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BACKGROUND: Adolescent mental health problems are becoming increasingly prevalent, and there are correlations between weight-related concerns and adolescent mental health. The aim of this study is to explore the association between three weight-related factors (actual weight, weight perception, and weight teasing) and mental health problems (depressive symptoms, anxiety symptoms, and loneliness) in Chinese adolescents. METHODS: 10,070 adolescents between the ages of 11-18 from schools in Shanghai, China were selected using a stratified random cluster sampling method. Self-reported questionnaires were collected to investigate weight-related factors and mental health problems. Logistic regression analysis was used to examine the relationship. RESULTS: The prevalence of depressive symptoms, loneliness, mild anxiety symptoms, and moderate to severe anxiety symptoms among adolescents were 18.0%, 53.8%, 26.5%, and 12.3%, respectively, with a higher prevalence found in females. After adjusting for weight perception and weight teasing, actual weight had no harmful impact on adolescents' mental health. Adolescents' perception of being overweight increased the risk of depressive symptoms, loneliness, mild anxiety symptoms, and moderate to severe anxiety symptoms, while the perception of being underweight had a similar but more profound impact (depressive symptoms OR = 1.590, 95% CI: 1.342-1.883; loneliness OR = 1.537, 95% CI: 1.353-1.746; mild anxiety symptoms OR = 1.368, 95% CI: 1.178-1.589; moderate to severe anxiety symptoms OR = 1.780, 95% CI: 1.449-2.186). Experiencing weight teasing more than once a year had a greater effect on adolescents' mental health, especially among adolescents with overweight/obesity (depressive symptoms OR = 2.970, 95% CI: 2.325-3.793; loneliness OR = 3.839, 95% CI: 3.119-4.727; mild anxiety symptoms OR = 2.822, 95% CI: 2.236-3.562; moderate to severe anxiety symptoms OR = 5.212, 95% CI: 3.846-7.065). CONCLUSIONS: The prevalence of mental health problems among adolescents was high, especially loneliness. Weight perception and weight teasing, but not the actual weight, independently influenced adolescent mental health.
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Mutations near allosteric sites can have a significant impact on the function of KRAS. Three specific mutations, K104Q, G12D/K104Q, and G12D/G75A, which are located near allosteric positions, were selected to investigate the molecular mechanisms behind mutation-induced influences on the activity of KRAS. Gaussian accelerated molecular dynamics (GaMD) simulations followed by the principal component analysis (PCA) were performed to improve the sampling of conformational states. The results revealed that these mutations significantly alter the structural flexibility, correlated motions, and dynamic behavior of the switch regions that are essential for KRAS binding to effectors or regulators. Furthermore, the mutations have a significant impact on the hydrogen bonding interactions between GDP and the switch regions, as well as on the electrostatic interactions of magnesium ions (Mg2+) with these regions. Our results verified that these mutations strongly influence the binding of KRAS to its effectors or regulators and allosterically regulate the activity. We believe that this work can provide valuable theoretical insights into a deeper understanding of KRAS function.Communicated by Ramaswamy H. Sarma.
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The HRAS protein is considered a critical target for drug development in cancers. It is vital for effective drug development to understand the effects of mutations on the binding of GTP and GDP to HRAS. We conducted Gaussian accelerated molecular dynamics (GaMD) simulations and free energy landscape (FEL) calculations to investigate the impacts of two mutations (A59E and K117R) on GTP and GDP binding and the conformational states of the switch domain. Our findings demonstrate that these mutations not only modify the flexibility of the switch domains, but also affect the correlated motions of these domains. Furthermore, the mutations significantly disrupt the dynamic behavior of the switch domains, leading to a conformational change in HRAS. Additionally, these mutations significantly impact the switch domain's interactions, including their hydrogen bonding with ligands and electrostatic interactions with magnesium ions. Since the switch domains are crucial for the binding of HRAS to effectors, any alterations in their interactions or conformational states will undoubtedly disrupt the activity of HRAS. This research provides valuable information for the design of drugs targeting HRAS.
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Simulação de Dinâmica Molecular , Transdução de Sinais , Mutação , Conformação Molecular , Guanosina Trifosfato/química , Conformação ProteicaRESUMO
BACKGROUND: The role of dietary intake on precocious puberty remains unclear. This study aimed to investigate the association between the amount and frequency of dietary intake and the risk of precocious puberty in Chinese girls. METHODS: In this case-control study, we enrolled 185 precocious puberty girls and 185 age-matched controls. Their dietary intake was assessed through a semi-quantitative food frequency questionnaire. Their sociodemographic and lifestyle data were collected. The associations between dietary intake and risk of precocious puberty were assessed by conditional logistic regression models. RESULTS: After multivariate adjustment, consuming a higher amount of red meat was associated with higher precocious puberty risk (OR = 2.74, 95% CI: 1.25-6.02), while a higher frequency of fruit ( P for trend = 0.024) and amount of vegetable intake was associated with a lower risk of precocious puberty (P for trend = 0.002). The high vegetable and protein dietary pattern was significantly negatively associated with precocious puberty (OR = 0.78, 95% CI: 0.63-0.97), whereas the high animal food and fruits dietary pattern was remarkably positively associated with precocious puberty (OR = 1.36, 95% CI: 1.09-1.69), after adjusting for age and body mass index. CONCLUSIONS: High vegetable and protein dietary pattern is a protective factor against precocious puberty, while high animal food and fruits dietary pattern is a risk factor for precocious puberty in Chinese girls. Attentions should be paid to a reasonable intake of red meat, eggs, and fruits in children's daily diet, increase their intake of vegetables, in order to reduce the risk of precocious puberty.
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Padrões Dietéticos , Puberdade Precoce , Feminino , Animais , Criança , Humanos , Estudos de Casos e Controles , Puberdade Precoce/epidemiologia , Dieta , Fatores de Risco , Frutas , Verduras , China/epidemiologiaRESUMO
Origin recognition complexes (ORCs) are vital in the control of DNA replication and the progression of the cell cycle, however the precise function and mechanism of ORC6 in non-small cell lung cancer (NSCLC) is still not well understood. The present study used bioinformatics methods to assess the predictive significance of ORC6 expression in NSCLC. Moreover, the expression of ORC6 was further evaluated using reverse transcription-quantitative PCR and western blotting, and its functional significance in lung cancer was assessed via knockdown experiments using small interfering RNA. A significant association was demonstrated between the expression of ORC6 and the clinical features of NSCLC. In particular, elevated levels of ORC6 were significantly strongly correlated with an unfavorable prognosis. Multivariate analysis demonstrated that increased ORC6 expression independently contributed to the risk of overall survival (HR 1.304; P=0.015) in individuals diagnosed with NSCLC. Analysis of Kaplan-Meier plots demonstrated that ORC6 expression served as a valuable indicator for diagnosing and predicting the prognosis of NSCLC. Moreover, in vitro studies demonstrated that modified ORC6 expression had a significant impact on the proliferation, migration and metastasis of NSCLC cells. NSCLC cell lines (H1299 and mH1650) exhibited markedly higher ORC6 expression than normal lung cell lines. The results of the present study indicated a strong association between the expression of ORC6 and the clinicopathological characteristics of NSCLC, which suggested its potential as a reliable biomarker for predicting NSCLC. Furthermore, ORC6 may have important therapeutic implications in the management of NSCLC.
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The accumulation of pesticide residues poses a significant threat to the health of people and the surrounding ecological systems. However, traditional methods are not only costly but require expertise in analysis. An electrochemiluminescence (ECL) aptasensor was developed using chitosan and molybdenum disulfide (CTS-MoS2), along with acetylene black (AB@CTS) for the rapid detection of malathion residues. Due to the weak interaction force, simple composite may lead to uneven dispersion; MoS2 and AB were dissolved in CTS solution, respectively, and utilized the biocompatibility of CTS to interact with each other on the electrode. The MoS2 nanosheets provided a large specific surface area, enhancing the utilization rate of catalytic materials, while AB exhibited excellent conductivity. Additionally, the dendritic polylysine (PLL) contained numerous amino groups to load abundant luminol to catalyze hydrogen peroxide (H2O2) and generate reactive oxygen species (ROS). The proposed ECL aptasensor obtained a low detection limit of 2.75 × 10-3 ng/mL (S/N = 3) with a good detection range from 1.0 × 10-2 ng/mL to 1.0 × 103 ng/mL, demonstrating excellent specificity, repeatability, and stability. Moreover, the ECL aptasensor was successfully applied for detecting malathion pesticide residues in authentic samples with recovery rates ranging from 94.21% to 99.63% (RSD < 2.52%). This work offers valuable insights for advancing ECL sensor technology in future applications.