Type 2 diabetes mellitus has central complications:Diabetes,a metabolic disorder primarily characterized by hyperglycemia due to insufficient insulin secretion,or impaired insulin signaling,has significant central com...Type 2 diabetes mellitus has central complications:Diabetes,a metabolic disorder primarily characterized by hyperglycemia due to insufficient insulin secretion,or impaired insulin signaling,has significant central complications.Type 2 diabetes mellitus(T2DM),the most prevalent type of diabetes,affects more than 38 million individuals in the United States(approximately 1 in 10)and is defined by chronic hyperglycemia and insulin resistance,which refers to a reduced cellular response to insulin.展开更多
The locus coeruleus(LC),a norepinephrine nucleus governing arousal states through tonic activity,requires precise regulatory mechanisms to maintain its dynamic activation levels.However,the neural circuitry underlying...The locus coeruleus(LC),a norepinephrine nucleus governing arousal states through tonic activity,requires precise regulatory mechanisms to maintain its dynamic activation levels.However,the neural circuitry underlying LC activity maintenance remains unclear.Here,we identify a glutamatergic projection from the ventrolateral periaqueductal gray(vlPAG)to the LC in mice as a critical regulator of arousal dynamics.Fiber photometry recordings revealed stress-induced Ca^(2+)dynamics in vlPAGCaMKIIα-LC axon terminals across diverse threat paradigms.Slice electrophysiology demonstrated that this pathway mediates LC-norepinephrine(LC-NE)neuronal activity via glutamatergic transmission.Low-frequency pathway activation(1 Hz)mainly induced anxiety-like behaviors,whereas high-frequency stimulation(10 Hz)evoked more panic-like hyperlocomotion,establishing a frequency-dependent continuum of arousal states.Conversely,pathway inhibition reduced pupil size,a reliable biomarker for arousal,concurrently suppressing threat avoidance behaviors and alleviating anxiety-related behaviors without altering environmental preference.These findings reveal that the vlPAGCaMKIIα-LC pathway maintains baseline arousal while dynamically scaling threat-induced hyperarousal.展开更多
Rapid diagnosis of Salmonella is crucial for the effective control of food safety incidents, especially in regions with poor hygiene conditions. Polymerase chain reaction(PCR), as a promising tool for Salmonella detec...Rapid diagnosis of Salmonella is crucial for the effective control of food safety incidents, especially in regions with poor hygiene conditions. Polymerase chain reaction(PCR), as a promising tool for Salmonella detection, is facing a lack of simple and fast sensing methods that are compatible with field applications in resource-limited areas. In this work, we developed a sensing approach to identify PCR-amplified Salmonella genomic DNA with the naked eye in a snapshot. Based on the ratiometric fiuorescence signals from SYBR Green Ⅰ and Hydroxyl naphthol blue, positive samples stood out from negative ones with a distinct color pattern under UV exposure. The proposed sensing scheme enabled highly specific identification of Salmonella with a detection limit at the single-copy level. Also, as a supplement to the intuitive naked-eye visualization results, numerical analysis of the colored images was available with a smartphone app to extract RGB values from colored images. This work provides a simple, rapid, and user-friendly solution for PCR identification, which promises great potential in molecular diagnosis of Salmonella and other pathogens in field.展开更多
Aggression,an evolutionarily conserved social behavior,is essential for animals to compete for valuable resources like food,territory,and mates,and to protect kin.Although aggression is required for the survival of bo...Aggression,an evolutionarily conserved social behavior,is essential for animals to compete for valuable resources like food,territory,and mates,and to protect kin.Although aggression is required for the survival of both sexes,it is often displayed in a sexually dimorphic manner,with males typically exhibiting higher levels of aggression than females.展开更多
The somatotopic representation of specific body parts is a well-established spatial organizational principle in the primary somatosensory and motor cortices.
Dynamical systems often exhibit multiple attractors representing significantly different functioning conditions.A global map of attraction basins can offer valuable guidance for stabilizing or transitioning system sta...Dynamical systems often exhibit multiple attractors representing significantly different functioning conditions.A global map of attraction basins can offer valuable guidance for stabilizing or transitioning system states.Such a map can be constructed without prior system knowledge by identifying attractors across a sufficient number of points in the state space.However,determining the attractor for each initial state can be a laborious task.Here,we tackle the challenge of reconstructing attraction basins using as few initial points as possible.In each iteration of our approach,informative points are selected through random seeding and are driven along the current classification boundary,promoting the eventual selection of points that are both diverse and enlightening.The results across various experimental dynamical systems demonstrate that our approach requires fewer points than baseline methods while achieving comparable mapping accuracy.Additionally,the reconstructed map allows us to accurately estimate the minimum escape distance required to transition the system state to a target basin.展开更多
The period of infancy is important for the formation of social behaviors due to the rapid postnatal development of the brain functions underlying emotions and social skills.Ilustration of the neural circuits involved ...The period of infancy is important for the formation of social behaviors due to the rapid postnatal development of the brain functions underlying emotions and social skills.Ilustration of the neural circuits involved in the developmental process of infant social behaviors could foster new therapies for some social impairments occurring in the infant period.展开更多
Social behaviors are crucial for gregarious animals,including humans.In order to exhibit appropriate behaviors in a complex social context,such as mating,aggression,avoidance,and cooperation,individuals need to rememb...Social behaviors are crucial for gregarious animals,including humans.In order to exhibit appropriate behaviors in a complex social context,such as mating,aggression,avoidance,and cooperation,individuals need to remember their previous experiences with other members and accurately recognize them when they meet again.This ability is called“social memory”[1].Many psychiatric disorders in humans,such as autism spectrum disorder,attention deficit hyperactivity disorder,and schizophrenia,are characterized by social memory impairments.Patients with these disorders,along with corresponding animal models,often show defects associated with the thalamic reticular nucleus(TRN).The TRN,a thin layer of neurons surrounding the thalamus,mainly regulates and coordinates the transfer of information between the cortex and the thalamus,playing a role in higher brain functions such as consciousness,attention,and sensory processing.However,whether the TRN is involved in social memory remains unknown.展开更多
Traditional diagnostic tools for depression,such as the Patient Health Questionnaire-9,are susceptible to subjective bias,increasing the risk of misdiagnosis and emphasizing the critical need for objective biomarkers....Traditional diagnostic tools for depression,such as the Patient Health Questionnaire-9,are susceptible to subjective bias,increasing the risk of misdiagnosis and emphasizing the critical need for objective biomarkers.This minireview evaluates the emerging role of portable electroencephalography(EEG)as a cost-effective,accessible solution for early depression detection.By synthesizing findings from 45 studies(selected from 764 screened articles),we highlight EEG’s capacity to identify aberrant neural oscillations associated with core depressive symptoms,including anhedonia,excessive guilt,and persistent low mood.Advances in portable systems demonstrate promising classification accuracy when integrated with machine learning algorithms,with long short-term memory models achieving>90%accuracy in recent trials.However,persistent challenges,such as signal quality variability,motion artifacts,and limited clinical validation,hinder widespread adoption.Further innovation in sensor optimization,multimodal data integration,and real-world clinical trials is essential to translate portable EEG into a reliable diagnostic tool.This minireview underscores the transformative potential of neurotechnology in psychiatry while advocating for rigorous standard ization to bridge the gap between research and clinical practice.展开更多
Hereditary spastic paraplegias(HSPs)refer to a genetically and clinically heterogeneous group of neurodegenerative disorders characterized by the degeneration of motor neurons.To date,a significant number of patients ...Hereditary spastic paraplegias(HSPs)refer to a genetically and clinically heterogeneous group of neurodegenerative disorders characterized by the degeneration of motor neurons.To date,a significant number of patients still have not received a definite genetic diagnosis.Therefore,identifying unreported causative genes continues to be of great importance.Here,we perform whole-exome sequencing in a cohort of Chinese HSP patients.Three homozygous variants(p.L604W,p.S517F,and p.T984A)within the sterol regulatory element-binding factor 2(SREBF2)gene are identified in one autosomal recessive family and two sporadic patients,respectively.Co-segregation is confirmed by Sanger sequencing in all available members.The three variants are rare in the public or in-house database and are predicted to be damaging.The biological impacts of variants in SREBF2 are examined by functional experiments in patient-derived fibroblasts and Drosophila.We find that the variants upregulate cellular cholesterol due to the overactivation of SREBP2,eventually impairing the autophagosomal and lysosomal functions.The overexpression of the mature form of SREBP2 leads to locomotion defects in Drosophila.Our findings identify SREBF2 as a causative gene for HSP and highlight the impairment of cholesterol as a critical pathway for HSP.展开更多
Empathy is one of the most important abilities for social animals.In a world that is largely socially constructed,when encountering altered affective states of others,particularly negative states,individuals often exh...Empathy is one of the most important abilities for social animals.In a world that is largely socially constructed,when encountering altered affective states of others,particularly negative states,individuals often exhibit evolutionarily conserved empathic behaviors,such as mirroring,consolation,and helping[l,2].Appropriate empathic behaviors can foster the consolidation of social relationships.Previous studies have suggested that both male and female rodents show some empathic behaviors when facing affective conspecifics[1].However,the role of sex in different empathic behaviors remains largely unexplored.Therefore,there is a need to probe whether animals show sex-dependent empathic behavior and which neural circuits modulate these distinct behaviors.展开更多
A growing interest in the comprehensive pathogenic mechanisms of psychiatric disorders from the perspective of the microbiome has been witnessed in recent decades;the intrinsic link between microbiota and brain functi...A growing interest in the comprehensive pathogenic mechanisms of psychiatric disorders from the perspective of the microbiome has been witnessed in recent decades;the intrinsic link between microbiota and brain function through the microbiota-gut-brain axis or other pathways has gradually been realized.However,little research has focused on viruses–entities characterized by smaller dimensions,simpler structures,greater diversity,and more intricate interactions with their surrounding milieu compared to bacteria.To date,alterations in several populations of bacteriophages and viruses have been documented in both mouse models and patients with psychiatric disorders,including schizophrenia,major depressive disorder,autism spectrum disorder,and Alzheimer’s disease,accompanied by metabolic disruptions that may directly or indirectly impact brain function.In addition,eukaryotic virus infection-mediated brain dysfunction provides insights into the psychiatric pathology involving viruses.Efforts towards virus-based diagnostic and therapeutic approaches have primarily been documented.However,limitations due to the lack of large-scale cohort studies,reliability,clinical applicability,and the unclear role of viruses in microbiota interactions pose a challenge for future studies.Nevertheless,it is conceivable that investigations into viruses herald a new era in the field of precise psychiatry.展开更多
Reward or stress,which exists extensively,causes resilient emotional fluctuations under common situations.However,reward or stress is a typical trigger for manic or depressive episodes of bipolar disorder(BD),which is...Reward or stress,which exists extensively,causes resilient emotional fluctuations under common situations.However,reward or stress is a typical trigger for manic or depressive episodes of bipolar disorder(BD),which is corroborated by psychological theory,biological findings,and psychosocial treatment approaches[1,2].During an episode of BD,the affective aberration can be persistent and switchable,accompanied by opposite constellations of cognitive and psychomotor symptoms.Characterized by uncontrollable mood ranging in severity,duration,and polarity,to disentangle the pathophysiology mechanism of BD is to delineate the mystery of affective fluctuations driven by reward or stress.展开更多
Anxiety disorder is a major symptom of autism spectrum disorder(ASD)with a comorbidity rate of~40%.However,the neural mechanisms of the emergence of anxiety in ASD remain unclear.In our study,we found that hyperactivi...Anxiety disorder is a major symptom of autism spectrum disorder(ASD)with a comorbidity rate of~40%.However,the neural mechanisms of the emergence of anxiety in ASD remain unclear.In our study,we found that hyperactivity of basolateral amygdala(BLA)pyramidal neurons(PNs)in Shank3 InsG3680 knock-in(InsG3680+/+)mice is involved in the development of anxiety.Electrophysiological results also showed increased excitatory input and decreased inhibitory input in BLA PNs.Chemogenetic inhibition of the excitability of PNs in the BLA rescued the anxiety phenotype of InsG3680+/+mice.Further study found that the diminished control of the BLA by medial prefrontal cortex(mPFC)and optogenetic activation of the mPFC-BLA pathway also had a rescue effect,which increased the feedforward inhibition of the BLA.Taken together,our results suggest that hyperactivity of the BLA and alteration of the mPFC-BLA circuitry are involved in anxiety in InsG3680+/+mice.展开更多
Objective:Whether vortioxetine has a utility as an adjuvant drug in the treatment of bipolar depression remains controversial.This study aimed to validate the efficacy and safety of vortioxetine in bipolar depression....Objective:Whether vortioxetine has a utility as an adjuvant drug in the treatment of bipolar depression remains controversial.This study aimed to validate the efficacy and safety of vortioxetine in bipolar depression.Methods:Patients with bipolarⅡdepression were enrolled in this prospective,two-center,randomized,12-week pilot trial.The main indicator for assessing treatment effectiveness was a Montgomery-Asberg Depression Rating Scale(MADRS)of≥50%.All eligible patients initially received four weeks of lurasidone monotherapy.Patients who responded well continued to receive this kind of monotherapy.However,no-response patients were randomly assigned to either valproate or vortioxetine treatment for eight weeks.By comprehensively comparing the results of MADRS over a period of 4-12 weeks,a systematic analysis was conducted to determine whether vortioxetine could be used as an adjuvant drug for treating bipolar depression.Results:Thirty-seven patients responded to lurasidone monotherapy,and 60 patients were randomly assigned to the valproate or vortioxetine group for eight weeks.After two weeks of combined valproate or vortioxetine treatment,the MADRS score in the vortioxetine group was significantly lower than that in the valproate group.There was no difference in the MADRS scores between the two groups at 8 and 12 weeks.The incidence of side effects did not significantly differ between the valproate and vortioxetine groups.Importantly,three patients in the vortioxetine group appeared to switch to mania or hypomania.Conclusions:This study suggested that lurasidone combination with vortioxetine might have potential benefits to bipolar II depression in the early stage,while disease progression should be monitored closely for the risk of switching to mania.展开更多
Chemotherapy-induced peripheral neurotoxicity(CIPN)is a severe dose-limiting adverse event of chemotherapy.Presently,the mechanism underlying the induction of CIPN remains unclear,and no effective treatment is availab...Chemotherapy-induced peripheral neurotoxicity(CIPN)is a severe dose-limiting adverse event of chemotherapy.Presently,the mechanism underlying the induction of CIPN remains unclear,and no effective treatment is available.In this study,through metabolomics analyses,we found that nab-paclitaxel therapy markedly increased serum serotonin[5-hydroxtryptamine(5-HT)]levels in both cancer patients and mice compared to the respective controls.Furthermore,nab-paclitaxel-treated enterochromaffin(EC)cells showed increased 5-HT synthesis,and serotonin-treated Schwann cells showed damage,as indicated by the activation of CREB3L3/MMP3/FAS signaling.Venlafaxine,an inhibitor of serotonin and norepinephrine reuptake,was found to protect against nerve injury by suppressing the activation of CREB3L3/MMP3/FAS signaling in Schwann cells.Remarkably,venlafaxine was found to significantly alleviate nab-paclitaxel-induced CIPN in patients without affecting the clinical efficacy of chemotherapy.In summary,our study reveals that EC cell-derived 5-HT plays a critical role in nab-paclitaxel-related neurotoxic lesions,and venlafaxine co-administration represents a novel approach to treating chronic cumulative neurotoxicity commonly reported in nab-paclitaxel-based chemotherapy.展开更多
Military psychiatry, a new subcategory of psychiatry, has become an invaluable, intangible effect of the war. In this review, we begin by examining related military research, summarizing the related epidemiological da...Military psychiatry, a new subcategory of psychiatry, has become an invaluable, intangible effect of the war. In this review, we begin by examining related military research, summarizing the related epidemiological data, neuropathology, and the research achievements of diagnosis and treatment technology, and discussing its comorbidity and sequelae. To date, advances in neuroimaging and molecular biology have greatly boosted the studies on military traumatic brain injury(TBI). In particular, in terms of pathophysiological mechanisms, several preclinical studies have identified abnormal protein accumulation, blood–brain barrier damage, and brain metabolism abnormalities involved in the development of TBI. As an important concept in the field of psychiatry, TBI is based on organic injury, which is largely different from many other mental disorders. Therefore, military TBI is both neuropathic and psychopathic, and is an emerging challenge at the intersection of neurology and psychiatry.展开更多
Neurons are highly interwoven to form intricate neural circuits that underlie the diverse functions of the brain.Dissecting the anatomical organization of neural circuits is key to deciphering how the brain processes ...Neurons are highly interwoven to form intricate neural circuits that underlie the diverse functions of the brain.Dissecting the anatomical organization of neural circuits is key to deciphering how the brain processes information,produces thoughts,and instructs behaviors.Over the past decades,recombinant viral vectors have become the most commonly used tracing tools to define circuit architecture.In this review,we introduce the current categories of viral tools and their proper application in circuit tracing.We further discuss some advances in viral tracing strategy and prospective innovations of viral tools for future study.展开更多
Cancer presents a significant global challenge,impacting individuals,communities,and healthcare systems worldwide[1,2].Fundamentally,cancer involves the uncontrolled growth and proliferation of cells,driven by genetic...Cancer presents a significant global challenge,impacting individuals,communities,and healthcare systems worldwide[1,2].Fundamentally,cancer involves the uncontrolled growth and proliferation of cells,driven by genetic and epigenetic alterations orchestrated by a complex array of molecular entities,including oncogenes,tumor suppressor genes,and various regulatory factors[3-5].This intricate interplay complicates early detection,often resulting in a significant mortality burden.Accounting for nearly 30%of premature deaths globally,cancer is a major barrier to increasing human life expectancy[6,7].The urgent need for continued research,innovation,and collaborative efforts highlights the importance of combating this relentless disease.展开更多
Defensive behaviors induced by innate fear or Pavlovian fear conditioning are crucial for animals to avoid threats and ensure survival.The zona incerta(ZI)has been demonstrated to play important roles in fear learning...Defensive behaviors induced by innate fear or Pavlovian fear conditioning are crucial for animals to avoid threats and ensure survival.The zona incerta(ZI)has been demonstrated to play important roles in fear learning and fear memory,as well as modulating auditory-induced innate defensive behavior.However,whether the neuronal subtypes in the ZI and specific circuits can mediate the innate fear response is largely unknown.Here,we found that somatostatin(SST)-positive neurons in the rostral ZI of mice were activated by a visual innate fear stimulus.Optogenetic inhibition of SST-positive neurons in the rostral ZI resulted in reduced flight responses to an overhead looming stimulus.Optogenetic activation of SST-positive neurons in the rostral ZI induced fear-like defensive behavior including increased immobility and bradycardia.In addition,we demonstrated that manipulation of the GABAergic projections from SST-positive neurons in the rostral ZI to the downstream nucleus reuniens(Re)mediated fear-like defensive behavior.Retrograde trans-synaptic tracing also revealed looming stimulus-activated neurons in the superior colliculus(SC)that projected to the Re-projecting SST-positive neurons in the rostral ZI(SC-ZIrSST-Re pathway).Together,our study elucidates the function of SST-positive neurons in the rostral ZI and the SC-ZIrSST-Re tri-synaptic circuit in mediating the innate fear response.展开更多
基金supported by grants from NIH T32(DK007260,to WC)the Steno North American Fellowship awarded by the Novo Nordisk Foundation(NNF23OC0087108,to WC)+6 种基金STI2030-Major Projects(2021ZD0202700,to HY)the National Natural Science Foundation of China(32241004,to HY)the Natural Science Foundation of Zhejiang Province of China(LR24C090001,to HY)Key R&D Program of Zhejiang Province(2024SSYS0017,to HY)CAMS Innovation Fund for Medical Sciences(2019-12M-5-057,to HY)Fundamental Research Funds for the Central Universities(226-2022-00193,to HY)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2023-PT310-01,to HY)。
文摘Type 2 diabetes mellitus has central complications:Diabetes,a metabolic disorder primarily characterized by hyperglycemia due to insufficient insulin secretion,or impaired insulin signaling,has significant central complications.Type 2 diabetes mellitus(T2DM),the most prevalent type of diabetes,affects more than 38 million individuals in the United States(approximately 1 in 10)and is defined by chronic hyperglycemia and insulin resistance,which refers to a reduced cellular response to insulin.
基金supported by grants from the National Natural Science Foundation of China(32171014 and 32000706)the National Science and Technology Major Project(2024ZD0530200)+5 种基金research funding by the Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences(2023-PT310-01)the Fundamental Research Funds for Central Universities(226-2024-00133)Nanhu Brain-computer Interface Institute(010904004)the Zhejiang Provincial Natural Science Foundation of China(LMS25C090004)The Fundamental Research Funds for Central Universities(2025ZFJH01-01)the China Postdoctoral Science Foundation(2020M681828 and 2023TQ0280).
文摘The locus coeruleus(LC),a norepinephrine nucleus governing arousal states through tonic activity,requires precise regulatory mechanisms to maintain its dynamic activation levels.However,the neural circuitry underlying LC activity maintenance remains unclear.Here,we identify a glutamatergic projection from the ventrolateral periaqueductal gray(vlPAG)to the LC in mice as a critical regulator of arousal dynamics.Fiber photometry recordings revealed stress-induced Ca^(2+)dynamics in vlPAGCaMKIIα-LC axon terminals across diverse threat paradigms.Slice electrophysiology demonstrated that this pathway mediates LC-norepinephrine(LC-NE)neuronal activity via glutamatergic transmission.Low-frequency pathway activation(1 Hz)mainly induced anxiety-like behaviors,whereas high-frequency stimulation(10 Hz)evoked more panic-like hyperlocomotion,establishing a frequency-dependent continuum of arousal states.Conversely,pathway inhibition reduced pupil size,a reliable biomarker for arousal,concurrently suppressing threat avoidance behaviors and alleviating anxiety-related behaviors without altering environmental preference.These findings reveal that the vlPAGCaMKIIα-LC pathway maintains baseline arousal while dynamically scaling threat-induced hyperarousal.
基金supported by the Macao Science and Technology Development Fund(FDCT)(Nos.FDCT 0029/2021/A1,FDCT0002/2021/AKP,004/2023/SKL,0036/2021/APD)University of Macao(No.MYRG-GRG2023-00034-IME,SRG2024-00057IME)+2 种基金Dr.Stanley Ho Medical Development Foundation(No.SHMDF-OIRFS/2024/001)Zhuhai Huafa Group(No.HF-006-2021)Guangdong Science and Technology Department(No.2022A0505030022)。
文摘Rapid diagnosis of Salmonella is crucial for the effective control of food safety incidents, especially in regions with poor hygiene conditions. Polymerase chain reaction(PCR), as a promising tool for Salmonella detection, is facing a lack of simple and fast sensing methods that are compatible with field applications in resource-limited areas. In this work, we developed a sensing approach to identify PCR-amplified Salmonella genomic DNA with the naked eye in a snapshot. Based on the ratiometric fiuorescence signals from SYBR Green Ⅰ and Hydroxyl naphthol blue, positive samples stood out from negative ones with a distinct color pattern under UV exposure. The proposed sensing scheme enabled highly specific identification of Salmonella with a detection limit at the single-copy level. Also, as a supplement to the intuitive naked-eye visualization results, numerical analysis of the colored images was available with a smartphone app to extract RGB values from colored images. This work provides a simple, rapid, and user-friendly solution for PCR identification, which promises great potential in molecular diagnosis of Salmonella and other pathogens in field.
基金supported by the New Cornerstone Science Foundation and the Key R&D Program of Zhejiang(2024SSYS0016).
文摘Aggression,an evolutionarily conserved social behavior,is essential for animals to compete for valuable resources like food,territory,and mates,and to protect kin.Although aggression is required for the survival of both sexes,it is often displayed in a sexually dimorphic manner,with males typically exhibiting higher levels of aggression than females.
文摘The somatotopic representation of specific body parts is a well-established spatial organizational principle in the primary somatosensory and motor cortices.
基金supported by the National Natural Science Foundation of China(Grant Nos.T2225022,12350710786,62088101,and 12161141016)Shuguang Program of Shanghai Education Development Foundation(Grant No.22SG21)Shanghai Municipal Education Commission,and the Fundamental Research Funds for the Central Universities。
文摘Dynamical systems often exhibit multiple attractors representing significantly different functioning conditions.A global map of attraction basins can offer valuable guidance for stabilizing or transitioning system states.Such a map can be constructed without prior system knowledge by identifying attractors across a sufficient number of points in the state space.However,determining the attractor for each initial state can be a laborious task.Here,we tackle the challenge of reconstructing attraction basins using as few initial points as possible.In each iteration of our approach,informative points are selected through random seeding and are driven along the current classification boundary,promoting the eventual selection of points that are both diverse and enlightening.The results across various experimental dynamical systems demonstrate that our approach requires fewer points than baseline methods while achieving comparable mapping accuracy.Additionally,the reconstructed map allows us to accurately estimate the minimum escape distance required to transition the system state to a target basin.
基金supported by grants from the National Natural Science Foundation of China(32125018,32071005,and 32171079)Zhejiang Provincial Natural Science Foundation of China(LD24H090002 and LZ24C090001)+2 种基金the Fundamental Research Funds for the Central Universities(226-2024-00133)the Innovative Research Team of High-level Local Universities in Shanghai(SHSMU-ZDCX20211102)the MOE Frontiers Science Center for Brain Science&Brain-Machine Integration of Zhejiang University.
文摘The period of infancy is important for the formation of social behaviors due to the rapid postnatal development of the brain functions underlying emotions and social skills.Ilustration of the neural circuits involved in the developmental process of infant social behaviors could foster new therapies for some social impairments occurring in the infant period.
基金supported by grants from the National Natural Science Foundation of China(32125018 and 32071005)Zhejiang Provincial Natural Science Foundation of China(LD24H090002)+3 种基金Nanhu Brain-computer Interface Institute(010904008)Innovative Research Team of High-level Local Universities in Shanghai(SHSMUZDCX20211102)Fundamental Research Funds for the Central Universities(226-2024-00133)the MOE Frontiers Science Center for Brain Science&Brain-Machine Integration of Zhejiang University.
文摘Social behaviors are crucial for gregarious animals,including humans.In order to exhibit appropriate behaviors in a complex social context,such as mating,aggression,avoidance,and cooperation,individuals need to remember their previous experiences with other members and accurately recognize them when they meet again.This ability is called“social memory”[1].Many psychiatric disorders in humans,such as autism spectrum disorder,attention deficit hyperactivity disorder,and schizophrenia,are characterized by social memory impairments.Patients with these disorders,along with corresponding animal models,often show defects associated with the thalamic reticular nucleus(TRN).The TRN,a thin layer of neurons surrounding the thalamus,mainly regulates and coordinates the transfer of information between the cortex and the thalamus,playing a role in higher brain functions such as consciousness,attention,and sensory processing.However,whether the TRN is involved in social memory remains unknown.
基金Supported by Ministry of Science and Technology of the People’s Republic of China-Major Projects,No.2022ZD0212400National Natural Science Foundation of China,No.82371453.
文摘Traditional diagnostic tools for depression,such as the Patient Health Questionnaire-9,are susceptible to subjective bias,increasing the risk of misdiagnosis and emphasizing the critical need for objective biomarkers.This minireview evaluates the emerging role of portable electroencephalography(EEG)as a cost-effective,accessible solution for early depression detection.By synthesizing findings from 45 studies(selected from 764 screened articles),we highlight EEG’s capacity to identify aberrant neural oscillations associated with core depressive symptoms,including anhedonia,excessive guilt,and persistent low mood.Advances in portable systems demonstrate promising classification accuracy when integrated with machine learning algorithms,with long short-term memory models achieving>90%accuracy in recent trials.However,persistent challenges,such as signal quality variability,motion artifacts,and limited clinical validation,hinder widespread adoption.Further innovation in sensor optimization,multimodal data integration,and real-world clinical trials is essential to translate portable EEG into a reliable diagnostic tool.This minireview underscores the transformative potential of neurotechnology in psychiatry while advocating for rigorous standard ization to bridge the gap between research and clinical practice.
基金supported by the grants from the National Natural Science Foundation of China to Zhi-Ying Wu(82230062,Beijing),Qiao Wei(82402156,Beijing),and Wanzhong Ge(31970668,Beijing)the research foundation for distinguished scholar of Zhejiang University(188020-193810101/089,Hangzhou)to Zhi-Ying Wu
文摘Hereditary spastic paraplegias(HSPs)refer to a genetically and clinically heterogeneous group of neurodegenerative disorders characterized by the degeneration of motor neurons.To date,a significant number of patients still have not received a definite genetic diagnosis.Therefore,identifying unreported causative genes continues to be of great importance.Here,we perform whole-exome sequencing in a cohort of Chinese HSP patients.Three homozygous variants(p.L604W,p.S517F,and p.T984A)within the sterol regulatory element-binding factor 2(SREBF2)gene are identified in one autosomal recessive family and two sporadic patients,respectively.Co-segregation is confirmed by Sanger sequencing in all available members.The three variants are rare in the public or in-house database and are predicted to be damaging.The biological impacts of variants in SREBF2 are examined by functional experiments in patient-derived fibroblasts and Drosophila.We find that the variants upregulate cellular cholesterol due to the overactivation of SREBP2,eventually impairing the autophagosomal and lysosomal functions.The overexpression of the mature form of SREBP2 leads to locomotion defects in Drosophila.Our findings identify SREBF2 as a causative gene for HSP and highlight the impairment of cholesterol as a critical pathway for HSP.
基金supported by grants from the National Natural Science Foundation of China(32125018 and 32071005)the National Key Research and Development Program of China(2021YFA1101701)+5 种基金Zhejiang Provincial Natural Science Foundation of China(LD24H090002)the Nanhu Brain-computer Interface Institute(010904008)the Fundamental Research Funds for the Central Universities(226-2024-00133)the Key R&D Program of Zhejiang(2024SSYS0016)the Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences(2023-PT310-01)the MOE Frontiers Science Center for Brain Science&Brain-Machine Integration of Zhejiang University.
文摘Empathy is one of the most important abilities for social animals.In a world that is largely socially constructed,when encountering altered affective states of others,particularly negative states,individuals often exhibit evolutionarily conserved empathic behaviors,such as mirroring,consolation,and helping[l,2].Appropriate empathic behaviors can foster the consolidation of social relationships.Previous studies have suggested that both male and female rodents show some empathic behaviors when facing affective conspecifics[1].However,the role of sex in different empathic behaviors remains largely unexplored.Therefore,there is a need to probe whether animals show sex-dependent empathic behavior and which neural circuits modulate these distinct behaviors.
基金supported by The Research Project of Jinan Microecological Biomedicine Shandong Laboratory(JNL-2023001B)The National Key Research and Development Program of China(2023YFC2506200)+2 种基金The Zhejiang Provincial Key Research and Development Program(2021C03107)The Leading Talent of Scientific and Technological Innovation-“Ten Thousand Talents Program”of Zhejiang Province(2021R52016)The Fundamental Research Funds for the Central Universities(226-2022-00193,226-2022-00002,2023ZFJH01-01,and 2024ZFJH01-01).
文摘A growing interest in the comprehensive pathogenic mechanisms of psychiatric disorders from the perspective of the microbiome has been witnessed in recent decades;the intrinsic link between microbiota and brain function through the microbiota-gut-brain axis or other pathways has gradually been realized.However,little research has focused on viruses–entities characterized by smaller dimensions,simpler structures,greater diversity,and more intricate interactions with their surrounding milieu compared to bacteria.To date,alterations in several populations of bacteriophages and viruses have been documented in both mouse models and patients with psychiatric disorders,including schizophrenia,major depressive disorder,autism spectrum disorder,and Alzheimer’s disease,accompanied by metabolic disruptions that may directly or indirectly impact brain function.In addition,eukaryotic virus infection-mediated brain dysfunction provides insights into the psychiatric pathology involving viruses.Efforts towards virus-based diagnostic and therapeutic approaches have primarily been documented.However,limitations due to the lack of large-scale cohort studies,reliability,clinical applicability,and the unclear role of viruses in microbiota interactions pose a challenge for future studies.Nevertheless,it is conceivable that investigations into viruses herald a new era in the field of precise psychiatry.
基金supported by the National Key Research and Development Program of China(2023YFC2506200)the Leading Talent of Scientific and Technological Innovation-"Ten Thousand Talents Program"of Zhejiang Province(2021R52016).
文摘Reward or stress,which exists extensively,causes resilient emotional fluctuations under common situations.However,reward or stress is a typical trigger for manic or depressive episodes of bipolar disorder(BD),which is corroborated by psychological theory,biological findings,and psychosocial treatment approaches[1,2].During an episode of BD,the affective aberration can be persistent and switchable,accompanied by opposite constellations of cognitive and psychomotor symptoms.Characterized by uncontrollable mood ranging in severity,duration,and polarity,to disentangle the pathophysiology mechanism of BD is to delineate the mystery of affective fluctuations driven by reward or stress.
基金supported by grants from the National Natural Science Foundation of China(31970902,U22A20306,and 3192010300)the Municipal Administration of Hospitals Incubating Program(PZ2023009)+1 种基金the Key-Area R&D Program of Guangdong Province(2019B030335001)the Autism Research Special Fund of Zhejiang Foundation for Disabled Persons(2022003).
文摘Anxiety disorder is a major symptom of autism spectrum disorder(ASD)with a comorbidity rate of~40%.However,the neural mechanisms of the emergence of anxiety in ASD remain unclear.In our study,we found that hyperactivity of basolateral amygdala(BLA)pyramidal neurons(PNs)in Shank3 InsG3680 knock-in(InsG3680+/+)mice is involved in the development of anxiety.Electrophysiological results also showed increased excitatory input and decreased inhibitory input in BLA PNs.Chemogenetic inhibition of the excitability of PNs in the BLA rescued the anxiety phenotype of InsG3680+/+mice.Further study found that the diminished control of the BLA by medial prefrontal cortex(mPFC)and optogenetic activation of the mPFC-BLA pathway also had a rescue effect,which increased the feedforward inhibition of the BLA.Taken together,our results suggest that hyperactivity of the BLA and alteration of the mPFC-BLA circuitry are involved in anxiety in InsG3680+/+mice.
基金partially supported by the Construction Fund of Key Medical Disciplines of Hangzhou(No.OO2020491)the National Key Research and Development Program of China(No.2023YFC2506200)+4 种基金the Zhejiang Provincial Key Research and Development Program(No.2021C03107)the Research Project of Jinan Microecological Biomedicine Shandong Laboratory(No.JNL-2023001B)the Leading Talent of Scientific and Technological Innovation-“Ten Thousand Talents Program”of Zhejiang Province(No.2021R52016)the Innovation Team for Precision Diagnosis and Treatment of Major Brain Diseases(No.2020R01001)the Chinese Medical Education Association(No.2022KTZ004).
文摘Objective:Whether vortioxetine has a utility as an adjuvant drug in the treatment of bipolar depression remains controversial.This study aimed to validate the efficacy and safety of vortioxetine in bipolar depression.Methods:Patients with bipolarⅡdepression were enrolled in this prospective,two-center,randomized,12-week pilot trial.The main indicator for assessing treatment effectiveness was a Montgomery-Asberg Depression Rating Scale(MADRS)of≥50%.All eligible patients initially received four weeks of lurasidone monotherapy.Patients who responded well continued to receive this kind of monotherapy.However,no-response patients were randomly assigned to either valproate or vortioxetine treatment for eight weeks.By comprehensively comparing the results of MADRS over a period of 4-12 weeks,a systematic analysis was conducted to determine whether vortioxetine could be used as an adjuvant drug for treating bipolar depression.Results:Thirty-seven patients responded to lurasidone monotherapy,and 60 patients were randomly assigned to the valproate or vortioxetine group for eight weeks.After two weeks of combined valproate or vortioxetine treatment,the MADRS score in the vortioxetine group was significantly lower than that in the valproate group.There was no difference in the MADRS scores between the two groups at 8 and 12 weeks.The incidence of side effects did not significantly differ between the valproate and vortioxetine groups.Importantly,three patients in the vortioxetine group appeared to switch to mania or hypomania.Conclusions:This study suggested that lurasidone combination with vortioxetine might have potential benefits to bipolar II depression in the early stage,while disease progression should be monitored closely for the risk of switching to mania.
基金supported by a Key Project of the Health Bureau of Zhejiang Province(WKJ-ZJ-2325)a Key Project of Zhejiang Provincial Natural Science Foundation(LZ23H160007)+5 种基金the National Natural Science Foundation of China(82373308)Basic Scientific Research Funds of Department of Education of Zhejiang Province(KYYB202212)Zhejiang Province Public Welfare Technology Application Research Project of China(LGF22H160080)Research Project of Zhejiang Provincial People’s Hospital(ZRY2020A005)Basic Scientific Research Funds of the Department of Education of Zhejiang Province(KYQN202128)General Research Projects of Zhejiang Provincial Department of Education(Y202249311).
文摘Chemotherapy-induced peripheral neurotoxicity(CIPN)is a severe dose-limiting adverse event of chemotherapy.Presently,the mechanism underlying the induction of CIPN remains unclear,and no effective treatment is available.In this study,through metabolomics analyses,we found that nab-paclitaxel therapy markedly increased serum serotonin[5-hydroxtryptamine(5-HT)]levels in both cancer patients and mice compared to the respective controls.Furthermore,nab-paclitaxel-treated enterochromaffin(EC)cells showed increased 5-HT synthesis,and serotonin-treated Schwann cells showed damage,as indicated by the activation of CREB3L3/MMP3/FAS signaling.Venlafaxine,an inhibitor of serotonin and norepinephrine reuptake,was found to protect against nerve injury by suppressing the activation of CREB3L3/MMP3/FAS signaling in Schwann cells.Remarkably,venlafaxine was found to significantly alleviate nab-paclitaxel-induced CIPN in patients without affecting the clinical efficacy of chemotherapy.In summary,our study reveals that EC cell-derived 5-HT plays a critical role in nab-paclitaxel-related neurotoxic lesions,and venlafaxine co-administration represents a novel approach to treating chronic cumulative neurotoxicity commonly reported in nab-paclitaxel-based chemotherapy.
基金supported by the Zhejiang Provincial Key Research and Development Program (2021C03107)。
文摘Military psychiatry, a new subcategory of psychiatry, has become an invaluable, intangible effect of the war. In this review, we begin by examining related military research, summarizing the related epidemiological data, neuropathology, and the research achievements of diagnosis and treatment technology, and discussing its comorbidity and sequelae. To date, advances in neuroimaging and molecular biology have greatly boosted the studies on military traumatic brain injury(TBI). In particular, in terms of pathophysiological mechanisms, several preclinical studies have identified abnormal protein accumulation, blood–brain barrier damage, and brain metabolism abnormalities involved in the development of TBI. As an important concept in the field of psychiatry, TBI is based on organic injury, which is largely different from many other mental disorders. Therefore, military TBI is both neuropathic and psychopathic, and is an emerging challenge at the intersection of neurology and psychiatry.
基金the National Key Research and Development Program of China(2021ZD0202700 and 2021ZD0202703)the National Natural Science Foundation of China(32070974).
文摘Neurons are highly interwoven to form intricate neural circuits that underlie the diverse functions of the brain.Dissecting the anatomical organization of neural circuits is key to deciphering how the brain processes information,produces thoughts,and instructs behaviors.Over the past decades,recombinant viral vectors have become the most commonly used tracing tools to define circuit architecture.In this review,we introduce the current categories of viral tools and their proper application in circuit tracing.We further discuss some advances in viral tracing strategy and prospective innovations of viral tools for future study.
基金supported by the Science and Technology Development Fund,Macao SAR (Nos.0015-2022-A1 and 005/2023/SKL)University of Macao (No.MYRG-GRG2023-00160-ICMS-UMDF)the Internal Research Grant of the State Key Laboratory of Quality Research in Chinese Medicine,University of Macao (No.SKL-QRCM-IRG2023-011).
文摘Cancer presents a significant global challenge,impacting individuals,communities,and healthcare systems worldwide[1,2].Fundamentally,cancer involves the uncontrolled growth and proliferation of cells,driven by genetic and epigenetic alterations orchestrated by a complex array of molecular entities,including oncogenes,tumor suppressor genes,and various regulatory factors[3-5].This intricate interplay complicates early detection,often resulting in a significant mortality burden.Accounting for nearly 30%of premature deaths globally,cancer is a major barrier to increasing human life expectancy[6,7].The urgent need for continued research,innovation,and collaborative efforts highlights the importance of combating this relentless disease.
基金supported by the Science and Technology Innovation 2030-Major Project of Brain Science and Brain-like Research(2021ZD0202700,2021ZD0202702)the Key-Area Research and Development Program of Guangdong Province(2019B030335001,2018B030334001)+6 种基金the Major Program of the National Natural Science Foundation of China(82090030,82090031)the CAMS Innovation Fund for Medical Sciences(2019-12M-5-057)the Ministry of Science and Technology(2019YFA0110103)the National Natural Science Foundation of China(81870898)the Fundamental Research Funds for the Central Universities(2021FZZX001-37)the Zhejiang Provincial Natural Science Foundation(LR18H090002)the Young Scientist Program of the National Natural Science Foundation of China(82001135).
文摘Defensive behaviors induced by innate fear or Pavlovian fear conditioning are crucial for animals to avoid threats and ensure survival.The zona incerta(ZI)has been demonstrated to play important roles in fear learning and fear memory,as well as modulating auditory-induced innate defensive behavior.However,whether the neuronal subtypes in the ZI and specific circuits can mediate the innate fear response is largely unknown.Here,we found that somatostatin(SST)-positive neurons in the rostral ZI of mice were activated by a visual innate fear stimulus.Optogenetic inhibition of SST-positive neurons in the rostral ZI resulted in reduced flight responses to an overhead looming stimulus.Optogenetic activation of SST-positive neurons in the rostral ZI induced fear-like defensive behavior including increased immobility and bradycardia.In addition,we demonstrated that manipulation of the GABAergic projections from SST-positive neurons in the rostral ZI to the downstream nucleus reuniens(Re)mediated fear-like defensive behavior.Retrograde trans-synaptic tracing also revealed looming stimulus-activated neurons in the superior colliculus(SC)that projected to the Re-projecting SST-positive neurons in the rostral ZI(SC-ZIrSST-Re pathway).Together,our study elucidates the function of SST-positive neurons in the rostral ZI and the SC-ZIrSST-Re tri-synaptic circuit in mediating the innate fear response.
