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| 1 | U-shaped association between telomere length and esophageal squamous cell carcinoma risk: a case-control study in Chinese population显示文摘在由维持 chromosomal 正直并且阻止染色体的生物变老的一个关键角色结束的 Telomeres 玩熔化。流行病学的研究建议了 telomere 长度的内部个人的差别能影响倾向到多重癌症,但是关于食道的有鳞的房间癌(ESCC ) 的证据仍然是不明确的。几 telomere 在白种人的长度相关的单个核苷酸多型性(TLSNP ) 在染色体宽的协会研究被报导了。然而,在 ESCC 开发的 telomere 长度和 TL-SNPs 的效果是不清楚的。因此,我们进行了盒子控制研究(1045 个 ESCC 案例和 1433 控制) 在中国人口评估在 telomere 长度, TL-SNPs,和 ESCC 风险之间的协会。作为结果, ESCC 案例显示出全面更短的相对 telomere 长度(RTL )( 中部:1.34 ) 比控制(中部:1.50, P < 0.001 ) 。更有趣地,一个明显的非线性的U字形的协会在 RTL 和 ESCC 风险之间被观察( P < 0.001 )与比率(95%信心间隔)等于到 2.40 的机会( 1.843.14 ), 1.36 ( 1.031.79 ), 1.01 ( 0.761.35 ),并且 1.37 ( 1.031.82 )为个人在第一(最短),第二,第三,并且 第5 (最长) quintile 分别地,在是的 第4 quintile 与那些相比引用组。没有重要协会在八报导 TL-SNPs 和 ESCC 危险性之间被观察。这些调查结果建议短或极其长的 telomeres 可以是为在中国人口的 ESCC 的风险因素。 | Jiangbo Du Wenjie Xue Yong Ji Xun Zhu Yayun Gu Meng Zhu Cheng Wang Yong Gao Juncheng Dai Hongxia Ma Yue Jiang Jiaping Chen Zhibin Hu Guangfu Jin Hongbing Shen | 2015 | Frontiers of Medicine2015，9，4： | 4 |
| 2 | Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma显示文摘Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer(NSCLC)risk,biological mechanisms of these variants remain largely unknown.By integrating a large-scale genotype data of 15581 lung adenocarcinoma(AD)cases,8350 squamous cell carcinoma(SqCC)cases,and 27355 controls,as well as multiple transcriptome and epigenomic databases,we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants.We identified 3064 credible risk variants for NSCLC,which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites.Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific.Functional annotation and genebased analysis implicated 894 target genes,including 274 specifics for AD and 123 for SqCC,which were overrepresented in somatic driver genes(ER=1.95,P=0.005).Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways,while SqCC genes were homologous recombination deficiency related.Our results illustrate the molecular basis of both wellstudied and new susceptibility loci of NSCLC,providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments. | Na Qin Yuancheng Li Cheng Wang Meng Zhu Juncheng Dai Tongtong Hong Demetrius Albanes Stephen Lam Adonina Tardon Chu Chen Gary Goodman Stig EBojesen Maria Teresa Landi Mattias Johansson Angela Risch H-Erich Wichmann Heike Bickeboller Gadi Rennert Susanne Arnold Paul Brennan John KField Sanjay Shete Loic Le Marchand Olle Melander Hans Brunnstrom Geoffrey Liu Rayjean JHung Angeline Andrew Lambertus AKiemeney Shan Zienolddiny Kjell Grankvist Mikael Johansson Neil Caporaso Penella Woll Philip Lazarus Matthew BSchabath Melinda CAldrich Victoria LStevens Guangfu Jin David CChristiani Zhibin Hu Christopher IAmos Hongxia Ma Hongbing Shen | 2021 | Frontiers of Medicine2021，15，2： | 3 |
| 3 | Gene amplification-driven RNA methyltransferase KIAA1429 promotes tumorigenesis by regulating BTG2 via m6A-YTHDF2-dependent in lung adenocarcinoma显示文摘Background:Epigenetic alterations have been shown to contribute immensely to human carcinogenesis.Dynamic and reversible N6-methyladenosine(m6A)RNA modification regulates gene expression and cell fate.However,the reasons for activation of KIAA1429(also known as VIRMA,an RNA methyltransferase)and its underlying mechanism in lung adenocarcinoma(LUAD)remain largely unexplored.In this study,we aimed to clarify the oncogenic role of KIAA1429 in the tumorigenesis of LUAD.Methods:Whole-genome sequencing and transcriptome sequencing of LUAD data were used to analyze the gene amplification of RNA methyltransferase.The in vitro and in vivo functions of KIAA1429 were investigated.Transcriptome sequencing,methylated RNA immunoprecipitation sequencing(MeRIP-seq),m6A dot blot assays and RNA immunoprecipitation(RIP)were performed to confirm the modified gene mediated by KIAA1429.RNA stability assays were used to detect the half-life of the target gene.Results:Copy number amplification drove higher expression of KIAA1429 in LUAD,whichwas correlatedwith poor overall survival.Manipulating the expression of KIAA1429 could regulate the proliferation and metastasis of LUAD.Mechanistically,the target genes of KIAA1429-mediated m6A modification were confirmed by transcriptome sequencing and MeRIP-seq assays.We also revealed that KIAA1429 could regulate BTG2 expression in an m6A-dependent manner.Knockdown of KIAA1429 significantly decreased the m6A levels of BTG2 mRNA,leading to enhanced YTH m6A RNA binding protein 2(YTHDF2,the m6A“reader”)-dependent BTG2 mRNA stability and promoted the expression of BTG2;thus,participating in the tumorigenesis of LUAD.Conclusions:Our data revealed the activation mechanism and important role of KIAA1429 in LUAD tumorigenesis,which may provide a novel view on the targeted molecular therapy of LUAD. | Chang Zhang Qi Sun Xu Zhang Na Qin Zhening Pu Yayun Gu Caiwang Yan Meng Zhu Juncheng Dai ChengWang Ni Li Guangfu Jin Hongxia Ma Zhibin Hu Erbao Zhang Fengwei Tan Hongbing Shen | 2022 | Cancer Communications2022，42，7： | 1 |
| 4 | Ergonomic and efficiency analysis of conventional apple harvest process显示文摘Apples are still manually harvested by workers using ladders and buckets.Though it is known that manual apple harvest would probably lead to occupational injuries(e.g.,back,neck,and shoulder strains),there has been little research that focuses on identifying the awkward activities/postures of pickers during the harvest process.After categorizing apple harvest work into 12 activities,this study used the method of Rapid Upper Limb Assessment(RULA)to identify awkward postures/activities that occurred during apple harvest.Awkward activities confirmed include descending a ladder,dumping apples,picking high and low apples on a ladder as well as on the ground,and moving a ladder,with potential reasons for each awkward activity provided.Meanwhile,it was demonstrated that pickers spent approximately 64%of working time under awkward postures that would lead to occupational diseases.In addition,this study analyzed picker harvest efficiency in terms of general and detail manners.The general mode assessed harvest activity in terms of picking and non-picking,with results showing that pickers averagely spent 76%(±7%)of harvest time in picking apples.Further analysis evaluated picking activities in terms of reaching,detaching,and transporting apples,with results showing that pickers spent averagely 30%(±6%)of time in detaching apples,which is the value time during apple harvest.Furthermore,valuable picking time ratio was obtained as the multiplication of picking time ratio and detaching time ratio.With a valuable ratio of 22%(±5%),it theoretically demonstrated the low harvest efficiency of the traditional harvest method.Since a majority of the awkward activities and the low efficiency were because of the ladders/buckets,using a harvest-assist unit may be a potential solution.Additionally,more efforts should be spent on the development of innovative mechanism to replace worker in placing attached apples to the bucket.Once the time for transporting apples is eliminated,the time for reaching apples is also removed,indicating the harvest efficiency would be improved significantly. | Zhao Zhang Yuanjie Wang Zhaohua Zhang Dapeng Li Zhengze Wu Rui Bai Guangfu Meng | 2019 | International Journal of Agricultural and Biological Engineering2019，12，2： | 1 |
| 5 | Fabrication of microwave-sensitized nanospheres of covalent organic framework with apatinib for tumor therapy显示文摘A new nanocomposite of hollow covalent organic framework(COF)conjugated with the apatinib(AP)and loading microwave-sensitizer(ionic liquid,IL)was prepared by layer by layer(LBL)method and hyaluronic acid(HA)coating,named as COF-AP-IL@HA.AP loading rate in COF hollow-spheres(~30 nm shell thickness)was~40.3%,due to the interactions of hydrogen andπ-πbonds between AP and COF shell,and acidic environment destroyed COF structure,promoting AP release.Microwave sensitization of loaded IL in COF hollow-spheres could enhance the microwave heat-effect,and combined AP therapeutic ability,leading to their higher inhibitation on tumor,due to targeting ability of HA and the local release of apatinib.88.9%of inhibition rate of COF-AP-IL@HA under microwave on the in vivo tumor was significantly higher than those without microwave(12.3%)and COF-IL@HA with microwave(37.5%),indicating a synergism of sensitized microwave hyperthermia and AP therapy on the reduced expression of VEGF via the downregulation pathway of hypoxia inducible factor.These results indicated that COF-AP-IL@HA was potential to the application in the combination therapy of tumor of the sensitized microwave hyperthermia and apatinib. | Qijun Du Jian Zou Zhongbing Huang Shimei Li Longfei Tan Xiangling Ren Guangfu Yin Yongfa Zheng Xianwei Meng | 2023 | Chinese Chemical Letters2023，34，5： | 0 |
| 6 | Lung cancer risk score for ever and never smokers in China显示文摘Background:Most lung cancer risk prediction models were developed in European and North-American cohorts of smokers aged≥55 years,while less is known about risk profiles in Asia,especially for never smokers or individuals aged<50 years.Hence,we aimed to develop and validate a lung cancer risk estimate tool for ever and never smokers across a wide age range.Methods:Based on the China Kadoorie Biobank cohort,we first systematically selected the predictors and explored the nonlinear association of predictors with lung cancer risk using restricted cubic splines.Then,we separately developed risk prediction models to construct a lung cancer risk score(LCRS)in 159,715 ever smokers and 336,526 never smokers.The LCRS was further validated in an independent cohort over a median follow-up of 13.6 years,consisting of 14,153 never smokers and 5,890 ever smokers.Results:A total of 13 and 9 routinely available predictors were identified for ever and never smokers,respectively.Of these predictors,cigarettes per day and quit years showed nonlinear associations with lung cancer risk(Pnon-linear<0.001).The curve of lung cancer incidence increased rapidly above 20 cigarettes per day and then was relatively flat until approximately 30 cigarettes per day.We also observed that lung cancer risk declined sharplywithin the first 5 years of quitting,and then continued to decrease but at a slower rate in the subsequent years.The 6-year area under the receiver operating curve for the ever and never smokers’models were respectively 0.778 and 0.733 in the derivation cohort,and 0.774 and 0.759 in the validation cohort.In the validation cohort,the 10-year cumulative incidence of lung cancerwas 0.39%and 2.57%for ever smokers with low(<166.2)and intermediate-high LCRS(≥166.2),respectively.Never smokers with a high LCRS(≥21.2)had a higher 10-year cumulative incidence rate than those with a low LCRS(<21.2;1.05%vs.0.22%).An online risk evaluation tool(LCKEY;http://gffzz0332d520339f4200h96kb9kuxnu696u6w.ffgz.tsg.suse.edu.cn/lckey/web)was developed to facilitate the use of LCRS.Conclusions:The LCRS can be an effective risk assessment tool designed for ever and never smokers aged 30 to 80 years. | Zhimin Ma Jun Lv Meng Zhu Canqing Yu Hongxia Ma Guangfu Jin Yu Guo Zheng Bian Ling Yang Yiping Chen Zhengming Chen Zhibin Hu Liming Li Hongbing Shen | 2023 | Cancer Communications2023，43，8： | 0 |
| 7 | A causal variant rs3769823 in 2q33.1 involved in apoptosis pathway leading to a decreased risk of non-small cell lung cancer显示文摘Objective:Although our previous genome-wide association study(GWAS)has identified chromosome 2q33.1 as a susceptibility locus for non-small cell lung cancer(NSCLC),the causal variants remain unclear.The aims of this study were to identify the causal variants in 2q33.1 and to explore their biological functions in NSCLC.Methods:CCK-8,colony formation,EdU incorporation,Transwell,and quantitative real-time polymerase chain reaction assays were applied to examine variant function.The tumor xenograft model was used to examine variant function in vivo.Caspase-8 activity assays,flow cytometry analysis,and co-immunoprecipitation assays were used to explore the molecular mechanism.Results:The missense variant rs3769823(A>G),which caused the substitution of lysine with arginine at amino acid 14 in caspase-8(caspase-8K14R),was identified as a potential causal candidate in 2q33.1.Compared with the wild type caspase-8(caspase8WT)group,the caspase-8K14R group had higher expression of caspase-8 and cleaved caspase-8.Caspase-8K14R inhibited the proliferation and metastasis of human lung cancer cell lines in vitro.Moreover,caspase-8K14R repressed lung cancer cell growth in vivo.Mechanistically,caspase-8K14R was more sensitive than caspase-8WT to tumor necrosis factor-related apoptosis-inducing ligand(TRAIL)-mediated apoptosis and showed higher binding of caspase-8 and FADD.Conclusions:These results suggested that rs3769823 is the causal variant in chromosome 2q33.1 and is involved in an apoptosis pathway,leading to a decreased risk of NSCLC. | Xu Zhang Na Qin Jingyi Fan Chang Zhang Qi Sun Yayun Gu Meng Zhu Erbao Zhang Juncheng Dai Guangfu Jin Hongxia Ma Zhibin Hu Hongbing Shen | 2022 | Cancer Biology & Medicine2022，19，9： | 0 |
| 8 | Fabrication of Tungsten Carbide Nanoparticles from Refluxing Derived Precursor显示文摘Tungsten carbide(WC) nanoparticles were fabricated from a novel refluxing-derived precursor. The precursor was prepared by acid hydrolysis of Na2WO4 with concentrated HCl in water followed by refl uxing with ethanol and n-Dedocane, respectively. Then it was heat-treated to 1 200 ℃ for 2 h in vacuum to obtain WC nanoparticles. X-ray studies reveal the formation of hexagonal tungsten carbide and the grain size of 24.3 nm. SEM image shows WC nanoparticles with particle size of 20-60 nm. Long time refl uxing results in alkane dehydrogenation and coke formation. The coke is the carbon source in the carbothermal reduction reaction. The novel route of two-stage refl uxing is quite general and can be applied in the synthesis of similar carbides. | 文季秋 LI Yongdi MENG Xiaopeng YIN Guangfu 姚亚东 | 2015 | Journal of Wuhan University of Technology(Materials Science)2015，30，2： | 0 |
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