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
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
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
Background:Brain volume measurement serves as a critical approach for assessing brain health status.Considering the close biological connection between the eyes and brain,this study aims to investigate the feasibility...Background:Brain volume measurement serves as a critical approach for assessing brain health status.Considering the close biological connection between the eyes and brain,this study aims to investigate the feasibility of estimating brain volume through retinal fundus imaging integrated with clinical metadata,and to offer a cost-effective approach for assessing brain health.Methods:Based on clinical information,retinal fundus images,and neuroimaging data derived from a multicenter,population-based cohort study,the Kai Luan Study,we proposed a cross-modal correlation representation(CMCR)network to elucidate the intricate co-degenerative relationships between the eyes and brain for 755 subjects.Specifically,individual clinical information,which has been followed up for as long as 12 years,was encoded as a prompt to enhance the accuracy of brain volume estimation.Independent internal validation and external validation were performed to assess the robustness of the proposed model.Root mean square error(RMSE),peak signal-tonoise ratio(PSNR),and structural similarity index measure(SSIM)metrics were employed to quantitatively evaluate the quality of synthetic brain images derived from retinal imaging data.Results:The proposed framework yielded average RMSE,PSNR,and SSIM values of 98.23,35.78 d B,and 0.64,respectively,which significantly outperformed 5 other methods:multi-channel Variational Autoencoder(mcVAE),Pixelto-Pixel(Pixel2pixel),transformer-based U-Net(Trans UNet),multi-scale transformer network(MT-Net),and residual vision transformer(ResViT).The two-(2D)and three-dimensional(3D)visualization results showed that the shape and texture of the synthetic brain images generated by the proposed method most closely resembled those of actual brain images.Thus,the CMCR framework accurately captured the latent structural correlations between the fundus and the brain.The average difference between predicted and actual brain volumes was 61.36 cm~3,with a relative error of 4.54%.When all of the clinical information(including age and sex,daily habits,cardiovascular factors,metabolic factors,and inflammatory factors)was encoded,the difference was decreased to 53.89 cm~3,with a relative error of 3.98%.Based on the synthesized brain magnetic resonance images from retinal fundus images,the volumes of brain tissues could be estimated with high accuracy.Conclusion:This study provides an innovative,accurate,and cost-effective approach to characterize brain health status through readily accessible retinal fundus images.展开更多
Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated...Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated with increased levels of circulato ry pro-inflammatory marke rs up to 1 year postTBI(Eagle et al.,2023).展开更多
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
This systematic review aims to comprehensively examine and compare deep learning methods for brain tumor segmentation and classification using MRI and other imaging modalities,focusing on recent trends from 2022 to 20...This systematic review aims to comprehensively examine and compare deep learning methods for brain tumor segmentation and classification using MRI and other imaging modalities,focusing on recent trends from 2022 to 2025.The primary objective is to evaluate methodological advancements,model performance,dataset usage,and existing challenges in developing clinically robust AI systems.We included peer-reviewed journal articles and highimpact conference papers published between 2022 and 2025,written in English,that proposed or evaluated deep learning methods for brain tumor segmentation and/or classification.Excluded were non-open-access publications,books,and non-English articles.A structured search was conducted across Scopus,Google Scholar,Wiley,and Taylor&Francis,with the last search performed in August 2025.Risk of bias was not formally quantified but considered during full-text screening based on dataset diversity,validation methods,and availability of performance metrics.We used narrative synthesis and tabular benchmarking to compare performance metrics(e.g.,accuracy,Dice score)across model types(CNN,Transformer,Hybrid),imaging modalities,and datasets.A total of 49 studies were included(43 journal articles and 6 conference papers).These studies spanned over 9 public datasets(e.g.,BraTS,Figshare,REMBRANDT,MOLAB)and utilized a range of imaging modalities,predominantly MRI.Hybrid models,especially ResViT and UNetFormer,consistently achieved high performance,with classification accuracy exceeding 98%and segmentation Dice scores above 0.90 across multiple studies.Transformers and hybrid architectures showed increasing adoption post2023.Many studies lacked external validation and were evaluated only on a few benchmark datasets,raising concerns about generalizability and dataset bias.Few studies addressed clinical interpretability or uncertainty quantification.Despite promising results,particularly for hybrid deep learning models,widespread clinical adoption remains limited due to lack of validation,interpretability concerns,and real-world deployment barriers.展开更多
Bamei pigs,an indigenous Chinese breed,yield meat with a delectable flavor and boast higher carcass fat content compared to commercial breeds,making them a rich food source for humans.However,the differences in lipid ...Bamei pigs,an indigenous Chinese breed,yield meat with a delectable flavor and boast higher carcass fat content compared to commercial breeds,making them a rich food source for humans.However,the differences in lipid and nutrient components between the adipose tissue of Bamei pigs and commercial pigs are still unclear.The study employed UPLC-MS/MS to quantify the composition of lipids and metabolites in the backfat of both Bamei and Large White pigs.A total of 428 lipids and 193 metabolites were significantly different between the 2 groups.Specifically,Bamei pig backfat exhibited altered levels of various lipids and metabolites that may potentially contribute to nutritional and flavor differences,including unsaturated triglycerides,free fatty acids,medium-chain triglycerides,essential amino acids,vitamins and antioxidants,while maintaining reduced cholesterol levels.Furthermore,we delved into the molecular mechanisms underlying these nutritional differences by analyzing significantly different 431 m RNAs and 865 proteins and integrating the regulatory network of protein-metabolite-lipid pathway.Importantly,in the pyruvate metabolic pathway of Bamei pigs,the bioprocess of lactate production was inhibited but the acetyl-Co A production was activated,suggesting the possibility that energy allocation favors the biogenesis of lipid precursors.These findings may contribute to guiding industrial food producers in enhancing the quality of lard at the genetic and molecular levels.展开更多
Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of kn...Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of knowledge about the underlying modes of action and optimal treatment modalities,a thorough translational investigation of noninvasive brain stimulation in preclinical animal models is urgently needed.Thus,we reviewed the current literature on the mechanistic underpinnings of noninvasive brain stimulation in models of central nervous system impairment,with a particular emphasis on traumatic brain injury and stroke.Due to the lack of translational models in most noninvasive brain stimulation techniques proposed,we found this review to the most relevant techniques used in humans,i.e.,transcranial magnetic stimulation and transcranial direct current stimulation.We searched the literature in Pub Med,encompassing the MEDLINE and PMC databases,for studies published between January 1,2020 and September 30,2024.Thirty-five studies were eligible.Transcranial magnetic stimulation and transcranial direct current stimulation demonstrated distinct strengths in augmenting rehabilitation post-stroke and traumatic brain injury,with emerging mechanistic evidence.Overall,we identified neuronal,inflammatory,microvascular,and apoptotic pathways highlighted in the literature.This review also highlights a lack of translational surrogate parameters to bridge the gap between preclinical findings and their clinical translation.展开更多
AIM:To investigate the effects of different light intensities and various mydriatic and miotic drugs on pupil accommodation in guinea pigs.METHODS:Forty-two-week-old guinea pigs were randomly divided into four groups ...AIM:To investigate the effects of different light intensities and various mydriatic and miotic drugs on pupil accommodation in guinea pigs.METHODS:Forty-two-week-old guinea pigs were randomly divided into four groups to assess pupillary responses under varying light intensities(100,250,500 lx)and pharmacological interventions(1%atropine,1%cyclopentolate,1%tropicamide,or 2%pilocarpine).Baseline pupil size and eccentricity were recorded using a non-contact Python-based imaging system integrating edge detection and pixel-to-distance conversion.Direct illumination effects were measured at sequential time points,followed by drug administration and longitudinal tracking of pupillary changes.The protocol was repeated at 12wk of age for developmental comparisons.Postexperiment,enucleated eyes were analyzed to evaluate in vitro vs in vivo differences.RESULTS:Significant age-dependent differences in pupil dynamics were observed.Both 2-and 12-week-old guinea pigs exhibited marked pupil constriction under direct illumination(P<0.001),with decreased eccentricity post-constriction(P<0.001).Indirect illumination caused inconsistent pupil size changes(2-week:P=0.68;12-week:P=0.49).Pharmacologically,atropine,cyclopentolate,and tropicamide induced pupil dilation(P<0.001),whereas pilocarpine caused constriction(P<0.001).All drug groups showed reduced eccentricity(P<0.001).In vivo/in vitro comparisons revealed significant structural differences.CONCLUSION:This study investigates pupillary responses in developing guinea pigs,revealing a direct pupillary light reflex(PLR)with light intensity-dependent responses,while indirect PLR was undetectable.The differential effects of muscarinic modulators on pupillary responses underscore the critical role of cholinergic signaling in ocular accommodation,with age-related variations in sensitivity.Additionally,a novel non-contact measurement methodology achieved a precision of 0.01 mm for pupillary quantification,enhancing accuracy in ocular studies.展开更多
Background The objective of this study was to investigate the impacts of different dietary soybean meal(SBM)levels on jejunal immunity in nursery pigs at different days post-weaning.Methods Forty-eight pigs(6.2±0...Background The objective of this study was to investigate the impacts of different dietary soybean meal(SBM)levels on jejunal immunity in nursery pigs at different days post-weaning.Methods Forty-eight pigs(6.2±0.3 kg),weaned at 21 days of age,were assigned to 2 dietary treatments(n=12)in a randomized complete block design and fed for 20 or 42 d in 3 phases(10,10,and 22 d,respectively).The dietary treatments consisted of low and high SBM diets.On d 20 and 42,jejunal mucosa and tissue samples were collected.Treatments were arranged in 2×2 factors with dietary SBM levels(low and high SBM diets)and days post-weaning(20 d and 42 d post-weaning).Results Pigs fed high SBM diets had greater(P<0.05)relative abundance(RA)of jejunal Prevotella,tended to have greater(P=0.091)jejunal IgA,had greater(P<0.05)crypt depth,and tended to have lower(P=0.064)villus height to crypt depth ratio(VH:CD)than pigs fed low SBM diets.Pigs at 20 d post-weaning had greater(P<0.05)RA of jejunal Lactobacillus and had greater(P<0.05)jejunal IL-8 and protein carbonyl than pigs at 42 d post-weaning.Pigs at 20 d post-weaning tended to have greater(P=0.090)jejunal IgG,tended to have lower(P=0.059)jejunal IgA,and had greater(P<0.05)proportion(%)of Ki-67+cells in the jejunal crypt than pigs at 42 d post-weaning.Conclusion Pigs fed high SBM diets showed greater RA of Staphylococcus,a greater immune response,and a decreased VH:CD in the jejunum than pigs fed low SBM diets.Pigs at 20 d post-weaning were more susceptible to jejunal inflammation and intestinal damage than pigs at 42 d post-weaning,but the negative impacts of high SBM diets on jejunal inflammation and intestinal damage were consistent compared to low SBM diets at 20 d and 42 d post-weaning.展开更多
Background:Midlife lifestyle factors,including physical activity,are associated with late-life brain health,yet the role of aerobic exercise on structural brain health in early and mid-adulthood remains poorly underst...Background:Midlife lifestyle factors,including physical activity,are associated with late-life brain health,yet the role of aerobic exercise on structural brain health in early and mid-adulthood remains poorly understood.This study aimed to examine the effect of aerobic exercise on structural brain age and to explore potential mediators.Methods:In a single-blind,12-month randomized clinical trial,130 healthy participants aged 26-58 years were randomized into a moderate-to-vigorous intensity aerobic exercise group or a usual-care control group.The exercise group attended two supervised 60-min sessions per week in a laboratory setting plus engaged in home-based exercise to achieve 150 min of exercise per week.Brain-predicted age difference(brain-PAD)and cardiorespiratory fitness(CRF)were assessed at baseline and 12 months.Both intention-to-treat(ITT)and completers analyses(including participants who completed post-intervention assessments)were performed.Results:The 130 participants(67.7%female)had an age of 41.28±9.93 years(mean±SD).At baseline,higher CRF(peak oxygen uptake,VO_(2peak))was associated with smaller brain-PAD(β=-0.309,p=0.012).After the intervention,the exercise group showed a decrease in brainPAD(estimated mean difference(EMD)=-0.60;95%confidence interval(95%CI):-1.15 to-0.04;p=0.034)compared to the control group(EMD=0.35;95%CI:-0.21 to 0.92;p=0.217);time×group interaction(between-group difference(BGD)=-0.95;95%CI:-1.72 to-0.17;p=0.019).VO2peak improved in the exercise group(EMD=1.60;95%CI:0.29-2.90;p=0.017)compared to the control group(EMD=-0.78;95%CI:-2.17 to 0.60;p=0.265);time×group interaction(BGD=2.38;95%CI:0.52-4.25;p=0.015).Body composition,blood pressure,and brain-derived neurotrophic factor levels were unaffected.None of the proposed pathways statistically mediated the effect of exercise on brain-PAD.The results from completers were similar.Conclusion:Engaging in 12 months of moderate-to-vigorous exercise reduced brain-PAD in early-to-midlife adults.The pathways by which these effects occur remain unknown.展开更多
Pericytes are multi-functional mural cells of the central nervous system that cover the capillary endothelial cells. Pericytes play a vital role in nervous system development, significantly influencing the formation, ...Pericytes are multi-functional mural cells of the central nervous system that cover the capillary endothelial cells. Pericytes play a vital role in nervous system development, significantly influencing the formation, maturation, and maintenance of the central nervous system. An expanding body of studies has revealed that pericytes establish carefully regulated interactions with oligodendrocytes, microglia, and astrocytes. These communications govern numerous critical brain processes, including angiogenesis, neurovascular unit homeostasis, blood–brain barrier integrity, cerebral blood flow regulation, and immune response initiation. Glial cells and pericytes participate in dynamic and reciprocal interactions, with each influencing and adjusting the functionality of the other. Pericytes have the ability to control astrocyte polarization, trigger differentiation of oligodendrocyte precursor cells, and initiate immunological responses in microglia. Various neurological disorders that compromise the integrity of the blood–brain barrier can disrupt these communications, impair waste clearance, and hinder cerebral blood circulation, contributing to neuroinflammation. In the context of neurodegeneration, these disruptions exacerbate pathological processes, such as neuronal damage, synaptic dysfunction, and impaired tissue repair. This article explores the complex interactions between pericytes and various glial cells in both healthy and pathological states of the central nervous system. It highlights their essential roles in neurovascular function and disease progression, providing important insights that may enhance our understanding of the molecular mechanisms underlying these interactions and guide potential therapeutic strategies for neurodegenerative disorders in future research.展开更多
Background:Excessive use of inorganic trace minerals(ITMs)in swine production leads to high fecal mineral excretion and environmental risks,while most studies on organic trace minerals(OTMs)focus on single elements,wi...Background:Excessive use of inorganic trace minerals(ITMs)in swine production leads to high fecal mineral excretion and environmental risks,while most studies on organic trace minerals(OTMs)focus on single elements,with limited data on the synergistic effects and molecular mechanisms of combined OTMs(Fe,Cu,Mn,Zn)in growing-finishing pigs.Methods:This study aimed to investigate the effects of graded levels of micromineral proteinates(combined OTMs)on growth performance,mineral metabolism,and mRNA expression of mineral regulatory proteins.A total of 360 crossbred Duroc×Landrace×Large White pigs(initial body weight 47.1±4.8 kg)were randomly assigned to 6 dietary treatments:basal diet without microminerals(CON),basal diet with ITMs at commercially recommended levels(IT),and basal diets with 15%(OT 15%),25%(OT 25%),35%(OT 35%)commercially recommended levels(CRL)of combined micromineral proteinates.After a 70-day feeding trial,samples were analyzed using ICP-OES,ELISA,and RT-qPCR.Results:Results showed that reduced levels(15-35%CRL)of micromineral proteinates did not significantly affect average daily gain,average daily feed intake,or feed conversion ratio(gain-to-feed ratio)compared to IT(P>0.05),but significantly increased plasma Cu(1.73-1.83μg/mL)and Zn(1.72-1.97μg/mL)concentrations(P<0.05)and elevated activities of Cu/Zn-superoxide dismutase(32.9-35.9 U/L)and manganese superoxide dismutase(20.5-24.1 U/L)compared to CON(P<0.05),with no significant differences from IT(P>0.05).Fecal excretion of Fe,Cu,Mn,and Zn was significantly reduced by 35-50%in OT 15%-OT 35%groups compared to IT(P<0.05).OT 25%group exhibited the highest apparent absorptivity of Fe(38.5%),Cu(27.8%),and Zn(42.4%)(P<0.05),which was associated with significantly regulated mRNA expression of mineral regulatory proteins:upregulated DMT1,FPN1,ZIP4,and MT1A in the duodenum,and modulated HAMP,ATP7B,ZIP14,and ZnT1 in the liver(P<0.05).Conclusion:In conclusion,dietary supplementation with 25%CRL or less of combined micromineral proteinates can fully meet the nutritional needs of growing-finishing pigs,improve mineral absorptivity,and reduce fecal mineral excretion by regulating intestinal and hepatic mineral transport and homeostatic proteins,providing a sustainable alternative to high-dose ITMs.展开更多
BACKGROUND Major depressive disorder(MDD)and obesity(OB)are bidirectionally comorbid conditions with common neurobiological underpinnings.However,the neurocognitive mechanisms of their comorbidity remain poorly unders...BACKGROUND Major depressive disorder(MDD)and obesity(OB)are bidirectionally comorbid conditions with common neurobiological underpinnings.However,the neurocognitive mechanisms of their comorbidity remain poorly understood.AIM To examine regional abnormalities in spontaneous brain activity among patients with MDD-OB comorbidity.METHODS This study adopted a regional homogeneity(ReHo)analysis of resting-state functional magnetic resonance imaging.The study included 149 hospital patients divided into four groups:Patients experiencing their first episode of drug-naive MDD with OB,patients with MDD without OB,and age-and sex-matched healthy individuals with and without OB.Whole-brain ReHo analysis was conducted using SPM12 software and RESTplus toolkits,with group comparisons via ANOVA and post-hoc tests.Correlations between ReHo values and behavioral measures were examined.RESULTS ANOVA revealed significant whole-brain ReHo differences among the four groups in four key regions:The left middle temporal gyrus(MTG.L),right cuneus,left precuneus,and left thalamus.Post-hoc analyses confirmed pairwise differences between all groups across these regions(P<0.05).OB was associated with ReHo alterations in the MTG.L,right cuneus,and left thalamus,whereas abnormalities in the precuneus suggested synergistic pathological mechanisms between MDD and OB.Statistically significant correlations were found between the drive and fun-seeking dimensions of the behavioral activation system,as well as behavioral inhibition and the corresponding ReHo values.CONCLUSION Our findings provide novel evidence for the neuroadaptive mechanisms underlying the MDD-OB comorbidity.Further validation could lead to personalized interventions targeting MTG.L hyperactivity and targeting healthy food cues.展开更多
Background:Early detection of harmful brain activity in critically ill patients using electroencephalography(EEG)is vital for timely and effective clinical intervention.Automating EEG analysis with deep learning techn...Background:Early detection of harmful brain activity in critically ill patients using electroencephalography(EEG)is vital for timely and effective clinical intervention.Automating EEG analysis with deep learning techniques holds significant promise for enhancing diagnostic efficiency and accuracy.Methods:We implemented EfficientNetB2,which leverages convolutional neural networks with a novel Temporal Squeeze-and-Excitation module to capture temporal EEG features,and WaveNet,a sequential model designed to effectively model temporal dependencies in EEG data using dilated causal convolutions and temporal self-attention.Both models were trained and evaluated using a publicly available EEG dataset,with performance assessed via 4-fold cross-validation and a step-wise learning rate reduction strategy.Results:Our results demonstrate a significant reduction in training loss from 0.6459 to 0.3055 and validation loss from 0.9602 to 0.5719 over six epochs.Consistent improvements were observed across cross-validation folds,highlighting the robustness of the models.Additionally,ensemble learning of the two architectures further enhanced classification performance.Conclusion:This comparative analysis sheds light on the strengths and limitations of EfficientNetB2 and WaveNet for automated harmful brain activity detection in EEG signals.The findings contribute to the advancement of reliable and efficient deep learning models,paving the way for their clinical application in managing critically ill patients.展开更多
Avian cognitive abilities rival those of primates.These capacities have been linked to high pallial neuronal density and prefrontal cortex-like dorsal ventricular ridge(DVR)circuitry.Although the DVR is now recognized...Avian cognitive abilities rival those of primates.These capacities have been linked to high pallial neuronal density and prefrontal cortex-like dorsal ventricular ridge(DVR)circuitry.Although the DVR is now recognized as a pallial structure homologous to the mammalian cortex,its morphological basis remains unclear.Here,we combine Nissl staining,Golgi-Cox labeling,and 3D reconstruction to map neuronal morphology across five telencephalic regions in the Rock Pigeon(Columba livia).From 64 fully reconstructed neurons,we quantified dendritic field area,total dendritic length,branching architecture,and radial arbor organization.DVR neurons showed the largest dendritic fields and the highest branching complexity.Single-nucleus transcriptomic data further revealed that the Nidopallium Caudolaterale(NCL),the core DVR subregion,expresses a neuronmorphogenesis gene module whose activity correlates with dendritic field size.Together,these results identify a molecular and morphological signature of DVR neurons and highlight the computational significance of Nidopallium Caudolaterale.This work provides an integrated comparison of telencephalic neuronal morphology and gene expression in birds.展开更多
The brain's functions are governed by molecular metabolic networks.However,due to the sophisticated spatial organization and diverse activities of the brain,characterizing both the minute and large-scale metabolic...The brain's functions are governed by molecular metabolic networks.However,due to the sophisticated spatial organization and diverse activities of the brain,characterizing both the minute and large-scale metabolic activity across the entire brain and its numerous micro-regions remains incredibly challenging.Here,we offer a high-definition spatially resolved metabolomics technique to better understand the metabolic specialization and interconnection throughout the mouse brain using improved ambient mass spectrometry imaging.This method allows for the simultaneous mapping of thousands of metabolites at a 30 μm spatial resolution across the mouse brain,ranging from structural lipids to functional neurotransmitters.This approach effectively reveals the distribution patterns of delicate microregions and their distinctive metabolic characteristics.Using an integrated database,we annotated 259 metabolites,demonstrating that the metabolome and metabolic pathways are unique to each brain microregion.The distribution of metabolites,closely linked to functionally connected brain regions and their interactions,offers profound insights into the complexity of chemical processes and their roles in brain function.An initial dataset for future metabolomics research might be obtained from the high-definition mouse brain's spatial metabolome atlas.展开更多
In the countryside of east Zhejiang Province,a quiet village has hit a home run.Xujiadai,once a place known for pig farming and environmental pollution,is drawing visitors from across China with a sport still uncommon...In the countryside of east Zhejiang Province,a quiet village has hit a home run.Xujiadai,once a place known for pig farming and environmental pollution,is drawing visitors from across China with a sport still uncommon in the country:baseball.展开更多
In recent years,development of strategies to treat central nervous system(CNS) diseases has attracted extensive attention.A major obstacle in this field is the blood-brain barrier(BBB),which significantly limits the e...In recent years,development of strategies to treat central nervous system(CNS) diseases has attracted extensive attention.A major obstacle in this field is the blood-brain barrier(BBB),which significantly limits the efficient delivery of therapeutic agents to the brain and hinders the treatment of CNS diseases.Overcoming the restrictive nature of the BBB has thus emerged as a key objective in CNS drug development.Nanomaterials have garnered growing interest due to their unique physicochemical properties and potential to traverse the BBB,enabling targeted drug delivery to brain tissue and improving therapeutic efficacy.In this review,we present current insights into the structure and function of the BBB and highlight a range of nanomaterial-based strategies for BBB penetration,including receptor-mediated transport(RMT),adsorptive-mediated transcytosis,reversible BBB disruption,and intranasal administration.Finally,we summarize recent advances in enhancing BBB permeability for CNS therapeutics and discuss persisting challenges,offering perspectives for future research in this field.展开更多
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.
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 the National Natural Science Foundation of China(62522119 and 62372358)the Beijing Natural Science Foundation(7242267)+2 种基金the Beijing Scholars Program([2015]160)the Natural Science Basic Research Program of Shaanxi(2023-JC-QN-0719)the Guangdong Basic and Applied Basic Research Foundation(2022A1515110453)。
文摘Background:Brain volume measurement serves as a critical approach for assessing brain health status.Considering the close biological connection between the eyes and brain,this study aims to investigate the feasibility of estimating brain volume through retinal fundus imaging integrated with clinical metadata,and to offer a cost-effective approach for assessing brain health.Methods:Based on clinical information,retinal fundus images,and neuroimaging data derived from a multicenter,population-based cohort study,the Kai Luan Study,we proposed a cross-modal correlation representation(CMCR)network to elucidate the intricate co-degenerative relationships between the eyes and brain for 755 subjects.Specifically,individual clinical information,which has been followed up for as long as 12 years,was encoded as a prompt to enhance the accuracy of brain volume estimation.Independent internal validation and external validation were performed to assess the robustness of the proposed model.Root mean square error(RMSE),peak signal-tonoise ratio(PSNR),and structural similarity index measure(SSIM)metrics were employed to quantitatively evaluate the quality of synthetic brain images derived from retinal imaging data.Results:The proposed framework yielded average RMSE,PSNR,and SSIM values of 98.23,35.78 d B,and 0.64,respectively,which significantly outperformed 5 other methods:multi-channel Variational Autoencoder(mcVAE),Pixelto-Pixel(Pixel2pixel),transformer-based U-Net(Trans UNet),multi-scale transformer network(MT-Net),and residual vision transformer(ResViT).The two-(2D)and three-dimensional(3D)visualization results showed that the shape and texture of the synthetic brain images generated by the proposed method most closely resembled those of actual brain images.Thus,the CMCR framework accurately captured the latent structural correlations between the fundus and the brain.The average difference between predicted and actual brain volumes was 61.36 cm~3,with a relative error of 4.54%.When all of the clinical information(including age and sex,daily habits,cardiovascular factors,metabolic factors,and inflammatory factors)was encoded,the difference was decreased to 53.89 cm~3,with a relative error of 3.98%.Based on the synthesized brain magnetic resonance images from retinal fundus images,the volumes of brain tissues could be estimated with high accuracy.Conclusion:This study provides an innovative,accurate,and cost-effective approach to characterize brain health status through readily accessible retinal fundus images.
文摘Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated with increased levels of circulato ry pro-inflammatory marke rs up to 1 year postTBI(Eagle et al.,2023).
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.
文摘This systematic review aims to comprehensively examine and compare deep learning methods for brain tumor segmentation and classification using MRI and other imaging modalities,focusing on recent trends from 2022 to 2025.The primary objective is to evaluate methodological advancements,model performance,dataset usage,and existing challenges in developing clinically robust AI systems.We included peer-reviewed journal articles and highimpact conference papers published between 2022 and 2025,written in English,that proposed or evaluated deep learning methods for brain tumor segmentation and/or classification.Excluded were non-open-access publications,books,and non-English articles.A structured search was conducted across Scopus,Google Scholar,Wiley,and Taylor&Francis,with the last search performed in August 2025.Risk of bias was not formally quantified but considered during full-text screening based on dataset diversity,validation methods,and availability of performance metrics.We used narrative synthesis and tabular benchmarking to compare performance metrics(e.g.,accuracy,Dice score)across model types(CNN,Transformer,Hybrid),imaging modalities,and datasets.A total of 49 studies were included(43 journal articles and 6 conference papers).These studies spanned over 9 public datasets(e.g.,BraTS,Figshare,REMBRANDT,MOLAB)and utilized a range of imaging modalities,predominantly MRI.Hybrid models,especially ResViT and UNetFormer,consistently achieved high performance,with classification accuracy exceeding 98%and segmentation Dice scores above 0.90 across multiple studies.Transformers and hybrid architectures showed increasing adoption post2023.Many studies lacked external validation and were evaluated only on a few benchmark datasets,raising concerns about generalizability and dataset bias.Few studies addressed clinical interpretability or uncertainty quantification.Despite promising results,particularly for hybrid deep learning models,widespread clinical adoption remains limited due to lack of validation,interpretability concerns,and real-world deployment barriers.
基金supported by the National Key Research and Development Program of China(2021YFF1000602)the National Natural Science Foundations(32202642)the earmarked fund for CARS-35-PIG.
文摘Bamei pigs,an indigenous Chinese breed,yield meat with a delectable flavor and boast higher carcass fat content compared to commercial breeds,making them a rich food source for humans.However,the differences in lipid and nutrient components between the adipose tissue of Bamei pigs and commercial pigs are still unclear.The study employed UPLC-MS/MS to quantify the composition of lipids and metabolites in the backfat of both Bamei and Large White pigs.A total of 428 lipids and 193 metabolites were significantly different between the 2 groups.Specifically,Bamei pig backfat exhibited altered levels of various lipids and metabolites that may potentially contribute to nutritional and flavor differences,including unsaturated triglycerides,free fatty acids,medium-chain triglycerides,essential amino acids,vitamins and antioxidants,while maintaining reduced cholesterol levels.Furthermore,we delved into the molecular mechanisms underlying these nutritional differences by analyzing significantly different 431 m RNAs and 865 proteins and integrating the regulatory network of protein-metabolite-lipid pathway.Importantly,in the pyruvate metabolic pathway of Bamei pigs,the bioprocess of lactate production was inhibited but the acetyl-Co A production was activated,suggesting the possibility that energy allocation favors the biogenesis of lipid precursors.These findings may contribute to guiding industrial food producers in enhancing the quality of lard at the genetic and molecular levels.
基金funded by the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation):project ID 431549029-SFB 1451the Marga-und-Walter-Boll-Stiftung(#210-10-15)(to MAR)a stipend from the'Gerok Program'(Faculty of Medicine,University of Cologne,Germany)。
文摘Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of knowledge about the underlying modes of action and optimal treatment modalities,a thorough translational investigation of noninvasive brain stimulation in preclinical animal models is urgently needed.Thus,we reviewed the current literature on the mechanistic underpinnings of noninvasive brain stimulation in models of central nervous system impairment,with a particular emphasis on traumatic brain injury and stroke.Due to the lack of translational models in most noninvasive brain stimulation techniques proposed,we found this review to the most relevant techniques used in humans,i.e.,transcranial magnetic stimulation and transcranial direct current stimulation.We searched the literature in Pub Med,encompassing the MEDLINE and PMC databases,for studies published between January 1,2020 and September 30,2024.Thirty-five studies were eligible.Transcranial magnetic stimulation and transcranial direct current stimulation demonstrated distinct strengths in augmenting rehabilitation post-stroke and traumatic brain injury,with emerging mechanistic evidence.Overall,we identified neuronal,inflammatory,microvascular,and apoptotic pathways highlighted in the literature.This review also highlights a lack of translational surrogate parameters to bridge the gap between preclinical findings and their clinical translation.
文摘AIM:To investigate the effects of different light intensities and various mydriatic and miotic drugs on pupil accommodation in guinea pigs.METHODS:Forty-two-week-old guinea pigs were randomly divided into four groups to assess pupillary responses under varying light intensities(100,250,500 lx)and pharmacological interventions(1%atropine,1%cyclopentolate,1%tropicamide,or 2%pilocarpine).Baseline pupil size and eccentricity were recorded using a non-contact Python-based imaging system integrating edge detection and pixel-to-distance conversion.Direct illumination effects were measured at sequential time points,followed by drug administration and longitudinal tracking of pupillary changes.The protocol was repeated at 12wk of age for developmental comparisons.Postexperiment,enucleated eyes were analyzed to evaluate in vitro vs in vivo differences.RESULTS:Significant age-dependent differences in pupil dynamics were observed.Both 2-and 12-week-old guinea pigs exhibited marked pupil constriction under direct illumination(P<0.001),with decreased eccentricity post-constriction(P<0.001).Indirect illumination caused inconsistent pupil size changes(2-week:P=0.68;12-week:P=0.49).Pharmacologically,atropine,cyclopentolate,and tropicamide induced pupil dilation(P<0.001),whereas pilocarpine caused constriction(P<0.001).All drug groups showed reduced eccentricity(P<0.001).In vivo/in vitro comparisons revealed significant structural differences.CONCLUSION:This study investigates pupillary responses in developing guinea pigs,revealing a direct pupillary light reflex(PLR)with light intensity-dependent responses,while indirect PLR was undetectable.The differential effects of muscarinic modulators on pupillary responses underscore the critical role of cholinergic signaling in ocular accommodation,with age-related variations in sensitivity.Additionally,a novel non-contact measurement methodology achieved a precision of 0.01 mm for pupillary quantification,enhancing accuracy in ocular studies.
文摘Background The objective of this study was to investigate the impacts of different dietary soybean meal(SBM)levels on jejunal immunity in nursery pigs at different days post-weaning.Methods Forty-eight pigs(6.2±0.3 kg),weaned at 21 days of age,were assigned to 2 dietary treatments(n=12)in a randomized complete block design and fed for 20 or 42 d in 3 phases(10,10,and 22 d,respectively).The dietary treatments consisted of low and high SBM diets.On d 20 and 42,jejunal mucosa and tissue samples were collected.Treatments were arranged in 2×2 factors with dietary SBM levels(low and high SBM diets)and days post-weaning(20 d and 42 d post-weaning).Results Pigs fed high SBM diets had greater(P<0.05)relative abundance(RA)of jejunal Prevotella,tended to have greater(P=0.091)jejunal IgA,had greater(P<0.05)crypt depth,and tended to have lower(P=0.064)villus height to crypt depth ratio(VH:CD)than pigs fed low SBM diets.Pigs at 20 d post-weaning had greater(P<0.05)RA of jejunal Lactobacillus and had greater(P<0.05)jejunal IL-8 and protein carbonyl than pigs at 42 d post-weaning.Pigs at 20 d post-weaning tended to have greater(P=0.090)jejunal IgG,tended to have lower(P=0.059)jejunal IgA,and had greater(P<0.05)proportion(%)of Ki-67+cells in the jejunal crypt than pigs at 42 d post-weaning.Conclusion Pigs fed high SBM diets showed greater RA of Staphylococcus,a greater immune response,and a decreased VH:CD in the jejunum than pigs fed low SBM diets.Pigs at 20 d post-weaning were more susceptible to jejunal inflammation and intestinal damage than pigs at 42 d post-weaning,but the negative impacts of high SBM diets on jejunal inflammation and intestinal damage were consistent compared to low SBM diets at 20 d and 42 d post-weaning.
基金funded by the National Institutes of Health and the National Heart,Lung,and Blood Institute(P01HL040962)。
文摘Background:Midlife lifestyle factors,including physical activity,are associated with late-life brain health,yet the role of aerobic exercise on structural brain health in early and mid-adulthood remains poorly understood.This study aimed to examine the effect of aerobic exercise on structural brain age and to explore potential mediators.Methods:In a single-blind,12-month randomized clinical trial,130 healthy participants aged 26-58 years were randomized into a moderate-to-vigorous intensity aerobic exercise group or a usual-care control group.The exercise group attended two supervised 60-min sessions per week in a laboratory setting plus engaged in home-based exercise to achieve 150 min of exercise per week.Brain-predicted age difference(brain-PAD)and cardiorespiratory fitness(CRF)were assessed at baseline and 12 months.Both intention-to-treat(ITT)and completers analyses(including participants who completed post-intervention assessments)were performed.Results:The 130 participants(67.7%female)had an age of 41.28±9.93 years(mean±SD).At baseline,higher CRF(peak oxygen uptake,VO_(2peak))was associated with smaller brain-PAD(β=-0.309,p=0.012).After the intervention,the exercise group showed a decrease in brainPAD(estimated mean difference(EMD)=-0.60;95%confidence interval(95%CI):-1.15 to-0.04;p=0.034)compared to the control group(EMD=0.35;95%CI:-0.21 to 0.92;p=0.217);time×group interaction(between-group difference(BGD)=-0.95;95%CI:-1.72 to-0.17;p=0.019).VO2peak improved in the exercise group(EMD=1.60;95%CI:0.29-2.90;p=0.017)compared to the control group(EMD=-0.78;95%CI:-2.17 to 0.60;p=0.265);time×group interaction(BGD=2.38;95%CI:0.52-4.25;p=0.015).Body composition,blood pressure,and brain-derived neurotrophic factor levels were unaffected.None of the proposed pathways statistically mediated the effect of exercise on brain-PAD.The results from completers were similar.Conclusion:Engaging in 12 months of moderate-to-vigorous exercise reduced brain-PAD in early-to-midlife adults.The pathways by which these effects occur remain unknown.
文摘Pericytes are multi-functional mural cells of the central nervous system that cover the capillary endothelial cells. Pericytes play a vital role in nervous system development, significantly influencing the formation, maturation, and maintenance of the central nervous system. An expanding body of studies has revealed that pericytes establish carefully regulated interactions with oligodendrocytes, microglia, and astrocytes. These communications govern numerous critical brain processes, including angiogenesis, neurovascular unit homeostasis, blood–brain barrier integrity, cerebral blood flow regulation, and immune response initiation. Glial cells and pericytes participate in dynamic and reciprocal interactions, with each influencing and adjusting the functionality of the other. Pericytes have the ability to control astrocyte polarization, trigger differentiation of oligodendrocyte precursor cells, and initiate immunological responses in microglia. Various neurological disorders that compromise the integrity of the blood–brain barrier can disrupt these communications, impair waste clearance, and hinder cerebral blood circulation, contributing to neuroinflammation. In the context of neurodegeneration, these disruptions exacerbate pathological processes, such as neuronal damage, synaptic dysfunction, and impaired tissue repair. This article explores the complex interactions between pericytes and various glial cells in both healthy and pathological states of the central nervous system. It highlights their essential roles in neurovascular function and disease progression, providing important insights that may enhance our understanding of the molecular mechanisms underlying these interactions and guide potential therapeutic strategies for neurodegenerative disorders in future research.
基金financially supported by the Hainan Province Science and Technology Special Fund(Grant no:ZDYF2024XDNY187).
文摘Background:Excessive use of inorganic trace minerals(ITMs)in swine production leads to high fecal mineral excretion and environmental risks,while most studies on organic trace minerals(OTMs)focus on single elements,with limited data on the synergistic effects and molecular mechanisms of combined OTMs(Fe,Cu,Mn,Zn)in growing-finishing pigs.Methods:This study aimed to investigate the effects of graded levels of micromineral proteinates(combined OTMs)on growth performance,mineral metabolism,and mRNA expression of mineral regulatory proteins.A total of 360 crossbred Duroc×Landrace×Large White pigs(initial body weight 47.1±4.8 kg)were randomly assigned to 6 dietary treatments:basal diet without microminerals(CON),basal diet with ITMs at commercially recommended levels(IT),and basal diets with 15%(OT 15%),25%(OT 25%),35%(OT 35%)commercially recommended levels(CRL)of combined micromineral proteinates.After a 70-day feeding trial,samples were analyzed using ICP-OES,ELISA,and RT-qPCR.Results:Results showed that reduced levels(15-35%CRL)of micromineral proteinates did not significantly affect average daily gain,average daily feed intake,or feed conversion ratio(gain-to-feed ratio)compared to IT(P>0.05),but significantly increased plasma Cu(1.73-1.83μg/mL)and Zn(1.72-1.97μg/mL)concentrations(P<0.05)and elevated activities of Cu/Zn-superoxide dismutase(32.9-35.9 U/L)and manganese superoxide dismutase(20.5-24.1 U/L)compared to CON(P<0.05),with no significant differences from IT(P>0.05).Fecal excretion of Fe,Cu,Mn,and Zn was significantly reduced by 35-50%in OT 15%-OT 35%groups compared to IT(P<0.05).OT 25%group exhibited the highest apparent absorptivity of Fe(38.5%),Cu(27.8%),and Zn(42.4%)(P<0.05),which was associated with significantly regulated mRNA expression of mineral regulatory proteins:upregulated DMT1,FPN1,ZIP4,and MT1A in the duodenum,and modulated HAMP,ATP7B,ZIP14,and ZnT1 in the liver(P<0.05).Conclusion:In conclusion,dietary supplementation with 25%CRL or less of combined micromineral proteinates can fully meet the nutritional needs of growing-finishing pigs,improve mineral absorptivity,and reduce fecal mineral excretion by regulating intestinal and hepatic mineral transport and homeostatic proteins,providing a sustainable alternative to high-dose ITMs.
基金Supported by Provincial Key Research Project of Henan Province,No.232102310081.
文摘BACKGROUND Major depressive disorder(MDD)and obesity(OB)are bidirectionally comorbid conditions with common neurobiological underpinnings.However,the neurocognitive mechanisms of their comorbidity remain poorly understood.AIM To examine regional abnormalities in spontaneous brain activity among patients with MDD-OB comorbidity.METHODS This study adopted a regional homogeneity(ReHo)analysis of resting-state functional magnetic resonance imaging.The study included 149 hospital patients divided into four groups:Patients experiencing their first episode of drug-naive MDD with OB,patients with MDD without OB,and age-and sex-matched healthy individuals with and without OB.Whole-brain ReHo analysis was conducted using SPM12 software and RESTplus toolkits,with group comparisons via ANOVA and post-hoc tests.Correlations between ReHo values and behavioral measures were examined.RESULTS ANOVA revealed significant whole-brain ReHo differences among the four groups in four key regions:The left middle temporal gyrus(MTG.L),right cuneus,left precuneus,and left thalamus.Post-hoc analyses confirmed pairwise differences between all groups across these regions(P<0.05).OB was associated with ReHo alterations in the MTG.L,right cuneus,and left thalamus,whereas abnormalities in the precuneus suggested synergistic pathological mechanisms between MDD and OB.Statistically significant correlations were found between the drive and fun-seeking dimensions of the behavioral activation system,as well as behavioral inhibition and the corresponding ReHo values.CONCLUSION Our findings provide novel evidence for the neuroadaptive mechanisms underlying the MDD-OB comorbidity.Further validation could lead to personalized interventions targeting MTG.L hyperactivity and targeting healthy food cues.
文摘Background:Early detection of harmful brain activity in critically ill patients using electroencephalography(EEG)is vital for timely and effective clinical intervention.Automating EEG analysis with deep learning techniques holds significant promise for enhancing diagnostic efficiency and accuracy.Methods:We implemented EfficientNetB2,which leverages convolutional neural networks with a novel Temporal Squeeze-and-Excitation module to capture temporal EEG features,and WaveNet,a sequential model designed to effectively model temporal dependencies in EEG data using dilated causal convolutions and temporal self-attention.Both models were trained and evaluated using a publicly available EEG dataset,with performance assessed via 4-fold cross-validation and a step-wise learning rate reduction strategy.Results:Our results demonstrate a significant reduction in training loss from 0.6459 to 0.3055 and validation loss from 0.9602 to 0.5719 over six epochs.Consistent improvements were observed across cross-validation folds,highlighting the robustness of the models.Additionally,ensemble learning of the two architectures further enhanced classification performance.Conclusion:This comparative analysis sheds light on the strengths and limitations of EfficientNetB2 and WaveNet for automated harmful brain activity detection in EEG signals.The findings contribute to the advancement of reliable and efficient deep learning models,paving the way for their clinical application in managing critically ill patients.
基金supported by the National Natural Science Foundation of China(Grant Nos.32170642 and 32370682)。
文摘Avian cognitive abilities rival those of primates.These capacities have been linked to high pallial neuronal density and prefrontal cortex-like dorsal ventricular ridge(DVR)circuitry.Although the DVR is now recognized as a pallial structure homologous to the mammalian cortex,its morphological basis remains unclear.Here,we combine Nissl staining,Golgi-Cox labeling,and 3D reconstruction to map neuronal morphology across five telencephalic regions in the Rock Pigeon(Columba livia).From 64 fully reconstructed neurons,we quantified dendritic field area,total dendritic length,branching architecture,and radial arbor organization.DVR neurons showed the largest dendritic fields and the highest branching complexity.Single-nucleus transcriptomic data further revealed that the Nidopallium Caudolaterale(NCL),the core DVR subregion,expresses a neuronmorphogenesis gene module whose activity correlates with dendritic field size.Together,these results identify a molecular and morphological signature of DVR neurons and highlight the computational significance of Nidopallium Caudolaterale.This work provides an integrated comparison of telencephalic neuronal morphology and gene expression in birds.
基金financial support from the National Natural Science Foundation of China (Nos.82473887 and 21927808)the Scientific and Technological Innovation Program of Shanghai (No.23DZ2202500)the CAMS Innovation Fund for Medical Sciences (No.2021-1-I2M-026)。
文摘The brain's functions are governed by molecular metabolic networks.However,due to the sophisticated spatial organization and diverse activities of the brain,characterizing both the minute and large-scale metabolic activity across the entire brain and its numerous micro-regions remains incredibly challenging.Here,we offer a high-definition spatially resolved metabolomics technique to better understand the metabolic specialization and interconnection throughout the mouse brain using improved ambient mass spectrometry imaging.This method allows for the simultaneous mapping of thousands of metabolites at a 30 μm spatial resolution across the mouse brain,ranging from structural lipids to functional neurotransmitters.This approach effectively reveals the distribution patterns of delicate microregions and their distinctive metabolic characteristics.Using an integrated database,we annotated 259 metabolites,demonstrating that the metabolome and metabolic pathways are unique to each brain microregion.The distribution of metabolites,closely linked to functionally connected brain regions and their interactions,offers profound insights into the complexity of chemical processes and their roles in brain function.An initial dataset for future metabolomics research might be obtained from the high-definition mouse brain's spatial metabolome atlas.
文摘In the countryside of east Zhejiang Province,a quiet village has hit a home run.Xujiadai,once a place known for pig farming and environmental pollution,is drawing visitors from across China with a sport still uncommon in the country:baseball.
基金funded by the Fundamental Research Funds for the Central Universities (No.2242022R42012)。
文摘In recent years,development of strategies to treat central nervous system(CNS) diseases has attracted extensive attention.A major obstacle in this field is the blood-brain barrier(BBB),which significantly limits the efficient delivery of therapeutic agents to the brain and hinders the treatment of CNS diseases.Overcoming the restrictive nature of the BBB has thus emerged as a key objective in CNS drug development.Nanomaterials have garnered growing interest due to their unique physicochemical properties and potential to traverse the BBB,enabling targeted drug delivery to brain tissue and improving therapeutic efficacy.In this review,we present current insights into the structure and function of the BBB and highlight a range of nanomaterial-based strategies for BBB penetration,including receptor-mediated transport(RMT),adsorptive-mediated transcytosis,reversible BBB disruption,and intranasal administration.Finally,we summarize recent advances in enhancing BBB permeability for CNS therapeutics and discuss persisting challenges,offering perspectives for future research in this field.
