Blood-brain barrier disruption and the neuroinflammatory response are significant pathological features that critically influence disease progression and treatment outcomes.This review systematically analyzes the curr...Blood-brain barrier disruption and the neuroinflammatory response are significant pathological features that critically influence disease progression and treatment outcomes.This review systematically analyzes the current understanding of the bidirectional relationship between blood-brain barrier disruption and neuroinflammation in traumatic brain injury,along with emerging combination therapeutic strategies.Literature review indicates that blood-brain barrier disruption and neuroinflammatory responses are key pathological features following traumatic brain injury.In the acute phase after traumatic brain injury,the pathological characteristics include primary blood-brain barrier disruption and the activation of inflammatory cascades.In the subacute phase,the pathological features are characterized by repair mechanisms and inflammatory modulation.In the chronic phase,the pathological features show persistent low-grade inflammation and incomplete recovery of the blood-brain barrier.Various physiological changes,such as structural alterations of the blood-brain barrier,inflammatory cascades,and extracellular matrix remodeling,interact with each other and are influenced by genetic,age,sex,and environmental factors.The dynamic balance between blood-brain barrier permeability and neuroinflammation is regulated by hormones,particularly sex hormones and stress-related hormones.Additionally,the role of gastrointestinal hormones is receiving increasing attention.Current treatment strategies for traumatic brain injury include various methods such as conventional drug combinations,multimodality neuromonitoring,hyperbaric oxygen therapy,and non-invasive brain stimulation.Artificial intelligence also shows potential in treatment decision-making and personalized therapy.Emerging sequential combination strategies and precision medicine approaches can help improve treatment outcomes;however,challenges remain,such as inadequate research on the mechanisms of the chronic phase traumatic brain injury and difficulties with technology integration.Future research on traumatic brain injury should focus on personalized treatment strategies,the standardization of techniques,costeffectiveness evaluations,and addressing the needs of patients with comorbidities.A multidisciplinary approach should be used to enhance treatment and improve patient outcomes.展开更多
Neuroinflammation contributes to a wide range of neurodegenerative diseases including Alzheimer's disease,Parkinson's disease,Huntington's disease,and multiple sclerosis.It is driven by non-neuronal glial ...Neuroinflammation contributes to a wide range of neurodegenerative diseases including Alzheimer's disease,Parkinson's disease,Huntington's disease,and multiple sclerosis.It is driven by non-neuronal glial cells,mainly microglia and astrocytes.Microglia are the resident immune cells of the central nervous system,while astrocytes are the main support cells for neuronal functions but can also participate in neuroimmune responses.Both these glial cell types can become reactive upon detection of certain endogenous intracellular molecules that appear in the extracellular space under specific circumstances;these can be pathology-associated abnormal structures,such as amyloidβproteins,or damage-associated molecular patterns released from injured cells,including their mitochondria.Once in the extracellular space,damage-associated molecular patterns act as ligands for specific pattern recognition receptors expressed by glia inducing their reactivity and neuroimmune responses.This review considers the following mitochondrial damage-associated molecular patterns:heme,cytochrome c,cardiolipin,adenosine triphosphate,mitochondrial DNA,mitochondrial transcription factor A,N-formyl peptides,and the tricarboxylic acid cycle metabolites:succinate,fumarate,and itaconate.We describe their well-established functions as damage-associated molecular patterns of the peripheral tissues before summarizing available evidence indicating these molecules may also play significant roles in the neuroimmune processes of the central nervous system.We highlight the pattern recognition receptors that mitochondrial damage-associated molecular patterns interact with and the cellular signaling mechanisms they modulate.Our review demonstrates that some mitochondrial damage-associated molecular patterns,such as cytochrome c,adenosine triphosphate,and mitochondrial transcription factor A,have already demonstrated significant effects on the central nervous system.In contrast,others including cardiolipin,mitochondrial DNA,N-formyl peptides,succinate,fumarate,and itaconate,will require additional studies corroborating their roles as damageassociated molecular patterns in the central nervous system.For all of the reviewed mitochondrial damage-associated molecular patterns,there is a shortage of studies using human cells and tissues,which is identified as a significant knowledge gap.We also assess the need for targeted research on the effects of mitochondrial damage-associated molecular patterns in the central nervous system pathologies where their roles are understudied.Such studies could identify novel treatment strategies for multiple neurodegenerative diseases,which are characterized by chronic neuroinflammation and currently lack effective therapies.展开更多
Background:P regnancy affects learning and memory in women.Thus,to investigate the effects of pregnancy,the authors examined the brain electrophysiology of pregnant mice.Methods:U sing the whole-c ell patch-c lamp tec...Background:P regnancy affects learning and memory in women.Thus,to investigate the effects of pregnancy,the authors examined the brain electrophysiology of pregnant mice.Methods:U sing the whole-c ell patch-c lamp technique on isolated brain slices,we detected and compared the electrophysiological changes in the hippocampal CA1(HIP CA1)region,medial prefrontal cortex(mPFC),and basolateral amygdala(BLA)among 15 pregnant and 15 nonpregnant mice.Results:In pregnant mice,there was a trend toward an increase in the frequency of miniature excitatory postsynaptic currents(mEPSCs)(p=0.092)and a trend toward a decrease in the amplitude of miniature inhibitory postsynaptic currents(mIPSC)(p=0.071)in the HIP CA1.In the BLA,both the amplitudes of mEPSCs and mIPSCs were significantly reduced(p=0.004 and 0.042,respectively).In the mPFC,the amplitudes of mEPSCs and hyperpolarization-a ctivated currents(Ih),as well as the frequencies of mIPSCs,were higher compared to nonpregnant mice(p=0.035,0.009,and 0.038,respectively).Conclusions:I n pregnant mice,the electrophysiological change in neurons in the mPFC and BLA might contribute to the cognitive and emotional changes during pregnancy.A trend toward electrophysiological change in the HIP CA1 revealed that the mechanism of cognitive change during pregnancy might differ from that of other conditions.展开更多
Intracranial hypertension is a major cause of morbidity and mortality of patients suffering from fulminant hepatic failure. The etiology of this intracranial hypertension is not fully determined, and is probably multi...Intracranial hypertension is a major cause of morbidity and mortality of patients suffering from fulminant hepatic failure. The etiology of this intracranial hypertension is not fully determined, and is probably multifactorial, combining a cytotoxic brain edema due to the astrocytic accumulation of glutamine, and an increase in cerebral blood volume and cerebral blood flow, in part due to inflammation, to glutamine and to toxic products of the diseased liver. Validated methods to control intracranial hypertension in fulminant hepatic failure patients mainly include mannitol, hypertonic saline, indomethacin, thiopental, and hyperventilation. However all these measures are often not sufficient in absence of liver transplantation, the only curative treatment of intracranial hypertension in fulminant hepatic failure to date. Induced moderate hypothermia seems very promising in this setting, but has to be validated by a controlled, randomized study. Artificial liver support systems have been under investigation for many decades. The bioartiflcial liver, based on both detoxification and swine liver cells, has shown some efficacy on reduction of intracranial pressure but did not show survival benefit in a controlled, randomized study. The Molecular Adsorbents Recirculating System has shown some efficacy in decreasing intracranial pressure in an animal model of liver failure, but has still to be evaluated in a phase Ⅲ trial.展开更多
Alzheimer’s disease is a prominent chronic neurodegenerative condition characterized by a gradual decline in memory leading to dementia.Growing evidence suggests that Alzheimer’s disease is associated with accumulat...Alzheimer’s disease is a prominent chronic neurodegenerative condition characterized by a gradual decline in memory leading to dementia.Growing evidence suggests that Alzheimer’s disease is associated with accumulating various amyloid-βoligomers in the brain,influenced by complex genetic and environmental factors.The memory and cognitive deficits observed during the prodromal and mild cognitive impairment phases of Alzheimer’s disease are believed to primarily result from synaptic dysfunction.Throughout life,environmental factors can lead to enduring changes in gene expression and the emergence of brain disorders.These changes,known as epigenetic modifications,also play a crucial role in regulating the formation of synapses and their adaptability in response to neuronal activity.In this context,we highlight recent advances in understanding the roles played by key components of the epigenetic machinery,specifically DNA methylation,histone modification,and microRNAs,in the development of Alzheimer’s disease,synaptic function,and activity-dependent synaptic plasticity.Moreover,we explore various strategies,including enriched environments,exposure to non-invasive brain stimulation,and the use of pharmacological agents,aimed at improving synaptic function and enhancing long-term potentiation,a process integral to epigenetic mechanisms.Lastly,we deliberate on the development of effective epigenetic agents and safe therapeutic approaches for managing Alzheimer’s disease.We suggest that addressing Alzheimer’s disease may require distinct tailored epigenetic drugs targeting different disease stages or pathways rather than relying on a single drug.展开更多
Hypnosis is a promising tool in the management of various conditions,such as anxiety and chronic pain.Preliminary studies have shown that hypnosis can directly affect the cardiovascular system,as it increases parasymp...Hypnosis is a promising tool in the management of various conditions,such as anxiety and chronic pain.Preliminary studies have shown that hypnosis can directly affect the cardiovascular system,as it increases parasympathetic activation and reduces sympathetic activity.However,the literature related to the effects of hypnosis on cardiovascular health is scarce,mainly due to misconceptions about hypnosis among researchers and medical professionals.This opinion paper examines the role that hypnosis may play in cardiovascular health,highlighting the physiological mechanisms behind it.The evidence suggests that hypnosis has both direct(e.g.,changes in the activity of the autonomic nervous system)and indirect(e.g.,changes in healthy behaviours)effects on the cardiovascular system;however,further studies are needed to properly define its mechanisms of action and its applicability in improving cardiovascular health.Thus,this opinion paper advocates the adoption of the term“hypno-cardiac physiology”to identify a new research area that gathers experts from neuroscience and cardiovascular science with the joint aim of seeking further understanding of the effects of hypnosis on the cardiovascular system.The adoption of a dedicated term to identify the study of the cardiovascular response to hypnosis will encourage its implementation in cardiovascular health interventions,promoting awareness of its effects among the public and the healthcare community,and promoting the formation of dedicated multidisciplinary research groups and dedicated educational training for healthcare professional interested in its applications.展开更多
N^6-methyladenosine(m6A)is identified as the most widespread and abundant internal chemical modification of RNA in eukaryotes.A series of proteins including methyltransferases(also known as“writers”),demethylases(al...N^6-methyladenosine(m6A)is identified as the most widespread and abundant internal chemical modification of RNA in eukaryotes.A series of proteins including methyltransferases(also known as“writers”),demethylases(also known as“erasers”),and m6A-binding proteins(also known as“readers”)were indicated to participate in the m6A methylation.m6A has emerged as a regulator of various cellular,developmental,and disease processes.Notably,there is highest abundance of m^6A methylation in brain than in other organs,which indicates that m^6A plays an essential role in brain functions.Here,we describe the general features,mechanisms,and functions of m^6A in the brain,and discuss the emerging roles of m6A in brain physiology and diseases.展开更多
Physiology is an important basic course for medical majors.The content of the nervous system is abstract,the theories are profound,the knowledge is updated rapidly,and it is most closely connected with clinical practi...Physiology is an important basic course for medical majors.The content of the nervous system is abstract,the theories are profound,the knowledge is updated rapidly,and it is most closely connected with clinical practice.Students generally report difficulties in understanding,resulting in low learning interest.To improve teaching quality,this study has attempted to organically integrate clinical cases,scientific research methods and classroom teaching in the teaching of the nervous system,and constructed a“clinical-research-teaching”trinity teaching model.With“clinical problem-driven,scientific research thinking-driven,teaching scenario reconstruction”as the main line,real cases,scientific research examples and cutting-edge research progress in neuroscience were introduced to stimulate students’learning interest and cultivate their scientific thinking and clinical application abilities.Practice has shown that this model can effectively improve teaching effectiveness and students’comprehensive quality.Compared with the traditional teaching model,this teaching model significantly improved students’final exam scores(p<0.01),scores of the Critical Thinking Disposition Inventory(p<0.01),and the number of approved college students’innovation and entrepreneurship projects.It is proved that the“trinity”teaching model can stimulate learning interest,cultivate integrated medical talents,and is an effective way to achieve in-depth connection between basic medicine and clinical practice.展开更多
The construction of the New Medical Sciences aims to cultivate interdisciplinary medical talents,placing higher demands on physiology experiment teaching.In light of the challenges of traditional teaching,such as outd...The construction of the New Medical Sciences aims to cultivate interdisciplinary medical talents,placing higher demands on physiology experiment teaching.In light of the challenges of traditional teaching,such as outdated content,a single assessment mechanism,low student engagement,and limited research experience among instructors,this study proposes a reform pathway centered on research competence development,supported by diversified evaluation methods and the deep integration of ideological and scenario-based teaching.By optimizing teaching content,introducing innovative projects,establishing a multidimensional assessment system,and strengthening faculty development,the proposed reforms effectively enhance students’Innovative ability and practical skills.This study provides theoretical insights and practical experience for training interdisciplinary medical professionals to meet the demands of the new era.展开更多
BACKGROUND Previous studies have reported the high predictive accuracy of 4C Mortality Score derived at hospital admission in coronavirus disease 2019(COVID-19)patients.Very few studies have assessed it at intensive c...BACKGROUND Previous studies have reported the high predictive accuracy of 4C Mortality Score derived at hospital admission in coronavirus disease 2019(COVID-19)patients.Very few studies have assessed it at intensive care unit(ICU)admission and compared it with the Acute Physiology and Chronic Health Evaluation(APACHE)II score.There are no studies comparing its accuracy with APACHE III score.AIM To describe the characteristics and outcomes of patients admitted to ICU with COVID-19 infection and to compare the accuracy of 4C score and APACHE score in predicting mortality in these patients.METHODS We conducted this retrospective cohort study using an electronic database in a tertiary ICU in Sydney.We included all adult patients(age>16 years)admitted to ICU with COVID-19 infection over a 5-month period(July 1,2021 to November 30,2021).We collected the data on demographics,clinical characteristics,interventions and outcomes for all patients.We calculated the 4C Mortality Score for each patient using eight variables as described previously.We compared the predictive accuracy of 4C Mortality Score at hospital and ICU admission and APACHE II and III scores by area under the receiver operating characteristic curve(AUROC).We determined the optimal cut-off value for each of these scores using the‘nearest’method and its 95%confidence interval by bootstrapping.RESULTS A total of 140 patients(62%males,mean age 56±17 years,mean APACHE II score 13±57)were included in the study.Nineteen(13.6%)of 140 patients died in the hospital.Compared to survivors,the non-survivors were older,males,had more comorbidities,higher rate of mechanical ventilation and vasopressor use.The AUROC for the 4C Mortality Score at hospital and ICU admission and APACHE II and II score was 0.75,0.80.0.75 and 0.79 respectively.The optimal cut-off value for these four scores was 9,10,14 and 56 respectively.The cut-point for all the scores had higher sensitivity than specificity.CONCLUSION The 4C score at ICU admission had a higher accuracy in predicting mortality than the 4C score at hospital admission.The predictive accuracy was similar to that for APACHE III score.The 4C score at ICU admission needs to be validated in future studies.展开更多
Stroke is a major cause of death and disability worldwide.It is characterized by a highly interconnected and multiphasic neuropathological cascade of events,in which an intense and protracted inflammatory response pla...Stroke is a major cause of death and disability worldwide.It is characterized by a highly interconnected and multiphasic neuropathological cascade of events,in which an intense and protracted inflammatory response plays a crucial role in worsening brain injury.Neuroinflammation,a key player in the pathophysiology of stroke,has a dual role.In the acute phase of stroke,neuroinflammation exacerbates brain injury,contributing to neuronal damage and blood–brain barrier disruption.This aspect of neuroinflammation is associated with poor neurological outcomes.Conversely,in the recovery phase following stroke,neuroinflammation facilitates brain repair processes,including neurogenesis,angiogenesis,and synaptic plasticity.The transition of neuroinflammation from a harmful to a reparative role is not well understood.Therefore,this review seeks to explore the mechanisms underlying this transition,with the goal of informing the development of therapeutic interventions that are both time-and context-specific.This review aims to elucidate the complex and dual role of neuroinflammation in stroke,highlighting the main actors,biomarkers of the disease,and potential therapeutic approaches.展开更多
Vegetation annual gross primary production(AGPP),the total yearly carbon assimilation via photosynthesis,serves as a key indicator of ecosystem carbon uptake.While AGPP variations are jointly influenced by both vegeta...Vegetation annual gross primary production(AGPP),the total yearly carbon assimilation via photosynthesis,serves as a key indicator of ecosystem carbon uptake.While AGPP variations are jointly influenced by both vegetation phenology and physiology,the effectiveness of satellite-derived indicators in capturing these variations has not been fully evaluated.This study develops and evaluates the satellite-derived phenology and physiology indicators for modeling AGPP variability.We assessed the performance of satellite-derived metrics,including solar-induced chlorophyll fluorescence(SIF),leaf area index(LAI),and enhanced vegetation index(EVI),in capturing AGPP variations.Among these,SIF-based indicators exhibited the highest accuracy(Pearson's r=0.79;root mean square error=414.7 gC·m^(-2)·year^(-1)),outperforming LAI-and EVI-based indicators.To further investigate the mechanisms driving AGPP variability,we used a structural equation model based on in situ observations to quantify the direct and indirect effects of climate on AGPP through phenology and physiology.Our results reveal that vegetation physiology,particularly the seasonal maximum gross primary production,plays a more dominant role in regulating AGPP than phenology.Furthermore,we found that globally,SIF-derived phenology indicators tend to be lower than those from LAI and EVI,whereas SIF-derived physiology indicators are elevated in tropical regions and the Southern Hemisphere.These findings highlight the potential of satellite-derived indicators in advancing AGPP modeling and emphasize the predominant role of vegetation physiology in regulating ecosystem carbon uptake.This study contributes to a refined understanding of global carbon cycle dynamics and provides insights for improving large-scale carbon assessments in the context of climate change.展开更多
BACKGROUND Liver transplantation aims to increase the survival of patients with end-stage liver diseases and improve their quality of life.The number of organs available for transplantation is lower than the demand.To...BACKGROUND Liver transplantation aims to increase the survival of patients with end-stage liver diseases and improve their quality of life.The number of organs available for transplantation is lower than the demand.To provide fair organ distribution,predictive mortality scores have been developed.AIM To compare the Acute Physiology and Chronic Health Evaluation IV(APACHE IV),balance of risk(BAR),and model for end-stage liver disease(MELD)scores as predictors of mortality.METHODS Retrospective cohort study,which included 283 adult patients in the postoperative period of deceased donor liver transplantation from 2014 to 2018.RESULTS The transplant recipients were mainly male,with a mean age of 58.1 years.Donors were mostly male,with a mean age of 41.6 years.The median cold ischemia time was 3.1 hours,and the median intensive care unit stay was 5 days.For APACHE IV,a mean of 59.6 was found,BAR 10.7,and MELD 24.2.The 28-day mortality rate was 9.5%,and at 90 days,it was 3.5%.The 28-day mortality prediction for APACHE IV was very good[area under the curve(AUC):0.85,P<0.001,95%CI:0.76-0.94],P<0.001,BAR(AUC:0.70,P<0.001,95%CI:0.58–0.81),and MELD(AUC:0.66,P<0.006,95%CI:0.55-0.78),P<0.008.At 90 days,the data for APACHE IV were very good(AUC:0.80,P<0.001,95%CI:0.71–0.90)and moderate for BAR and MELD,respectively,(AUC:0.66,P<0.004,95%CI:0.55–0.77),(AUC:0.62,P<0.026,95%CI:0.51–0.72).All showed good discrimination between deaths and survivors.As for the best value for liver transplantation,it was significant only for APACHE IV(P<0.001).CONCLUSION The APACHE IV assessment score was more accurate than BAR and MELD in predicting mortality in deceased donor liver transplant recipients.展开更多
Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microgl...Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microglia play an important role in secondary injury and can be activated in response to traumatic brain injury.In this article,we review the origin and classification of microglia as well as the dynamic changes of microglia in traumatic brain injury.We also clarify the microglial polarization pathways and the therapeutic drugs targeting activated microglia.We found that regulating the signaling pathways involved in pro-inflammatory and anti-inflammatory microglia,such as the Toll-like receptor 4/nuclear factor-kappa B,mitogen-activated protein kinase,Janus kinase/signal transducer and activator of transcription,phosphoinositide 3-kinase/protein kinase B,Notch,and high mobility group box 1 pathways,can alleviate the inflammatory response triggered by microglia in traumatic brain injury,thereby exerting neuroprotective effects.We also reviewed the strategies developed on the basis of these pathways,such as drug and cell replacement therapies.Drugs that modulate inflammatory factors,such as rosuvastatin,have been shown to promote the polarization of antiinflammatory microglia and reduce the inflammatory response caused by traumatic brain injury.Mesenchymal stem cells possess anti-inflammatory properties,and clinical studies have confirmed their significant efficacy and safety in patients with traumatic brain injury.Additionally,advancements in mesenchymal stem cell-delivery methods—such as combinations of novel biomaterials,genetic engineering,and mesenchymal stem cell exosome therapy—have greatly enhanced the efficiency and therapeutic effects of mesenchymal stem cells in animal models.However,numerous challenges in the application of drug and mesenchymal stem cell treatment strategies remain to be addressed.In the future,new technologies,such as single-cell RNA sequencing and transcriptome analysis,can facilitate further experimental studies.Moreover,research involving non-human primates can help translate these treatment strategies to clinical practice.展开更多
Publisher Correction to:Journal of Forestry Research(2025)36:29 https://doi.org/10.1007/s11676-025-01823-0 In Fig.4c of this article,the lower part of the figure was unintentionally cropped and incomplete during the p...Publisher Correction to:Journal of Forestry Research(2025)36:29 https://doi.org/10.1007/s11676-025-01823-0 In Fig.4c of this article,the lower part of the figure was unintentionally cropped and incomplete during the publisher's production process.The published incorrect version and the corrected version of Fig.4 are given below.展开更多
In the article titled“Disentangling brain PrPC proteoforms and their roles in physiology and disease”,published on pages 963-965,Issue 5,Volume 19 of Neural Regeneration Research(Vanni and Romolo,2024;doi:10.4103/16...In the article titled“Disentangling brain PrPC proteoforms and their roles in physiology and disease”,published on pages 963-965,Issue 5,Volume 19 of Neural Regeneration Research(Vanni and Romolo,2024;doi:10.4103/1673-5374.385302),the name of the second author appears incorrectly.The correct name is Romolo Nonno.展开更多
Primates exhibit complex brain structures that augment cognitive function.The neocortex fulfills high-cognitive functions through billions of connected neurons.These neurons have distinct transcriptomic,morphological,...Primates exhibit complex brain structures that augment cognitive function.The neocortex fulfills high-cognitive functions through billions of connected neurons.These neurons have distinct transcriptomic,morphological,and electrophysiological properties,and their connectivity principles vary.These features endow the primate brain atlas with a multimodal nature.The recent integration of next-generation sequencing with modified patch-clamp techniques is revolutionizing the way to census the primate neocortex,enabling a multimodal neuronal atlas to be established in great detail:(1)single-cell/single-nucleus RNA-seq technology establishes high-throughput transcriptomic references,covering all major transcriptomic cell types;(2)patch-seq links the morphological and electrophysiological features to the transcriptomic reference;(3)multicell patch-clamp delineates the principles of local connectivity.Here,we review the applications of these technologies in the primate neocortex and discuss the current advances and tentative gaps for a comprehensive understanding of the primate neocortex.展开更多
Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have rev...Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have revealed that gut microbiota can communicate bidirectionally with the brain through the gut microbiota–brain axis.This axis indicates that gut microbiota is closely related to the development and prognosis of intracerebral hemorrhage and its associated secondary white matter injury.The NACHT,LRR,and pyrin domain-containing protein 3(NLRP3)inflammasome plays a crucial role in this context.This review summarizes the dysbiosis of gut microbiota following intracerebral hemorrhage and explores the mechanisms by which this imbalance may promote the activation of the NLRP3 inflammasome.These mechanisms include metabolic pathways(involving short-chain fatty acids,lipopolysaccharides,lactic acid,bile acids,trimethylamine-N-oxide,and tryptophan),neural pathways(such as the vagus nerve and sympathetic nerve),and immune pathways(involving microglia and T cells).We then discuss the relationship between the activated NLRP3 inflammasome and secondary white matter injury after intracerebral hemorrhage.The activation of the NLRP3 inflammasome can exacerbate secondary white matter injury by disrupting the blood–brain barrier,inducing neuroinflammation,and interfering with nerve regeneration.Finally,we outline potential treatment strategies for intracerebral hemorrhage and its secondary white matter injury.Our review highlights the critical role of the gut microbiota–brain axis and the NLRP3 inflammasome in white matter injury following intracerebral hemorrhage,paving the way for exploring potential therapeutic approaches.展开更多
Functional recovery in penetrating neurological injury is hampered by a lack of clinical regenerative therapies.Biomaterial therapies show promise as medical materials for neural repair through immunomodulation,struct...Functional recovery in penetrating neurological injury is hampered by a lack of clinical regenerative therapies.Biomaterial therapies show promise as medical materials for neural repair through immunomodulation,structural support,and delivery of therapeutic biomolecules.However,a lack of facile and pathology-mimetic models for therapeutic testing is a bottleneck in neural tissue engineering research.We have deployed a two-dimensional,high-density multicellular cortical brain sheet to develop a facile model of injury(macrotransection/scratch wound)in vitro.The model encompasses the major neural cell types involved in pathological responses post-injury.Critically,we observed hallmark pathological responses in injury foci including cell scarring,immune cell infiltration,precursor cell migration,and shortrange axonal sprouting.Delivering test magnetic particles to evaluate the potential of the model for biomaterial screening shows a high uptake of introduced magnetic particles by injury-activated immune cells,mimicking in vivo findings.Finally,we proved it is feasible to create reproducible traumatic injuries in the brain sheet(in multielectrode array devices in situ)characterized by focal loss of electrical spiking in injury sites,offering the potential for longer term,electrophysiology plus histology assays.To our knowledge,this is the first in vitro simulation of transecting injury in a two-dimensional multicellular cortical brain cell sheet,that allows for combined histological and electrophysiological readouts of damage/repair.The patho-mimicry and adaptability of this simplified model of brain injury could benefit the testing of biomaterial therapeutics in regenerative neurology,with the option for functional electrophysiological readouts.展开更多
Noninvasive detection of human physiology plays a key role for diagnosis or therapeutic assessment of various diseases.In the past,many functional modalities,such as electrocardiograph(ECG),electroencephalogram(EEG),f...Noninvasive detection of human physiology plays a key role for diagnosis or therapeutic assessment of various diseases.In the past,many functional modalities,such as electrocardiograph(ECG),electroencephalogram(EEG),fluorescence microscope,and positron emission computed tomography(PETS)have been applied to clinic for probing human heart,brain waves or tissue metabolism,owing to rapid development in fields of electromagnetism,optics or particle physics.Nowadays,a few smart sensing technologies are emerging for human physiology detection in more wide range.展开更多
基金supported by Open Scientific Research Program of Military Logistics,No.BLB20J009(to YZhao).
文摘Blood-brain barrier disruption and the neuroinflammatory response are significant pathological features that critically influence disease progression and treatment outcomes.This review systematically analyzes the current understanding of the bidirectional relationship between blood-brain barrier disruption and neuroinflammation in traumatic brain injury,along with emerging combination therapeutic strategies.Literature review indicates that blood-brain barrier disruption and neuroinflammatory responses are key pathological features following traumatic brain injury.In the acute phase after traumatic brain injury,the pathological characteristics include primary blood-brain barrier disruption and the activation of inflammatory cascades.In the subacute phase,the pathological features are characterized by repair mechanisms and inflammatory modulation.In the chronic phase,the pathological features show persistent low-grade inflammation and incomplete recovery of the blood-brain barrier.Various physiological changes,such as structural alterations of the blood-brain barrier,inflammatory cascades,and extracellular matrix remodeling,interact with each other and are influenced by genetic,age,sex,and environmental factors.The dynamic balance between blood-brain barrier permeability and neuroinflammation is regulated by hormones,particularly sex hormones and stress-related hormones.Additionally,the role of gastrointestinal hormones is receiving increasing attention.Current treatment strategies for traumatic brain injury include various methods such as conventional drug combinations,multimodality neuromonitoring,hyperbaric oxygen therapy,and non-invasive brain stimulation.Artificial intelligence also shows potential in treatment decision-making and personalized therapy.Emerging sequential combination strategies and precision medicine approaches can help improve treatment outcomes;however,challenges remain,such as inadequate research on the mechanisms of the chronic phase traumatic brain injury and difficulties with technology integration.Future research on traumatic brain injury should focus on personalized treatment strategies,the standardization of techniques,costeffectiveness evaluations,and addressing the needs of patients with comorbidities.A multidisciplinary approach should be used to enhance treatment and improve patient outcomes.
基金supported by grants from the Jack Brown and Family Alzheimer’s Disease Research Foundationthe Natural Sciences and Engineering Research Council of Canada(No.2020-04407)+1 种基金the University of British Columbia Okanagan CampusThe authors also thank Gentmed SIA for financial assistance。
文摘Neuroinflammation contributes to a wide range of neurodegenerative diseases including Alzheimer's disease,Parkinson's disease,Huntington's disease,and multiple sclerosis.It is driven by non-neuronal glial cells,mainly microglia and astrocytes.Microglia are the resident immune cells of the central nervous system,while astrocytes are the main support cells for neuronal functions but can also participate in neuroimmune responses.Both these glial cell types can become reactive upon detection of certain endogenous intracellular molecules that appear in the extracellular space under specific circumstances;these can be pathology-associated abnormal structures,such as amyloidβproteins,or damage-associated molecular patterns released from injured cells,including their mitochondria.Once in the extracellular space,damage-associated molecular patterns act as ligands for specific pattern recognition receptors expressed by glia inducing their reactivity and neuroimmune responses.This review considers the following mitochondrial damage-associated molecular patterns:heme,cytochrome c,cardiolipin,adenosine triphosphate,mitochondrial DNA,mitochondrial transcription factor A,N-formyl peptides,and the tricarboxylic acid cycle metabolites:succinate,fumarate,and itaconate.We describe their well-established functions as damage-associated molecular patterns of the peripheral tissues before summarizing available evidence indicating these molecules may also play significant roles in the neuroimmune processes of the central nervous system.We highlight the pattern recognition receptors that mitochondrial damage-associated molecular patterns interact with and the cellular signaling mechanisms they modulate.Our review demonstrates that some mitochondrial damage-associated molecular patterns,such as cytochrome c,adenosine triphosphate,and mitochondrial transcription factor A,have already demonstrated significant effects on the central nervous system.In contrast,others including cardiolipin,mitochondrial DNA,N-formyl peptides,succinate,fumarate,and itaconate,will require additional studies corroborating their roles as damageassociated molecular patterns in the central nervous system.For all of the reviewed mitochondrial damage-associated molecular patterns,there is a shortage of studies using human cells and tissues,which is identified as a significant knowledge gap.We also assess the need for targeted research on the effects of mitochondrial damage-associated molecular patterns in the central nervous system pathologies where their roles are understudied.Such studies could identify novel treatment strategies for multiple neurodegenerative diseases,which are characterized by chronic neuroinflammation and currently lack effective therapies.
基金Guangdong Province Medical Research Fund,Grant/Award Number:A2021108。
文摘Background:P regnancy affects learning and memory in women.Thus,to investigate the effects of pregnancy,the authors examined the brain electrophysiology of pregnant mice.Methods:U sing the whole-c ell patch-c lamp technique on isolated brain slices,we detected and compared the electrophysiological changes in the hippocampal CA1(HIP CA1)region,medial prefrontal cortex(mPFC),and basolateral amygdala(BLA)among 15 pregnant and 15 nonpregnant mice.Results:In pregnant mice,there was a trend toward an increase in the frequency of miniature excitatory postsynaptic currents(mEPSCs)(p=0.092)and a trend toward a decrease in the amplitude of miniature inhibitory postsynaptic currents(mIPSC)(p=0.071)in the HIP CA1.In the BLA,both the amplitudes of mEPSCs and mIPSCs were significantly reduced(p=0.004 and 0.042,respectively).In the mPFC,the amplitudes of mEPSCs and hyperpolarization-a ctivated currents(Ih),as well as the frequencies of mIPSCs,were higher compared to nonpregnant mice(p=0.035,0.009,and 0.038,respectively).Conclusions:I n pregnant mice,the electrophysiological change in neurons in the mPFC and BLA might contribute to the cognitive and emotional changes during pregnancy.A trend toward electrophysiological change in the HIP CA1 revealed that the mechanism of cognitive change during pregnancy might differ from that of other conditions.
文摘Intracranial hypertension is a major cause of morbidity and mortality of patients suffering from fulminant hepatic failure. The etiology of this intracranial hypertension is not fully determined, and is probably multifactorial, combining a cytotoxic brain edema due to the astrocytic accumulation of glutamine, and an increase in cerebral blood volume and cerebral blood flow, in part due to inflammation, to glutamine and to toxic products of the diseased liver. Validated methods to control intracranial hypertension in fulminant hepatic failure patients mainly include mannitol, hypertonic saline, indomethacin, thiopental, and hyperventilation. However all these measures are often not sufficient in absence of liver transplantation, the only curative treatment of intracranial hypertension in fulminant hepatic failure to date. Induced moderate hypothermia seems very promising in this setting, but has to be validated by a controlled, randomized study. Artificial liver support systems have been under investigation for many decades. The bioartiflcial liver, based on both detoxification and swine liver cells, has shown some efficacy on reduction of intracranial pressure but did not show survival benefit in a controlled, randomized study. The Molecular Adsorbents Recirculating System has shown some efficacy in decreasing intracranial pressure in an animal model of liver failure, but has still to be evaluated in a phase Ⅲ trial.
基金supported by a grant from the Massachusetts Alzheimer’s Disease Research Center(5P50 AG 005134)(to SL).
文摘Alzheimer’s disease is a prominent chronic neurodegenerative condition characterized by a gradual decline in memory leading to dementia.Growing evidence suggests that Alzheimer’s disease is associated with accumulating various amyloid-βoligomers in the brain,influenced by complex genetic and environmental factors.The memory and cognitive deficits observed during the prodromal and mild cognitive impairment phases of Alzheimer’s disease are believed to primarily result from synaptic dysfunction.Throughout life,environmental factors can lead to enduring changes in gene expression and the emergence of brain disorders.These changes,known as epigenetic modifications,also play a crucial role in regulating the formation of synapses and their adaptability in response to neuronal activity.In this context,we highlight recent advances in understanding the roles played by key components of the epigenetic machinery,specifically DNA methylation,histone modification,and microRNAs,in the development of Alzheimer’s disease,synaptic function,and activity-dependent synaptic plasticity.Moreover,we explore various strategies,including enriched environments,exposure to non-invasive brain stimulation,and the use of pharmacological agents,aimed at improving synaptic function and enhancing long-term potentiation,a process integral to epigenetic mechanisms.Lastly,we deliberate on the development of effective epigenetic agents and safe therapeutic approaches for managing Alzheimer’s disease.We suggest that addressing Alzheimer’s disease may require distinct tailored epigenetic drugs targeting different disease stages or pathways rather than relying on a single drug.
文摘Hypnosis is a promising tool in the management of various conditions,such as anxiety and chronic pain.Preliminary studies have shown that hypnosis can directly affect the cardiovascular system,as it increases parasympathetic activation and reduces sympathetic activity.However,the literature related to the effects of hypnosis on cardiovascular health is scarce,mainly due to misconceptions about hypnosis among researchers and medical professionals.This opinion paper examines the role that hypnosis may play in cardiovascular health,highlighting the physiological mechanisms behind it.The evidence suggests that hypnosis has both direct(e.g.,changes in the activity of the autonomic nervous system)and indirect(e.g.,changes in healthy behaviours)effects on the cardiovascular system;however,further studies are needed to properly define its mechanisms of action and its applicability in improving cardiovascular health.Thus,this opinion paper advocates the adoption of the term“hypno-cardiac physiology”to identify a new research area that gathers experts from neuroscience and cardiovascular science with the joint aim of seeking further understanding of the effects of hypnosis on the cardiovascular system.The adoption of a dedicated term to identify the study of the cardiovascular response to hypnosis will encourage its implementation in cardiovascular health interventions,promoting awareness of its effects among the public and the healthcare community,and promoting the formation of dedicated multidisciplinary research groups and dedicated educational training for healthcare professional interested in its applications.
基金This work was supported by the National Key Research and Development Program of China(No.2017YFA0104303)the National Natural Science Foundation of China(No.81673410 and No.81761138048)+1 种基金the Jiangsu Innovation&Entrepreneurship Team Program,the Major Project of National Science and Technology(No.2020 ZX09201015)and the Fundamental Research Funds for the Central Universities(No.2242020K40134).
文摘N^6-methyladenosine(m6A)is identified as the most widespread and abundant internal chemical modification of RNA in eukaryotes.A series of proteins including methyltransferases(also known as“writers”),demethylases(also known as“erasers”),and m6A-binding proteins(also known as“readers”)were indicated to participate in the m6A methylation.m6A has emerged as a regulator of various cellular,developmental,and disease processes.Notably,there is highest abundance of m^6A methylation in brain than in other organs,which indicates that m^6A plays an essential role in brain functions.Here,we describe the general features,mechanisms,and functions of m^6A in the brain,and discuss the emerging roles of m6A in brain physiology and diseases.
基金General Program of Guangdong Provincial Natural Science Foundation(Project No.:2214050002848)College Students’Innovation and Entrepreneurship Projects(Project No.:202310582018,622A0243,S202410582051)+2 种基金Key Teaching Reform Project of Jiaying University(Project No.:423A0613)2025 Teaching Quality and Teaching Reform Project of Jiaying University(Project No.:27)2023 University-level Teaching Quality and Teaching Reform Project(Project No.:ZLGC2023101)。
文摘Physiology is an important basic course for medical majors.The content of the nervous system is abstract,the theories are profound,the knowledge is updated rapidly,and it is most closely connected with clinical practice.Students generally report difficulties in understanding,resulting in low learning interest.To improve teaching quality,this study has attempted to organically integrate clinical cases,scientific research methods and classroom teaching in the teaching of the nervous system,and constructed a“clinical-research-teaching”trinity teaching model.With“clinical problem-driven,scientific research thinking-driven,teaching scenario reconstruction”as the main line,real cases,scientific research examples and cutting-edge research progress in neuroscience were introduced to stimulate students’learning interest and cultivate their scientific thinking and clinical application abilities.Practice has shown that this model can effectively improve teaching effectiveness and students’comprehensive quality.Compared with the traditional teaching model,this teaching model significantly improved students’final exam scores(p<0.01),scores of the Critical Thinking Disposition Inventory(p<0.01),and the number of approved college students’innovation and entrepreneurship projects.It is proved that the“trinity”teaching model can stimulate learning interest,cultivate integrated medical talents,and is an effective way to achieve in-depth connection between basic medicine and clinical practice.
基金supported by the Key Teaching Reform and Practice Project of Pingdingshan University in 2023,titled“Research and Practice on Innovation and Entrepreneurship Pathways for Medical Students under the New Medical Discipline Framework”(Project No.2023-JYZD15)Additionally,this study received support from the Henan Province Higher Education Teaching Reform Research and Practice Project,titled“Research on the Integration Path of Medical Education and Innovation&Entrepreneurship Education under the‘Project-based+Mentorship System’Model”(Project No.2024SJGLX0495).
文摘The construction of the New Medical Sciences aims to cultivate interdisciplinary medical talents,placing higher demands on physiology experiment teaching.In light of the challenges of traditional teaching,such as outdated content,a single assessment mechanism,low student engagement,and limited research experience among instructors,this study proposes a reform pathway centered on research competence development,supported by diversified evaluation methods and the deep integration of ideological and scenario-based teaching.By optimizing teaching content,introducing innovative projects,establishing a multidimensional assessment system,and strengthening faculty development,the proposed reforms effectively enhance students’Innovative ability and practical skills.This study provides theoretical insights and practical experience for training interdisciplinary medical professionals to meet the demands of the new era.
文摘BACKGROUND Previous studies have reported the high predictive accuracy of 4C Mortality Score derived at hospital admission in coronavirus disease 2019(COVID-19)patients.Very few studies have assessed it at intensive care unit(ICU)admission and compared it with the Acute Physiology and Chronic Health Evaluation(APACHE)II score.There are no studies comparing its accuracy with APACHE III score.AIM To describe the characteristics and outcomes of patients admitted to ICU with COVID-19 infection and to compare the accuracy of 4C score and APACHE score in predicting mortality in these patients.METHODS We conducted this retrospective cohort study using an electronic database in a tertiary ICU in Sydney.We included all adult patients(age>16 years)admitted to ICU with COVID-19 infection over a 5-month period(July 1,2021 to November 30,2021).We collected the data on demographics,clinical characteristics,interventions and outcomes for all patients.We calculated the 4C Mortality Score for each patient using eight variables as described previously.We compared the predictive accuracy of 4C Mortality Score at hospital and ICU admission and APACHE II and III scores by area under the receiver operating characteristic curve(AUROC).We determined the optimal cut-off value for each of these scores using the‘nearest’method and its 95%confidence interval by bootstrapping.RESULTS A total of 140 patients(62%males,mean age 56±17 years,mean APACHE II score 13±57)were included in the study.Nineteen(13.6%)of 140 patients died in the hospital.Compared to survivors,the non-survivors were older,males,had more comorbidities,higher rate of mechanical ventilation and vasopressor use.The AUROC for the 4C Mortality Score at hospital and ICU admission and APACHE II and II score was 0.75,0.80.0.75 and 0.79 respectively.The optimal cut-off value for these four scores was 9,10,14 and 56 respectively.The cut-point for all the scores had higher sensitivity than specificity.CONCLUSION The 4C score at ICU admission had a higher accuracy in predicting mortality than the 4C score at hospital admission.The predictive accuracy was similar to that for APACHE III score.The 4C score at ICU admission needs to be validated in future studies.
基金supported by European Union-NextGeneration EU under the Italian University and Research(MUR)National Innovation Ecosystem grant ECS00000041-VITALITY-CUP E13C22001060006(to MdA)。
文摘Stroke is a major cause of death and disability worldwide.It is characterized by a highly interconnected and multiphasic neuropathological cascade of events,in which an intense and protracted inflammatory response plays a crucial role in worsening brain injury.Neuroinflammation,a key player in the pathophysiology of stroke,has a dual role.In the acute phase of stroke,neuroinflammation exacerbates brain injury,contributing to neuronal damage and blood–brain barrier disruption.This aspect of neuroinflammation is associated with poor neurological outcomes.Conversely,in the recovery phase following stroke,neuroinflammation facilitates brain repair processes,including neurogenesis,angiogenesis,and synaptic plasticity.The transition of neuroinflammation from a harmful to a reparative role is not well understood.Therefore,this review seeks to explore the mechanisms underlying this transition,with the goal of informing the development of therapeutic interventions that are both time-and context-specific.This review aims to elucidate the complex and dual role of neuroinflammation in stroke,highlighting the main actors,biomarkers of the disease,and potential therapeutic approaches.
基金support from the National Natural Science Foundation of China(Nos.42450226,42371483,and 42171308)the Natural Science Foundation of Guangdong Province,China(No.2025A1515010770)the Postdoctoral Fellowship Program of CPSF(No.GZB20240880).
文摘Vegetation annual gross primary production(AGPP),the total yearly carbon assimilation via photosynthesis,serves as a key indicator of ecosystem carbon uptake.While AGPP variations are jointly influenced by both vegetation phenology and physiology,the effectiveness of satellite-derived indicators in capturing these variations has not been fully evaluated.This study develops and evaluates the satellite-derived phenology and physiology indicators for modeling AGPP variability.We assessed the performance of satellite-derived metrics,including solar-induced chlorophyll fluorescence(SIF),leaf area index(LAI),and enhanced vegetation index(EVI),in capturing AGPP variations.Among these,SIF-based indicators exhibited the highest accuracy(Pearson's r=0.79;root mean square error=414.7 gC·m^(-2)·year^(-1)),outperforming LAI-and EVI-based indicators.To further investigate the mechanisms driving AGPP variability,we used a structural equation model based on in situ observations to quantify the direct and indirect effects of climate on AGPP through phenology and physiology.Our results reveal that vegetation physiology,particularly the seasonal maximum gross primary production,plays a more dominant role in regulating AGPP than phenology.Furthermore,we found that globally,SIF-derived phenology indicators tend to be lower than those from LAI and EVI,whereas SIF-derived physiology indicators are elevated in tropical regions and the Southern Hemisphere.These findings highlight the potential of satellite-derived indicators in advancing AGPP modeling and emphasize the predominant role of vegetation physiology in regulating ecosystem carbon uptake.This study contributes to a refined understanding of global carbon cycle dynamics and provides insights for improving large-scale carbon assessments in the context of climate change.
文摘BACKGROUND Liver transplantation aims to increase the survival of patients with end-stage liver diseases and improve their quality of life.The number of organs available for transplantation is lower than the demand.To provide fair organ distribution,predictive mortality scores have been developed.AIM To compare the Acute Physiology and Chronic Health Evaluation IV(APACHE IV),balance of risk(BAR),and model for end-stage liver disease(MELD)scores as predictors of mortality.METHODS Retrospective cohort study,which included 283 adult patients in the postoperative period of deceased donor liver transplantation from 2014 to 2018.RESULTS The transplant recipients were mainly male,with a mean age of 58.1 years.Donors were mostly male,with a mean age of 41.6 years.The median cold ischemia time was 3.1 hours,and the median intensive care unit stay was 5 days.For APACHE IV,a mean of 59.6 was found,BAR 10.7,and MELD 24.2.The 28-day mortality rate was 9.5%,and at 90 days,it was 3.5%.The 28-day mortality prediction for APACHE IV was very good[area under the curve(AUC):0.85,P<0.001,95%CI:0.76-0.94],P<0.001,BAR(AUC:0.70,P<0.001,95%CI:0.58–0.81),and MELD(AUC:0.66,P<0.006,95%CI:0.55-0.78),P<0.008.At 90 days,the data for APACHE IV were very good(AUC:0.80,P<0.001,95%CI:0.71–0.90)and moderate for BAR and MELD,respectively,(AUC:0.66,P<0.004,95%CI:0.55–0.77),(AUC:0.62,P<0.026,95%CI:0.51–0.72).All showed good discrimination between deaths and survivors.As for the best value for liver transplantation,it was significant only for APACHE IV(P<0.001).CONCLUSION The APACHE IV assessment score was more accurate than BAR and MELD in predicting mortality in deceased donor liver transplant recipients.
基金supported by the Natural Science Foundation of Yunnan Province,No.202401AS070086(to ZW)the National Key Research and Development Program of China,No.2018YFA0801403(to ZW)+1 种基金Yunnan Science and Technology Talent and Platform Plan,No.202105AC160041(to ZW)the Natural Science Foundation of China,No.31960120(to ZW)。
文摘Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microglia play an important role in secondary injury and can be activated in response to traumatic brain injury.In this article,we review the origin and classification of microglia as well as the dynamic changes of microglia in traumatic brain injury.We also clarify the microglial polarization pathways and the therapeutic drugs targeting activated microglia.We found that regulating the signaling pathways involved in pro-inflammatory and anti-inflammatory microglia,such as the Toll-like receptor 4/nuclear factor-kappa B,mitogen-activated protein kinase,Janus kinase/signal transducer and activator of transcription,phosphoinositide 3-kinase/protein kinase B,Notch,and high mobility group box 1 pathways,can alleviate the inflammatory response triggered by microglia in traumatic brain injury,thereby exerting neuroprotective effects.We also reviewed the strategies developed on the basis of these pathways,such as drug and cell replacement therapies.Drugs that modulate inflammatory factors,such as rosuvastatin,have been shown to promote the polarization of antiinflammatory microglia and reduce the inflammatory response caused by traumatic brain injury.Mesenchymal stem cells possess anti-inflammatory properties,and clinical studies have confirmed their significant efficacy and safety in patients with traumatic brain injury.Additionally,advancements in mesenchymal stem cell-delivery methods—such as combinations of novel biomaterials,genetic engineering,and mesenchymal stem cell exosome therapy—have greatly enhanced the efficiency and therapeutic effects of mesenchymal stem cells in animal models.However,numerous challenges in the application of drug and mesenchymal stem cell treatment strategies remain to be addressed.In the future,new technologies,such as single-cell RNA sequencing and transcriptome analysis,can facilitate further experimental studies.Moreover,research involving non-human primates can help translate these treatment strategies to clinical practice.
文摘Publisher Correction to:Journal of Forestry Research(2025)36:29 https://doi.org/10.1007/s11676-025-01823-0 In Fig.4c of this article,the lower part of the figure was unintentionally cropped and incomplete during the publisher's production process.The published incorrect version and the corrected version of Fig.4 are given below.
文摘In the article titled“Disentangling brain PrPC proteoforms and their roles in physiology and disease”,published on pages 963-965,Issue 5,Volume 19 of Neural Regeneration Research(Vanni and Romolo,2024;doi:10.4103/1673-5374.385302),the name of the second author appears incorrectly.The correct name is Romolo Nonno.
基金supported by the Natural Science Foundation of China(81961128021 and 82371095)the National Key R&D Program of China(2022YEF0203200)+1 种基金the Guangdong Provincial Key R&D Programs(2018B030335001)the Science and Technology Program of Guangzhou(202007030011 and 202007030010).
文摘Primates exhibit complex brain structures that augment cognitive function.The neocortex fulfills high-cognitive functions through billions of connected neurons.These neurons have distinct transcriptomic,morphological,and electrophysiological properties,and their connectivity principles vary.These features endow the primate brain atlas with a multimodal nature.The recent integration of next-generation sequencing with modified patch-clamp techniques is revolutionizing the way to census the primate neocortex,enabling a multimodal neuronal atlas to be established in great detail:(1)single-cell/single-nucleus RNA-seq technology establishes high-throughput transcriptomic references,covering all major transcriptomic cell types;(2)patch-seq links the morphological and electrophysiological features to the transcriptomic reference;(3)multicell patch-clamp delineates the principles of local connectivity.Here,we review the applications of these technologies in the primate neocortex and discuss the current advances and tentative gaps for a comprehensive understanding of the primate neocortex.
基金supported by the Guangdong Basic and Applied Basic Research Foundation,No.2023A1515030045(to HS)Presidential Foundation of Zhujiang Hospital of Southern Medical University,No.yzjj2022ms4(to HS)。
文摘Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have revealed that gut microbiota can communicate bidirectionally with the brain through the gut microbiota–brain axis.This axis indicates that gut microbiota is closely related to the development and prognosis of intracerebral hemorrhage and its associated secondary white matter injury.The NACHT,LRR,and pyrin domain-containing protein 3(NLRP3)inflammasome plays a crucial role in this context.This review summarizes the dysbiosis of gut microbiota following intracerebral hemorrhage and explores the mechanisms by which this imbalance may promote the activation of the NLRP3 inflammasome.These mechanisms include metabolic pathways(involving short-chain fatty acids,lipopolysaccharides,lactic acid,bile acids,trimethylamine-N-oxide,and tryptophan),neural pathways(such as the vagus nerve and sympathetic nerve),and immune pathways(involving microglia and T cells).We then discuss the relationship between the activated NLRP3 inflammasome and secondary white matter injury after intracerebral hemorrhage.The activation of the NLRP3 inflammasome can exacerbate secondary white matter injury by disrupting the blood–brain barrier,inducing neuroinflammation,and interfering with nerve regeneration.Finally,we outline potential treatment strategies for intracerebral hemorrhage and its secondary white matter injury.Our review highlights the critical role of the gut microbiota–brain axis and the NLRP3 inflammasome in white matter injury following intracerebral hemorrhage,paving the way for exploring potential therapeutic approaches.
基金supported by awards from the EPSRC Centre for Doctoral Training in Regenerative Medicine(EP/L014904/1,to JW)an NHS bursary(to RHB)an EPSRC Healthcare Technologies award(EP/T013885/1,to DMC)。
文摘Functional recovery in penetrating neurological injury is hampered by a lack of clinical regenerative therapies.Biomaterial therapies show promise as medical materials for neural repair through immunomodulation,structural support,and delivery of therapeutic biomolecules.However,a lack of facile and pathology-mimetic models for therapeutic testing is a bottleneck in neural tissue engineering research.We have deployed a two-dimensional,high-density multicellular cortical brain sheet to develop a facile model of injury(macrotransection/scratch wound)in vitro.The model encompasses the major neural cell types involved in pathological responses post-injury.Critically,we observed hallmark pathological responses in injury foci including cell scarring,immune cell infiltration,precursor cell migration,and shortrange axonal sprouting.Delivering test magnetic particles to evaluate the potential of the model for biomaterial screening shows a high uptake of introduced magnetic particles by injury-activated immune cells,mimicking in vivo findings.Finally,we proved it is feasible to create reproducible traumatic injuries in the brain sheet(in multielectrode array devices in situ)characterized by focal loss of electrical spiking in injury sites,offering the potential for longer term,electrophysiology plus histology assays.To our knowledge,this is the first in vitro simulation of transecting injury in a two-dimensional multicellular cortical brain cell sheet,that allows for combined histological and electrophysiological readouts of damage/repair.The patho-mimicry and adaptability of this simplified model of brain injury could benefit the testing of biomaterial therapeutics in regenerative neurology,with the option for functional electrophysiological readouts.
文摘Noninvasive detection of human physiology plays a key role for diagnosis or therapeutic assessment of various diseases.In the past,many functional modalities,such as electrocardiograph(ECG),electroencephalogram(EEG),fluorescence microscope,and positron emission computed tomography(PETS)have been applied to clinic for probing human heart,brain waves or tissue metabolism,owing to rapid development in fields of electromagnetism,optics or particle physics.Nowadays,a few smart sensing technologies are emerging for human physiology detection in more wide range.
