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RAB42 is a member of the RAS family. However, the roles and driving forces for RAB42 in tumors remain elusive. In this study, we performed a comprehensive pan-cancer analysis of the roles and regulatory mechanisms of RAB42 using bioinformatics and experiments. Online databases such as Sanger Box, ACLBI and TIDE were used to search for the expression levels, prognostic value and immune features of RAB42. We observed that RAB42 expression was upregulated in most tumors and was closely associated with poor prognosis. Enrichment analysis indicated that RAB42 was related to multiple biological functions, especially the immune process. RAB42 expression had a positive correlation with immune cell infiltration and immune checkpoint gene expression. RAB42 had a high predictive value for immunotherapy efficiency. Our study screened out susceptible drugs for the RAB42 protein by sensitivity analysis and virtual screening. Many key driver genes such as TP53 contributed to RAB42 expression. DNA methylation, super-enhancer and non-coding RNAs were the epigenetic factors responsible for RAB42 expression. In brief, RAB42 could serve as a diagnostic and prognostic biomarker in many tumor types. RAB42 might be a predictive biomarker and a new target for immunotherapy. Genetic and epigenetic factors were essential for RAB42 overexpression in tumors. [ABSTRACT FROM AUTHOR]

Simple Summary: Based on the latest research, cancer cells prefer glutamine to glucose. Therefore, it is more worthwhile to explore the regulatory mechanism of glutamine metabolism in cancer cells. Super enhancers are critical for the gene transcriptional programs responsible for cell fate by interacting with various transcription factors. The transcription factor HSF1 exerts a multifaced role in tumorigenesis. However, the relevance of HSF1 to super enhancers in tumors remains obscure. Therefore, this study focused on the mechanism underlying super-enhancer activation and its relationship to HSF1 in CRC. Here, we performed a super-enhancer landscape in CRC and we screened out an HSF1-mediated super enhancer, lncRNA-LINC00857, by lncRNA microarray. We discovered that HSF1 could stimulate acetyltransferase P300-mediated super-enhancer activity to facilitate LINC00857 expression, contributing to SLC1A5/ASCT2-mediated glutamine transport. In addition, we validated that targeting the HSF1/LINC00857/ANXA11 axis may provide a valuable therapeutic strategy against CRC. Super enhancers are critical for the gene transcription responsible for cell fate by interacting with transcription factors. However, the relevance of HSF1 to super enhancers in tumors remains obscure. We profiled H3K27ac enrichment by chromatin immunoprecipitation sequencing. HSF1-mediated lncRNAs were identified by lncRNA microarray. The characteristics of LINC00857 were explored by in vitro and in vivo assays. The mechanism was studied via chromatin immunoprecipitation, RNA immunoprecipitation, and HSF1/ANXA11 knockout mice. We found that super enhancers occupied multiple gene loci in colorectal cancer. We screened out an HSF1-mediated super enhancer, lncRNA-LINC00857, which exerts its characteristics in promoting cell growth via regulating glutamine metabolism. Notably, HSF1 could stimulate the super-enhancer activity of LINC00857 by the enrichment of acetyltransferase P300 to its gene loci, contributing to LINC00857 transcription. In turn, nuclear LINC00857 cooperated with HSF1 to promote ANXA11 transcription, which modulated SLC1A5/ASCT2 protein expression by binding competitively to miR-122-5p. The knockout of ANXA11 attenuated colorectal cancer formation in vivo. Collectively, we shed light on a closely cooperative machinery between HSF1 and super enhancers. HSF1 could stimulate acetyltransferase P300-mediated super-enhancer activity to facilitate LINC00857 expression, contributing to SLC1A5-mediated glutamine transport. Targeting the HSF1/LINC00857/ANXA11 axis may provide a valuable therapeutic strategy against colorectal cancer. [ABSTRACT FROM AUTHOR]

Background: The independent association of neck circumference (NC) on elevated blood pressure is still uncertain in adults of China. The aim of this study is to explore such association and investigate the predictive value of NC on hypertension.Methods: A total of 4279 adults aged 20-80 years participated in the cross-sectional study in 2014. Anthropometric information, NC, body composition indexes such as waist circumference, hip circumference and body fat percentage, and blood pressure were measured. General linear regression model was used to explore the association between NC and blood pressure; Logistic regression models were fitted to calculate the multi-variable adjusted prevalence, and the association of NC with hypertension.Results: The overall prevalence of hypertension and pre-hypertension were 11.05 and 23.63%, respectively. NC was positively associated with both SBP and DBP (p < 0.001). The adjusted prevalence of hypertension increased with elevated NC quartiles in both sexes (p for trend < 0.001), from 17.81 to 42.93% in male and 9.72 to 21.31% in female. For male, NC was only associated with hypertension (OR: 1.15, 95% CI: 1.05-1.25) but not with pre-hypertension (OR: 0.97, 95% CI: 0.88-1.06). However, in female, NC was associated with both pre-hypertension and hypertension, the BMI adjusted ORs were 1.15 (1.03-1.28) and 1.24 (1.14-1.34). The sex-specific AUCs for NC predicting hypertension were 0.633 in male and 0.663 in female, similar with AUCs of other body fat indexes.Conclusions: NC was associated with both pre-HTN and HTN independent from other body composition indexes. NC is a simple and useful anthropometric index to identify elevated blood pressure in Chinese adults. [ABSTRACT FROM AUTHOR]

Kidney fibrosis is usually the final manifestation of a wide variety of renal diseases. Recent years, research reported that long non‐coding RNAs (lncRNAs) played important roles in a variety of human diseases. However, the role and underlying mechanisms of lncRNAs in kidney fibrosis were complicated and largely unclear. In our study, we constructed the cell model of renal fibrosis in HK2 cells using transforming growth factor β1 (TGF‐β1) and found that lncRNA maternally expressed gene 3 (MEG3) was downregulated in TGF‐β1‐induced renal fibrosis. We then found that overexpressed MEG3 inhibited the TGF‐β1‐induced promotion of epithelial–mesenchymal transition, cell viability, and proliferation. Furthermore, we demonstrated that DNA methyltransferases 1 (DNMT1) regulated the MEG3 expression by altering the CpGs methylation level of MEG3 promoter in TGF‐β1‐induced renal fibrosis. In addition, we further revealed that miR‐185 could regulate the DNMT1 expression and thus, modulate the MEG3 in TGF‐β1‐induced renal fibrosis. Ultimately, our study illustrated that the modulation of the miR‐185/ DNMT1/ MEG3 pathway exerted important roles in TGF‐β1‐induced renal fibrosis. In summary, our finding displayed a novel regulatory mechanism for TGF‐β1‐induced renal fibrosis, which provided a new potential therapeutic target for renal fibrosis. [ABSTRACT FROM AUTHOR]

Specific to the trajectory planning of intelligent electric vehicles with multi-constraints in some unknown environment, using rolling optimization principle of predictive model control for reference, an online trajectory planning algorithm based on a rolling window is proposed. Making full use of the local environmental information measured in real-time by intelligent electric vehicle, the path of continuous curvature is generated in the planning window by the Quintic Bézier curve and is optimized by the sequential quadratic planning algorithm. Furthermore, the optimal speed sequence for a given path is planed using the S-shaped curve velocity algorithm. Combining with the actual application scenario of an intelligent electric vehicle, the algorithm is simulated, and the trajectory planning experiment is carried out based on the actual environmental data. The results show that a safe trajectory with continuous curvature and optimal speed can be produced by using this algorithm in some unknown environment scenarios. [ABSTRACT FROM AUTHOR]

The study aimed to explore the independent association between expanded normal weight obesity categories and blood pressure among adults aged 20–80 years in China. By cross-sectional design, a total of 4279 adults living in Shaanxi Province, China, were selected from communities via multi-stage stratified cluster sampling in 2014. Information on anthropometric, body composition and blood pressure was collected and analysed. Expanded normal weight obesity (ENWO) categories were used to identify the level of bodyweight based on the combination of body mass index (BMI) and body fat percentage (BFP) categories. The age- and sex-standardised prevalence of hypertension increased within ENWO groups, from 10.12% in the underweight-low body fat group to 45.92% in the obesity-high body fat group. In under or normal weight participants, body fat percentage was found independently associated with hypertension in men, with an adjusted odds ratio of 3.69 in the fourth quartile of BFP compared with the first one. However, this effect was not observed in women. BFP was independently associated with increased risk of hypertension, especially in men. People with normal BMI should be re-identified as a high-risk population based on BFP level when it comes to hypertension prevention in primary healthcare settings. [ABSTRACT FROM AUTHOR]

Purpose: Adiposity is one of the important determinants of blood pressure. The aim of this study is to evaluate the association between blood pressure and body composition indices throughout the whole lifespan of healthy adults. Patients and Methods: This study was from an ongoing cross-sectional survey of the Chinese health wherein data included basic physiological parameters. Partial Pearson correlation analysis was used to assess the correlation between blood pressure and body composition indices. Multiple linear regression analysis was used to assess the association of body mass index, lean mass percent, and visceral fat rating against blood pressure in each age group. Results: In the whole population stratified by gender, while body mass index had the highest r-value of correlation with systolic blood pressure in both males (r = 0.296, p < 0.001) and females(r = 0.237, p < 0.001), and fat mass percent had the highest r -value of correlation with diastolic blood pressure in males (r = 0.351, p < 0.001) and females(r = 0.277, p < 0.001), the strength of association with blood pressure were similar across most of the body composition indices. In multiple linear regression analysis, both body mass index and visceral fat rating were positively while lean mass percent was negatively associated with blood pressure in all age groups in both genders, whereas all the association was weaker in the elderly compared to the younger. Conclusion: Maintain the total body fat in a favorable range and appropriately increase the body muscle mass is a strategy to reduce the occurrence of cardiovascular event by decreasing the risk of hypertension through the whole adult life. [ABSTRACT FROM AUTHOR]

Background: Absolute handgrip strength has been correlated withmetabolic profile and metabolic disease. Whether relative handgrip strength is also associated with metabolic disease has not been assessed. This study aimed at assessing the association of relative handgrip strength with metabolic profile and metabolic disease in the general population in China. Methods: Data were derived from an ongoing cross-sectional survey of the 2013 National Physical and Health in Shanxi Province, which involved 5520 participants. Multiple linear regression or multiple logistic regression analysis were used to assess the association of absolute/relative handgrip strength with the metabolic profile, preclinical, and established stages of metabolic diseases. Results: This study revealed that relative handgrip strength, that is when normalized to BMI, was associated with: (1) in both genders for more favorable blood lipid levels of high-density lipoprotein cholesterol [males: b = 0.19 (0.15, 0.23); females: b = 0.22 (0.17, 0.28)], low-density lipoprotein cholesterol [males: b = -0.14 (-0.23, -0.05); females: b = -0.19 (-0.31, -0.18)], triglycerides [males: b = -0.58 (-0.74, -0.43); females: b = -0.55 (-0.74, -0.36)] and total cholesterol [males: b = -0.20 (-0.31, -0.10); females: b = -0.19 (-0.32, -0.06)]; and better serum glucose levels in males [b = -0.30 (-0.46, -0.15)]. (2) lower risk of impaired fasting glucose in males {third quartile [OR = 0.66 (0.45-0.95)] and fourth quartile [OR = 0.46 (0.30-0.71)] vs. first quartile} and dyslipidemia in both genders {third quartile [males: OR = 0.65 (0.48-0.87); females: OR = 0.68 (0.53-0.86)] and fourth quartile [males: OR = 0.47 (0.35-0.64); females: OR = 0.47(0.36-0.61)] vs. first quartile}. (3) lower risk of hyperlipidemia in both genders third quartile [males: OR = 0.66 (0.50-0.87); females: OR = 0.57 (0.43-0.75)] and fourth quartile [males: OR = 0.35 (0.26-0.47); females: OR = 0.51 (0.38-0.70)] vs. first quartile. However, contrary to relative handgrip strength, higher absolute handgrip strength was associated with unfavorable metabolic profiles and higher risk of metabolic diseases. These paradoxical associations were retained even after adjusted for BMI by employed a multivariate analysis. Conclusion: We conclude that measurement of relative handgrip strength can be used as a reasonable clinical predictor of metabolic health and disease. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the prevalence of dyslipidemia and its risk factors in children and adolescents aged 7 to 18 years in China. Methods: A cross‐sectional study was conducted from November, 2013 to July, 2014. A total of 2283 children and adolescents from urban and rural areas in Hainan (South China) and Shaanxi Provinces (Northwest China) were selected using multi‐stage stratified cluster sampling method. Each participant underwent anthropometric and serum biochemical tests which included serum lipids and hepatitis B virus surface antigen (HBsAg). Results: The overall prevalence of high total cholesterol (TC), high triglyceride (TG), high low‐density lipoprotein cholesterol (LDL‐C), low high‐density lipoprotein cholesterol (HDL‐C), hyperlipidemia and dyslipidemia were 6.5%, 7.5%, 5.2%, 9.1%, 14.3%, and 20.6%, respectively. After standardization by age, girls had higher prevalence of high TC (8.2%), high LDL‐C (6.6%), and hyperlipidemia (16.4%), but lower prevalence of low HDL‐C (8.21%) than boys (4.2%, 3.4%, 11.9%, and 11.3%, respectively). The risk of dyslipidemia increased with age (OR = 1.067, 95% CI: 1.030‐1.106). Boys had a decreased risk of dyslipidemia (OR = 0.798, 95% CI: 0.640‐0.994). The restricted cubic spline revealed a linear relationship between BMI and the risk of dyslipidemia (P < .001). Subjects who were HBsAg positive had higher risk of dyslipidemia (OR = 1.550, 95% CI: 1.050‐2.287) compared with those who were HBsAg negative. Conclusions: Our study highlights the high prevalence of dyslipidemia in youth in China, and is the first study to reveal a positive association between positive status for HBsAg and abnormal lipid levels in children and adolescents. [ABSTRACT FROM AUTHOR]

Background: The present study was the first one aimed to investigate the current muscle fitness and its associated factors among children and adolescents in mainland China.Methods: From Nov 2013 to Jul 2014, 2283 children and adolescents aged 7-18 were recruited in Hainan and Shaanxi Provinces in China by cross-sectional design. Information on anthropometry and muscle fitness, measured by hand grip strength (GS), vertical jump (VJ) and sit-and-reach (SR), were collected. Analysis of covariance was performed by using general linear regression models to identify the association between BMI and muscle fitness.Results: The means of GS, VJ and SR in boys were 22.30 ± 11.55 kg, 22.93 ± 6.80 cm and 3.58 ± 7.31 cm, respectively, and in girls were 16.61 ± 6.87 kg, 18.11 ± 4.08 cm and 7.18 ± 5.72 cm, respectively. GS (from 8.26 kg in the 7-8-year-old group to 27.91 kg in the 17-18 group) and SR (from 1.75 cm in the-8-year-old group to 10.12 cm in the 17-18 group) increased with age (both p for trend < 0.001). Boys had higher GS and VJ, but significantly lower SR than girls in each age group (p < 0.001). After adjusting for age, sex, residential areas and study regions, GS increased with elevated BMI (compared with normal weight group, the regression coefficient for thinness and overweight/obesity were - 2.997(95%CI: -3.693 to - 2.301) and 1.220 (95%CI: 0.285 to 2.155), respectively. With the p values less than 0.001 and 0.011, respectively). For VJ, there was no difference found between normal weight group and overweight/obesity group (p = 0.550), but the thinness group had the lowest performance (regression coefficient = - 2.681, 95%CI from - 3.965 to - 1.397, p < 0.001). For SR, compared with normal weight group, the regression coefficients for thinness and overweight/obesity were - 1.313(95%CI: -2.228 to - 0.399) and - 1.623(95%CI: -3.216 to - 0.030) respectively, both p < 0.05.Conclusions: Increased body weight may have a positive association with isometric muscle strength measured by grip strength, but a negative one with strength of lifting the body. Sex difference was also found in the performance of flexibility. [ABSTRACT FROM AUTHOR]

Physical activity (PA) plays an important role in maintaining a healthy weight. To develop targeted strategies that encourage physical activity, knowledge of associations between intensity of physical activity (PA) levels and body mass index (BMI) is essential. We aimed to examine the relationship between sufficient and vigorous PA and BMI distribution among adults in northwest China using quantile regression. We conducted a cross-sectional study in Shaanxi Province in 2013, using proportional probability sampling. BMI was calculated using measured height and weight. The Global Physical Activity Questionnaire was used to define and measure sufficient and vigorous PA. Associations of sufficient/vigorous PA and BMI were modelled using quantile regression. Mean BMI was 24.18 ± 3.51 and BMI distribution with age showed an inverse U shape. A total 9045 (88.97%) participants demonstrated sufficient PA and 3119 (30.68%) reported vigorous PA. After adjusting for relevant sociodemographic, dietary, and lifestyle parameters in quantile regression modelling, sufficient PA was positively associated with BMI score distribution from the 1st to 30th quantile, with β from 0.32 (95% confidence interval (CI): 0.07 to 0.63) to 0.85 (95% CI: 0.40 to 1.19). Vigorous PA was negatively associated with BMI score distribution from the 30th to 93th quantiles, with β from −0.18 (95% CI: −0.31 to −0.02) to −0.81 (95% CI: −1.10 to −0.45). Sufficient PA was positively associated with underweight and normal weight whereas vigorous PA was negatively associated with overweight and obesity. [ABSTRACT FROM AUTHOR]