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Mutual prediction is crucial for understanding the mediation of bodily actions in social interactions. Despite this importance, limited studies have investigated neurobehavioral patterns under the mutual prediction hypothesis in natural competitive scenarios. To address this gap, our study employed functional near-infrared spectroscopy hyperscanning to examine the dynamics of real-time rock-paper-scissors games using a computerized paradigm with 54 participants. Firstly, our results revealed activations in the right inferior frontal gyrus, bilateral dorsolateral prefrontal cortex, and bilateral frontopolar cortex, each displaying distinct temporal profiles indicative of diverse cognitive processes during the task. Subsequently, a task-related increase in inter-brain synchrony was explicitly identified in the right dorsolateral prefrontal cortex, which supported the mutual prediction hypothesis across the two brains. Moreover, our investigation uncovered a close association between the coherence value in the right dorsolateral prefrontal cortex and the dynamic predictive performances of dyads using inter-subject representational similarity analysis. Finally, heightened inter-brain synchrony values were observed in the right dorsolateral prefrontal cortex before a draw compared to a no-draw scenario in the second block, suggesting that cross-brain signal patterns could be reflected in behavioral responses during competition. In summary, these findings provided initial support for expanding the understanding of cognitive processes underpinning natural competitive engagements.
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Conducta Cooperativa , Espectroscopía Infrarroja Corta , Humanos , Espectroscopía Infrarroja Corta/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/fisiología , Corteza Cerebral , Mapeo Encefálico/métodos , Relaciones InterpersonalesRESUMEN
BACKGROUND: Gastric cancer (GC) lacks serum biomarkers with clinical diagnostic value. Multi-omics analysis is an important approach to discovering cancer biomarkers. This study aimed to identify and validate serum biomarkers for GC diagnosis by cross-analysis of proteomics and transcriptomics datasets. METHODS: A cross-omics analysis was performed to identify overlapping differentially expressed genes (DEGs) between our previous aptamer-based GC serum proteomics dataset and the GC tissue RNA-Seq dataset in The Cancer Genome Atlas (TCGA) database, followed by lasso regression and random forest analysis to select key overlapping DEGs as candidate biomarkers for GC. The mRNA levels and diagnostic performance of these candidate biomarkers were analyzed in the original and independent GC datasets to select valuable candidate biomarkers. The valuable candidate biomarkers were subjected to bioinformatics analysis to select those closely associated with the biological behaviors of GC as potential biomarkers. The clinical diagnostic value of the potential biomarkers was validated using serum samples, and their expression levels and functions in GC cells were validated using in vitro cell experiments. RESULTS: Four candidate biomarkers (ILF2, PGM2L1, CHD7, and JCHAIN) were selected. Their mRNA levels differed significantly between tumor and normal tissues and showed different diagnostic performances for GC, with areas under the receiver operating characteristic curve (AUROCs) of 0.629-0.950 in the TCGA dataset and 0.736-0.840 in the Gene Expression Omnibus (GEO) dataset. In the bioinformatics analysis, only ILF2 (interleukin enhancer-binding factor 2) gene levels were associated with immune cell infiltration, some checkpoint gene expression, chemotherapy sensitivity, and immunotherapy response. Serum levels of ILF2 were higher in GC patients than in controls, with an AUROC of 0.944 for the diagnosis of GC, and it was also detected in the supernatants of GC cells. Knockdown of ILF2 by siRNA significantly reduced the proliferation and colony formation of GC cells. Overexpression of ILF2 significantly promotes the proliferation and colony formation of gastric cancer cells. CONCLUSIONS: Trans-omics analysis of proteomics and transcriptomics is an efficient approach for discovering serum biomarkers, and ILF2 is a potential diagnostic biomarker and therapeutic target of gastric cancer.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Biomarcadores de Tumor/metabolismo , Perfilación de la Expresión Génica , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteína del Factor Nuclear 45/genéticaRESUMEN
INTRODUCTION: Even though existing amounts of results have shown that school bullying could be related to the main components of executive functions (EFs) (inhibitory control, working memory, and cognitive flexibility), research focused on this association yields inconsistent results. METHOD: To address this research gap, the current study conducted a three-level meta-analysis approach and simultaneously considered the two perspectives of the bully and victim to clarify the relationship between school bullying experienced by children and EFs. It also explored the moderating variables that affect the relationship between school bullying and EFs. RESULTS: Based on 18 studies reporting 73 effect sizes (N = 21,725), the results revealed that the overall effect size for the association between both the bullies and victims of school bullying incidents with EFs (rbullies = -0.154, p < .05; rvictims = -0.187, p < .001). Moderator analyses revealed that the negative correlation between bullies of school bullying and EFs was moderated by EF components, but it was not affected by gender, age, and the EF measurement method. Moreover, the negative correlation between victims of school bullying and EFs was not affected by the form of bullying, source of report, facet of EFs, EF measurement, gender, age, and culture. CONCLUSIONS: The present meta-analysis revealed a relationship between school bullying and EFs. Both bullies and victims appear to have lower EF levels. The results also emphasized that lower inhibitory control was more likely to be a crucial risk factor for bullying behavior.
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Ganoderma lucidum, known as the "herb of spiritual potency", is used for the treatment and prevention of various diseases, but the responsible constituents for its therapeutic effects are largely unknown. For the purpose of obtaining insight into the chemical and biological profiling of meroterpenoids in G. lucidum, various chromatographic approaches were utilized for the title fungus. As a result, six undescribed meroterpenoids, chizhienes A-F (1-6), containing two pairs of enantiomers (4 and 5), were isolated. Their structures were identified using spectroscopic and computational methods. In addition, the anti-inflammatory activities of all the isolates were evaluated by Western blot analysis in LPS-induced macrophage cells (RAW264.7), showing that 1 and 3 could dose dependently inhibit iNOS but not COX-2 expression. Further, 1 and 3 were found to inhibit nitric oxide (NO) production using the Greiss reagent test. The current study will aid in enriching the structural and biological diversity of Ganoderma-derived meroterpenoids.
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Ganoderma , Reishi , Reishi/química , Ganoderma/química , Antiinflamatorios/farmacología , Línea Celular , Macrófagos , Estructura MolecularRESUMEN
K metal battery is a kind of high-energy-density storage device with economic advantages. However, due to the dendrite growth and difficult processing characteristics, it is difficult to prepare stable K metal anode with thin thickness and fixed area capacity, which severely limits its development. In this work, a multi-functional 3D skeleton (rGCA) is synthesized by simple vacuum filtration and thermal reduction, and K metal anodes with controllable thickness and area capacity (K content) can be fabricated by changing the raw material mass and graphene layer spacing of rGCA. Moreover, the graphene sheet layer of rGCA can relax stress and relieve volume expansion; carbon nanotubes can serve as the fast transport channel of electrons, reducing internal impedance and local current density; Ag nanoparticles can induce the uniform nucleation and deposition of K+ . The K metal composite anodes (rGCA-K) based on the conductive skeleton can effectively suppress dendrites and exhibit excellent electrochemical performance in symmetric and full cells. The controllable fabrication process of stable K metal anode is expected to help K metal batteries move toward the stage of commercial production.
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Preclinical and human studies on the relationship between obesity/metabolic syndrome (MetS) and lower urinary tract dysfunction (LUTD) are inconsistent. We compared the temporal effects of feeding four different diets used to induce obesity/MetS, including 60% fructose, 2% cholesterol +10% lard, 30% fructose + 20% lard, or 32.5% lard diet, up to 42 wk, on metabolic parameters and bladder function in male Sprague-Dawley rats. Rats fed a 30% fructose + 20% lard or 32.5% lard diet consumed less food (grams), but only the 32.5% lard diet group took in more calories. Feeding rats a 60% fructose or 30% fructose + 20% lard diet led to glucose intolerance and increased blood pressure. Higher body weight and increased cholesterol levels were observed in the rats maintained on a 2% cholesterol +10% lard diet, whereas exposure to a 32.5% lard diet affected most of the above parameters. Voiding behavior measurement showed that voiding frequency and the total voided volume were lower in the experimental diet groups except for the 30% fructose + 20% lard group. The mean voided volume was lower in the 30% fructose + 20% lard and 32.5% lard groups compared with the control group. Cystometric analysis revealed a decreased bladder capacity, mean voided volume, intermicturition interval, and compliance in the 32.5% lard diet group. In conclusion, experimental diets including 60% fructose, 30% fructose + 20% lard, or 2% cholesterol + 10% lard diet differently affected physiological and metabolic parameters and bladder function to a limited extent, while exposure to a 32.5% lard diet had a greater impact.
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Síndrome Metabólico , Humanos , Ratas , Masculino , Animales , Síndrome Metabólico/etiología , Ratas Sprague-Dawley , Triglicéridos , Vejiga Urinaria/metabolismo , Obesidad/etiología , Obesidad/metabolismo , Dieta , Colesterol , Fructosa/efectos adversosRESUMEN
Preharvest sprouting (PHS) is an unfavorable trait in cereal crops and causes serious yield loss. However, the molecular mechanism underlying PHS remains largely elusive. Here, we identified a member of 9-cis-epoxycarotenoid dioxygenase family, OsNCED3, which regulates PHS and grain development in rice (Oryza sativa L.). OsNCED3 encodes a chloroplast-localized abscisic acid (ABA) biosynthetic enzyme highly expressed in the embryo of developing seeds. Disruption of OsNCED3 by CRISPR/Cas9-mediated mutagenesis led to a lower ABA and higher gibberellic acid (GA) levels (thus a skewed ABA/GA ratio) in the embryo, promoting embryos growth and breaking seed dormancy before seed maturity and harvest, thus decreased seed dormancy and enhanced PHS in rice. However, the overexpression of OsNCED3 enhanced PHS resistance by regulating proper ABA/GA ratio in the embryo. Intriguingly, the overexpression of OsNCED3 resulted in increased grain size and weight, whereas the disruption of OsNCED3 function decreased grain size and weight. Nucleotide diversity analyses suggested that OsNCED3 may be selected during japonica populations adaptation of seed dormancy and germination. Taken together, we have identified a new OsNCED regulator involved rice PHS and grain development, and provide a potential target gene for improving PHS resistance and grain development in rice.
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Grano Comestible , Oryza , Grano Comestible/fisiología , Oryza/fisiología , Germinación/genética , Latencia en las Plantas/genética , Ácido Abscísico , Semillas/fisiología , Regulación de la Expresión Génica de las PlantasRESUMEN
Diabetes mellitus (DM) is a severe chronic diseases with a global prevalence of 9%, leading to poor health and high health care costs, and is a direct cause of millions of deaths each year. The rising epidemic of diabetes and its complications, such as retinal and peripheral nerve disease, is a huge burden globally. A better understanding of the molecular pathways involved in the development and progression of diabetes and its complications can facilitate individualized prevention and treatment. High diabetes mellitus incidence rate is caused mainly by lack of non-invasive and reliable methods for early diagnosis, such as plasma biomarkers. The incidence of diabetes and its complications in the world still grows so it is crucial to develop a new, faster, high specificity and more sensitive diagnostic technologies. With the advancement of analytical techniques, metabolomics can identify and quantify multiple biomarkers simultaneously in a high-throughput manner, and effective biomarkers can greatly improve the efficiency of diabetes and its complications. By providing information on potential metabolic pathways, metabolomics can further define the mechanisms underlying the progression of diabetes and its complications, help identify potential therapeutic targets, and improve the prevention and management of T2D and its complications. The application of amino acid metabolomics in epidemiological studies has identified new biomarkers of diabetes mellitus (DM) and its complications, such as branched-chain amino acids, phenylalanine and arginine metabolites. This study focused on the analysis of metabolic amino acid profiling as a method for identifying biomarkers for the detection and screening of diabetes and its complications. The results presented are all from recent studies, and in all cases analyzed, there were significant changes in the amino acid profile of patients in the experimental group compared to the control group. This study demonstrates the potential of amino acid profiles as a detection method for diabetes and its complications.
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Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Humanos , Aminoácidos/metabolismo , Diabetes Mellitus/metabolismo , Biomarcadores , Metabolómica/métodos , Aminoácidos de Cadena Ramificada , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnósticoRESUMEN
Aquilariperoxide A (1), an unprecedented sesquiterpene dimer characterized by a dioxepane ring connecting two sesquiterpene units via a C-C bond, was isolated from agarwood of Aquilaria sinensis-containing resins. The structure was elucidated by spectroscopic and computational methods. A bioassay revealed that 1 significantly inhibits cell proliferation and migration in human cancer cells. The mechanism of 1 against cancer cells was briefly discussed by analysis of RNA sequence data and epithelial-mesenchymal transition. Besides, the antimalarial activity of 1 was also evaluated.
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Antimaláricos , Sesquiterpenos , Thymelaeaceae , Humanos , Antimaláricos/farmacología , Secuencia de Bases , Thymelaeaceae/química , Thymelaeaceae/genética , Sesquiterpenos/farmacología , Sesquiterpenos/químicaRESUMEN
The neurotoxic effects of prenatal exposure to per- and polyfluoroalkyl substances (PFAS) on offspring animals are well-documented. However, epidemiological evidence for legacy PFAS is inconclusive, and for alternative PFAS, it is little known. In this investigation, we selected 718 mother-child pairs from the Chinese Maoming Birth Cohort Study and measured 17 legacy and alternative PFAS in the third-trimester serum. Neuropsychological developments (communication, gross motor function, fine motor function, problem solving ability, and personal-social skills) were assessed at 3, 6, 12, 18, 24, and 36 months using the Ages and Stages Questionnaires 3rd edition. Trajectories of each subscale were classified into persistently low and persistently high groups via group-based trajectory modeling. Logistic regression and grouped weighted quantile sum were fitted to assess the potential effects of individual PFAS and their mixtures, respectively. Higher linear PFHxS levels were associated with elevated odds for the persistently low trajectories of communication (OR = 1.73; 95% CI: 1.12, 2.66) and problem solving ability (OR = 2.11; 95% CI: 1.14, 3.90). Similar findings were observed for linear PFOS, 1m-PFOS, PFDA, PFDoDA, PFUnDA, and legacy PFAS mixture. However, no association was observed for alternative PFAS and their mixture. We provided insights into the longitudinal links between prenatal legacy/alternative PFAS exposure and neuropsychological development trajectories over the first 3 years of life.
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Ácidos Alcanesulfónicos , Contaminantes Ambientales , Fluorocarburos , Efectos Tardíos de la Exposición Prenatal , Humanos , Embarazo , Femenino , Contaminantes Ambientales/toxicidad , Estudios de Cohortes , Fluorocarburos/toxicidad , Ácidos Alcanesulfónicos/toxicidadRESUMEN
Glucocorticoid plays a key role in the growth and organ maturation of fetus. However, the effect of glucocorticoid on the association between per- and polyfluoroalkyl substance (PFAS) exposure and fetal growth is still unknown. We detected cord cortisol (active glucocorticoid in human) and 34 PFAS concentrations in the maternal serum samples, which were collected from 202 mother-fetus pairs in the Maoming Birth Cohort from 2015 to 2018. The mediation effect of cord cortisol on the association between maternal PFAS and the neonatal growth index (NGI) was estimated. We found that higher PFAS concentrations were associated with lower NGI in terms of ponderal index, birth weight (BW), head circumference (HC), and its z-scores (BWZ and HCZ) (P < 0.05). Fetal cortisol could mediate 12.6-27.3% of the associations between PFAS and NGI. Specifically, cord cortisol mediated the association between branched perfluorooctane sulfonate (branched PFOS) and HCZ by 20.4% and between perfluorooctanoate (PFOA) and HCZ by 27.3%. Our findings provide the first epidemiological data evincing that fetal cortisol could mediate the association between prenatal PFAS exposure and fetal growth. Further investigations are recommended to elucidate the interactions among cord cortisol, PFAS, and fetal growth.
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Ácidos Alcanesulfónicos , Contaminantes Ambientales , Fluorocarburos , Embarazo , Recién Nacido , Femenino , Humanos , Estudios de Cohortes , Glucocorticoides , Hidrocortisona , FetoRESUMEN
Zizhines V, W, Y, Z, (±)-zizhines X, and Z1-Z3, and (±)-ganosinensol L, thirteen new compounds including four pairs of enantiomers and a known compound (-)-ganosinensol L, were isolated from the fruiting bodies of Ganoderma sinensis. Their structures were identified by spectroscopic, computational methods, and CD (circular dichroism spectroscopy) comparisons. Zizhines V-Z and Z1-Z3 are meroterpenoids consisting of the phenolic and the terpenoidal parts. All the compounds except zizhine Z3 bear a common trans-p-hydroxycinnamoyl group. Biological evaluation shows that (-)-zizhine Z1 inhibits cell migration in the MDA-MB-231â cell lines. The present study discloses the chemical profiling of G. sinensis and paves the way for its development as functional products to benefit chronic disorders.
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Ganoderma , Terpenos , Cuerpos Fructíferos de los Hongos/química , Ganoderma/química , Estructura Molecular , Terpenos/química , Cinamatos/químicaRESUMEN
Although many empirical studies have aimed to find variances in positive mental health among different groups and the relationship between mental health and other variables, few studies examined the developmental trend of mental health levels and the cross-lagged relationship between self-efficacy, social rhythm, and mental health. Furthermore, few of them explored the interrelationship between self-efficacy and social rhythm among college students over time. This study thus aimed to clarify the longitudinal cross-lagged relationship between self-efficacy, social rhythm, and positive mental health among college students. A total of 764 students (627 females, mean age 21.03 ± 0.84 years at T1) participated in a 3-year-long study (T1, T2, T3) and were asked to complete the General Self-Efficacy, the Brief Social Rhythm, and the Positive Mental Health Scales. The results indicate that the development of positive mental health among college students showed an upward trend during those 3 years. There was a significant relationship between positive mental health, social rhythm, and self-efficacy. Positive mental health and social rhythm significantly predicted self-efficacy in the following year. Positive mental health in T2 could predict both T3 social rhythm marginally and T3 self-efficacy significantly. However, T1 social rhythm was not indirectly associated with T3 mental health via T2 self-efficacy, and T1 self-efficacy was not indirectly associated with T3 mental health via T2 social rhythm. This finding clarified the relationship between positive mental health, self-efficacy, and social rhythm, and provided evidence that positive mental health is the basis for self-efficacy and social rhythm among young adults. Therefore, school psychologists in universities should pay close attention to the positive mental health of young adults to form high levels of self-efficacy and social rhythm.
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OBJECTIVE: To identify and utilize gene signatures for the prognostic evaluation of postoperative patients with hepatocellular carcinoma (HCC). METHODS: The gene mRNA expression profiles and corresponding clinicopathological data of postoperative patients with HCC were downloaded from The Cancer Genome Atlas (TCGA) database. Highly differentially expressed genes (DEGs) in tumor tissues compared to adjacent tissues were identified, and their associations with the overall survival (OS) of HCC patients were analyzed. The strongly associated genes were used to develop a prognostic score for the survival stratification of HCC, and the underlying mechanisms were analyzed using bioinformatics. RESULTS: A total of 376 DEGs were identified and four DEGs (ADH4, COL15A1, RET and KCNJ16) were independently associated with OS. A prognostic score derived from the four genes could effectively stratify HCC patients with different OS outcomes, independent of clinical parameters. Patients with high scores exhibited poorer OS than patients with low scores (HR 5.526, 95% CI: 2.451-12.461, p < .001). The four genes were involved in cancer-related biological processes and were independent of each other in bioinformatics analyses. CONCLUSION: Four genes strongly associated with the prognosis of postoperative patients with HCC were identified, and the derived prognostic score was simple and valuable for overall survival prediction.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/cirugía , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirugía , Pronóstico , ARN MensajeroRESUMEN
OBJECTIVE: HIV positive (HIV+) individuals with otherwise normal hearing ability show central auditory processing deficits as evidenced by worse performance in speech-in-noise perception compared with HIV negative (HIV-) controls. HIV infection and treatment are also associated with lower neurocognitive screening test scores, suggesting underlying central nervous system damage. To determine how central auditory processing deficits in HIV+ individuals relate to brain alterations in the cortex involved with auditory processing, we compared auditory network (AN) functional connectivity between HIV+ adults with or without speech-in-noise perception difficulties and age-matched HIV- controls using resting-state fMRI. DESIGN: Based on the speech recognition threshold of the hearing-in-noise test, twenty-seven HIV+ individuals were divided into a group with speech-in-noise perception abnormalities (HIV+SPabnl, 38.2 ± 6.8 years; 11 males and 2 females) and one without (HIV+SPnl 34.4 ± 8.8 years; 14 males). An HIV- group with normal speech-in-noise perception (HIV-, 31.3 ± 5.2 years; 9 males and 3 females) was also enrolled. All of these younger and middle-aged adults had normal peripheral hearing determined by audiometry. Participants were studied using resting-state fMRI. Independent component analysis was applied to identify the AN. Group differences in the AN were identified using statistical parametric mapping. RESULTS: Both HIV+ groups had increased functional connectivity (FC) in parts of the AN including the superior temporal gyrus, middle temporal gyrus, supramarginal gyrus, and Rolandic operculum compared to the HIV- group. Compared with the HIV+SPnl group, the HIV+SPabnl group showed greater FC in parts of the AN including the middle frontal and inferior frontal gyri. CONCLUSIONS: The classical auditory areas in the temporal lobe are affected by HIV regardless of speech perception ability. Increased temporal FC in HIV+ individuals might reflect functional compensation to achieve normal primary auditory perception. Furthermore, increased frontal FC in the HIV+SPabnl group compared with the HIV+SPnl group suggest that speech-in-noise perception difficulties in HIV-infected adults also affect areas involved in higher-level cognition, providing imaging evidence consistent with the hypothesis that HIV-related neurocognitive deficits can include central auditory processing deficits.
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Corteza Auditiva , Infecciones por VIH , Percepción del Habla , Adulto , Audiometría , Umbral Auditivo/fisiología , Femenino , Infecciones por VIH/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Ruido , Percepción del Habla/fisiologíaRESUMEN
A growing body of research suggests that mathematical anxiety (MA) seriously affects an individual's math achievement. However, few studies have focused on the cognitive mechanisms of MA in elementary school children. Based on attention control theory (ACT), this research aimed to explore the cognitive mechanism of MA in elementary school children using two studies. In Study 1, the dual-task paradigm of number memory and computation span was used to investigate the difference in processing efficiency between the high-mathematical anxiety (HMA) group and the low-mathematical anxiety (LMA) group. In total, 59 students with HMA and 54 students with LMA participated in Study 1. The results showed that students with HMA had lower processing efficiency in dealing with high-load math tasks. To further investigate the underlying mechanism of low processing efficiency for students with HMA, Study 2 explored the attention bias toward math-related stimuli of students with HMA using the Posner paradigm. In total, 48 students with HMA and 49 students with LMA participated in Study 2. The results showed that math trials put children with HMA in a state of heightened vigilance in general, which might be related to the low processing efficiency in dealing with high-load math tasks. These findings support the ACT and further reveal the mechanism of MA in elementary school children from a cognitive perspective.
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Logro , Ansiedad , Ansiedad/psicología , Niño , Cognición , Humanos , Matemática , Instituciones AcadémicasRESUMEN
Attention plays an important role in children's development and learning, and neurofeedback training (NFT) has been proposed as a promising method to improve attention, mainly in population with attention problems such as attention deficit hyperactivity disorder. However, whether this approach has a positive effect on attention in normal developing children has been rarely investigated. This pilot study conducted ten sessions of alpha/theta ratio (ATR) NFT on eight primary students in school environment, with two to three sessions per week. The results showed inter-individual difference in NFT learning efficacy that was assessed by the slope of ATR over training sessions. In addition, the attention performance was significantly improved after NFT. Importantly, the improvement of attention performance was positively correlated with the NFT learning efficacy. It thus highlighted the need for optimizing ATR NFT protocol for the benefits on attention at the individual level. Future work can employ a double-blind placebo-controlled design with larger sample size to validate the benefits of ATR NFT for attention in normal developing children.
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Trastorno por Déficit de Atención con Hiperactividad , Neurorretroalimentación , Trastorno por Déficit de Atención con Hiperactividad/terapia , Niño , Método Doble Ciego , Electroencefalografía/métodos , Humanos , Neurorretroalimentación/métodos , Proyectos PilotoRESUMEN
MECP2 gain-of-function and loss-of-function in genetically engineered monkeys recapitulates typical phenotypes in patients with autism, yet where MECP2 mutation affects the monkey brain and whether/how it relates to autism pathology remain unknown. Here we report a combination of gene-circuit-behavior analyses including MECP2 coexpression network, locomotive and cognitive behaviors, and EEG and fMRI findings in 5 MECP2 overexpressed monkeys (Macaca fascicularis; 3 females) and 20 wild-type monkeys (Macaca fascicularis; 11 females). Whole-genome expression analysis revealed MECP2 coexpressed genes significantly enriched in GABA-related signaling pathways, whereby reduced ß-synchronization within fronto-parieto-occipital networks was associated with abnormal locomotive behaviors. Meanwhile, MECP2-induced hyperconnectivity in prefrontal and cingulate networks accounted for regressive deficits in reversal learning tasks. Furthermore, we stratified a cohort of 49 patients with autism and 72 healthy controls of 1112 subjects using functional connectivity patterns, and identified dysconnectivity profiles similar to those in monkeys. By establishing a circuit-based construct link between genetically defined models and stratified patients, these results pave new avenues to deconstruct clinical heterogeneity and advance accurate diagnosis in psychiatric disorders.SIGNIFICANCE STATEMENT Autism spectrum disorder (ASD) is a complex disorder with co-occurring symptoms caused by multiple genetic variations and brain circuit abnormalities. To dissect the gene-circuit-behavior causal chain underlying ASD, animal models are established by manipulating causative genes such as MECP2 However, it is unknown whether such models have captured any circuit-level pathology in ASD patients, as demonstrated by human brain imaging studies. Here, we use transgenic macaques to examine the causal effect of MECP2 overexpression on gene coexpression, brain circuits, and behaviors. For the first time, we demonstrate that the circuit abnormalities linked to MECP2 and autism-like traits in the monkeys can be mapped to a homogeneous ASD subgroup, thereby offering a new strategy to deconstruct clinical heterogeneity in ASD.
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Trastorno del Espectro Autista/fisiopatología , Encéfalo/fisiología , Locomoción/genética , Proteína 2 de Unión a Metil-CpG/genética , Vías Nerviosas/fisiopatología , Animales , Animales Modificados Genéticamente , Mapeo Encefálico/métodos , Modelos Animales de Enfermedad , Electroencefalografía , Femenino , Neuronas GABAérgicas/fisiología , Duplicación de Gen , Humanos , Macaca fascicularis , Imagen por Resonancia Magnética , MasculinoRESUMEN
All-solid-state lithium batteries (ASSLBs) adopting sulfide electrolytes and high-voltage layered oxide cathodes have moved into the mainstream owing to their superior safety and immense potential in high energy density. However, the poor electrochemical compatibility between oxide cathodes and sulfide electrolytes remains a challenge for high-performance ASSLBs. In this study, a nanoscale Li1.4 Al0.4 Ti1.6 (PO4 )3 (LATP) phosphate coating is reasonably constructed on the surface of single-crystal LiNi0.6 Co0.2 Mn0.2 O2 particles to achieve cathode/electrolyte interfacial stability. The conformal LATP layer with inherent high-voltage stability can effectively suppress the oxidation decomposition of the electrolyte and demonstrate chemical inertness to both the oxide cathode and Li10 SnP2 S12 electrolyte. ASSLBs with an LATP-modified cathode exhibited a high initial discharge capacity (152.1 mAh g-1 ), acceptable rate capability, and superior cycling performance with a capacity retention of 87.6% after 100 cycles at 0.1 C. Interfacial modification is an effective approach for achieving high-performance sulfide-based ASSLBs with superior interfacial stability.
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Several randomized clinical trials (RCTs) that investigated the effectiveness of remdesivir for the treatment of coronavirus disease-2019 (COVID-19) have generated inconsistent evidence. The present study aimed to synthesize available RCT evidence using network meta-analyses (NMAs). Both blinded and open-label RCTs in PubMed database from inception to 7 June 2020 that contained "remdesivir", "Covid-19", and "trial" in the abstracts conducted on hospitalized COVID-19 persons were identified and screened. The studies must have at least one remdesivir arm and evaluated one of the pre-specified outcomes. The outcomes were clinical improvement between days 10 to 15 after randomization and clinical recovery during the follow-up period. The identified literature was supplemented with relatively recent studies that were known to the researchers if not already included. Frequentist NMAs with random effects were conducted. Both 10-day and 5-day remdesivir regimens were associated with higher odds of clinical improvement (odds ratio [OR] of 10-day regimen: 1.35, 95% confidence interval [CI], 1.09-1.67); OR of 5-day regimen: 1.81, 95% CI, 1.32-2.45, and higher probabilities of clinical recovery (relative risk [RR] of 10-day regimen: 1.24, 95% CI, 1.07-1.43; RR of 5-day regimen: 1.47, 95% CI, 1.16-1.87 compared with placebo. Remdesivir may have clinical benefits among hospitalized COVID-19 persons.