Objective: Genome-wide association studies(GWAS) have identified over 150 risk loci linked to colorectal cancer(CRC), including the 17p13.3 locus with the tag single nucleotide polymorphism(SNP) rs12603526 in the Asia...Objective: Genome-wide association studies(GWAS) have identified over 150 risk loci linked to colorectal cancer(CRC), including the 17p13.3 locus with the tag single nucleotide polymorphism(SNP) rs12603526 in the Asian population. However, the specific causal gene and the functional regulatory mechanisms in this region remain unresolved, necessitating further investigation to elucidate the underlying mechanisms of CRC.Methods: We employed an RNA interference-based functional approach to identify genes critical for CRC cell proliferation at the GWAS locus 17p13.3. Bioinformatic fine-mapping analysis was conducted to prioritize causal variants. A large-scale study involving 7,013 cases and 7,329 controls from a Chinese population, along with another cohort of 5,158 cases and 20,632 controls from the UK Biobank, was performed to validate the association between the candidate variant and the gene. A series of biological experiments was conducted to explore the function of the candidate gene and its regulatory mechanisms.Results: We identified FAM57A as a key oncogene that promotes CRC cell proliferation, and confirmed its carcinogenic role through in vitro proliferation assays. The variant rs526835 was prioritized as a causal candidate for CRC risk, located in a functional region with enhancer properties, and showed a significant quantitative association with FAM57A expression. The rs526835 [T] variant was associated with a 1.17-fold increase in CRC risk [95%confidence interval(95% CI): 1.11-1.23, P=1.23×10^(−9)] in the large-scale Chinese cohort, which was further corroborated in the UK Biobank cohort. Mechanistically, we demonstrated that rs526835 enhances a promoterenhancer interaction mediated by the transcription factor JUN, leading to increased expression of FAM57A.Conclusions: We reveal the underlying mechanisms of CRC predisposition at the GWAS locus 17p13.3.Additionally, our findings highlight the critical role of FAM57A in CRC pathogenesis and introduce a novel enhancer-promoter interaction between FAM57A and rs526835, which could inform future precision prevention and personalized cancer therapies.展开更多
The purpose of this study is to deeply explore the impact of physical education(PE)curriculum reform on students’PE test results.By comparing the data of students’PE tests before and after the reform,analyzing the r...The purpose of this study is to deeply explore the impact of physical education(PE)curriculum reform on students’PE test results.By comparing the data of students’PE tests before and after the reform,analyzing the results of the questionnaire survey,and interviewing teachers and students,this paper reveals the significant effect of curriculum reform in improving students’PE test results.It is found that the curriculum reform effectively stimulates students’interest and participation in sports through optimizing teaching content,innovating teaching methods,improving evaluation systems,and increasing extracurricular sports activities,thus improving students’physical fitness and physical test scores.This study provides an empirical basis and suggestions for further promoting PE curriculum reform.展开更多
Purpose:The purpose of this study was to examine the relationships between children's situational motivation and physical activity(PA)levels in a Dance Dance Revolution(DDR)program,and perceived PA enjoyment.Metho...Purpose:The purpose of this study was to examine the relationships between children's situational motivation and physical activity(PA)levels in a Dance Dance Revolution(DDR)program,and perceived PA enjoyment.Methods:A sample of 215 elementary children participated in a weekly 30-min DDR program.Children's situational motivation toward DDR(intrinsic motivation,identified regulation,external regulation,and amotivation)was measured,followed by the measurement of their accel-erometer-determined moderate to vigorous PA(MVPA)in DDR.Children then reported their PA enjoyment.Results:Only intrinsic motivation was positively related with children's MVPA in DDR and PA enjoyment.However,other motivational beliefs were not significantly related to MVPA and PA enjoyment.Regression analyses further suggested intrinsic motivation was the significant predictor for MVPA and PA enjoyment.Conclusion:Children who experienced fun and learned new things when playing DDR reached high PA levels in DDR,as well as developed generalized feeling states of enjoyment.展开更多
Background:Findings on the association of genetic factors and colorectal cancer(CRC)survival are limited and inconsistent,and revealing the mechanism underlying their prognostic roles is of great importance.This study...Background:Findings on the association of genetic factors and colorectal cancer(CRC)survival are limited and inconsistent,and revealing the mechanism underlying their prognostic roles is of great importance.This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism.Methods:We first systematically performed expression quantitative trait locus(eQTL)analysis using The Cancer Genome Atlas(TCGA)dataset.Then,the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets(TCGA and GSE39582 dataset from the Gene Expression Omnibus database).The seven most potentially functional eQTL single nucleotide polymorphisms(SNPs)associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data.The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments.Results:The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1(ERAP1)was significantly associated with the prognosis of CRC(additive model,hazard ratio[HR]:1.43,95%confidence interval[CI]:1.08-1.88,P=0.012).The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3(TCF3)and subsequently reduce the expression of ERAP1.The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and was significantly associated with severe survival outcomes.Conclusion:The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1.Trial Registration:No.NCT00454519(https://clinicaltrials.gov/)展开更多
Radiotherapy uses high-energy X-rays or other particles to destroy cancer cells and medical practitioners have used this approach extensively for cancer treatment(Hachadorian et al.,2020).However,it is accompanied by ...Radiotherapy uses high-energy X-rays or other particles to destroy cancer cells and medical practitioners have used this approach extensively for cancer treatment(Hachadorian et al.,2020).However,it is accompanied by risks because it seriously harms normal cells while killing cancer cells.The side effects can lower cancer patients’quality of life and are very unpredictable due to individual differences(Bentzen,2006).展开更多
Obesity has become a major health crisis in the past∼50 years.The fat mass and obesity-associated(FTO)gene,identified by genome-wide association studies(GWAS),was first reported to be positively associated with obesi...Obesity has become a major health crisis in the past∼50 years.The fat mass and obesity-associated(FTO)gene,identified by genome-wide association studies(GWAS),was first reported to be positively associated with obesity in humans.Mice with more copies of the FTO gene were observed to be obese,while loss of the gene in mice was found to protect from obesity.Later,FTO was found to encode an m6 A RNA demethylase and has a profound effect on many biological and metabolic processes.In this review,we first summarize recent studies that demonstrate the critical roles and regulatory mechanisms of FTO in obesity and metabolic disease.Second,we discuss the ongoing debates concerning the association between FTO polymorphisms and obesity.Third,since several small molecule drugs and micronutrients have been found to regulate metabolic homeostasis through controlling the expression or activity of FTO,we highlight the broad potential of targeting FTO for obesity treatment.Improving our understanding of FTO and the underlying mechanisms may provide new approaches for treating obesity and metabolic diseases.展开更多
基金supported by the Program of National Science Fund for Distinguished Young Scholars of China(No.81925032)Key Program of National Natural Science Foundation of China(No.82130098)National Natural Science Foundation of China(No.82304232)。
文摘Objective: Genome-wide association studies(GWAS) have identified over 150 risk loci linked to colorectal cancer(CRC), including the 17p13.3 locus with the tag single nucleotide polymorphism(SNP) rs12603526 in the Asian population. However, the specific causal gene and the functional regulatory mechanisms in this region remain unresolved, necessitating further investigation to elucidate the underlying mechanisms of CRC.Methods: We employed an RNA interference-based functional approach to identify genes critical for CRC cell proliferation at the GWAS locus 17p13.3. Bioinformatic fine-mapping analysis was conducted to prioritize causal variants. A large-scale study involving 7,013 cases and 7,329 controls from a Chinese population, along with another cohort of 5,158 cases and 20,632 controls from the UK Biobank, was performed to validate the association between the candidate variant and the gene. A series of biological experiments was conducted to explore the function of the candidate gene and its regulatory mechanisms.Results: We identified FAM57A as a key oncogene that promotes CRC cell proliferation, and confirmed its carcinogenic role through in vitro proliferation assays. The variant rs526835 was prioritized as a causal candidate for CRC risk, located in a functional region with enhancer properties, and showed a significant quantitative association with FAM57A expression. The rs526835 [T] variant was associated with a 1.17-fold increase in CRC risk [95%confidence interval(95% CI): 1.11-1.23, P=1.23×10^(−9)] in the large-scale Chinese cohort, which was further corroborated in the UK Biobank cohort. Mechanistically, we demonstrated that rs526835 enhances a promoterenhancer interaction mediated by the transcription factor JUN, leading to increased expression of FAM57A.Conclusions: We reveal the underlying mechanisms of CRC predisposition at the GWAS locus 17p13.3.Additionally, our findings highlight the critical role of FAM57A in CRC pathogenesis and introduce a novel enhancer-promoter interaction between FAM57A and rs526835, which could inform future precision prevention and personalized cancer therapies.
基金2021 Guangdong Province Undergraduate College Teaching Quality and Teaching Reform Project Construction Project“Research on Strengthening and Perfecting the Evaluation System of Physical Education Courses in Ordinary Colleges and Universities under the Background of Education Evaluation Reform in the New Era-Taking Guangdong University of Foreign Studies as an Example”(Higher Education Teaching Reform and Construction Project No.203)。
文摘The purpose of this study is to deeply explore the impact of physical education(PE)curriculum reform on students’PE test results.By comparing the data of students’PE tests before and after the reform,analyzing the results of the questionnaire survey,and interviewing teachers and students,this paper reveals the significant effect of curriculum reform in improving students’PE test results.It is found that the curriculum reform effectively stimulates students’interest and participation in sports through optimizing teaching content,innovating teaching methods,improving evaluation systems,and increasing extracurricular sports activities,thus improving students’physical fitness and physical test scores.This study provides an empirical basis and suggestions for further promoting PE curriculum reform.
文摘Purpose:The purpose of this study was to examine the relationships between children's situational motivation and physical activity(PA)levels in a Dance Dance Revolution(DDR)program,and perceived PA enjoyment.Methods:A sample of 215 elementary children participated in a weekly 30-min DDR program.Children's situational motivation toward DDR(intrinsic motivation,identified regulation,external regulation,and amotivation)was measured,followed by the measurement of their accel-erometer-determined moderate to vigorous PA(MVPA)in DDR.Children then reported their PA enjoyment.Results:Only intrinsic motivation was positively related with children's MVPA in DDR and PA enjoyment.However,other motivational beliefs were not significantly related to MVPA and PA enjoyment.Regression analyses further suggested intrinsic motivation was the significant predictor for MVPA and PA enjoyment.Conclusion:Children who experienced fun and learned new things when playing DDR reached high PA levels in DDR,as well as developed generalized feeling states of enjoyment.
基金supported by grants from the National Natural Science Foundation of China(Nos.82273713 and 82103929)the Young Elite Scientists Sponsorship Program by CAST(No.2022QNRC001)+6 种基金the Fundamental Research Funds for the Central Universities(No.WHU:2042022kf1205)the Knowledge Innovation Program of Wuhan(No.whkxjsj011)the Distinguished Young Scholars of China(No.81925032)the Key Program of National Natural Science Foundation of China(No.82130098)the Hubei Provincial Natural Science Foundation of China(No.2019CFA009)the Youth Program of National Natural Science Foundation of China(No.82003547)the Fundamental Research Funds for the Central Universities(No.WHU:2042022kf 1031)
文摘Background:Findings on the association of genetic factors and colorectal cancer(CRC)survival are limited and inconsistent,and revealing the mechanism underlying their prognostic roles is of great importance.This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism.Methods:We first systematically performed expression quantitative trait locus(eQTL)analysis using The Cancer Genome Atlas(TCGA)dataset.Then,the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets(TCGA and GSE39582 dataset from the Gene Expression Omnibus database).The seven most potentially functional eQTL single nucleotide polymorphisms(SNPs)associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data.The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments.Results:The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1(ERAP1)was significantly associated with the prognosis of CRC(additive model,hazard ratio[HR]:1.43,95%confidence interval[CI]:1.08-1.88,P=0.012).The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3(TCF3)and subsequently reduce the expression of ERAP1.The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and was significantly associated with severe survival outcomes.Conclusion:The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1.Trial Registration:No.NCT00454519(https://clinicaltrials.gov/)
基金supported by the National Natural Science Foundation of China(Nos.21876176,21777163,21705152,and 22076190)the Youth Innovation Promotion Association,Chinese Academy of Sciences(No.2019432)+3 种基金the Presidential Foundation of Hefei Institute of Physical Sciences of Chinese Academy of Sciences(No.YZJJZX202009)the Functional Development Program of Instrument and Equipment in Chinese Academy of Sciences(No.Y9BS0C1291)the Anhui Provincial Key R&D Program(No.202104d07020003)the Joint Fund of the Second Affiliated Hospital of Anhui Medical University and the Center of Medical Physics and Technology of Hefei Institute of Physical Sciences of the Chinese Academy of Sciences(No.LHJJ2020006)。
文摘Radiotherapy uses high-energy X-rays or other particles to destroy cancer cells and medical practitioners have used this approach extensively for cancer treatment(Hachadorian et al.,2020).However,it is accompanied by risks because it seriously harms normal cells while killing cancer cells.The side effects can lower cancer patients’quality of life and are very unpredictable due to individual differences(Bentzen,2006).
基金supported by the National Key R&D Program(No.2018YFD0500405).
文摘Obesity has become a major health crisis in the past∼50 years.The fat mass and obesity-associated(FTO)gene,identified by genome-wide association studies(GWAS),was first reported to be positively associated with obesity in humans.Mice with more copies of the FTO gene were observed to be obese,while loss of the gene in mice was found to protect from obesity.Later,FTO was found to encode an m6 A RNA demethylase and has a profound effect on many biological and metabolic processes.In this review,we first summarize recent studies that demonstrate the critical roles and regulatory mechanisms of FTO in obesity and metabolic disease.Second,we discuss the ongoing debates concerning the association between FTO polymorphisms and obesity.Third,since several small molecule drugs and micronutrients have been found to regulate metabolic homeostasis through controlling the expression or activity of FTO,we highlight the broad potential of targeting FTO for obesity treatment.Improving our understanding of FTO and the underlying mechanisms may provide new approaches for treating obesity and metabolic diseases.
