RESUMO
Human mutations in neuropeptide Y (NPY) have been linked to high body mass index but not altered dietary patterns1. Here we uncover the mechanism by which NPY in sympathetic neurons2,3 protects from obesity. Imaging of cleared mouse brown and white adipose tissue (BAT and WAT, respectively) established that NPY+ sympathetic axons are a smaller subset that mostly maps to the perivasculature; analysis of single-cell RNA sequencing datasets identified mural cells as the main NPY-responsive cells in adipose tissues. We show that NPY sustains the proliferation of mural cells, which are a source of thermogenic adipocytes in both BAT and WAT4-6. We found that diet-induced obesity leads to neuropathy of NPY+ axons and concomitant depletion of mural cells. This defect was replicated in mice with NPY abrogated from sympathetic neurons. The loss of NPY in sympathetic neurons whitened interscapular BAT, reducing its thermogenic ability and decreasing energy expenditure before the onset of obesity. It also caused adult-onset obesity of mice fed on a regular chow diet and rendered them more susceptible to diet-induced obesity without increasing food consumption. Our results indicate that, relative to central NPY, peripheral NPY produced by sympathetic nerves has the opposite effect on body weight by sustaining energy expenditure independently of food intake.
Assuntos
Tecido Adiposo Marrom , Tecido Adiposo Branco , Neurônios , Neuropeptídeo Y , Obesidade , Sistema Nervoso Simpático , Termogênese , Animais , Feminino , Masculino , Camundongos , Adipócitos/metabolismo , Tecido Adiposo Marrom/citologia , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/citologia , Tecido Adiposo Branco/metabolismo , Axônios/metabolismo , Axônios/patologia , Peso Corporal/fisiologia , Proliferação de Células , Conjuntos de Dados como Assunto , Dieta Hiperlipídica/efeitos adversos , Metabolismo Energético , Comportamento Alimentar/fisiologia , Neurônios/citologia , Neurônios/metabolismo , Neurônios/patologia , Neuropeptídeo Y/deficiência , Neuropeptídeo Y/genética , Neuropeptídeo Y/metabolismo , Obesidade/metabolismo , Obesidade/patologia , Análise da Expressão Gênica de Célula Única , Sistema Nervoso Simpático/citologia , Sistema Nervoso Simpático/metabolismoRESUMO
AIMS: Chronic kidney disease (CKD) and diabetes mellitus increase atherosclerotic cardiovascular diseases (ASCVD) risk. However, the association between renal outcome of diabetic kidney disease (DKD) and ASCVD risk is unclear. METHODS: This retrospective study enrolled 218 type 2 diabetic patients with biopsy-proven DKD, and without known cardiovascular diseases. Baseline characteristics were obtained and the 10-year ASCVD risk score was calculated using the Pooled Cohort Equation (PCE). Renal outcome was defined as progression to end-stage renal disease (ESRD). The association between ASCVD risk and renal function and outcome was analyzed with logistic regression and Cox analysis. RESULTS: Among all patients, the median 10-year ASCVD risk score was 14.1%. The median of ASCVD risk score in CKD stage 1, 2, 3, and 4 was 10.9%, 12.3%, 16.5%, and 14.8%, respectively (p = 0.268). Compared with patients with lower ASCVD risk (ï¼14.1%), those with higher ASCVD risk had lower eGFR, higher systolic blood pressure, and more severe renal interstitial inflammation. High ASCVD risk (>14.1%) was an independent indicator of renal dysfunction in multivariable-adjusted logistic analysis (OR, 3.997; 95%CI, 1.385-11.530; p = 0.010), though failed to be an independent risk factor for ESRD in patients with DKD in univariate and multivariate Cox analysis. CONCLUSIONS: DKD patients even in CKD stage 1 had comparable ASCVD risk score to patients in CKD stage 2, 3, and 4. Higher ASCVD risk indicated severe renal insufficiency, while no prognostic value of ASVCD risk for renal outcome was observed, which implied macroangiopathy and microangiopathy in patients with DKD were related, but relatively independent.
Assuntos
Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/complicações , Falência Renal Crônica/epidemiologia , Aterosclerose/epidemiologia , Aterosclerose/etiologia , Doenças Cardiovasculares/etiologia , China/epidemiologia , Nefropatias Diabéticas/patologia , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Falência Renal Crônica/etiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
The integration of Computer-Aided Diagnosis (CAD) with Large Language Models (LLMs) presents a promising frontier in clinical applications, notably in automating diagnostic processes akin to those performed by radiologists and providing consultations similar to a virtual family doctor. Despite the promising potential of this integration, current works face at least two limitations: (1) From the perspective of a radiologist, existing studies typically have a restricted scope of applicable imaging domains, failing to meet the diagnostic needs of different patients. Also, the insufficient diagnostic capability of LLMs further undermine the quality and reliability of the generated medical reports. (2) Current LLMs lack the requisite depth in medical expertise, rendering them less effective as virtual family doctors due to the potential unreliability of the advice provided during patient consultations. To address these limitations, we introduce ChatCAD+, to be universal and reliable. Specifically, it is featured by two main modules: (1) Reliable Report Generation and (2) Reliable Interaction. The Reliable Report Generation module is capable of interpreting medical images from diverse domains and generate high-quality medical reports via our proposed hierarchical in-context learning. Concurrently, the interaction module leverages up-to-date information from reputable medical websites to provide reliable medical advice. Together, these designed modules synergize to closely align with the expertise of human medical professionals, offering enhanced consistency and reliability for interpretation and advice. The source code is available at GitHub.
RESUMO
BACKGROUND: The global rise in developmental delays underscores the critical need for a thorough understanding and timely interventions during early childhood. Addressing this issue, the Chinese Baby Connectome Project (CBCP)'s behavior branch is dedicated to examining language acquisition, social-emotional development, and environmental factors affecting Chinese children. The research framework is built around three primary objectives: developing a 0-6 Child Development Assessment Toolkit, implementing an Intelligent Coding System, and investigating environmental influence. METHODS: Utilizing an accelerated longitudinal design, the CBCP aims to enlist a minimum of 1000 typically developing Chinese children aged 0-6. The data collected in this branch constitutes parental questionnaires, behavioral assessments, and observational experiments to capture their developmental milestones and environmental influences holistically. The parental questionnaires will gauge children's developmental levels in language and social-emotional domains, alongside parental mental well-being, life events, parenting stress, parenting styles, and family relationships. Behavioral assessments will involve neurofunctional developmental evaluations using tools such as the Griffiths Development Scales and Wechsler Preschool and Primary Scale of Intelligence. Additionally, the assessments will encompass measuring children's executive functions (e.g., Head-Toe-Knee-Shoulder), social cognitive abilities (e.g., theory of mind), and language development (e.g., Early Chinese Vocabulary Test). A series of behavior observation. experiments will be conducted targeting children of different age groups, focusing primarily on aspects such as behavioral inhibition, compliance, self-control, and social-emotional regulation. To achieve the objectives, established international questionnaires will be adapted to suit local contexts and devise customized metrics for evaluating children's language and social-emotional development; deep learning algorithms will be developed in the observational experiments to enable automated behavioral analysis; and statistical models will be built to factor in various environmental variables to comprehensively outline developmental trajectories and relationships. DISCUSSION: This study's integration of diverse assessments and AI technology will offer a detailed analysis of early childhood development in China, particularly in the realms of language acquisition and social-emotional skills. The development of a comprehensive assessment toolkit and coding system will enhance our ability to understand and support the development of Chinese children, contributing significantly to the field of early childhood development research. TRIAL REGISTRATION: This study was registered with clinicaltrials.gov NCT05040542 on September 10, 2021.
Assuntos
Desenvolvimento Infantil , Conectoma , Desenvolvimento da Linguagem , Humanos , Pré-Escolar , Lactente , Masculino , China , Feminino , Conectoma/métodos , Criança , Recém-Nascido , Emoções , Comportamento Infantil/psicologia , Estudos Longitudinais , População do Leste AsiáticoRESUMO
Many clinical studies have shown that facial expression recognition and cognitive function are impaired in depressed patients. Different from spontaneous facial expression mimicry (SFEM), 164 subjects (82 in a case group and 82 in a control group) participated in our voluntary facial expression mimicry (VFEM) experiment using expressions of neutrality, anger, disgust, fear, happiness, sadness and surprise. Our research is as follows. First, we collected a large amount of subject data for VFEM. Second, we extracted the geometric features of subject facial expression images for VFEM and used Spearman correlation analysis, a random forest, and logistic regression-based recursive feature elimination (LR-RFE) to perform feature selection. The features selected revealed the difference between the case group and the control group. Third, we combined geometric features with the original images and improved the advanced deep learning facial expression recognition (FER) algorithms in different systems. We propose the E-ViT and E-ResNet based on VFEM. The accuracies and F1 scores were higher than those of the baseline models, respectively. Our research proved that it is effective to use feature selection to screen geometric features and combine them with a deep learning model for depression facial expression recognition.