Adult neurogenesis persists after birth in the subventricular zone, with new neurons migrating to the granule cell layer and glomerular layers of the olfactory bulb, where they integrate into existing circuitry as inh...Adult neurogenesis persists after birth in the subventricular zone, with new neurons migrating to the granule cell layer and glomerular layers of the olfactory bulb, where they integrate into existing circuitry as inhibitory interneurons. The generation of these new neurons in the olfactory bulb supports both structural and functional plasticity, aiding in circuit remodeling triggered by memory and learning processes. However, the presence of these neurons, coupled with the cellular diversity within the olfactory bulb, presents an ongoing challenge in understanding its network organization and function. Moreover,the continuous integration of new neurons in the olfactory bulb plays a pivotal role in regulating olfactory information processing. This adaptive process responds to changes in epithelial composition and contributes to the formation of olfactory memories by modulating cellular connectivity within the olfactory bulb and interacting intricately with higher-order brain regions. The role of adult neurogenesis in olfactory bulb functions remains a topic of debate. Nevertheless, the functionality of the olfactory bulb is intricately linked to the organization of granule cells around mitral and tufted cells. This organizational pattern significantly impacts output, network behavior, and synaptic plasticity, which are crucial for olfactory perception and memory. Additionally, this organization is further shaped by axon terminals originating from cortical and subcortical regions. Despite the crucial role of olfactory bulb in brain functions and behaviors related to olfaction, these complex and highly interconnected processes have not been comprehensively studied as a whole. Therefore, this manuscript aims to discuss our current understanding and explore how neural plasticity and olfactory neurogenesis contribute to enhancing the adaptability of the olfactory system. These mechanisms are thought to support olfactory learning and memory, potentially through increased complexity and restructuring of neural network structures, as well as the addition of new granule granule cells that aid in olfactory adaptation. Additionally, the manuscript underscores the importance of employing precise methodologies to elucidate the specific roles of adult neurogenesis amidst conflicting data and varying experimental paradigms. Understanding these processes is essential for gaining insights into the complexities of olfactory function and behavior.展开更多
A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigati...A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.展开更多
Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic nerve.Still,it is unknown whether olfactory enshea...Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic nerve.Still,it is unknown whether olfactory ensheathing glia also have neuroprotective properties.Olfactory ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion cells.Therefore,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve crush.Olfactory ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive treatments.Anatomical and gene expression analyses were performed.Olfactory bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡmolecules.Allogeneically and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an epimembrane.In axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 days.In these retinas,microglial anatomical activation was higher than after optic nerve crush alone.In intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or immunosuppression.However,neuroprotection of axotomized retinal ganglion cells did not improve with these treatments.The different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.展开更多
Iron is the most abundant transition metal in the brain and is essential for brain development and neuronal function;however,its abnormal accumulation is also implicated in various neurological disorders.The olfactory...Iron is the most abundant transition metal in the brain and is essential for brain development and neuronal function;however,its abnormal accumulation is also implicated in various neurological disorders.The olfactory bulb(OB),an early target in neurodegenerative diseases,acts as a gateway for environmental toxins and contains diverse neuronal populations with distinct roles.This study explored the cell-specific vulnerability to iron in the OB using a mouse model of intranasal administration of ferric ammonium citrate(FAC).Olfactory function was assessed through olfactory discrimination tests,while iron levels in OB tissues,cerebrospinal fluid(CSF),and serum were quantified using inductively coupled plasma mass spectrometry(ICP-MS),immunohistochemical staining,and iron assays.Transcriptomic changes and immune responses were assessed using RNA sequencing and immune cell infiltration analysis.Results showed that intranasal FAC administration impaired olfactory function,accompanied by iron deposition in the olfactory mucosa and OB,as well as damage to olfactory sensory neurons.Notably,these effects occurred without elevations in CSF or serum iron levels.OB iron accumulation activated multiple immune cells,including microglia and astrocytes,but did not trigger ferroptosis.Spatial transcriptomic sequencing of healthy adult mouse OBs revealed significant cellular heterogeneity,with an abundance of neuroglia and neurons.Among neurons,GABAergic neurons were the most prevalent,followed by glutamatergic and dopaminergic neurons,while cholinergic and serotonergic neurons were sparsely distributed.Under iron-stressed conditions,oligodendrocytes,dopaminergic neurons,and glutamatergic neurons exhibited significant damage,while GABAergic neurons remained unaffected.These findings highlight the selective vulnerability of neuronal and glial populations to iron-induced stress,offering novel insights into the loss of specific cell types in the OB during iron dysregulation.展开更多
Olfactory receptors(ORs),the largest vertebrate multigene family,exhibit wide copy number variation among taxa,ranging from~100 to 4000.The ecological importance of smell has been suggested to positively correlate wit...Olfactory receptors(ORs),the largest vertebrate multigene family,exhibit wide copy number variation among taxa,ranging from~100 to 4000.The ecological importance of smell has been suggested to positively correlate with OR gene number,though debate exists on whether the number of total ORs,functional ORs,or the percentage of pseudogenes matters most.While olfaction has been poorly studied in most birds,Turkey Vultures(Cathartes aura)demonstrate keen olfactory ability,capable of foraging using smell alone.In contrast,Black Vultures(Coragyps atratus)have been thought to primarily use vision to locate food.Comparison of the OR genes in these two New World vultures presents an opportunity to examine the dynamics of OR evolution in related avian species that may differ in olfactory abilities.Using a PCR and cloning approach with degenerate primers,we sampled the OR subgenome in Turkey and Black Vultures,as well as Red-tailed Hawks(Buteo jamaicensis)and the distantly related Chicken(Gallus gallus),neither of which are thought to use olfaction extensively.Our results indicate that Turkey Vultures have many more OR genes than Red-tailed Hawks or chickens.Surprisingly,Black Vultures had an intermediate number of OR genes.The number of OR genes we estimated in the Turkey Vulture was much greater than previously reported in studies that used short-read sequencing.Additionally,we found that OR genes from New World vultures and Red-tailed Hawks form clades that were distinct from the clade that included most chicken OR genes,indicating that chickens share few OR orthologs with New World vultures or hawks.As previously observed in other animal groups,pseudogenes appeared throughout all clades and their percentage varied among taxa.These findings suggest the OR gene family is highly dynamic,changing rapidly over evolutionary time,and that taxa may have distinct suites of ORs in their genomes.展开更多
Chemicals that modify pest behavior are developed to reduce crop damage by altering pest behavior, using specific genes within the olfactory system as molecular targets. The identification of these molecular targets i...Chemicals that modify pest behavior are developed to reduce crop damage by altering pest behavior, using specific genes within the olfactory system as molecular targets. The identification of these molecular targets in Bactrocera dorsalis, also known as the functional study of key olfactory genes, relies on CRISPR/Cas9-mediated gene knockout techniques. However, these techniques face limitations when applied to lethal genes. Transgenic technology offers a solution since it enables precise manipulation of gene expression in specific tissues or during certain developmental stages. Consequently, this study developed a piggyBac-mediated transgenic system in B. dorsalis to investigate reporter gene expression in olfactory organs, and assessed the olfactory behavior andantennal electrophysiological responses in transgenic lines. The goal was to assess the potential of this approach for future research on olfactory gene function. A universally expressed housekeeping gene from the BdorActin family was identified using the developmental transcriptome dataset. Its candidate promoter region(BdorActinA3a-1^(P–2k)) was then cloned into the piggyBac plasmid. We subsequently established two stable transgenic lines with specific TTAA insertion sites on chromosomes 4 and 5, consistent with the characteristics of piggyBac transposition. The transgenic strains exhibited essentially normal survival, with hatchability and adult lifespan unaffected, althoughthere were slight reductions in the emergence rate and oviposition capacity. The fluorescent reporter has been successfully expressed in olfactory-related organs, such as the antennae, proboscis, maxillary palp, legs, external genitalia, and brain. The antennal electrophysiological responses to representative chemicals in the transgenic lines were consistent with those of the wild type. However, some olfactory-related behaviors, such as pheromone response and mating, were significantly affected in the transgenic lines. These findings suggest that our system could potentially be applied in future olfactory research, such as driving the expression of exogenous elements that are effective in olfactory organs. However, caution is advised regarding its impact when applied to some olfactoryrelated behavioral phenotypes.展开更多
Background:Parkinson’s disease(PD)is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra(SN).Activation of the neuroinflammatory response has a pivotal role ...Background:Parkinson’s disease(PD)is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra(SN).Activation of the neuroinflammatory response has a pivotal role in PD.Mesenchymal stem cells(MSCs)have emerged as a promising therapeutic approach for various nerve injuries,but there are limited reports on their use in PD and the underlying mechanisms remain unclear.Methods:We investigated the effects of clinical-grade hypoxia-preconditioned olfactory mucosa(hOM)-MSCs on neural functional recovery in both PD models and patients,as well as the preventive effects on mouse models of PD.To assess improvement in neuroinflammatory response and neural functional recovery induced by hOM-MSCs exposure,we employed single-cell RNA sequencing(scRNA-seq),assay for transposase accessible chromatin with high-throughput sequencing(ATAC-seq)combined with full-length transcriptome isoform-sequencing(ISO-seq),and functional assay.Furthermore,we present the findings from an initial cohort of patients enrolled in a phaseⅠfirstinhuman clinical trial evaluating the safety and efficacy of intraspinal transplantation of hOM-MSC transplantation into severe PD patients.Results:A functional assay identified that transforming growth factor-β1(TGF-β1),secreted from hOM-MSCs,played a critical role in modulating mitochondrial function recovery in dopaminergic neurons.This effect was achieved through improving microglia immune regulation and autophagy homeostasis in the SN,which are closely associated with neuroinflammatory responses.Mechanistically,exposure to hOM-MSCs led to an improvement in neuroinflammation and neural function recovery partially mediated by TGF-β1 via activation of the anaplastic lymphoma kinase/phosphatidylinositol-3-kinase/protein kinase B(ALK/PI3K/Akt)signaling pathway in microglia located in the SN of PD patients.Furthermore,intraspinal transplantation of hOM-MSCs improved the recovery of neurologic function and regulated the neuroinflammatory response without any adverse reactions observed in patients with PD.Conclusions:These findings provide compelling evidence for the involvement of TGF-β1 in mediating the beneficial effects of hOM-MSCs on neural functional recovery in PD.Treatment and prevention of hOM-MSCs could be a promising and effective neuroprotective strategy for PD.Additionally,TGF-β1 may be used alone or combined with hOM-MSCs therapy for treating PD.展开更多
Changes in olfactory function are considered to be early biomarkers of Parkinson’s disease.Olfactory dysfunction is one of the earliest non-motor features of Parkinson’s disease,appearing in about 90%of patients wit...Changes in olfactory function are considered to be early biomarkers of Parkinson’s disease.Olfactory dysfunction is one of the earliest non-motor features of Parkinson’s disease,appearing in about 90%of patients with early-stage Parkinson’s disease,and can often predate the diagnosis by years.Therefore,olfactory dysfunction should be considered a reliable marker of the disease.However,the mechanisms responsible for olfactory dysfunction are currently unknown.In this article,we clearly explain the pathology and medical definition of olfactory function as a biomarker for early-stage Parkinson’s disease.On the basis of the findings of clinical olfactory function tests and animal model experiments as well as neurotransmitter expression levels,we further characterize the relationship between olfactory dysfunction and neurodegenerative diseases as well as the molecular mechanisms underlying olfactory dysfunction in the pathology of early-stage Parkinson’s disease.The findings highlighted in this review suggest that olfactory dysfunction is an important biomarker for preclinical-stage Parkinson’s disease.Therefore,therapeutic drugs targeting non-motor symptoms such as olfactory dysfunction in the early stage of Parkinson’s disease may prevent or delay dopaminergic neurodegeneration and reduce motor symptoms,highlighting the potential of identifying effective targets for treating Parkinson’s disease by inhibiting the deterioration of olfactory dysfunction.展开更多
A highly sensitive olfactory system allows insects to precisely identify and position volatile compounds from different sources in their habitats,and plays a crucial role in their foraging,mating,and oviposition activ...A highly sensitive olfactory system allows insects to precisely identify and position volatile compounds from different sources in their habitats,and plays a crucial role in their foraging,mating,and oviposition activities.During evolution,insects have successfully developed a large and complex olfactory system to adapt to heterogeneous environments,enabling the maintenance of inset population.A comprehensive examination of the olfactory system of insects may therefore yield novel insights into the development of innovative pest control and prevention strategies,as well as the study of olfactory mechanisms in vertebrates and even humans.This paper outlines the current state of research into the signal transduction mechanism by which insects perceive the olfactory molecules of their habitats.The aim of this review is to provide a reference point for future studies into the olfactory perception mechanism and its potential applications in pest management.展开更多
The olfactory bulb(OB)is the first relay station in the olfactory system and functions as a crucial hub.It can represent odor information precisely and accurately in an ever-changing environment.As the only output neu...The olfactory bulb(OB)is the first relay station in the olfactory system and functions as a crucial hub.It can represent odor information precisely and accurately in an ever-changing environment.As the only output neurons in the OB,mitral/tufted cells encode information such as odor identity and concentration.Recently,the neural strategies and mechanisms underlying odor representation and encoding in the OB have been investigated extensively.Here we review the main progress on this topic.We first review the neurons and circuits involved in odor representation,including the different cell types in the OB and the neural circuits within and beyond the OB.We will then discuss how two different coding strategies—spatial coding and temporal coding—work in the rodent OB.Finally,we discuss potential future directions for this research topic.Overall,this review provides a comprehensive description of our current understanding of how odor information is represented and encoded by mitral/tufted cells in the OB.展开更多
A gas sensor can convert external gas concentration or species into electric voltage or current signals by physical adsorption or chemical changes. As a result, a gas sensor in a nonlinear circuit can be used as a sen...A gas sensor can convert external gas concentration or species into electric voltage or current signals by physical adsorption or chemical changes. As a result, a gas sensor in a nonlinear circuit can be used as a sensitive sensor for detecting external gas signals from the olfactory system. In this paper, a gas sensor and a field-effect transistor are incorporated into a simple FithzHugh–Nagumo neural circuit for capturing and encoding external gas signals. An improved functional neural circuit is obtained, and the effect of gas concentration, gas species and neuronal activity can be discerned as the gate voltage, threshold voltage and activation coefficient of the field-effect transistor, respectively. The gas concentration can affect the neural activities from quiescent to normal working and, finally, to saturation state in bursting, spiking, periodic and chaotic firings with different frequencies. The effects of gas species and neuronal activity on the firing state can also be achieved in this functional neural circuit. In addition, variations in the gate voltage, threshold voltage and activation coefficient can cause switching between different firing modes. These results can be helpful in designing artificial olfactory devices for bionic gas recognition and other coupled systems arising in applied sciences.展开更多
Simulating the human olfactory nervous system is one of the key issues in the field of neuromorphic computing.Olfac-tory neurons interact with gas molecules,transmitting and storing odor information to the olfactory c...Simulating the human olfactory nervous system is one of the key issues in the field of neuromorphic computing.Olfac-tory neurons interact with gas molecules,transmitting and storing odor information to the olfactory center of the brain.In order to emulate the complex functionalities of olfactory neurons,this study presents a flexible olfactory synapse transistor(OST)based on pentacene/C8-BTBT organic heterojunction.By modulating the interface between the energy bands of the organic semiconductor layers,this device demonstrates high sensitivity(ppb level)and memory function for NH3 sensing.Typi-cal synaptic behaviors triggered by NH_(3) pulses have been successfully demonstrated,such as inhibitory postsynaptic currents(IPSC),paired-pulse depression(PPD),long-term potentiation/depression(LTP/LTD),and transition from short-term depression(STD)to long-term depression(LTD).Furthermore,this device maintains stable olfactory synaptic functions even under differ-ent bending conditions,which can present new insights and possibilities for flexible synaptic systems and bio-inspired elec-tronic products.展开更多
To explore the target of action of LHQW-XYS on the main components of COVID-19 olfactory impairment by using network pharmacological methods and try to reveal its mechanism of action in the treatment related to COVID-...To explore the target of action of LHQW-XYS on the main components of COVID-19 olfactory impairment by using network pharmacological methods and try to reveal its mechanism of action in the treatment related to COVID-19 induced olfactory impairment,we used the TCMSP platform to obtain potential active ingredients through oral utilization and drug-like properties screening;the Swiss TargetPrediction platform to predict the targets of the active ingredients and construct a drug-ingredient-target network,and then obtained the gene targets of COVID-19 olfactory injury through GeneCards,OMIM,and TTD platforms to intersect the drug targets and disease genes to obtain common targets.The drug targets and disease genes were intersected to obtain common targets.STRING and Cytoscape 3.8.2 software were used to construct the target-disease gene PPI network,screen the key targets and core gene clusters,and analyze the key targets by GO and KEGG enrichment analyses with the help of the Metascape platform,and then map the screened core active ingredients and their targets into the pathway to construct the core active ingredients-targets-pathway network.The core active ingredient-target-pathway network was constructed,and finally,molecular docking was carried out.The results showed that there were 4669 potential targets,5609 disease targets,and 17 drug-disease cross-targets for the active ingredients of LHQW-XYS.The GO and KEGG enrichment analyses indicated that the mechanism of LHQW-XYS in the treatment of olfactory impairment in COVID-19 may be due to the regulation of related signaling pathways,such as Serotonergic synapse and Regulation of lipolysis in adipocytes.Molecular docking showed that six active components(quercetin,luteolin,kaempferol,7-methoxy-2-methylisoflavone,wogonin,medicarpin)and two key genes(PTGS2,PPARG)had good binding properties.In the end,we conclude that LHQW-XYS may act on Serotonergic synapse and Regulation of lipolysis in adipocyte pathways to achieve anti-COVID-19 olfactory impairment-associated effects.展开更多
Olfactory ensheathing cells(OECs) from the olfactory bulb(OB) and the olfactory mucosa(OM) have the capacity to repair nerve injury. However, the difference in the therapeutic effect between OB-derived OECs and OM-der...Olfactory ensheathing cells(OECs) from the olfactory bulb(OB) and the olfactory mucosa(OM) have the capacity to repair nerve injury. However, the difference in the therapeutic effect between OB-derived OECs and OM-derived OECs remains unclear. In this study, we extracted OECs from OB and OM and compared the gene and protein expression profiles of the cells using transcriptomics and non-quantitative proteomics techniques. The results revealed that both OB-derived OECs and OM-derived OECs highly expressed genes and proteins that regulate cell growth, proliferation, apoptosis and vascular endothelial cell regeneration. The differentially expressed genes and proteins of OB-derived OECs play a key role in regulation of nerve regeneration and axon regeneration and extension, transmission of nerve impulses and response to axon injury. The differentially expressed genes and proteins of OM-derived OECs mainly participate in the positive regulation of inflammatory response, defense response, cytokine binding, cell migration and wound healing. These findings suggest that differentially expressed genes and proteins may explain why OB-derived OECs and OM-derived OECs exhibit different therapeutic roles. This study was approved by the Animal Ethics Committee of the General Hospital of Ningxia Medical University(approval No. 2017-073) on February 13, 2017.展开更多
Objective Combine olfactory ensheathing glia （OEG） implantation with ex vivo non-viral vector-based neurotrophin- 3 （NT-3） gene therapy in attempting to enhance regeneration after thoracic spinal cord injury （SCI...Objective Combine olfactory ensheathing glia （OEG） implantation with ex vivo non-viral vector-based neurotrophin- 3 （NT-3） gene therapy in attempting to enhance regeneration after thoracic spinal cord injury （SCI）. Methods Primary OEG were transfected with cationic liposome-mediated recombinant plasmid pcDNA3.1 （＋）-NT3 and subsequently implanted into adult Wistar rats directly after the thoracic spinal cord （T9） contusion by the New York University impactor. The animals in 3 different groups received 4x 1050EG transfected with pcDNA3.1 （＋）-NT3 or pcDNA3.1 （＋） plasmids, or the OEGs without any plasmid transfection, respectively; the fourth group was untreated group, in which no OEG was implanted. Results NT-3 production was seen increased both ex vivo and in vivo in pcDNA3.1 （＋）-NT3 transfected OEGs. Three months after implantation of NT-3-transfected OEGs, behavioral analysis revealed that the hindlimb function of SCI rats was improved. All spinal cords were filled with regenerated neurofilament-positive axons. Retrograde tracing revealed enhanced regenerative axonal sprouting. Conclusion Non-viral vector-mediated genetic engineering of OEG was safe and more effective in producing NT- 3 and promoting axonal outgrowth followed by enhancing SCI recovery in rats.展开更多
Forty-three patients with chronic spinal cord injury for over 6 months were transplanted with bryonic olfactory ensheathing cells, 2-4 × 106, into multiple sites in the injured area under the sur-gical microscope...Forty-three patients with chronic spinal cord injury for over 6 months were transplanted with bryonic olfactory ensheathing cells, 2-4 × 106, into multiple sites in the injured area under the sur-gical microscope. The sympathetic skin response in patients was measured with an electromyo-graphy/evoked potential instrument 1 day before transplantation and 3-8 weeks after trans-tion. Spinal nerve function of patients was assessed using the American Spinal Injury Association impairment scale. The sympathetic skin response was elicited in 32 cases before olfactory en-sheathing celltransplantation, while it was observed in 34 cases after transplantation. tantly, sympathetic skin response latency decreased significantly and amplitude increased cantly after transplantation. Transplantation of olfactory ensheathing cells also improved American Spinal Injury Association scores for movement, pain and light touch. Our findings indicate that factory ensheathing celltransplantation improves motor, sensory and autonomic nerve functions in patients with chronic spinal cord injury.展开更多
[ Objective ] With Cupressustorulosa, Cinnamomum camphora and Cyclobalanopsis Oerst as test materials, the paper studied the effects of different non- host plants on olfactory responses of Tomicus yunnanensis. [ Metho...[ Objective ] With Cupressustorulosa, Cinnamomum camphora and Cyclobalanopsis Oerst as test materials, the paper studied the effects of different non- host plants on olfactory responses of Tomicus yunnanensis. [ Method ] The needles of Pinus yunnanensis were mixed with the leaves of Cupressustondosa, C. cam- phora and C. Oerst according to the ratios of 0 g ： 6 g, 1 g ： 5 g, 2 g ： 4 g, 3 g ： 3 g, 4 g ： 2 g, 5 g ： 1 g and 6 g ： 0 g, and the mixtures were put in the re- spanse arm of Y-tube olfactometer as odor source to observe the olfactory behavior of T. yunnanensis, the empty arm was set as control. [ Result ] When the needles of P. yunnanensis were mixed with the leaves of non-hest plants according to the ratio of 1 g ： 5 g and 2 g ： 4 g, they had less difference on attractive rate to T. yun- nanensis compared with complete P. yunnanensis needles in mixture （ratio： 6 g ： 0 g）, and the maximum difference was 14%. When the needles ofP. yunnanen- sis were mixed with non-host leaves according to the ratio of 1 g ： 5 g, 2 g ： 4 g, the attractive rate to T. yunnanensis decreased compared with complete P. yun- nanensis needles in mixture （ ratio： 6 g ： 0 g）, and the decrease value in maximum was 40%. [ Conclusion] When the ratio of non-host plants was relatively small in mixed leaves, non-host had less impact on olfactory responses of T. yunnanensis. As the proportion of non-hest leaves gradually increased, the attractive rate of leaf mixtures to T. yunnanensis was gradually small. The results could provide reference for determination of mixed ratio in construction of mixed forest and the de- velopment of botanical attractive and repellent of T. yunnanensis.展开更多
This paper presents a novel strategy for the response enhancement of olfactory sensory neurons (OSNs)-based biosensors by monitoring the enhancive responses of OSNs to odorants. An OSNs-based biosensor was developed o...This paper presents a novel strategy for the response enhancement of olfactory sensory neurons (OSNs)-based biosensors by monitoring the enhancive responses of OSNs to odorants. An OSNs-based biosensor was developed on the basis of the light addressable potentiometric sensor (LAPS), in which rat OSNs were cultured on the surface of LAPS chip and served as sensing elements. LY294002, the specific inhibitor of phosphatidylinositol 3-kinase (PI3K), was used to enhance the responses of OSNs to odorants. The responses of OSNs to odorants with and without the treatment of LY294002 were recorded by LAPS. The results show that the enhancive effect of LY294002 was recorded efficiently by LAPS and the responses of this OSNs-LAPS hybrid biosensor were enhanced by LY294002 by about 1.5-fold. We conclude that this method can enhance the responses of OSNs-LAPS hybrid biosensors, which may provide a novel strategy for the bioelectrical signal monitor of OSNs in biosensors. It is also suggested that this strategy may be applicable to other kinds of OSNs-based biosensors for cellular activity detection, such as microelectrode array (MEA) and field effect transistor (FET).展开更多
Conventional methods for harvesting, culturing and purifying olfactory ensheathing cells are complicated, time-consuming, and poorly reproducible. Olfactory bulbs were detached from adult Sprague Dawley rats and olfac...Conventional methods for harvesting, culturing and purifying olfactory ensheathing cells are complicated, time-consuming, and poorly reproducible. Olfactory bulbs were detached from adult Sprague Dawley rats and olfactory ensheathing cells were isolated using shearing, dispersion processes. After the primary cultures reached confluence, the cells were purified using a three-step process. The olfactory ensheathing cells attached and grew rapidly. The purity of the olfactory ensheathing cells increased following the three purification steps, eventually exceeding 95%. These cells could be maintained for an extended period time in culture. This simple, inexpensive, reproducible method of harvesting, culturing and purifying olfactory ensheathing cells shortens the culture cycle and provides sufficient olfactory ensheathing cells of controllable purity.展开更多
文摘Adult neurogenesis persists after birth in the subventricular zone, with new neurons migrating to the granule cell layer and glomerular layers of the olfactory bulb, where they integrate into existing circuitry as inhibitory interneurons. The generation of these new neurons in the olfactory bulb supports both structural and functional plasticity, aiding in circuit remodeling triggered by memory and learning processes. However, the presence of these neurons, coupled with the cellular diversity within the olfactory bulb, presents an ongoing challenge in understanding its network organization and function. Moreover,the continuous integration of new neurons in the olfactory bulb plays a pivotal role in regulating olfactory information processing. This adaptive process responds to changes in epithelial composition and contributes to the formation of olfactory memories by modulating cellular connectivity within the olfactory bulb and interacting intricately with higher-order brain regions. The role of adult neurogenesis in olfactory bulb functions remains a topic of debate. Nevertheless, the functionality of the olfactory bulb is intricately linked to the organization of granule cells around mitral and tufted cells. This organizational pattern significantly impacts output, network behavior, and synaptic plasticity, which are crucial for olfactory perception and memory. Additionally, this organization is further shaped by axon terminals originating from cortical and subcortical regions. Despite the crucial role of olfactory bulb in brain functions and behaviors related to olfaction, these complex and highly interconnected processes have not been comprehensively studied as a whole. Therefore, this manuscript aims to discuss our current understanding and explore how neural plasticity and olfactory neurogenesis contribute to enhancing the adaptability of the olfactory system. These mechanisms are thought to support olfactory learning and memory, potentially through increased complexity and restructuring of neural network structures, as well as the addition of new granule granule cells that aid in olfactory adaptation. Additionally, the manuscript underscores the importance of employing precise methodologies to elucidate the specific roles of adult neurogenesis amidst conflicting data and varying experimental paradigms. Understanding these processes is essential for gaining insights into the complexities of olfactory function and behavior.
基金supported by the National Natural Science Foundation of China,No.82001155(to LL)the Natural Science Foundation of Zhejiang Province,No.LY23H090004(to LL)+5 种基金the Natural Science Foundation of Ningbo,No.2023J068(to LL)the Fundamental Research Funds for the Provincial Universities of Zhejiang Province,No.SJLY2023008(to LL)the College Students'Scientific and Technological Innovation Project(Xin Miao Talent Plan)of Zhejiang Province,No.2022R405A045(to CC)the Student ResearchInnovation Program(SRIP)of Ningbo University,Nos.20235RIP1919(to CZ),2023SRIP1938(to YZ)the K.C.Wong Magna Fund in Ningbo University。
文摘A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.
基金supported by the Spanish Ministry of Economy and Competitiveness,No.PID2019-106498GB-I00(to MVS)the Instituto de Salud CarlosⅢ,Fondo Europeo de Desarrollo Regional“Una manera de hacer Europa”,No.PI19/00071(to MAB)+1 种基金Ministerio de Ciencia e Innovación Project,No.SAF2017-82736-C2-1-R(to MTMF)in Universidad Autónoma de MadridFundación Universidad Francisco de Vitoria(to JS)。
文摘Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic nerve.Still,it is unknown whether olfactory ensheathing glia also have neuroprotective properties.Olfactory ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion cells.Therefore,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve crush.Olfactory ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive treatments.Anatomical and gene expression analyses were performed.Olfactory bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡmolecules.Allogeneically and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an epimembrane.In axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 days.In these retinas,microglial anatomical activation was higher than after optic nerve crush alone.In intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or immunosuppression.However,neuroprotection of axotomized retinal ganglion cells did not improve with these treatments.The different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.
基金supported by the National Natural Science Foundation of China (32471188,32170984,82301787)。
文摘Iron is the most abundant transition metal in the brain and is essential for brain development and neuronal function;however,its abnormal accumulation is also implicated in various neurological disorders.The olfactory bulb(OB),an early target in neurodegenerative diseases,acts as a gateway for environmental toxins and contains diverse neuronal populations with distinct roles.This study explored the cell-specific vulnerability to iron in the OB using a mouse model of intranasal administration of ferric ammonium citrate(FAC).Olfactory function was assessed through olfactory discrimination tests,while iron levels in OB tissues,cerebrospinal fluid(CSF),and serum were quantified using inductively coupled plasma mass spectrometry(ICP-MS),immunohistochemical staining,and iron assays.Transcriptomic changes and immune responses were assessed using RNA sequencing and immune cell infiltration analysis.Results showed that intranasal FAC administration impaired olfactory function,accompanied by iron deposition in the olfactory mucosa and OB,as well as damage to olfactory sensory neurons.Notably,these effects occurred without elevations in CSF or serum iron levels.OB iron accumulation activated multiple immune cells,including microglia and astrocytes,but did not trigger ferroptosis.Spatial transcriptomic sequencing of healthy adult mouse OBs revealed significant cellular heterogeneity,with an abundance of neuroglia and neurons.Among neurons,GABAergic neurons were the most prevalent,followed by glutamatergic and dopaminergic neurons,while cholinergic and serotonergic neurons were sparsely distributed.Under iron-stressed conditions,oligodendrocytes,dopaminergic neurons,and glutamatergic neurons exhibited significant damage,while GABAergic neurons remained unaffected.These findings highlight the selective vulnerability of neuronal and glial populations to iron-induced stress,offering novel insights into the loss of specific cell types in the OB during iron dysregulation.
基金supported by a grant from the Singer Biology Fund at the University of Florida。
文摘Olfactory receptors(ORs),the largest vertebrate multigene family,exhibit wide copy number variation among taxa,ranging from~100 to 4000.The ecological importance of smell has been suggested to positively correlate with OR gene number,though debate exists on whether the number of total ORs,functional ORs,or the percentage of pseudogenes matters most.While olfaction has been poorly studied in most birds,Turkey Vultures(Cathartes aura)demonstrate keen olfactory ability,capable of foraging using smell alone.In contrast,Black Vultures(Coragyps atratus)have been thought to primarily use vision to locate food.Comparison of the OR genes in these two New World vultures presents an opportunity to examine the dynamics of OR evolution in related avian species that may differ in olfactory abilities.Using a PCR and cloning approach with degenerate primers,we sampled the OR subgenome in Turkey and Black Vultures,as well as Red-tailed Hawks(Buteo jamaicensis)and the distantly related Chicken(Gallus gallus),neither of which are thought to use olfaction extensively.Our results indicate that Turkey Vultures have many more OR genes than Red-tailed Hawks or chickens.Surprisingly,Black Vultures had an intermediate number of OR genes.The number of OR genes we estimated in the Turkey Vulture was much greater than previously reported in studies that used short-read sequencing.Additionally,we found that OR genes from New World vultures and Red-tailed Hawks form clades that were distinct from the clade that included most chicken OR genes,indicating that chickens share few OR orthologs with New World vultures or hawks.As previously observed in other animal groups,pseudogenes appeared throughout all clades and their percentage varied among taxa.These findings suggest the OR gene family is highly dynamic,changing rapidly over evolutionary time,and that taxa may have distinct suites of ORs in their genomes.
基金the support from the Shenzhen Science and Technology Program, China (KQTD2018041 1143628272)the special funds for Science Technology Innovation and Industrial Development of Shenzhen Dapeng New District, China (PT202101-02)the National Key Research and Development Program of China (2022YFD1700201)。
文摘Chemicals that modify pest behavior are developed to reduce crop damage by altering pest behavior, using specific genes within the olfactory system as molecular targets. The identification of these molecular targets in Bactrocera dorsalis, also known as the functional study of key olfactory genes, relies on CRISPR/Cas9-mediated gene knockout techniques. However, these techniques face limitations when applied to lethal genes. Transgenic technology offers a solution since it enables precise manipulation of gene expression in specific tissues or during certain developmental stages. Consequently, this study developed a piggyBac-mediated transgenic system in B. dorsalis to investigate reporter gene expression in olfactory organs, and assessed the olfactory behavior andantennal electrophysiological responses in transgenic lines. The goal was to assess the potential of this approach for future research on olfactory gene function. A universally expressed housekeeping gene from the BdorActin family was identified using the developmental transcriptome dataset. Its candidate promoter region(BdorActinA3a-1^(P–2k)) was then cloned into the piggyBac plasmid. We subsequently established two stable transgenic lines with specific TTAA insertion sites on chromosomes 4 and 5, consistent with the characteristics of piggyBac transposition. The transgenic strains exhibited essentially normal survival, with hatchability and adult lifespan unaffected, althoughthere were slight reductions in the emergence rate and oviposition capacity. The fluorescent reporter has been successfully expressed in olfactory-related organs, such as the antennae, proboscis, maxillary palp, legs, external genitalia, and brain. The antennal electrophysiological responses to representative chemicals in the transgenic lines were consistent with those of the wild type. However, some olfactory-related behaviors, such as pheromone response and mating, were significantly affected in the transgenic lines. These findings suggest that our system could potentially be applied in future olfactory research, such as driving the expression of exogenous elements that are effective in olfactory organs. However, caution is advised regarding its impact when applied to some olfactoryrelated behavioral phenotypes.
基金supported by the Key Research and Development Program of Hunan Province of China(2020SK2102)the Hunan Provincial Natural Science Foundation of China(2023JJ40420)+5 种基金the Changsha Municipal Natural Science Foundation(kq2208154)the Scientific Research Project of Hunan Provincial Health Commission(B202304088074)the Scientific Research Project of Hunan Provincial Health Commission(202203105045)the National Natural Science Foundation of China(82301435,82201484)the Hunan Provincial Natural Science Foundation of China(2024JJ4083)the Graduate Research and Innovation Project of Hunan Education Department(CX20220528).
文摘Background:Parkinson’s disease(PD)is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra(SN).Activation of the neuroinflammatory response has a pivotal role in PD.Mesenchymal stem cells(MSCs)have emerged as a promising therapeutic approach for various nerve injuries,but there are limited reports on their use in PD and the underlying mechanisms remain unclear.Methods:We investigated the effects of clinical-grade hypoxia-preconditioned olfactory mucosa(hOM)-MSCs on neural functional recovery in both PD models and patients,as well as the preventive effects on mouse models of PD.To assess improvement in neuroinflammatory response and neural functional recovery induced by hOM-MSCs exposure,we employed single-cell RNA sequencing(scRNA-seq),assay for transposase accessible chromatin with high-throughput sequencing(ATAC-seq)combined with full-length transcriptome isoform-sequencing(ISO-seq),and functional assay.Furthermore,we present the findings from an initial cohort of patients enrolled in a phaseⅠfirstinhuman clinical trial evaluating the safety and efficacy of intraspinal transplantation of hOM-MSC transplantation into severe PD patients.Results:A functional assay identified that transforming growth factor-β1(TGF-β1),secreted from hOM-MSCs,played a critical role in modulating mitochondrial function recovery in dopaminergic neurons.This effect was achieved through improving microglia immune regulation and autophagy homeostasis in the SN,which are closely associated with neuroinflammatory responses.Mechanistically,exposure to hOM-MSCs led to an improvement in neuroinflammation and neural function recovery partially mediated by TGF-β1 via activation of the anaplastic lymphoma kinase/phosphatidylinositol-3-kinase/protein kinase B(ALK/PI3K/Akt)signaling pathway in microglia located in the SN of PD patients.Furthermore,intraspinal transplantation of hOM-MSCs improved the recovery of neurologic function and regulated the neuroinflammatory response without any adverse reactions observed in patients with PD.Conclusions:These findings provide compelling evidence for the involvement of TGF-β1 in mediating the beneficial effects of hOM-MSCs on neural functional recovery in PD.Treatment and prevention of hOM-MSCs could be a promising and effective neuroprotective strategy for PD.Additionally,TGF-β1 may be used alone or combined with hOM-MSCs therapy for treating PD.
基金supported by the National Natural Science Foundation of China,No.82104421the China Postdoctoral Science Foundation,No.2022M721726+1 种基金the Innovation and Entrepreneurship Training Program for College Students of Jiangsu Province,No.202210304155Ythe Research Startup Fund Program of Nantong University,No.135421623023(all to XZ).
文摘Changes in olfactory function are considered to be early biomarkers of Parkinson’s disease.Olfactory dysfunction is one of the earliest non-motor features of Parkinson’s disease,appearing in about 90%of patients with early-stage Parkinson’s disease,and can often predate the diagnosis by years.Therefore,olfactory dysfunction should be considered a reliable marker of the disease.However,the mechanisms responsible for olfactory dysfunction are currently unknown.In this article,we clearly explain the pathology and medical definition of olfactory function as a biomarker for early-stage Parkinson’s disease.On the basis of the findings of clinical olfactory function tests and animal model experiments as well as neurotransmitter expression levels,we further characterize the relationship between olfactory dysfunction and neurodegenerative diseases as well as the molecular mechanisms underlying olfactory dysfunction in the pathology of early-stage Parkinson’s disease.The findings highlighted in this review suggest that olfactory dysfunction is an important biomarker for preclinical-stage Parkinson’s disease.Therefore,therapeutic drugs targeting non-motor symptoms such as olfactory dysfunction in the early stage of Parkinson’s disease may prevent or delay dopaminergic neurodegeneration and reduce motor symptoms,highlighting the potential of identifying effective targets for treating Parkinson’s disease by inhibiting the deterioration of olfactory dysfunction.
基金Supported by China Agriculture Research System of MOF and MARA(CARS-26)Innovation Platform Construction Project of Zhaoqing University(202413004)+1 种基金Innovation and Entrepreneurship Training Program Project of Guangdong Province College Student(X202310580113)Scientific Research Fund Funding Project of Zhaoqing University in 2023(QN202331).
文摘A highly sensitive olfactory system allows insects to precisely identify and position volatile compounds from different sources in their habitats,and plays a crucial role in their foraging,mating,and oviposition activities.During evolution,insects have successfully developed a large and complex olfactory system to adapt to heterogeneous environments,enabling the maintenance of inset population.A comprehensive examination of the olfactory system of insects may therefore yield novel insights into the development of innovative pest control and prevention strategies,as well as the study of olfactory mechanisms in vertebrates and even humans.This paper outlines the current state of research into the signal transduction mechanism by which insects perceive the olfactory molecules of their habitats.The aim of this review is to provide a reference point for future studies into the olfactory perception mechanism and its potential applications in pest management.
基金supported by the National Natural Science Foundation of China(Nos.32271055 and 32070995)the Jiangsu Province Innovative and Entrepreneurial Team Program,and the Guangdong Medical University(No.GDMUB2022048),China.
文摘The olfactory bulb(OB)is the first relay station in the olfactory system and functions as a crucial hub.It can represent odor information precisely and accurately in an ever-changing environment.As the only output neurons in the OB,mitral/tufted cells encode information such as odor identity and concentration.Recently,the neural strategies and mechanisms underlying odor representation and encoding in the OB have been investigated extensively.Here we review the main progress on this topic.We first review the neurons and circuits involved in odor representation,including the different cell types in the OB and the neural circuits within and beyond the OB.We will then discuss how two different coding strategies—spatial coding and temporal coding—work in the rodent OB.Finally,we discuss potential future directions for this research topic.Overall,this review provides a comprehensive description of our current understanding of how odor information is represented and encoded by mitral/tufted cells in the OB.
基金supported by the Natural Science Foundation of Chongqing (Grant No. CSTB2024NSCQ-MSX0944)。
文摘A gas sensor can convert external gas concentration or species into electric voltage or current signals by physical adsorption or chemical changes. As a result, a gas sensor in a nonlinear circuit can be used as a sensitive sensor for detecting external gas signals from the olfactory system. In this paper, a gas sensor and a field-effect transistor are incorporated into a simple FithzHugh–Nagumo neural circuit for capturing and encoding external gas signals. An improved functional neural circuit is obtained, and the effect of gas concentration, gas species and neuronal activity can be discerned as the gate voltage, threshold voltage and activation coefficient of the field-effect transistor, respectively. The gas concentration can affect the neural activities from quiescent to normal working and, finally, to saturation state in bursting, spiking, periodic and chaotic firings with different frequencies. The effects of gas species and neuronal activity on the firing state can also be achieved in this functional neural circuit. In addition, variations in the gate voltage, threshold voltage and activation coefficient can cause switching between different firing modes. These results can be helpful in designing artificial olfactory devices for bionic gas recognition and other coupled systems arising in applied sciences.
基金supported by the National Key Research and Development Program of China (2021YFA120260)the NSFC (92064009,22175042,12474071)+3 种基金the Science and Technology Commission of Shanghai Municipality (22501100900)Natural Science Foundation of Shandong Province (ZR2024YQ051)the China Postdoctoral Science Foundation (2022TQ0068,2023M740644)the Shanghai Sailing Program (23YF1402200,23YF1402400).
文摘Simulating the human olfactory nervous system is one of the key issues in the field of neuromorphic computing.Olfac-tory neurons interact with gas molecules,transmitting and storing odor information to the olfactory center of the brain.In order to emulate the complex functionalities of olfactory neurons,this study presents a flexible olfactory synapse transistor(OST)based on pentacene/C8-BTBT organic heterojunction.By modulating the interface between the energy bands of the organic semiconductor layers,this device demonstrates high sensitivity(ppb level)and memory function for NH3 sensing.Typi-cal synaptic behaviors triggered by NH_(3) pulses have been successfully demonstrated,such as inhibitory postsynaptic currents(IPSC),paired-pulse depression(PPD),long-term potentiation/depression(LTP/LTD),and transition from short-term depression(STD)to long-term depression(LTD).Furthermore,this device maintains stable olfactory synaptic functions even under differ-ent bending conditions,which can present new insights and possibilities for flexible synaptic systems and bio-inspired elec-tronic products.
基金National Natural Science Foundation of China General Project(Grant No.82374195).
文摘To explore the target of action of LHQW-XYS on the main components of COVID-19 olfactory impairment by using network pharmacological methods and try to reveal its mechanism of action in the treatment related to COVID-19 induced olfactory impairment,we used the TCMSP platform to obtain potential active ingredients through oral utilization and drug-like properties screening;the Swiss TargetPrediction platform to predict the targets of the active ingredients and construct a drug-ingredient-target network,and then obtained the gene targets of COVID-19 olfactory injury through GeneCards,OMIM,and TTD platforms to intersect the drug targets and disease genes to obtain common targets.The drug targets and disease genes were intersected to obtain common targets.STRING and Cytoscape 3.8.2 software were used to construct the target-disease gene PPI network,screen the key targets and core gene clusters,and analyze the key targets by GO and KEGG enrichment analyses with the help of the Metascape platform,and then map the screened core active ingredients and their targets into the pathway to construct the core active ingredients-targets-pathway network.The core active ingredient-target-pathway network was constructed,and finally,molecular docking was carried out.The results showed that there were 4669 potential targets,5609 disease targets,and 17 drug-disease cross-targets for the active ingredients of LHQW-XYS.The GO and KEGG enrichment analyses indicated that the mechanism of LHQW-XYS in the treatment of olfactory impairment in COVID-19 may be due to the regulation of related signaling pathways,such as Serotonergic synapse and Regulation of lipolysis in adipocytes.Molecular docking showed that six active components(quercetin,luteolin,kaempferol,7-methoxy-2-methylisoflavone,wogonin,medicarpin)and two key genes(PTGS2,PPARG)had good binding properties.In the end,we conclude that LHQW-XYS may act on Serotonergic synapse and Regulation of lipolysis in adipocyte pathways to achieve anti-COVID-19 olfactory impairment-associated effects.
基金supported by Key Research Projects of Ningxia Hui Autonomous Region of China,No.2018BCG01002(to HCX)the Natural Science Foundation of Ningxia Hui Autonomous Region of China,No.NZ17150(to PY)。
文摘Olfactory ensheathing cells(OECs) from the olfactory bulb(OB) and the olfactory mucosa(OM) have the capacity to repair nerve injury. However, the difference in the therapeutic effect between OB-derived OECs and OM-derived OECs remains unclear. In this study, we extracted OECs from OB and OM and compared the gene and protein expression profiles of the cells using transcriptomics and non-quantitative proteomics techniques. The results revealed that both OB-derived OECs and OM-derived OECs highly expressed genes and proteins that regulate cell growth, proliferation, apoptosis and vascular endothelial cell regeneration. The differentially expressed genes and proteins of OB-derived OECs play a key role in regulation of nerve regeneration and axon regeneration and extension, transmission of nerve impulses and response to axon injury. The differentially expressed genes and proteins of OM-derived OECs mainly participate in the positive regulation of inflammatory response, defense response, cytokine binding, cell migration and wound healing. These findings suggest that differentially expressed genes and proteins may explain why OB-derived OECs and OM-derived OECs exhibit different therapeutic roles. This study was approved by the Animal Ethics Committee of the General Hospital of Ningxia Medical University(approval No. 2017-073) on February 13, 2017.
文摘Objective Combine olfactory ensheathing glia （OEG） implantation with ex vivo non-viral vector-based neurotrophin- 3 （NT-3） gene therapy in attempting to enhance regeneration after thoracic spinal cord injury （SCI）. Methods Primary OEG were transfected with cationic liposome-mediated recombinant plasmid pcDNA3.1 （＋）-NT3 and subsequently implanted into adult Wistar rats directly after the thoracic spinal cord （T9） contusion by the New York University impactor. The animals in 3 different groups received 4x 1050EG transfected with pcDNA3.1 （＋）-NT3 or pcDNA3.1 （＋） plasmids, or the OEGs without any plasmid transfection, respectively; the fourth group was untreated group, in which no OEG was implanted. Results NT-3 production was seen increased both ex vivo and in vivo in pcDNA3.1 （＋）-NT3 transfected OEGs. Three months after implantation of NT-3-transfected OEGs, behavioral analysis revealed that the hindlimb function of SCI rats was improved. All spinal cords were filled with regenerated neurofilament-positive axons. Retrograde tracing revealed enhanced regenerative axonal sprouting. Conclusion Non-viral vector-mediated genetic engineering of OEG was safe and more effective in producing NT- 3 and promoting axonal outgrowth followed by enhancing SCI recovery in rats.
文摘Forty-three patients with chronic spinal cord injury for over 6 months were transplanted with bryonic olfactory ensheathing cells, 2-4 × 106, into multiple sites in the injured area under the sur-gical microscope. The sympathetic skin response in patients was measured with an electromyo-graphy/evoked potential instrument 1 day before transplantation and 3-8 weeks after trans-tion. Spinal nerve function of patients was assessed using the American Spinal Injury Association impairment scale. The sympathetic skin response was elicited in 32 cases before olfactory en-sheathing celltransplantation, while it was observed in 34 cases after transplantation. tantly, sympathetic skin response latency decreased significantly and amplitude increased cantly after transplantation. Transplantation of olfactory ensheathing cells also improved American Spinal Injury Association scores for movement, pain and light touch. Our findings indicate that factory ensheathing celltransplantation improves motor, sensory and autonomic nerve functions in patients with chronic spinal cord injury.
基金Supported by 948 Project of State Forestry Administration(2009-4-38)~~
文摘[ Objective ] With Cupressustorulosa, Cinnamomum camphora and Cyclobalanopsis Oerst as test materials, the paper studied the effects of different non- host plants on olfactory responses of Tomicus yunnanensis. [ Method ] The needles of Pinus yunnanensis were mixed with the leaves of Cupressustondosa, C. cam- phora and C. Oerst according to the ratios of 0 g ： 6 g, 1 g ： 5 g, 2 g ： 4 g, 3 g ： 3 g, 4 g ： 2 g, 5 g ： 1 g and 6 g ： 0 g, and the mixtures were put in the re- spanse arm of Y-tube olfactometer as odor source to observe the olfactory behavior of T. yunnanensis, the empty arm was set as control. [ Result ] When the needles of P. yunnanensis were mixed with the leaves of non-hest plants according to the ratio of 1 g ： 5 g and 2 g ： 4 g, they had less difference on attractive rate to T. yun- nanensis compared with complete P. yunnanensis needles in mixture （ratio： 6 g ： 0 g）, and the maximum difference was 14%. When the needles ofP. yunnanen- sis were mixed with non-host leaves according to the ratio of 1 g ： 5 g, 2 g ： 4 g, the attractive rate to T. yunnanensis decreased compared with complete P. yun- nanensis needles in mixture （ ratio： 6 g ： 0 g）, and the decrease value in maximum was 40%. [ Conclusion] When the ratio of non-host plants was relatively small in mixed leaves, non-host had less impact on olfactory responses of T. yunnanensis. As the proportion of non-hest leaves gradually increased, the attractive rate of leaf mixtures to T. yunnanensis was gradually small. The results could provide reference for determination of mixed ratio in construction of mixed forest and the de- velopment of botanical attractive and repellent of T. yunnanensis.
基金supported by the National Natural Science Foundation ofChina (No. 60725102)the Natural Science Foundation of Zhejiang Province, China (No. R205505)
文摘This paper presents a novel strategy for the response enhancement of olfactory sensory neurons (OSNs)-based biosensors by monitoring the enhancive responses of OSNs to odorants. An OSNs-based biosensor was developed on the basis of the light addressable potentiometric sensor (LAPS), in which rat OSNs were cultured on the surface of LAPS chip and served as sensing elements. LY294002, the specific inhibitor of phosphatidylinositol 3-kinase (PI3K), was used to enhance the responses of OSNs to odorants. The responses of OSNs to odorants with and without the treatment of LY294002 were recorded by LAPS. The results show that the enhancive effect of LY294002 was recorded efficiently by LAPS and the responses of this OSNs-LAPS hybrid biosensor were enhanced by LY294002 by about 1.5-fold. We conclude that this method can enhance the responses of OSNs-LAPS hybrid biosensors, which may provide a novel strategy for the bioelectrical signal monitor of OSNs in biosensors. It is also suggested that this strategy may be applicable to other kinds of OSNs-based biosensors for cellular activity detection, such as microelectrode array (MEA) and field effect transistor (FET).
基金Research Innovation Program for College Graduates of Jiangsu Province, No ZY320717General Scientific Research of Health Department of Jiangsu Province, No H200920
文摘Conventional methods for harvesting, culturing and purifying olfactory ensheathing cells are complicated, time-consuming, and poorly reproducible. Olfactory bulbs were detached from adult Sprague Dawley rats and olfactory ensheathing cells were isolated using shearing, dispersion processes. After the primary cultures reached confluence, the cells were purified using a three-step process. The olfactory ensheathing cells attached and grew rapidly. The purity of the olfactory ensheathing cells increased following the three purification steps, eventually exceeding 95%. These cells could be maintained for an extended period time in culture. This simple, inexpensive, reproducible method of harvesting, culturing and purifying olfactory ensheathing cells shortens the culture cycle and provides sufficient olfactory ensheathing cells of controllable purity.
