Racial and Ethnic Differences in Orthorexia Nervosa Symptomatology and Other Disordered Eating

While some research has explored racial and ethnic differences in disordered eating, this study may be the first to examine these differences in orthorexia nervosa, involving obsessive-compulsive thoughts and behaviors concerning healthy eating, which negatively impact one’s life. Adult participants, recruited from college courses and social media, completed an online survey with the Orthorexia Nervosa Inventory (ONI) and the Eating Attitudes Test-26 (EAT-26). Regarding racial and ethnic background, 743 were White, 249 were Hispanic, 87 were Black, 61 were Asian or Pacific Islander, and 110 were biracial/multiracial. A MANCOVA revealed that the racial and ethnic groups did not differ on the ONI subscales assessing orthorexic behaviors, impairments, and emotions, after accounting for gender, BMI, and EAT-26 total scores that were covariates. In contrast, a second MANCOVA did reveal group differences on the EAT-26 subscales, after accounting for gender, BMI, and ONI total scores that were covariates. Black participants scored significantly lower than the other racial and ethnic groups on the subscale assessing dieting behaviors characteristic of anorexia nervosa, and the subscale assessing binge-eating and purging behaviors characteristic of bulimia nervosa. Further, Hispanic participants scored significantly lower than White participants on the latter subscale. These findings suggest that while orthorexic symptomatology does not differ based on race and ethnicity, a Black race and Hispanic ethnicity may be protective factors against disordered eating, perhaps related either to cultural norms concerning body image or to the resiliency and social support among the Black and Hispanic communities.

Disordered Structure and Reversible Phase Transformation from K-Birnessite to Zn-Buserite Enable High-Performance Aqueous Zinc-lon Batteries

The layeredδ-MnO_(2)(dMO)is an excellent cathode material for rechargeable aqueous zinc-ion batteries owing to its large interlayer distance(~0.7 nm),high capacity,and low cost;however,such cathodes suffer from structural degradation during the long-term cycling process,leading to capacity fading.In this study,a Co-doped dMO composite with reduced graphene oxide(GC-dMO)is developed using a simple cost-effective hydrothermal method.The degree of disorderness increases owing to the hetero-atom doping and graphene oxide composites.It is demonstrated that layered dMO and GC-dMO undergo a structural transition from K-birnessite to the Zn-buserite phase upon the first discharge,which enhances the intercalation of Zn^(2+)ions,H_(2)O molecules in the layered structure.The GC-dMO cathode exhibits an excellent capacity of 302 mAh g^(-1)at a current density of 100 mAg^(-1)after 100 cycles as compared with the dMO cathode(159 mAhg^(-1)).The excellent electrochemical performance of the GC-dMO cathode owing to Co-doping and graphene oxide sheets enhances the interlayer gap and disorderness,and maintains structural stability,which facilitates the easy reverse intercalation and de-intercalation of Zn^(2+)ions and H_(2)O molecules.Therefore,GC-dMO is a promising cathode material for large-scale aqueous ZIBs.

A class of Ga-Al-P-based compounds with disordered lattice as advanced anode materials for Li-ion batteries

Phosphides possess large reversible capacity, small voltage hysteresis, and high energy efficiency, thus promising to be new anode candidates to replace commercial graphite for Li-ion batteries(LIBs).Through a facile mechanochemistry method, we prepare a novel ternary phosphide of Ga0.5Al0.5P whose crystalline structure is determined to be a cation-disordered cubic zinc sulfide structure according to XRD refinement. As an anode for LIBs, the Ga0.5Al0.5P delivers a reversible capacity of 1,352 mA h g^(-1)at100 mA g^(-1)with an initial Coulombic efficiency(ICE) up to 90.0% based on a reversible Li-storage mechanism integrating intercalation and subsequent conversion processes as confirmed by various characterizations techniques including in-situ XRD, ex-situ Raman, and XPS and electrochemical characterizations.Graphite-modified Ga0.5Al0.5P exhibits a long-lasting cycling stability of retaining 1,182 mA h g^(-1)after300 cycles at 100 m A g^(-1), and 625 mA h g^(-1)after 800 cycles at 2,000 mA g^(-1), and a high-rate performance of remaining 342 m A h g^(-1)at 20,000 mA g^(-1). The outstanding electrochemical performances can be attributed to enhanced reaction kinetics enabled by the capacitive behaviors and the faster Liion diffusion enabled by the cation-mixing. Importantly, by tuning the cationic ratio, we develop a novel series of cation-mixed compounds of Ga_(1/3)Al_(2/3)P, Ga_(1/4)Al_(3/4)P, Ga_(1/5)Al_(4/5)P, Ga_(2/3)Al_(1/3)P, Ga_(3/4)Al_(1/4)P, and Ga_(4/5)Al_(1/5)P, which demonstrate large capacity, high ICE, and suitable anode potentials. Broadly, these compounds with disordered lattices probably present novel physicochemical properties, and high electrochemical performances, thus providing a new perspective for new materials design.

Single-Phase Ternary Compounds with a Disordered Lattice and Liquid Metal Phase for High-Performance Li-Ion Battery Anodes

Si is considered as the promising anode materials for lithium-ion batteries(LIBs)owing to their high capacities of 4200 mAh g-1and natural abundancy.However,severe electrode pulverization and poor electronic and Li-ionic conductivities hinder their practical applications.To resolve the afore-mentioned problems,we first demonstrate a cation-mixed disordered lattice and unique Li storage mechanism of single-phase ternary GaSiP_(2)compound,where the liquid metallic Ga and highly reactive P are incorporated into Si through a ball milling method.As confirmed by experimental and theoretical analyses,the introduced Ga and P enables to achieve the stronger resistance against volume variation and metallic conductivity,respectively,while the cation-mixed lattice provides the faster Li-ionic diffusion capability than those of the parent GaP and Si phases.The resulting GaSiP_(2)electrodes delivered the high specific capacity of 1615 mAh g-1and high initial Coulombic efficiency of 91%,while the graphite-modified GaSiP_(2)(GaSiP_(2)@C)achieved 83%of capacity retention after 900 cycles and high-rate capacity of 800 at 10,000 mA g-1.Furthermore,the LiNi_(0.8)Co_(0.1)Mn_(0.1)O_(2)//Ga SiP_(2)@C full cells achieved the high specific capacity of 1049 mAh g-1after 100 cycles,paving a way for the rational design of high-performance LIB anode materials.

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.

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).

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.

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.

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.

Heteroatom dopant strategy triggered high-potential plateau to non-graphitized carbon with highly disordered microstructure for high-performance sodium ion storage

Non-graphitized carbon(NGC)has been extensively utilized as carbonaceous anode in sodium-ion batteries(SIBs).However,more optimization to achieve competitive capacity and stability is still challenging for SIBs.In the study,the dopant strategy is utilized to construct nitrogen/sulfur-doped non-graphitized carbon(N-NGC or S-NGC)shell decorated on three-dimensional graphene foam(GF)as a self-support electrode.The highly disordered microstructures of heteroatom doped carbons are produced by applying a low-temperature pyrolysis treatment to precursors containing nitrogen and sulfur.The DFT calculations of Na-ion adsorption energies at diverse heteroatom sites show marginal-S,pyrrolic N and pyridinic N with more intensive Na-ion adsorption ability than middle-S,C=O and pristine carbon.The N-NGC with dominant small graphitic regions delivers adsorption ability to Na-ion,while the S-NGC with significant single carbon lattice stripes demonstrates redox reaction with Na-ion.Evidently,in comparison with only adsorption-driven slope regions at high potential for N-NGC,the redox reaction-generated potentialplateau enables non-graphitized S-NGC superior discharge/charge capacity and cycle-stability in the slope region.This work could provide deep insight into the rational design of non-graphitized carbon with rich microstructure and composition.

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.

Disordered Rocksalts with Lattice Oxygen Activation as Efficient Oxygen Evolution Electrocatalysts

The lattice oxygen oxidation mechanism(LOM)provides an efficient pathway for accelerating the oxygen evolution reaction(OER)in certain electrocatalysts by activating and involving lattice oxygen in the catalytic OER process.We investigated the potential of disordered rocksalts as catalysts for accelerating the OER through the LOM process,leveraging their unique metastable Li-O-Li bond states.Theoretical calculations were employed to predict the catalytic pathways and activities of disordered rocksalts(DRX),such as Li_(1.2)Co_(0.4)Ti_(0.5)O_(2)(LCTO).The results revealed that benefiting from the unhybridized Li-O electronic orbitals and the resulting metastable states of Li-O-Li bonds in DRX,LCTO exhibited a typical LOM pathway,and the lattice oxygen was easily activated and participated in the OER.The experimental results showed that LCTO exhibited a remarkable pH-dependent OER activity through the LOM pathway,with an overpotential of 241 mV at a current density of 10 mA/cm^(2),and excellent long-term stability.This work provides a novel chemical space for designing highly active and stable OER electrocatalysts by leveraging the LOM reaction pathway.

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.

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.

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.

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.

Cognition and movement in neurodegenerative disorders:a dynamic duo

People with neurodegenerative disorders often experience problems across a variety of functional domains,including cognition,movement,and psychosocial functioning.The classification of these disorders is based on the phenotypical manifestations that represent the most prominent clinical features.For example,Parkinson's disease and Huntington's disease are typically regarded as movement disorders,whereas Alzheimer's disease(AD) and other dementias are regarded as cognitive disorders.

Evidence supporting the relationship between maternal asthma and risk for autism spectrum disorders

During pregnancy,maternal immune activation(MIA),due to infection,chronic inflammatory disorders,or toxic exposures,can result in lasting health impacts on the developing fetus.MIA has been associated with an increased risk of neurodevelopmental disorders,such as autism spectrum disorder(ASD)in the offspring.ASD is characterized by increased repetitive and stereotyped behaviors and decreased sociability.As of 2020,1 in 36 children are diagnosed with ASD by the age of 8 years,with ASD rates continuing to increase in prevalence in USA(Tamayo et al.,2023).Post-mortem brain studies,biomarker and transcriptomic studies,and epidemiology studies have provided compelling evidence of immune dysregulation in the circulation and brain of individuals diagnosed with ASD.Currently,the etiology of ASD is largely unknown,however,genetic components and environmental factors can contribute to increased susceptibility.Maternal allergic asthma(MAA),a form of MIA,has been identified as a potential risk factor for developing neurodevelopmental disorders(Patel et al.,2020).Asthma is a chronic inflammatory condition driven by a T-helper type(TH)2 immune response.

Mental disorders after myocardial infarction:potential mediator role for chemokines in heart-brain interaction?

Acute myocardial infarction(MI)remains one of the leading causes of mortality and morbidity in the global communities.A prevailing topic that has attracted increasing attentions over the past few decades is the so-called heart-brain interaction,in particular following a major traumatic event such as MI.Increased prevalence of depression and other mental disorders has been recognized in cardiac patients after MI,coronary catheterization,or cardiothoracic surgeries.In this review,we focus on the potential pathogenic mechanisms and pre-clinical transcriptomic evidence for identifying potential mediators of post-MI depression.We first summarize the conventional mechanistic understanding that leads to the current clinical management of post-MI depression with the use of selective serotonin reuptake inhibitors(SSRIs)and cognitive behavior and exercise therapies.We further envisage a possible role played by certain chemokines,e.g.,Chemokine(C-X-C motif)ligand 12(CXCL12)and Chemokine(C-C motif)ligand 2(CCL22),in serving as signaling molecules to connect the MI-induced heart damage to the pro-depressive changes in brain during the post-MI period.Future in-depth investigations into this chemokine hypothesis will be instrumental in developing new chemokine-targeted therapies for better management of the cardiac patients suffering from post-MI depression.

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.