage of imaging methods, scientists have found an accessible approach to unraveling the mystery of neuroscience. Among these methods, optical imaging techniques are widely used due to their high molecular specificity and single-molecule sensitivity. Here, we overview several optical imaging techniques in neuroscience of recent years, including brain clearing, the micro-optical sectioning tomography system, and deep tissue imaging.展开更多
Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in s...Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.展开更多
Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have rev...Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have revealed that gut microbiota can communicate bidirectionally with the brain through the gut microbiota–brain axis.This axis indicates that gut microbiota is closely related to the development and prognosis of intracerebral hemorrhage and its associated secondary white matter injury.The NACHT,LRR,and pyrin domain-containing protein 3(NLRP3)inflammasome plays a crucial role in this context.This review summarizes the dysbiosis of gut microbiota following intracerebral hemorrhage and explores the mechanisms by which this imbalance may promote the activation of the NLRP3 inflammasome.These mechanisms include metabolic pathways(involving short-chain fatty acids,lipopolysaccharides,lactic acid,bile acids,trimethylamine-N-oxide,and tryptophan),neural pathways(such as the vagus nerve and sympathetic nerve),and immune pathways(involving microglia and T cells).We then discuss the relationship between the activated NLRP3 inflammasome and secondary white matter injury after intracerebral hemorrhage.The activation of the NLRP3 inflammasome can exacerbate secondary white matter injury by disrupting the blood–brain barrier,inducing neuroinflammation,and interfering with nerve regeneration.Finally,we outline potential treatment strategies for intracerebral hemorrhage and its secondary white matter injury.Our review highlights the critical role of the gut microbiota–brain axis and the NLRP3 inflammasome in white matter injury following intracerebral hemorrhage,paving the way for exploring potential therapeutic approaches.展开更多
The somatotopic representation of specific body parts is a well-established spatial organizational principle in the primary somatosensory and motor cortices.
Macrophages in the brain barrier system include microglia in the brain parenchyma,border-associated macrophages at the brain’s borders,and recruited macrophages.They are responsible for neural development,maintenance...Macrophages in the brain barrier system include microglia in the brain parenchyma,border-associated macrophages at the brain’s borders,and recruited macrophages.They are responsible for neural development,maintenance of homeostasis,and orchestrating immune responses.With the rapid exploitation and development of new technologies,there is a deeper understanding of macrophages in the brain barrier system.Here we review the origin,development,important molecules,and functions of macrophages,mainly focusing on microglia and border-associated macrophages.We also highlight some advances in single-cell sequencing and significant cell markers.We anticipate that more advanced methods will emerge to study resident and recruited macrophages in the future,opening new horizons for neuroimmunology and related peripheral immune fields.展开更多
Understanding the connection between brain and behavior in animals requires precise monitoring of their behaviors in three-dimensional(3-D)space.However,there is no available three-dimensional behavior capture system ...Understanding the connection between brain and behavior in animals requires precise monitoring of their behaviors in three-dimensional(3-D)space.However,there is no available three-dimensional behavior capture system that focuses on rodents.Here,we present MouseVenue3D,an automated and low-cost system for the efficient capture of 3-D skeleton trajectories in markerless rodents.We improved the most time-consuming step in 3-D behavior capturing by developing an automatic calibration module.Then,we validated this process in behavior recognition tasks,and showed that 3-D behavioral data achieved higher accuracy than 2-D data.Subsequently,MouseVenue3D was combined with fast high-resolution miniature two-photon microscopy for synchronous neural recording and behavioral tracking in the freely-moving mouse.Finally,we successfully decoded spontaneous neuronal activity from the 3-D behavior of mice.Our findings reveal that subtle,spontaneous behavior modules are strongly correlated with spontaneous neuronal activity patterns.展开更多
Malfunction of the ventral subiculum(vSub),the main subregion controlling the output connections from the hippocampus,is associated with major depressive disorder(MDD).Although the vSub receives cholinergic innervatio...Malfunction of the ventral subiculum(vSub),the main subregion controlling the output connections from the hippocampus,is associated with major depressive disorder(MDD).Although the vSub receives cholinergic innervation from the medial septum and diagonal band of Broca(MSDB),whether and how the MSDB-to-vSub cholinergic circuit is involved in MDD is elusive.Here,we found that chronic unpredictable mild stress(CUMS)induced depression-like behaviors with hyperactivation of vSub neurons,measured by c-fos staining and whole-cell patch-clamp recording.By retrograde and anterograde tracing,we confirmed the dense MSDB cholinergic innervation of the vSub.In addition,transient restraint stress in CUMS increased the level of ACh in the vSub.Furthermore,chemogenetic stimulation of this MSDB-vSub innervation in ChAT-Cre mice induced hyperactivation of vSub pyramidal neurons along with depression-like behaviors;and local infusion of atropine,a muscarinic receptor antagonist,into the vSub attenuated the depression-like behaviors induced by chemogenetic stimulation of this pathway and CUMS.Together,these findings suggest that activating the MSDB-vSub cholinergic pathway induces hyperactivation of vSub pyramidal neurons and depression-like behaviors,revealing a novel circuit underlying vSub pyramidal neuronal hyperactivation and its associated depression.展开更多
The interactions between neural stem cells(NSCs)and their niche are essential for their maintenance,proliferation,differentiation,and migration,which contribute to brain plasticity,learning and memory,and cognition[1]...The interactions between neural stem cells(NSCs)and their niche are essential for their maintenance,proliferation,differentiation,and migration,which contribute to brain plasticity,learning and memory,and cognition[1].As one of the key components of the NSC niche,astrocytes are vital in regulating the processes underlying brain development such as neuro-/gliogenesis,angiogenesis,axonal outgrowth,synaptogenesis,and synaptic pruning[2].Chemical and electrical signals mediated by adhesion molecules,the extracellular matrix,paracrine secretion.展开更多
Objective Previous studies have shown that the autonomic nervous system(ANS),which can be affected by emotions,is important in the occurrence or progression of glaucoma.The autonomic innervation distributed in the ant...Objective Previous studies have shown that the autonomic nervous system(ANS),which can be affected by emotions,is important in the occurrence or progression of glaucoma.The autonomic innervation distributed in the anterior chamber(AC)structures might play an efferent role in the neural regulation of intraocular pressure(IOP).This study aimed to investigate the anatomic neural connection from the emotional brain to autonomic innervation in the AC.Methods A retrograde trans-multisynaptic pseudorabies virus encoded with an enhanced green fluorescent protein(PRV531)and non-trans-synaptic tracer FAST Dil were injected into the right eye of mice,respectively.Fluorescent localization in the emotional brain and preganglionic nuclei was studied.Five and a half days after PRV531 injection into the right AC,fluorescent signals were observed in several emotional brain regions,including the amygdala,agranular insular cortex,lateral septal nuclei,periaqueductal gray,and hypothalamus.Autonomic preganglionic nuclei,including Edinger-Westphal nucleus,superior salivatory nucleus,and intermediolateral nucleus,were labeled using PRV531.Results The sensory trigeminal nuclei were not labeled using PRV531.The fluorescence signals in the nuclei mentioned above showed bilateral distribution,primarily on the ipsilateral side.Seven days after injecting FAST Dil into the AC,we observed no FAST Dil-labeled neurons in the central nervous system.Conclusion Our results indicate a neural connection from the emotional brain to autonomic innervation in the AC,which provides anatomical support for the emotional influence of IOP via the ANS.展开更多
In the mammalian central nervous system(CNS),astrocytes are the ubiquitous glial cells that have complex morphological and molecular characteristics.These fascinating cells play essential neurosupportive and homeostat...In the mammalian central nervous system(CNS),astrocytes are the ubiquitous glial cells that have complex morphological and molecular characteristics.These fascinating cells play essential neurosupportive and homeostatic roles in the healthy CNS and undergo morphological,molecular,and functional changes to adopt so-called‘reactive’states in response to CNS injury or disease.In recent years,interest in astrocyte research has increased dramatically and some new biological features and roles of astrocytes in physiological and pathological conditions have been discovered thanks to technological advances.Here,we will review and discuss the wellestablished and emerging astroglial biology and functions,with emphasis on their potential as therapeutic targets for CNS injury,including traumatic and ischemic injury.This review article will highlight the importance of astrocytes in the neuropathological process and repair of CNS injury.展开更多
The automatic diagnosis of depression plays a crucial role in preventing the deterioration of depression symptoms.The interview-based method is the most wildly adopted technique in depression diagnosis.However,the siz...The automatic diagnosis of depression plays a crucial role in preventing the deterioration of depression symptoms.The interview-based method is the most wildly adopted technique in depression diagnosis.However,the size of the collected conversation data is limited,and the sample distributions from different participants usually differ drastically.These factors present a great challenge in building a decent deep learning model for automatic depression diagnosis.Recently,large language models have demonstrated impressive capabilities and achieved human-level performance in various tasks under zero-shot and few-shot scenarios.This sheds new light on the development of AI solutions for domainspecific tasks with limited data.In this paper,we propose a two-stage approach that exploits the current most capable and cost-effective language model,ChatGPT,to make a depression diagnosis on interview-based data.Specifically,in the first stage,we use ChatGPT to summarize the raw dialogue sample,thereby facilitating the extraction of depression-related information.In the second stage,we use ChatGPT to classify the summarised data to predict the depressed state of the sample.Our method can achieve approximately 76%accuracy with a text-only modality on the DAIC-WOZ dataset.In addition,our method outperforms the performance of the state-of-the-art model by 6.2%in the D4 dataset.Our work highlights the potential of using large language models for diagnosis-based depression diagnosis.展开更多
Oxytocin is classically termed a‘prosocial neuropeptide’because of its evolutionarily conserved role in promoting affiliative behaviors.Endogenous oxytocin is mainly synthesized by hypothalamic oxytocin neurons and ...Oxytocin is classically termed a‘prosocial neuropeptide’because of its evolutionarily conserved role in promoting affiliative behaviors.Endogenous oxytocin is mainly synthesized by hypothalamic oxytocin neurons and signals through oxytocin receptors(OxtRs).Recent studies with cell type-specific and circuit-specific interrogation have uncovered that oxytocin signals exert pleiotropic neuromodulatory effects through anatomically widespread axonal projections and ubiquitously distributed OxtRs.Dysfunctions of oxytocin signals are closely relevant to brain disorders/diseases.While intranasal oxytocin administration has been demonstrated to be one potential strategy to alleviate some brain disorders/diseases,such as autism,obesity,and anxiety,conflicting clinical outcomes highlight the imperative for precision-targeted neuromodulation strategies.Dissecting the molecular,cellular,and neural circuitry mechanisms underlying oxytocinergic modulation is a prerequisite to achieving this goal.This review provides an overview of the current understanding of the oxytocin system in terms of anatomical structure,neuronal modulation,and signal pathways,and discusses the modulatory roles of oxytocin in social,feeding,emotional,and sensory-related brain functions and brain diseases.展开更多
Gait coordination in lower limbs plays a critical role in maintaining stability of the human body during walking.For transfemoral amputees,the absence of limbs disrupts this coordination,reducing prosthesis control ac...Gait coordination in lower limbs plays a critical role in maintaining stability of the human body during walking.For transfemoral amputees,the absence of limbs disrupts this coordination,reducing prosthesis control accuracy.Hip-knee coordination mapping offers a feasible solution for lower-limb prosthesis control,involving the generation of a reference trajectory for the knee joint by leveraging information from the hip.However,current reference trajectories are usually derived from static models,which cannot generate reference trajectories robustly when dealing with perturbations.Therefore,this paper introduces a time-dependent model based on the Delayed Feedback Reservoir(DFR)for hip-knee coordination in lower-limb prosthetic control.Experimental results show that DFR outperforms classical gait planning approaches when facing perturbations,achieving a 20%lower Root Mean Square Error(RMSE)and reducing residuals by up to 18.14 degrees.This research contributes to understanding gait mapping approaches and emphasizes the potential of time-dependent models for robust and strong lower-limb prosthetic control.The discovery provides a novel way to enhance the perturbation adaptability of prosthetic control.展开更多
Genome rearrangement is an important process that leads to genetic diversity,including mutation-related insertions,deletions,or inversions in the genome[1,2].
Finding suitable initial noise that retains the original image’s information is crucial for image-to-image(I2I)translation using text-to-image(T2I)diffusion models.A common approach is to add random noise directly to...Finding suitable initial noise that retains the original image’s information is crucial for image-to-image(I2I)translation using text-to-image(T2I)diffusion models.A common approach is to add random noise directly to the original image,as in SDEdit.However,we have observed that this can result in“semantic discrepancy”issues,wherein T2I diffusion models misinterpret the semantic relationships and generate content not present in the original image.We identify that the noise introduced by SDEdit disrupts the semantic integrity of the image,leading to unintended associations between unrelated regions after U-Net upsampling.Building on the widely-used latent diffusion model,Stable Diffusion,we propose a training-free,plugand-play method to alleviate semantic discrepancy and enhance the fidelity of the translated image.By leveraging the deterministic nature of denoising diffusion implicit models(DDIMs)inversion,we correct the erroneous features and correlations from the original generative process with accurate ones from DDIM inversion.This approach alleviates semantic discrepancy and surpasses recent DDIM-inversion-based methods such as PnP with fewer priors,achieving a speedup of 11.2 times in experiments conducted on COCO,ImageNet,and ImageNet-R datasets across multiple I2I translation tasks.展开更多
In the Acknowledgements section of this article,the grant number"2020YFE0205900"relating to"National Key R&D Program of China"was missing,it has been included and the corrected Acknowledgements...In the Acknowledgements section of this article,the grant number"2020YFE0205900"relating to"National Key R&D Program of China"was missing,it has been included and the corrected Acknowledgements section is given below.展开更多
The period of infancy is important for the formation of social behaviors due to the rapid postnatal development of the brain functions underlying emotions and social skills.Ilustration of the neural circuits involved ...The period of infancy is important for the formation of social behaviors due to the rapid postnatal development of the brain functions underlying emotions and social skills.Ilustration of the neural circuits involved in the developmental process of infant social behaviors could foster new therapies for some social impairments occurring in the infant period.展开更多
Infectious keratitis(IK)is a leading cause of blindness worldwide,primarily resulting from improper contact lens use,trauma,and a compromised immune response.The pathogenic microorganisms responsible for IK include ba...Infectious keratitis(IK)is a leading cause of blindness worldwide,primarily resulting from improper contact lens use,trauma,and a compromised immune response.The pathogenic microorganisms responsible for IK include bacteria,fungi,viruses,and Acanthamoeba.This review examines standard therapeutic agents for treating IK,including broad-spectrum empiric antibiotics for bacterial keratitis(BK),antifungals such as voriconazole and natamycin for fungal infections,and antiviral nucleoside analogues for viral keratitis(VK).Additionally,this review discusses therapeutic agents,such as polyhexamethylene biguanide(PHMB),for the treatment of Acanthamoeba keratitis(AK).The review also addresses emerging drugs and the challenges associated with their clinical application,including antibiofilm agents that combat drug resistance and nuclear factor kappa-B(NF-κB)pathway-targeted therapies to mitigate inflammation.Furthermore,methods of Photodynamic Antimicrobial Therapy(PDAT)are explored.This review underscores the importance of integrating novel and traditional therapies to tackle drug resistance and enhance drug delivery,with the goal of advancing treatment strategies for IK.展开更多
Empathy is one of the most important abilities for social animals.In a world that is largely socially constructed,when encountering altered affective states of others,particularly negative states,individuals often exh...Empathy is one of the most important abilities for social animals.In a world that is largely socially constructed,when encountering altered affective states of others,particularly negative states,individuals often exhibit evolutionarily conserved empathic behaviors,such as mirroring,consolation,and helping[l,2].Appropriate empathic behaviors can foster the consolidation of social relationships.Previous studies have suggested that both male and female rodents show some empathic behaviors when facing affective conspecifics[1].However,the role of sex in different empathic behaviors remains largely unexplored.Therefore,there is a need to probe whether animals show sex-dependent empathic behavior and which neural circuits modulate these distinct behaviors.展开更多
Otitis media is an infection of the middle ear mainly caused by bacteria,and current treatments rely heavily on antibiotics.However,the emergence of antibiotic-resistant bacterial strains seriously affects their effic...Otitis media is an infection of the middle ear mainly caused by bacteria,and current treatments rely heavily on antibiotics.However,the emergence of antibiotic-resistant bacterial strains seriously affects their efficacy.In our study,we found that extracellular vesicles(EVs)derived from human natural killer cells(NKs)inhibit the proliferation of both standard and levofloxacin(LVX)-resistant strains of Staphylococcus aureus in a dose-dependent manner.Moreover,compared to LVX,EVs were more effective at reducing effusion and rescuing hearing thresholds in animal models.For LVX-sensitive strains,EVs were significantly more effective in terms of curative time but not curative rate.For LVX-resistant strains,EVs were significantly more effective in terms of both curative rate and curative time when applied alone or applied jointly with LVX.In summary,we found that NK EVs are highly effective in treating otitis media,providing an alternative approach for treating this common disease.展开更多
基金supported by the National Basic Research Development Program(973 Program)of China(2015CB352005)the National Natural Science Foundation of China(6142780065,81527901,and 31571110)+1 种基金Natural Science Foundation of Zhejiang Province of China(Y16F050002)Fundamental Research Funds for the Central Universities of China
文摘As the control center of organisms, the brain remains little understood due to its complexity. Taking advantage of imaging methods, scientists have found an accessible approach to unraveling the mystery of neuroscience. Among these methods, optical imaging techniques are widely used due to their high molecular specificity and single-molecule sensitivity. Here, we overview several optical imaging techniques in neuroscience of recent years, including brain clearing, the micro-optical sectioning tomography system, and deep tissue imaging.
基金supported by the National Natural Science Foundation of China,Nos.82072165 and 82272256(both to XM)the Key Project of Xiangyang Central Hospital,No.2023YZ03(to RM)。
文摘Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.
基金supported by the Guangdong Basic and Applied Basic Research Foundation,No.2023A1515030045(to HS)Presidential Foundation of Zhujiang Hospital of Southern Medical University,No.yzjj2022ms4(to HS)。
文摘Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have revealed that gut microbiota can communicate bidirectionally with the brain through the gut microbiota–brain axis.This axis indicates that gut microbiota is closely related to the development and prognosis of intracerebral hemorrhage and its associated secondary white matter injury.The NACHT,LRR,and pyrin domain-containing protein 3(NLRP3)inflammasome plays a crucial role in this context.This review summarizes the dysbiosis of gut microbiota following intracerebral hemorrhage and explores the mechanisms by which this imbalance may promote the activation of the NLRP3 inflammasome.These mechanisms include metabolic pathways(involving short-chain fatty acids,lipopolysaccharides,lactic acid,bile acids,trimethylamine-N-oxide,and tryptophan),neural pathways(such as the vagus nerve and sympathetic nerve),and immune pathways(involving microglia and T cells).We then discuss the relationship between the activated NLRP3 inflammasome and secondary white matter injury after intracerebral hemorrhage.The activation of the NLRP3 inflammasome can exacerbate secondary white matter injury by disrupting the blood–brain barrier,inducing neuroinflammation,and interfering with nerve regeneration.Finally,we outline potential treatment strategies for intracerebral hemorrhage and its secondary white matter injury.Our review highlights the critical role of the gut microbiota–brain axis and the NLRP3 inflammasome in white matter injury following intracerebral hemorrhage,paving the way for exploring potential therapeutic approaches.
文摘The somatotopic representation of specific body parts is a well-established spatial organizational principle in the primary somatosensory and motor cortices.
基金supported by Ministry of Science and Technology China Brain Initiative Grant,No.2022ZD0204702(to ZY)the National Natural Science Foundation of China,No.82371357(to LC)+2 种基金Foundation for Military Medicine,No.16QNP085(to ZY)Navy Medical University Basic Medical College“Yi Zhang”Basic Medical Talent Development and Support Program,Nos.JCYZRC-D-022(to TC)and JCYZRC-D-024(to HD)Science and Technology Innovation Special Fund of Shanghai Baoshan District,No.2023-E-05(to YW).
文摘Macrophages in the brain barrier system include microglia in the brain parenchyma,border-associated macrophages at the brain’s borders,and recruited macrophages.They are responsible for neural development,maintenance of homeostasis,and orchestrating immune responses.With the rapid exploitation and development of new technologies,there is a deeper understanding of macrophages in the brain barrier system.Here we review the origin,development,important molecules,and functions of macrophages,mainly focusing on microglia and border-associated macrophages.We also highlight some advances in single-cell sequencing and significant cell markers.We anticipate that more advanced methods will emerge to study resident and recruited macrophages in the future,opening new horizons for neuroimmunology and related peripheral immune fields.
基金the Key Area R&D Program of Guangdong Province,China(2018B030338001 and 2018B030331001)the National Key R&D Program of China(2018YFA0701403)+11 种基金the National Natural Science Foundation of China(31500861,31630031,91732304,and 31930047)Chang Jiang Scholars Program,the International Big Science Program Cultivating Project of the Chinese Academy of Science(CAS172644KYS820170004)the Strategic Priority Research Program of the CAS(XDB32030100)the Youth Innovation Promotion Association of the CAS(2017413)the CAS Key Laboratory of Brain Connectome and Manipulation(2019DP173024)Shenzhen Government Basic Research Grants(JCYJ20170411140807570,JCYJ20170413164535041)the Science,Technology and Innovation Commission of Shenzhen Municipality(JCYJ20160429185235132)a Helmholtz-CAS Joint Research grant(GJHZ1508)Guangdong Provincial Key Laboratory of Brain Connectome and Behavior(2017B030301017)the Ten Thousand Talent Program,the Guangdong Special Support Program,Key Laboratory of Shenzhen Institute of Advanced Technology(2019DP173024)the Shenzhen Key Science and Technology Infrastructure Planning Project(ZDKJ20190204002).
文摘Understanding the connection between brain and behavior in animals requires precise monitoring of their behaviors in three-dimensional(3-D)space.However,there is no available three-dimensional behavior capture system that focuses on rodents.Here,we present MouseVenue3D,an automated and low-cost system for the efficient capture of 3-D skeleton trajectories in markerless rodents.We improved the most time-consuming step in 3-D behavior capturing by developing an automatic calibration module.Then,we validated this process in behavior recognition tasks,and showed that 3-D behavioral data achieved higher accuracy than 2-D data.Subsequently,MouseVenue3D was combined with fast high-resolution miniature two-photon microscopy for synchronous neural recording and behavioral tracking in the freely-moving mouse.Finally,we successfully decoded spontaneous neuronal activity from the 3-D behavior of mice.Our findings reveal that subtle,spontaneous behavior modules are strongly correlated with spontaneous neuronal activity patterns.
基金supported by grants from National Natural Science Foundation of China(82071508,31771190,31730035).
文摘Malfunction of the ventral subiculum(vSub),the main subregion controlling the output connections from the hippocampus,is associated with major depressive disorder(MDD).Although the vSub receives cholinergic innervation from the medial septum and diagonal band of Broca(MSDB),whether and how the MSDB-to-vSub cholinergic circuit is involved in MDD is elusive.Here,we found that chronic unpredictable mild stress(CUMS)induced depression-like behaviors with hyperactivation of vSub neurons,measured by c-fos staining and whole-cell patch-clamp recording.By retrograde and anterograde tracing,we confirmed the dense MSDB cholinergic innervation of the vSub.In addition,transient restraint stress in CUMS increased the level of ACh in the vSub.Furthermore,chemogenetic stimulation of this MSDB-vSub innervation in ChAT-Cre mice induced hyperactivation of vSub pyramidal neurons along with depression-like behaviors;and local infusion of atropine,a muscarinic receptor antagonist,into the vSub attenuated the depression-like behaviors induced by chemogenetic stimulation of this pathway and CUMS.Together,these findings suggest that activating the MSDB-vSub cholinergic pathway induces hyperactivation of vSub pyramidal neurons and depression-like behaviors,revealing a novel circuit underlying vSub pyramidal neuronal hyperactivation and its associated depression.
基金AcknowledgementsThis research highlight was supported by STI 2030-Major Projects(2021ZD0203201),the National Natural Science Foundation of China(81971034,32271047),The Innovative Research Team of High-level Local Universities in Shanghai,Natural Science Foundation of Shanghai(22ZR1413800),The Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learning,Shanghai Municipal Science and Technology Major Project(2018SHZDZX01),ZJ Lab,and Shanghai Center for Brain Science and Brain-Inspired Technology,Lingang Laboratory(LGQS-202203-12),Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTDC-202008),and Shanghai Style of TCM for Inheritance and Innovation Team from Shanghai Municipal Health Commission(2021LPTD-007),Shanghai Artificial Intelligence Innovation and Development Project-Intelligent Dermatology Clinic Based on Modern TCM Diagnostic Technology,No.2020-RGZN-02038.
文摘The interactions between neural stem cells(NSCs)and their niche are essential for their maintenance,proliferation,differentiation,and migration,which contribute to brain plasticity,learning and memory,and cognition[1].As one of the key components of the NSC niche,astrocytes are vital in regulating the processes underlying brain development such as neuro-/gliogenesis,angiogenesis,axonal outgrowth,synaptogenesis,and synaptic pruning[2].Chemical and electrical signals mediated by adhesion molecules,the extracellular matrix,paracrine secretion.
文摘Objective Previous studies have shown that the autonomic nervous system(ANS),which can be affected by emotions,is important in the occurrence or progression of glaucoma.The autonomic innervation distributed in the anterior chamber(AC)structures might play an efferent role in the neural regulation of intraocular pressure(IOP).This study aimed to investigate the anatomic neural connection from the emotional brain to autonomic innervation in the AC.Methods A retrograde trans-multisynaptic pseudorabies virus encoded with an enhanced green fluorescent protein(PRV531)and non-trans-synaptic tracer FAST Dil were injected into the right eye of mice,respectively.Fluorescent localization in the emotional brain and preganglionic nuclei was studied.Five and a half days after PRV531 injection into the right AC,fluorescent signals were observed in several emotional brain regions,including the amygdala,agranular insular cortex,lateral septal nuclei,periaqueductal gray,and hypothalamus.Autonomic preganglionic nuclei,including Edinger-Westphal nucleus,superior salivatory nucleus,and intermediolateral nucleus,were labeled using PRV531.Results The sensory trigeminal nuclei were not labeled using PRV531.The fluorescence signals in the nuclei mentioned above showed bilateral distribution,primarily on the ipsilateral side.Seven days after injecting FAST Dil into the AC,we observed no FAST Dil-labeled neurons in the central nervous system.Conclusion Our results indicate a neural connection from the emotional brain to autonomic innervation in the AC,which provides anatomical support for the emotional influence of IOP via the ANS.
基金supported by the National Natural Science Foundation of China(82171386,81971161,and 82201536)the Shanghai Science and Technology Development Foundation(22YF1458600)+1 种基金the Scientifc Foundation from Naval Medical University(2021QN08)the STI2030-Major Projects from Ministry of Science and Technology of China(2022ZD0204700).
文摘In the mammalian central nervous system(CNS),astrocytes are the ubiquitous glial cells that have complex morphological and molecular characteristics.These fascinating cells play essential neurosupportive and homeostatic roles in the healthy CNS and undergo morphological,molecular,and functional changes to adopt so-called‘reactive’states in response to CNS injury or disease.In recent years,interest in astrocyte research has increased dramatically and some new biological features and roles of astrocytes in physiological and pathological conditions have been discovered thanks to technological advances.Here,we will review and discuss the wellestablished and emerging astroglial biology and functions,with emphasis on their potential as therapeutic targets for CNS injury,including traumatic and ischemic injury.This review article will highlight the importance of astrocytes in the neuropathological process and repair of CNS injury.
基金supported by the Science and Technology Innovation 2030 Project of China(2021ZD0202600).
文摘The automatic diagnosis of depression plays a crucial role in preventing the deterioration of depression symptoms.The interview-based method is the most wildly adopted technique in depression diagnosis.However,the size of the collected conversation data is limited,and the sample distributions from different participants usually differ drastically.These factors present a great challenge in building a decent deep learning model for automatic depression diagnosis.Recently,large language models have demonstrated impressive capabilities and achieved human-level performance in various tasks under zero-shot and few-shot scenarios.This sheds new light on the development of AI solutions for domainspecific tasks with limited data.In this paper,we propose a two-stage approach that exploits the current most capable and cost-effective language model,ChatGPT,to make a depression diagnosis on interview-based data.Specifically,in the first stage,we use ChatGPT to summarize the raw dialogue sample,thereby facilitating the extraction of depression-related information.In the second stage,we use ChatGPT to classify the summarised data to predict the depressed state of the sample.Our method can achieve approximately 76%accuracy with a text-only modality on the DAIC-WOZ dataset.In addition,our method outperforms the performance of the state-of-the-art model by 6.2%in the D4 dataset.Our work highlights the potential of using large language models for diagnosis-based depression diagnosis.
基金supported by grants from the Noncommunicable Chronic Diseases-National Science and Technology Major Project(2023ZD0506800)the National Natural Science Foundation of China(32371058,81970727,31900738)+3 种基金the Open Research Fund of Basic Medicine College(JCKFKT-MS-010)the Autism Research Fund of the Zhejiang Foundation for Disabled Persons(2024002)Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)ZJ Lab,and Shanghai Center for Brain Science and Brain-Inspired Technology.
文摘Oxytocin is classically termed a‘prosocial neuropeptide’because of its evolutionarily conserved role in promoting affiliative behaviors.Endogenous oxytocin is mainly synthesized by hypothalamic oxytocin neurons and signals through oxytocin receptors(OxtRs).Recent studies with cell type-specific and circuit-specific interrogation have uncovered that oxytocin signals exert pleiotropic neuromodulatory effects through anatomically widespread axonal projections and ubiquitously distributed OxtRs.Dysfunctions of oxytocin signals are closely relevant to brain disorders/diseases.While intranasal oxytocin administration has been demonstrated to be one potential strategy to alleviate some brain disorders/diseases,such as autism,obesity,and anxiety,conflicting clinical outcomes highlight the imperative for precision-targeted neuromodulation strategies.Dissecting the molecular,cellular,and neural circuitry mechanisms underlying oxytocinergic modulation is a prerequisite to achieving this goal.This review provides an overview of the current understanding of the oxytocin system in terms of anatomical structure,neuronal modulation,and signal pathways,and discusses the modulatory roles of oxytocin in social,feeding,emotional,and sensory-related brain functions and brain diseases.
基金supported by the National Natural Science Foundation of China(Grant Nos.12372065,12372022,and 11932015)Shanghai Pilot Program for Basic Research—Fudan University(Grant No.21TQ1400100-22TQ009).
文摘Gait coordination in lower limbs plays a critical role in maintaining stability of the human body during walking.For transfemoral amputees,the absence of limbs disrupts this coordination,reducing prosthesis control accuracy.Hip-knee coordination mapping offers a feasible solution for lower-limb prosthesis control,involving the generation of a reference trajectory for the knee joint by leveraging information from the hip.However,current reference trajectories are usually derived from static models,which cannot generate reference trajectories robustly when dealing with perturbations.Therefore,this paper introduces a time-dependent model based on the Delayed Feedback Reservoir(DFR)for hip-knee coordination in lower-limb prosthetic control.Experimental results show that DFR outperforms classical gait planning approaches when facing perturbations,achieving a 20%lower Root Mean Square Error(RMSE)and reducing residuals by up to 18.14 degrees.This research contributes to understanding gait mapping approaches and emphasizes the potential of time-dependent models for robust and strong lower-limb prosthetic control.The discovery provides a novel way to enhance the perturbation adaptability of prosthetic control.
基金supported by grants(92168103,32171417,2019CXJQ01)from the National Nature Science Foundation of China,Shanghai Municipal GovernmentPeak Disciplines(Type IV)of Institutions of Higher Learning in Shanghai.
文摘Genome rearrangement is an important process that leads to genetic diversity,including mutation-related insertions,deletions,or inversions in the genome[1,2].
基金supported in part by the National Natural Science Foundation of China(62176059)supported by The Pennsylvania State University.
文摘Finding suitable initial noise that retains the original image’s information is crucial for image-to-image(I2I)translation using text-to-image(T2I)diffusion models.A common approach is to add random noise directly to the original image,as in SDEdit.However,we have observed that this can result in“semantic discrepancy”issues,wherein T2I diffusion models misinterpret the semantic relationships and generate content not present in the original image.We identify that the noise introduced by SDEdit disrupts the semantic integrity of the image,leading to unintended associations between unrelated regions after U-Net upsampling.Building on the widely-used latent diffusion model,Stable Diffusion,we propose a training-free,plugand-play method to alleviate semantic discrepancy and enhance the fidelity of the translated image.By leveraging the deterministic nature of denoising diffusion implicit models(DDIMs)inversion,we correct the erroneous features and correlations from the original generative process with accurate ones from DDIM inversion.This approach alleviates semantic discrepancy and surpasses recent DDIM-inversion-based methods such as PnP with fewer priors,achieving a speedup of 11.2 times in experiments conducted on COCO,ImageNet,and ImageNet-R datasets across multiple I2I translation tasks.
文摘In the Acknowledgements section of this article,the grant number"2020YFE0205900"relating to"National Key R&D Program of China"was missing,it has been included and the corrected Acknowledgements section is given below.
基金supported by grants from the National Natural Science Foundation of China(32125018,32071005,and 32171079)Zhejiang Provincial Natural Science Foundation of China(LD24H090002 and LZ24C090001)+2 种基金the Fundamental Research Funds for the Central Universities(226-2024-00133)the Innovative Research Team of High-level Local Universities in Shanghai(SHSMU-ZDCX20211102)the MOE Frontiers Science Center for Brain Science&Brain-Machine Integration of Zhejiang University.
文摘The period of infancy is important for the formation of social behaviors due to the rapid postnatal development of the brain functions underlying emotions and social skills.Ilustration of the neural circuits involved in the developmental process of infant social behaviors could foster new therapies for some social impairments occurring in the infant period.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82070928 and 82371060)the Sichuan Science and Technology Program(Program No.:2024JDRC0048).
文摘Infectious keratitis(IK)is a leading cause of blindness worldwide,primarily resulting from improper contact lens use,trauma,and a compromised immune response.The pathogenic microorganisms responsible for IK include bacteria,fungi,viruses,and Acanthamoeba.This review examines standard therapeutic agents for treating IK,including broad-spectrum empiric antibiotics for bacterial keratitis(BK),antifungals such as voriconazole and natamycin for fungal infections,and antiviral nucleoside analogues for viral keratitis(VK).Additionally,this review discusses therapeutic agents,such as polyhexamethylene biguanide(PHMB),for the treatment of Acanthamoeba keratitis(AK).The review also addresses emerging drugs and the challenges associated with their clinical application,including antibiofilm agents that combat drug resistance and nuclear factor kappa-B(NF-κB)pathway-targeted therapies to mitigate inflammation.Furthermore,methods of Photodynamic Antimicrobial Therapy(PDAT)are explored.This review underscores the importance of integrating novel and traditional therapies to tackle drug resistance and enhance drug delivery,with the goal of advancing treatment strategies for IK.
基金supported by grants from the National Natural Science Foundation of China(32125018 and 32071005)the National Key Research and Development Program of China(2021YFA1101701)+5 种基金Zhejiang Provincial Natural Science Foundation of China(LD24H090002)the Nanhu Brain-computer Interface Institute(010904008)the Fundamental Research Funds for the Central Universities(226-2024-00133)the Key R&D Program of Zhejiang(2024SSYS0016)the Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences(2023-PT310-01)the MOE Frontiers Science Center for Brain Science&Brain-Machine Integration of Zhejiang University.
文摘Empathy is one of the most important abilities for social animals.In a world that is largely socially constructed,when encountering altered affective states of others,particularly negative states,individuals often exhibit evolutionarily conserved empathic behaviors,such as mirroring,consolation,and helping[l,2].Appropriate empathic behaviors can foster the consolidation of social relationships.Previous studies have suggested that both male and female rodents show some empathic behaviors when facing affective conspecifics[1].However,the role of sex in different empathic behaviors remains largely unexplored.Therefore,there is a need to probe whether animals show sex-dependent empathic behavior and which neural circuits modulate these distinct behaviors.
基金supported by grants from the Ministry of Science and Technology of China(2021YFA1101302)the National Natural Science Foundation of China(82171141 and 82192862)the Science and Technology Commission of Shanghai Municipality(21 JC401000).
文摘Otitis media is an infection of the middle ear mainly caused by bacteria,and current treatments rely heavily on antibiotics.However,the emergence of antibiotic-resistant bacterial strains seriously affects their efficacy.In our study,we found that extracellular vesicles(EVs)derived from human natural killer cells(NKs)inhibit the proliferation of both standard and levofloxacin(LVX)-resistant strains of Staphylococcus aureus in a dose-dependent manner.Moreover,compared to LVX,EVs were more effective at reducing effusion and rescuing hearing thresholds in animal models.For LVX-sensitive strains,EVs were significantly more effective in terms of curative time but not curative rate.For LVX-resistant strains,EVs were significantly more effective in terms of both curative rate and curative time when applied alone or applied jointly with LVX.In summary,we found that NK EVs are highly effective in treating otitis media,providing an alternative approach for treating this common disease.
