Purpose:The aim of the current study was to investigate the association of accelerometer-measured sleep duration and different intensities of physical activity(PA)with the risk of incident type 2 diabetes in a populat...Purpose:The aim of the current study was to investigate the association of accelerometer-measured sleep duration and different intensities of physical activity(PA)with the risk of incident type 2 diabetes in a population-based prospective cohort study.Methods:Altogether,88,000 participants(mean age=62.2±7.9 years,mean±SD)were included from the UK Biobank.Sleep duration(short:<6 h/day;normal:6-8 h/day;long:>8 h/day)and PA of different intensities were measured using a wrist-won accelerometer over a 7-day period between 2013 and 2015.PA was classified according to the median or World Health Organization-recommendation:total volume of PA(high,low),moderate-to-vigorous PA(MVPA)(recommended,not recommended),and light-intensity PA(high,low).Incidence of type 2diabetes was ascertained using hospital records or death registries.Results:During a median follow-up of 7.0 years,1615 incident type 2 diabetes cases were documented.Compared with normal sleep duration,short(hazard ratio(HR)=1.21,95%confidence interval(95%CI):1.03-1.41)but not long sleep duration(HR=1.01,95%CI:0.89-1.15)was associated with excessive type 2 diabetes risk.This increased risk among short sleepers seems to be protected against by PA.Compared with normal sleepers with high or recommended PA,short sleepers with low volume of PA(HR=1.81,95%CI:1.46-2.25),not recommended(below the World Health Organization-recommended level of)MVPA(HR=1.92,95%CI:1.55-2.36),or low light-intensity PA(HR=1.49,95%CI:1.13-1.90)had a higher risk of type 2 diabetes,while short sleepers with a high volume of PA(HR=1.14,95%CI:0.88-1.49),recommended MVPA(HR=1.02,95%CI:0.71-1.48),or high light-intensity PA(HR=1.14,95%CI:0.92-1.41)did not.Conclusion:Accelerometer-measured short but not long sleep duration was associated with a higher risk of incident type 2 diabetes.A higher level of PA,regardless of intensity,potentially ameliorates this excessive risk.展开更多
Strong evidence has accumulated to show a correlation between depression symptoms and inflammatory responses.Moreover,anti-inflammatory treatment has shown partial effectiveness in alleviating depression symptoms.Lyci...Strong evidence has accumulated to show a correlation between depression symptoms and inflammatory responses.Moreover,anti-inflammatory treatment has shown partial effectiveness in alleviating depression symptoms.Lycium barbarum polysaccharide(LBP),derived from Goji berries,exhibits notable antioxidative and anti-inflammatory properties.In our recent double-blinded randomized placebo-controlled trial,we found that LBP significantly reduced depressive symptoms in adolescents with subthreshold depression.It is presumed that the antidepressant effect of LBP may be associated with its influence on inflammatory cytokines.In the double-blinded randomized controlled trial,we enrolled 29 adolescents with subthreshold depression and randomly divided them into an LBP group and a placebo group.In the LBP group,adolescents were given 300 mg/d LBP.A 6-week follow up was completed by 24 adolescents,comprising 14 adolescents from the LBP group(15.36±2.06 years,3 men and 11 women)and 10 adolescents from the placebo group(14.9±1.6 years,2 men and 8 women).Our results showed that after 6 weeks of treatment,the interleukin-17A level in the LBP group was lower than that in the placebo group.Network analysis showed that LBP reduced the correlations and connectivity between inflammatory factors,which were associated with the improvement in depressive symptoms.These findings suggest that 6-week administration of LBP suppresses the immune response by reducing interleukin-17A level,thereby exerting an antidepressant effect.展开更多
BACKGROUND Lithium carbonate is used to manage various mood disorders,but it can cause thyroid abnormalities,including goiter,hypothyroidism,and hyperthyroidism.In rare cases,it can lead to giant goiter and subclinica...BACKGROUND Lithium carbonate is used to manage various mood disorders,but it can cause thyroid abnormalities,including goiter,hypothyroidism,and hyperthyroidism.In rare cases,it can lead to giant goiter and subclinical hyperthyroidism,which may require surgical intervention in severe cases.CASE SUMMARY This case represents a rare development of giant goiter and subclinical hyperthyroidism in a schizophrenia patient who was subjected to prolonged lithium carbonate treatment.The enlarged thyroid gland caused pressure on the airway and recurrent laryngeal nerve,which led to respiratory distress,hoarseness,and dysphagia.The immediate danger of suffocation required urgent surgical intervention.In this report,we describe the case of a 41-year-old Chinese woman.This sheds light on the etiology and challenges associated with managing a giant goiter.The patient underwent a subtotal thyroidectomy to relieve airway compression and facilitate airway expansion.Prior to the procedure,the patient was given iodine to prepare.Concurrently,changes were made to the psychiatric medication regimen.Following surgery,the patient's respiratory function and vocal cord functionality improved significantly,and her mental state remained stable.CONCLUSION It is essential to monitor thyroid function,test thyroid antibody levels,and perform thyroid ultrasounds consistently in all patients undergoing long-term lithium carbonate treatment.This vigilance helps prevent severe and potentially life-threatening thyroid enlargement.展开更多
Background Understanding the evolution of circadian rhythm dysfunction and psychopathology in the high-risk population has important implications for the prevention of bipolar disorder.Nevertheless,some of the previou...Background Understanding the evolution of circadian rhythm dysfunction and psychopathology in the high-risk population has important implications for the prevention of bipolar disorder.Nevertheless,some of the previous studies on the emergence of psychopathologies and circadian dysfunction among high-risk populations were inconsistent and limited.Aims To examine the prevalence rates of sleep and circadian dysfunctions,mental disorders and their symptoms in the offspring of parents with(O-BD)and without bipolar disorder(O-control).Methods The study included 191 O-BD and 202 O-control subjects aged 6-21 years from the Greater Bay Area,China.The diagnoses and symptoms of sleep/circadian rhythm and mental disorders were assessed by the Diagnostic Interview for Sleep Patterns and Disorders,and the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version,respectively.Generalised estimating equations and shared frailty proportional hazards models of survival analysis were applied to compare the outcomes in the offspring.Results Adjusting for age,sex and region of recruitment,there was a significantly higher risk of delayed sleep phase symptoms(9.55%vs 2.58%,adjusted OR:4.04)in O-BD than in O-control.O-BD had a nearly fivefold higher risk of mood disorders(11.70%vs 3.47%,adjusted OR:4.68)and social anxiety(6.28%vs 1.49%,adjusted OR:4.70),a fourfold higher risk of depressive disorders(11.17%vs 3.47%,adjusted OR:3.99)and a threefold higher risk of mood symptoms(20.74%vs 10.40%,adjusted OR:2.59)than O-control.Subgroup analysis revealed that O-BD children(aged under 12 years)had a nearly 2-fold higher risk of any mental and behavioural symptoms than O-control,while there was a nearly 4-fold higher risk of delayed sleep phase symptoms,a 7.5-fold higher risk of social anxiety and a 3-fold higher risk of mood symptoms in O-BD adolescents(aged 12 years and over).Conclusions There was an increase in delayed sleep phase symptoms in O-BD adolescents compared with their control counterparts,confirming the central role of circadian rhythm dysfunction in bipolar disorder.The findings of the specific age-related and stage-related developmental patterns of psychopathologies and circadian dysfunction in children and adolescent offspring of parents with bipolar disorder paved the way to develop specific and early clinical intervention and prevention strategies.展开更多
Background Individuals with type 2 diabetes mellitus(T2DM)are more vulnerable to social disconnection compared with the general population;however,there are few relevant studies investigating this issue.Aims To invest...Background Individuals with type 2 diabetes mellitus(T2DM)are more vulnerable to social disconnection compared with the general population;however,there are few relevant studies investigating this issue.Aims To investigate whether social isolation or loneliness may be associated with subsequent risk of developing major adverse cardiovascular events,whether these associations vary according to fatal and non-fatal outcomes and how behavioural,psychological and physiological factors mediate these associations.Methods This longitudinal analysis included data from 19360 individuals with T2DM at baseline(2006-2010)from the UK Biobank.Social isolation and loneliness were measured using self-report questionnaires.The study outcomes included the first events of myocardial infarction(MI)or stroke(n=2273)and all-cause(n=2820)or cardiovascular disease-related mortality through linked hospital data ordeath registries.Results Over a median follow-up of 12.4 years(interquartile range(IQR):11.6-13.3 years),participants who were more socially isolated(most social isolation vs least social isolation)experienced increased risks for all-cause(hazard ratio(HR):1.33,95%confidence interval(Cl):1.19 to 1.47)and cardiovascular disease(HR:1.36,95%Cl:1.17 to 1.59)mortality but not first Ml or stroke.Loneliness(yes vs no)was associated with a greater risk for a composite of incident MI or stroke(HR:1.37,95%Cl:1.19 to 1.57)but not mortality.Social isolation was associated with fatal Ml and stroke,whereas loneliness was associated with non-fatal Ml and stroke.The significant associations of social isolation and loneliness with outcomes were mainly mediated by behavioural factors(mediating proportion:17.8%-28.2%and 17.6%-17.8%,respectively).Conclusions Among individuals with T2DM,social isolation and loneliness are associated with a greater risk of developing major adverse cardiovascular events,with differences in both risks stratified according to fatal and non-fatal events and underlying mediating factors.展开更多
In the present study,Fmr1 knockout mice （KO mice） were used as the model for fragile X syndrome.The results of step-through and step-down tests demonstrated that Fmr1 KO mice had shorter latencies and more error cou...In the present study,Fmr1 knockout mice （KO mice） were used as the model for fragile X syndrome.The results of step-through and step-down tests demonstrated that Fmr1 KO mice had shorter latencies and more error counts,indicating a learning and memory disorder.After treatment with 30,60,90,120,or 200 mg/kg lithium chloride,the learning and memory abilities of the Fmr1 KO mice were significantly ameliorated,in particular,the 200 mg/kg lithium chloride treatment had the most significant effect.Western blot analysis showed that lithium chloride significantly enhanced the expression of phosphorylated glycogen synthase kinase 3 beta,an inactive form of glycogen synthase kinase 3 beta,in the cerebral cortex and hippocampus of the Fmr1 KO mice.These results indicated that lithium chloride improved learning and memory in the Fmr1 KO mice,possibly by inhibiting glycogen synthase kinase 3 beta activity.展开更多
BACKGROUND Lymphangiomas in the gastrointestinal tract are extremely rare in adults.As a benign lesion,small intestine lymphangiomas often remain asymptomatic and pose challenges for definitive diagnosis.However,lymph...BACKGROUND Lymphangiomas in the gastrointestinal tract are extremely rare in adults.As a benign lesion,small intestine lymphangiomas often remain asymptomatic and pose challenges for definitive diagnosis.However,lymphangiomas can give rise to complications such as abdominal pain,bleeding,volvulus,and intussusception.Here,we report a case of jejunal cavernous lymphangioma that presented with intermittent melena and refractory anemia in a male adult.CASE SUMMARY A 66-year-old man presented with intermittent melena,fatigue and refractory anemia nine months prior.Esophagogastroduodenoscopy and colonoscopy were performed many times and revealed no apparent bleeding.Conservative management,including transfusion,hemostasis,gastric acid secretion inhibition and symptomatic treatment,was performed,but the lesions tended to recur shortly after surgery.Ultimately,the patient underwent capsule endoscopy,which revealed a more than 10 cm lesion accompanied by active bleeding.After singleballoon enteroscopy and biopsy,a diagnosis of jejunal cavernous lymphangioma was confirmed,and the patient underwent surgical resection.No complications or recurrences were observed postoperatively.CONCLUSION Jejunal cavernous lymphangioma should be considered a cause of obscure gastrointestinal bleeding.Capsule endoscopy and single-balloon enteroscopy can facilitate diagnosis.Surgical resection is an effective management method.展开更多
The formation of nerve bundles,which is partially regulated by neural cell adhesion molecule 1(NCAM1),is important for neural network organization during peripheral nerve regeneration.However,little is known about how...The formation of nerve bundles,which is partially regulated by neural cell adhesion molecule 1(NCAM1),is important for neural network organization during peripheral nerve regeneration.However,little is known about how the extracellular matrix(ECM)microenvironment affects this process.Here,we seeded dorsal root ganglion tissue blocks on different ECM substrates of peripheral nerve ECM-derived matrixgel,Matrigel,laminin 521,collagen I,and collagen IV,and observed well-aligned axon bundles growing in the peripheral nerve ECM-derived environment.We confirmed that NCAM1 is necessary but not sufficient to trigger this phenomenon.A protein interaction assay identified collagen VI as an extracellular partner of NCAM1 in the regulation of axonal fasciculation.Collagen VI interacted with NCAM1 by directly binding to the FNIII domain,thereby increasing the stability of NCAM1 at the axolemma.Our in vivo experiments on a rat sciatic nerve defect model also demonstrated orderly nerve bundle regeneration with improved projection accuracy and functional recovery after treatment with 10 mg/m L Matrigel and 20μg/m L collagen VI.These findings suggest that the collagen VI-NCAM1 pathway plays a regulatory role in nerve bundle formation.This study was approved by the Animal Ethics Committee of Guangzhou Medical University(approval No.GY2019048)on April 30,2019.展开更多
Loneliness is associated with high prevalences of major psychiatric illnesses such as major depression.However,the underlying emotional mechanisms of loneliness remained unclear.We hypothesized that loneliness origina...Loneliness is associated with high prevalences of major psychiatric illnesses such as major depression.However,the underlying emotional mechanisms of loneliness remained unclear.We hypothesized that loneliness originates from both decreases in positive emotional processing and increases in negative emotion processing.To test this,we conducted a systematic review of 29 previous studies(total participants n=19560,mean age=37.16 years,female proportion=59.7%),including 18 studies that included ques-tionnaire measures of emotions only,and 11 studies that examined the brain correlates of emotions.The main findings were that loneliness was negatively correlated with general positive emotions and positively correlated with general negative emotions.Fur-thermore,limited evidence indicates loneliness exhibited negative and positive correlations with the brain positive(e.g.the striatum)and negative(e.g.insula)emotion systems,respectively,but the sign of correlation was not entirely consistent.Additionally,loneli-ness was associated with the structure and function of the brain emotion regulation systems,particularly the prefrontal cortex,but the direction of this relationship remained ambiguous.We concluded that the existing evidence supported a bivalence model of lone-liness,but several critical gaps existed that could be addressed by future studies that include adolescent and middle-aged samples,use both questionnaire and task measures of emotions,distinguish between general emotion and social emotion as well as between positive and negative emotion regulation,and adopt a longitudinal design that allows us to ascertain the causal relationships between loneliness and emotion dysfunction.Our findings provide new insights into the underlying emotion mechanisms of loneliness that can inform interventions for lonely individuals.展开更多
Focal epilepsy accounts for 60% of all forms of epilepsy, but the pathogenic mechanism is not well understood. In this study,three novel mutations in NPRL3(nitrogen permease regulator-like 3), c.937_945del, c.1514dup ...Focal epilepsy accounts for 60% of all forms of epilepsy, but the pathogenic mechanism is not well understood. In this study,three novel mutations in NPRL3(nitrogen permease regulator-like 3), c.937_945del, c.1514dup C and 6,706-bp genomic DNA(g DNA) deletion, were identified in three families with focal epilepsy by linkage analysis, whole exome sequencing(WES) and Sanger sequencing. NPRL3 protein is a component of the GATOR1 complex, a major inhibitor of m TOR signaling. These mutations led to truncation of the NPRL3 protein and hampered the binding between NPRL3 and DEPDC5, which is another component of the GATOR1 complex. Consequently, the mutant proteins enhanced m TOR signaling in cultured cells, possibly due to impaired inhibition of m TORC1 by GATOR1. Knockdown of nprl3 in Drosophila resulted in epilepsy-like behavior and abnormal synaptic development. Taken together, these findings expand the genotypic spectrum of NPRL3-associated focal epilepsy and provide further insight into how NPRL3 mutations lead to epilepsy.展开更多
Ion channels are crucial in the generation and modulation of excitability in the nervous system and have been implicated in human epilepsy. Forty-one epilepsyassociated ion channel genes and their mutations are system...Ion channels are crucial in the generation and modulation of excitability in the nervous system and have been implicated in human epilepsy. Forty-one epilepsyassociated ion channel genes and their mutations are systematically reviewed. In this paper, we analyzed the genotypes, functional alterations（funotypes）, and phenotypes of these mutations. Eleven genes featured loss-offunction mutations and six had gain-of-function mutations.Nine genes displayed diversified funotypes, among which a distinct funotype-phenotype correlation was found in SCN1A. These data suggest that the funotype is an essential consideration in evaluating the pathogenicity of mutations and a distinct funotype or funotype-phenotype correlation helps to define the pathogenic potential of a gene.展开更多
N-methyl-D-aspartate receptors（NMDARs）, a subtype of glutamate-gated ion channels, play a central role in epileptogenesis. Recent studies have identified an increasing number of GRIN2 A（a gene encoding the NMDAR Gl...N-methyl-D-aspartate receptors（NMDARs）, a subtype of glutamate-gated ion channels, play a central role in epileptogenesis. Recent studies have identified an increasing number of GRIN2 A（a gene encoding the NMDAR GluN2A subunit） mutations in patients with epilepsy. Phenotypes of GRIN2 A mutations include epilepsy-aphasia disorders and other epileptic encephalopathies, which pose challenges in clinical treatment. Here we identified a heterozygous GRIN2 A mutation（c.1341 T[A, p.N447 K） from a boy with Rolandic epilepsy by whole-exome sequencing. The patient became seizurefree with a combination of valproate and lamotrigine.Functional investigation was carried out using recombinant NMDARs containing a GluN2A-N447 K mutant that is located in the ligand-binding domain of the GluN2A subunit. Whole-cell current recordings in HEK 293 T cells revealed that the N447 K mutation increased the NMDAR current density by;.2-fold, enhanced the glutamate potency by 2-fold, and reduced the sensitivity to Mg;inhibition. These results indicated that N447 K is a gain-offunction mutation. Interestingly, alternative substitutions by alanine and glutamic acid at the same residue（N447 A and N447 E） did not change NMDAR function, suggesting a residual dependence of this mutation in altering NMDAR function. Taken together, this study identified human GluN2A N447 K as a novel mutation associated with epilepsy and validated its functional consequences in vitro.Identification of this mutation is also helpful for advancing our understanding of the role of NMDARs in epilepsy and provides new insights for precision therapeutics in epilepsy.展开更多
Paroxysmal dyskinesias are a group of neurological diseases characterized by intermittent episodes of involuntary movements with different causes.Paroxysmal kinesigenic dyskinesia(PKD)is the most common type of paroxy...Paroxysmal dyskinesias are a group of neurological diseases characterized by intermittent episodes of involuntary movements with different causes.Paroxysmal kinesigenic dyskinesia(PKD)is the most common type of paroxysmal dyskinesia and can be divided into primary and secondary types based on the etiology.Clinically,PKD is characterized by recurrent and transient attacks of involuntary movements precipitated by a sudden voluntary action.The major cause of primary PKD is genetic abnormalities,and the inheritance pattern of PKD is mainly autosomal-dominant with incomplete penetrance.The proline-rich transmembrane protein 2(PRRT2)was the first identified causative gene of PKD,accounting for the majority of PKD cases worldwide.An increasing number of studies has revealed the clinical and genetic characteristics,as well as the underlying mechanisms of PKD.By seeking the views of domestic experts,we propose an expert consensus regarding the diagnosis and treatment of PKD to help establish standardized clinical evaluation and therapies for PKD.In this consensus,we review the clinical manifestations,etiology,clinical diagnostic criteria and therapeutic recommendations for PKD,and results of genetic analyses in PKD patients performed in domestic hospitals.展开更多
The multiple PDZ domain crumbs cell polarity complex component gene(MPDZ;MIM:603785),is highly expressed in the brain across the whole lifespan.It encodes the multiple PDZ domain protein,which is a member of the NMDAR...The multiple PDZ domain crumbs cell polarity complex component gene(MPDZ;MIM:603785),is highly expressed in the brain across the whole lifespan.It encodes the multiple PDZ domain protein,which is a member of the NMDAR signaling complex that may play a role in the control of AMPAR potentiation and synaptic plasticity in excitatory synapses."Previously,MPDZ variants have been demonstrated to be associated with autosomal recessive congenital hydrocephalus-2(HYC2;MIM:615219)which is commonly complicated by brain abnormalities and developmental delay.Seizures were reported in only one case.The association between MPDz and epilepsy requires clarification.展开更多
LIM kinase 1 （LIMK1）, a cytosolic serine/threonine kinase, regulates actin filament dynamics and reorganization and is involved in neuronal development and brain function. Abnormal expression of LIMK1 is associated ...LIM kinase 1 （LIMK1）, a cytosolic serine/threonine kinase, regulates actin filament dynamics and reorganization and is involved in neuronal development and brain function. Abnormal expression of LIMK1 is associated with several neurological disorders. In this study, we performed a conservation analysis using Vector NTI （8.0） software. The dualluciferase reporter assay and real-time quantitative RT-PCR were used to assess the protein and mRNA levels of the reporter gene, respectively. We found that a region ranging from nt ＋884 to ＋966 in the human LIMK1 3＇ untranslated region （UTR） was highly conserved in the mouse Limkl 3＇ UTR and formed a structure containing several loops and stems. Luciferase assay showed that the relative luciferase activity of the mutated construct with the conserved region deleted, pGL4-hLIMK1-3U-M, in SH-SY5Y and HEK-293 cells was only -60% of that of the wild-type construct pGL4-hLIMK1-3U, indicating that the conserved region is critical for the reporter gene expression. Real-time quantitative RT-PCR analysis demonstrated that the relative Luc2 mRNA levels in SH-SY5Y and HEK293 cells transfected with pGL4-hLIMK1-3U-M decreased to50% of that in cells transfected with pGL4-hLIMK1- 3U, suggesting an important role of the conserved region in maintaining Luc2 mRNA stability. Our study suggests that the conserved region in the LIMK1 3＇ UTR is involved in regulating LIMK1 expression at the post-transcriptional level, which may help reveal the mechanism underlying the regulation of LIMK1 expression in the central nervous system and explore the relationship between the 3＇-UTR mutant and neuroloqical disorders.展开更多
A novel fluorescent probe 9-（4-（1,2-diamine）benzene-N1-phenyl）acridine（DABPA） was synthesized for the detection of nitric oxide（NO） and characterized by IR, 1H-NMR and EI-MS spectroscopy. Based on a photoelect...A novel fluorescent probe 9-（4-（1,2-diamine）benzene-N1-phenyl）acridine（DABPA） was synthesized for the detection of nitric oxide（NO） and characterized by IR, 1H-NMR and EI-MS spectroscopy. Based on a photoelectron transfer mechanism, the fl uorescence intensities of DABPA were investigated with the different concentrations of NO. Under the optimal experimental conditions, the fl uorescence intensity of DABPA had a good linear relationship（R2=0.9977） with NO concentration in the range from 1×10-7 to 1.5×10-6 mol/L with a detection limit of 1×10-8 mol/L. The cytotoxicity induced by DABPA was evaluated by the MTT（3-（4,5-dimethylthiazol-2-yl）-2,5diphenyl tetrazolium bromide） assay for biological application. Furthermore, the probe DABPA had also been successfully applied to real-time image NO produced in PC12 cells in the presence of L-arginine.展开更多
Transcription factors（TFs）play critical roles in the development of the nervous system,but the transcriptional regulatory mechanisms of these genes are poorly understood.Here we analyzed 5-kb of the 5＇ flanking gen...Transcription factors（TFs）play critical roles in the development of the nervous system,but the transcriptional regulatory mechanisms of these genes are poorly understood.Here we analyzed 5-kb of the 5＇ flanking genomic DNA sequences of 41 TF genes involved in neuronal development.The results showed that the TF genes tend to have higher GC contents in the proximal region and most of the TF genes have at least one proximal GC-rich（GC content60%）promoter with a CpG island.The promoter distribution analysis showed that the GC-poor promoters were sporadically distributed within the 5-kb flanking genomic sequence（FGS）;however,more than half（37 of 70）of the GC-rich promoters were located in the proximal region between nucleotides—1 and—500.Luciferase assays showed that partial GC-rich promoters increased gene expression in SH-SY5Y cells and that CpG methylation repressed the promoter activity.This study suggests a potential general mechanism for regulation of TF expression.展开更多
The ARHGAP4 gene(OMIM*300,023),also known as Rho GTPase activating protein 4,encodes a protein that has an essential role in the regulation of small GTP-binding.ARHGAP4 message RNA(mRNA)is highly expressed during the ...The ARHGAP4 gene(OMIM*300,023),also known as Rho GTPase activating protein 4,encodes a protein that has an essential role in the regulation of small GTP-binding.ARHGAP4 message RNA(mRNA)is highly expressed during the developing and adult nervous system.At the protein level,ARHGAP4 is exclusively present in certain brain regions,such as the mesial temporal lobe,specifically the stratum lucidum of the CA3 region[1].ARHGAP4 enhances the GTPase activity of Rho proteins,which modulate morphological alterations in neuron development and synaptic plasticity by interacting with the actin cytoskeleton[2].展开更多
基金supported by the National Key R&D Program of China(2021YFC2501500)National Natural Science Foundation of China(82171476)。
文摘Purpose:The aim of the current study was to investigate the association of accelerometer-measured sleep duration and different intensities of physical activity(PA)with the risk of incident type 2 diabetes in a population-based prospective cohort study.Methods:Altogether,88,000 participants(mean age=62.2±7.9 years,mean±SD)were included from the UK Biobank.Sleep duration(short:<6 h/day;normal:6-8 h/day;long:>8 h/day)and PA of different intensities were measured using a wrist-won accelerometer over a 7-day period between 2013 and 2015.PA was classified according to the median or World Health Organization-recommendation:total volume of PA(high,low),moderate-to-vigorous PA(MVPA)(recommended,not recommended),and light-intensity PA(high,low).Incidence of type 2diabetes was ascertained using hospital records or death registries.Results:During a median follow-up of 7.0 years,1615 incident type 2 diabetes cases were documented.Compared with normal sleep duration,short(hazard ratio(HR)=1.21,95%confidence interval(95%CI):1.03-1.41)but not long sleep duration(HR=1.01,95%CI:0.89-1.15)was associated with excessive type 2 diabetes risk.This increased risk among short sleepers seems to be protected against by PA.Compared with normal sleepers with high or recommended PA,short sleepers with low volume of PA(HR=1.81,95%CI:1.46-2.25),not recommended(below the World Health Organization-recommended level of)MVPA(HR=1.92,95%CI:1.55-2.36),or low light-intensity PA(HR=1.49,95%CI:1.13-1.90)had a higher risk of type 2 diabetes,while short sleepers with a high volume of PA(HR=1.14,95%CI:0.88-1.49),recommended MVPA(HR=1.02,95%CI:0.71-1.48),or high light-intensity PA(HR=1.14,95%CI:0.92-1.41)did not.Conclusion:Accelerometer-measured short but not long sleep duration was associated with a higher risk of incident type 2 diabetes.A higher level of PA,regardless of intensity,potentially ameliorates this excessive risk.
基金supported by the National Natural Science Foundation of China,No.81671347(to KL)the Science and Technology Program of Guangzhou of China,No.202007030012(to KFS and KL)the Science and Technology Program of Guangzhou of China,No 202102020735(to RW).
文摘Strong evidence has accumulated to show a correlation between depression symptoms and inflammatory responses.Moreover,anti-inflammatory treatment has shown partial effectiveness in alleviating depression symptoms.Lycium barbarum polysaccharide(LBP),derived from Goji berries,exhibits notable antioxidative and anti-inflammatory properties.In our recent double-blinded randomized placebo-controlled trial,we found that LBP significantly reduced depressive symptoms in adolescents with subthreshold depression.It is presumed that the antidepressant effect of LBP may be associated with its influence on inflammatory cytokines.In the double-blinded randomized controlled trial,we enrolled 29 adolescents with subthreshold depression and randomly divided them into an LBP group and a placebo group.In the LBP group,adolescents were given 300 mg/d LBP.A 6-week follow up was completed by 24 adolescents,comprising 14 adolescents from the LBP group(15.36±2.06 years,3 men and 11 women)and 10 adolescents from the placebo group(14.9±1.6 years,2 men and 8 women).Our results showed that after 6 weeks of treatment,the interleukin-17A level in the LBP group was lower than that in the placebo group.Network analysis showed that LBP reduced the correlations and connectivity between inflammatory factors,which were associated with the improvement in depressive symptoms.These findings suggest that 6-week administration of LBP suppresses the immune response by reducing interleukin-17A level,thereby exerting an antidepressant effect.
文摘BACKGROUND Lithium carbonate is used to manage various mood disorders,but it can cause thyroid abnormalities,including goiter,hypothyroidism,and hyperthyroidism.In rare cases,it can lead to giant goiter and subclinical hyperthyroidism,which may require surgical intervention in severe cases.CASE SUMMARY This case represents a rare development of giant goiter and subclinical hyperthyroidism in a schizophrenia patient who was subjected to prolonged lithium carbonate treatment.The enlarged thyroid gland caused pressure on the airway and recurrent laryngeal nerve,which led to respiratory distress,hoarseness,and dysphagia.The immediate danger of suffocation required urgent surgical intervention.In this report,we describe the case of a 41-year-old Chinese woman.This sheds light on the etiology and challenges associated with managing a giant goiter.The patient underwent a subtotal thyroidectomy to relieve airway compression and facilitate airway expansion.Prior to the procedure,the patient was given iodine to prepare.Concurrently,changes were made to the psychiatric medication regimen.Following surgery,the patient's respiratory function and vocal cord functionality improved significantly,and her mental state remained stable.CONCLUSION It is essential to monitor thyroid function,test thyroid antibody levels,and perform thyroid ultrasounds consistently in all patients undergoing long-term lithium carbonate treatment.This vigilance helps prevent severe and potentially life-threatening thyroid enlargement.
基金supported by the Health and Medical Research Fund of the Food and Health Bureau of Hong Kong(03140636)and the donation fund from Mr Yip WT and Mrs Yip。
文摘Background Understanding the evolution of circadian rhythm dysfunction and psychopathology in the high-risk population has important implications for the prevention of bipolar disorder.Nevertheless,some of the previous studies on the emergence of psychopathologies and circadian dysfunction among high-risk populations were inconsistent and limited.Aims To examine the prevalence rates of sleep and circadian dysfunctions,mental disorders and their symptoms in the offspring of parents with(O-BD)and without bipolar disorder(O-control).Methods The study included 191 O-BD and 202 O-control subjects aged 6-21 years from the Greater Bay Area,China.The diagnoses and symptoms of sleep/circadian rhythm and mental disorders were assessed by the Diagnostic Interview for Sleep Patterns and Disorders,and the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version,respectively.Generalised estimating equations and shared frailty proportional hazards models of survival analysis were applied to compare the outcomes in the offspring.Results Adjusting for age,sex and region of recruitment,there was a significantly higher risk of delayed sleep phase symptoms(9.55%vs 2.58%,adjusted OR:4.04)in O-BD than in O-control.O-BD had a nearly fivefold higher risk of mood disorders(11.70%vs 3.47%,adjusted OR:4.68)and social anxiety(6.28%vs 1.49%,adjusted OR:4.70),a fourfold higher risk of depressive disorders(11.17%vs 3.47%,adjusted OR:3.99)and a threefold higher risk of mood symptoms(20.74%vs 10.40%,adjusted OR:2.59)than O-control.Subgroup analysis revealed that O-BD children(aged under 12 years)had a nearly 2-fold higher risk of any mental and behavioural symptoms than O-control,while there was a nearly 4-fold higher risk of delayed sleep phase symptoms,a 7.5-fold higher risk of social anxiety and a 3-fold higher risk of mood symptoms in O-BD adolescents(aged 12 years and over).Conclusions There was an increase in delayed sleep phase symptoms in O-BD adolescents compared with their control counterparts,confirming the central role of circadian rhythm dysfunction in bipolar disorder.The findings of the specific age-related and stage-related developmental patterns of psychopathologies and circadian dysfunction in children and adolescent offspring of parents with bipolar disorder paved the way to develop specific and early clinical intervention and prevention strategies.
基金funded by the National Natural Science Foundation of China(32100880)Guangzhou Municipal Key Discipline in Medicine(2021-2023)Guangzhou High-level Clinical Key Specialty and Guangzhou Research-oriented Hospital.
文摘Background Individuals with type 2 diabetes mellitus(T2DM)are more vulnerable to social disconnection compared with the general population;however,there are few relevant studies investigating this issue.Aims To investigate whether social isolation or loneliness may be associated with subsequent risk of developing major adverse cardiovascular events,whether these associations vary according to fatal and non-fatal outcomes and how behavioural,psychological and physiological factors mediate these associations.Methods This longitudinal analysis included data from 19360 individuals with T2DM at baseline(2006-2010)from the UK Biobank.Social isolation and loneliness were measured using self-report questionnaires.The study outcomes included the first events of myocardial infarction(MI)or stroke(n=2273)and all-cause(n=2820)or cardiovascular disease-related mortality through linked hospital data ordeath registries.Results Over a median follow-up of 12.4 years(interquartile range(IQR):11.6-13.3 years),participants who were more socially isolated(most social isolation vs least social isolation)experienced increased risks for all-cause(hazard ratio(HR):1.33,95%confidence interval(Cl):1.19 to 1.47)and cardiovascular disease(HR:1.36,95%Cl:1.17 to 1.59)mortality but not first Ml or stroke.Loneliness(yes vs no)was associated with a greater risk for a composite of incident MI or stroke(HR:1.37,95%Cl:1.19 to 1.57)but not mortality.Social isolation was associated with fatal Ml and stroke,whereas loneliness was associated with non-fatal Ml and stroke.The significant associations of social isolation and loneliness with outcomes were mainly mediated by behavioural factors(mediating proportion:17.8%-28.2%and 17.6%-17.8%,respectively).Conclusions Among individuals with T2DM,social isolation and loneliness are associated with a greater risk of developing major adverse cardiovascular events,with differences in both risks stratified according to fatal and non-fatal events and underlying mediating factors.
基金the National Natural Science Foundation of China,No.30870876the Natural Science Foundation of Guangdong Province,No.815101700100005+2 种基金the Science and Technology Program of Guangdong Province,No.2005B60302004,2008B030301371,2009B030801368the Traditional Chinese Medicineand Combination of Traditional Chinese and Western Medicine Program of Guangzhou,No.2008A52the Medical and Health Scientific Research Program of Guangzhou,No.2009-YB-167
文摘In the present study,Fmr1 knockout mice （KO mice） were used as the model for fragile X syndrome.The results of step-through and step-down tests demonstrated that Fmr1 KO mice had shorter latencies and more error counts,indicating a learning and memory disorder.After treatment with 30,60,90,120,or 200 mg/kg lithium chloride,the learning and memory abilities of the Fmr1 KO mice were significantly ameliorated,in particular,the 200 mg/kg lithium chloride treatment had the most significant effect.Western blot analysis showed that lithium chloride significantly enhanced the expression of phosphorylated glycogen synthase kinase 3 beta,an inactive form of glycogen synthase kinase 3 beta,in the cerebral cortex and hippocampus of the Fmr1 KO mice.These results indicated that lithium chloride improved learning and memory in the Fmr1 KO mice,possibly by inhibiting glycogen synthase kinase 3 beta activity.
文摘BACKGROUND Lymphangiomas in the gastrointestinal tract are extremely rare in adults.As a benign lesion,small intestine lymphangiomas often remain asymptomatic and pose challenges for definitive diagnosis.However,lymphangiomas can give rise to complications such as abdominal pain,bleeding,volvulus,and intussusception.Here,we report a case of jejunal cavernous lymphangioma that presented with intermittent melena and refractory anemia in a male adult.CASE SUMMARY A 66-year-old man presented with intermittent melena,fatigue and refractory anemia nine months prior.Esophagogastroduodenoscopy and colonoscopy were performed many times and revealed no apparent bleeding.Conservative management,including transfusion,hemostasis,gastric acid secretion inhibition and symptomatic treatment,was performed,but the lesions tended to recur shortly after surgery.Ultimately,the patient underwent capsule endoscopy,which revealed a more than 10 cm lesion accompanied by active bleeding.After singleballoon enteroscopy and biopsy,a diagnosis of jejunal cavernous lymphangioma was confirmed,and the patient underwent surgical resection.No complications or recurrences were observed postoperatively.CONCLUSION Jejunal cavernous lymphangioma should be considered a cause of obscure gastrointestinal bleeding.Capsule endoscopy and single-balloon enteroscopy can facilitate diagnosis.Surgical resection is an effective management method.
基金supported by the National Natural Science Foundation of China,No.31800892(to JLZ)the Natural Science Foundation of Guangdong Province of China,No.2018A030310254(to YY)a grant from Guangzhou Medical University Start-up Project of China,No.B195002002048(to JLZ)。
文摘The formation of nerve bundles,which is partially regulated by neural cell adhesion molecule 1(NCAM1),is important for neural network organization during peripheral nerve regeneration.However,little is known about how the extracellular matrix(ECM)microenvironment affects this process.Here,we seeded dorsal root ganglion tissue blocks on different ECM substrates of peripheral nerve ECM-derived matrixgel,Matrigel,laminin 521,collagen I,and collagen IV,and observed well-aligned axon bundles growing in the peripheral nerve ECM-derived environment.We confirmed that NCAM1 is necessary but not sufficient to trigger this phenomenon.A protein interaction assay identified collagen VI as an extracellular partner of NCAM1 in the regulation of axonal fasciculation.Collagen VI interacted with NCAM1 by directly binding to the FNIII domain,thereby increasing the stability of NCAM1 at the axolemma.Our in vivo experiments on a rat sciatic nerve defect model also demonstrated orderly nerve bundle regeneration with improved projection accuracy and functional recovery after treatment with 10 mg/m L Matrigel and 20μg/m L collagen VI.These findings suggest that the collagen VI-NCAM1 pathway plays a regulatory role in nerve bundle formation.This study was approved by the Animal Ethics Committee of Guangzhou Medical University(approval No.GY2019048)on April 30,2019.
基金supported by the National Natural Science Foundation of China (grant numbers 82371558)to R.S.
文摘Loneliness is associated with high prevalences of major psychiatric illnesses such as major depression.However,the underlying emotional mechanisms of loneliness remained unclear.We hypothesized that loneliness originates from both decreases in positive emotional processing and increases in negative emotion processing.To test this,we conducted a systematic review of 29 previous studies(total participants n=19560,mean age=37.16 years,female proportion=59.7%),including 18 studies that included ques-tionnaire measures of emotions only,and 11 studies that examined the brain correlates of emotions.The main findings were that loneliness was negatively correlated with general positive emotions and positively correlated with general negative emotions.Fur-thermore,limited evidence indicates loneliness exhibited negative and positive correlations with the brain positive(e.g.the striatum)and negative(e.g.insula)emotion systems,respectively,but the sign of correlation was not entirely consistent.Additionally,loneli-ness was associated with the structure and function of the brain emotion regulation systems,particularly the prefrontal cortex,but the direction of this relationship remained ambiguous.We concluded that the existing evidence supported a bivalence model of lone-liness,but several critical gaps existed that could be addressed by future studies that include adolescent and middle-aged samples,use both questionnaire and task measures of emotions,distinguish between general emotion and social emotion as well as between positive and negative emotion regulation,and adopt a longitudinal design that allows us to ascertain the causal relationships between loneliness and emotion dysfunction.Our findings provide new insights into the underlying emotion mechanisms of loneliness that can inform interventions for lonely individuals.
基金supported by the National Natural Science Foundation of China (32270663, 31871262, U20A20355,32022035)Shanghai Municipal Science and Technology Major Project(2018SHZDZX05)the Ministry of Science and Technology of China STI2030-Major Projects (2021ZD0203202)。
文摘Focal epilepsy accounts for 60% of all forms of epilepsy, but the pathogenic mechanism is not well understood. In this study,three novel mutations in NPRL3(nitrogen permease regulator-like 3), c.937_945del, c.1514dup C and 6,706-bp genomic DNA(g DNA) deletion, were identified in three families with focal epilepsy by linkage analysis, whole exome sequencing(WES) and Sanger sequencing. NPRL3 protein is a component of the GATOR1 complex, a major inhibitor of m TOR signaling. These mutations led to truncation of the NPRL3 protein and hampered the binding between NPRL3 and DEPDC5, which is another component of the GATOR1 complex. Consequently, the mutant proteins enhanced m TOR signaling in cultured cells, possibly due to impaired inhibition of m TORC1 by GATOR1. Knockdown of nprl3 in Drosophila resulted in epilepsy-like behavior and abnormal synaptic development. Taken together, these findings expand the genotypic spectrum of NPRL3-associated focal epilepsy and provide further insight into how NPRL3 mutations lead to epilepsy.
基金supported by the National Natural Science Foundation of China (81571273,81571274,81501124,81271434,and 81301107)Omics-based precision medicine of epilepsy being entrusted by Key Research Project of the Ministry of Science and Technology of China (2016YFC0904400)+5 种基金the Natural Science Foundation of Guangdong Province,China (2014A030313489)Science and Technology Planning Projects of Guangdong Province,China (2012B031800404 and 2013B051000084)the Department of Education of Guangdong Province,China (2013CXZDA022,2013KJCX0156,and 2012KJCX009)the Foundation for High-level Talents in Higher Education of Guangdong Province,China (2013-167)Yangcheng Scholar Research Projects of Guangzhou Municipal College (12A016S and 12A017G)Science and Technology Projects of Guangzhou,Guangdong Province,China (2014J4100069,201508020011,201604020161,and 201607010002)
文摘Ion channels are crucial in the generation and modulation of excitability in the nervous system and have been implicated in human epilepsy. Forty-one epilepsyassociated ion channel genes and their mutations are systematically reviewed. In this paper, we analyzed the genotypes, functional alterations（funotypes）, and phenotypes of these mutations. Eleven genes featured loss-offunction mutations and six had gain-of-function mutations.Nine genes displayed diversified funotypes, among which a distinct funotype-phenotype correlation was found in SCN1A. These data suggest that the funotype is an essential consideration in evaluating the pathogenicity of mutations and a distinct funotype or funotype-phenotype correlation helps to define the pathogenic potential of a gene.
基金supported by the grants of the National Natural Science Foundation of China(81671162,81521062,81561168,and 81571273)the National Basic Research Development Program of China(2014CB910300 and 2013CB530904)Key Research Project of the Ministry of Science and Technology of China(2016YFC0904400)
文摘N-methyl-D-aspartate receptors（NMDARs）, a subtype of glutamate-gated ion channels, play a central role in epileptogenesis. Recent studies have identified an increasing number of GRIN2 A（a gene encoding the NMDAR GluN2A subunit） mutations in patients with epilepsy. Phenotypes of GRIN2 A mutations include epilepsy-aphasia disorders and other epileptic encephalopathies, which pose challenges in clinical treatment. Here we identified a heterozygous GRIN2 A mutation（c.1341 T[A, p.N447 K） from a boy with Rolandic epilepsy by whole-exome sequencing. The patient became seizurefree with a combination of valproate and lamotrigine.Functional investigation was carried out using recombinant NMDARs containing a GluN2A-N447 K mutant that is located in the ligand-binding domain of the GluN2A subunit. Whole-cell current recordings in HEK 293 T cells revealed that the N447 K mutation increased the NMDAR current density by;.2-fold, enhanced the glutamate potency by 2-fold, and reduced the sensitivity to Mg;inhibition. These results indicated that N447 K is a gain-offunction mutation. Interestingly, alternative substitutions by alanine and glutamic acid at the same residue（N447 A and N447 E） did not change NMDAR function, suggesting a residual dependence of this mutation in altering NMDAR function. Taken together, this study identified human GluN2A N447 K as a novel mutation associated with epilepsy and validated its functional consequences in vitro.Identification of this mutation is also helpful for advancing our understanding of the role of NMDARs in epilepsy and provides new insights for precision therapeutics in epilepsy.
文摘Paroxysmal dyskinesias are a group of neurological diseases characterized by intermittent episodes of involuntary movements with different causes.Paroxysmal kinesigenic dyskinesia(PKD)is the most common type of paroxysmal dyskinesia and can be divided into primary and secondary types based on the etiology.Clinically,PKD is characterized by recurrent and transient attacks of involuntary movements precipitated by a sudden voluntary action.The major cause of primary PKD is genetic abnormalities,and the inheritance pattern of PKD is mainly autosomal-dominant with incomplete penetrance.The proline-rich transmembrane protein 2(PRRT2)was the first identified causative gene of PKD,accounting for the majority of PKD cases worldwide.An increasing number of studies has revealed the clinical and genetic characteristics,as well as the underlying mechanisms of PKD.By seeking the views of domestic experts,we propose an expert consensus regarding the diagnosis and treatment of PKD to help establish standardized clinical evaluation and therapies for PKD.In this consensus,we review the clinical manifestations,etiology,clinical diagnostic criteria and therapeutic recommendations for PKD,and results of genetic analyses in PKD patients performed in domestic hospitals.
基金funded by the National Natural Science Foundation of China(No.82201609)Shandong Medical and Health Science and Technology Development Plan(China)(No.202106010271)+2 种基金Scientific Research Project of Hunan Provincial Health Commission(China)(No.D202303077290)Guangdong Basic and Applied Basic Research Foundation(China)(No.2021A1515111064)Science and Technology Project of Guangzhou,Guangdong,China(No.202102021059,202201020106,202235395).
文摘The multiple PDZ domain crumbs cell polarity complex component gene(MPDZ;MIM:603785),is highly expressed in the brain across the whole lifespan.It encodes the multiple PDZ domain protein,which is a member of the NMDAR signaling complex that may play a role in the control of AMPAR potentiation and synaptic plasticity in excitatory synapses."Previously,MPDZ variants have been demonstrated to be associated with autosomal recessive congenital hydrocephalus-2(HYC2;MIM:615219)which is commonly complicated by brain abnormalities and developmental delay.Seizures were reported in only one case.The association between MPDz and epilepsy requires clarification.
基金supported by the National Natural Science Foundation of China (81171073, 30870876 and 31070928)the Guangzhou Municipal Scholar Project, Guangdong Province, China (10A011G)Scientific Research Program of Guangzhou Municipal Colleges and Universities (10A211)
文摘LIM kinase 1 （LIMK1）, a cytosolic serine/threonine kinase, regulates actin filament dynamics and reorganization and is involved in neuronal development and brain function. Abnormal expression of LIMK1 is associated with several neurological disorders. In this study, we performed a conservation analysis using Vector NTI （8.0） software. The dualluciferase reporter assay and real-time quantitative RT-PCR were used to assess the protein and mRNA levels of the reporter gene, respectively. We found that a region ranging from nt ＋884 to ＋966 in the human LIMK1 3＇ untranslated region （UTR） was highly conserved in the mouse Limkl 3＇ UTR and formed a structure containing several loops and stems. Luciferase assay showed that the relative luciferase activity of the mutated construct with the conserved region deleted, pGL4-hLIMK1-3U-M, in SH-SY5Y and HEK-293 cells was only -60% of that of the wild-type construct pGL4-hLIMK1-3U, indicating that the conserved region is critical for the reporter gene expression. Real-time quantitative RT-PCR analysis demonstrated that the relative Luc2 mRNA levels in SH-SY5Y and HEK293 cells transfected with pGL4-hLIMK1-3U-M decreased to50% of that in cells transfected with pGL4-hLIMK1- 3U, suggesting an important role of the conserved region in maintaining Luc2 mRNA stability. Our study suggests that the conserved region in the LIMK1 3＇ UTR is involved in regulating LIMK1 expression at the post-transcriptional level, which may help reveal the mechanism underlying the regulation of LIMK1 expression in the central nervous system and explore the relationship between the 3＇-UTR mutant and neuroloqical disorders.
基金Funded by the National Natural Science Foundation of China(Nos.50802069,81100890,51272191)the Fundamental Research Funds for the Central Unversities(WUT:2013-IV-010)the Students Innovation and Entrepreneurship Training Program of WHUT(20141049701012)
文摘A novel fluorescent probe 9-（4-（1,2-diamine）benzene-N1-phenyl）acridine（DABPA） was synthesized for the detection of nitric oxide（NO） and characterized by IR, 1H-NMR and EI-MS spectroscopy. Based on a photoelectron transfer mechanism, the fl uorescence intensities of DABPA were investigated with the different concentrations of NO. Under the optimal experimental conditions, the fl uorescence intensity of DABPA had a good linear relationship（R2=0.9977） with NO concentration in the range from 1×10-7 to 1.5×10-6 mol/L with a detection limit of 1×10-8 mol/L. The cytotoxicity induced by DABPA was evaluated by the MTT（3-（4,5-dimethylthiazol-2-yl）-2,5diphenyl tetrazolium bromide） assay for biological application. Furthermore, the probe DABPA had also been successfully applied to real-time image NO produced in PC12 cells in the presence of L-arginine.
基金supported by the National Natural Science Foundation of China (Nos. 31070928, 30600198, 30870876 and 81000558)the Guangzhou Scholar Project (Nos. 10A011G and 10A012G)the Scientific Research of Guangzhou Municipal Colleges and Universities (No. 10A211).
文摘Transcription factors（TFs）play critical roles in the development of the nervous system,but the transcriptional regulatory mechanisms of these genes are poorly understood.Here we analyzed 5-kb of the 5＇ flanking genomic DNA sequences of 41 TF genes involved in neuronal development.The results showed that the TF genes tend to have higher GC contents in the proximal region and most of the TF genes have at least one proximal GC-rich（GC content60%）promoter with a CpG island.The promoter distribution analysis showed that the GC-poor promoters were sporadically distributed within the 5-kb flanking genomic sequence（FGS）;however,more than half（37 of 70）of the GC-rich promoters were located in the proximal region between nucleotides—1 and—500.Luciferase assays showed that partial GC-rich promoters increased gene expression in SH-SY5Y cells and that CpG methylation repressed the promoter activity.This study suggests a potential general mechanism for regulation of TF expression.
基金funded by the National Natural Science Foundation of China(Grant No.82301639 to Bin Li,Grant No.82171441 to Xu-Qin Chen,and Grant No.82201609 to Jie Wang).
文摘The ARHGAP4 gene(OMIM*300,023),also known as Rho GTPase activating protein 4,encodes a protein that has an essential role in the regulation of small GTP-binding.ARHGAP4 message RNA(mRNA)is highly expressed during the developing and adult nervous system.At the protein level,ARHGAP4 is exclusively present in certain brain regions,such as the mesial temporal lobe,specifically the stratum lucidum of the CA3 region[1].ARHGAP4 enhances the GTPase activity of Rho proteins,which modulate morphological alterations in neuron development and synaptic plasticity by interacting with the actin cytoskeleton[2].
