Thecoronavirusdisease2019(COVID-19)pandemic continues to pose a global threat to the human population. Identifying animal species susceptible to infection with the SARS-CoV-2/HCoV-19 pathogen is essential for controll...Thecoronavirusdisease2019(COVID-19)pandemic continues to pose a global threat to the human population. Identifying animal species susceptible to infection with the SARS-CoV-2/HCoV-19 pathogen is essential for controlling the outbreak and for testing valid prophylactics or therapeutics based on animal model studies. Here,different aged Chinese tree shrews(adult group, 1 year old;old group, 5–6 years old), which are close relatives to primates, were infected with SARS-CoV-2. X-ray, viral shedding, laboratory, and histological analyses were performed on different days postinoculation(dpi). Results showed that Chinese tree shrews could be infected by SARS-CoV-2. Lung infiltrates were visible in X-ray radiographs in most infected animals. Viral RNA was consistently detected in lung tissues from infected animals at 3,5, and 7 dpi, along with alterations in related parameters from routine blood tests and serum biochemistry, including increased levels of aspartate aminotransferase(AST) and blood urea nitrogen(BUN). Histological analysis of lung tissues from animals at 3 dpi(adult group) and 7 dpi(old group) showed thickened alveolar septa and interstitial hemorrhage. Several differences were found between the two different aged groups in regard to viral shedding peak. Our results indicate that Chinese tree shrews have the potential to be used as animal models for SARS-CoV-2 infection.展开更多
Major depressive disorder(MDD),also referred to as depression,is one of the most common psychiatric disorders with a high economic burden.The etiology of depression is still not clear,but it is generally believed that...Major depressive disorder(MDD),also referred to as depression,is one of the most common psychiatric disorders with a high economic burden.The etiology of depression is still not clear,but it is generally believed that MDD is a multifactorial disease caused by the interaction of social,psychological,and biological aspects.Therefore,there is no exact pathological theory that can independently explain its pathogenesis,involving genetics,neurobiology,and neuroimaging.At present,there are many treatment measures for patients with depression,including drug therapy,psychotherapy,and neuromodulation technology.In recent years,great progress has been made in the development of new antidepressants,some of which have been applied in the clinic.This article mainly reviews the research progress,pathogenesis,and treatment of MDD.展开更多
Alzheimer’s disease(AD)is the most common type of dementia,and no disease-modifying treatments are available to halt or slow its progression.Amyloid-beta(Aβ)is suggested to play a pivotal role in the pathogenesis of...Alzheimer’s disease(AD)is the most common type of dementia,and no disease-modifying treatments are available to halt or slow its progression.Amyloid-beta(Aβ)is suggested to play a pivotal role in the pathogenesis of AD,and clearance of Aβfrom the brain becomes a main therapeutic strategy for AD.Recent studies found that Aβclearance in the periphery contributes substantially to reducing Aβaccumulation in the brain.Therefore,understanding the mechanism of how Aβis cleared in the periphery is important for the development of effective therapies for AD.In this review,we summarized recent findings on the mechanisms of Aβefflux from the brain to the periphery and discuss where and how the brain-derived Aβis cleared in the periphery.Based on these findings,we propose future strategies to enhance peripheral Aβclearance for the prevention and treatment of AD.This review provides a novel perspective to understand the pathogenesis of AD and develop interventions for this disease from a systemic approach.展开更多
Hippocampal morphological change is one of the main hallmarks of Alzheimer’s disease(AD).However,whether hippocampal radiomic features are robust as predictors of progression from mild cognitive impairment(MCI)to AD ...Hippocampal morphological change is one of the main hallmarks of Alzheimer’s disease(AD).However,whether hippocampal radiomic features are robust as predictors of progression from mild cognitive impairment(MCI)to AD dementia and whether these features provide any neurobiological foundation remains unclear.The primary aim of this study was to verify whether hippocampal radiomic features can serve as robust magnetic resonance imaging(MRI)markers for AD.Multivariate classifier-based support vector machine(SVM)analysis provided individual-level predictions for distinguishing AD patients(n=261)from normal controls(NCs;n=231)with an accuracy of 88.21%and intersite crossvalidation.Further analyses of a large,independent the Alzheimer’s Disease Neuroimaging Initiative(ADNI)dataset(n=1228)reinforced these findings.In MCI groups,a systemic analysis demonstrated that the identified features were significantly associated with clinical features(e.g.,apolipoprotein E(APOE)genotype,polygenic risk scores,cerebrospinal fluid(CSF)Ab,CSF Tau),and longitudinal changes in cognition ability;more importantly,the radiomic features had a consistently altered pattern with changes in the MMSE scores over 5 years of follow-up.These comprehensive results suggest that hippocampal radiomic features can serve as robust biomarkers for clinical application in AD/MCI,and further provide evidence for predicting whether an MCI subject would convert to AD based on the radiomics of the hippocampus.The results of this study are expected to have a substantial impact on the early diagnosis of AD/MCI.展开更多
Reproductive biology is a uniquely important topic since it is about germ cells, which are central for transmitting genetic information from generation to generation. In this review, we discuss recent advances in mamm...Reproductive biology is a uniquely important topic since it is about germ cells, which are central for transmitting genetic information from generation to generation. In this review, we discuss recent advances in mammalian germ cell development,including preimplantation development, fetal germ cell development and postnatal development of oocytes and sperm. We also discuss the etiologies of female and male infertility and describe the emerging technologies for studying reproductive biology such as gene editing and single-cell technologies.展开更多
Integrating multisensory inputs to generate accurate perception and guide behavior is among the most critical functions of the brain.Subcortical regions such as the amygdala are involved in sensory processing includin...Integrating multisensory inputs to generate accurate perception and guide behavior is among the most critical functions of the brain.Subcortical regions such as the amygdala are involved in sensory processing including vision and audition,yet their roles in multisensory integration remain unclear.In this study,we systematically investigated the function of neurons in the amygdala and adjacent regions in integrating audiovisual sensory inputs using a semi-chronic multi-electrode array and multiple combinations of audiovisual stimuli.From a sample of 332 neurons,we showed the diverse response patterns to audiovisual stimuli and the neural characteristics of bimodal over unimodal modulation,which could be classified into four types with differentiated regional origins.Using the hierarchical clustering method,neurons were further clustered into five groups and associated with different integrating functions and sub-regions.Finally,regions distinguishing congruent and incongruent bimodal sensory inputs were identified.Overall,visual processing dominates audiovisual integration in the amygdala and adjacent regions.Our findings shed new light on the neural mechanisms of multisensory integration in the primate brain.展开更多
In fluorescence microscopy,computational algorithms have been developed to suppress noise,enhance contrast,and even enable super-resolution(SR).However,the local quality of the images may vary on multiple scales,and t...In fluorescence microscopy,computational algorithms have been developed to suppress noise,enhance contrast,and even enable super-resolution(SR).However,the local quality of the images may vary on multiple scales,and these differences can lead to misconceptions.Current mapping methods fail to finely estimate the local quality,challenging to associate the SR scale content.Here,we develop a rolling Fourier ring correlation(rFRC)method to evaluate the reconstruction uncertainties down to SR scale.To visually pinpoint regions with low reliability,a filtered rFRC is combined with a modified resolution-scaled error map(RSM),offering a comprehensive and concise map for further examination.We demonstrate their performances on various SR imaging modalities,and the resulting quantitative maps enable better SR images integrated from different reconstructions.Overall,we expect that our framework can become a routinely used tool for biologists in assessing their image datasets in general and inspire further advances in the rapidly developing field of computational imaging.展开更多
Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain injury.However,whether bioactiv...Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain injury.However,whether bioactive materials can repair the damage caused by ischemic stroke by activating endogenous neurogenesis and angiogenesis is still unknown.In this study,we applied chitosan gel loaded with basic fibroblast growth factor to the stroke cavity 7 days after ischemic stroke in rats.The gel slowly released basic fibroblast growth factor,which improved the local microenvironment,activated endogenous neural stem/progenitor cells,and recruited these cells to migrate toward the penumbra and stroke cavity and subsequently differentiate into neurons,while enhancing angiogenesis in the penumbra and stroke cavity and ultimately leading to partial functional recovery.This study revealed the mechanism by which bioactive materials repair ischemic strokes,thus providing a new strategy for the clinical application of bioactive materials in the treatment of ischemic stroke.展开更多
Neural circuits provide an anatomical basis for functional networks.Therefore,dissecting the structure of neural circuits is essential to understanding how the brain works.Recombinant neurotropic viruses are important...Neural circuits provide an anatomical basis for functional networks.Therefore,dissecting the structure of neural circuits is essential to understanding how the brain works.Recombinant neurotropic viruses are important tools for neural circuit tracing with many advantages over non-viral tracers:they allow for anterograde,retrograde,and trans-synaptic delivery of tracers in a cell type-specific,circuit-selective manner.In this review,we summarize the recent developments in the viral tools for neural circuit tracing,discuss the key principles of using viral tools in neuroscience research,and highlight innovations for developing and optimizing viral tools for neural circuit tracing across diverse animal species,including nonhuman primates.展开更多
Previous studies have shown that Lycium barbarum polysaccharide,the main active component of Lycium barbarum,exhibits antiinflammatory and antioxidant effects in treating neurological diseases.However,the therapeutic ...Previous studies have shown that Lycium barbarum polysaccharide,the main active component of Lycium barbarum,exhibits antiinflammatory and antioxidant effects in treating neurological diseases.However,the therapeutic action of Lycium barbarum polysaccharide on depression has not been studied.In this investigation,we established mouse models of depression using aversive stimuli including exposure to fox urine,air puff and foot shock and physical restraint.Concurrently,we administered 5 mg/kg per day Lycium barbarum polysaccharide-glycoprotein to each mouse intragastrically for the 28 days.Our results showed that long-term exposure to aversive stimuli significantly enhanced depressive-like behavior evaluated by the sucrose preference test and the forced swimming test and increased anxietylike behaviors evaluated using the open field test.In addition,aversive stimuli-induced depressed mice exhibited aberrant neuronal activity in the lateral habenula.Importantly,concurrent Lycium barbarum polysaccharide-glycoprotein treatment significantly reduced these changes.These findings suggest that Lycium barbarum polysaccharide-glycoprotein is a potential preventative intervention for depression and may act by preventing aberrant neuronal activity and microglial activation in the lateral habenula.The study was approved by the Jinan University Institutional Animal Care and Use Committee(approval No.20170301003)on March 1,2017.展开更多
Although the mTOR-4E-BP1 signaling pathway is implicated in aging and aging-related disorders,the role of 4E-BP1 in regulating human stem cell homeostasis remains largely unknown.Here,we report that the expression of ...Although the mTOR-4E-BP1 signaling pathway is implicated in aging and aging-related disorders,the role of 4E-BP1 in regulating human stem cell homeostasis remains largely unknown.Here,we report that the expression of 4E-BP1 decreases along with the senescence of human mesenchymal stem celis(hMSCs).Genetic inactivation of 4E-BP1 in hMSCs compromises mitochondrial respiration,increases mitochondrial reactive oxygen species(Ros)production,and accelerates cellular senescence.Mechanistically,the absence of 4E-BP1 destabilizes proteins in mitochondrial respiration complexes,especially several key subunits of complex III including UQCRC2.Ectopic expression of 4E-BP1 attenuates mitochondrial abnormalities and alleviates cellular senescence in 4E-BP1-deficient hMSCs as well as in physiologically aged hMSCs.These findings together demonstrate that 4E-BP1 functions as a geroprotector to mitigate human stem cell senescence and maintain mitochondrial homeostasis,particularly for the mitochondrial respiration complex Il,thus providing a new potential target to counteract human stem cell senescence.展开更多
Circadian rhythms orchestrate biochemical and physi-ological processes in living organisms to respond the day/night cycle. In mammals, nearly all cells hold self- sustained circadian clocks meanwhile couple the intrin...Circadian rhythms orchestrate biochemical and physi-ological processes in living organisms to respond the day/night cycle. In mammals, nearly all cells hold self- sustained circadian clocks meanwhile couple the intrinsic rhythms to systemic changes in a hierarchical manner. The suprachiasmatic nucleus （SCN） of the hypothalamus functions as the master pacemaker to initiate daily synchronization according to the photope-riod, in turn determines the phase of peripheral cellular clocks through a variety of signaling relays, including endocrine rhythms and metabolic cycles. With aging, circadian desynchrony occurs at the expense of peripheral metabolic pathologies and central neurode- generative disorders with sleep symptoms, and genetic ablation of circadian genes in model organisms resem- bled the aging-related features. Notably, a number of studies have linked longevity nutrient sensing pathways in modulating circadian clocks. Therapeutic strategies that bridge the nutrient sensing pathways and circadian clock might be rational designs to defy aging.展开更多
With the current limited drug therapy for the core symptoms of autism spectrum disorder(ASD),we herein report a randomized,double-blind,placebo-controlled trial to investigate the efficacy,safety,and potential neural ...With the current limited drug therapy for the core symptoms of autism spectrum disorder(ASD),we herein report a randomized,double-blind,placebo-controlled trial to investigate the efficacy,safety,and potential neural mechanism of bumetanide in children with ASD aged 3-6 years old.A total of 120 children were enrolled into the study and randomly assigned to either 0.5 mg bumetanide or placebo.In the final sample,119 children received at least one dose of bumetanide(59 children) or placebo(60 children) were included in the final analysis.The primary outcome was a reduction in the Childhood Autism Rating Scale(CARS) score,and the secondary outcomes were the Clinical Global Impressions Scale(CGI)-Global Improvement(CGI-I) score at 3 months and the change from baseline to 3-month in the Autism Diagnostic Observation Schedule(ADOS).Magnetic resonance spectroscopy(MRS) was used to measure y-aminobutyric acid(GABA) and glutamate neurotransmitter concentrations in the insular cortex(IC) before and after the treatment.As compared with the placebo,bumetanide treatment was significantly better in reducing the severity.No patient withdrew from the trial due to adverse events.The superiority of bumetanide to placebo in reducing insular GABA,measured using MRS,was demonstrated.The clinical improvement was associated with a decrease in insular GABA in the bumetanide group.In conclusion,this trial in a large group of young children with predominantly moderate and severe ASD demonstrated that bumetanide is safe and effective in improving the core symptoms of ASD.However,the clinical significance remains uncertain,and future multi-center clinical trials are required to replicate these findings and confirm the clinical significance using a variety of outcome measures.展开更多
The global trend toward aging populations has resulted in an increase in the occurrence of Alzheimer's disease(AD)and associated socioeconomic burdens.Abnormal metabolism of amyloid-β(Aβ)has been proposed as a s...The global trend toward aging populations has resulted in an increase in the occurrence of Alzheimer's disease(AD)and associated socioeconomic burdens.Abnormal metabolism of amyloid-β(Aβ)has been proposed as a significant pathomechanism in AD,supported by results of recent clinical trials using anti-Aβantibodies.Nonetheless,the cognitive benefits of the current treatments are limited.The etiology of AD is multifactorial,encompassing Aβand tau accumulation,neuroinflammation,demyelination,vascular dysfunction,and comorbidities,which collectively lead to widespread neurodegeneration in the brain and cognitive impairment.Hence,solely removing Aβfrom the brain may be insufficient to combat neurodegeneration and preserve cognition.To attain effective treatment for AD,it is necessary to(1)conduct extensive research on various mechanisms that cause neurodegeneration,including advances in neuroimaging techniques for earlier detection and a more precise characterization of molecular events at scales ranging from cellular to the full system level;(2)identify neuroprotective intervention targets against different neurodegeneration mechanisms;and(3)discover novel and optimal combinations of neuroprotective intervention strategies to maintain cognitive function in AD patients.The Alzheimer's Disease Neuroprotection Research Initiative's objective is to facilitate coordinated,multidisciplinary efforts to develop systemic neuroprotective strategies to combat AD.The aim is to achieve mitigation of the full spectrum of pathological processes underlying AD,with the goal of halting or even reversing cognitive decline.展开更多
All animals possess a plethora of innate behaviors that do not require extensive learning and are fundamental for their survival and propagation.With the advent of newly-developed techniques such as viral tracing and ...All animals possess a plethora of innate behaviors that do not require extensive learning and are fundamental for their survival and propagation.With the advent of newly-developed techniques such as viral tracing and optogenetic and chemogenetic tools,recent studies are gradually unraveling neural circuits underlying different innate behaviors.Here,we summarize current development in our understanding of the neural circuits controlling predation,feeding,male-typical mating,and urination,highlighting the role of genetically defined neurons and their connections in sensory triggering,sensory to motor/motivation transformation,motor/motivation encoding during these different behaviors.Along the way,we discuss possible mechanisms underlying binge-eating disorder and the pro-social effects of the neuropeptide oxytocin,elucidating the clinical relevance of studying neural circuits underlying essential innate functions.Finally,we discuss some exciting brain structures recurrently appearing in the regulation of different behaviors,which suggests both divergence and convergence in the neural encoding of specific innate behaviors.Going forward,we emphasize the importance of multi-angle and cross-species dissections in delineating neural circuits that control innate behaviors.展开更多
Hearing loss is one of the most common sensory disorders worldwide,affecting approximately 466 million people,including 34 million children[1].Genetic mutations accounts for approximately 60%of inherited hearing loss ...Hearing loss is one of the most common sensory disorders worldwide,affecting approximately 466 million people,including 34 million children[1].Genetic mutations accounts for approximately 60%of inherited hearing loss cases[2,3].These genetic changes result in a wide variety of clinical manifestations,ranging from nonsyndromic hearing loss(NSHL)to over 400 syndromes involving hearing loss and from mild adult-onset hearing loss to profound congenital deafness,covering the entire spectrum of Mendelian inheritance.展开更多
A deficit in spatial memory has been taken as an early predictor of Alzheimer’s disease(AD) or mild cognitive impairment(MCI). The uncinate fasciculus(UF) is a long-range white-matter tract that connects the anterior...A deficit in spatial memory has been taken as an early predictor of Alzheimer’s disease(AD) or mild cognitive impairment(MCI). The uncinate fasciculus(UF) is a long-range white-matter tract that connects the anterior temporal lobe with the orbitofrontal cortex(OFC)in primates. Previous studies have shown that the UF impairment associated with spatial memory deficits may be an important pathological change in aging and AD, but its exact role in spatial memory is not well understood. The pathway arising from the postrhinal cortex(POR) and projecting to the ventrolateral orbitofrontal cortex(vlOFC)performs most of the functions of the UF in rodents.Although the literature suggests an association between spatial memory and the regions connected by the POR–vlOFC pathway, the function of the pathway in spatialmemory is relatively unknown. To further illuminate the function of the UF in spatial memory, we dissected the POR–vlOFC pathway in mice. We determined that the POR–vlOFC pathway is a glutamatergic structure, and that glutamatergic neurons in the POR regulate spatial memory retrieval. We also demonstrated that the POR–vlOFC pathway specifically transmits spatial information to participate in memory retrieval. These findings provide a deeper understanding of UF function and dysfunction related to disorders of memory, as in MCI and AD.展开更多
Autism spectrum disorder(ASD)is a highly heritable neurodevelopmental disorder characterized by deficits in social interactions and repetitive behaviors.Although hundreds of ASD risk genes,implicated in synaptic forma...Autism spectrum disorder(ASD)is a highly heritable neurodevelopmental disorder characterized by deficits in social interactions and repetitive behaviors.Although hundreds of ASD risk genes,implicated in synaptic formation and transcriptional regulation,have been identified through human genetic studies,the East Asian ASD cohorts are still under-represented in genome-wide genetic studies.Here,we applied whole-exome sequencing to 369 ASD trios including probands and unaffected parents of Chinese origin.Using a joint-calling analytical pipeline based on GATK toolkits,we identified numerous de novo mutations including 55 high-impact variants and 165 moderate-impact variants,as well as de novo copy number variations containing known ASD-related genes.Importantly,combined with single-cell sequencing data from the developing human brain,we found that the expression of genes with de novo mutations was specifically enriched in the pre-,post-central gyrus(PRC,PC)and banks of the superior temporal(BST)regions in the human brain.By further analyzing the brain imaging data with ASD and healthy controls,we found that the gray volume of the right BST in ASD patients was significantly decreased compared to healthy controls,suggesting the potential structural deficits associated with ASD.Finally,we found a decrease in the seed-based functional connectivity between BST/PC/PRC and sensory areas,the insula,as well as the frontal lobes in ASD patients.This work indicated that combinatorial analysis with genome-wide screening,single-cell sequencing,and brain imaging data reveal the brain regions contributing to the etiology of ASD.展开更多
Amyloid-b,tau pathology,and biomarkers of neurodegeneration make up the core diagnostic biomarkers of Alzheimer disease(AD).However,these proteins represent only a fraction of the complex biological processes underlyi...Amyloid-b,tau pathology,and biomarkers of neurodegeneration make up the core diagnostic biomarkers of Alzheimer disease(AD).However,these proteins represent only a fraction of the complex biological processes underlying AD,and individuals with other brain diseases in which AD pathology is a comorbidity also test positive for these diagnostic biomarkers.More ADspecific early diagnostic and disease staging biomarkers are needed.In this study,we performed tandem mass tag proteomic analysis of paired cerebrospinal fluid(CSF)and serum samples in a discovery cohort comprising 98 participants.Candidate biomarkers were validated by parallel reaction monitoring–based targeted proteomic assays in an independent multicenter cohort comprising 288 participants.We quantified 3,238 CSF and 1,702 serum proteins in the discovery cohort,identifying 171 and 860 CSF proteins and 37 and 323 serum proteins as potential early diagnostic and staging biomarkers,respectively.In the validation cohort,58 and 21 CSF proteins,as well as 12 and 18 serum proteins,were verified as early diagnostic and staging biomarkers,respectively.Separate 19-protein CSF and an 8-protein serum biomarker panels were built by machine learning to accurately classify mild cognitive impairment(MCI)due to AD from normal cognition with areas under the curve of 0.984 and 0.881,respectively.The 19-protein CSF biomarker panel also effectively discriminated patients with MCI due to AD from patients with other neurodegenerative diseases.Moreover,we identified 21 CSF and 18 serum stage-associated proteins re-flecting AD stages.Our findings provide a foundation for developing bloodbased tests for AD screening and staging in clinical practice.展开更多
Many complex behaviors that do not require learning are displayed and are termed innate. Although traditionally the subject matter of ethology, innate behaviors offer a unique entry point for neuroscientists to dissec...Many complex behaviors that do not require learning are displayed and are termed innate. Although traditionally the subject matter of ethology, innate behaviors offer a unique entry point for neuroscientists to dissect the physiological mechanisms governing complex behaviors. Since the last century, converging evidence has implicated the hypothalamus as the central brain area that controls innate behaviors. Recent studies using cutting-edge tools have revealed that genetically-defined populations of neurons residing in distinct hypothalamic nuclei and their associated neural pathways regulate the initiation and maintenance of diverse behaviors including feeding, sleep, aggression, and parental care. Here, we review the newly-defined hypothalamic pathways that regulate each innate behavior. In addition, emerging general principles of the neural control of complex behaviors are discussed.展开更多
基金partly supported by the National Key R&D Program of China(2020YFC0842000 to Y.T.Z.)National Natural Science Foundation of China(U1902215 to Y.G.Y.)+2 种基金National Science and Technology Major Projects of Infectious Disease Funds(2017ZX10304402 to Y.T.Z.)Yunnan Province(2018FB046 to D.D.Y.)CAS“Light of West China”Program(xbzg-zdsys-201909to Y.G.Y.and Y.T.Z.)。
文摘Thecoronavirusdisease2019(COVID-19)pandemic continues to pose a global threat to the human population. Identifying animal species susceptible to infection with the SARS-CoV-2/HCoV-19 pathogen is essential for controlling the outbreak and for testing valid prophylactics or therapeutics based on animal model studies. Here,different aged Chinese tree shrews(adult group, 1 year old;old group, 5–6 years old), which are close relatives to primates, were infected with SARS-CoV-2. X-ray, viral shedding, laboratory, and histological analyses were performed on different days postinoculation(dpi). Results showed that Chinese tree shrews could be infected by SARS-CoV-2. Lung infiltrates were visible in X-ray radiographs in most infected animals. Viral RNA was consistently detected in lung tissues from infected animals at 3,5, and 7 dpi, along with alterations in related parameters from routine blood tests and serum biochemistry, including increased levels of aspartate aminotransferase(AST) and blood urea nitrogen(BUN). Histological analysis of lung tissues from animals at 3 dpi(adult group) and 7 dpi(old group) showed thickened alveolar septa and interstitial hemorrhage. Several differences were found between the two different aged groups in regard to viral shedding peak. Our results indicate that Chinese tree shrews have the potential to be used as animal models for SARS-CoV-2 infection.
基金This review was supported by the National Basic Research Development Program of China(2016YFC1307100)the National Natural Science Foundation of China(81930033 and 81771465+6 种基金81401127)Shanghai Key Project of Science&Technology(2018SHZDZX05)Shanghai Jiao Tong University Medical Engineering Foundation(YG2016MS48)Shanghai Jiao Tong University School of Medicine(19XJ11006)the Sanming Project of Medicine in Shenzhen Municipality(SZSM201612006)the National Key Technologies R&D Program of China(2012BAI01B04)the Innovative Research Team of High-level Local Universities in Shanghai.
文摘Major depressive disorder(MDD),also referred to as depression,is one of the most common psychiatric disorders with a high economic burden.The etiology of depression is still not clear,but it is generally believed that MDD is a multifactorial disease caused by the interaction of social,psychological,and biological aspects.Therefore,there is no exact pathological theory that can independently explain its pathogenesis,involving genetics,neurobiology,and neuroimaging.At present,there are many treatment measures for patients with depression,including drug therapy,psychotherapy,and neuromodulation technology.In recent years,great progress has been made in the development of new antidepressants,some of which have been applied in the clinic.This article mainly reviews the research progress,pathogenesis,and treatment of MDD.
基金This review was supported by the National Natural Science Foundation of China(grant no.81930028,91749206,81625007 and 31921003).
文摘Alzheimer’s disease(AD)is the most common type of dementia,and no disease-modifying treatments are available to halt or slow its progression.Amyloid-beta(Aβ)is suggested to play a pivotal role in the pathogenesis of AD,and clearance of Aβfrom the brain becomes a main therapeutic strategy for AD.Recent studies found that Aβclearance in the periphery contributes substantially to reducing Aβaccumulation in the brain.Therefore,understanding the mechanism of how Aβis cleared in the periphery is important for the development of effective therapies for AD.In this review,we summarized recent findings on the mechanisms of Aβefflux from the brain to the periphery and discuss where and how the brain-derived Aβis cleared in the periphery.Based on these findings,we propose future strategies to enhance peripheral Aβclearance for the prevention and treatment of AD.This review provides a novel perspective to understand the pathogenesis of AD and develop interventions for this disease from a systemic approach.
基金partially supported by the National Key Research and Development Program of China (2016YFC1305904)the National Natural Science Foundation of China (81871438, 81901101, 61633018, 81571062, 81400890, 81871398)+10 种基金the Strategic Priority Research Program (B) of the Chinese Academy of Sciences (XDB32020200)the Beijing Municipal Science & Technology Commission (Z171100000117001, Z171100000117002)the Primary Research & Development Plan of Shandong Province (2017GGX10112)the Open Project Program of the National Laboratory of Pattern Recognition (NLPR) (201900021)Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904)DOD ADNI (Department of Defense award number W81XWH-12-2-0012)funded by the National Institute on Agingthe National Institute of Biomedical Imaging and Bioengineeringgenerous contributions from Abb Vie, Alzheimer’s AssociationAlzheimer’s Drug Discovery FoundationThe Canadian Institutes of Health Research provide funds to support ADNI clinical sites in Canada。
文摘Hippocampal morphological change is one of the main hallmarks of Alzheimer’s disease(AD).However,whether hippocampal radiomic features are robust as predictors of progression from mild cognitive impairment(MCI)to AD dementia and whether these features provide any neurobiological foundation remains unclear.The primary aim of this study was to verify whether hippocampal radiomic features can serve as robust magnetic resonance imaging(MRI)markers for AD.Multivariate classifier-based support vector machine(SVM)analysis provided individual-level predictions for distinguishing AD patients(n=261)from normal controls(NCs;n=231)with an accuracy of 88.21%and intersite crossvalidation.Further analyses of a large,independent the Alzheimer’s Disease Neuroimaging Initiative(ADNI)dataset(n=1228)reinforced these findings.In MCI groups,a systemic analysis demonstrated that the identified features were significantly associated with clinical features(e.g.,apolipoprotein E(APOE)genotype,polygenic risk scores,cerebrospinal fluid(CSF)Ab,CSF Tau),and longitudinal changes in cognition ability;more importantly,the radiomic features had a consistently altered pattern with changes in the MMSE scores over 5 years of follow-up.These comprehensive results suggest that hippocampal radiomic features can serve as robust biomarkers for clinical application in AD/MCI,and further provide evidence for predicting whether an MCI subject would convert to AD based on the radiomics of the hippocampus.The results of this study are expected to have a substantial impact on the early diagnosis of AD/MCI.
文摘Reproductive biology is a uniquely important topic since it is about germ cells, which are central for transmitting genetic information from generation to generation. In this review, we discuss recent advances in mammalian germ cell development,including preimplantation development, fetal germ cell development and postnatal development of oocytes and sperm. We also discuss the etiologies of female and male infertility and describe the emerging technologies for studying reproductive biology such as gene editing and single-cell technologies.
基金supported by the National Natural Science Foundation of China(U20A2017 and 31830037)Guangdong Basic and Applied Basic Research Foundation(2020A1515010785,2020A1515111118,and 2022A1515010134)+5 种基金the Youth Innovation Promotion Association of the Chinese Academy of Sciences(2017120)the Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions(NYKFKT2019009)Shenzhen Technological Research Center for Primate Translational Medicine(F-2021-Z99-504979)the Strategic Research Program of the Chinese Academy of Sciences(XDBS01030100 and XDB32010300)Scientific and Technological Innovation 2030(2021ZD0204300)the Fundamental Research Funds for the Central Universities.
文摘Integrating multisensory inputs to generate accurate perception and guide behavior is among the most critical functions of the brain.Subcortical regions such as the amygdala are involved in sensory processing including vision and audition,yet their roles in multisensory integration remain unclear.In this study,we systematically investigated the function of neurons in the amygdala and adjacent regions in integrating audiovisual sensory inputs using a semi-chronic multi-electrode array and multiple combinations of audiovisual stimuli.From a sample of 332 neurons,we showed the diverse response patterns to audiovisual stimuli and the neural characteristics of bimodal over unimodal modulation,which could be classified into four types with differentiated regional origins.Using the hierarchical clustering method,neurons were further clustered into five groups and associated with different integrating functions and sub-regions.Finally,regions distinguishing congruent and incongruent bimodal sensory inputs were identified.Overall,visual processing dominates audiovisual integration in the amygdala and adjacent regions.Our findings shed new light on the neural mechanisms of multisensory integration in the primate brain.
基金supported by the National Natural Science Foundation of China(grant no.T2222009 to H.L.,grant no.32227802 to L.C.,grant no.81925022 to L.C.,grant no.92054301 to L.C.,grant no.62305083 to W.Z.,grant no.12174208 to P.L.,grant no.32301257 to S.Z.,grant no.32222022 to Y.J.,grant no.32071458 to H.M.)the National Key Research and Development Program of China(grant no.2022YFC3400600 to L.C.)+4 种基金the Natural Science Foundation of Heilongjiang Province(grant no.YQ2021F013 to H.L.)the Beijing Natural Science Foundation(grant no.Z20J00059 to L.C.)the Guangdong Major Project of Basic and Applied Basic Research(grant no.2020B0301030009 to P.L.)the China Postdoctoral Science Foundation(grant no.2023T160163 to W.Z.,grant no.2022M720971 to W.Z.)the Heilongjiang Provincial Postdoctoral Science Foundation(grant no.LBH-Z22027 to W.Z.).L.C.acknowledges support from the High-performance Computing Platform of Peking University。
文摘In fluorescence microscopy,computational algorithms have been developed to suppress noise,enhance contrast,and even enable super-resolution(SR).However,the local quality of the images may vary on multiple scales,and these differences can lead to misconceptions.Current mapping methods fail to finely estimate the local quality,challenging to associate the SR scale content.Here,we develop a rolling Fourier ring correlation(rFRC)method to evaluate the reconstruction uncertainties down to SR scale.To visually pinpoint regions with low reliability,a filtered rFRC is combined with a modified resolution-scaled error map(RSM),offering a comprehensive and concise map for further examination.We demonstrate their performances on various SR imaging modalities,and the resulting quantitative maps enable better SR images integrated from different reconstructions.Overall,we expect that our framework can become a routinely used tool for biologists in assessing their image datasets in general and inspire further advances in the rapidly developing field of computational imaging.
基金supported by the National Natural Science Foundation of China,Nos.81941011(to XL),31771053(to HD),31730030(to XL),31971279(to ZY),31900749(to PH),31650001(to XL),31320103903(to XL),31670988(to ZY)the Natural Science Foundation of Beijing,Nos.7222004(to HD)+1 种基金a grant from Ministry of Science and Technology of China,Nos.2017YFC1104002(to ZY),2017YFC1104001(to XL)a grant from Beihang University,No.JKF-YG-22-B001(to FH)。
文摘Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain injury.However,whether bioactive materials can repair the damage caused by ischemic stroke by activating endogenous neurogenesis and angiogenesis is still unknown.In this study,we applied chitosan gel loaded with basic fibroblast growth factor to the stroke cavity 7 days after ischemic stroke in rats.The gel slowly released basic fibroblast growth factor,which improved the local microenvironment,activated endogenous neural stem/progenitor cells,and recruited these cells to migrate toward the penumbra and stroke cavity and subsequently differentiate into neurons,while enhancing angiogenesis in the penumbra and stroke cavity and ultimately leading to partial functional recovery.This study revealed the mechanism by which bioactive materials repair ischemic strokes,thus providing a new strategy for the clinical application of bioactive materials in the treatment of ischemic stroke.
基金This review was supported by the National Science and Technology Innovation 2030(2021ZD0201003)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB32030200)+1 种基金the National Natural Science Foundation of China(31830035)the Shenzhen Key Laboratory of Viral Vectors for Biomedicine(ZDSYS20200811142401005).
文摘Neural circuits provide an anatomical basis for functional networks.Therefore,dissecting the structure of neural circuits is essential to understanding how the brain works.Recombinant neurotropic viruses are important tools for neural circuit tracing with many advantages over non-viral tracers:they allow for anterograde,retrograde,and trans-synaptic delivery of tracers in a cell type-specific,circuit-selective manner.In this review,we summarize the recent developments in the viral tools for neural circuit tracing,discuss the key principles of using viral tools in neuroscience research,and highlight innovations for developing and optimizing viral tools for neural circuit tracing across diverse animal species,including nonhuman primates.
基金supported by the National Natural Science Foundation of China,Nos.31900825(to SL),31922030(to CRR),31771170(to CRR)Science and Technology Program of Guangdong Province of China,No.2018B030334001(to CRR)+3 种基金Science and Techology of Guangzhou of China,No.202007030012(to CRR)Guangdong Special Support Program of China,No.2017TQ04R173(to CRR)Pearl River S&T Nova Program of Guangzhou Province of China,No.201806010198(to CRR)Outstanding Scholar Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory of China,No.2018GZR110102002(to KFS)。
文摘Previous studies have shown that Lycium barbarum polysaccharide,the main active component of Lycium barbarum,exhibits antiinflammatory and antioxidant effects in treating neurological diseases.However,the therapeutic action of Lycium barbarum polysaccharide on depression has not been studied.In this investigation,we established mouse models of depression using aversive stimuli including exposure to fox urine,air puff and foot shock and physical restraint.Concurrently,we administered 5 mg/kg per day Lycium barbarum polysaccharide-glycoprotein to each mouse intragastrically for the 28 days.Our results showed that long-term exposure to aversive stimuli significantly enhanced depressive-like behavior evaluated by the sucrose preference test and the forced swimming test and increased anxietylike behaviors evaluated using the open field test.In addition,aversive stimuli-induced depressed mice exhibited aberrant neuronal activity in the lateral habenula.Importantly,concurrent Lycium barbarum polysaccharide-glycoprotein treatment significantly reduced these changes.These findings suggest that Lycium barbarum polysaccharide-glycoprotein is a potential preventative intervention for depression and may act by preventing aberrant neuronal activity and microglial activation in the lateral habenula.The study was approved by the Jinan University Institutional Animal Care and Use Committee(approval No.20170301003)on March 1,2017.
基金supported by the National Key Research and Development Program of China(2018YFC2000100)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16000000)+9 种基金the National Natural Science Foundation of China(8190143281921006,82125011,92149301,92168201,91949209,92049304,92049116,32121001,82192863,82122024,82071588,81861168034,81922027,81870228,32100937,31900524,82201727)the National Key Research and Development Program of China(2020YFA0804000,2020YFA0113400,2020YFA0112200,2018YFA0107203,the STI2030-Major Projects-2021ZD0202400,2021YFF1201005,2022YFA1103700,2022YFA1103800)CAS Project for Young Scientists in Basic Research(YSBR-076,YSBR-012)the Program of the Beijing Natural Science Foundation(Z190019,JQ20031)K.C.Wong Education Foundation(GJTD-2019-06,GJTD-2019-08)Young Elite Scientists Sponsorship Program by CAST(YESS20200012)Youth Innovation Promotion Association of CAS(EiCAZW0401)the Pilot Project for Public Welfare Development and Reform of Beijing-affliated Medical Research Institutes(11000022T000000461062)the Informatization Plan of Chinese Academy of Sciences(CAS-WX2021SF-0301,CASWX2022SDC-XK14)CAS Special Research Assistant(SRA)Program,and the Tencent Foundation(2021-1045).
文摘Although the mTOR-4E-BP1 signaling pathway is implicated in aging and aging-related disorders,the role of 4E-BP1 in regulating human stem cell homeostasis remains largely unknown.Here,we report that the expression of 4E-BP1 decreases along with the senescence of human mesenchymal stem celis(hMSCs).Genetic inactivation of 4E-BP1 in hMSCs compromises mitochondrial respiration,increases mitochondrial reactive oxygen species(Ros)production,and accelerates cellular senescence.Mechanistically,the absence of 4E-BP1 destabilizes proteins in mitochondrial respiration complexes,especially several key subunits of complex III including UQCRC2.Ectopic expression of 4E-BP1 attenuates mitochondrial abnormalities and alleviates cellular senescence in 4E-BP1-deficient hMSCs as well as in physiologically aged hMSCs.These findings together demonstrate that 4E-BP1 functions as a geroprotector to mitigate human stem cell senescence and maintain mitochondrial homeostasis,particularly for the mitochondrial respiration complex Il,thus providing a new potential target to counteract human stem cell senescence.
文摘Circadian rhythms orchestrate biochemical and physi-ological processes in living organisms to respond the day/night cycle. In mammals, nearly all cells hold self- sustained circadian clocks meanwhile couple the intrinsic rhythms to systemic changes in a hierarchical manner. The suprachiasmatic nucleus （SCN） of the hypothalamus functions as the master pacemaker to initiate daily synchronization according to the photope-riod, in turn determines the phase of peripheral cellular clocks through a variety of signaling relays, including endocrine rhythms and metabolic cycles. With aging, circadian desynchrony occurs at the expense of peripheral metabolic pathologies and central neurode- generative disorders with sleep symptoms, and genetic ablation of circadian genes in model organisms resem- bled the aging-related features. Notably, a number of studies have linked longevity nutrient sensing pathways in modulating circadian clocks. Therapeutic strategies that bridge the nutrient sensing pathways and circadian clock might be rational designs to defy aging.
基金the Shanghai Municipal Commission of Health and Family Planning(2018BR33,2017EKHWYX-02,and GWV-10.1-XK07)the Shanghai Shenkang Hospital Development Center(16CR2025B)+9 种基金the Shanghai Clinical Key Subject Construction Project(shslczdzk02902)the National Natural Science Foundation of China(81761128035,81930095,81873909,82001771,and 31860306)the Shanghai Committee of Science and Technology(17XD1403200,20ZR1404900,and 19410713500)Xinhua Hospital of Shanghai Jiao Tong University School of Medicine(2018YJRC03)the National Human Genetic Resources Sharing Service Platform(2005DKA21300)the National Key Research and Development Program of China(2018YFC0910503)111 Project(B18015)the Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)Guangdong Key Project in‘‘Development of New Tools for Diagnosis and Treatment of Autism”(2018B030335001)the Science and Technology Department of Yunnan Province(202001AV070010)。
文摘With the current limited drug therapy for the core symptoms of autism spectrum disorder(ASD),we herein report a randomized,double-blind,placebo-controlled trial to investigate the efficacy,safety,and potential neural mechanism of bumetanide in children with ASD aged 3-6 years old.A total of 120 children were enrolled into the study and randomly assigned to either 0.5 mg bumetanide or placebo.In the final sample,119 children received at least one dose of bumetanide(59 children) or placebo(60 children) were included in the final analysis.The primary outcome was a reduction in the Childhood Autism Rating Scale(CARS) score,and the secondary outcomes were the Clinical Global Impressions Scale(CGI)-Global Improvement(CGI-I) score at 3 months and the change from baseline to 3-month in the Autism Diagnostic Observation Schedule(ADOS).Magnetic resonance spectroscopy(MRS) was used to measure y-aminobutyric acid(GABA) and glutamate neurotransmitter concentrations in the insular cortex(IC) before and after the treatment.As compared with the placebo,bumetanide treatment was significantly better in reducing the severity.No patient withdrew from the trial due to adverse events.The superiority of bumetanide to placebo in reducing insular GABA,measured using MRS,was demonstrated.The clinical improvement was associated with a decrease in insular GABA in the bumetanide group.In conclusion,this trial in a large group of young children with predominantly moderate and severe ASD demonstrated that bumetanide is safe and effective in improving the core symptoms of ASD.However,the clinical significance remains uncertain,and future multi-center clinical trials are required to replicate these findings and confirm the clinical significance using a variety of outcome measures.
基金National Natural Science Foundation of China,Grant/Award Numbers:92249305,82120108010,81930028,31921003Academy of Medical Sciences(Newton Advanced Fellowship),Grant/Award Number:NAF/R11/1010National Institutes of Health,Grant/Award Number:R01DA056739。
文摘The global trend toward aging populations has resulted in an increase in the occurrence of Alzheimer's disease(AD)and associated socioeconomic burdens.Abnormal metabolism of amyloid-β(Aβ)has been proposed as a significant pathomechanism in AD,supported by results of recent clinical trials using anti-Aβantibodies.Nonetheless,the cognitive benefits of the current treatments are limited.The etiology of AD is multifactorial,encompassing Aβand tau accumulation,neuroinflammation,demyelination,vascular dysfunction,and comorbidities,which collectively lead to widespread neurodegeneration in the brain and cognitive impairment.Hence,solely removing Aβfrom the brain may be insufficient to combat neurodegeneration and preserve cognition.To attain effective treatment for AD,it is necessary to(1)conduct extensive research on various mechanisms that cause neurodegeneration,including advances in neuroimaging techniques for earlier detection and a more precise characterization of molecular events at scales ranging from cellular to the full system level;(2)identify neuroprotective intervention targets against different neurodegeneration mechanisms;and(3)discover novel and optimal combinations of neuroprotective intervention strategies to maintain cognitive function in AD patients.The Alzheimer's Disease Neuroprotection Research Initiative's objective is to facilitate coordinated,multidisciplinary efforts to develop systemic neuroprotective strategies to combat AD.The aim is to achieve mitigation of the full spectrum of pathological processes underlying AD,with the goal of halting or even reversing cognitive decline.
基金supported by the National Key Research and Development Program of China(2017YFA0104200)the National Natural Science Foundation of China(31871066,31922028,31900721 and 32122039)+2 种基金the Shanghai Municipal Science and Technology Major Project(2018SHZDZX05)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB32000000)the Shanghai Science and Technology Committee of Shanghai City(19140903800 and 21XD1422700)。
文摘All animals possess a plethora of innate behaviors that do not require extensive learning and are fundamental for their survival and propagation.With the advent of newly-developed techniques such as viral tracing and optogenetic and chemogenetic tools,recent studies are gradually unraveling neural circuits underlying different innate behaviors.Here,we summarize current development in our understanding of the neural circuits controlling predation,feeding,male-typical mating,and urination,highlighting the role of genetically defined neurons and their connections in sensory triggering,sensory to motor/motivation transformation,motor/motivation encoding during these different behaviors.Along the way,we discuss possible mechanisms underlying binge-eating disorder and the pro-social effects of the neuropeptide oxytocin,elucidating the clinical relevance of studying neural circuits underlying essential innate functions.Finally,we discuss some exciting brain structures recurrently appearing in the regulation of different behaviors,which suggests both divergence and convergence in the neural encoding of specific innate behaviors.Going forward,we emphasize the importance of multi-angle and cross-species dissections in delineating neural circuits that control innate behaviors.
基金supported by the STI2030-Major Projects(2022ZD0205400)the National Natural Science Foundation of China(82192861,81922018,82271170,and 82101218)+3 种基金the Foundation from Science and Technology Commission of Shanghai Municipality(22140900800 and 20JC1419500)the Foundation from Shanghai Municipal Health Commission(20234Z0007)the China Postdoctoral Science Foundation(2021M700824 and 2022T150133)the Shanghai Super Postdoctoral Incentive Program.
文摘Hearing loss is one of the most common sensory disorders worldwide,affecting approximately 466 million people,including 34 million children[1].Genetic mutations accounts for approximately 60%of inherited hearing loss cases[2,3].These genetic changes result in a wide variety of clinical manifestations,ranging from nonsyndromic hearing loss(NSHL)to over 400 syndromes involving hearing loss and from mild adult-onset hearing loss to profound congenital deafness,covering the entire spectrum of Mendelian inheritance.
基金supported by the National Major Science and Technology Program of China(2016YFC1306700)the National Natural Science Foundation of China(81420108012,81671046,81425010 and 31630031)+1 种基金the Jiangsu Provincial Medical Program for Distinguished Scholars(2016006)Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX18_0167),China
文摘A deficit in spatial memory has been taken as an early predictor of Alzheimer’s disease(AD) or mild cognitive impairment(MCI). The uncinate fasciculus(UF) is a long-range white-matter tract that connects the anterior temporal lobe with the orbitofrontal cortex(OFC)in primates. Previous studies have shown that the UF impairment associated with spatial memory deficits may be an important pathological change in aging and AD, but its exact role in spatial memory is not well understood. The pathway arising from the postrhinal cortex(POR) and projecting to the ventrolateral orbitofrontal cortex(vlOFC)performs most of the functions of the UF in rodents.Although the literature suggests an association between spatial memory and the regions connected by the POR–vlOFC pathway, the function of the pathway in spatialmemory is relatively unknown. To further illuminate the function of the UF in spatial memory, we dissected the POR–vlOFC pathway in mice. We determined that the POR–vlOFC pathway is a glutamatergic structure, and that glutamatergic neurons in the POR regulate spatial memory retrieval. We also demonstrated that the POR–vlOFC pathway specifically transmits spatial information to participate in memory retrieval. These findings provide a deeper understanding of UF function and dysfunction related to disorders of memory, as in MCI and AD.
基金This work was supported by the National Natural Science Foundation of China(31625013,81941015,32000726,and 61973086)the Shanghai Brain-Intelligence Project from STCSM(16JC1420501)+2 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDBS01060200)the Program of Shanghai Academic Research LeaderThe Open Large Infrastructure Research of the Chinese Academy of Sciences,and the Shanghai Municipal Science and Technology Major Project(2018SHZDZX01).
文摘Autism spectrum disorder(ASD)is a highly heritable neurodevelopmental disorder characterized by deficits in social interactions and repetitive behaviors.Although hundreds of ASD risk genes,implicated in synaptic formation and transcriptional regulation,have been identified through human genetic studies,the East Asian ASD cohorts are still under-represented in genome-wide genetic studies.Here,we applied whole-exome sequencing to 369 ASD trios including probands and unaffected parents of Chinese origin.Using a joint-calling analytical pipeline based on GATK toolkits,we identified numerous de novo mutations including 55 high-impact variants and 165 moderate-impact variants,as well as de novo copy number variations containing known ASD-related genes.Importantly,combined with single-cell sequencing data from the developing human brain,we found that the expression of genes with de novo mutations was specifically enriched in the pre-,post-central gyrus(PRC,PC)and banks of the superior temporal(BST)regions in the human brain.By further analyzing the brain imaging data with ASD and healthy controls,we found that the gray volume of the right BST in ASD patients was significantly decreased compared to healthy controls,suggesting the potential structural deficits associated with ASD.Finally,we found a decrease in the seed-based functional connectivity between BST/PC/PRC and sensory areas,the insula,as well as the frontal lobes in ASD patients.This work indicated that combinatorial analysis with genome-wide screening,single-cell sequencing,and brain imaging data reveal the brain regions contributing to the etiology of ASD.
基金This work was supported by grants from the Key Research and Development project of Zhejiang Province(2019C03039)the National Natural Science Foundation of China(81970998)+1 种基金the Science Innovation 2030-Brain Science and Brain-Inspired Intelligence Technology Major Projects(nos.2021ZD0201103 and 2021ZD0201803)the Integrative Traditional Chinese and Western Medicine Innovation Team for Neurodegenerative Diseases of Zhejiang Province.
文摘Amyloid-b,tau pathology,and biomarkers of neurodegeneration make up the core diagnostic biomarkers of Alzheimer disease(AD).However,these proteins represent only a fraction of the complex biological processes underlying AD,and individuals with other brain diseases in which AD pathology is a comorbidity also test positive for these diagnostic biomarkers.More ADspecific early diagnostic and disease staging biomarkers are needed.In this study,we performed tandem mass tag proteomic analysis of paired cerebrospinal fluid(CSF)and serum samples in a discovery cohort comprising 98 participants.Candidate biomarkers were validated by parallel reaction monitoring–based targeted proteomic assays in an independent multicenter cohort comprising 288 participants.We quantified 3,238 CSF and 1,702 serum proteins in the discovery cohort,identifying 171 and 860 CSF proteins and 37 and 323 serum proteins as potential early diagnostic and staging biomarkers,respectively.In the validation cohort,58 and 21 CSF proteins,as well as 12 and 18 serum proteins,were verified as early diagnostic and staging biomarkers,respectively.Separate 19-protein CSF and an 8-protein serum biomarker panels were built by machine learning to accurately classify mild cognitive impairment(MCI)due to AD from normal cognition with areas under the curve of 0.984 and 0.881,respectively.The 19-protein CSF biomarker panel also effectively discriminated patients with MCI due to AD from patients with other neurodegenerative diseases.Moreover,we identified 21 CSF and 18 serum stage-associated proteins re-flecting AD stages.Our findings provide a foundation for developing bloodbased tests for AD screening and staging in clinical practice.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences, China (XDB02030005)
文摘Many complex behaviors that do not require learning are displayed and are termed innate. Although traditionally the subject matter of ethology, innate behaviors offer a unique entry point for neuroscientists to dissect the physiological mechanisms governing complex behaviors. Since the last century, converging evidence has implicated the hypothalamus as the central brain area that controls innate behaviors. Recent studies using cutting-edge tools have revealed that genetically-defined populations of neurons residing in distinct hypothalamic nuclei and their associated neural pathways regulate the initiation and maintenance of diverse behaviors including feeding, sleep, aggression, and parental care. Here, we review the newly-defined hypothalamic pathways that regulate each innate behavior. In addition, emerging general principles of the neural control of complex behaviors are discussed.
