The oral cavity is a complex physiological community encompassing a wide range of microorganisms.Dysbiosis of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even...The oral cavity is a complex physiological community encompassing a wide range of microorganisms.Dysbiosis of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative diseases.Recent studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention strategies.In this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and neurodegeneration.We also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.展开更多
Schizophrenia is characterized by psychotic symptoms,negative symptoms,and cognitive deficits,profoundly affecting individuals and their families.The etiology is multifactorial,involving genetic,endocrine,and immunolo...Schizophrenia is characterized by psychotic symptoms,negative symptoms,and cognitive deficits,profoundly affecting individuals and their families.The etiology is multifactorial,involving genetic,endocrine,and immunological risk factors.It is thought that schizophrenia is exclusively linked to alterations in brain structure and function,while the relationship between the brain and many organs may lack sufficient attention.Increasing evidence indicates abnormalities of the interactions between the brain and many organs in patients with schizophrenia.Inter-organ crosstalk affects the onset,course,and management of schizophrenia.Besides,the complex relationship between autonomic nervous system,endocrine system,and immune system further facilitates the development of schizophrenia.The present review summarizes the relationships between the brain and multiple organ systems in schizophrenia,providing new perspectives on the underlying pathophysiological mechanisms of schizophrenia.展开更多
BACKGROUND Cognitive reserve(CR)and the catechol-O-methyltransferase(COMT)Val/Met polymorphism are reportedly linked to negative symptoms in schizophrenia.However,the regulatory effect of the COMT genotype on the rela...BACKGROUND Cognitive reserve(CR)and the catechol-O-methyltransferase(COMT)Val/Met polymorphism are reportedly linked to negative symptoms in schizophrenia.However,the regulatory effect of the COMT genotype on the relationship between CR and negative symptoms is still unexamined.AIM To investigate whether the relationship between CR and negative symptoms could be regulated by the COMT Val/Met polymorphism.METHODS In a cross-sectional study,54 clinically stable patients with schizophrenia underwent assessments for the COMT genotype,CR,and negative symptoms.CR was estimated using scores in the information and similarities subtests of a short form of the Chinese version of the Wechsler Adult Intelligence Scale.RESULTS COMT Met-carriers exhibited fewer negative symptoms than Val homozygotes.In the total sample,significant negative correlations were found between negative symptoms and information,similarities.Associations between information,similarities and negative symptoms were observed in Val homozygotes only,with information and similarities showing interaction effects with the COMT genotype in relation to negative symptoms(information,β=-0.282,95%CI:-0.552 to-0.011,P=0.042;similarities,β=-0.250,95%CI:-0.495 to-0.004,P=0.046).CONCLUSION This study provides initial evidence that the association between negative symptoms and CR is under the regulation of the COMT genotype in schizophrenia.展开更多
BACKGROUND Blonanserin(BNS)is a well-tolerated and effective drug for treating schizophrenia.AIM To investigate which types of patients would obtain the most benefit from BNS treatment.METHODS A total of 3306 particip...BACKGROUND Blonanserin(BNS)is a well-tolerated and effective drug for treating schizophrenia.AIM To investigate which types of patients would obtain the most benefit from BNS treatment.METHODS A total of 3306 participants were evaluated in a 12-week,prospective,multicenter,open-label post-marketing surveillance study of BNS.Brief psychiatric rating scale(BPRS)scores were calculated to evaluate the effectiveness of BNS,and its safety was assessed with the incidence of adverse drug reactions.Linear regression was used to screen the influencing factors for the reduction of BPRS total score,and logistic regression was used to identify patients with a better response to BNS.RESULTS The baseline BPRS total score(48.8±15.03)decreased to 27.7±10.08 at 12 weeks(P<0.001).Extrapyramidal symptoms(14.6%)were found to be the most frequent adverse drug reactions.The acute phase,baseline BPRS total score,current episode duration,number of previous episodes,dose of concomitant antipsychotics,and number of types of sedative-hypnotic agents were found to be independent factors affecting the reduction of BPRS total score after treatment initiation.Specifically,patients in the acute phase with baseline BPRS total score≥45,current episode duration<3 months,and≤3 previous episodes derived greater benefit from 12-week treatment with BNS.CONCLUSION Patients in the acute phase with more severe symptoms,shorter current episode duration,fewer previous episodes,and a lower psychotropic drug load derived the greatest benefit from treatment with BNS.展开更多
Background:Q uantifying the rich home-c age activities of tree shrews provides a reliable basis for understanding their daily routines and building disease models.However,due to the lack of effective behavioral method...Background:Q uantifying the rich home-c age activities of tree shrews provides a reliable basis for understanding their daily routines and building disease models.However,due to the lack of effective behavioral methods,most efforts on tree shrew behavior are limited to simple measures,resulting in the loss of much behavioral information.Methods:T o address this issue,we present a deep learning(DL)approach to achieve markerless pose estimation and recognize multiple spontaneous behaviors of tree shrews,including drinking,eating,resting,and staying in the dark house,etc.Results:T his high-t hroughput approach can monitor the home-cage activities of 16 tree shrews simultaneously over an extended period.Additionally,we demonstrated an innovative system with reliable apparatus,paradigms,and analysis methods for investigating food grasping behavior.The median duration for each bout of grasping was 0.20 s.Conclusion:T his study provides an efficient tool for quantifying and understand tree shrews'natural behaviors.展开更多
Solute carriers(SLCs)are the largest family of transmembrane transporters that determine the exchange of various substances,including nutrients,ions,metabolites,and drugs across biological membranes.To date,the presen...Solute carriers(SLCs)are the largest family of transmembrane transporters that determine the exchange of various substances,including nutrients,ions,metabolites,and drugs across biological membranes.To date,the presence of about 287 SLC genes have been identified in the brain,among which mutations or the resultant dysfunctions of 71 SLC genes have been reported to be correlated with human brain disorders.Although increasing interest in SLCs have focused on drug development,SLCs are currently still under-explored as drug targets,especially in the brain.We summarize the main substrates and functions of SLCs that are expressed in the brain,with an emphasis on selected SLCs that are important physiologically,pathologically,and pharmacologically in the blood-brain barrier,astrocytes,and neurons.Evidence suggests that a fraction of SLCs are regulated along with the occurrences of brain disorders,among which epilepsy,neurodegenerative diseases,and autism are representative.Given the review of SLCs involved in the onset and procession of brain disorders,we hope these SLCs will be screened as promising drug targets to improve drug delivery to the brain.展开更多
3-Hydroxy-3-methylglutaryl-CoA synthase(HMGS) is the first committed enzyme in the MVA pathway and involved in the biosynthesis of terpenes in Tripterygium wilfordii. The full-length cDNA and a 515 bp RNAi target frag...3-Hydroxy-3-methylglutaryl-CoA synthase(HMGS) is the first committed enzyme in the MVA pathway and involved in the biosynthesis of terpenes in Tripterygium wilfordii. The full-length cDNA and a 515 bp RNAi target fragment of TwHMGS were ligated into the p H7 WG2 D and p K7 GWIWG2 D vectors to respectively overexpress and silence, Tw HMGS was overexpressed and silenced in T. wilfordii suspension cells using biolistic-gun mediated transformation, which resulted in 2-fold increase and a drop to70% in the expression level compared to cells with empty vector controls. During Tw HMGS overexpression, the expression of TwHMGR, TwDXR and TwTPS7 v2 was significantly upregulated to the control. In the RNAi group, the expression of Tw HMGR,TwDXS, TwDXR and TwMCT visibly displayed downregulation to the control. The cells with TwHMGS overexpressed produced twice higher than the control value. These results proved that differential expression of Tw HMGS determined the production of triptolide in T.wilfordii and laterally caused different trends of relative gene expression in the terpene biosynthetic pathway. Finally, the substrate acetyl-Co A was docked into the active site of TwHMGS, suggesting the key residues including His247, Lys256 and Arg296 undergo electrostatic or H-bond interactions with acetyl-CoA.展开更多
Behavioral analysis of macaques provides important experimental evidence in the field of neuroscience.In recent years,video-based automatic animal behavior analysis has received widespread attention.However,methods ca...Behavioral analysis of macaques provides important experimental evidence in the field of neuroscience.In recent years,video-based automatic animal behavior analysis has received widespread attention.However,methods capable of extracting and analyzing daily movement trajectories of macaques in their daily living cages remain underdeveloped,with previous approaches usually requiring specific environments to reduce interference from occlusion or environmental change.Here,we introduce a novel method,called MonkeyTrail,which satisfies the above requirements by frequently generating virtual empty backgrounds and using background subtraction to accurately obtain the foreground of moving animals.The empty background is generated by combining the frame difference method(FDM)and deep learning-based model(YOLOv5).The entire setup can be operated with low-cost hardware and can be applied to the daily living environments of individually caged macaques.To test MonkeyTrail performance,we labeled a dataset containing>8000 video frames with the bounding boxes of macaques under various conditions as ground-truth.Results showed that the tracking accuracy and stability of MonkeyTrail exceeded that of two deep learningbased methods(YOLOv5 and Single-Shot MultiBox Detector),traditional frame difference method,and na?ve background subtraction method.Using MonkeyTrail to analyze long-term surveillance video recordings,we successfully assessed changes in animal behavior in terms of movement amount and spatial preference.Thus,these findings demonstrate that MonkeyTrail enables low-cost,large-scale daily behavioral analysis of macaques.展开更多
Bipolar disorder(BD) is a chronic and recurrent disorder characterized by biphasic mood episodes of mania or hypomania and depression.It affects more than 1% of the global population and is a leading cause of disabili...Bipolar disorder(BD) is a chronic and recurrent disorder characterized by biphasic mood episodes of mania or hypomania and depression.It affects more than 1% of the global population and is a leading cause of disability in young people.Currently available treatments for BD are still fairly limited in terms of efficacy,with high rates of non-adherence,non-response,and undesirable side effects.Traditional Chinese medicine(TCM) has a long history and rich experience in stabilizing mania and improving quality of life.Aiming at rebalancing Yin and Yang in BD,therapy of replenishing Yin and regulating Yang(RYRY therapy) has been in clinical use for years in China.The present prospective,double-blind,randomized controlled trial is designed to investigate the efficacy and safety of RYRY therapy for bipolar mania and its possible mechanism from the point of regulating gut microbiota and anti-inflammation.A total of 60 eligible participants will be recruited from Beijing Anding Hospital.They will be randomized to either the study group or the control group in a ratio of 1∶1.Participants allocated to the study group will receive RYRY granule,while placebo granule will be applied in the control group.Participants in both groups will be prescribed conventional therapy for manic episode in BD.Four scheduled visits will be conducted over 4 weeks.Outcome measurements include Young Mania Rating Scale,TCM Symptom Pattern Rating Scale,Treatment Emergent Symptom Scale,levels of C-reactive protein,interleukin-6 and tumor necrosis factor-α and the gut microbial community profile of stool samples.Safety outcomes and adverse events will also be recorded.In this study,we set a number of scientific and objective assessments to evaluate the efficacy of RYRY therapy and study into its possible mechanism,hopefully offering clinicians an alternative approach to BD.展开更多
Autism spectrum disorders are a group of neurodevelopmental disorders involving more than 1100 genes,including Ctnnd2 as a candidate gene.Ctnnd2knockout mice,serving as an animal model of autis m,have been demonstrate...Autism spectrum disorders are a group of neurodevelopmental disorders involving more than 1100 genes,including Ctnnd2 as a candidate gene.Ctnnd2knockout mice,serving as an animal model of autis m,have been demonstrated to exhibit decreased density of dendritic spines.The role of melatonin,as a neuro hormone capable of effectively alleviating social interaction deficits and regulating the development of dendritic spines,in Ctnnd2 deletion-induced nerve injury remains unclea r.In the present study,we discove red that the deletion of exon 2 of the Ctnnd2 gene was linked to social interaction deficits,spine loss,impaired inhibitory neurons,and suppressed phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt) signal pathway in the prefrontal cortex.Our findings demonstrated that the long-term oral administration of melatonin for 28 days effectively alleviated the aforementioned abnormalities in Ctnnd2 gene-knockout mice.Furthermore,the administration of melatonin in the prefro ntal cortex was found to improve synaptic function and activate the PI3K/Akt signal pathway in this region.The pharmacological blockade of the PI3K/Akt signal pathway with a PI3K/Akt inhibitor,wo rtmannin,and melatonin receptor antagonists,luzindole and 4-phenyl-2-propionamidotetralin,prevented the melatonin-induced enhancement of GABAergic synaptic function.These findings suggest that melatonin treatment can ameliorate GABAe rgic synaptic function by activating the PI3K/Akt signal pathway,which may contribute to the improvement of dendritic spine abnormalities in autism spectrum disorders.展开更多
The hippocampus is essential for learning and memory,but it also plays an important role in regulating emotional behavior,as hippocampal excitability and plasticity affect anxiety and fear.Brain synaptic plasticity ma...The hippocampus is essential for learning and memory,but it also plays an important role in regulating emotional behavior,as hippocampal excitability and plasticity affect anxiety and fear.Brain synaptic plasticity may be regulated by tissue inhibitor of matrix metalloproteinase 1(TIMP1),a known protein inhibitor of extracellular matrix(ECM),and the expression of TIMP1 in the hippocampus can be induced by neuronal excitation and various stimuli.However,the involvement of Timp1 in fear learning,anxiety,and hippocampal synaptic function remains to be established.Our study of Timp1 function in vivo revealed that Timp1 knockout mice exhibit anxiety-like behavior but normal fear learning.Electrophysiological results suggested that Timp1 knockout mice showed hyperactivity in the ventral CA1 region,but the basic synaptic transmission and plasticity were normal in the Schaffer collateral pathway.Taken together,our results suggest that deletion of Timp1 in vivo leads to the occurrence of anxiety behaviors,but that Timp1 is not crucial for fear learning.展开更多
Background This study aimed to investigate the relationship between overall obesity,central obesity and brain volumes,as well as to determine the extent to which cardiometabolic and inflammatory measures act as mediat...Background This study aimed to investigate the relationship between overall obesity,central obesity and brain volumes,as well as to determine the extent to which cardiometabolic and inflammatory measures act as mediators in the association between body mass index(BMI),waist-hip ratio(WHR)and brain volumes.Methods In the context of counterfactual framework,mediation analysis was used to explore the potential mediation in which cardiometabolic and inflammatory measures may mediate the relationship between BMI,WHR,and brain volumes.Results Among 2413 community-dwelling participants,those with high BMI or WHR levels experienced an approximately brain ageing of 4 years.Especially,individuals with high WHR or BMI under the age of 65 exhibited white matter hyperintensity volume(WMHV)differences equivalent to around 5 years of ageing.Conversely,in the high-level WHR population over the age of 65,premature brain ageing in gray matter volume(GMV)exceeded 4.5 years.For GMV,more than 45%of the observed effect of WHR was mediated by glycaemic metabolism indicators.This proportion increases to 78.70%when blood pressure,triglyceride,leucocyte count,and neutrophil count are jointly considered with glycaemic metabolism indicators.Regarding WHR and BMI’s association with WMHV,cardiometabolic and inflammatory indicators,along with high-density lipoprotein cholesterol,mediated 35.50%and 20.20%of the respective effects.Conclusions Overall obesity and central obesity were associated with lower GMV and higher WMHV,a process that is partially mediated by the presence of cardiometabolic and inflammatory measures.展开更多
Dear Editor,Ischemic stroke,a well-known age-related disorder(Cai et al.,2022b),resulting from the occlusion of cerebral blood vessels and the ensuing neuronal damage,has emerged as a leading cause of mortality and di...Dear Editor,Ischemic stroke,a well-known age-related disorder(Cai et al.,2022b),resulting from the occlusion of cerebral blood vessels and the ensuing neuronal damage,has emerged as a leading cause of mortality and disability worldwide(Zhang and Chopp,2009).It represents a significant global health challenge.The pursuit of innovative treatment strategies for ischemic stroke has become an urgent scientific priority.Stem cell therapy has gained prominence as a promising therapeutic modality for attenuating ischemic brain injury and facilitating repair in affected regions(Zhu et al.,2023).Among these,mesenchymal stem cells(MSCs)have garnered particular attention for their potential in ischemic stroke therapy,attributed to their capacity to secrete therapeutic biomolecules that provide neuroprotection,stimulate angiogenesis,and modulate immune responses(Stonesifer et al.,2017).Despite their promise,a multitude of challenges impede the realization of MSCs'therapeutic potential.展开更多
The innate immune signaling network follows a canonical format for signal transmission.The innate immune pathway is crucial for defense against pathogens,yet its mechanistic crosstalk with aging processes remains larg...The innate immune signaling network follows a canonical format for signal transmission.The innate immune pathway is crucial for defense against pathogens,yet its mechanistic crosstalk with aging processes remains largely unexplored.Retinoic acid-inducible gene-Ⅰ(RIG-Ⅰ),a key mediator of antiviral immunity within this pathway,has an enigmatic role in stem cell senescence.Our study reveals that RIG-Ⅰlevels increase in human genetic and physiological cellular aging models,and its accumulation drives cellular senescence.Conversely,CRISPR/Cas9-mediated RIG-Ⅰdeletion or pharmacological inhibition in human mesenchymal stem cells(h MSCs)confers resistance to senescence.Mechanistically,RIG-Ⅰbinds to endogenous m RNAs,with CDKN1A m RNA being a prominent target.Specifically,RIG-Ⅰstabilizes CDKN1A m RNA,resulting in elevated CDKN1A transcript levels and increased p21 Cip1 protein expression,which precipitates senescence.Collectively,our findings establish RIG-Ⅰas a post-transcriptional regulator of senescence and suggest potential targets for the mitigation of aging-related diseases.展开更多
Dear Editor,Cellular senescence is characterized by growth arrest and the onset of a senescence-associated secretory phenotype (SASP)(Consortium et al., 2023;Liu et al., 2023;Zhang et al., 2023). Consequently, senesce...Dear Editor,Cellular senescence is characterized by growth arrest and the onset of a senescence-associated secretory phenotype (SASP)(Consortium et al., 2023;Liu et al., 2023;Zhang et al., 2023). Consequently, senescent cells that accumulate within aged organs have the capacity to disseminate pro-senescence and pro-inflammatory signals, promoting structural tissue deterioration and functional decline, culminating in organismal aging (Cai et al., 2022;Consortium et al., 2024).展开更多
Environmental pollution is an important but often overlooked risk factor for cardiovascular diseases such as heart failure.Triclocarban(3,4,4′-trichlorocarbanilide,TCC)is a broad-spectrum antibacterial agent commonly...Environmental pollution is an important but often overlooked risk factor for cardiovascular diseases such as heart failure.Triclocarban(3,4,4′-trichlorocarbanilide,TCC)is a broad-spectrum antibacterial agent commonly used in personal care products such as antibacterial soaps,detergents,toothpaste,and cosmetics[1].Unfortunately,due to its widespread use,TCC has become one of the top ten most common water pollutants globally,and it is present in the atmosphere,soil,and aquatic sediments[2].展开更多
Hepatocellular carcinoma(HCC)is the fourth leading cause of cancer-associated death worldwide.Angiogenesis,the process of formation of new blood vessels,is required for cancer cells to obtain nutrients and oxygen.HCC ...Hepatocellular carcinoma(HCC)is the fourth leading cause of cancer-associated death worldwide.Angiogenesis,the process of formation of new blood vessels,is required for cancer cells to obtain nutrients and oxygen.HCC is a typical hypervascular solid tumor with an aberrant vascular network and angiogenesis that contribute to its growth,progression,invasion,and metastasis.Current anti-angiogenic therapies target mainly tyrosine kinases,vascular endothelial growth factor receptor(VEGFR),and plateletderived growth factor receptor(PDGFR),and are considered effective strategies for HCC,particularly advanced HCC.However,because the survival benefits conferred by these anti-angiogenic therapies are modest,new anti-angiogenic targets must be identified.Several recent studies have determined the underlying molecular mechanisms,including pro-angiogenic factors secreted by HCC cells,the tumor microenvironment,and cancer stem cells.In this review,we summarize the roles of pro-angiogenic factors;the involvement of endothelial cells,hepatic stellate cells,tumor-associated macrophages,and tumor-associated neutrophils present in the tumor microenvironment;and the regulatory influence of cancer stem cells on angiogenesis in HCC.Furthermore,we discuss some of the clinically approved anti-angiogenic therapies and potential novel therapeutic targets for angiogenesis in HCC.A better understanding of the mechanisms underlying angiogenesis may lead to the development of more optimized anti-angiogenic treatment modalities for HCC.展开更多
BACKGROUND Recently,the efficacy of cognitive behavioral therapy(CBT)-based intervention on health outcomes in patients with coronary heart disease(CHD)has been recognized in randomized controlled trials(RCTs),but no ...BACKGROUND Recently,the efficacy of cognitive behavioral therapy(CBT)-based intervention on health outcomes in patients with coronary heart disease(CHD)has been recognized in randomized controlled trials(RCTs),but no comprehensive systematic review has been conducted.To address this research gap,our study aimed to evaluate whether comprehensive CBT-based interventions positively affect health outcomes in CHD patients.It was hypothesized that CBT-based interventions are effective in:(1)Reducing depression,anxiety,and stress symptoms;(2)Reducing body mass index,blood pressure,and lipid levels;and(3)Improving quality of life,and exercise endurance.AIM To verify the effectiveness of CBT-based interventions on CHD patients through a meta-analysis of previous publications.METHODS Relevant RCTs published in English were obtained by searching electronic databases,including PubMed,Embase,Cochrane Central Register of Controlled Trials,Scopus,and Proquest,with the retrieval time from inception to August 2020.The primary outcomes were psychological factors(depression,anxiety,and stress symptoms),physiological factors(body mass index,blood pressure,blood lipids).The secondary outcomes included quality of life and exercise endurance.We used Review Manager 5.3 to conduct the meta-analysis and used the Physiotherapy Evidence Database tool to evaluate the quality of studies.RESULTS A total of 22 RCTs comprising 4991 patients with CHD were included in the systematic review and meta-analysis.The main analysis revealed that CBT-based intervention can reduce depression symptoms:-2.00[95%confidence interval(CI):-2.83 to-1.16,P<0.001];anxiety symptoms:-2.07(95%CI:-3.39 to-0.75,P=0.002);stress symptoms:-3.33(95%CI:-4.23 to-2.44,P<0.001);body mass index:-0.47(95%CI:-0.81 to-0.13,P=0.006);and improve physical functioning:3.36(95%CI:1.63 to 5.10,P=0.000)and mental functioning:6.91(95%CI:4.10 to 9.73,P<0.001).Moreover,subgroup analysis results showed that CBT-based interventions were more effective for symptoms of depression and anxiety in CHD patients when individual,as opposed to group treatment,and psycho-education,behavioral and cognitive strategies were applied as the core treatment approaches.CONCLUSION CBT-based interventions are effective treatment strategies for CHD patients,significantly improving their symptoms of depression,anxiety and stress,body mass index,and health-related quality of life.展开更多
Objective To identify the representative attributes of the five elements of a person with a qualitative methodology and provide the basis for the clinical diagnosis and treatment of“people with the five elements in t...Objective To identify the representative attributes of the five elements of a person with a qualitative methodology and provide the basis for the clinical diagnosis and treatment of“people with the five elements in traditional Chinese medicine(TCM).”Methods Data collected from the literature review,two sessions of brainstorming of experts with related experience in“people with the five elements in TCM”from October 2020 to December 2020,and six rounds of in-depth interviews with 30 participants who had various attributes of the five elements from March 2021 to October 2021 were analyzed.Triangulation was used in this study,and theming and synthesizing were used to analyze the data.Results A total of 31 experts and 30 interviewees participated in this study.The median age of the experts and interviewees were 48.0 and 38.5 years,respectively;51.66%and 54.8%of experts and interviewees,respectively,were men.The descriptors of facial diagrams of“people with the five elements in TCM”were complexion,shape,distribution state of facial bones,convergence trend of facial muscles,and facial expression.A theoretical model of“people with the five elements in TCM”was shaped based on these findings.Conclusion The study suggests a possibility for bridging the gap between personality and bodily state,identifying an avenue for personality research from the perspective of TCM.展开更多
Source localization of focal electrical activity from scalp electroencephalogram (sEEG) signal is generally modeled as an inverse problem that is highly ill-posed. In this paper, a novel source localization method is ...Source localization of focal electrical activity from scalp electroencephalogram (sEEG) signal is generally modeled as an inverse problem that is highly ill-posed. In this paper, a novel source localization method is proposed to model the EEG inverse problem using spatio-temporal long-short term memory recurrent neural networks (LSTM). The network model consists of two parts, sEEG encoding and source decoding, to model the sEEG signal and receive the regression of source location. As there does not exist enough annotated sEEG signals correspond to specific source locations, simulated data is generated with forward model using finite element method (FEM) to act as a part of training signals. A framework for source localization is proposed to estimate the source position based on simulated training data. Experiments are done on simulated testing data. The results on simulated data exhibit good robustness on noise signal, and the proposed network solves the EEG inverse problem with spatio-temporal deep network. The result show that the proposed method overcomes the highly ill-posed linear inverse problem with data driven learning.展开更多
基金supported by the National Natural Science Foundation of China,No.81921006(to GHL)。
文摘The oral cavity is a complex physiological community encompassing a wide range of microorganisms.Dysbiosis of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative diseases.Recent studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention strategies.In this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and neurodegeneration.We also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.
基金Supported by Beijing Traditional Chinese Medicine Scientific and Technological Development Fund Project,No.BJZYYB-2023-66Beijing Natural Science Foundation,No.7212050the Capital’s Funds for Health Improvement and Research,No.2020-4-2126.
文摘Schizophrenia is characterized by psychotic symptoms,negative symptoms,and cognitive deficits,profoundly affecting individuals and their families.The etiology is multifactorial,involving genetic,endocrine,and immunological risk factors.It is thought that schizophrenia is exclusively linked to alterations in brain structure and function,while the relationship between the brain and many organs may lack sufficient attention.Increasing evidence indicates abnormalities of the interactions between the brain and many organs in patients with schizophrenia.Inter-organ crosstalk affects the onset,course,and management of schizophrenia.Besides,the complex relationship between autonomic nervous system,endocrine system,and immune system further facilitates the development of schizophrenia.The present review summarizes the relationships between the brain and multiple organ systems in schizophrenia,providing new perspectives on the underlying pathophysiological mechanisms of schizophrenia.
基金Supported by the National Natural Science Foundation of China,No.81971250 and No.82171501Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support,No.ZLRK202335Early Psychosis Cohort Program of Beijing Anding Hospital,No.ADDL-03.
文摘BACKGROUND Cognitive reserve(CR)and the catechol-O-methyltransferase(COMT)Val/Met polymorphism are reportedly linked to negative symptoms in schizophrenia.However,the regulatory effect of the COMT genotype on the relationship between CR and negative symptoms is still unexamined.AIM To investigate whether the relationship between CR and negative symptoms could be regulated by the COMT Val/Met polymorphism.METHODS In a cross-sectional study,54 clinically stable patients with schizophrenia underwent assessments for the COMT genotype,CR,and negative symptoms.CR was estimated using scores in the information and similarities subtests of a short form of the Chinese version of the Wechsler Adult Intelligence Scale.RESULTS COMT Met-carriers exhibited fewer negative symptoms than Val homozygotes.In the total sample,significant negative correlations were found between negative symptoms and information,similarities.Associations between information,similarities and negative symptoms were observed in Val homozygotes only,with information and similarities showing interaction effects with the COMT genotype in relation to negative symptoms(information,β=-0.282,95%CI:-0.552 to-0.011,P=0.042;similarities,β=-0.250,95%CI:-0.495 to-0.004,P=0.046).CONCLUSION This study provides initial evidence that the association between negative symptoms and CR is under the regulation of the COMT genotype in schizophrenia.
文摘BACKGROUND Blonanserin(BNS)is a well-tolerated and effective drug for treating schizophrenia.AIM To investigate which types of patients would obtain the most benefit from BNS treatment.METHODS A total of 3306 participants were evaluated in a 12-week,prospective,multicenter,open-label post-marketing surveillance study of BNS.Brief psychiatric rating scale(BPRS)scores were calculated to evaluate the effectiveness of BNS,and its safety was assessed with the incidence of adverse drug reactions.Linear regression was used to screen the influencing factors for the reduction of BPRS total score,and logistic regression was used to identify patients with a better response to BNS.RESULTS The baseline BPRS total score(48.8±15.03)decreased to 27.7±10.08 at 12 weeks(P<0.001).Extrapyramidal symptoms(14.6%)were found to be the most frequent adverse drug reactions.The acute phase,baseline BPRS total score,current episode duration,number of previous episodes,dose of concomitant antipsychotics,and number of types of sedative-hypnotic agents were found to be independent factors affecting the reduction of BPRS total score after treatment initiation.Specifically,patients in the acute phase with baseline BPRS total score≥45,current episode duration<3 months,and≤3 previous episodes derived greater benefit from 12-week treatment with BNS.CONCLUSION Patients in the acute phase with more severe symptoms,shorter current episode duration,fewer previous episodes,and a lower psychotropic drug load derived the greatest benefit from treatment with BNS.
基金supported by grants from the National Key Research and Development Program of China(2023YFF0724902)the China Postdoctoral Science Foundation(2020?M670027,2023TQ0183)the Local Standards Research of BeiJing Laboratory Tree Shrew(CHYX-2023-DGB001)。
文摘Background:Q uantifying the rich home-c age activities of tree shrews provides a reliable basis for understanding their daily routines and building disease models.However,due to the lack of effective behavioral methods,most efforts on tree shrew behavior are limited to simple measures,resulting in the loss of much behavioral information.Methods:T o address this issue,we present a deep learning(DL)approach to achieve markerless pose estimation and recognize multiple spontaneous behaviors of tree shrews,including drinking,eating,resting,and staying in the dark house,etc.Results:T his high-t hroughput approach can monitor the home-cage activities of 16 tree shrews simultaneously over an extended period.Additionally,we demonstrated an innovative system with reliable apparatus,paradigms,and analysis methods for investigating food grasping behavior.The median duration for each bout of grasping was 0.20 s.Conclusion:T his study provides an efficient tool for quantifying and understand tree shrews'natural behaviors.
基金This work was supported by Nation Science and Technology Major Projects for Major New Drugs Innovation and Development(2018ZX09711003-004-002 to L.C.)Ministry of Science and Technology of China National Key R&D Programs(2018YFA0506903 to L.C.)National Natural Science Foundation of China grants(91857108 to L.C.).
文摘Solute carriers(SLCs)are the largest family of transmembrane transporters that determine the exchange of various substances,including nutrients,ions,metabolites,and drugs across biological membranes.To date,the presence of about 287 SLC genes have been identified in the brain,among which mutations or the resultant dysfunctions of 71 SLC genes have been reported to be correlated with human brain disorders.Although increasing interest in SLCs have focused on drug development,SLCs are currently still under-explored as drug targets,especially in the brain.We summarize the main substrates and functions of SLCs that are expressed in the brain,with an emphasis on selected SLCs that are important physiologically,pathologically,and pharmacologically in the blood-brain barrier,astrocytes,and neurons.Evidence suggests that a fraction of SLCs are regulated along with the occurrences of brain disorders,among which epilepsy,neurodegenerative diseases,and autism are representative.Given the review of SLCs involved in the onset and procession of brain disorders,we hope these SLCs will be screened as promising drug targets to improve drug delivery to the brain.
基金supported by the National Natural Science Foundation of China(No.81773830)Beijing Natural Science Foundation Program+3 种基金Scientific Research Key Program of Beijing Municipal Commission of Education(No.KZ201710025022)the Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five–year Plan(No.CIT&TCD20170324)National Program for Special Support of Eminent ProfessionalsKey project at central government level:The ability establishment of sustainable use for valuable Chinese medicine resources(No.2060302)
文摘3-Hydroxy-3-methylglutaryl-CoA synthase(HMGS) is the first committed enzyme in the MVA pathway and involved in the biosynthesis of terpenes in Tripterygium wilfordii. The full-length cDNA and a 515 bp RNAi target fragment of TwHMGS were ligated into the p H7 WG2 D and p K7 GWIWG2 D vectors to respectively overexpress and silence, Tw HMGS was overexpressed and silenced in T. wilfordii suspension cells using biolistic-gun mediated transformation, which resulted in 2-fold increase and a drop to70% in the expression level compared to cells with empty vector controls. During Tw HMGS overexpression, the expression of TwHMGR, TwDXR and TwTPS7 v2 was significantly upregulated to the control. In the RNAi group, the expression of Tw HMGR,TwDXS, TwDXR and TwMCT visibly displayed downregulation to the control. The cells with TwHMGS overexpressed produced twice higher than the control value. These results proved that differential expression of Tw HMGS determined the production of triptolide in T.wilfordii and laterally caused different trends of relative gene expression in the terpene biosynthetic pathway. Finally, the substrate acetyl-Co A was docked into the active site of TwHMGS, suggesting the key residues including His247, Lys256 and Arg296 undergo electrostatic or H-bond interactions with acetyl-CoA.
基金supported by the National Key Research and Development Program of China(2017YFA0105203,2017YFA0105201)National Science Foundation of China(31771076,81925011)+2 种基金Strategic Priority Research Program of the Chinese Academy of Sciences(CAS)(XDB32040201)Beijing Academy of Artificial IntelligenceKey-Area Research and Development Program of Guangdong Province(2019B030335001)。
文摘Behavioral analysis of macaques provides important experimental evidence in the field of neuroscience.In recent years,video-based automatic animal behavior analysis has received widespread attention.However,methods capable of extracting and analyzing daily movement trajectories of macaques in their daily living cages remain underdeveloped,with previous approaches usually requiring specific environments to reduce interference from occlusion or environmental change.Here,we introduce a novel method,called MonkeyTrail,which satisfies the above requirements by frequently generating virtual empty backgrounds and using background subtraction to accurately obtain the foreground of moving animals.The empty background is generated by combining the frame difference method(FDM)and deep learning-based model(YOLOv5).The entire setup can be operated with low-cost hardware and can be applied to the daily living environments of individually caged macaques.To test MonkeyTrail performance,we labeled a dataset containing>8000 video frames with the bounding boxes of macaques under various conditions as ground-truth.Results showed that the tracking accuracy and stability of MonkeyTrail exceeded that of two deep learningbased methods(YOLOv5 and Single-Shot MultiBox Detector),traditional frame difference method,and na?ve background subtraction method.Using MonkeyTrail to analyze long-term surveillance video recordings,we successfully assessed changes in animal behavior in terms of movement amount and spatial preference.Thus,these findings demonstrate that MonkeyTrail enables low-cost,large-scale daily behavioral analysis of macaques.
基金Supported by Beijing Municipal Administration of Hospitals Incubating Program(No.PZ2021031),which plays no role in the design of the studycollection,analysis,and interpretation of data,and in writing the manuscript。
文摘Bipolar disorder(BD) is a chronic and recurrent disorder characterized by biphasic mood episodes of mania or hypomania and depression.It affects more than 1% of the global population and is a leading cause of disability in young people.Currently available treatments for BD are still fairly limited in terms of efficacy,with high rates of non-adherence,non-response,and undesirable side effects.Traditional Chinese medicine(TCM) has a long history and rich experience in stabilizing mania and improving quality of life.Aiming at rebalancing Yin and Yang in BD,therapy of replenishing Yin and regulating Yang(RYRY therapy) has been in clinical use for years in China.The present prospective,double-blind,randomized controlled trial is designed to investigate the efficacy and safety of RYRY therapy for bipolar mania and its possible mechanism from the point of regulating gut microbiota and anti-inflammation.A total of 60 eligible participants will be recruited from Beijing Anding Hospital.They will be randomized to either the study group or the control group in a ratio of 1∶1.Participants allocated to the study group will receive RYRY granule,while placebo granule will be applied in the control group.Participants in both groups will be prescribed conventional therapy for manic episode in BD.Four scheduled visits will be conducted over 4 weeks.Outcome measurements include Young Mania Rating Scale,TCM Symptom Pattern Rating Scale,Treatment Emergent Symptom Scale,levels of C-reactive protein,interleukin-6 and tumor necrosis factor-α and the gut microbial community profile of stool samples.Safety outcomes and adverse events will also be recorded.In this study,we set a number of scientific and objective assessments to evaluate the efficacy of RYRY therapy and study into its possible mechanism,hopefully offering clinicians an alternative approach to BD.
基金supported by the Chongqing Science and Technology CommitteeNatural Science Foundation of Chongqing,No.cstc2021jcyj-msxmX0065 (to YL)。
文摘Autism spectrum disorders are a group of neurodevelopmental disorders involving more than 1100 genes,including Ctnnd2 as a candidate gene.Ctnnd2knockout mice,serving as an animal model of autis m,have been demonstrated to exhibit decreased density of dendritic spines.The role of melatonin,as a neuro hormone capable of effectively alleviating social interaction deficits and regulating the development of dendritic spines,in Ctnnd2 deletion-induced nerve injury remains unclea r.In the present study,we discove red that the deletion of exon 2 of the Ctnnd2 gene was linked to social interaction deficits,spine loss,impaired inhibitory neurons,and suppressed phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt) signal pathway in the prefrontal cortex.Our findings demonstrated that the long-term oral administration of melatonin for 28 days effectively alleviated the aforementioned abnormalities in Ctnnd2 gene-knockout mice.Furthermore,the administration of melatonin in the prefro ntal cortex was found to improve synaptic function and activate the PI3K/Akt signal pathway in this region.The pharmacological blockade of the PI3K/Akt signal pathway with a PI3K/Akt inhibitor,wo rtmannin,and melatonin receptor antagonists,luzindole and 4-phenyl-2-propionamidotetralin,prevented the melatonin-induced enhancement of GABAergic synaptic function.These findings suggest that melatonin treatment can ameliorate GABAe rgic synaptic function by activating the PI3K/Akt signal pathway,which may contribute to the improvement of dendritic spine abnormalities in autism spectrum disorders.
基金supported by grants from the Key-Area Research and Development Program of Guangdong Province(2019B030335001)the National Natural Science Foundation of China(81925011,92149304,and 32200636)+2 种基金the R&D Program of Beijing Municipal Education Commission(KM202310025028)the High-Level Teachers project(CIT&TCD20190334)the Youth Beijing Scholars Program(015).
文摘The hippocampus is essential for learning and memory,but it also plays an important role in regulating emotional behavior,as hippocampal excitability and plasticity affect anxiety and fear.Brain synaptic plasticity may be regulated by tissue inhibitor of matrix metalloproteinase 1(TIMP1),a known protein inhibitor of extracellular matrix(ECM),and the expression of TIMP1 in the hippocampus can be induced by neuronal excitation and various stimuli.However,the involvement of Timp1 in fear learning,anxiety,and hippocampal synaptic function remains to be established.Our study of Timp1 function in vivo revealed that Timp1 knockout mice exhibit anxiety-like behavior but normal fear learning.Electrophysiological results suggested that Timp1 knockout mice showed hyperactivity in the ventral CA1 region,but the basic synaptic transmission and plasticity were normal in the Schaffer collateral pathway.Taken together,our results suggest that deletion of Timp1 in vivo leads to the occurrence of anxiety behaviors,but that Timp1 is not crucial for fear learning.
基金supported by National Key R&D Programme of China(No.2022YFC3602500,2022YFC3602505)National Natural Science Foundation of China(81971091)+3 种基金Outstanding Young Talents Project of Capital Medical University(A2105)Capital’s Funds for Health Improvement and Research(2020-1-2041)Key Science&Technologies R&D Programme of Lishui City(2019ZDYF18)Zhejiang Provincial Programme for the Cultivation of High-level Innovative Health talents and AstraZeneca Investment(China)Co.,Ltd.
文摘Background This study aimed to investigate the relationship between overall obesity,central obesity and brain volumes,as well as to determine the extent to which cardiometabolic and inflammatory measures act as mediators in the association between body mass index(BMI),waist-hip ratio(WHR)and brain volumes.Methods In the context of counterfactual framework,mediation analysis was used to explore the potential mediation in which cardiometabolic and inflammatory measures may mediate the relationship between BMI,WHR,and brain volumes.Results Among 2413 community-dwelling participants,those with high BMI or WHR levels experienced an approximately brain ageing of 4 years.Especially,individuals with high WHR or BMI under the age of 65 exhibited white matter hyperintensity volume(WMHV)differences equivalent to around 5 years of ageing.Conversely,in the high-level WHR population over the age of 65,premature brain ageing in gray matter volume(GMV)exceeded 4.5 years.For GMV,more than 45%of the observed effect of WHR was mediated by glycaemic metabolism indicators.This proportion increases to 78.70%when blood pressure,triglyceride,leucocyte count,and neutrophil count are jointly considered with glycaemic metabolism indicators.Regarding WHR and BMI’s association with WMHV,cardiometabolic and inflammatory indicators,along with high-density lipoprotein cholesterol,mediated 35.50%and 20.20%of the respective effects.Conclusions Overall obesity and central obesity were associated with lower GMV and higher WMHV,a process that is partially mediated by the presence of cardiometabolic and inflammatory measures.
基金supported by the National Key R&D Program of China STI2030-Major Projects-2021ZD0202400the National Natural Science Foundation of China (Grant Nos. 82125011, 81921006, 92149301, 92168201, 82122024)+11 种基金the National Key Research and Development Program of China (2020YFA0804000, 2022YFA1103700, 2020YFA0112200, 2022YFA1103802, 2021YFF1201000, 2023YFC3605400)the National Natural Science Foundation of China (82330044, 32341001, 92049304, 92049116, 32121001, 82192863, 82361148131, 82071588, 82361148130, 8231101626, 82201727, 82488301)CAS Project for Young Scientists in Basic Research (YSBR-076, YSBR-012)the Program of the Beijing Natural Science Foundation (Z230011, Z240018, JQ24044)the Informatization Plan of Chinese Academy of Sciences (CAS-WX2022SDC-XK14)New Cornerstone Science Foundation through the XPLORER PRIZE (2021-1045)Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes (JYY2023-13)CAS Youth Interdisciplinary Team,Key Laboratory of Alzheimer’s Disease of Zhejiang Province (ZJAD-2024001)Excellent Young Talents Program of Capital Medical University (12300927)the Project for Technology Development of Beijing-affiliated Medical Research Institutes (11000023T000002036310)Excellent Young Talents Training Program for the Construction of Beijing Municipal University Teacher Team (BPHR202203105)Beijing Hospitals Authority Youth Programme (QML20230806)
文摘Dear Editor,Ischemic stroke,a well-known age-related disorder(Cai et al.,2022b),resulting from the occlusion of cerebral blood vessels and the ensuing neuronal damage,has emerged as a leading cause of mortality and disability worldwide(Zhang and Chopp,2009).It represents a significant global health challenge.The pursuit of innovative treatment strategies for ischemic stroke has become an urgent scientific priority.Stem cell therapy has gained prominence as a promising therapeutic modality for attenuating ischemic brain injury and facilitating repair in affected regions(Zhu et al.,2023).Among these,mesenchymal stem cells(MSCs)have garnered particular attention for their potential in ischemic stroke therapy,attributed to their capacity to secrete therapeutic biomolecules that provide neuroprotection,stimulate angiogenesis,and modulate immune responses(Stonesifer et al.,2017).Despite their promise,a multitude of challenges impede the realization of MSCs'therapeutic potential.
基金supported by the National Natural Science Foundation of China(82192863,82361148131,82125011,81921006,92149301,92168201,82122024,82322025,82330044,32341001,92049304,92049116,32121001,82071588,82361148130,8231101626,82201714,82271600)the National Key Research and Development Program of China(2020YFA0804000,2022YFA1103700,2020YFA0112200+13 种基金the STI2030-Major Projects-2021ZD0202400,2021YFF1201000,2021YFA1101000)CAS Project for Young Scientists in Basic Research(YSBR-076,YSBR-012)the Program of the Beijing Natural Science Foundation(Z230011,Z240018,JQ24044)the Informatization Plan of Chinese Academy of Sciences(CASWX2022SDC-XK14)New Cornerstone Science Foundation through the XPLORER PRIZE(2021-1045)Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes(JYY2023-13)CAS Youth Interdisciplinary Team,Key Laboratory of Alzheimer’s Disease of Zhejiang Province(ZJAD-2024001)Excellent Young Talents Program of Capital Medical University(12300927)The Project for Technology Development of Beijingaffiliated Medical Research Institutes(11000023T000002036310)Excellent Young Talents Training Program for the Construction of Beijing Municipal University Teacher Team(BPHR202203105)Young Elite Scientists Sponsorship Program by CAST(2021QNRC001)Youth Innovation Promotion Association of CAS(2022083)The Fellowship of China Postdoctoral Science Foundation(2022M712216)Initiative Scientific Research Program,Institute of Zoology,Chinese Academy of Sciences(2023IOZ0102)。
文摘The innate immune signaling network follows a canonical format for signal transmission.The innate immune pathway is crucial for defense against pathogens,yet its mechanistic crosstalk with aging processes remains largely unexplored.Retinoic acid-inducible gene-Ⅰ(RIG-Ⅰ),a key mediator of antiviral immunity within this pathway,has an enigmatic role in stem cell senescence.Our study reveals that RIG-Ⅰlevels increase in human genetic and physiological cellular aging models,and its accumulation drives cellular senescence.Conversely,CRISPR/Cas9-mediated RIG-Ⅰdeletion or pharmacological inhibition in human mesenchymal stem cells(h MSCs)confers resistance to senescence.Mechanistically,RIG-Ⅰbinds to endogenous m RNAs,with CDKN1A m RNA being a prominent target.Specifically,RIG-Ⅰstabilizes CDKN1A m RNA,resulting in elevated CDKN1A transcript levels and increased p21 Cip1 protein expression,which precipitates senescence.Collectively,our findings establish RIG-Ⅰas a post-transcriptional regulator of senescence and suggest potential targets for the mitigation of aging-related diseases.
基金supported by the National Natural Science Foundation of China (82125011, 81921006, 92149301, 82322025, 82122024)the National Key Research and Development Program of China(2020YFA0804000, 2022YFA1103700, 2020YFA0112200, 2021YFF1201000, the STI2030-Major Projects-2021ZD0202400)+9 种基金the National Natural Science Foundation of China (92168201, 82330044, 32341001, 92049304, 92049116, 32121001, 82192863, 82071588, 82361148130, 82361148131, 82271600)CAS Project for Young Scientists in Basic Research (YSBR-076, YSBR-012)the Program of the Beijing Natural Science Foundation (Z230011)the Informatization Plan of Chinese Academy of Sciences (CAS-WX2022SDC-XK14)New Cornerstone Science Foundation through the XPLORER PRIZE (2021-1045)Youth Innovation Promotion Association of CAS (E1CAZW0401, 2022083)Excellent Young Talents Program of Capital Medical University (12300927)The Project for Technology Development of Beijing-affiliated Medical Research Institutes (11000023T000002036310)Excellent Young Talents Training Program for the Construction of Beijing Municipal University Teacher Team (BPHR202203105)Young Elite Scientists Sponsorship Program by CAST (2021QNRC001)。
文摘Dear Editor,Cellular senescence is characterized by growth arrest and the onset of a senescence-associated secretory phenotype (SASP)(Consortium et al., 2023;Liu et al., 2023;Zhang et al., 2023). Consequently, senescent cells that accumulate within aged organs have the capacity to disseminate pro-senescence and pro-inflammatory signals, promoting structural tissue deterioration and functional decline, culminating in organismal aging (Cai et al., 2022;Consortium et al., 2024).
基金supported by the National High Technology Research and Development Program of China(2020YFA0803700 and 2023YFA1800904)the Natural Science Foundation of Beijing,China(L232031 and J230039)+2 种基金the Postdoctoral Fellowship Program of CPSF(GZC20240068)the China Postdoctoral Science Foundation(2021M690252 and 2021TQ0019)the National Natural Science Foundation of China(82371363)。
文摘Environmental pollution is an important but often overlooked risk factor for cardiovascular diseases such as heart failure.Triclocarban(3,4,4′-trichlorocarbanilide,TCC)is a broad-spectrum antibacterial agent commonly used in personal care products such as antibacterial soaps,detergents,toothpaste,and cosmetics[1].Unfortunately,due to its widespread use,TCC has become one of the top ten most common water pollutants globally,and it is present in the atmosphere,soil,and aquatic sediments[2].
基金supported by the National Key Research and Development Program of China(Grant No.2020YFA0803700)the National Natural Science Foundation of China(Grant Nos.91639108,81770272,and 81970425)+1 种基金the Beijing Natural Science Foundation(Grant No.7212044)the Beijing Hospital Authority Youth Program(Grant No.QML20190306)。
文摘Hepatocellular carcinoma(HCC)is the fourth leading cause of cancer-associated death worldwide.Angiogenesis,the process of formation of new blood vessels,is required for cancer cells to obtain nutrients and oxygen.HCC is a typical hypervascular solid tumor with an aberrant vascular network and angiogenesis that contribute to its growth,progression,invasion,and metastasis.Current anti-angiogenic therapies target mainly tyrosine kinases,vascular endothelial growth factor receptor(VEGFR),and plateletderived growth factor receptor(PDGFR),and are considered effective strategies for HCC,particularly advanced HCC.However,because the survival benefits conferred by these anti-angiogenic therapies are modest,new anti-angiogenic targets must be identified.Several recent studies have determined the underlying molecular mechanisms,including pro-angiogenic factors secreted by HCC cells,the tumor microenvironment,and cancer stem cells.In this review,we summarize the roles of pro-angiogenic factors;the involvement of endothelial cells,hepatic stellate cells,tumor-associated macrophages,and tumor-associated neutrophils present in the tumor microenvironment;and the regulatory influence of cancer stem cells on angiogenesis in HCC.Furthermore,we discuss some of the clinically approved anti-angiogenic therapies and potential novel therapeutic targets for angiogenesis in HCC.A better understanding of the mechanisms underlying angiogenesis may lead to the development of more optimized anti-angiogenic treatment modalities for HCC.
文摘BACKGROUND Recently,the efficacy of cognitive behavioral therapy(CBT)-based intervention on health outcomes in patients with coronary heart disease(CHD)has been recognized in randomized controlled trials(RCTs),but no comprehensive systematic review has been conducted.To address this research gap,our study aimed to evaluate whether comprehensive CBT-based interventions positively affect health outcomes in CHD patients.It was hypothesized that CBT-based interventions are effective in:(1)Reducing depression,anxiety,and stress symptoms;(2)Reducing body mass index,blood pressure,and lipid levels;and(3)Improving quality of life,and exercise endurance.AIM To verify the effectiveness of CBT-based interventions on CHD patients through a meta-analysis of previous publications.METHODS Relevant RCTs published in English were obtained by searching electronic databases,including PubMed,Embase,Cochrane Central Register of Controlled Trials,Scopus,and Proquest,with the retrieval time from inception to August 2020.The primary outcomes were psychological factors(depression,anxiety,and stress symptoms),physiological factors(body mass index,blood pressure,blood lipids).The secondary outcomes included quality of life and exercise endurance.We used Review Manager 5.3 to conduct the meta-analysis and used the Physiotherapy Evidence Database tool to evaluate the quality of studies.RESULTS A total of 22 RCTs comprising 4991 patients with CHD were included in the systematic review and meta-analysis.The main analysis revealed that CBT-based intervention can reduce depression symptoms:-2.00[95%confidence interval(CI):-2.83 to-1.16,P<0.001];anxiety symptoms:-2.07(95%CI:-3.39 to-0.75,P=0.002);stress symptoms:-3.33(95%CI:-4.23 to-2.44,P<0.001);body mass index:-0.47(95%CI:-0.81 to-0.13,P=0.006);and improve physical functioning:3.36(95%CI:1.63 to 5.10,P=0.000)and mental functioning:6.91(95%CI:4.10 to 9.73,P<0.001).Moreover,subgroup analysis results showed that CBT-based interventions were more effective for symptoms of depression and anxiety in CHD patients when individual,as opposed to group treatment,and psycho-education,behavioral and cognitive strategies were applied as the core treatment approaches.CONCLUSION CBT-based interventions are effective treatment strategies for CHD patients,significantly improving their symptoms of depression,anxiety and stress,body mass index,and health-related quality of life.
基金financially supported by the Beijing Hospital Management Center“Dengfeng”plan[DFL20191901]。
文摘Objective To identify the representative attributes of the five elements of a person with a qualitative methodology and provide the basis for the clinical diagnosis and treatment of“people with the five elements in traditional Chinese medicine(TCM).”Methods Data collected from the literature review,two sessions of brainstorming of experts with related experience in“people with the five elements in TCM”from October 2020 to December 2020,and six rounds of in-depth interviews with 30 participants who had various attributes of the five elements from March 2021 to October 2021 were analyzed.Triangulation was used in this study,and theming and synthesizing were used to analyze the data.Results A total of 31 experts and 30 interviewees participated in this study.The median age of the experts and interviewees were 48.0 and 38.5 years,respectively;51.66%and 54.8%of experts and interviewees,respectively,were men.The descriptors of facial diagrams of“people with the five elements in TCM”were complexion,shape,distribution state of facial bones,convergence trend of facial muscles,and facial expression.A theoretical model of“people with the five elements in TCM”was shaped based on these findings.Conclusion The study suggests a possibility for bridging the gap between personality and bodily state,identifying an avenue for personality research from the perspective of TCM.
基金supported by the National Natural Science Foundation of China (No. 61672070, 61501007, 11675199, 61572004 and 81501155)the Key Project of Beijing Municipal Education Commission (No. KZ201910005008)+3 种基金general project of science and technology project of Beijing Municipal Education Commission (No. KM201610005023)the Beijing Municipal Natural Science Foundation (No. 4182005)Clinical Technology Innovation Program of Beijing Municipal Administration of Hospitals (No. XMLX201805)Beijing Municipal Science & Tech Commission (No. Z171100000117004)
文摘Source localization of focal electrical activity from scalp electroencephalogram (sEEG) signal is generally modeled as an inverse problem that is highly ill-posed. In this paper, a novel source localization method is proposed to model the EEG inverse problem using spatio-temporal long-short term memory recurrent neural networks (LSTM). The network model consists of two parts, sEEG encoding and source decoding, to model the sEEG signal and receive the regression of source location. As there does not exist enough annotated sEEG signals correspond to specific source locations, simulated data is generated with forward model using finite element method (FEM) to act as a part of training signals. A framework for source localization is proposed to estimate the source position based on simulated training data. Experiments are done on simulated testing data. The results on simulated data exhibit good robustness on noise signal, and the proposed network solves the EEG inverse problem with spatio-temporal deep network. The result show that the proposed method overcomes the highly ill-posed linear inverse problem with data driven learning.
