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.

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.

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.

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.

A Pilot Study of a Videoconferencing-Based Binge Eating Disorder Program in Overweight or Obese Females.

Background:There has been increasing interest in using videoconferencing in health care, but limited research was conducted in Binge Eating Disorder (BED) patients. This 3-month pilot study aimed to assess the feasibility, acceptability, and preliminary efficacy of a videoconferencing (VC)-based treatment program in overweight and obese females with BED.Methods:Eighteen participants, aged 20-73, were diagnosed and randomized into either a face-to-face (F2F) group or a VC-based group. In the F2F group, participants received 12 one-on-one weekly counseling sessions from a Licensed Mental Health Counselor and Registered Dietitian Nutritionist. In the VC group, participants received the same counseling through an online telemedicine software. Measured outcomes include retention, adherence to treatment, and attitudinal and behavioral changes of participants.Results:In the end of study, of the 9 participants randomized into each group, 8 (88.9%) F2F participants and 4 (44.4%) VC participants completed the study. On average, F2F finishers attended 94.8% of sessions and completed 66.2% of dietary diaries. VC finishers attended 95.8% of sessions and completed 55.4% of diaries. No changes in weight and binge eating episode were observed in either group. F2F finishers had significant improvement on uncontrolled eating (p = 0.01), emotional eating (p = 0.004), food addiction diagnosis (p = 0.04), loss of control (p = 0.04), and clinical significance (p = 0.04). VC finishers observed significant improvements in eating disorder examination shape concern (p = 0.03) and global score (p = 0.03).Conclusion:VC-based treatment program is feasible and could be effective for BED patients. Long-term large-scale randomized clinical trials are warranted to further assess the efficacy.

Anti-G250 nanobody-functionalized nanobubbles targeting renal cell carcinoma cells for ultrasound molecular imaging.

Traditional imaging examinations have difficulty in identifying benign and malignant changes in renal masses. This difficulty may be solved by ultrasound molecular imaging based on targeted nanobubbles, which could specifically enhance the ultrasound imaging of renal cell carcinomas (RCC) so as to discriminate benign and malignant renal masses. In this study, we aimed to prepare anti-G250 nanobody-functionalized targeted nanobubbles (anti-G250 NTNs) by coupling anti-G250 nanobodies to lipid nanobubbles and to verify their target specificity and binding ability to RCC cells that express G250 antigen and their capacity to enhance ultrasound imaging of RCC xenografts. Anti-G250 nanobodies were coupled to the lipid nanobubbles using the biotin-streptavidin bridge method. The average particle diameter of the prepared anti-G250 NTNs was 446 nm. Immunofluorescence confirmed that anti-G250 nanobodies were uniformly distributed on the surfaces of nanobubbles. In vitro experiments showed that the anti-G250 NTNs specifically bound to G250-positive 786-O cells and HeLa cells with affinities of 88.13% ± 4.37% and 71.8% ± 5.7%, respectively, and that they did not bind to G250-negative ACHN cells. The anti-G250 NTNs could significantly enhance the ultrasound imaging of xenograft tumors arising from 786-O cells and HeLa cells compared with blank nanobubbles, while the enhancement was not significant for xenograft tumors arising from ACHN cells. Immunofluorescence of tumor tissue slices confirmed that the anti-G250 NTNs could enter the tissue space through tumor blood vessels and bind to tumor cells specifically. In conclusion, anti-G250 nanobody-functionalized targeted nanobubbles could specifically bind to G250-positive RCC cells and enhance the ultrasound imaging of G250-positive RCC xenografts. This study has high-potential clinical application value for the diagnosis and differential diagnosis of renal tumors.

Sex differences in disordered eating and food addiction among college students.

This cross-sectional study aimed to assess sex differences and weight status differences in disordered eating behaviors (DEB) and food addiction (FA) along with their co-occurrence among college students. Self-reported demographic and weight information, the Eating Attitude Test (EAT-26), and Yale Food Addiction Scale (YFAS) were collected from 965 college students. Participants included 703 (72.8%) female, 720 (74.8%) white, and ranged in age from 18 to 25 years old. Female college students had a significantly higher prevalence of DEB (11.6% vs. 5.7%, p = 0.007, odds ratio (OR) = 2.19) and higher prevalence of FA (12.3% vs. 4.6%, p < 0.0001, OR = 3.04) than male students. The co-occurrence was also significantly higher in female students than in male students (5.4% vs. 1.9%, p = 0.022, OR = 3.03). Male and female obese participants versus healthy weight participants had higher prevalence of DEB (15.1% vs.8.6%, p = 0.047, OR = 1.91) and FA (19.4% vs. 8.9%, p = 0.002, OR = 2.51). Higher prevalence of DEB was positively associated with FA regardless of sex and weight status. The findings indicate higher prevalence of disordered eating in female college students than male students and add to the research on sex differences in food addiction. The co-occurrence of both and association between high prevalence of DEB and FA warrant additional research on the incidence as well as factors that contribute to sex differences. Understanding sex differences and comorbidity regarding DEB and FA is critical for the prevention and treatment of eating related disorders.

Clinical therapeutic effect and safety of celecoxib in treating knee osteoarthritis.

The clinical therapeutic effect and safety of celecoxib in treating knee osteoarthritis were observed. 180 patients who have been confirmed with knee osteoarthritis in our hospital were selected as research objects. They were randomly divided into research group and control group, each containing 90 patients. The control group was given with diclofenac sodium therapy, while the research group was subjected to celecoxib therapy. The total therapeutic response rates between the two groups were observed and compared. The total therapeutic response rate of research groups was relatively higher, P<0.05. There was no significant difference in pain score, erythrocyte sedimentation rate (ESR), quality of life score (QLS) between two groups before treatment, P>0.05. However, these indexes of research group were superior then the control group after treatment，P<0.05. In addition, the rate of adverse reaction of research group was also lower than that of control group, P<0.05. Using celecoxib to treat knee osteoarthritis can significantly improve the total therapeutic rate and reduce the rate of adverse effect.

Double-Balanced Graphene Integrated Mixer with Outstanding Linearity.

A monolithic double-balanced graphene mixer integrated circuit (IC) has been successfully designed and fabricated. The IC adopted the cross-coupled resistive mixer topology, integrating four 500 nm-gate-length graphene field-effect transistors (GFETs), four on-chip inductors, and four on-chip capacitors. Passive-first-active-last fabrication flow was developed on 200 mm CMOS wafers. CMOS back-end-of-line processes were utilized to realize most fabrication steps followed by GFET-customized processes. Test results show excellent output spectrum purity with suppressed radio frequency (RF) and local oscillation (LO) signals feedthroughs, and third-order input intercept (IIP3) reaches as high as 21 dBm. The results are compared with a fabricated single-GEFT mixer, which generates IIP3 of 16.5 dBm. Stand-alone 500 nm-gate-length GFETs feature cutoff frequency 22 GHz and maximum oscillation frequency 20.7 GHz RF performance. The double-balanced mixer IC operated with off-chip baluns realizing a print-circuit-board level electronic system. It demonstrates graphene's potential to compete with other semiconductor technologies in RF front-end applications.

Stable self-compliance resistive switching in AlOδ/Ta2O(5-x)/TaOy triple layer devices.

Stable self-compliance property was observed in the AlOδ/Ta2O(5-x)/TaOy triple-layer resistive random access memory structure. The impact of AlOδ barrier layer was studied with different thicknesses. Endurance of more than 10(10) cycles and data retention for more than 3 h at 125 °C were demonstrated. All the measurements were carried out without external current compliance and no hard breakdown was observed. Systematic analysis reveals the self-compliance property is due to the built-in series resistance of the thin AlOδ barrier layer. A model is proposed to explain this self-compliance property.

Atomistic study of dynamics for metallic filament growth in conductive-bridge random access memory.

The growth dynamics for metallic filaments in conductive-bridge resistive-switching random access memory (CBRAM) are studied using the kinetic Monte Carlo (KMC) method. The physical process at the atomistic level is revealed in explaining the experimental observation that filament growth can originate at either the cathode or the anode. The statistical nature of the filament growth is best shown by the random topography of dendrite-like conductive paths obtained. Critical material properties, such as charged-particle mobility in the switching layer of a solid electrolyte or a dielectric, are mapped to KMC model parameters through activation energy, etc. The accuracy of the simulator is established by the good agreement between the simulated forming time and the measured data.

A first-principle investigation of double-side CVD catalyst metal/graphene contacts.

In this paper, the double-side contact (DSC) properties of CVD catalyst metals and graphene (Gr) are studied by first-principle methods. Our calculation shows that two special catalyst metals Pt and Ir would have extremely small contact resistances in DSC and the physical origination of such phenomenon is explicitly analyzed. Different from the common physisorption metal which would keep Gr's intrinsic conical dispersion, the simulation results of Pt and Ir in DSC show chemisorption characters due to the charge redistribution triggered exchange-transfer mechanism. The symmetry Pauli-exclusion and charge transfer effects in DSC complexes are found to play an important role in the intriguing transition. These results may bring new information to seek a suitable lead structure for 2D materials.

Association between NINJ2 gene polymorphisms and ischemic stroke: a family-based case-control study.

Novel susceptibility genes related to ischemic stroke (IS) are proposed in recent literatures. Population-based replicate studies would cause false positive results due to population stratification. 229 recruit IS patients and their 229 non-IS siblings were used in this study to avoid population stratification. The family-based study was conducted in Beijing from June 2005 to June 2012. Association between SNPs and IS was found in the sibship discordant tests, and the conditional logistic regression was performed to identify effect size and explore gene-environment interactions. Significant allelic association was identified between NINJ2 gene rs11833579 (P = 0.008), protein kinase C η gene rs2230501 (P = 0.039) and IS. The AA genotype of rs11833579 increased 1.51-fold risk (95% CI 1.04-3.46; P = 0.043) of IS, and it conferred susceptibility to IS only in a dominant model (OR 2.69; 95% CI 1.06-6.78; P = 0.036]. Risk of IS was higher (HR 3.58; 95% CI 1.54-8.31; P = 0.003) especially when the carriers of rs11833579 AA genotype were smokers. The present study suggests A allele of rs11833579 may play a role in mediating susceptibility to IS and it may increase the risk of IS together with smoking.

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.

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.

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.

Extensimonas vulgaris gen. nov., sp. nov., a member of the family Comamonadaceae.

A novel strain, named S4(T), was obtained from industrial wastewater in Xiaoshan, Zhejiang Province, China. Cells were Gram-negative, neutrophilic and non-spore-forming and moved by means of a polar flagellum. Normal cells were 0.8-0.9 × 1.3-1.9 µm and the cells elongated to 10-25 µm when cultivated at high temperatures. Strain S4(T) grew at 15-50 °C (optimum at 48 °C), pH 5.5-8.5 (optimum 7.0-7.5) and 0-2% (optimum 0.5%) (w/v) NaCl. Ubiquinone-8 was the predominant respiratory quinone. C16:0, summed feature 3 (C16:1ω7c and/or iso-C15:0 2-OH) and C17:0 cyclo were the major cellular fatty acids. The major 3-OH fatty acid was C10:0 3-OH. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and an unknown aminoglycolipid. The genomic DNA G+C content was 68.8 mol%. Based on 16S rRNA gene sequences alignment, the most closely related strains were members of the genera Comamonas (94.6-95.6% similarities), Giesbergeria (94.9-95.6%), Acidovorax (94.8-95.4%), Brachymonas (94.1-95.2%) and Macromonas (95.1%). Phylogenetic analysis showed the closest relatives of strain S4(T) were members of the genus Macromonas. Based on phenotypic and phylogenetic characteristics, we suggest that strain S4(T) represents a novel species of a new genus of the family Comamonadaceae, for which the name Extensimonas vulgaris gen. nov., sp. nov. is proposed. The type strain of Extensimonas vulgaris is S4(T) (=CGMCC 1.10977(T)=JCM 17803(T)).

A theoretical model for metal-graphene contact resistance using a DFT-NEGF method.

The contact resistance (R(c)) between graphene and metal electrodes is of crucial importance for achieving potentially high performances for graphene devices. However, previous analytical models based on Landauer's approach have failed to include the Fermi velocity difference between the graphene under the metal and the pure graphene channel. Hereby we report a theoretical model to estimate the R(c) using density-functional theory and non-equilibrium Green's function methods. Our model not only presents a clear physical picture of the metal-graphene contacts, but also generates R(c) values which are in good agreement with the experimental results: 210 Ω µm for double-sided Pd contacts compared with 403 Ω µm for single-sided Pd contact.

[Association study between PDE4D gene polymorphism and ischemic stroke].

OBJECTIVE: To investigate the linkage and association between rs966221 (SNP 83) in PDE4D gene with stroke and related traits in ischemic stroke families. METHODS: Ischemic stroke families including ischemic stroke patients and their siblings and/or parents were recruited. Generalized estimating equation (GEE) was used to adjust for with-in family correlations and other potential confounding factors. Non-parameter linkage analysis and family based association test (FBAT) were applied to explore the relationship between rs966221 polymorphism and ischemic stroke together with its related traits. RESULTS: In the study 276 ischemic stroke families with totally 776 participants were enrolled. Apolipoprotein B (apoB), carotid intima media thickness (cIMT), high-density lipoprotein cholesterol and blood pressure were associated with ischemic stroke. In family based association test, after being adjusted for related chronic diseases, rs966221 C allele was found to be associated with cIMT in the dominant model (P=0.019), TT genotype (P=0.019) and CT genotype (P=0.007) were associated with cIMT significantly. After being adjusted for potential confounding factors, evidence of linkage was observed for rs966221 with apoB (P<0.001), high-sensitivity C-reactive protein (P=0.003) and systolic blood pressure (P=0.036). CONCLUSION: Abnormal serum lipid, blood pressure and increasing cIMT were associated with ischemic stroke, and linkage was observed for with apoB, high-sensitivity C-reactive protein, and systolic blood pressure; rs966221 C allele was probably associated with cIMT.

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.