Gauss radial basis functions(GRBF)are frequently employed in data fitting and machine learning.Their linear independence property can theoretically guarantee the avoidance of data redundancy.In this paper,one of the m...Gauss radial basis functions(GRBF)are frequently employed in data fitting and machine learning.Their linear independence property can theoretically guarantee the avoidance of data redundancy.In this paper,one of the main contributions is proving this property using linear algebra instead of profound knowledge.This makes it easy to read and understand this fundamental fact.The proof of linear independence of a set of Gauss functions relies on the constructing method for one-dimensional space and on the deducing method for higher dimensions.Additionally,under the condition of preserving the same moments between the original function and interpolating function,both the interpolating existence and uniqueness are proven for GRBF in one-dimensional space.The final work demonstrates the application of the GRBF method to locate lunar olivine.By combining preprocessed data using GRBF with the removing envelope curve method,a program is created to find the position of lunar olivine based on spectrum data,and the numerical experiment shows that it is an effective scheme.展开更多
Functional gastrointestinal disorders(FGIDs),including irritable bowel syndrome(IBS),functional dyspepsia(FD),and gastroesophageal reflux disease(GERD),present persistent diagnostic and therapeutic challenges due to s...Functional gastrointestinal disorders(FGIDs),including irritable bowel syndrome(IBS),functional dyspepsia(FD),and gastroesophageal reflux disease(GERD),present persistent diagnostic and therapeutic challenges due to symptom heterogeneity and the absence of reliable biomarkers.Artificial intelligence(AI)enables the integration of multimodal data to enhance FGID management through precision diagnostics and preventive healthcare.This minireview summarizes recent advancements in AI applications for FGIDs,highlighting progress in diagnostic accuracy,subtype classification,personalized interventions,and preventive strategies inspired by the traditional Chinese medicine concept of“treating the undiseased”.Machine learning and deep learning algorithms have demonstrated value in improving IBS diagnosis,refining FD neuro-gastrointestinal subtyping,and screening for GERD-related complications.Moreover,AI supports dietary,psychological,and integrative medicine-based interventions to improve patient adherence and quality of life.Nonetheless,key challenges remain,including data heterogeneity,limited model interpretability,and the need for robust clinical validation.Future directions emphasize interdisciplinary collaboration,the development of multimodal and explainable AI models,and the creation of patientcentered platforms to facilitate a shift from reactive treatment to proactive prevention.This review provides a systematic framework to guide the clinical application and theoretical innovation of AI in FGIDs.展开更多
Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in s...Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.展开更多
Five-valued Boolean functions play an important role in the design of symmetric cryptography.While the design and properties of single-output almost optimal five-valued spectra Boolean functions have been extensively ...Five-valued Boolean functions play an important role in the design of symmetric cryptography.While the design and properties of single-output almost optimal five-valued spectra Boolean functions have been extensively studied over the past few decades,there has been limited research on the construction of almost optimal five-valued spectra vectorial Boolean functions.In this paper,we present a construction method for even-variable 2-output almost optimal five-valued spectra balanced Boolean functions,whose Walsh spectra values belong to the set{0,±2^(n/2),±2^(n/2+1)},at the same time,we discuss the existence of sufficient conditions in the construction.Additionally,this paper presents a novel construction method for balanced single-output Boolean functions with even variables featuring a special five-valued spectral structure,whose Walsh spectra values are constrained to the set{0,±2^(n/2),±3·2^(n/2)}.These functions provide new canonical examples for the study of Boolean function spectral theory.展开更多
BACKGROUND Suicide constitutes the second leading cause of death among adolescents globally and represents a critical public health concern.The neural mechanisms underlying suicidal behavior in adolescents with major ...BACKGROUND Suicide constitutes the second leading cause of death among adolescents globally and represents a critical public health concern.The neural mechanisms underlying suicidal behavior in adolescents with major depressive disorder(MDD)remain poorly understood.Aberrant resting-state functional connectivity(rsFC)in the amygdala,a key region implicated in emotional regulation and threat detection,is strongly implicated in depression and suicidal behavior.AIM To investigate rsFC alterations between amygdala subregions and whole-brain networks in adolescent patients with depression and suicide attempts.METHODS Resting-state functional magnetic resonance imaging data were acquired from 32 adolescents with MDD and suicide attempts(sMDD)group,33 adolescents with MDD but without suicide attempts(nsMDD)group,and 34 demographically matched healthy control(HC)group,with the lateral and medial amygdala(MeA)defined as regions of interest.The rsFC patterns of amygdala subregions were compared across the three groups,and associations between aberrant rsFC values and clinical symptom severity scores were examined.RESULTS Compared with the nsMDD group,the sMDD group exhibited reduced rsFC between the right lateral amygdala(LA)and the right inferior occipital gyrus as well as the left middle occipital gyrus.Compared with the HC group,the abnormal brain regions of rsFC in the sMDD group and nsMDD group involve the parahippocampal gyrus(PHG)and fusiform gyrus.In the sMDD group,right MeA and right temporal pole:Superior temporal gyrus rsFC value negatively correlated with the Rosenberg Self-Esteem Scale scores(r=-0.409,P=0.025),while left LA and right PHG rsFC value positively correlated with the Adolescent Self-Rating Life Events Checklist interpersonal relationship scores(r=0.372,P=0.043).CONCLUSION Aberrant rsFC changes between amygdala subregions and these brain regions provide novel insights into the underlying neural mechanisms of suicide attempts in adolescents with MDD.展开更多
BACKGROUND An echocardiogram is an essential tool in the evaluation of potential kidney transplant recipients(KTRs).Despite cardiac clearance,potential KTRs still have structural and functional abnormalities.Identifyi...BACKGROUND An echocardiogram is an essential tool in the evaluation of potential kidney transplant recipients(KTRs).Despite cardiac clearance,potential KTRs still have structural and functional abnormalities.Identifying the prevalence of these abnormalities and understanding their predictors is vital for optimizing pretransplant risk stratification and improving post-transplant outcomes.AIM To determine the prevalence of left ventricular hypertrophy(LVH),left ventricular systolic dysfunction(LVSD),diastolic dysfunction(DD),pulmonary hypertension(PH),and their predictors,and to assess their impact on graft function in pre-transplant candidates.METHODS The study included all successful transplant candidates older than 14 who had a baseline echocardiogram.Binary logistic regression models were constructed to identify factors associated with LVH,LVSD,DD,and PH.RESULTS Out of 259 patients,LVH was present in 64%(166),12%(31)had LVSD,27.5%(71)had DD,and 66(25.5%)had PH.Independent predictors of LVH included male gender[odds ratio(OR):2.51;95%CI:1.17-5.41 P=0.02],PH(OR=2.07;95%CI:1.11-3.86;P=0.02),DD(OR:2.47;95%CI:1.29-4.73;P=0.006),and dyslipidemia(OR=1.94;95%CI:1.07-3.53;P=0.03).Predictors for LVSD included patients with DD(OR=3.3,95%CI:1.41-7.81;P=0.006)and a family history of coronary artery disease(OR=4.50,95%CI:1.33-15.20;P=0.015).Peritoneal dialysis was an independent predictor for DD(OR=10.03;95%CI:1.71-58.94,P=0.011).The presence of LVH(OR=3.32,95%CI:1.05-10.55,P=0.04)and mild to moderate or moderate to severe mitral regurgitation(OR=4.63,95%CI:1.45-14.78,P=0.01)were significant factors associated with PH.These abnormalities had no significant impact on estimated glomerular filtration at discharge,6 months,1 year,or 2 years post-transplant.CONCLUSION Significant echocardiographic abnormalities persist in a potential transplant candidate despite cardiac clearance,although they don’t affect future graft function.Understanding the risk factors associated with these abnormalities may help clinicians address these factors pre-and post-transplant to achieve better outcomes.展开更多
BACKGROUND Dry eye disease(DED)is a multifactorial ocular surface disorder with rising prevalence.It is closely related to systemic health and psychological factors,such as sleep and mood disorders,which significantly...BACKGROUND Dry eye disease(DED)is a multifactorial ocular surface disorder with rising prevalence.It is closely related to systemic health and psychological factors,such as sleep and mood disorders,which significantly impact the quality of life of patients.AIM To explore the correlations between ocular surface function,sleep quality,and anxiety/depression in patients with DED.METHODS This was a cross-sectional investigative study that included 358 patients with DED between January 2022 and January 2025.Ocular surface was assessed using the ocular surface disease index(OSDI),tear film break-up time,fluorescein staining score,and Schirmer I test.The Pittsburgh Sleep Quality Index(PSQI),Self-Rating Anxiety Scale(SAS),and Self-Rating Depression Scale(SDS)were used to evaluate sleep quality and anxiety/depression levels.Correlation and linear regression analyses were used to explore the relationships.RESULTS The mean PSQI score of the patients was 9.94±2.18;the mean SAS score was 47.30±4.90,and the mean SDS score was 50.08±5.52.These suggested a prevalence of sleep and psychological abnormalities.There was a significant correlation between the indicators of ocular surface function(OSDI,tear film break-up time,fluorescein staining,and Schirmer I test)and PSQI,SAS,and SDS scores(P<0.05).Moreover,multiple regression revealed that age≥50 years(β=1.55,P=0.029),PSQI scores(β=0.58,P<0.001),SAS scores(β=0.17,P=0.017),and SDS scores(β=0.15,P=0.019)were independent predictors of the OSDI scores.CONCLUSION Ocular surface function in patients with DED is closely related to sleep quality and anxiety/depression,emphasizing the need for holistic clinical management.展开更多
BACKGROUND The therapeutic role of neurodynamic mobilization in improving lower limb function in patients with mild post-traumatic knee osteoarthritis remains poorly understood.AIM To further elucidate the role of neu...BACKGROUND The therapeutic role of neurodynamic mobilization in improving lower limb function in patients with mild post-traumatic knee osteoarthritis remains poorly understood.AIM To further elucidate the role of neurodynamic mobilization in facilitating knee joint functional recovery.METHODS Thirty-two patients with post-traumatic knee osteoarthritis treated at Chonghua Hospital of Traditional Chinese Medicine(Guilin)from March 2024 to August 2025 were randomly assigned to a control group(n=16)or an intervention group(n=16).Both groups received eight weeks of conventional treatment;and the intervention group additionally underwent neurodynamic mobilization.Outcomes including pain assessed by the visual analogue scale,active range of motion,Lysholm score,stork stand test,single hop test,and Y-balance test were assessed before and after the intervention.RESULTS There were no significant differences between the two groups in baseline characteristics,including gender,age,body mass index,or surgical side(P>0.05).Two-way repeated-measures analysis of variance demonstrated significant time×group interaction effects for the visual analogue scale score(F=13.364,P<0.05),Lysholm knee score(F=20.385,P<0.05),stork stand test(F=103.756,P<0.05),and Y-balance test score(F=8.089,P<0.05).CONCLUSION Neurodynamic mobilization effectively reduces pain,improves knee function,and enhances lower limb balance in patients with mild post-traumatic knee osteoarthritis.展开更多
AIM:To investigate the effects of shortening the duration of silicone oil tamponade on retinal structure and function in patients undergoing silicone oil removal(SOR)after surgery for primary rhegmatogenous retinal de...AIM:To investigate the effects of shortening the duration of silicone oil tamponade on retinal structure and function in patients undergoing silicone oil removal(SOR)after surgery for primary rhegmatogenous retinal detachment(RRD).METHODS:A total of 58 eligible patients were enrolled and randomly assigned to two groups based on tamponade duration:the short-term group(30-45d)and the conventional group(≥90d).Comprehensive evaluations were performed before and after SOR,including slitlamp examination,best-corrected visual acuity(BCVA)measurement,intraocular pressure(IOP)testing,optical coherence tomography(OCT),optical coherence tomography angiography(OCTA),microperimetry,electroretinography(ERG),and visual evoked potential(VEP)assessment.RESULTS:A total of 33 patients(23 males and 10 females;33 eyes)were enrolled in the short-term SO tamponade group with mean age of 52.45±9.35y,and 25 patients(15 males and 10 females;25 eyes)were enrolled in the conventional SO tamponade group with mean age of 50.80±12.06y.Compared with the conventional group,the short-term silicone oil tamponade group had a significantly lower incidence of silicone oil emulsification and cataract progression,with no significant difference in retinal reattachment success rate.Structurally,short-term tamponade was associated with increased thickness of the retinal ganglion cell layer(RGCL)in the nasal and superior macular regions and improved recovery of superficial retinal vascular density in these areas.Functionally,the shortterm group showed better BCVA and retinal sensitivity both before and 1mo after SOR;additionally,the P100 amplitude in VEP tests was significantly increased in this group.CONCLUSION:Shortening the duration of silicone oil tamponade effectively reduces damage to retinal structure and function without compromising the success rate of retinal reattachment in patients with primary RRD.展开更多
Spinal cord injury(SCI) often results in permanent dysfunction of locomotion,sensation,and autonomic regulation,imposing a substantial burden on both individuals and society(Anjum et al.,2020).SCI has a complex pathop...Spinal cord injury(SCI) often results in permanent dysfunction of locomotion,sensation,and autonomic regulation,imposing a substantial burden on both individuals and society(Anjum et al.,2020).SCI has a complex pathophysiology:an initial primary injury(mechanical trauma,axonal disruption,and hemorrhage) is followed by a progressive secondary injury cascade that involves ischemia,neuronal loss,and inflammation.Given the challenges in achieving regeneration of the injured spinal cord,neuroprotection has been at the forefront of clinical research.展开更多
Exogenous neural stem cell transplantation has become one of the most promising treatment methods for chronic stroke.Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after inju...Exogenous neural stem cell transplantation has become one of the most promising treatment methods for chronic stroke.Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after injury,which limits the ability to observe long-term behavioral recovery.Here,we used a severe stroke rat model with 150 minutes of ischemia,which produced severe behavioral deficiencies that persisted at 12 weeks,to study the therapeutic effect of neural stem cells on neural restoration in chronic stroke.Our study showed that stroke model rats treated with human neural stem cells had long-term sustained recovery of motor function,reduced infarction volume,long-term human neural stem cell survival,and improved local inflammatory environment and angiogenesis.We also demonstrated that transplanted human neural stem cells differentiated into mature neurons in vivo,formed stable functional synaptic connections with host neurons,and exhibited the electrophysiological properties of functional mature neurons,indicating that they replaced the damaged host neurons.The findings showed that human fetal-derived neural stem cells had long-term effects for neurological recovery in a model of severe stroke,which suggests that human neural stem cells-based therapy may be effective for repairing damaged neural circuits in stroke patients.展开更多
Amphibious vehicles are more prone to attitude instability compared to ships,making it crucial to develop effective methods for monitoring instability risks.However,large inclination events,which can lead to instabili...Amphibious vehicles are more prone to attitude instability compared to ships,making it crucial to develop effective methods for monitoring instability risks.However,large inclination events,which can lead to instability,occur frequently in both experimental and operational data.This infrequency causes events to be overlooked by existing prediction models,which lack the precision to accurately predict inclination attitudes in amphibious vehicles.To address this gap in predicting attitudes near extreme inclination points,this study introduces a novel loss function,termed generalized extreme value loss.Subsequently,a deep learning model for improved waterborne attitude prediction,termed iInformer,was developed using a Transformer-based approach.During the embedding phase,a text prototype is created based on the vehicle’s operation log data is constructed to help the model better understand the vehicle’s operating environment.Data segmentation techniques are used to highlight local data variation features.Furthermore,to mitigate issues related to poor convergence and slow training speeds caused by the extreme value loss function,a teacher forcing mechanism is integrated into the model,enhancing its convergence capabilities.Experimental results validate the effectiveness of the proposed method,demonstrating its ability to handle data imbalance challenges.Specifically,the model achieves over a 60%improvement in root mean square error under extreme value conditions,with significant improvements observed across additional metrics.展开更多
The organization of biological neuronal networks into functional modules has intrigued scientists and inspired engineers to develop artificial systems.These networks are characterized by two key properties.First,they ...The organization of biological neuronal networks into functional modules has intrigued scientists and inspired engineers to develop artificial systems.These networks are characterized by two key properties.First,they exhibit dense interconnectivity(Braitenburg and Schüz,1998;Campagnola et al.,2022).The strength and probability of connectivity depend on cell type,inter-neuronal distance,and species.Still,every cortical neuron receives input from thousands of other neurons while transmitting output to a similar number of neurons.Second,communication between neurons occurs primarily via chemical or electrical synapses.展开更多
Cell function has a tight relationship with cell architecture.Distribution of proteins to the correct compartment is one of the functions of the traffic pathway through the Golgi apparatus.The others are to ensure pro...Cell function has a tight relationship with cell architecture.Distribution of proteins to the correct compartment is one of the functions of the traffic pathway through the Golgi apparatus.The others are to ensure proper protein folding,the addition of post-translational modifications,and delivering to intracellular and extracellular destinations.Astrocytes are fundamental homeostatic cells,controlling multiple aspects of the central nervous system physiology,such as ion balance,nutrients,blood flow,neurotransmitters,and responses to insults.Astrocytes are polarized cells,and,such as neurons,extensively use the secretory pathway for secreting factors and exposing functional receptors,channels,and transporters on the plasma membrane.In this review,we will underline the importance of studying the Golgi apparatus and the secretory pathway in astrocytes,based on the possible tight connection between the Golgi apparatus and astrocytes’homeostatic function.Given the topic of this review,we will provide examples mostly about the Golgi apparatus structure,function,localization,and its involvement in astrocytes’homeostatic response,with an insight into congenital glycosylation disorders,as an example of a potential future field in the study of astrocyte homeostatic failure and Golgi apparatus alteration.展开更多
Invasive as well as non-invasive neurotechnologies conceptualized to interface the central and peripheral nervous system have been probed for the past decades,which refer to electroencephalography,electrocorticography...Invasive as well as non-invasive neurotechnologies conceptualized to interface the central and peripheral nervous system have been probed for the past decades,which refer to electroencephalography,electrocorticography and microelectrode arrays.The challenges of these mentioned approaches are characterized by the bandwidth of the spatiotemporal resolution,which in turn is essential for large-area neuron recordings(Abiri et al.,2019).展开更多
In the words of the late Sir Colin Blakemore,neurologists have historically sought to infer brain functions in a manner akin to to king a hammer to a computeranalyzing localized anatomical lesions caused by trauma,tum...In the words of the late Sir Colin Blakemore,neurologists have historically sought to infer brain functions in a manner akin to to king a hammer to a computeranalyzing localized anatomical lesions caused by trauma,tumors,or strokes,noting deficits,and inferring what functions certain brain regions may be responsible for.This approach exemplifies a deletion heuristic,where the absence of a specific function reveals insights about the underlying structures or mechanisms responsible for it.By observing what is lost when a particular brain region is damaged,throughout the history of the field,neurologists have pieced together the intricate relationship between anatomy and function.展开更多
The mature central nervous system(CNS,composed of the brain,spinal cord,olfactory and optic nerves)is unable to regenerate spontaneously after an insult,both in the cases of neurodegenerative diseases(for example Alzh...The mature central nervous system(CNS,composed of the brain,spinal cord,olfactory and optic nerves)is unable to regenerate spontaneously after an insult,both in the cases of neurodegenerative diseases(for example Alzheimer's or Parkinson's disease)or traumatic injuries(such as spinal cord lesions).In the last 20 years,the field has made significant progress in unlocking axon regrowth.展开更多
Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological s...Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological stimuli.These functional states can be visualized using a combination of multi-omics techniques(e.g.,gene and protein expression,posttranslational modifications,mRNA profiling,and metabolomics),and,in the case of homeostatic microglia,are largely defined by the global(e.g.,genetic variations,organism’s age,sex,circadian rhythms,and gut microbiota)as well as local(specific area of the brain,immediate microglial surrounding,neuron-glia interactions and synaptic density/activity)signals(Paolicelli et al.,2022).While phenomics(i.e.,ultrastructural microglial morphology and motility)is also one of the key microglial state-defining parameters,it is known that cells with similar morphology can belong to different functional states.展开更多
Spontaneous recovery frequently proves maladaptive or insufficient because the plasticity of the injured adult mammalian central nervous system is limited.This limited plasticity serves as a primary barrier to functio...Spontaneous recovery frequently proves maladaptive or insufficient because the plasticity of the injured adult mammalian central nervous system is limited.This limited plasticity serves as a primary barrier to functional recovery after brain injury.Neuromodulation technologies represent one of the fastest-growing fields in medicine.These techniques utilize electricity,magnetism,sound,and light to restore or optimize brain functions by promoting reorganization or long-term changes that support functional recovery in patients with brain injury.Therefore,this review aims to provide a comprehensive overview of the effects and underlying mechanisms of neuromodulation technologies in supporting motor function recovery after brain injury.Many of these technologies are widely used in clinical practice and show significant improvements in motor function across various types of brain injury.However,studies report negative findings,potentially due to variations in stimulation protocols,differences in observation periods,and the severity of functional impairments among participants across different clinical trials.Additionally,we observed that different neuromodulation techniques share remarkably similar mechanisms,including promoting neuroplasticity,enhancing neurotrophic factor release,improving cerebral blood flow,suppressing neuroinflammation,and providing neuroprotection.Finally,considering the advantages and disadvantages of various neuromodulation techniques,we propose that future development should focus on closed-loop neural circuit stimulation,personalized treatment,interdisciplinary collaboration,and precision stimulation.展开更多
Diabetic retinopathy is a prominent cause of blindness in adults,with early retinal ganglion cell loss contributing to visual dysfunction or blindness.In the brain,defects inγ-aminobutyric acid synaptic transmission ...Diabetic retinopathy is a prominent cause of blindness in adults,with early retinal ganglion cell loss contributing to visual dysfunction or blindness.In the brain,defects inγ-aminobutyric acid synaptic transmission are associated with pathophysiological and neurodegenerative disorders,whereas glucagon-like peptide-1 has demonstrated neuroprotective effects.However,it is not yet clear whether diabetes causes alterations in inhibitory input to retinal ganglion cells and whether and how glucagon-like peptide-1 protects against neurodegeneration in the diabetic retina through regulating inhibitory synaptic transmission to retinal ganglion cells.In the present study,we used the patch-clamp technique to recordγ-aminobutyric acid subtype A receptor-mediated miniature inhibitory postsynaptic currents in retinal ganglion cells from streptozotocin-induced diabetes model rats.We found that early diabetes(4 weeks of hyperglycemia)decreased the frequency of GABAergic miniature inhibitory postsynaptic currents in retinal ganglion cells without altering their amplitude,suggesting a reduction in the spontaneous release ofγ-aminobutyric acid to retinal ganglion cells.Topical administration of glucagon-like peptide-1 eyedrops over a period of 2 weeks effectively countered the hyperglycemia-induced downregulation of GABAergic mIPSC frequency,subsequently enhancing the survival of retinal ganglion cells.Concurrently,the protective effects of glucagon-like peptide-1 on retinal ganglion cells in diabetic rats were eliminated by topical administration of exendin-9-39,a specific glucagon-like peptide-1 receptor antagonist,or SR95531,a specific antagonist of theγ-aminobutyric acid subtype A receptor.Furthermore,extracellular perfusion of glucagon-like peptide-1 was found to elevate the frequencies of GABAergic miniature inhibitory postsynaptic currents in both ON-and OFF-type retinal ganglion cells.This elevation was shown to be mediated by activation of the phosphatidylinositol-phospholipase C/inositol 1,4,5-trisphosphate receptor/Ca2+/protein kinase C signaling pathway downstream of glucagon-like peptide-1 receptor activation.Moreover,multielectrode array recordings revealed that glucagon-like peptide-1 functionally augmented the photoresponses of ON-type retinal ganglion cells.Optomotor response tests demonstrated that diabetic rats exhibited reductions in visual acuity and contrast sensitivity that were significantly ameliorated by topical administration of glucagon-like peptide-1.These results suggest that glucagon-like peptide-1 facilitates the release ofγ-aminobutyric acid onto retinal ganglion cells through the activation of glucagon-like peptide-1 receptor,leading to the de-excitation of retinal ganglion cell circuits and the inhibition of excitotoxic processes associated with diabetic retinopathy.Collectively,our findings indicate that theγ-aminobutyric acid system has potential as a therapeutic target for mitigating early-stage diabetic retinopathy.Furthermore,the topical administration of glucagon-like peptide-1 eyedrops represents a non-invasive and effective treatment approach for managing early-stage diabetic retinopathy.展开更多
基金Supported by the National Basic Research Program of China(2012CB025904)Zhengzhou Shengda University of Economics,Business and Management(SD-YB2025085)。
文摘Gauss radial basis functions(GRBF)are frequently employed in data fitting and machine learning.Their linear independence property can theoretically guarantee the avoidance of data redundancy.In this paper,one of the main contributions is proving this property using linear algebra instead of profound knowledge.This makes it easy to read and understand this fundamental fact.The proof of linear independence of a set of Gauss functions relies on the constructing method for one-dimensional space and on the deducing method for higher dimensions.Additionally,under the condition of preserving the same moments between the original function and interpolating function,both the interpolating existence and uniqueness are proven for GRBF in one-dimensional space.The final work demonstrates the application of the GRBF method to locate lunar olivine.By combining preprocessed data using GRBF with the removing envelope curve method,a program is created to find the position of lunar olivine based on spectrum data,and the numerical experiment shows that it is an effective scheme.
基金Supported by The Natural Science Foundation of China,No.82374292the Plans for Major Provincial Science and Technology Projects of Anhui Province,No.202303a07020003the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine,No.ZYYCXTD-C-202401.
文摘Functional gastrointestinal disorders(FGIDs),including irritable bowel syndrome(IBS),functional dyspepsia(FD),and gastroesophageal reflux disease(GERD),present persistent diagnostic and therapeutic challenges due to symptom heterogeneity and the absence of reliable biomarkers.Artificial intelligence(AI)enables the integration of multimodal data to enhance FGID management through precision diagnostics and preventive healthcare.This minireview summarizes recent advancements in AI applications for FGIDs,highlighting progress in diagnostic accuracy,subtype classification,personalized interventions,and preventive strategies inspired by the traditional Chinese medicine concept of“treating the undiseased”.Machine learning and deep learning algorithms have demonstrated value in improving IBS diagnosis,refining FD neuro-gastrointestinal subtyping,and screening for GERD-related complications.Moreover,AI supports dietary,psychological,and integrative medicine-based interventions to improve patient adherence and quality of life.Nonetheless,key challenges remain,including data heterogeneity,limited model interpretability,and the need for robust clinical validation.Future directions emphasize interdisciplinary collaboration,the development of multimodal and explainable AI models,and the creation of patientcentered platforms to facilitate a shift from reactive treatment to proactive prevention.This review provides a systematic framework to guide the clinical application and theoretical innovation of AI in FGIDs.
基金supported by the National Natural Science Foundation of China,Nos.82072165 and 82272256(both to XM)the Key Project of Xiangyang Central Hospital,No.2023YZ03(to RM)。
文摘Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.
基金National Natural Science Foundation of China(62272360)。
文摘Five-valued Boolean functions play an important role in the design of symmetric cryptography.While the design and properties of single-output almost optimal five-valued spectra Boolean functions have been extensively studied over the past few decades,there has been limited research on the construction of almost optimal five-valued spectra vectorial Boolean functions.In this paper,we present a construction method for even-variable 2-output almost optimal five-valued spectra balanced Boolean functions,whose Walsh spectra values belong to the set{0,±2^(n/2),±2^(n/2+1)},at the same time,we discuss the existence of sufficient conditions in the construction.Additionally,this paper presents a novel construction method for balanced single-output Boolean functions with even variables featuring a special five-valued spectral structure,whose Walsh spectra values are constrained to the set{0,±2^(n/2),±3·2^(n/2)}.These functions provide new canonical examples for the study of Boolean function spectral theory.
基金Supported by Suzhou Clinical Medical Center for Mood Disorders,No.Szlcyxzx202109Suzhou Key Laboratory,No.SZS2024016Multicenter Clinical Research on Major Diseases in Suzhou,No.DZXYJ202413.
文摘BACKGROUND Suicide constitutes the second leading cause of death among adolescents globally and represents a critical public health concern.The neural mechanisms underlying suicidal behavior in adolescents with major depressive disorder(MDD)remain poorly understood.Aberrant resting-state functional connectivity(rsFC)in the amygdala,a key region implicated in emotional regulation and threat detection,is strongly implicated in depression and suicidal behavior.AIM To investigate rsFC alterations between amygdala subregions and whole-brain networks in adolescent patients with depression and suicide attempts.METHODS Resting-state functional magnetic resonance imaging data were acquired from 32 adolescents with MDD and suicide attempts(sMDD)group,33 adolescents with MDD but without suicide attempts(nsMDD)group,and 34 demographically matched healthy control(HC)group,with the lateral and medial amygdala(MeA)defined as regions of interest.The rsFC patterns of amygdala subregions were compared across the three groups,and associations between aberrant rsFC values and clinical symptom severity scores were examined.RESULTS Compared with the nsMDD group,the sMDD group exhibited reduced rsFC between the right lateral amygdala(LA)and the right inferior occipital gyrus as well as the left middle occipital gyrus.Compared with the HC group,the abnormal brain regions of rsFC in the sMDD group and nsMDD group involve the parahippocampal gyrus(PHG)and fusiform gyrus.In the sMDD group,right MeA and right temporal pole:Superior temporal gyrus rsFC value negatively correlated with the Rosenberg Self-Esteem Scale scores(r=-0.409,P=0.025),while left LA and right PHG rsFC value positively correlated with the Adolescent Self-Rating Life Events Checklist interpersonal relationship scores(r=0.372,P=0.043).CONCLUSION Aberrant rsFC changes between amygdala subregions and these brain regions provide novel insights into the underlying neural mechanisms of suicide attempts in adolescents with MDD.
文摘BACKGROUND An echocardiogram is an essential tool in the evaluation of potential kidney transplant recipients(KTRs).Despite cardiac clearance,potential KTRs still have structural and functional abnormalities.Identifying the prevalence of these abnormalities and understanding their predictors is vital for optimizing pretransplant risk stratification and improving post-transplant outcomes.AIM To determine the prevalence of left ventricular hypertrophy(LVH),left ventricular systolic dysfunction(LVSD),diastolic dysfunction(DD),pulmonary hypertension(PH),and their predictors,and to assess their impact on graft function in pre-transplant candidates.METHODS The study included all successful transplant candidates older than 14 who had a baseline echocardiogram.Binary logistic regression models were constructed to identify factors associated with LVH,LVSD,DD,and PH.RESULTS Out of 259 patients,LVH was present in 64%(166),12%(31)had LVSD,27.5%(71)had DD,and 66(25.5%)had PH.Independent predictors of LVH included male gender[odds ratio(OR):2.51;95%CI:1.17-5.41 P=0.02],PH(OR=2.07;95%CI:1.11-3.86;P=0.02),DD(OR:2.47;95%CI:1.29-4.73;P=0.006),and dyslipidemia(OR=1.94;95%CI:1.07-3.53;P=0.03).Predictors for LVSD included patients with DD(OR=3.3,95%CI:1.41-7.81;P=0.006)and a family history of coronary artery disease(OR=4.50,95%CI:1.33-15.20;P=0.015).Peritoneal dialysis was an independent predictor for DD(OR=10.03;95%CI:1.71-58.94,P=0.011).The presence of LVH(OR=3.32,95%CI:1.05-10.55,P=0.04)and mild to moderate or moderate to severe mitral regurgitation(OR=4.63,95%CI:1.45-14.78,P=0.01)were significant factors associated with PH.These abnormalities had no significant impact on estimated glomerular filtration at discharge,6 months,1 year,or 2 years post-transplant.CONCLUSION Significant echocardiographic abnormalities persist in a potential transplant candidate despite cardiac clearance,although they don’t affect future graft function.Understanding the risk factors associated with these abnormalities may help clinicians address these factors pre-and post-transplant to achieve better outcomes.
文摘BACKGROUND Dry eye disease(DED)is a multifactorial ocular surface disorder with rising prevalence.It is closely related to systemic health and psychological factors,such as sleep and mood disorders,which significantly impact the quality of life of patients.AIM To explore the correlations between ocular surface function,sleep quality,and anxiety/depression in patients with DED.METHODS This was a cross-sectional investigative study that included 358 patients with DED between January 2022 and January 2025.Ocular surface was assessed using the ocular surface disease index(OSDI),tear film break-up time,fluorescein staining score,and Schirmer I test.The Pittsburgh Sleep Quality Index(PSQI),Self-Rating Anxiety Scale(SAS),and Self-Rating Depression Scale(SDS)were used to evaluate sleep quality and anxiety/depression levels.Correlation and linear regression analyses were used to explore the relationships.RESULTS The mean PSQI score of the patients was 9.94±2.18;the mean SAS score was 47.30±4.90,and the mean SDS score was 50.08±5.52.These suggested a prevalence of sleep and psychological abnormalities.There was a significant correlation between the indicators of ocular surface function(OSDI,tear film break-up time,fluorescein staining,and Schirmer I test)and PSQI,SAS,and SDS scores(P<0.05).Moreover,multiple regression revealed that age≥50 years(β=1.55,P=0.029),PSQI scores(β=0.58,P<0.001),SAS scores(β=0.17,P=0.017),and SDS scores(β=0.15,P=0.019)were independent predictors of the OSDI scores.CONCLUSION Ocular surface function in patients with DED is closely related to sleep quality and anxiety/depression,emphasizing the need for holistic clinical management.
基金Supported by the Central Guided Local Science and Technology Development Fund Project for Science and Technology Innovation Base Construction,No.Guike ZY24212046National Natural Science Foundation of China,No.U22A2092+3 种基金Guangxi Education Science“the 14th Five-Year Plan”2024 Special Project“Research on Steam Education Practice in Rehabilitation Engineering”,No.2024ZJY304the Research Basic Ability Enhancement Program for Young and Middle-aged Teachers of Guangxi,No.2025KY2255the Innovation Project of GUET Graduate Education,No.2025YCXB010Natural Science Research Project of Guilin Life and Health Career Technical College,No.2025GKKY04.
文摘BACKGROUND The therapeutic role of neurodynamic mobilization in improving lower limb function in patients with mild post-traumatic knee osteoarthritis remains poorly understood.AIM To further elucidate the role of neurodynamic mobilization in facilitating knee joint functional recovery.METHODS Thirty-two patients with post-traumatic knee osteoarthritis treated at Chonghua Hospital of Traditional Chinese Medicine(Guilin)from March 2024 to August 2025 were randomly assigned to a control group(n=16)or an intervention group(n=16).Both groups received eight weeks of conventional treatment;and the intervention group additionally underwent neurodynamic mobilization.Outcomes including pain assessed by the visual analogue scale,active range of motion,Lysholm score,stork stand test,single hop test,and Y-balance test were assessed before and after the intervention.RESULTS There were no significant differences between the two groups in baseline characteristics,including gender,age,body mass index,or surgical side(P>0.05).Two-way repeated-measures analysis of variance demonstrated significant time×group interaction effects for the visual analogue scale score(F=13.364,P<0.05),Lysholm knee score(F=20.385,P<0.05),stork stand test(F=103.756,P<0.05),and Y-balance test score(F=8.089,P<0.05).CONCLUSION Neurodynamic mobilization effectively reduces pain,improves knee function,and enhances lower limb balance in patients with mild post-traumatic knee osteoarthritis.
基金Supported by the Key Science&Technology Project of Guangzhou(No.202103000045)the National Natural Science Foundation of China(No.82070972,No.82271093).
文摘AIM:To investigate the effects of shortening the duration of silicone oil tamponade on retinal structure and function in patients undergoing silicone oil removal(SOR)after surgery for primary rhegmatogenous retinal detachment(RRD).METHODS:A total of 58 eligible patients were enrolled and randomly assigned to two groups based on tamponade duration:the short-term group(30-45d)and the conventional group(≥90d).Comprehensive evaluations were performed before and after SOR,including slitlamp examination,best-corrected visual acuity(BCVA)measurement,intraocular pressure(IOP)testing,optical coherence tomography(OCT),optical coherence tomography angiography(OCTA),microperimetry,electroretinography(ERG),and visual evoked potential(VEP)assessment.RESULTS:A total of 33 patients(23 males and 10 females;33 eyes)were enrolled in the short-term SO tamponade group with mean age of 52.45±9.35y,and 25 patients(15 males and 10 females;25 eyes)were enrolled in the conventional SO tamponade group with mean age of 50.80±12.06y.Compared with the conventional group,the short-term silicone oil tamponade group had a significantly lower incidence of silicone oil emulsification and cataract progression,with no significant difference in retinal reattachment success rate.Structurally,short-term tamponade was associated with increased thickness of the retinal ganglion cell layer(RGCL)in the nasal and superior macular regions and improved recovery of superficial retinal vascular density in these areas.Functionally,the shortterm group showed better BCVA and retinal sensitivity both before and 1mo after SOR;additionally,the P100 amplitude in VEP tests was significantly increased in this group.CONCLUSION:Shortening the duration of silicone oil tamponade effectively reduces damage to retinal structure and function without compromising the success rate of retinal reattachment in patients with primary RRD.
文摘Spinal cord injury(SCI) often results in permanent dysfunction of locomotion,sensation,and autonomic regulation,imposing a substantial burden on both individuals and society(Anjum et al.,2020).SCI has a complex pathophysiology:an initial primary injury(mechanical trauma,axonal disruption,and hemorrhage) is followed by a progressive secondary injury cascade that involves ischemia,neuronal loss,and inflammation.Given the challenges in achieving regeneration of the injured spinal cord,neuroprotection has been at the forefront of clinical research.
文摘Exogenous neural stem cell transplantation has become one of the most promising treatment methods for chronic stroke.Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after injury,which limits the ability to observe long-term behavioral recovery.Here,we used a severe stroke rat model with 150 minutes of ischemia,which produced severe behavioral deficiencies that persisted at 12 weeks,to study the therapeutic effect of neural stem cells on neural restoration in chronic stroke.Our study showed that stroke model rats treated with human neural stem cells had long-term sustained recovery of motor function,reduced infarction volume,long-term human neural stem cell survival,and improved local inflammatory environment and angiogenesis.We also demonstrated that transplanted human neural stem cells differentiated into mature neurons in vivo,formed stable functional synaptic connections with host neurons,and exhibited the electrophysiological properties of functional mature neurons,indicating that they replaced the damaged host neurons.The findings showed that human fetal-derived neural stem cells had long-term effects for neurological recovery in a model of severe stroke,which suggests that human neural stem cells-based therapy may be effective for repairing damaged neural circuits in stroke patients.
基金Supported by the National Defense Basic Scientific Research Program of China.
文摘Amphibious vehicles are more prone to attitude instability compared to ships,making it crucial to develop effective methods for monitoring instability risks.However,large inclination events,which can lead to instability,occur frequently in both experimental and operational data.This infrequency causes events to be overlooked by existing prediction models,which lack the precision to accurately predict inclination attitudes in amphibious vehicles.To address this gap in predicting attitudes near extreme inclination points,this study introduces a novel loss function,termed generalized extreme value loss.Subsequently,a deep learning model for improved waterborne attitude prediction,termed iInformer,was developed using a Transformer-based approach.During the embedding phase,a text prototype is created based on the vehicle’s operation log data is constructed to help the model better understand the vehicle’s operating environment.Data segmentation techniques are used to highlight local data variation features.Furthermore,to mitigate issues related to poor convergence and slow training speeds caused by the extreme value loss function,a teacher forcing mechanism is integrated into the model,enhancing its convergence capabilities.Experimental results validate the effectiveness of the proposed method,demonstrating its ability to handle data imbalance challenges.Specifically,the model achieves over a 60%improvement in root mean square error under extreme value conditions,with significant improvements observed across additional metrics.
基金supported in part by the Rosetrees Trust(#CF-2023-I-2_113)by the Israel Ministry of Innovation,Science,and Technology(#7393)(to ES).
文摘The organization of biological neuronal networks into functional modules has intrigued scientists and inspired engineers to develop artificial systems.These networks are characterized by two key properties.First,they exhibit dense interconnectivity(Braitenburg and Schüz,1998;Campagnola et al.,2022).The strength and probability of connectivity depend on cell type,inter-neuronal distance,and species.Still,every cortical neuron receives input from thousands of other neurons while transmitting output to a similar number of neurons.Second,communication between neurons occurs primarily via chemical or electrical synapses.
文摘Cell function has a tight relationship with cell architecture.Distribution of proteins to the correct compartment is one of the functions of the traffic pathway through the Golgi apparatus.The others are to ensure proper protein folding,the addition of post-translational modifications,and delivering to intracellular and extracellular destinations.Astrocytes are fundamental homeostatic cells,controlling multiple aspects of the central nervous system physiology,such as ion balance,nutrients,blood flow,neurotransmitters,and responses to insults.Astrocytes are polarized cells,and,such as neurons,extensively use the secretory pathway for secreting factors and exposing functional receptors,channels,and transporters on the plasma membrane.In this review,we will underline the importance of studying the Golgi apparatus and the secretory pathway in astrocytes,based on the possible tight connection between the Golgi apparatus and astrocytes’homeostatic function.Given the topic of this review,we will provide examples mostly about the Golgi apparatus structure,function,localization,and its involvement in astrocytes’homeostatic response,with an insight into congenital glycosylation disorders,as an example of a potential future field in the study of astrocyte homeostatic failure and Golgi apparatus alteration.
文摘Invasive as well as non-invasive neurotechnologies conceptualized to interface the central and peripheral nervous system have been probed for the past decades,which refer to electroencephalography,electrocorticography and microelectrode arrays.The challenges of these mentioned approaches are characterized by the bandwidth of the spatiotemporal resolution,which in turn is essential for large-area neuron recordings(Abiri et al.,2019).
文摘In the words of the late Sir Colin Blakemore,neurologists have historically sought to infer brain functions in a manner akin to to king a hammer to a computeranalyzing localized anatomical lesions caused by trauma,tumors,or strokes,noting deficits,and inferring what functions certain brain regions may be responsible for.This approach exemplifies a deletion heuristic,where the absence of a specific function reveals insights about the underlying structures or mechanisms responsible for it.By observing what is lost when a particular brain region is damaged,throughout the history of the field,neurologists have pieced together the intricate relationship between anatomy and function.
基金supported by ANR(ANR-21CE16-0008-01)ANR(ANR-21-CE16-0008-02 and ANR-23CE52-0007)+1 种基金UNADEV(A22018CS)(to HN)UNADEV(A22020CS)(to SB)。
文摘The mature central nervous system(CNS,composed of the brain,spinal cord,olfactory and optic nerves)is unable to regenerate spontaneously after an insult,both in the cases of neurodegenerative diseases(for example Alzheimer's or Parkinson's disease)or traumatic injuries(such as spinal cord lesions).In the last 20 years,the field has made significant progress in unlocking axon regrowth.
基金supported by Deutsche Forschungsgemeinschaft,German Research Foundation grant GA 654/13-2 to OG.
文摘Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological stimuli.These functional states can be visualized using a combination of multi-omics techniques(e.g.,gene and protein expression,posttranslational modifications,mRNA profiling,and metabolomics),and,in the case of homeostatic microglia,are largely defined by the global(e.g.,genetic variations,organism’s age,sex,circadian rhythms,and gut microbiota)as well as local(specific area of the brain,immediate microglial surrounding,neuron-glia interactions and synaptic density/activity)signals(Paolicelli et al.,2022).While phenomics(i.e.,ultrastructural microglial morphology and motility)is also one of the key microglial state-defining parameters,it is known that cells with similar morphology can belong to different functional states.
基金supported by the National Natural Science Foundation of China,No.82371399(to YY)the Natural Science Foundation of Jiangsu Province,No.BK20221206(to YY)+1 种基金the Young Elite Scientists Sponsorship Program of Jiangsu Province,No.TJ-2022-028(to YY)the Scientific Research Program of Wuxi Health Commission,No.Z202302(to LY)。
文摘Spontaneous recovery frequently proves maladaptive or insufficient because the plasticity of the injured adult mammalian central nervous system is limited.This limited plasticity serves as a primary barrier to functional recovery after brain injury.Neuromodulation technologies represent one of the fastest-growing fields in medicine.These techniques utilize electricity,magnetism,sound,and light to restore or optimize brain functions by promoting reorganization or long-term changes that support functional recovery in patients with brain injury.Therefore,this review aims to provide a comprehensive overview of the effects and underlying mechanisms of neuromodulation technologies in supporting motor function recovery after brain injury.Many of these technologies are widely used in clinical practice and show significant improvements in motor function across various types of brain injury.However,studies report negative findings,potentially due to variations in stimulation protocols,differences in observation periods,and the severity of functional impairments among participants across different clinical trials.Additionally,we observed that different neuromodulation techniques share remarkably similar mechanisms,including promoting neuroplasticity,enhancing neurotrophic factor release,improving cerebral blood flow,suppressing neuroinflammation,and providing neuroprotection.Finally,considering the advantages and disadvantages of various neuromodulation techniques,we propose that future development should focus on closed-loop neural circuit stimulation,personalized treatment,interdisciplinary collaboration,and precision stimulation.
基金supported by the National Natural Science Foundation of China,Nos.32070989(to YMZ),31872766(to YMZ),81790640(to XLY),and 82070993(to SJW)the grant from Sanming Project of Medicine in Shenzhen,No.SZSM202011015(to XLY)。
文摘Diabetic retinopathy is a prominent cause of blindness in adults,with early retinal ganglion cell loss contributing to visual dysfunction or blindness.In the brain,defects inγ-aminobutyric acid synaptic transmission are associated with pathophysiological and neurodegenerative disorders,whereas glucagon-like peptide-1 has demonstrated neuroprotective effects.However,it is not yet clear whether diabetes causes alterations in inhibitory input to retinal ganglion cells and whether and how glucagon-like peptide-1 protects against neurodegeneration in the diabetic retina through regulating inhibitory synaptic transmission to retinal ganglion cells.In the present study,we used the patch-clamp technique to recordγ-aminobutyric acid subtype A receptor-mediated miniature inhibitory postsynaptic currents in retinal ganglion cells from streptozotocin-induced diabetes model rats.We found that early diabetes(4 weeks of hyperglycemia)decreased the frequency of GABAergic miniature inhibitory postsynaptic currents in retinal ganglion cells without altering their amplitude,suggesting a reduction in the spontaneous release ofγ-aminobutyric acid to retinal ganglion cells.Topical administration of glucagon-like peptide-1 eyedrops over a period of 2 weeks effectively countered the hyperglycemia-induced downregulation of GABAergic mIPSC frequency,subsequently enhancing the survival of retinal ganglion cells.Concurrently,the protective effects of glucagon-like peptide-1 on retinal ganglion cells in diabetic rats were eliminated by topical administration of exendin-9-39,a specific glucagon-like peptide-1 receptor antagonist,or SR95531,a specific antagonist of theγ-aminobutyric acid subtype A receptor.Furthermore,extracellular perfusion of glucagon-like peptide-1 was found to elevate the frequencies of GABAergic miniature inhibitory postsynaptic currents in both ON-and OFF-type retinal ganglion cells.This elevation was shown to be mediated by activation of the phosphatidylinositol-phospholipase C/inositol 1,4,5-trisphosphate receptor/Ca2+/protein kinase C signaling pathway downstream of glucagon-like peptide-1 receptor activation.Moreover,multielectrode array recordings revealed that glucagon-like peptide-1 functionally augmented the photoresponses of ON-type retinal ganglion cells.Optomotor response tests demonstrated that diabetic rats exhibited reductions in visual acuity and contrast sensitivity that were significantly ameliorated by topical administration of glucagon-like peptide-1.These results suggest that glucagon-like peptide-1 facilitates the release ofγ-aminobutyric acid onto retinal ganglion cells through the activation of glucagon-like peptide-1 receptor,leading to the de-excitation of retinal ganglion cell circuits and the inhibition of excitotoxic processes associated with diabetic retinopathy.Collectively,our findings indicate that theγ-aminobutyric acid system has potential as a therapeutic target for mitigating early-stage diabetic retinopathy.Furthermore,the topical administration of glucagon-like peptide-1 eyedrops represents a non-invasive and effective treatment approach for managing early-stage diabetic retinopathy.
