Acquired brain injury(ABI)is an injury that affects the brain structure and function.Traditional ABI treatment strategies,including medications and rehabilitation therapy,exhibit their ability to improve its impairmen...Acquired brain injury(ABI)is an injury that affects the brain structure and function.Traditional ABI treatment strategies,including medications and rehabilitation therapy,exhibit their ability to improve its impairments in cognition,emotion,and physical activity.Recently,near-infrared(NIR)photobiomodulation(PBM)has emerged as a promising physical intervention method for ABI,demonstrating that low-level light therapy can modulate cellular metabolic processes,reduce the in flammation and reactive oxygen species of ABI microenvironments,and promote neural repair and regeneration.Preclinical studies using ABI models have been carried out,revealing the potential of PBM in promoting brain injury recovery although its clinical application is still in its early stages.In this review,we first inspected the possible physical and biological mechanisms of NIR-PBM,and then reported the pathophysiology and physiology of ABI underlying NIR-PBM intervention.Therefore,the potential of NIR-PBM as a therapeutic intervention in ABI was demonstrated and it is also expected that further work can facilitate its clinical applications.展开更多
Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apopt...Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apoptosis in glaucoma.Modulation of Kir4.1 expression in Müller cells may therefore be a potential strategy for attenuating retinal ganglion cell damage in glaucoma.In this study,we identified seven predicted phosphorylation sites in Kir4.1 and constructed lentiviral expression systems expressing Kir4.1 mutated at each site to prevent phosphorylation.Following this,we treated Müller glial cells in vitro and in vivo with the m Glu R I agonist DHPG to induce Kir4.1 or Kir4.1 Tyr^(9)Asp overexpression.We found that both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited activation of Müller glial cells.Subsequently,we established a rat model of chronic ocular hypertension by injecting microbeads into the anterior chamber and overexpressed Kir4.1 or Kir4.1 Tyr^(9)Asp in the eye,and observed similar results in Müller cells in vivo as those seen in vitro.Both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited Müller cell activation,regulated the balance of Bax/Bcl-2,and reduced the m RNA and protein levels of pro-inflammatory factors,including interleukin-1βand tumor necrosis factor-α.Furthermore,we investigated the regulatory effects of Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression on the release of pro-inflammatory factors in a co-culture system of Müller glial cells and microglia.In this co-culture system,we observed elevated adenosine triphosphate concentrations in activated Müller cells,increased levels of translocator protein(a marker of microglial activation),and elevated interleukin-1βm RNA and protein levels in microglia induced by activated Müller cells.These changes could be reversed by Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression in Müller cells.Kir4.1 overexpression,but not Kir4.1 Tyr^(9)Asp overexpression,reduced the number of proliferative and migratory microglia induced by activated Müller cells.Collectively,these results suggest that the tyrosine residue at position nine in Kir4.1 may serve as a functional modulation site in the retina in an experimental model of glaucoma.Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression attenuated Müller cell activation,reduced ATP/P2X receptor–mediated interactions between glial cells,inhibited microglial activation,and decreased the synthesis and release of pro-inflammatory factors,consequently ameliorating retinal ganglion cell apoptosis in glaucoma.展开更多
Diabetic retinopathy is a prominent cause of blindness in adults,with early retinal ganglion cell loss contributing to visual dysfunction or blindness.In the brain,defects inγ-aminobutyric acid synaptic transmission ...Diabetic retinopathy is a prominent cause of blindness in adults,with early retinal ganglion cell loss contributing to visual dysfunction or blindness.In the brain,defects inγ-aminobutyric acid synaptic transmission are associated with pathophysiological and neurodegenerative disorders,whereas glucagon-like peptide-1 has demonstrated neuroprotective effects.However,it is not yet clear whether diabetes causes alterations in inhibitory input to retinal ganglion cells and whether and how glucagon-like peptide-1 protects against neurodegeneration in the diabetic retina through regulating inhibitory synaptic transmission to retinal ganglion cells.In the present study,we used the patch-clamp technique to recordγ-aminobutyric acid subtype A receptor-mediated miniature inhibitory postsynaptic currents in retinal ganglion cells from streptozotocin-induced diabetes model rats.We found that early diabetes(4 weeks of hyperglycemia)decreased the frequency of GABAergic miniature inhibitory postsynaptic currents in retinal ganglion cells without altering their amplitude,suggesting a reduction in the spontaneous release ofγ-aminobutyric acid to retinal ganglion cells.Topical administration of glucagon-like peptide-1 eyedrops over a period of 2 weeks effectively countered the hyperglycemia-induced downregulation of GABAergic mIPSC frequency,subsequently enhancing the survival of retinal ganglion cells.Concurrently,the protective effects of glucagon-like peptide-1 on retinal ganglion cells in diabetic rats were eliminated by topical administration of exendin-9-39,a specific glucagon-like peptide-1 receptor antagonist,or SR95531,a specific antagonist of theγ-aminobutyric acid subtype A receptor.Furthermore,extracellular perfusion of glucagon-like peptide-1 was found to elevate the frequencies of GABAergic miniature inhibitory postsynaptic currents in both ON-and OFF-type retinal ganglion cells.This elevation was shown to be mediated by activation of the phosphatidylinositol-phospholipase C/inositol 1,4,5-trisphosphate receptor/Ca2+/protein kinase C signaling pathway downstream of glucagon-like peptide-1 receptor activation.Moreover,multielectrode array recordings revealed that glucagon-like peptide-1 functionally augmented the photoresponses of ON-type retinal ganglion cells.Optomotor response tests demonstrated that diabetic rats exhibited reductions in visual acuity and contrast sensitivity that were significantly ameliorated by topical administration of glucagon-like peptide-1.These results suggest that glucagon-like peptide-1 facilitates the release ofγ-aminobutyric acid onto retinal ganglion cells through the activation of glucagon-like peptide-1 receptor,leading to the de-excitation of retinal ganglion cell circuits and the inhibition of excitotoxic processes associated with diabetic retinopathy.Collectively,our findings indicate that theγ-aminobutyric acid system has potential as a therapeutic target for mitigating early-stage diabetic retinopathy.Furthermore,the topical administration of glucagon-like peptide-1 eyedrops represents a non-invasive and effective treatment approach for managing early-stage diabetic retinopathy.展开更多
Hypoglossal motor neurons(HMNs) innervate tongue muscles and play key roles in a variety of physiological functions,including swallowing,mastication,suckling,vocalization,and respiration.Dysfunction of HMNs is associa...Hypoglossal motor neurons(HMNs) innervate tongue muscles and play key roles in a variety of physiological functions,including swallowing,mastication,suckling,vocalization,and respiration.Dysfunction of HMNs is associated with several diseases,such as obstructive sleep apnea(OSA) and sudden infant death syndrome.OS A is a serious breathing disorder associated with the activity of HMNs during different sleep-wake states.Identifying the neural mechanisms by which the statedependent activities of HMNs are controlled may be helpful in providing a theoretical basis for effective therapy for OSA.However,the presynaptic partners governing the activity of HMNs remain to be elucidated.In the present study,we used a cell-type-specific retrograde tracing system based on a modified rabies virus along with a Cre/loxP gene-expression strategy to map the whole-brain monosynaptic inputs to HMNs in mice.We identified 53 nuclei targeting HMNs from six brain regions:the amygdala,hypothalamus,midbrain,pons,medulla,and cerebellum.We discovered that GAB Aergic neurons in the central amygdaloid nucleus,as well as calretinin neurons in the parasubthalamic nucleus,sent monosynaptic projections to HMNs.In addition,HMNs received direct inputs from several regions associated with respiration,such as the preBotzinger complex,parabrachial nucleus,nucleus of the solitary tract,and hypothalamus.Some regions engaged in sleep-wake regulation(the parafacial zone,parabrachial nucleus,ventral medulla,sublaterodorsal tegmental nucleus,dorsal raphe nucleus,periaqueductal gray,and hypothalamus) also provided primary inputs to HMNs.These results contribute to further elucidating the neural circuits underlying disorders caused by the dysfunction of HMNs.展开更多
The conventional approach to investigating functional connectivity in the block-designed study usually concatenates task blocks or employs residuals of task activation.While providing many insights into brain function...The conventional approach to investigating functional connectivity in the block-designed study usually concatenates task blocks or employs residuals of task activation.While providing many insights into brain functions,the block design adds more manipulation in functional network analysis that may reduce the purity of the blood oxygenation level-dependent signal.Recent studies utilized one single long run for task trials of the same condition,the so-called continuous design,to investigate functional connectivity based on task functional magnetic resonance imaging.Continuous brain activities associated with the single-task condition can be directly utilized for task-related functional connectivity assessment,which has been examined for working memory,sensory,motor,and semantic task experiments in previous research.But it remains unclear how the block and continuous design influence the assessment of task-related functional connectivity networks.This study aimed to disentangle the separable effects of block/continuous design and working memory load on task-related functional connectivity networks,by using repeated-measures analysis of variance.Across 50 young healthy adults,behavioral results of accuracy and reaction time showed a significant main effect of design as well as interaction between design and load.Imaging results revealed that the cingulo-opercular,fronto-parietal,and default model networks were associated with not only task activation,but significant main effects of design and load as well as their interaction on intra-and inter-network functional connectivity and global network topology.Moreover,a significant behavior-brain association was identified for the continuous design.This work has extended the evidence that continuous design can be used to study task-related functional connectivity and subtle brain-behavioral relationships.展开更多
OBJECTIVE： To explain the mechanisms of tuhe synthesis, secretion and regulation of brain natriuretic peptide （BNP）, and analyze its role in central nervous system diseases. DATA SOURCES： An online search of Pubme...OBJECTIVE： To explain the mechanisms of tuhe synthesis, secretion and regulation of brain natriuretic peptide （BNP）, and analyze its role in central nervous system diseases. DATA SOURCES： An online search of Pubmed was undertaken to identify articles related to BNP published in English from January 1990 to February 2007 by using the key words of ＂brain natriuretic pepfide （BNP）, central nervous system, subarachnoid hemorrhage （SAH）, brain edema, epilepsy＂. Other articles were searched in China Hospital Knowledge Database （CHKD） by concrete name of journals and title of articles. STUDY SELECTION： The collected articles were primarily screened, those about BNP and its association with central nervous system diseases were selected, whereas the obviously irrelative ones excluded, and the full-texts of the other literatures were searched manually. DATA EXTRACTION： Totally 96 articles were collected, 40 of them were enrolled, and the other 56 were excluded due to repetitive studies or reviews. DATA SYNTHESIS： At present, there are penetrating studies on BNP in the preclinical medicine and clinical medicine of cerebrovascular and cardiovascular diseases, and the investigative outcomes have been gradually applied in clinical practice, and satisfactory results have been obtained. However, the application of BNP in diagnosing and treating central nervous system diseases is still at the experimental phase without - outstanding outcomes, thus the preclinical and clinical studies should be enhanced. CONCLUSION： As a kind of central medium or modulator, BNP plays a certain role in the occurrence, development and termination of central nervous system diseases, the BNP level in serum has certain changing law in SAH, brain edema, epilepsy, etc., but the specific mechanisms are unclear.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
Alzheimer'sdisease(AD)isaprogressive neurodegenerative disorder characterized by cognitive impairment and distinct neuropathological features,including amyloid-βplaques,neurofibrillary tangles,and reactive astrog...Alzheimer'sdisease(AD)isaprogressive neurodegenerative disorder characterized by cognitive impairment and distinct neuropathological features,including amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis.Developing effective diagnostic,preventative,and therapeutic strategies for AD necessitates the establishment of animal models that accurately recapitulate the pathophysiological processes of the disease.Existing transgenic mouse models have significantly contributed to understanding AD pathology but often fail to replicate the complexity of human AD.Additionally,these models are limited in their ability to elucidate the interplay among amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis due to the absence of spatially and temporally specific genetic manipulation.In this study,we introduce a novel AD mouse model(APP/PS1-TauP301L-Adeno mice)designed to rapidly induce pathological symptoms and enhance understanding of AD mechanisms.Neurofibrillary tangles and severe reactive astrogliosis were induced by injecting AAVDJ-EF1a-hTauP301L-EGFP and Adeno-GFAP-GFP viruses into the hippocampi of 5-month-old APP/PS1 mice.Three months post-injection,these mice exhibited pronounced astrogliosis,substantial amyloid-βplaque accumulation,extensiveneurofibrillarytangles,accelerated neuronal loss,elevated astrocytic GABA levels,and significant spatial memory deficits.Notably,these pathological features were less severe in AAVTauP301L-expressing APP/PS1 mice without augmented reactive astrogliosis.These findings indicate an exacerbating role of severe reactive astrogliosis in amyloid-βplaque and neurofibrillary tangle-associated pathology.The APP/PS1-TauP301L-Adeno mouse model provides a valuable tool for advancing therapeutic research aimed at mitigating the progression of AD.展开更多
The visual cortex is an essential part of the brain for processing visual information.It exhibits structural and functional plasticity,which is crucial for adapting to complex visual environments.The quintessential ma...The visual cortex is an essential part of the brain for processing visual information.It exhibits structural and functional plasticity,which is crucial for adapting to complex visual environments.The quintessential manifestation of visual cortical plasticity is ocular dominance plasticity during the critical period,which involves numerous cellular and molecular events.While previous studies have emphasized the role of visual cortical neurons and their associated functional molecules in visual plasticity,recent findings have revealed that structural factors such as the extracellular matrix and glia are also involved.Investigating how these molecules interact to form a complex network that facilitates plasticity in the visual cortex is crucial to our understanding of the development of the visual system and the advancement of therapeutic strategies for visual disorders like amblyopia.展开更多
The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency i...The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson's disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson's disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore,bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico–striato–pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson's disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson's disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson's disease,particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremordominant and non-tremor-dominant Parkinson's disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia–thalamus network. Therefore, the composition of the globus pallidus neurons, the neurotransmitters that act on them, their electrical activity,and the neural circuits they form can guide the search for new multi-target drugs to treat Parkinson's disease in clinical practice. Examining the potential intra-nuclear and neural circuit mechanisms of deep brain stimulation associated with the globus pallidus can facilitate the management of both motor and non-motor symptoms while minimizing the side effects caused by deep brain stimulation.展开更多
Throughout the lifespan,an animal can encounter predators frequently,thus the ability to avoid attacks from predators is crucial for its survival.The chances of evading danger can be greatly improved if the animal can...Throughout the lifespan,an animal can encounter predators frequently,thus the ability to avoid attacks from predators is crucial for its survival.The chances of evading danger can be greatly improved if the animal can respond immediately to the threat.Therefore,when an animal detects a threat through its visual system,it must quickly direct its gaze and attention toward the source of danger,assess the threat level,and take appropriate action.展开更多
Piezo2,a mechanosensitive ion channel,serves as a crucial mechanotransducer in dental primary afferent(DPA)neurons and is potentially involved in hypersensitivity to mild mechanical irritations observed in dental pati...Piezo2,a mechanosensitive ion channel,serves as a crucial mechanotransducer in dental primary afferent(DPA)neurons and is potentially involved in hypersensitivity to mild mechanical irritations observed in dental patients.Given Piezo2’s widespread expression across diverse subpopulations of DPA neurons,this study aimed to characterize the mechanosensory properties of Piezo2-expressing DPA neurons with a focus on distinct features of voltage-gated sodium channels(VGSCs)and neuropeptide profiles.Using whole-cell patch-clamp recordings,we observed mechanically activated action potentials(APs)and classified AP waveforms based on the presence or absence of a hump during the repolarization phase.Single-cell reverse transcription polymerase chain reaction combined with patch-clamp recordings revealed specific associations between AP waveforms and molecular properties,including tetrodotoxin-resistant VGSCs(NaV1.8 and NaV1.9)and TRPV1 expression.Reanalysis of the transcriptomic dataset of DPA neurons identified correlations between neuropeptides—including two CGRP isoforms(α-CGRP andβ-CGRP),Substance P,and Galanin—and the expression of NaV1.8 and NaV1.9,which were linked to defined AP subtypes.These molecular associations were further validated in Piezo2+DPA neurons using fluorescence in situ hybridization.Together,these findings highlight the electrophysiological and neurochemical heterogeneity of Piezo2-expressing DPA neurons and their specialized roles in distinct mechanosensory signal transmission.展开更多
DDeeaarr EEddiittoorr,,The encoding and retrieval of emotional memories demands intricate interplay within the limbic network,where the network state is subject to significant reconfiguration by learning-induced plast...DDeeaarr EEddiittoorr,,The encoding and retrieval of emotional memories demands intricate interplay within the limbic network,where the network state is subject to significant reconfiguration by learning-induced plasticity,behavioral state,and contextual information[1].展开更多
The advancement in catalysis techniques for sustainable environmental applications,particularly an alternative to the current Haber-Bosch process for NH_(3),has recently gained widespread attention.Although photocatal...The advancement in catalysis techniques for sustainable environmental applications,particularly an alternative to the current Haber-Bosch process for NH_(3),has recently gained widespread attention.Although photocatalytic conversion of N_(2) to NH_(3) using solar energy is an eco-friendly method,it has the limitation of low quantum yield.Recently,2D Bi-based photocatalysts which exhibit higher visible light absorption than TiO_(2) and higher stability than MXene have been an active research topic,and their performance can be enhanced through improved visible light absorption properties by incorporating plasmonic gold nanoparticles while nitrogen adsorption could be enhanced through oxygen vacancy(OV)processes.In the present study,we explore the application of 2D nanosized Bi_(2)O_(3–x) and gold nanoparticles for visible light photo generation of NH_(3).HRTEM and XPS reveal that the formation of AuNP and nano-sized Bi_(2)O_(3–x) in AuNP/Bi_(2)O_(3–x) heterozygote structure promotes the charge carrier mobility and charge transport at the interface,resulting in a 2.6-fold increase in the photocatalytic activity compared to micro-sized Bi_(2)O_(3–x) with AuNP.The improved photocatalytic performance can be ascribed to significant enhancement of visible light absorption by plasmonic nanoparticles,fast charge transport and mobility(due to sheet morphology)and the N_(2) activation by OV in AuNP/Bi_(2)O_(3–x) heterozygote.Through a systematic experimental investigation involving catalysts,concentration,pH,and scavengers,the highest photocatalytic performance was achieved with the heterozygote structures of AuNP/n-Bi_(2)O_(3–x) under optimized conditions,yielding 432.5μmol gcat^(-1) h^(-1) of NH_(3).展开更多
Neuraxial opioids,widely used in obstetric and perioperative pain management,often lead to unwanted itch,reducing patient satisfaction.While theμ-opioid receptor has been implicated in opioid-induced itch,the genetic...Neuraxial opioids,widely used in obstetric and perioperative pain management,often lead to unwanted itch,reducing patient satisfaction.While theμ-opioid receptor has been implicated in opioid-induced itch,the genetic basis for variable itch incidence remains unknown.This study examined 3616 patients receiving epidural opioids,revealing an itch occurrence of 26.55%,with variations among opioid types and gender.Analysis of the OPRM1 gene identified six single-nucleotide polymorphisms,notably rs1799971(A118G),that correlated with opioid-induced itch.Mouse models with an equivalent A112G mutation showed reduced neuraxial opioid-induced itch and light touch-evoked itch,mirroring human findings.The 118G allele demonstrated an anti-itch effect without impacting analgesia,addiction,or tolerance,offering insights for risk stratification and potential anti-itch pretreatment strategies.展开更多
The various bioacoustics signals obtained with auscultation contain complex clinical information that has been traditionally used as biomarkers,however,they are not extensively used in clinical studies owing to their ...The various bioacoustics signals obtained with auscultation contain complex clinical information that has been traditionally used as biomarkers,however,they are not extensively used in clinical studies owing to their spatiotemporal limitations.In this study,we developed a wearable stethoscope for wireless,skinattachable,low-power,continuous,real-time auscultation using a lung-sound-monitoring-patch(LSMP).LSMP can monitor respiratory function through a mobile app and classify normal and adventitious breathing by comparing their unique acoustic characteristics.The human heart and breathing sounds from humans can be distinguished from complex sound signals consisting of a mixture of bioacoustic signals and external noise.The performance of the LSMP sensor was further demonstrated in pediatric patients with asthma and elderly chronic obstructive pulmonary disease(COPD)patients where wheezing sounds were classified at specific frequencies.In addition,we developed a novel method for counting wheezing events based on a two-dimensional convolutional neural network deep-learning model constructed de novo and trained with our augmented fundamental lung-sound data set.We implemented a counting algorithm to identify wheezing events in real-time regardless of the respiratory cycle.The artificial intelligence-based adventitious breathing event counter distinguished>80%of the events(especially wheezing)in long-term clinical applications in patients with COPD.展开更多
Astrocytes in the spinal dorsal horn(SDH)exhibit diverse reactive phenotypes under neuropathic conditions,yet the mechanisms driving this diversity and its implications in chronic pain remain unclear.Here,we report th...Astrocytes in the spinal dorsal horn(SDH)exhibit diverse reactive phenotypes under neuropathic conditions,yet the mechanisms driving this diversity and its implications in chronic pain remain unclear.Here,we report that spared nerve injury(SNI)induces marked upregulation of both complement component 3(C3⁺,A1-like)and S100 calcium-binding protein A10(S100A10⁺,A2-like)astrocyte subpopulations in the SDH,with elevated microglial cytokines including interleukin-1α,tumor necrosis factor-α,and complement component 1q.Transcriptomic,immunohistochemical,and Western blot analyses reveal co-activation of multiple reactive astrocyte states over a unidirectional shift toward an A1-like phenotype.Fibroblast growth factor 8(FGF8),a neuroprotective factor via FGFR3,mitigated microglia-induced C3⁺astrocyte reactivity in vitro and suppressed spinal C3 expression and mechanical allodynia following intrathecal administration in SNI mice.These findings reveal a microglia–astrocyte signaling axis that promotes A1 reactivity and position FGF8 as a promising therapeutic candidate for neuropathic pain by modulating astrocyte heterogeneity.展开更多
Polystyrene nanoparticles pose significant toxicological risks to aquatic ecosystems,yet their impact on zebrafish(Danio rerio)embryonic development,particularly erythropoiesis,remains underexplored.This study used si...Polystyrene nanoparticles pose significant toxicological risks to aquatic ecosystems,yet their impact on zebrafish(Danio rerio)embryonic development,particularly erythropoiesis,remains underexplored.This study used single-cell RNA sequencing to comprehensively evaluate the effects of polystyrene nanoparticle exposure on erythropoiesis in zebrafish embryos.In vivo validation experiments corroborated the transcriptomic findings,revealing that polystyrene nanoparticle exposure disrupted erythrocyte differentiation,as evidenced by the decrease in mature erythrocytes and concomitant increase in immature erythrocytes.Additionally,impaired heme synthesis further contributed to the diminished erythrocyte population.These findings underscore the toxic effects of polystyrene nanoparticles on hematopoietic processes,highlighting their potential to compromise organismal health in aquatic environments.展开更多
Dear Editor,Sleep plays a vital role in physical health,influencing chronic diseases,memory,and overall quality of life[1,2].In recent years,the relationship between sleep health and physical activity has gained atten...Dear Editor,Sleep plays a vital role in physical health,influencing chronic diseases,memory,and overall quality of life[1,2].In recent years,the relationship between sleep health and physical activity has gained attention,with a particular focus on how daily step count affects various sleep metrics.展开更多
Astrocyte maturation is crucial for brain function,yet the mechanisms regulating this process remain poorly understood.In this study,we identify the bHLH transcription factors Olig1 and Olig2 as essential coordinators...Astrocyte maturation is crucial for brain function,yet the mechanisms regulating this process remain poorly understood.In this study,we identify the bHLH transcription factors Olig1 and Olig2 as essential coordinators of cortical astrocyte maturation.We demonstrate that Olig1 and Olig2 work synergistically to regulate cortical astrocyte maturation by modulating Bmp7 expression.Genetic ablation of both Olig1 and Olig2 results in defective astrocyte morphology,including reduced process complexity and an immature gene expression profile.Single-cell RNA sequencing reveals a shift towards a less mature astrocyte state,marked by elevated levels of HOPX and GFAP,resembling human astrocytes.Mechanistically,Olig1 and Olig2 bind directly to the Bmp7 enhancer,repressing its expression to promote astrocyte maturation.Overexpression of Bmp7 in vivo replicates the astrocyte defects seen in Olig1/2 double mutants,confirming the critical role of BMP7 signaling in this process.These findings provide insights into the transcriptional and signaling pathways regulating astrocyte development and highlight Olig1 and Olig2 as key regulators of cortical astrocyte maturation,with potential implications for understanding glial dysfunction in neurological diseases.展开更多
基金supported by the University of Macao(MYRG2022-00054-FHS and MYRGGRG2023-00038-FHS-UMDF)the Macao Science and Technology Development Fund(FDCT0048/2021/AGJ and FDCT0020/2019/AMJ)Natural Science Foundation of Guangdong Province(EF017/FHS-YZ/2021/GDSTC).
文摘Acquired brain injury(ABI)is an injury that affects the brain structure and function.Traditional ABI treatment strategies,including medications and rehabilitation therapy,exhibit their ability to improve its impairments in cognition,emotion,and physical activity.Recently,near-infrared(NIR)photobiomodulation(PBM)has emerged as a promising physical intervention method for ABI,demonstrating that low-level light therapy can modulate cellular metabolic processes,reduce the in flammation and reactive oxygen species of ABI microenvironments,and promote neural repair and regeneration.Preclinical studies using ABI models have been carried out,revealing the potential of PBM in promoting brain injury recovery although its clinical application is still in its early stages.In this review,we first inspected the possible physical and biological mechanisms of NIR-PBM,and then reported the pathophysiology and physiology of ABI underlying NIR-PBM intervention.Therefore,the potential of NIR-PBM as a therapeutic intervention in ABI was demonstrated and it is also expected that further work can facilitate its clinical applications.
基金supported by the National Natural Science Foundation of China,Nos.32271043(to ZW)and 82171047(to YM)the both Science and Technology Major Project of Shanghai,No.2018SHZDZX01 and ZJLabShanghai Center for Brain Science and Brain-Inspired Technology(to ZW)。
文摘Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apoptosis in glaucoma.Modulation of Kir4.1 expression in Müller cells may therefore be a potential strategy for attenuating retinal ganglion cell damage in glaucoma.In this study,we identified seven predicted phosphorylation sites in Kir4.1 and constructed lentiviral expression systems expressing Kir4.1 mutated at each site to prevent phosphorylation.Following this,we treated Müller glial cells in vitro and in vivo with the m Glu R I agonist DHPG to induce Kir4.1 or Kir4.1 Tyr^(9)Asp overexpression.We found that both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited activation of Müller glial cells.Subsequently,we established a rat model of chronic ocular hypertension by injecting microbeads into the anterior chamber and overexpressed Kir4.1 or Kir4.1 Tyr^(9)Asp in the eye,and observed similar results in Müller cells in vivo as those seen in vitro.Both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited Müller cell activation,regulated the balance of Bax/Bcl-2,and reduced the m RNA and protein levels of pro-inflammatory factors,including interleukin-1βand tumor necrosis factor-α.Furthermore,we investigated the regulatory effects of Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression on the release of pro-inflammatory factors in a co-culture system of Müller glial cells and microglia.In this co-culture system,we observed elevated adenosine triphosphate concentrations in activated Müller cells,increased levels of translocator protein(a marker of microglial activation),and elevated interleukin-1βm RNA and protein levels in microglia induced by activated Müller cells.These changes could be reversed by Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression in Müller cells.Kir4.1 overexpression,but not Kir4.1 Tyr^(9)Asp overexpression,reduced the number of proliferative and migratory microglia induced by activated Müller cells.Collectively,these results suggest that the tyrosine residue at position nine in Kir4.1 may serve as a functional modulation site in the retina in an experimental model of glaucoma.Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression attenuated Müller cell activation,reduced ATP/P2X receptor–mediated interactions between glial cells,inhibited microglial activation,and decreased the synthesis and release of pro-inflammatory factors,consequently ameliorating retinal ganglion cell apoptosis in glaucoma.
基金supported by the National Natural Science Foundation of China,Nos.32070989(to YMZ),31872766(to YMZ),81790640(to XLY),and 82070993(to SJW)the grant from Sanming Project of Medicine in Shenzhen,No.SZSM202011015(to XLY)。
文摘Diabetic retinopathy is a prominent cause of blindness in adults,with early retinal ganglion cell loss contributing to visual dysfunction or blindness.In the brain,defects inγ-aminobutyric acid synaptic transmission are associated with pathophysiological and neurodegenerative disorders,whereas glucagon-like peptide-1 has demonstrated neuroprotective effects.However,it is not yet clear whether diabetes causes alterations in inhibitory input to retinal ganglion cells and whether and how glucagon-like peptide-1 protects against neurodegeneration in the diabetic retina through regulating inhibitory synaptic transmission to retinal ganglion cells.In the present study,we used the patch-clamp technique to recordγ-aminobutyric acid subtype A receptor-mediated miniature inhibitory postsynaptic currents in retinal ganglion cells from streptozotocin-induced diabetes model rats.We found that early diabetes(4 weeks of hyperglycemia)decreased the frequency of GABAergic miniature inhibitory postsynaptic currents in retinal ganglion cells without altering their amplitude,suggesting a reduction in the spontaneous release ofγ-aminobutyric acid to retinal ganglion cells.Topical administration of glucagon-like peptide-1 eyedrops over a period of 2 weeks effectively countered the hyperglycemia-induced downregulation of GABAergic mIPSC frequency,subsequently enhancing the survival of retinal ganglion cells.Concurrently,the protective effects of glucagon-like peptide-1 on retinal ganglion cells in diabetic rats were eliminated by topical administration of exendin-9-39,a specific glucagon-like peptide-1 receptor antagonist,or SR95531,a specific antagonist of theγ-aminobutyric acid subtype A receptor.Furthermore,extracellular perfusion of glucagon-like peptide-1 was found to elevate the frequencies of GABAergic miniature inhibitory postsynaptic currents in both ON-and OFF-type retinal ganglion cells.This elevation was shown to be mediated by activation of the phosphatidylinositol-phospholipase C/inositol 1,4,5-trisphosphate receptor/Ca2+/protein kinase C signaling pathway downstream of glucagon-like peptide-1 receptor activation.Moreover,multielectrode array recordings revealed that glucagon-like peptide-1 functionally augmented the photoresponses of ON-type retinal ganglion cells.Optomotor response tests demonstrated that diabetic rats exhibited reductions in visual acuity and contrast sensitivity that were significantly ameliorated by topical administration of glucagon-like peptide-1.These results suggest that glucagon-like peptide-1 facilitates the release ofγ-aminobutyric acid onto retinal ganglion cells through the activation of glucagon-like peptide-1 receptor,leading to the de-excitation of retinal ganglion cell circuits and the inhibition of excitotoxic processes associated with diabetic retinopathy.Collectively,our findings indicate that theγ-aminobutyric acid system has potential as a therapeutic target for mitigating early-stage diabetic retinopathy.Furthermore,the topical administration of glucagon-like peptide-1 eyedrops represents a non-invasive and effective treatment approach for managing early-stage diabetic retinopathy.
基金supported by the National Natural Science Foundation of China (31530035,81420108015, 31671099,31871072,81570081,81770083 and 31971110)the National Basic Research Development Program of China (2015CB856401)+2 种基金the Program for Shanghai Outstanding Academic Leaders (to ZLH)the Shanghai Municipal Science and Technology Major Project (2018SHZDZX01)the National Key Research and Development Program of China (2018YFC1313600)。
文摘Hypoglossal motor neurons(HMNs) innervate tongue muscles and play key roles in a variety of physiological functions,including swallowing,mastication,suckling,vocalization,and respiration.Dysfunction of HMNs is associated with several diseases,such as obstructive sleep apnea(OSA) and sudden infant death syndrome.OS A is a serious breathing disorder associated with the activity of HMNs during different sleep-wake states.Identifying the neural mechanisms by which the statedependent activities of HMNs are controlled may be helpful in providing a theoretical basis for effective therapy for OSA.However,the presynaptic partners governing the activity of HMNs remain to be elucidated.In the present study,we used a cell-type-specific retrograde tracing system based on a modified rabies virus along with a Cre/loxP gene-expression strategy to map the whole-brain monosynaptic inputs to HMNs in mice.We identified 53 nuclei targeting HMNs from six brain regions:the amygdala,hypothalamus,midbrain,pons,medulla,and cerebellum.We discovered that GAB Aergic neurons in the central amygdaloid nucleus,as well as calretinin neurons in the parasubthalamic nucleus,sent monosynaptic projections to HMNs.In addition,HMNs received direct inputs from several regions associated with respiration,such as the preBotzinger complex,parabrachial nucleus,nucleus of the solitary tract,and hypothalamus.Some regions engaged in sleep-wake regulation(the parafacial zone,parabrachial nucleus,ventral medulla,sublaterodorsal tegmental nucleus,dorsal raphe nucleus,periaqueductal gray,and hypothalamus) also provided primary inputs to HMNs.These results contribute to further elucidating the neural circuits underlying disorders caused by the dysfunction of HMNs.
基金supported by the National Natural Science Foundation of China(62071109 and 61871420)the Provincial Natural Science Foundation of Sichuan(2022NSFSC0504).
文摘The conventional approach to investigating functional connectivity in the block-designed study usually concatenates task blocks or employs residuals of task activation.While providing many insights into brain functions,the block design adds more manipulation in functional network analysis that may reduce the purity of the blood oxygenation level-dependent signal.Recent studies utilized one single long run for task trials of the same condition,the so-called continuous design,to investigate functional connectivity based on task functional magnetic resonance imaging.Continuous brain activities associated with the single-task condition can be directly utilized for task-related functional connectivity assessment,which has been examined for working memory,sensory,motor,and semantic task experiments in previous research.But it remains unclear how the block and continuous design influence the assessment of task-related functional connectivity networks.This study aimed to disentangle the separable effects of block/continuous design and working memory load on task-related functional connectivity networks,by using repeated-measures analysis of variance.Across 50 young healthy adults,behavioral results of accuracy and reaction time showed a significant main effect of design as well as interaction between design and load.Imaging results revealed that the cingulo-opercular,fronto-parietal,and default model networks were associated with not only task activation,but significant main effects of design and load as well as their interaction on intra-and inter-network functional connectivity and global network topology.Moreover,a significant behavior-brain association was identified for the continuous design.This work has extended the evidence that continuous design can be used to study task-related functional connectivity and subtle brain-behavioral relationships.
基金the National Natural Science Foundation of China, No. 30371451
文摘OBJECTIVE： To explain the mechanisms of tuhe synthesis, secretion and regulation of brain natriuretic peptide （BNP）, and analyze its role in central nervous system diseases. DATA SOURCES： An online search of Pubmed was undertaken to identify articles related to BNP published in English from January 1990 to February 2007 by using the key words of ＂brain natriuretic pepfide （BNP）, central nervous system, subarachnoid hemorrhage （SAH）, brain edema, epilepsy＂. Other articles were searched in China Hospital Knowledge Database （CHKD） by concrete name of journals and title of articles. STUDY SELECTION： The collected articles were primarily screened, those about BNP and its association with central nervous system diseases were selected, whereas the obviously irrelative ones excluded, and the full-texts of the other literatures were searched manually. DATA EXTRACTION： Totally 96 articles were collected, 40 of them were enrolled, and the other 56 were excluded due to repetitive studies or reviews. DATA SYNTHESIS： At present, there are penetrating studies on BNP in the preclinical medicine and clinical medicine of cerebrovascular and cardiovascular diseases, and the investigative outcomes have been gradually applied in clinical practice, and satisfactory results have been obtained. However, the application of BNP in diagnosing and treating central nervous system diseases is still at the experimental phase without - outstanding outcomes, thus the preclinical and clinical studies should be enhanced. CONCLUSION： As a kind of central medium or modulator, BNP plays a certain role in the occurrence, development and termination of central nervous system diseases, the BNP level in serum has certain changing law in SAH, brain edema, epilepsy, etc., but the specific mechanisms are unclear.
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.
基金supported by the National Research Foundation of Korea (NRF)funded by the Ministry of Science,ICT&Future Planning (2022R1A2C2006229,2022R1A6A3A01086868)Korea Dementia Research Project through the Korea Dementia Research Center (KDRC)funded by the Ministry of Health&Welfare and Ministry of Science and ICT,Republic of Korea (RS-2024-00345328)KIST Institutional Grant (2E32851)。
文摘Alzheimer'sdisease(AD)isaprogressive neurodegenerative disorder characterized by cognitive impairment and distinct neuropathological features,including amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis.Developing effective diagnostic,preventative,and therapeutic strategies for AD necessitates the establishment of animal models that accurately recapitulate the pathophysiological processes of the disease.Existing transgenic mouse models have significantly contributed to understanding AD pathology but often fail to replicate the complexity of human AD.Additionally,these models are limited in their ability to elucidate the interplay among amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis due to the absence of spatially and temporally specific genetic manipulation.In this study,we introduce a novel AD mouse model(APP/PS1-TauP301L-Adeno mice)designed to rapidly induce pathological symptoms and enhance understanding of AD mechanisms.Neurofibrillary tangles and severe reactive astrogliosis were induced by injecting AAVDJ-EF1a-hTauP301L-EGFP and Adeno-GFAP-GFP viruses into the hippocampi of 5-month-old APP/PS1 mice.Three months post-injection,these mice exhibited pronounced astrogliosis,substantial amyloid-βplaque accumulation,extensiveneurofibrillarytangles,accelerated neuronal loss,elevated astrocytic GABA levels,and significant spatial memory deficits.Notably,these pathological features were less severe in AAVTauP301L-expressing APP/PS1 mice without augmented reactive astrogliosis.These findings indicate an exacerbating role of severe reactive astrogliosis in amyloid-βplaque and neurofibrillary tangle-associated pathology.The APP/PS1-TauP301L-Adeno mouse model provides a valuable tool for advancing therapeutic research aimed at mitigating the progression of AD.
基金supported by the National Natural Science Foundation of China(81770956,81371049,32471055 and 82171090)Project of Tianjin 131 Innovative Talent Team(201936)+4 种基金the Science and Technology Planning Project of Tianjin(21JCYBJC00780)the Science and Technology Fund for Health of Tianjin(TJWJ2023ZD008)Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)ZJLab,Shanghai Center for Brain Science and Brain-Inspired Technology,the Lingang Laboratory(LG-QS-202203-12)Tianjin Key Medical Discipline(Specialty)Construction Project(TJYXZDXK‑016A).
文摘The visual cortex is an essential part of the brain for processing visual information.It exhibits structural and functional plasticity,which is crucial for adapting to complex visual environments.The quintessential manifestation of visual cortical plasticity is ocular dominance plasticity during the critical period,which involves numerous cellular and molecular events.While previous studies have emphasized the role of visual cortical neurons and their associated functional molecules in visual plasticity,recent findings have revealed that structural factors such as the extracellular matrix and glia are also involved.Investigating how these molecules interact to form a complex network that facilitates plasticity in the visual cortex is crucial to our understanding of the development of the visual system and the advancement of therapeutic strategies for visual disorders like amblyopia.
基金supported by the National Natural Science Foundation of China,No.31771143 (to QZ)Shanghai Municipal Science and Technology Major Project,ZJ Lab+1 种基金Shanghai Center for Brain Science and Brain-Inspired Technology,No.2018SHZDZX01 (to LC)Shanghai Zhou Liangfu Medical Development Foundation “Brain Science and Brain Diseases Youth Innovation Program”(to ZQ)。
文摘The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson's disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson's disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore,bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico–striato–pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson's disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson's disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson's disease,particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremordominant and non-tremor-dominant Parkinson's disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia–thalamus network. Therefore, the composition of the globus pallidus neurons, the neurotransmitters that act on them, their electrical activity,and the neural circuits they form can guide the search for new multi-target drugs to treat Parkinson's disease in clinical practice. Examining the potential intra-nuclear and neural circuit mechanisms of deep brain stimulation associated with the globus pallidus can facilitate the management of both motor and non-motor symptoms while minimizing the side effects caused by deep brain stimulation.
基金supported by the National Natural Science Foundation of China(32471055 and 82171090)Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)ZJLab,Shanghai Center for Brain Science and Brain-Inspired Technology,the Lingang Laboratory(LG-QS-202203-12).
文摘Throughout the lifespan,an animal can encounter predators frequently,thus the ability to avoid attacks from predators is crucial for its survival.The chances of evading danger can be greatly improved if the animal can respond immediately to the threat.Therefore,when an animal detects a threat through its visual system,it must quickly direct its gaze and attention toward the source of danger,assess the threat level,and take appropriate action.
基金supported by the National Research Foundation(NRF)of Korea(grant number:RS-2022-NR072217 to P.RL,RS-2021-NR059709,RS-2023-00264409,and RS-2024-00441103)funded by the Korean government(MSIT).
文摘Piezo2,a mechanosensitive ion channel,serves as a crucial mechanotransducer in dental primary afferent(DPA)neurons and is potentially involved in hypersensitivity to mild mechanical irritations observed in dental patients.Given Piezo2’s widespread expression across diverse subpopulations of DPA neurons,this study aimed to characterize the mechanosensory properties of Piezo2-expressing DPA neurons with a focus on distinct features of voltage-gated sodium channels(VGSCs)and neuropeptide profiles.Using whole-cell patch-clamp recordings,we observed mechanically activated action potentials(APs)and classified AP waveforms based on the presence or absence of a hump during the repolarization phase.Single-cell reverse transcription polymerase chain reaction combined with patch-clamp recordings revealed specific associations between AP waveforms and molecular properties,including tetrodotoxin-resistant VGSCs(NaV1.8 and NaV1.9)and TRPV1 expression.Reanalysis of the transcriptomic dataset of DPA neurons identified correlations between neuropeptides—including two CGRP isoforms(α-CGRP andβ-CGRP),Substance P,and Galanin—and the expression of NaV1.8 and NaV1.9,which were linked to defined AP subtypes.These molecular associations were further validated in Piezo2+DPA neurons using fluorescence in situ hybridization.Together,these findings highlight the electrophysiological and neurochemical heterogeneity of Piezo2-expressing DPA neurons and their specialized roles in distinct mechanosensory signal transmission.
基金supported by the National Natural Science Foundation of China(T2394531)the National Key R&D Program of China(2024YFF1206500)+1 种基金the Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)ZJ Lab,and the Shanghai Center for Brain Science and Brain-Inspired Technology,China.
文摘DDeeaarr EEddiittoorr,,The encoding and retrieval of emotional memories demands intricate interplay within the limbic network,where the network state is subject to significant reconfiguration by learning-induced plasticity,behavioral state,and contextual information[1].
基金Financial support for this work by the National Research Foundation of Korea(2022R1F1A1074682,2022R1A4A1031687)Korea University,and the KU-KIST Research Fund.
文摘The advancement in catalysis techniques for sustainable environmental applications,particularly an alternative to the current Haber-Bosch process for NH_(3),has recently gained widespread attention.Although photocatalytic conversion of N_(2) to NH_(3) using solar energy is an eco-friendly method,it has the limitation of low quantum yield.Recently,2D Bi-based photocatalysts which exhibit higher visible light absorption than TiO_(2) and higher stability than MXene have been an active research topic,and their performance can be enhanced through improved visible light absorption properties by incorporating plasmonic gold nanoparticles while nitrogen adsorption could be enhanced through oxygen vacancy(OV)processes.In the present study,we explore the application of 2D nanosized Bi_(2)O_(3–x) and gold nanoparticles for visible light photo generation of NH_(3).HRTEM and XPS reveal that the formation of AuNP and nano-sized Bi_(2)O_(3–x) in AuNP/Bi_(2)O_(3–x) heterozygote structure promotes the charge carrier mobility and charge transport at the interface,resulting in a 2.6-fold increase in the photocatalytic activity compared to micro-sized Bi_(2)O_(3–x) with AuNP.The improved photocatalytic performance can be ascribed to significant enhancement of visible light absorption by plasmonic nanoparticles,fast charge transport and mobility(due to sheet morphology)and the N_(2) activation by OV in AuNP/Bi_(2)O_(3–x) heterozygote.Through a systematic experimental investigation involving catalysts,concentration,pH,and scavengers,the highest photocatalytic performance was achieved with the heterozygote structures of AuNP/n-Bi_(2)O_(3–x) under optimized conditions,yielding 432.5μmol gcat^(-1) h^(-1) of NH_(3).
基金supported by the National Natural Science Foundation of China(32271047)the National Key Research and Development Program of China(2020YFC2008405)+1 种基金The Innovative Research Team of High-level Local Universities in Shanghai,the Natural Science Foundation of Shanghai(22ZR1413800)Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)。
文摘Neuraxial opioids,widely used in obstetric and perioperative pain management,often lead to unwanted itch,reducing patient satisfaction.While theμ-opioid receptor has been implicated in opioid-induced itch,the genetic basis for variable itch incidence remains unknown.This study examined 3616 patients receiving epidural opioids,revealing an itch occurrence of 26.55%,with variations among opioid types and gender.Analysis of the OPRM1 gene identified six single-nucleotide polymorphisms,notably rs1799971(A118G),that correlated with opioid-induced itch.Mouse models with an equivalent A112G mutation showed reduced neuraxial opioid-induced itch and light touch-evoked itch,mirroring human findings.The 118G allele demonstrated an anti-itch effect without impacting analgesia,addiction,or tolerance,offering insights for risk stratification and potential anti-itch pretreatment strategies.
基金supported by the Korea Environment Industry&Technology Institute(KEITI)through Digital Infrastructure Building Project for Monitoring,Surveying and Evaluating the Environmental Health program,funded by the Korea Ministry of Environment(MOE)(2021003330008)supported by the KIST Internal program(2E32851)+1 种基金supported by the Korea Health Technology Research and Development(R&D)Project through the Korea Health Industry Development Institute(KHIDI)and Korea Dementia Research Center(KDRC),funded by the Ministry of Health&Welfare and Ministry of Science and ICT,Republic of Korea(HU20C0164)the Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(2022R1A6A3A01087298)。
文摘The various bioacoustics signals obtained with auscultation contain complex clinical information that has been traditionally used as biomarkers,however,they are not extensively used in clinical studies owing to their spatiotemporal limitations.In this study,we developed a wearable stethoscope for wireless,skinattachable,low-power,continuous,real-time auscultation using a lung-sound-monitoring-patch(LSMP).LSMP can monitor respiratory function through a mobile app and classify normal and adventitious breathing by comparing their unique acoustic characteristics.The human heart and breathing sounds from humans can be distinguished from complex sound signals consisting of a mixture of bioacoustic signals and external noise.The performance of the LSMP sensor was further demonstrated in pediatric patients with asthma and elderly chronic obstructive pulmonary disease(COPD)patients where wheezing sounds were classified at specific frequencies.In addition,we developed a novel method for counting wheezing events based on a two-dimensional convolutional neural network deep-learning model constructed de novo and trained with our augmented fundamental lung-sound data set.We implemented a counting algorithm to identify wheezing events in real-time regardless of the respiratory cycle.The artificial intelligence-based adventitious breathing event counter distinguished>80%of the events(especially wheezing)in long-term clinical applications in patients with COPD.
基金supported by the Science and Technology Innovation(STI)2030-Major Projects(2025ZD0214900-02 and 2021ZD0203200-05)the National Natural Science Foundation of China(82130032)+1 种基金the Natural Science Foundation of Shanghai(24ZR1413900 and 25ZR1402460)and the China Postdoctoral Science Foundation(2021M690685).
文摘Astrocytes in the spinal dorsal horn(SDH)exhibit diverse reactive phenotypes under neuropathic conditions,yet the mechanisms driving this diversity and its implications in chronic pain remain unclear.Here,we report that spared nerve injury(SNI)induces marked upregulation of both complement component 3(C3⁺,A1-like)and S100 calcium-binding protein A10(S100A10⁺,A2-like)astrocyte subpopulations in the SDH,with elevated microglial cytokines including interleukin-1α,tumor necrosis factor-α,and complement component 1q.Transcriptomic,immunohistochemical,and Western blot analyses reveal co-activation of multiple reactive astrocyte states over a unidirectional shift toward an A1-like phenotype.Fibroblast growth factor 8(FGF8),a neuroprotective factor via FGFR3,mitigated microglia-induced C3⁺astrocyte reactivity in vitro and suppressed spinal C3 expression and mechanical allodynia following intrathecal administration in SNI mice.These findings reveal a microglia–astrocyte signaling axis that promotes A1 reactivity and position FGF8 as a promising therapeutic candidate for neuropathic pain by modulating astrocyte heterogeneity.
基金supported by the Institute for Basic Science (IBS-R022-D1)Global Learning&Academic Research Institution for Master’s/Ph D students and Post-Doc Program of the National Research Foundation of Korea Grant funded by the Ministry of Education (RS-2023-00301938)+1 种基金National Research Foundation of Korea Grant funded by the Korean government (RS-2024-00406152,MSIT)Additional financial support was provided by the 2024 Post-Doc Development Program of Pusan National University,Korea Medical Institute,and KREONET。
文摘Polystyrene nanoparticles pose significant toxicological risks to aquatic ecosystems,yet their impact on zebrafish(Danio rerio)embryonic development,particularly erythropoiesis,remains underexplored.This study used single-cell RNA sequencing to comprehensively evaluate the effects of polystyrene nanoparticle exposure on erythropoiesis in zebrafish embryos.In vivo validation experiments corroborated the transcriptomic findings,revealing that polystyrene nanoparticle exposure disrupted erythrocyte differentiation,as evidenced by the decrease in mature erythrocytes and concomitant increase in immature erythrocytes.Additionally,impaired heme synthesis further contributed to the diminished erythrocyte population.These findings underscore the toxic effects of polystyrene nanoparticles on hematopoietic processes,highlighting their potential to compromise organismal health in aquatic environments.
文摘Dear Editor,Sleep plays a vital role in physical health,influencing chronic diseases,memory,and overall quality of life[1,2].In recent years,the relationship between sleep health and physical activity has gained attention,with a particular focus on how daily step count affects various sleep metrics.
基金supported by the National Natural Science Foundation of China(82271197,81974175,31820103006,32070971,32200792,32200776).
文摘Astrocyte maturation is crucial for brain function,yet the mechanisms regulating this process remain poorly understood.In this study,we identify the bHLH transcription factors Olig1 and Olig2 as essential coordinators of cortical astrocyte maturation.We demonstrate that Olig1 and Olig2 work synergistically to regulate cortical astrocyte maturation by modulating Bmp7 expression.Genetic ablation of both Olig1 and Olig2 results in defective astrocyte morphology,including reduced process complexity and an immature gene expression profile.Single-cell RNA sequencing reveals a shift towards a less mature astrocyte state,marked by elevated levels of HOPX and GFAP,resembling human astrocytes.Mechanistically,Olig1 and Olig2 bind directly to the Bmp7 enhancer,repressing its expression to promote astrocyte maturation.Overexpression of Bmp7 in vivo replicates the astrocyte defects seen in Olig1/2 double mutants,confirming the critical role of BMP7 signaling in this process.These findings provide insights into the transcriptional and signaling pathways regulating astrocyte development and highlight Olig1 and Olig2 as key regulators of cortical astrocyte maturation,with potential implications for understanding glial dysfunction in neurological diseases.
