The phytohormone auxin plays crucial roles in nearly every aspect of plant growth and development.Auxin signaling is activated through the phytohormone-induced proteasomal degradation of the Auxin/INDOLE-3-ACETIC ACID...The phytohormone auxin plays crucial roles in nearly every aspect of plant growth and development.Auxin signaling is activated through the phytohormone-induced proteasomal degradation of the Auxin/INDOLE-3-ACETIC ACID(Aux/IAA)family of transcriptional repressors.Notably,many auxin-modulated physiological processes are also regulated by nitric oxide(NO)that executes its biological effects predominantly through protein S-nitrosylation at specific cysteine residues.However,little is known about the molecular mechanisms in regulating the interactive NO and auxin networks.Here,we show that NO represses auxin signaling by inhibiting IAA17 protein degradation.NO induces the S-nitrosylation of Cys-70 located in the intrinsically disordered region of IAA17,which inhibits the TIR1-IAA17 interaction and consequently the proteasomal degradation of IAA17.The accumulation of a higher level of IAA17 attenuates auxin response.Moreover,an IAA17^(C70W)nitrosomimetic mutation renders the accumulation of a higher level of the mutated protein,thereby causing partial resistance to auxin and defective lateral root development.Taken together,these results suggest that S-nitrosylation of IAA17 at Cys-70 inhibits its interaction with TIR1,thereby negatively regulating auxin signaling.This study provides unique molecular insights into the redox-based auxin signaling in regulating plant growth and development.展开更多
BACKGROUND The burden of mental disorders(MD)in the Western Pacific Region(WPR)re-mains a critical public health concern,with substantial variations across demogra-phics and countries.AIM To analyze the burden of MD i...BACKGROUND The burden of mental disorders(MD)in the Western Pacific Region(WPR)re-mains a critical public health concern,with substantial variations across demogra-phics and countries.AIM To analyze the burden of MD in the WPR from 1990 to 2021,along with associated risk factors,to reveal changing trends and emerging challenges.METHODS We used data from the Global Burden of Disease 2021,analyzing prevalence,incidence,and disability-adjusted life years(DALYs)of MD from 1990 to 2021.Statistical methods included age-standardisation and uncertainty analysis to address variations in population structure and data completeness.RESULTS Between 1990 and 2021,the prevalence of MD rose from 174.40 million cases[95%uncertainty interval(UI):160.17-189.84]to 234.90 million cases(95%UI:219.04-252.50),with corresponding DALYs increasing from 22.8 million(95%UI:17.22-28.79)to 32.07 million(95%UI:24.50-40.68).During this period,the burden of MD shifted towards older age groups.Depressive and anxiety disorders were predominant,with females showing higher DALYs for depressive and anxiety disorders,and males more affected by conduct disorders,attention-deficit hyperactivity disorder,and autism spectrum disorders.Australia,New Zealand,and Malaysia reported the highest burdens,whereas Vietnam,China,and Brunei Darussalam reported the lowest.Additionally,childhood sexual abuse and bullying,and intimate partner violence emerged as significant risk factors.CONCLUSION This study highlights the significant burden of MD in the WPR,with variations by age,gender,and nation.The coronavirus disease 2019 pandemic has exacerbated the situation,emphasizing the need for a coordinated response.展开更多
Attention-deficit/hyperactivity disorder(ADHD)is one of the most common neurodevelopmental disorders of childhood,yet its diagnosis remains complex and fraught with challenges.Pediatricians,often the first point of co...Attention-deficit/hyperactivity disorder(ADHD)is one of the most common neurodevelopmental disorders of childhood,yet its diagnosis remains complex and fraught with challenges.Pediatricians,often the first point of contact for concerned families,play a pivotal role in the diagnostic process.However,they face numerous obstacles that can hinder accurate and timely diagnosis,particularly in resource-limited or culturally diverse settings such as the Middle East and North Africa(MENA)and Arabian Gulf regions.This narrative review explores the key challenges pediatricians face in diagnosing ADHD and highlights practical and emerging solutions.The article offers both a global perspective and a contextualized view relevant to the MENA region.A narrative literature review was conducted using PubMed,Scopus,and Google Scholar,focusing on peer-reviewed studies,clinical guidelines,and epidemiological data from 2010 to 2025 related to pediatric ADHD diagnosis,especially in MENA regions.The review identifies six major diagnostic barriers:(1)Symptom overlap with other conditions[e.g.,autism spectrum disorder(ASD),anxiety,learning disabilities];(2)Reliance on subjective informant reports;(3)Cultural and societal influences including stigma and gender bias;(4)Variability in ADHD training and time constraints in clinical practice;(5)Limited access to multidisciplinary evaluations;and(6)Systemic referral and communication inefficiencies.Comorbidities are highly prevalent and frequently complicate the diagnostic picture.Delayed or inaccurate diagnosis can lead to academic underperformance,family stress,missed interventions,and long-term psychological consequences.Emerging solutions include digital screening tools,artificial intelligence-assisted analysis,structured reporting platforms,and improved training and referral models.Regional data from the Arabian Gulf highlight variable prevalence rates(1.3%-22%)and underscore the need for culturally sensitive diagnostic strategies.To improve diagnostic accuracy and patient outcomes,pediatricians must be supported through better training,interdisciplinary collaboration,validated tools,and policy-level reforms.Tailoring these approaches to local contexts will be key to addressing the growing burden of ADHD,particularly in the MENA region.展开更多
Developmental disorders(DDs)are a kind of chronic maladies,which can cause serious irreversible detriment to children’s physical and mental health.It is predominantly regulated by the interaction of environment and h...Developmental disorders(DDs)are a kind of chronic maladies,which can cause serious irreversible detriment to children’s physical and mental health.It is predominantly regulated by the interaction of environment and heredity.Cold regions are mainly located in the high latitudes of China.Their living environment is characterized by frequent cold wave,huge temperature difference,severe air pollution,high calorie diet,less exercise,smoking,drinking,etc.In recent years,substantial advances have been made in studies of the correlation between the living environment features in cold regions and the DDs.Accordingly,this article reviews the impact of the peculiar living environment of cold regions on DDs,with a view to provide fresh prevention strategies for reducing the morbidity of DDs in China cold regions by ameliorating living environment.展开更多
Biomolecular condensates comprise a diverse array of molecular entities,with intrinsically disordered regions(IDRs)receiving mounting attention due to their pivotal roles.In recent years,significant progress has been ...Biomolecular condensates comprise a diverse array of molecular entities,with intrinsically disordered regions(IDRs)receiving mounting attention due to their pivotal roles.In recent years,significant progress has been made in understanding the linear and conformational molecular grammar of IDRs in biomolecular condensates.This review will focus on the advances in studying IDR conformational ensembles and their relationship to func-tion,with a particular emphasis on molecular dynamics(MD)simulations and the emerging synergy between MD and machine learning(ML)methods.Nevertheless,the inherent flexibility and dynamic nature of IDRs continue to present substantial challenges for conformation analysis.The integration of advanced experimental techniques,computational methods,and evolutionary analysis promises to unveil the conformational mysteries and thera-peutic potential of IDRs in condensates.展开更多
Objective Little is known about the brain systems that contribute to vulnerability to post-traumatic stress disorder （PTSD）. Comparison of the resting-state patterns of intrinsic functional synchronization, as measu...Objective Little is known about the brain systems that contribute to vulnerability to post-traumatic stress disorder （PTSD）. Comparison of the resting-state patterns of intrinsic functional synchronization, as measured by functional magnetic resonance imaging （fMRI）, between groups with and without PTSD following a traumatic event can help identify the neural mechanisms of the disorder and targets for intervention. Methods Fifty-four PTSD patients and 72 matched traumatized subjects who experienced the 2008 Sichuan earthquake were imaged with blood oxygen level-dependent （BOLD） fMRI and analyzed using the measure of regional homogeneity （ReHo） during the resting state. Results PTSD patients presented enhanced ReHo in the left inferior parietal lobule and right superior frontal gyrus, and reduced ReHo in the right middle temporal gyrus and lingual gyrus, relative to traumatized individuals without PTSD. Conclusion Our findings showed that abnormal brain activity exists under resting conditions in PTSD patients who had been exposed to a major earthquake. Alterations in the local functional connectivity of cortical regions are likely to contribute to the neural mechanisms underlying PTSD.展开更多
Phase separation(PS)plays a fundamental role in organizing aggregates during the viral lifecycle,providing significant opportunities for in viral disease treatment by inhibiting PS.Intrinsically disordered regions(IDR...Phase separation(PS)plays a fundamental role in organizing aggregates during the viral lifecycle,providing significant opportunities for in viral disease treatment by inhibiting PS.Intrinsically disordered regions(IDRs)have been extensively studied and found to be critical for PS.However,the discovery of small molecules that target residues within IDRs remains underexplored,particularly in the field of pesticides.Herein,we report a novel phytovirucide compound 29,which was screened from a series of vanillin derivatives designed with sulfonylpiperazine motifs.The inactivation efficacy of compound 29 against tomato spotted wilt virus(TSWV)was significantly superior to that of the control agents vanisulfane and ribavirin.Mechanistically,compound 29 binds to the TSWV nucleocapsid protein(NP)at residues Lys68(K68),Thr92(T92),and Arg94(R94),with T92 and R94 located in the IDRs of NP.Mutations at these sites impair the ability to form aggregates.Furthermore,a host factor,GTP(Guanosine Triphosphate)-binding nuclear protein Ran-like(Niben101scf08341g01001,NbRANL),which interacts with NP and promotes its aggregation,was identified.Compound 29 also suppresses the expression of NbRANL,resulting in the dual inhibition of ribonucleoprotein complexes(RNPs)formation.This unique mechanism of action provides insights into IDRs-based virucide discovery.展开更多
Deep brain sti mulation(DBS)is a neuromodulation tool that involves the delivery of electrical impulses to specific brain regions through implanted electrodes.The principle behind DBS is to modulate dysfunctional neur...Deep brain sti mulation(DBS)is a neuromodulation tool that involves the delivery of electrical impulses to specific brain regions through implanted electrodes.The principle behind DBS is to modulate dysfunctional neural circuits without the need for permanent structural alterations to the brain.Initially developed as a treatment for movement disorders such as Parkinson's disease(PD),DBS has expanded to encompass various neurological and psychiatric disorders.展开更多
Regional homogeneity（ReHo）and the amplitude of low-frequency fluctuation（ALFF）are two approaches to depicting different regional characteristics of resting-state functional magnetic resonance imaging（RS-fMRI）dat...Regional homogeneity（ReHo）and the amplitude of low-frequency fluctuation（ALFF）are two approaches to depicting different regional characteristics of resting-state functional magnetic resonance imaging（RS-fMRI）data.Whether they can complementarily reveal brain regional functional abnormalities in attention-deficit/hyperactivity disorder（ADHD）remains unknown.In this study,we applied ReHo and ALFF to 23 medication-na ve boys diagnosed with ADHD and 25 age-matched healthy male controls using whole-brain voxel-wise analysis.Correlation analyses were conducted in the ADHD group to investigate the relationship between the regional spontaneous brain activity measured by the two approaches and the clinical symptoms of ADHD.We found that the ReHo method showed widely-distributed differences between the two groups in the fronto-cingulo-occipitocerebellar circuitry,while the ALFF method showed a difference only in the right occipital area.When a larger smoothing kernel and a more lenient threshold were used for ALFF,more overlapped regions were found between ALFF and ReHo,and ALFF even found some new regions with group differences.The ADHD symptom scores were correlated with the ReHo values in the right cerebellum,dorsal anterior cingulate cortex and left lingual gyrus in the ADHD group,while no correlation was detected between ALFF and ADHD symptoms.In conclusion,ReHo may be more sensitive to regional abnormalities,at least in boys with ADHD,than ALFF.And ALFF may be complementary to ReHo in measuring local spontaneous activity.Combination of the two may yield a more comprehensive pathophy-siological framework for ADHD.展开更多
Machine learning approaches are increasingly being applied to neuroimaging data from patients with psychiatric disorders to extract brain-based features for diagnosis and prognosis.The goal of this review is to discus...Machine learning approaches are increasingly being applied to neuroimaging data from patients with psychiatric disorders to extract brain-based features for diagnosis and prognosis.The goal of this review is to discuss recent practices for evaluating machine learning applications to obsessive-compulsive and related disorders and to advance a novel strategy of building machine learning models based on a set of core brain regions for better performance,interpretability,and generalizability.Specifically,we argue that a core set of co-altered brain regions(namely‘core regions’)comprising areas central to the underlying psychopathology enables the efficient construction of a predictive model to identify distinct symptom dimensions/clusters in individual patients.Hypothesis-driven and data-driven approaches are further introduced showing how core regions are identified from the entire brain.We demonstrate a broadly applicable roadmap for leveraging this core set-based strategy to accelerate the pursuit of neuroimaging-based markers for diagnosis and prognosis in a variety of psychiatric disorders.展开更多
BACKGROUND： Serotonin transporter （5-HTT） polymorphisms comprise 5-HTT gene-linked polymorphism region （5-HTTLPR） and variable number of tandem repeats （VNTR）. Studies have revealed an association between 5-HTT...BACKGROUND： Serotonin transporter （5-HTT） polymorphisms comprise 5-HTT gene-linked polymorphism region （5-HTTLPR） and variable number of tandem repeats （VNTR）. Studies have revealed an association between 5-HTT polymorphism and major depressive disorder, which suggests that the ＂S＂ allele of 5-HTTLPR and Stin2.9 of 5-HTTVNTR are associated with major depressive disorder. However, there are a number of studies that do not support the 5-HTT polymorphism effect in major depressive disorder. OBJECTIVE： To study the relationship between 5-HTT gene polymorphism and major depressive disorder in Chinese Han population. DESIGN, TIME AND SETTING： Case-controlled study of 5-HTT gene polymorphism. The experiment was performed at the Central Laboratory, Third Affiliated Hospital of Sun Yat-sen University, China from March 2005 to January 2006. PARTICIPANTS： A total of 99 depressive patients of Chinese Han nationality were recruited for this study. All patients met DSM-IV diagnostic criteria for major depressive disorder and had a total score of Hamilton Depression Scale （24 items） ≥21 points. In addition, 101 healthy subjects, matched for age and gender, served as the control group. METHODS： Venous blood was collected from all subjects. 5-HTT genotypes and alleles were determined by polymerase chain reaction. Consistent with the Hardy-Weinberg equilibrium, the association between 5-HTT gene polymorphism and major depressive disorder were analyzed by Chi-square test. MAIN OUTCOME MEASURES： 5-HTTLPR and 5-HTTVNTR genotypes and allele frequencies were measured. RESULTS： No significant differences in 5-HTTLPR genotypes and allele frequencies were determined between patients and controls （P 〉 0.05）. However, significant differences in 5-HTTVNTR genotypes and allele frequencies were detected （P 〈 0.01 ）. The Stin2.10 allele and 10/10 genotype associated with major depressive disorder （OR = 2.61,7.7, P 〈 0.05; analysis of dose-response relationships Х^2 = 12.35, P 〈 0.01）. CONCLUSION： Results from the present study revealed no association between 5-HTTLPR and major depressive disorder. However, a significant association between 5-HTTVNTR and major depressive disorder existed in a population of Chinese Han. The presence of Stin2.10 and 10/10 genotypes increased the risk for major depressive disorder in a dose-dependent manner.展开更多
基金supported by grants from the National Natural Science Foundation of China (31830017)Chinese Academy of Sciences (XDB27030207)+1 种基金the Hainan Excellent Talent TeamState Key Laboratory of Plant Genomics (SKLPG2023-22)
文摘The phytohormone auxin plays crucial roles in nearly every aspect of plant growth and development.Auxin signaling is activated through the phytohormone-induced proteasomal degradation of the Auxin/INDOLE-3-ACETIC ACID(Aux/IAA)family of transcriptional repressors.Notably,many auxin-modulated physiological processes are also regulated by nitric oxide(NO)that executes its biological effects predominantly through protein S-nitrosylation at specific cysteine residues.However,little is known about the molecular mechanisms in regulating the interactive NO and auxin networks.Here,we show that NO represses auxin signaling by inhibiting IAA17 protein degradation.NO induces the S-nitrosylation of Cys-70 located in the intrinsically disordered region of IAA17,which inhibits the TIR1-IAA17 interaction and consequently the proteasomal degradation of IAA17.The accumulation of a higher level of IAA17 attenuates auxin response.Moreover,an IAA17^(C70W)nitrosomimetic mutation renders the accumulation of a higher level of the mutated protein,thereby causing partial resistance to auxin and defective lateral root development.Taken together,these results suggest that S-nitrosylation of IAA17 at Cys-70 inhibits its interaction with TIR1,thereby negatively regulating auxin signaling.This study provides unique molecular insights into the redox-based auxin signaling in regulating plant growth and development.
基金Supported by National Key Research and Development Program of China,No.2022YFC3600903Key Discipline Project under Shanghai's Three-Year Action Plan for Strengthening the Public Health System(2023-2025),No.GWVI-11.1-44.
文摘BACKGROUND The burden of mental disorders(MD)in the Western Pacific Region(WPR)re-mains a critical public health concern,with substantial variations across demogra-phics and countries.AIM To analyze the burden of MD in the WPR from 1990 to 2021,along with associated risk factors,to reveal changing trends and emerging challenges.METHODS We used data from the Global Burden of Disease 2021,analyzing prevalence,incidence,and disability-adjusted life years(DALYs)of MD from 1990 to 2021.Statistical methods included age-standardisation and uncertainty analysis to address variations in population structure and data completeness.RESULTS Between 1990 and 2021,the prevalence of MD rose from 174.40 million cases[95%uncertainty interval(UI):160.17-189.84]to 234.90 million cases(95%UI:219.04-252.50),with corresponding DALYs increasing from 22.8 million(95%UI:17.22-28.79)to 32.07 million(95%UI:24.50-40.68).During this period,the burden of MD shifted towards older age groups.Depressive and anxiety disorders were predominant,with females showing higher DALYs for depressive and anxiety disorders,and males more affected by conduct disorders,attention-deficit hyperactivity disorder,and autism spectrum disorders.Australia,New Zealand,and Malaysia reported the highest burdens,whereas Vietnam,China,and Brunei Darussalam reported the lowest.Additionally,childhood sexual abuse and bullying,and intimate partner violence emerged as significant risk factors.CONCLUSION This study highlights the significant burden of MD in the WPR,with variations by age,gender,and nation.The coronavirus disease 2019 pandemic has exacerbated the situation,emphasizing the need for a coordinated response.
文摘Attention-deficit/hyperactivity disorder(ADHD)is one of the most common neurodevelopmental disorders of childhood,yet its diagnosis remains complex and fraught with challenges.Pediatricians,often the first point of contact for concerned families,play a pivotal role in the diagnostic process.However,they face numerous obstacles that can hinder accurate and timely diagnosis,particularly in resource-limited or culturally diverse settings such as the Middle East and North Africa(MENA)and Arabian Gulf regions.This narrative review explores the key challenges pediatricians face in diagnosing ADHD and highlights practical and emerging solutions.The article offers both a global perspective and a contextualized view relevant to the MENA region.A narrative literature review was conducted using PubMed,Scopus,and Google Scholar,focusing on peer-reviewed studies,clinical guidelines,and epidemiological data from 2010 to 2025 related to pediatric ADHD diagnosis,especially in MENA regions.The review identifies six major diagnostic barriers:(1)Symptom overlap with other conditions[e.g.,autism spectrum disorder(ASD),anxiety,learning disabilities];(2)Reliance on subjective informant reports;(3)Cultural and societal influences including stigma and gender bias;(4)Variability in ADHD training and time constraints in clinical practice;(5)Limited access to multidisciplinary evaluations;and(6)Systemic referral and communication inefficiencies.Comorbidities are highly prevalent and frequently complicate the diagnostic picture.Delayed or inaccurate diagnosis can lead to academic underperformance,family stress,missed interventions,and long-term psychological consequences.Emerging solutions include digital screening tools,artificial intelligence-assisted analysis,structured reporting platforms,and improved training and referral models.Regional data from the Arabian Gulf highlight variable prevalence rates(1.3%-22%)and underscore the need for culturally sensitive diagnostic strategies.To improve diagnostic accuracy and patient outcomes,pediatricians must be supported through better training,interdisciplinary collaboration,validated tools,and policy-level reforms.Tailoring these approaches to local contexts will be key to addressing the growing burden of ADHD,particularly in the MENA region.
基金This work was supported by the Key Project of Harbin Medical University Cultivation Fund.
文摘Developmental disorders(DDs)are a kind of chronic maladies,which can cause serious irreversible detriment to children’s physical and mental health.It is predominantly regulated by the interaction of environment and heredity.Cold regions are mainly located in the high latitudes of China.Their living environment is characterized by frequent cold wave,huge temperature difference,severe air pollution,high calorie diet,less exercise,smoking,drinking,etc.In recent years,substantial advances have been made in studies of the correlation between the living environment features in cold regions and the DDs.Accordingly,this article reviews the impact of the peculiar living environment of cold regions on DDs,with a view to provide fresh prevention strategies for reducing the morbidity of DDs in China cold regions by ameliorating living environment.
基金supported by the National Natural Science Foun-dation of China(T2325003 and 32470575)the National Key Re-search and Development Program of China(2023YFF1204703 and 2021YFF1200900)Beijing Natural Science Foundation(Z230014).
文摘Biomolecular condensates comprise a diverse array of molecular entities,with intrinsically disordered regions(IDRs)receiving mounting attention due to their pivotal roles.In recent years,significant progress has been made in understanding the linear and conformational molecular grammar of IDRs in biomolecular condensates.This review will focus on the advances in studying IDR conformational ensembles and their relationship to func-tion,with a particular emphasis on molecular dynamics(MD)simulations and the emerging synergy between MD and machine learning(ML)methods.Nevertheless,the inherent flexibility and dynamic nature of IDRs continue to present substantial challenges for conformation analysis.The integration of advanced experimental techniques,computational methods,and evolutionary analysis promises to unveil the conformational mysteries and thera-peutic potential of IDRs in condensates.
基金supported by the National Natural Science Foundation of China (30830046,30625024, 81171286)the National Science and Technology Program of China (2007BAI17B02)+2 种基金the National Basic Research Development Program (973 Program) of China(2009CB918303)the Science and Technology Program of the Ministry of Education, China (20090162110011)the National High-Tech Research and Development Program of China (863 program:2008AA02Z408)
文摘Objective Little is known about the brain systems that contribute to vulnerability to post-traumatic stress disorder （PTSD）. Comparison of the resting-state patterns of intrinsic functional synchronization, as measured by functional magnetic resonance imaging （fMRI）, between groups with and without PTSD following a traumatic event can help identify the neural mechanisms of the disorder and targets for intervention. Methods Fifty-four PTSD patients and 72 matched traumatized subjects who experienced the 2008 Sichuan earthquake were imaged with blood oxygen level-dependent （BOLD） fMRI and analyzed using the measure of regional homogeneity （ReHo） during the resting state. Results PTSD patients presented enhanced ReHo in the left inferior parietal lobule and right superior frontal gyrus, and reduced ReHo in the right middle temporal gyrus and lingual gyrus, relative to traumatized individuals without PTSD. Conclusion Our findings showed that abnormal brain activity exists under resting conditions in PTSD patients who had been exposed to a major earthquake. Alterations in the local functional connectivity of cortical regions are likely to contribute to the neural mechanisms underlying PTSD.
基金support from the National Natural Science Foundation of China(Nos.32330087 and 32302388)the Key Technologies R&D Program of Guizhou Province in China(No.2017-5788-1)the Scientific Research Innovation Team of Guizhou University(No.202403).
文摘Phase separation(PS)plays a fundamental role in organizing aggregates during the viral lifecycle,providing significant opportunities for in viral disease treatment by inhibiting PS.Intrinsically disordered regions(IDRs)have been extensively studied and found to be critical for PS.However,the discovery of small molecules that target residues within IDRs remains underexplored,particularly in the field of pesticides.Herein,we report a novel phytovirucide compound 29,which was screened from a series of vanillin derivatives designed with sulfonylpiperazine motifs.The inactivation efficacy of compound 29 against tomato spotted wilt virus(TSWV)was significantly superior to that of the control agents vanisulfane and ribavirin.Mechanistically,compound 29 binds to the TSWV nucleocapsid protein(NP)at residues Lys68(K68),Thr92(T92),and Arg94(R94),with T92 and R94 located in the IDRs of NP.Mutations at these sites impair the ability to form aggregates.Furthermore,a host factor,GTP(Guanosine Triphosphate)-binding nuclear protein Ran-like(Niben101scf08341g01001,NbRANL),which interacts with NP and promotes its aggregation,was identified.Compound 29 also suppresses the expression of NbRANL,resulting in the dual inhibition of ribonucleoprotein complexes(RNPs)formation.This unique mechanism of action provides insights into IDRs-based virucide discovery.
文摘Deep brain sti mulation(DBS)is a neuromodulation tool that involves the delivery of electrical impulses to specific brain regions through implanted electrodes.The principle behind DBS is to modulate dysfunctional neural circuits without the need for permanent structural alterations to the brain.Initially developed as a treatment for movement disorders such as Parkinson's disease(PD),DBS has expanded to encompass various neurological and psychiatric disorders.
基金supported by the Commonwealth Sciences Foundation, Ministry of Health, China (200802073)the National Basic Research Development Program, Ministry of Science and Technology, China (2007BAI17B03)+1 种基金the National Natural Sciences Foundation of China (30970802, 81000593, 81020108022, 81271652)the Open Research Fund of the State Key Laboratory of Cognitive Neuroscience and Learning
文摘Regional homogeneity（ReHo）and the amplitude of low-frequency fluctuation（ALFF）are two approaches to depicting different regional characteristics of resting-state functional magnetic resonance imaging（RS-fMRI）data.Whether they can complementarily reveal brain regional functional abnormalities in attention-deficit/hyperactivity disorder（ADHD）remains unknown.In this study,we applied ReHo and ALFF to 23 medication-na ve boys diagnosed with ADHD and 25 age-matched healthy male controls using whole-brain voxel-wise analysis.Correlation analyses were conducted in the ADHD group to investigate the relationship between the regional spontaneous brain activity measured by the two approaches and the clinical symptoms of ADHD.We found that the ReHo method showed widely-distributed differences between the two groups in the fronto-cingulo-occipitocerebellar circuitry,while the ALFF method showed a difference only in the right occipital area.When a larger smoothing kernel and a more lenient threshold were used for ALFF,more overlapped regions were found between ALFF and ReHo,and ALFF even found some new regions with group differences.The ADHD symptom scores were correlated with the ReHo values in the right cerebellum,dorsal anterior cingulate cortex and left lingual gyrus in the ADHD group,while no correlation was detected between ALFF and ADHD symptoms.In conclusion,ReHo may be more sensitive to regional abnormalities,at least in boys with ADHD,than ALFF.And ALFF may be complementary to ReHo in measuring local spontaneous activity.Combination of the two may yield a more comprehensive pathophy-siological framework for ADHD.
基金supported by the Key-Area Research and Development Program of Guangdong Province(2019B030335001)the National Natural Science Foundation of China(82151303)+1 种基金the National Key R&D Program of China(2021ZD0204002)Peking-Tsinghua Centre for Life Sciences.Qian Lv was supported by a Postdoctoral Fellowship of the Peking-Tsinghua Center for Life Sciences.
文摘Machine learning approaches are increasingly being applied to neuroimaging data from patients with psychiatric disorders to extract brain-based features for diagnosis and prognosis.The goal of this review is to discuss recent practices for evaluating machine learning applications to obsessive-compulsive and related disorders and to advance a novel strategy of building machine learning models based on a set of core brain regions for better performance,interpretability,and generalizability.Specifically,we argue that a core set of co-altered brain regions(namely‘core regions’)comprising areas central to the underlying psychopathology enables the efficient construction of a predictive model to identify distinct symptom dimensions/clusters in individual patients.Hypothesis-driven and data-driven approaches are further introduced showing how core regions are identified from the entire brain.We demonstrate a broadly applicable roadmap for leveraging this core set-based strategy to accelerate the pursuit of neuroimaging-based markers for diagnosis and prognosis in a variety of psychiatric disorders.
基金a grant from the Foundation of Guangdong Province of Science and Technology,No. 2003C3380
文摘BACKGROUND： Serotonin transporter （5-HTT） polymorphisms comprise 5-HTT gene-linked polymorphism region （5-HTTLPR） and variable number of tandem repeats （VNTR）. Studies have revealed an association between 5-HTT polymorphism and major depressive disorder, which suggests that the ＂S＂ allele of 5-HTTLPR and Stin2.9 of 5-HTTVNTR are associated with major depressive disorder. However, there are a number of studies that do not support the 5-HTT polymorphism effect in major depressive disorder. OBJECTIVE： To study the relationship between 5-HTT gene polymorphism and major depressive disorder in Chinese Han population. DESIGN, TIME AND SETTING： Case-controlled study of 5-HTT gene polymorphism. The experiment was performed at the Central Laboratory, Third Affiliated Hospital of Sun Yat-sen University, China from March 2005 to January 2006. PARTICIPANTS： A total of 99 depressive patients of Chinese Han nationality were recruited for this study. All patients met DSM-IV diagnostic criteria for major depressive disorder and had a total score of Hamilton Depression Scale （24 items） ≥21 points. In addition, 101 healthy subjects, matched for age and gender, served as the control group. METHODS： Venous blood was collected from all subjects. 5-HTT genotypes and alleles were determined by polymerase chain reaction. Consistent with the Hardy-Weinberg equilibrium, the association between 5-HTT gene polymorphism and major depressive disorder were analyzed by Chi-square test. MAIN OUTCOME MEASURES： 5-HTTLPR and 5-HTTVNTR genotypes and allele frequencies were measured. RESULTS： No significant differences in 5-HTTLPR genotypes and allele frequencies were determined between patients and controls （P 〉 0.05）. However, significant differences in 5-HTTVNTR genotypes and allele frequencies were detected （P 〈 0.01 ）. The Stin2.10 allele and 10/10 genotype associated with major depressive disorder （OR = 2.61,7.7, P 〈 0.05; analysis of dose-response relationships Х^2 = 12.35, P 〈 0.01）. CONCLUSION： Results from the present study revealed no association between 5-HTTLPR and major depressive disorder. However, a significant association between 5-HTTVNTR and major depressive disorder existed in a population of Chinese Han. The presence of Stin2.10 and 10/10 genotypes increased the risk for major depressive disorder in a dose-dependent manner.
