Positive health:An integrated quantitative approach in patients with chronic gastrointestinal and hepato-pancreatico-biliary disorders

BACKGROUND The concept of positive health(PH)supports an integrated approach for patients by taking into account six dimensions of health.This approach is especially relevant for patients with chronic disorders.Chronic gastrointestinal and hepatopancreatico-biliary(GI-HPB)disorders are among the top-6 of the most prevalent chronically affected organ systems.The impact of chronic GI-HPB disorders on individuals may be disproportionally high because:(1)The affected organ system frequently contributes to a malnourished state;and(2)persons with chronic GIHPB disorders are often younger than persons with chronic diseases in other organ systems.AIM To describe and quantify the dimensions of PH in patients with chronic GI-HPB disorders.METHODS Prospective,observational questionnaire study performed between 2019 and 2021 in 235 patients with a chronic GIHPB disorder attending the Outpatient Department of the Maastricht University Medical Center.Validated questionnaires and data from patient files were used to quantify the six dimensions of PH.Internal consistency was tested with McDonald’s Omega.Zero-order Pearson correlations and t-tests were used to assess associations and differences.A P value<0.05 was considered significant.RESULTS The GI-HPB patients scored significantly worse in all dimensions of PH compared to control data or norm scores from the general population.Regarding quality of life,participation and daily functioning,GI-HPB patients scored in the same range as patients with chronic disorders in other organ systems,but depressive symptoms(in 35%)and malnutrition(in 45%)were more frequent in patients with chronic GI-HPB disorders.Intercorrelation scores between the six dimensions were only very weak to weak,forcing us to quantify each domain separately.CONCLUSION All six dimensions of PH are impaired in the GI-HPB patients.Malnutrition and depressive symptoms are more prevalent compared to patients with chronic disorders in other organ systems.

Targeting TrkB–PSD-95 coupling to mitigate neurological disorders

Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and memory.The activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term potentiation.Postsynaptically,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term potentiation.In this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and depression.Treatment with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 isoform.Although TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific functions.Targeting TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

Cognitive impairment in patients with bipolar disorder alone versus those with bipolar disorder comorbid with borderline personality disorder

BACKGROUND Bipolar disorder(BD)is a severe mental illness.BD often coexists with borderline personality disorders,making the condition more complex.AIM To explore the differences in cognitive impairment between patients with BD and those with BD comorbid with borderline personality disorder.METHODS Eighty patients with BD and comorbid borderline personality disorder and 80 patients with BD alone were included in groups A and B,respectively,and 80 healthy volunteers were included as controls.Cognitive function in each group was evaluated using the Chinese version of the repeatable battery for the assess-ment of neuropsychological status(RBANS),the Stroop color-word test,and the Wechsler intelligence scale-revised(WAIS-RC).RESULTS The indices of the RBANS,Stroop color-word test,and WAIS-RC in groups A and B were significantly lower than those of the control group(P<0.05).Group A had significantly longer Stroop color-word test times for single-character,single-color,double-character,and double-color,lower scores of immediate memory,visual breadth,verbal function dimensions and total score of the RBANS,as well as lower scores of verbal IQ,performance IQ,and overall IQ of the WAIS-RC compared with group B(P<0.05).Compared to group B,group A exhibited significantly longer single-character time,single-color time,double-character time,and double-color time in the Stroop color-word test(P<0.05).CONCLUSION The cognitive function of patients with BD complicated with borderline personality disorder is lower than that of patients with BD.

Glyphosate Exposure Associated with Human Neurodegenerative Disorders: A Scoping Review

Chemically engineered agricultural products such as pesticides, insecticides, and herbicides, although used considerably for both industrialized and personal agricultural use, have recently been associated with a number of serious human health disorders. This rapid literature review aims to accumulate and analyze research from the last ten years, focusing specifically on the effects of exposure to glyphosate-based herbicide products such as Roundup as associated with the formation of various neurological disorders. Specifically, this review focuses on laboratory research using animal models or human cell cultures as well as human population-based epidemiological studies. It associates exposure to glyphosate or glyphosate-based products with the formation or exacerbation of neurological disorders such as Parkinson’s disease, Alzheimer’s disease, seizures, and autism spectrum disorder. In addition, it examines the correlation between the gut-brain axis, exposure to glyphosate, and neurodegeneration.

From Signals to Solutions: Exploring Early Detection of Neuropsychiatric and Neurodevelopment Disorders through Biomarkers

In 2013, the percentage of children ranging from 5 to 17 years who reported being diagnosed with autism surged to 1.2% from 0.1% in 1997 [1]. Alongside this increase in the incidence of autism in children, there were findings of a 21% increase in children who displayed behavioral and conduct problems from 2019 to 2020 [2]. Early detection of neuropsychiatric and neurodevelopmental disorders in children is critical for timely intervention and improved long-term outcomes. With early intervention, there is better aptitude to support healthy development and give proper treatment to attain a better quality of life. This paper explores studies aimed at enhancing the early detection of these disorders through the use of biomarkers with the aim of creating a bridge between the worlds of research and clinical practice. The disorders in this paper specifically discussed are Major Depressive Disorder, Bipolar Disorder, and Autism Spectrum Disorder. With this bridge, we can foster collaborations and encourage further advancement in the field of early detection and intervention.

Brain Research on Mental Disorders: A Criticism

Objective: To expose the problems and inherent limitations of neuroscience-based brain research on mental disorders. Method: Discussion of the theory underlying brain research on mental disorders, followed by a systematic evaluation of typical studies. Results: The fundamental problem is that brain researchers fail to differentiate between biological mental disorders in which brain processes cause the disorder (notably schizophrenia, bipolar disorder, and melancholic depression) and learned mental disorders in which brain processes mediate but do not cause the disorder (which is the case with reactive depression, reactive anxiety, OCD, and PTSD). Researchers have been unsuccessful in identifying mechanisms in the brain that cause biological mental disorders, and will never be able to locate the innumerable specific neural connections that mediate learned mental disorders. Moreover, the author’s review of typical studies in this field shows that they have serious problems with theory, measurement, and data analysis, and that their findings cannot be trusted. Conclusions: Neuroscience-based brain research on mental disorders, unlike other neurological research, has been an expensive failure and it is not worth continuing.

Exercise-with-melatonin therapy improves sleep disorder and motor dysfunction in a rat model of ischemic stroke

Exercise-with-melatonin therapy has complementary and synergistic effects on spinal cord injury and Alzheimer's disease,but its effect on stroke is still poorly understood.In this study,we established a rat model of ischemic stroke by occluding the middle cerebral artery for 60 minutes.We treated the rats with exercise and melatonin therapy for 7 consecutive days.Results showed that exercise-with-melatonin therapy significantly prolonged sleep duration in the model rats,increased delta power values,and regularized delta power rhythm.Additionally,exercise-with-melatonin therapy improved coordination,endurance,and grip strength,as well as learning and memory abilities.At the same time,it led to higher hippocampal CA1 neuron activity and postsynaptic density thickness and lower expression of glutamate receptor 2 than did exercise or melatonin therapy alone.These findings suggest that exercise-withmelatonin therapy can alleviate sleep disorder and motor dysfunction by increasing glutamate receptor 2 protein expression and regulating hippocampal CA1 synaptic plasticity.

Mental emotional disorder is a predictor of stroke incidence in adults:Ten year results of the Bogor Cohort Study on Non-Communicable Disease Risk Factors in Indonesia

Objective:To determine the stroke predictors for the 10-year of follow-up in Bogor City,Indonesia.Methods:The prospective study analyzed the data of 4445 stroke-free subjects aged 25 years and above that was part of"the Bogor Cohort Study on Non-Communicable Disease Risk Factors".Data were collected by interview method with structured questionnaires,physical measurements three times a year,and laboratory examination every two years during a 10-year follow-up(2011-2021,without examination in 2020).The incidence of stroke is based on anamnesis results and examination by a neurologist.Other stroke predictor variables include characteristics,biological conditions,and risk behavior.We analysed 4445 stroke-free samples with Cox proportional hazard regression test.Results:During the 10-year observation,stroke incidence was 440 person-years per 100000 population(95%CI 370-530).During the follow-up of ten years,the main predictor of stroke was mental-emotional disorders with HR 4.2(95%CI 2.8-6.3)after adjustment by age,hypertension,obesity,abdominal obesity,and high LDL-cholesterol levels.Conclusions:Mental-emotional disorders are the strongest predictor of stroke incidence.Hence,psychological factors must be controlled in a stroke prevention program.

Next-generation vaccines for substance use disorders

Substance use disorders(SUDs)impact an estimated 300 million people worldwide,significantly impairing both health and social functioning.These disorders are marked by an inability to regulate substance use,despite the harmful consequences.Addiction affects various neurotransmitter systems,including dopamine,serotonin,γ-aminobutyric acid(GABA),and glutamate,each of which plays a role in the reward,stress,and self-control pathways of the brain(Koob&Volkow,2016).While significant advances have been made in neuroscience,our understanding of how these neurotransmitter systems interact and contribute to addiction is still evolving.This knowledge gap represents a significant challenge in the formulation of effective treatments for SUDs.At present,the US Food and Drug Administration(FDA)has approved pharmacological treatments for alcohol,nicotine,and opioid use disorders(Vasiliu,2022);however,no such treatments have been authorized for SUDs in general,or specifically for stimulant use disorders,such as cocaine and methamphetamine addiction.Notably,the FDA has not approved any new drugs for SUD treatment in the past 40 years.

Hybrid treatment of varied orthodontic appliances for a patient with skeletal class II and temporomandibular joint disorders:A case report and review of literature

BACKGROUND The relation between orthodontic treatment and temporomandibular disorders(TMDs)is under debate;the management of TMD during orthodontic treatment has always been a challenge.If TMD symptoms occur during orthodontic treatment,an immediate pause of orthodontic adjustments is recommended;the treatment can resume when the symptoms are managed and stabilized.CASE SUMMARY This case report presents a patient(26-year-old,female)with angle class I,skeletal class II and TMDs.The treatment was a hybrid of clear aligners,fixed appliances and temporary anchorage devices(TADs).After 3 mo resting and treatment on her TMD,the patient’s TMD symptom alleviated,but her anterior occlusion displayed deep overbite.Therefore,the fixed appliances with TAD were used to correct the anterior deep-bite and level maxillary and mandibular deep curves.After the levelling,the patient showed dual bite with centric relation and maximum intercuspation discrepancy on her occlusion.After careful examination of temporomandibular joints(TMJ)position,the stable bite splint and Invisible Mandibular Advancement appliance were used to reconstruct her occlusion.Eventually,the improved facial appearance and relatively stable occlusion were achieved.The 1-year follow-up records showed there was no obvious change in TMJ morphology,and her occlusion was stable.CONCLUSION TMD screening and monitoring is of great clinical importance in the TMD susceptible patients.Hybrid treatment with clear aligners and fixed appliances and TADs is an effective treatment modality for the complex cases.

Application value research of swallowing treatment device combined with swallowing rehabilitation training in the treatment of swallowing disorders after stroke

BACKGROUND Stroke is a common disabling disease,whether it is ischemic stroke or hemorrhagic stroke,both can result in neuronal damage,leading to various manifestations of neurological dysfunction.AIM To explore of the application value of swallowing treatment device combined with swallowing rehabilitation training in the treatment of swallowing disorders after stroke.METHODS This study selected 86 patients with swallowing disorders after stroke admitted to our rehabilitation department from February 2022 to December 2023 as research subjects.They were divided into a control group(n=43)and an observation group(n=43)according to the treatment.The control group received swallowing rehabilitation training,while the observation group received swallowing treatment device in addition to the training.Both groups underwent continuous intervention for two courses of treatment.RESULTS The total effective rate in the observation group(93.02%)was higher than that in the control group(76.74%)(P=0.035).After intervention,the oral transit time,swallowing response time,pharyngeal transit time,and laryngeal closure time decreased in both groups compared to before intervention.In the observation group,the oral transit time,swallowing response time,and pharyngeal transit time were shorter than those in the control group after intervention.However,the laryngeal closure time after intervention in the observation group was compared with that in the control group(P=0.142).After intervention,average amplitude value and duration of the genioglossus muscle group during empty swallowing and swallowing 5 mL of water are reduced compared to before intervention in both groups.After intervention,the scores of the chin-tuck swallowing exercise and the Standardized Swallowing Assessment are both reduced compared to pre-intervention levels in both groups.However,the observation group scores lower than the control group after intervention.Additionally,the Functional Oral Intake Scale scores of both groups are increased after intervention compared to pre-intervention levels,with the observation group scoring higher than the control group after intervention(P<0.001).The cumulative incidence of complications in the observation group is 9.30%,which is lower than the 27.91%in the control group(P=0.027).CONCLUSION The combination of swallowing therapy equipment with swallowing rehabilitation training can improve the muscle movement level of the genioglossus muscle group,enhance swallowing function,and prevent the occurrence of swallowing-related complications after stroke.

Exploring the influences of education,intelligence and income on mental disorders

Background Previous studies have shown that educational attainment(EA),intelligence and income are key factors associated with mental disorders.However,the direct effects of each factor on major mental disorders are unclear.Aims We aimed to evaluate the overall and independent causal effects of the three psychosocial factors on common mental disorders.Methods Using genome-wide association study summary datasets,we performed Mendelian randomisation(MR)and multivariable MR(MVMR)analyses to assess potential associations between the 3 factors(EA,N=766345;household income,N=392422;intelligence,N=146808)and 13 common mental disorders,with sample sizes ranging from 9907 to 807553.Inverse-variance weighting was employed as the main method in the MR analysis.Results Our MR analysis showed that(1)higher EA was a protective factor for eight mental disorders but contributed to anorexia nervosa,obsessive-compulsive disorder(OCD),bipolar disorder(BD)and autism spectrum disorder(ASD);(2)higher intelligence was a protective factor for five mental disorders but a risk factor for OCD and ASD;(3)higher household income protected against 10 mental disorders but confers risk for anorexia nervosa.Our MVMR analysis showed that(1)higher EA was a direct protective factor for attention-deficit/hyperactivity disorder(ADHD)and insomnia but a direct risk factor for schizophrenia,BD and ASD;(2)higher intelligence was a direct protective factor for schizophrenia but a direct risk factor for major depressive disorder(MDD)and ASD;(3)higher income was a direct protective factor for seven mental disorders,including schizophrenia,BD,MDD,ASD,post-traumatic stress disorder,ADHD and anxiety disorder.Conclusions Our study reveals that education,intelligence and income intertwine with each other.For each factor,its independent effects on mental disorders present a more complex picture than its overall effects.

K^(+) channel-mediated retarded maturation of interneurons and its role in neurodevelopmental disorders

De novo mutations in genes encoding K^(+)channels are implicated in many severe neurodevelopmental disorders.Specifically,mutations in KCNA2,encoding the Shaker-type voltage-gated K^(+)channel Kv1.2,and KCNJ2,encoding the inwardly rectifying K^(+)channel Kir2.1,associate with focal and generalized epilepsies,brain atrophy,autism,ataxia and hereditary spastic paraplegia(Syrbe et al.,2015;Masnada et al.,2017;Cheng et al.,2021).

Genetically predicted fatty liver disease and risk of psychiatric disorders: A mendelian randomization study

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)and alcohol-related liver disease(Ar-LD)constitute the primary forms of chronic liver disease,and their incidence is progressively increasing with changes in lifestyle habits.Earlier studies have do-cumented a correlation between the occurrence and development of prevalent mental disorders and fatty liver.AIM To investigate the correlation between fatty liver and mental disorders,thus ne-cessitating the implementation of a mendelian randomization(MR)study to elu-cidate this association.METHODS Data on NAFLD and ArLD were retrieved from the genome-wide association studies catalog,while information on mental disorders,including Alzheimer's disease,schizophrenia,anxiety disorder,attention deficit hyperactivity disorder(ADHD),bipolar disorder,major depressive disorder,multiple personality dis-order,obsessive-compulsive disorder(OCD),post-traumatic stress disorder(PTSD),and schizophrenia was acquired from the psychiatric genomics consor-tium.A two-sample MR method was applied to investigate mediators in signifi-cant associations.RESULTS After excluding weak instrumental variables,a causal relationship was identified between fatty liver disease and the occurrence and development of some psychia-tric disorders.Specifically,the findings indicated that ArLD was associated with a significantly elevated risk of developing ADHD(OR:5.81,95%CI:5.59-6.03,P<0.01),bipolar disorder(OR:5.73,95%CI:5.42-6.05,P=0.03),OCD(OR:6.42,95%CI:5.60-7.36,P<0.01),and PTSD(OR:5.66,95%CI:5.33-6.01,P<0.01).Meanwhile,NAFLD significantly increased the risk of developing bipolar disorder(OR:55.08,95%CI:3.59-845.51,P<0.01),OCD(OR:61.50,95%CI:6.69-565.45,P<0.01),and PTSD(OR:52.09,95%CI:4.24-639.32,P<0.01).CONCLUSION Associations were found between genetic predisposition to fatty liver disease and an increased risk of a broad range of psychiatric disorders,namely bipolar disorder,OCD,and PTSD,highlighting the significance of preven-tive measures against psychiatric disorders in patients with fatty liver disease.

Peripheral mitochondrial DNA as a neuroinflammatory biomarker for major depressive disorder

In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.

MicroRNAs as potential biomarkers for diagnosis of attention deficit hyperactivity disorder

Inappropriate levels of hyperactivity,impulsivity,and inattention characterize attention deficit hyperactivity disorder,a common childhood-onset neuropsychiatric disorder.The cognitive function and learning ability of children with attention deficit hyperactivity disorder are affected,and these symptoms may persist to adulthood if they are not treated.The diagnosis of attention deficit hyperactivity disorder is only based on symptoms and objective tests for attention deficit hyperactivity disorder are missing.Treatments for attention deficit hyperactivity disorder in children include medications,behavior therapy,counseling,and education services which can relieve many of the symptoms of attention deficit hyperactivity disorder but cannot cure it.There is a need for a molecular biomarker to distinguish attention deficit hyperactivity disorder from healthy subjects and other neurological conditions,which would allow for an earlier and more accurate diagnosis and appropriate treatment to be initiated.Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of attention deficit hyperactivity disorder.The recent studies reviewed had performed microRNA profiling in whole blood,white blood cells,blood plasma,and blood serum of children with attention deficit hyperactivity disorder.A large number of microRNAs were dysregulated when compared to healthy controls and with some overlap between individual studies.From the studies that had included a validation set of patients and controls,potential candidate biomarkers for attention deficit hyperactivity disorder in children could be miR-140-3p,let-7g-5p,-30e-5p,-223-3p,-142-5p,-486-5p,-151a-3p,-151a-5p,and-126-5p in total white blood cells,and miR-4516,-6090,-4763-3p,-4281,-4466,-101-3p,-130a-3p,-138-5p,-195-5p,and-106b-5p in blood serum.Further studies are warranted with children and adults with attention deficit hyperactivity disorder,and consideration should be given to utilizing rat models of attention deficit hyperactivity disorder.Animal studies could be used to confirm microRNA findings in human patients and to test the effects of targeting specific microRNAs on disease progression and behavior.

Disorder effects in NbTiN superconducting resonators

Disordered superconducting materials like NbTiN possess a high kinetic inductance fraction and an adjustable critical temperature, making them a good choice for low-temperature detectors. Their energy gap(D), critical temperature(T_(c)),and quasiparticle density of states(QDOS) distribution, however, deviate from the classical BCS theory due to the disorder effects. The Usadel equation, which takes account of elastic scattering, non-elastic scattering, and electro–phonon coupling,can be applied to explain and describe these deviations. This paper presents numerical simulations of the disorder effects based on the Usadel equation to investigate their effects on the △, Tc, QDOS distribution, and complex conductivity of the NbTiN film. Furthermore, NbTiN superconducting resonators with coplanar waveguide(CPW) structures are fabricated and characterized at different temperatures to validate our numerical simulations. The pair-breaking parameter α and the critical temperature in the pure state T_(c)^(P) of our NbTiN film are determined from the experimental results and numerical simulations. This study has significant implications for the development of low-temperature detectors made of disordered superconducting materials.

Function and dysfunction of GEMIN5:understanding a novel neurodevelopmental disorder

The recent identification of a neurodevelopmental disorder with cerebellar atrophy and motor dysfunction(NEDCAM)has resulted in an increased interest in GEMIN5,a multifunction RNA-binding protein.As the largest member of the survival motor neuron complex,GEMIN5 plays a key role in the biogenesis of small nuclear ribonucleoproteins while also exhibiting translational regulatory functions as an independent protein.Although many questions remain regarding both the pathogenesis and pathophysiology of this new disorder,considerable progress has been made in the brief time since its discovery.In this review,we examine GEMIN5 within the context of NEDCAM,focusing on the structure,function,and expression of the protein specifically in regard to the disorder itself.Additionally,we explore the current animal models of NEDCAM,as well as potential molecular pathways for treatment and future directions of study.This review provides a comprehensive overview of recent advances in our understanding of this unique member of the survival motor neuron complex.

The Role of Adipose Tissue-derived Exosomes in Chronic Metabolic Disorders

Excessive fat deposition in obese subjects promotes the occurrence of metabolic diseases,such as type 2 diabetes mellitus(T2DM),cardiovascular diseases,and non-alcoholic fatty liver disease(NAFLD).Adipose tissue is not only the main form of energy storage but also an endocrine organ that not only secretes adipocytokines but also releases many extracellular vesicles(EVs)that play a role in the regulation of whole-body metabolism.Exosomes are a subtype of EVs,and accumulating evidence indicates that adipose tissue exosomes(AT Exos)mediate crosstalk between adipose tissue and multiple organs by being transferred to targeted cells or tissues through paracrine or endocrine mechanisms.However,the roles of AT Exos in crosstalk with metabolic organs remain to be fully elucidated.In this review,we summarize the latest research progress on the role of AT Exos in the regulation of metabolic disorders.Moreover,we discuss the potential role of AT Exos as biomarkers in metabolic diseases and their clinical application.

Dietary L-proline supplementation ameliorates autism-like behaviors and modulates gut microbiota in the valproic acid-induced mouse model of autism spectrum disorder

The effective intervention strategy for autism spectrum disorder(ASD)are currently limited.Herein,we attempted to evaluate the potential of L-proline(Pro),a multifunctional amino acid,in ameliorating autismlike behaviors and clarify the molecular mechanisms involved by using the typical valproic acid(VPA)-induced mouse model of ASD.Pro significantly attenuates repetitive behaviors and social dysfunction in ASD mice.The correlation analysis revealed that the beneficial effects of Pro on autism-like behaviors are related to the modulation of gut microbiota structure and composition.The histological analysis revealed that Pro could reverse the decrease of Nissl-positive cells in the prefrontal cortex(PFC)induced by VPA exposure.RNA sequencing demonstrated that Pro can also alter the PFC transcriptomic profile distinguished by the regulation of genes involved in Parkinson disease,neuroactive ligand-receptor interaction,oxidative phosphorylation,and mitogen activated protein kinase signaling pathway.Overall,dietary Pro supplementation may be a promising intervention strategy for ASD.