Comparison of dietary inflammatory index and inflammatory biomarkers between vegetarians and omnivores in Chinese population.

Most previous studies on the association between vegetarian diet and inflammation have used only one inflammatory biomarker e.g., C-reactive protein (CRP) and the findings were generally inconsistent. Therefore, we conducted a cross-sectional study to investigate the correlation between diet and inflammation in Chinese vegetarians using dietary indices and multiple inflammatory biomarkers. 279 vegetarians and omnivores of the same sex and age recruited in Shanghai, 2016. 24-h dietary review questionnaire was collected and used to calculate Dietary inflammatory index (DII) and Energy-adjusted inflammatory index (E-DII) of both groups. In addition, energy intake matched vegetarian and omnivore recipes were designed by registed dietitions and used to calculate a theoretical DII. Five serum inflammatory biomarkers CRP, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were measured. We found that vegetarians had significantly lower E-DII and theoretical DII than omnivores (P < 0.001). In contrast, the raw DII of vegetarians was almost the same with that of omnivores, probably due to lower energy intake in vegetarians than in omnivores (1367.97 ± 479.75 vs. 1724.78 ± 568.13, P < 0.001). Levels of TNF-α, IL-6, NLR and PLR were significantly higher in vegetarians than in omnivores while no statistical differences were found in CRP. In conclusion, a theoretical vegetarian diet with adequate energy intake as well as a balanced dietary intake showed good anti-inflammatory effects, though this was not fully reflected in vegetarian population in the real world, probably due to insufficient energy intake in the vegetarian population.

Association between weight, weight perception, weight teasing and mental health among adolescents.

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.

Mutations influence the conformational dynamics of the GDP/KRAS complex.

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.

Conformational States of the GDP- and GTP-Bound HRAS Affected by A59E and K117R: An Exploration from Gaussian Accelerated Molecular Dynamics.

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.

ORC6 acts as an effective prognostic predictor for non­small cell lung cancer and is closely associated with tumor progression.

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.

Dietary pattern and precocious puberty risk in Chinese girls: a case-control study.

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.

YTHDC1 as a tumor progression suppressor through modulating FSP1-dependent ferroptosis suppression in lung cancer.

Ferroptosis is a regulated cell death process initiated by iron-dependent phospholipid peroxidation and is mainly suppressed by GPX4-dependent and FSP1-dependent surveillance mechanisms. However, how the ferroptosis surveillance system is regulated during cancer development remains largely unknown. Here, we report that the YTHDC1-mediated m6A epigenetic regulation of FSP1 alleviates the FSP1-dependent ferroptosis suppression that partially contributes to the tumor suppressive role of YTHDC1 in lung cancer progression. YTHDC1 knockdown promoted the lung tumor progression and upregulated FSP1 protein level that resulted in ferroptosis resistance of lung cancer cells. Silencing FSP1 abrogated YTHDC1 knockdown-induced proliferation increase and ferroptosis resistance. Mechanistically, YTHDC1 binding to the m6A sites in the FSP1 3'-UTR recruited the alternative polyadenylation regulator CSTF3 to generate a less stable shorter 3'-UTR contained FSP1 mRNA, whereas YTHDC1 downregulation generated the longer 3'-UTR contained FSP1 mRNA that is stabilized by RNA binding protein HuR and thus led to the enhanced FSP1 protein level. Therefore, our findings identify YTHDC1 as a tumor progression suppressor in lung cancer and a ferroptosis regulator through modulating the FSP1 mRNA stability and thus suggest a ferroptosis-related therapeutic option for YTHDC1high lung cancer.

Dynamical characterization and multiple unbinding paths of two PreQ1 ligands in one pocket.

Riboswitches naturally regulate gene expression in bacteria by binding to specific small molecules. Class 1 preQ1 riboswitch aptamer is an important model not only for RNA folding but also as a target for designing small molecule antibiotics due to its well-known minimal aptamer domain. Here, we ran a total of 62.4 µs conventional and enhanced-sampling molecular dynamics (MD) simulations to characterize the determinants underlying the binding of the preQ1-II riboswitch aptamer to two preQ1 ligands in one binding pocket. Decomposition of binding free energy suggested that preQ1 ligands at α and ß sites interact with four nucleotides (G5, C17, C18, and A30) and two nucleotides (A12 and C31), respectively. Mg2+ ions play a crucial role in both stabilizing the binding pocket and facilitating ligand binding. The flexible preQ1 ligand at the ß site leads to the top of the binding pocket loosening and thus pre-organizes the riboswitch for ligand entry. Enhanced sampling simulations further revealed that the preQ1 ligand at the α site unbinds through two orthogonal pathways, which are dependent on whether or not a ß site preQ1 ligand is present. One of the two preQ1 ligands has been identified in the binding pocket, which will aid to identify the second preQ1 Ligand. Our work provides new information for designing robust ligands.

The characteristics and risk factors of e-cigarette use among adolescents in Shanghai: A case-control study.

INTRODUCTION: This study was conducted to explore the characteristics and risk factors of e-cigarette use in adolescents, aiming for tobacco control and reducing e-cigarette use in this population. METHODS: Using 1:1 matching, 88 students from three vocational high schools in Shanghai were recruited to conduct a case (using e-cigarettes) - control (not using e-cigarettes) study. Group interviews and questionnaire surveys were used for this qualitative and quantitative mixed-methods study. The keywords were extracted from the interview data and analyzed by the Colaizzi seven-step method. RESULTS: The characteristics of adolescents' use of e-cigarettes include young age at first use, consumption of a large amount, as well as smoking in discrete locations in order to hide from adults. The reasons for using e-cigarettes include curiosity and wanting to replace traditional cigarettes. The risk factors of using e-cigarettes include insufficient understanding of the harm of e-cigarettes at the individual level (The positive outcome expectancy points: Z= -3.746, p<0.001; The negative outcome expectancy points: Z= -3.882, p<0.001), peer influence at the interpersonal level (χ2=6.510, p<0.01), and the influence of social and environmental factors such as e-cigarette sales in the stores and WeChat Moments (p<0.05 for all associations). CONCLUSIONS: Having friends who use e-cigarettes, curiosity and sales exposure about e-cigarettes are important factors affecting the use of e-cigarettes by adolescents. It is necessary to strengthen the publicity of the potential hazards of e-cigarettes and to reduce overall usage by improving relevant laws and regulations.

Vegetarians have an indirect positive effect on sleep quality through depression condition.

This study aimed to assess the association between a vegetarian diet and sleep quality among Chinese healthy adults and explore potential contributing factors. A cross-sectional study was conducted with 280 vegetarians and 280 age- and sex-matched omnivores from Shanghai, China. The Pittsburgh Sleep Quality Index (PSQI) and the Central Depression Scale (CES-D) were used to assess sleep and depression condition, respectively. A validated semi-quantitative food frequency questionnaires (SQFFQ) was employed to assess dietary intakes, and body composition was measured with InBody720. Multi-linear regression and logistic regression analysis were performed for the data analysis. The sleep quality was significantly better in the vegetarians than in the omnivores (PSQI score: 2.80 ± 2.02 vs. 3.27 ± 1.90, p = 0.005). The proportion of vegetarians who reported self-satisfied sleep was also higher than that of the omnivores (84.6% vs. 76.1%, p = 0.011). However, after adjusted for the depression condition (CES-D scores), the difference in sleep quality between vegetarians and omnivores became insignificant (p = 0.053). Compared to omnivores, vegetarians had lower depression scores (CES-D: 9.37 ± 6.24 vs. 10.94 ± 7.00, p = 0.006). After controlling for confounding factors, there was positive association between depression condition and sleep quality (ß = 0.106, 95%CI: 0.083 to 0.129, p < 0.001). Similarly, participants with better CES-D score had a lower risk of sleep disorders after controlling for the same confounding factors (OR = 1.109, 95%CI: 1.072 to 1.147, p < 0.001). Different contributing factors were reported in the vegetarian group and omnivore group. In conclusion, a vegetarian diet might improve sleep quality by moderating mental health, particularly depression condition.

Investigation of Diagnostic and Prognostic Value of CLEC4M of Non-Small Cell Lung Carcinoma Associated with Immune Microenvironment.

Purpose: C-type lectin domain family 4 member M (CLEC4M) has been found to be involved in the occurrence and development of cancer, but its role in NSCLC remains to be fully explored. Our work aims to evaluate the diagnostic and prognostic value of CLEC4M in NSCLC and to investigate the underlying mechanisms of CLEC4M in the immune microenvironment of NSCLC. Methods: Integrating publicly accessible data and clinical tissue samples to verify the expression of CLEC4M in NSCLC. The diagnostic value of CLEC4M was determined by receiver operating characteristic (ROC) curve. Kaplan-Meier survival analysis, nomogram plot, univariate and multivariate Cox regression models were performed to evaluate the prognostic impact of CLEC4M on NSCLC patients. The correlation between CLEC4M and tumor immune infiltration was estimated using TIMER and UALCAN databases. Functional assessments including GO, KEGG pathway and GSEA analyses were implemented to illustrate the potential mechanisms of CLEC4M in NSCLC. Results: CLEC4M was significantly downregulated in NSCLC tissue, as confirmed by immunohistochemistry of clinical tissues. The high AUC value of ROC curves demonstrated the diagnostic accuracy of CLEC4M in NSCLC. Additionally, low CLEC4M expression was associated with poor survival in NSCLC patients. Furthermore, CLEC4M was found to be significantly associated with tumor immune infiltration, and CLEC4M may be involved in immune activation and proliferation inhibition through the functional assessment, suggesting that CLEC4M may be a therapeutic target for NSCLC patients. Conclusion: Our findings reveal CLEC4M is significantly downregulated in NSCLC tissues, and illustrate the diagnostic and prognostic value of CLEC4M in NSCLC, as well as its potential serve as an immune-related therapeutic target.

Clinical-functional characteristics and risk of exacerbation and mortality among more symptomatic patients with chronic obstructive pulmonary disease: a retrospective cohort study.

OBJECTIVES: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 classified chronic obstructive pulmonary disease (COPD) patients into more and less symptomatic groups. This study aimed to analyze the clinical characteristics, risk of future exacerbation and mortality among patients in more symptomatic group. DESIGN: A retrospective cohort study. SETTING: Data were obtained from patients enrolled in a database setup by Second Xiangya Hospital of Central South University. PARTICIPANTS: 1729 stable COPD patients listed from September 2017 to December 2019 in the database. The patients were classified into more and less symptomatic groups based on GOLD 2017 report. OUTCOMES: All patients were followed up for 18 months. We collected baseline data and recorded the number of exacerbations and mortality during follow-up. RESULTS: The more symptomatic patients were older, had higher Clinical COPD Questionnaire (CCQ) scores, more severe airflow limitation and higher number of exacerbations and hospitalizations in the past year (P < 0.05). Logistic regression showed that having more symptoms correlated with the CCQ scores and exacerbations in the past year (P < 0.05). After patients were followed up, there were higher numbers of exacerbations, hospitalizations and mortality rates in more symptomatic patients (P < 0.05). The multivariate model showed that age more than 65 years (OR = 2.047, 95% CI = 1.020-4.107) and COPD assessment test scores more than 30 (OR = 2.609, 95% CI = 1.339-5.085) were independent risk factors for mortality, whereas current smoker (OR = 1.565, 95% CI = 1.052-2.328), modified Medical Research Council scores (OR = 1.274, 95% CI = 1.073-1.512) and exacerbations in the past year (OR = 1.061, 95% CI = 1.013-1.112) were independent risk factors for exacerbation in more symptomatic patients (P < 0.05). CONCLUSIONS: More symptomatic COPD patients have worse outcomes. In addition, several independent risk factors for exacerbation and mortality were identified. Therefore, clinicians should be aware of these risk factors and take them into account during interventions.

The effects of different inhalation therapies on less symptomatic chronic obstructive pulmonary disease patients in a Chinese population: a real-world study.

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) document suggests that patients with chronic obstructive pulmonary disease (COPD) should be divided into a less symptomatic group. Moreover, single-inhaled drugs are recommended as initial inhalation therapy for them. However, many less symptomatic patients are provided double or triple-inhaled drugs as initial therapy in the real world. This study aimed to describe the inhalation prescriptions and compare the effects of different inhalation therapies on less symptomatic COPD patients. PATIENTS AND METHODS: This was an observational study. Stable COPD patients were recruited and divided into a less symptomatic group including Groups A and C based on the GOLD 2019 document. We collected the data of inhalation therapies prescriptions. Then, the patients were classified into long-acting muscarinic antagonist (LAMA), long-acting ß2-agonist (LABA) + inhaled corticosteroid (ICS), LABA + LAMA, and LABA + LAMA + ICS groups. All the patients were followed up for 1 year to collect exacerbation and mortality data. RESULTS: We found that only 45.4% of patients in Group A and 43.6% of patients in Group C received reasonable inhalation therapy in reference to the GOLD document. In addition, the LAMA group had a higher forced expiratory volume in one second (FEV1), FEV1%pred, FEV1/forced vital capacity and peak expiratory flow compared with LABA + ICS, LABA + LAMA and LABA + LAMA + ICS groups. However, we did not find any significant differences of exacerbation, hospitalization and mortality during the follow-up among different inhalation therapies groups on less symptomatic COPD patients. CONCLUSION: Over half of the less symptomatic patients received inhalation therapy that were inconsistent with the GOLD document recommendations in a Chinese population in the real world. In fact, the single inhaled drug of LAMA should be recommended and pulmonary function is not a good indicator for the choice of initial inhalation therapy in less symptomatic COPD patients.KEY MESSAGESOver half of the less symptomatic COPD patients received inhalation therapy that were inconsistent with the GOLD document recommendations in a Chinese population in the real world.The clinicians should offer a single inhaled drug of LAMA to less symptomatic COPD patients and pulmonary function is not a good indicator for the choice of initial inhalation therapy.

Eating Disorders and Metabolic Diseases.

Eating disorders are complex diseases with multifactorial causes. According to the Diagnostic and Statistical Manual of Mental Disorders text version (DSM-5-TR) and the WHO International Classification of Diseases and Related Health Problems (ICD-11), the major types of eating disorders include anorexia nervosa, bulimia nervosa, and binge eating disorder. The prevalence of eating disorders is alarmingly increasing globally. Moreover, the COVID-19 pandemic has led to more development and worsening of eating disorders. Patients with eating disorders exhibit high rates of psychiatric comorbidities and medical comorbidities such as obesity, diabetes, and metabolic syndrome. This paper aims to review and discuss the comorbidities of eating disorders with those metabolic diseases. Eating disorder treatment typically includes a combination of some or all approaches such as psychotherapy, nutrition education, and medications. Early detection and intervention are important for the treatment of eating disorders.

Human umbilical cord mesenchymal stem cells prevent glucocorticoid-induced osteonecrosis of the femoral head by promoting angiogenesis.

The impairment of angiogenesis is an outstanding pathogenic characteristic of glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH). Human umbilical cord mesenchymal stem cells (hUC-MSCs) have been used in several diseases models, which were reported to be involved in the angiogenesis. However, whether hUC-MSCs suppress the GC-induced ONFH via promoting angiogenesis is still unclear. hUC-MSCs were isolated from the Wharton's jelly using the explant culture method. A GC-induced ONFH model was established in vitro and in vivo. The angiogenesis, proliferation and migration ability of HMECs were determined using the tube-forming, CCK-8, transwell and scratching assays in vitro. The protective role of hUC-MSCs in GC-induced ONFH was evaluated using micro-CT scanning and histological, immunohistochemical (IHC) and Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assays in vivo. The results showed that hUC-MSCs treatment improved the tube-forming, proliferation and migration ability of HMECs in vitro. Moreover, hUC-MSCs treatment enhanced the integrity of trabecular bone of the femoral head, and the tube-forming ability in vivo. hUC-MSCs prevent the femoral head against necrosis and damage caused by GCs though promoting angiogenesis.

Electrochemiluminescence Sensor Based on CTS-MoS2 and AB@CTS with Functionalized Luminol for Detection of Malathion Pesticide Residues.

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.

Deciphering Conformational Changes of the GDP-Bound NRAS Induced by Mutations G13D, Q61R, and C118S through Gaussian Accelerated Molecular Dynamic Simulations.

The conformational changes in switch domains significantly affect the activity of NRAS. Gaussian-accelerated molecular dynamics (GaMD) simulations of three separate replicas were performed to decipher the effects of G13D, Q16R, and C118S on the conformational transformation of the GDP-bound NRAS. The analyses of root-mean-square fluctuations and dynamics cross-correlation maps indicated that the structural flexibility and motion modes of the switch domains involved in the binding of NRAS to effectors are highly altered by the G13D, Q61R, and C118Smutations. The free energy landscapes (FELs) suggested that mutations induce more energetic states in NRAS than the GDP-bound WT NRAS and lead to high disorder in the switch domains. The FELs also indicated that the different numbers of sodium ions entering the GDP binding regions compensate for the changes in electrostatic environments caused by mutations, especially for G13D. The GDP-residue interactions revealed that the disorder in the switch domains was attributable to the unstable hydrogen bonds between GDP and two residues, V29 and D30. This work is expected to provide information on the energetic basis and dynamics of conformational changes in switch domains that can aid in deeply understanding the target roles of NRAS in anticancer treatment.

Synaptopathy in Guinea Pigs Induced by Noise Mimicking Human Experience and Associated Changes in Auditory Signal Processing.

Noise induced synaptopathy (NIS) has been researched extensively since a large amount of synaptic loss without permanent threshold shift (PTS) was found in CBA mice after a brief noise exposure. However, efforts to translate these results to humans have met with little success-and might not be possible since noise exposure used in laboratory animals is generally different from what is experienced by human subjects in real life. An additional problem is a lack of morphological data and reliable functional methods to quantify loss of afferent synapses in humans. Based on evidence for disproportionate synaptic loss for auditory nerve fibers (ANFs) with low spontaneous rates (LSR), coding-in-noise deficits (CIND) have been speculated to be the major difficulty associated with NIS without PTS. However, no robust evidence for this is available in humans or animals. This has led to a re-examination of the role of LSR ANFs in signal coding in high-level noise. The fluctuation profile model has been proposed to support a role for high-SR ANFs in the coding of high-level noise in combination with efferent control of cochlear gain. This study aimed to induce NIS by a low-level, intermittent noise exposure mimicking what is experienced in human life and examined the impact of the NIS on temporal processing under masking. It also evaluated the role of temporal fluctuation in evoking efferent feedback and the effects of NIS on this feedback.

Body Weight, Weight Self-Perception, Weight Teasing and Their Association with Health Behaviors among Chinese Adolescents-The Shanghai Youth Health Behavior Survey.

Weight-related status has been associated with the physical and psychological health of adolescents. This cross-sectional study evaluated three different kinds of weight-related statuses (Body Mass Index (BMI), weight self-perception and weight teasing from others) among Chinese adolescents and identified their associations with health risk behaviors (lack of healthy dietary behavior, unhealthy dietary behavior, binge eating behavior, lack of physical activity (PA), sedentary behaviors (SB) and sleep disturbance). A stratified random cluster sampling method was used to select 10,070 students aged 11−18 years old from schools in Shanghai. Self-reported questionnaires were collected, weight-related statuses were divided into three categories and six specific health risk behaviors were classified into two groups: positive or negative. Overall, 27.82% of the adolescents were classified as being overweight and obese (35.61% of boys and 18.21% of girls), 43.45% perceived themselves as too heavy and 30.46% experienced weight teasing in the past. Among overweight or obese participants, 50.55% have been teased about their weight, and 77.48% perceived themselves as too heavy. Weight perception and weight teasing were significantly associated with health risk behaviors rather than the actual body weight status based on BMI, especially regarding binge eating behavior (body weight status (BMI): p > 0.05, underweight perception: OR = 1.18, 95%CI 1.03−1.34; weight teasing for more than once a year: OR = 2.00, 95%CI 1.76−2.27). In addition, weight perception and weight teasing were significantly associated with health risk behaviors, mainly in normal and overweight/obese groups but not in underweight groups. Weight teasing and weight self-perception play an independent and stronger role than actual body weight in the health behaviors of adolescents. This calls for more attention and intervention to reduce peer bullying and stigmas on weight among adolescents.