61 results on '"Zhengdong Zhang"'
Search Results
2. Global internet search trends related to gastrointestinal symptoms predict regional COVID-19 outbreaks
- Author
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Yan Jiang, Mulong Du, David C. Christiani, Junyi Xin, Li Su, Shuai Ben, Meilin Wang, Zhengdong Zhang, Qianyu Yuan, and Silu Chen
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Microbiology (medical) ,Internet ,Google trends ,Coronavirus disease 2019 (COVID-19) ,SARS-CoV-2 ,business.industry ,Incidence (epidemiology) ,Generalized additive model ,COVID-19 ,Outbreak ,Article ,Gastrointestinal symptoms ,Disease Outbreaks ,Correlation ,Epidemiologic Studies ,Diarrhea ,Infectious Diseases ,Time-series analysis ,Humans ,Medicine ,The Internet ,Autoregressive integrated moving average ,medicine.symptom ,business ,Demography - Abstract
Background Real-time surveillance of search behavior on the internet has achieved accessibility in measuring disease activity. In this study, we systematically assessed the associations between internet search trends of gastrointestinal (GI) symptom terms and daily newly confirmed COVID-19 cases at both global and regional levels. Methods Relative search volumes (RSVs) of GI symptom terms were derived from internet search engines. Time-series analyses with autoregressive integrated moving average models were conducted to fit and forecast the RSV trends of each GI symptom term before and after the COVID-19 outbreak. Generalized additive models were used to quantify the effects of RSVs of GI symptom terms on the incidence of COVID-19. In addition, dose-response analyses were applied to estimate the shape of the associations. Results The RSVs of GI symptom terms could be characterized by seasonal variation and a high correlation with symptoms of “fever” and “cough” at both global and regional levels; in particular, “diarrhea” and “loss of taste” were abnormally increased during the outbreak period of COVID-19, with elevated point changes of 1.31 and 8 times, respectively. In addition, these symptom terms could effectively predict a COVID-19 outbreak in advance, underlying the lag correlation at 12 and 5 days, respectively, and with mutual independence. The dose-response curves showed a consistent increase in daily COVID-19 risk with increasing search volumes of “diarrhea” and “loss of taste”. Conclusion This is the first and largest epidemiologic study that comprehensively revealed the advanced prediction of COVID-19 outbreaks at both global and regional levels via GI symptom indicators.
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- 2022
3. Photocathodic protection of 304 stainless steel by coating muscovite/TiO2 heterostructure
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Ao Jiang, Yuli Di, Shanhua Chen, Dafu Zhang, Xingyu Chen, Zhengdong Zhang, Xinyi Zhang, and Qi Dong
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Geochemistry and Petrology ,Geology - Published
- 2023
4. linc01515 regulates PM2.5-induced oxidative stress via targeting NRF2 in airway epithelial cells
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Xi Wang, Huanhuan Zhu, Guanting Sun, Meiyu Zhou, Huilin Zhang, Hanting Liu, Meilin Wang, Zhengdong Zhang, and Haiyan Chu
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Health, Toxicology and Mutagenesis ,General Medicine ,Toxicology ,Pollution - Published
- 2023
5. Inhibition of the pyroptosis-associated inflammasome pathway: The important potential mechanism of ginsenosides in ameliorating diabetes and its complications
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Pan Liu, Zhengdong Zhang, Yichen Cai, Yunjiao Yang, Jun Yuan, and Qiu Chen
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Pharmacology ,Organic Chemistry ,Drug Discovery ,General Medicine - Published
- 2023
6. Halloysite nanotubes supported BiVO4/BaSnO3 p-n heterojunction photocatalysts for the enhanced degradation of methylene blue under visible light
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Xingyu Chen, Qi Dong, Shanhua Chen, Zhengdong Zhang, Xinyi Zhang, Yuli Di, Ao Jiang, Dafu Zhang, and Taishan Li
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Colloid and Surface Chemistry - Published
- 2023
7. Exosomal circCLIP1 regulates PM2.5-induced airway obstruction via targeting SEPT10 in vitro
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Huanhuan Zhu, Xiying Tang, Huilin Zhang, Meiyu Zhou, Hanting Liu, Haiyan Chu, and Zhengdong Zhang
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Health, Toxicology and Mutagenesis ,Public Health, Environmental and Occupational Health ,General Medicine ,Pollution - Published
- 2023
8. Hydrogen production by glycerol reforming in a two-fixed-bed reactor
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Qingli, Xu, primary, Zhengdong, Zhang, additional, Lifang, Liao, additional, Ping, Lan, additional, Rui, Wang, additional, Shoutao, Chen, additional, Pize, Li, additional, and Chenyang, Zhang, additional
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- 2022
- Full Text
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9. Integrated multi-omics approach to distinct molecular characterization and classification of early-onset colorectal cancer
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Mulong Du, Dongying Gu, Junyi Xin, Ulrike Peters, Mingyang Song, Guoshuai Cai, Shuwei Li, Shuai Ben, Yixuan Meng, Haiyan Chu, Lianmin Chen, Qianghu Wang, Lingjun Zhu, Zan Fu, Zhengdong Zhang, and Meilin Wang
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General Biochemistry, Genetics and Molecular Biology - Published
- 2023
10. Prognostic evaluation of polygenic risk score underlying pan-cancer analysis: evidence from two large-scale cohorts
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Junyi Xin, Xia Jiang, Huiqin Li, Silu Chen, Zhengdong Zhang, Meilin Wang, Dongying Gu, Mulong Du, and David C. Christiani
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General Medicine ,General Biochemistry, Genetics and Molecular Biology - Published
- 2023
11. Synthesis of halloysite nanotubes supported Bi-modified BaSnO3 photocatalysts for the enhanced degradation of methylene blue under visible light
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Xingyu Chen, Zhengdong Zhang, Shanhua Chen, Qi Dong, Xinyi Zhang, Yuli Di, Ao Jiang, Dafu Zhang, and Taishan Li
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Inorganic Chemistry ,Organic Chemistry ,Electrical and Electronic Engineering ,Physical and Theoretical Chemistry ,Atomic and Molecular Physics, and Optics ,Spectroscopy ,Electronic, Optical and Magnetic Materials - Published
- 2022
12. Synergistic interaction of Z-scheme TiO2/g-C3N4 photocatalyst and peroxymonosulfate for improving the photocatalytic efficiency of Rhodamine B
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Zhengdong Zhang, Xingyu Chen, Shanhua Chen, Qi Dong, Xinyi Zhang, Ao Jiang, Dafu Zhang, Yuli Di, and Taishan Li
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Inorganic Chemistry ,Organic Chemistry ,Electrical and Electronic Engineering ,Physical and Theoretical Chemistry ,Atomic and Molecular Physics, and Optics ,Spectroscopy ,Electronic, Optical and Magnetic Materials - Published
- 2022
13. Fine particulate matter induces METTL3-mediated m6A modification of BIRC5 mRNA in bladder cancer
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Hanting Liu, Jingjing Gu, Zhengkai Huang, Zhichao Han, Junyi Xin, Lin Yuan, Mulong Du, Haiyan Chu, Meilin Wang, and Zhengdong Zhang
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Environmental Engineering ,Health, Toxicology and Mutagenesis ,Environmental Chemistry ,Pollution ,Waste Management and Disposal - Published
- 2022
14. Ni supported on MgO modified attapulgite as catalysts for hydrogen production from glycerol steam reforming
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Qingli, Xu, primary, Zhengdong, Zhang, additional, Kai, Huang, additional, Shanzhi, Xin, additional, Chuang, Mao, additional, Chenge, Chen, additional, Huan, Yang, additional, Yang, Yue, additional, and Yongjie, Yan, additional
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- 2021
- Full Text
- View/download PDF
15. Long non-coding RNA FLJ22763 is involved in the progression and prognosis of gastric cancer
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Zhengdong Zhang, Meilin Wang, Gang Zhang, Yuqiu Ge, Gaoxiang Ma, Haiyan Chu, Qiaoyan Wang, Jiafei Lu, and Mulong Du
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Male ,0301 basic medicine ,Microarray ,Kaplan-Meier Estimate ,Biology ,medicine.disease_cause ,Genome ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Stomach Neoplasms ,Cell Line, Tumor ,Biomarkers, Tumor ,Genetics ,medicine ,Animals ,Humans ,Aged ,Cell Proliferation ,Mice, Inbred BALB C ,Microarray analysis techniques ,Gene Expression Profiling ,Cancer ,General Medicine ,Middle Aged ,Prognosis ,medicine.disease ,Xenograft Model Antitumor Assays ,Long non-coding RNA ,030104 developmental biology ,ROC Curve ,Depth of invasion ,030220 oncology & carcinogenesis ,Disease Progression ,Cancer research ,Female ,RNA, Long Noncoding ,Ectopic expression ,Carcinogenesis - Abstract
Long noncoding RNAs (lncRNAs) play important roles in carcinogenesis. It is necessary to uncover the detailed pattern of comprehensive lncRNA expression in the genome during the development of gastric cancer (GC). We implemented lncRNA microarray analysis in 5 paired GC tissues to detect the lncRNA expression profile. Moreover, we set out to explore the biological function, clinical application and molecular basis of the aberrant lncRNA in GC. In addition, we used the high-throughput microarray to identify the target gene of the aberrant lncRNA. We found that FLJ22763, a novel lncRNA, had significantly lower expression in GC tissues. Decreased expression of FLJ22763 was positively correlated with a lower-level histological grade and the depth of invasion. The ectopic expression of lncRNA FLJ22763 significantly suppressed the biological malignant behavior of GC cells and inhibited xenograft tumor growth (both P 0.001). Notably, FLJ22763 displayed a considerable predictive effect in the prognosis of GC (log-rank, P = 0.003). Furthermore, we found that FLJ22763 was negatively associated with ACLY, regulating the mRNA and protein levels of ACLY. Our findings suggested that FLJ22763 may act as a suppressor gene to regulate the expression of ACLY, and its down-expression may be an independent prognostic factor in patients with GC.
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- 2019
16. A numerical method for analyzing the influence of underwater vehicle flow field on dynamic behavior of towed sonar cable array
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Hang Cui, Zhengdong Zhang, and Xiaoxu Du
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Environmental Engineering ,Discretization ,business.industry ,Numerical analysis ,Acoustics ,Propeller ,020101 civil engineering ,Ocean Engineering ,02 engineering and technology ,Computational fluid dynamics ,01 natural sciences ,Sonar ,010305 fluids & plasmas ,0201 civil engineering ,Physics::Fluid Dynamics ,Computer Science::Robotics ,Nonlinear system ,Drag ,0103 physical sciences ,Point (geometry) ,business ,Geology - Abstract
Simulations of the dynamic behavior of a sonar cable array towed by an underwater vehicle considering the influence of flow field disturbed by the underwater vehicle and its propeller are challenging tasks. In present paper, the strongly nonlinear towed sonar cable array is modeled by the Lumped-Mass method where the cable array is discretized into a series of massless springs and lumped-mass points. The drag force on the towed sonar cable array is obtained by calculating the drag force on each lumped-mass point considering the flow field of the underwater vehicle and its propeller, which is computed by CFD methods. The dynamic behavior of the towed sonar cable array is simulated by 4th Runge–Kutta method applying Newton's second law. Simulations of the three underwater vehicle motion modes including linear motions, turning motions and surfacing motions are performed. The results show that the numerical method proposed is reasonable, and the lateral deflection of the towed sonar cable array is related to the speeds and the motion modes of the underwater vehicle.
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- 2019
17. Ambient fine particulate matter (PM2.5) induces oxidative stress and pro-inflammatory response via up-regulating the expression of CYP1A1/1B1 in human bronchial epithelial cells in vitro
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Zhengdong Zhang, Yaoyao Chen, Xiaobo Li, Haiyan Chu, and Qi Yuan
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0301 basic medicine ,chemistry.chemical_classification ,Gene knockdown ,Reactive oxygen species ,biology ,Health, Toxicology and Mutagenesis ,010501 environmental sciences ,medicine.disease_cause ,complex mixtures ,01 natural sciences ,In vitro ,Cell biology ,03 medical and health sciences ,030104 developmental biology ,chemistry ,Cell culture ,Gene expression ,Genetics ,biology.protein ,medicine ,Secretion ,STAT3 ,Oxidative stress ,0105 earth and related environmental sciences - Abstract
We investigated the mechanism responsible for the oxidative stress and pro-inflammatory response triggered by PM2.5 collected from Nanjing of China. Two human bronchial epithelia cell lines (HBE and BEAS-2B) were used. Human gene expression profile microarray was performed to investigate the alteration of gene expression in PM2.5-treated HBE cells. The results of ROS assay and ELISA indicated that PM2.5 (150 μg/ml) increased the level of cellular reactive oxygen species (ROS) and promoted the release of interleukin-6 (IL-6) in HBE cells. CYP1A1 and CYP1B1 were the top two up-regulated genes by PM2.5 (150 μg/ml, 48 h of exposure) in HBE cells. Co-knockdown of CYP1A1/1B1 by siRNA substantially inhibited PM2.5-induced ROS generation, IL-6/IL-8 secretion and STAT3/P-STAT3 expression. Similarly, the knockdown of STAT3 also effectively inhibited PM2.5-induced rise in ROS level and IL-6/IL-8 secretion. In summary, PM2.5 mediated oxidative stress and pro-inflammatory response via up-regulating the expression of CYP1A1/1B1 in two human bronchial epithelial cell lines.
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- 2019
18. Synthesis of novel muscovite loaded nano Ag/Cu2-Fe O composites with excellent visible-light responsive photocatalysis
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Xingyu Chen, Endong Liu, Dafu Zhang, Zhengdong Zhang, Qi Dong, Xinyi Zhang, Xiaoyu Ding, Shanhua Chen, and Xiaodong Zhu
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Inorganic Chemistry ,Organic Chemistry ,Electrical and Electronic Engineering ,Physical and Theoretical Chemistry ,Atomic and Molecular Physics, and Optics ,Spectroscopy ,Electronic, Optical and Magnetic Materials - Published
- 2022
19. Genetic variants in splicing factor genes and susceptibility to bladder cancer
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Meilin Wang, Zheng Guo, Yunyan Wang, Xi Wang, Chao Qin, Zhengdong Zhang, Lin Yuan, Haiyan Chu, Junyi Xin, and Huanhuan Zhu
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Oncology ,Candidate gene ,medicine.medical_specialty ,Nerve Tissue Proteins ,Single-nucleotide polymorphism ,Biology ,medicine.disease_cause ,Polymorphism, Single Nucleotide ,Asian People ,Internal medicine ,Biomarkers, Tumor ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Genetic association ,Bladder cancer ,Cancer ,Antigens, Nuclear ,General Medicine ,Odds ratio ,medicine.disease ,Gene Expression Regulation, Neoplastic ,Urinary Bladder Neoplasms ,Case-Control Studies ,Biomarker (medicine) ,RNA Splicing Factors ,Carcinogenesis - Abstract
Background Genome-wide association studies have demonstrated that genetic variants are closely related to tumorigenesis and progression of cancer. However, the correlation between genetic variants in splicing factor genes and bladder cancer susceptibility remains unclear. Method A case-control study with 580 cases of bladder cancer and 1,101 controls was conducted to explore the association of single-nucleotide polymorphisms (SNPs) in splicing factors with bladder cancer susceptibility by logistic regression models, and multiple testing errors were justified by the false discovery rate (FDR) method. Next, we used the Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) datasets to further analyze the differential expression of candidate genes. Results We found that rs978416 G>A in RBFOX3 contributed to a reduced risk of bladder cancer [adjusted odds ratio (OR) = 0.72, 95% confidence internal (CI) = 0.62–0.84, P = 3.54 × 10−5], especially in individuals who never smoked (P = 7.83 × 10−5). Stratified analysis showed that the protective effect of rs978416 was more significant in the subgroup of low grade and non-muscle invasive bladder cancer. Furthermore, the RBFOX3 mRNA expression was decreased in bladder tumor tissues. However, the relatively high expression of RBFOX3 was related to a higher bladder cancer stage. Conclusions Our findings indicated that SNP rs978416 G>A in RBFOX3 may be related to bladder cancer predisposition in Chinese population and might serve as a novel biomarker for bladder cancer risk.
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- 2022
20. Genetic variants in PI3K/Akt/mTOR pathway genes contribute to gastric cancer risk
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Haixiao Wang, Hanting Liu, Guoquan Tao, Haiyan Chu, Meilin Wang, Qinghong Zhao, Gaoxiang Ma, Mulong Du, Yuqiu Ge, Xiaonan Qiu, and Zhengdong Zhang
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Male ,0301 basic medicine ,Quantitative Trait Loci ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Phosphatidylinositol 3-Kinases ,03 medical and health sciences ,Stomach Neoplasms ,Cell Line, Tumor ,Genotype ,Genetics ,Humans ,SNP ,Genetic Predisposition to Disease ,Allele ,Promoter Regions, Genetic ,Protein kinase B ,Genetic Association Studies ,PI3K/AKT/mTOR pathway ,Aged ,TOR Serine-Threonine Kinases ,Promoter ,General Medicine ,Middle Aged ,Survival Analysis ,Molecular biology ,Up-Regulation ,Logistic Models ,030104 developmental biology ,Case-Control Studies ,Expression quantitative trait loci ,Female ,Proto-Oncogene Proteins c-akt ,Signal Transduction - Abstract
PI3K/Akt/mTOR pathway is involved in tumor initiation and progression, including gastric cancer (GC). However, the single nucleotide polymorphisms (SNPs) in this pathway and underlying molecular mechanism remain largely unexplored. A case-control study of 1275 GC patients and 1436 controls was performed to explore the associations of potentially functional SNPs in PI3K/Akt/mTOR pathway genes with the risk of GC. In the logistic regression analyses, one SNP rs7536272 out of the four candidate SNPs showed a significant association with GC risk (additive model: OR = 1.16, 95% CI = 1.03–1.30; co-dominant model: AG vs. AA, OR = 1.30, 95% CI = 1.11–1.53; dominant model: AG/GG vs. AA, OR = 1.28, 95% CI = 1.10–1.49).The luciferase assay indicated that rs7536272 G allele significantly enhanced the transcriptional activity, compared with A allele. Further expression quantitative trait loci (eQTL) analysis showed that GC patients with rs7536272 AG/GG genotypes had remarkably higher PIK3R3 levels than those with AA genotype, suggesting that rs7536272 polymorphism influenced the expression of PIK3R3. Additionally, we observed that GC patients with high expression of PIK3R3 had significant poorer outcome than those with low expression (HR = 1.29, 95% CI = 1.09–1.53). Our result demonstrated that SNP rs7536272, a functional risk variant located in the promoter region of PIK3R3, showed association with increased transcriptional activity and upregulation of PIK3R3 expression, thus involved in GC development.
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- 2018
21. Dynamics model and maneuverability of a novel AUV with a deflectable duct propeller
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Hang Cui, Zhengdong Zhang, and Xiaoxu Du
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0209 industrial biotechnology ,Environmental Engineering ,Computer science ,business.industry ,Ocean Engineering ,02 engineering and technology ,Computational fluid dynamics ,Propulsion ,01 natural sciences ,010305 fluids & plasmas ,symbols.namesake ,020901 industrial engineering & automation ,3d space ,0103 physical sciences ,Euler's formula ,symbols ,Duct (flow) ,Underwater ,business ,Marine engineering - Abstract
The vector propulsion systems have been equipped in numerous autonomous underwater vehicles (AUVs) nowadays. In most cases, the vector propulsion is achieved by changing the direction of the entire vector propulsion system, which requires a spacious room for complex mechanical structures at the tail of the AUV. The deflectable duct propeller, however, as a new way to achieve vector propulsion, can generate lateral force and moment enabling the AUV to perform various motions. In this work, the 6-DOF notion model of the novel AUV with a deflectable duct propeller is developed based on the Newton's and Euler's equation, considering the forces and moments generated by the deflectable duct propeller. And a CFD model is proposed to estimate performance of a deflectable duct propeller. The motion simulations including 2D longitudinal motions, 2D lateral motions and 3D space motions, are conducted to analyze the maneuvering performance of the novel AUV with a deflectable duct propeller, and simulation results illustrate that the novel AUV with a deflectable duct propeller has a better maneuverability than traditional propeller-rudder system.
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- 2018
22. Influencing factors of viscosity measurement by rotational method
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Mengmeng Huang, Xiaoping Dai, Zhengdong Zhang, Guiling Zheng, Yinglan Zhang, Ying Kan, and lianying liu
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Materials science ,Polymers and Plastics ,Rheometer ,Organic Chemistry ,0211 other engineering and technologies ,Sampling (statistics) ,02 engineering and technology ,Repeatability ,Mechanics ,021001 nanoscience & nanotechnology ,Measure (mathematics) ,Viscosity measurement ,Condensed Matter::Soft Condensed Matter ,Physics::Fluid Dynamics ,Viscosity ,Volume (thermodynamics) ,Rheology ,021105 building & construction ,0210 nano-technology - Abstract
Rotational rheometer was used to measure the shear viscosity of a liquid reference material of viscosity named GBW13604. The influences of heat balance time, bath temperature, environment temperature and sampling volume on results of measurements were investigated. Furthermore, a comparison of accuracy and repeatability of shear viscosity results between two commonly used systems with cone–plate and coaxial cylinder geometry was performed. Rheological tests indicate that the coaxial cylinder method is applicable to tests requiring high accuracy, while the cone-plate method is suitable for measurements that demand low sampling volume and fast speed.
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- 2018
23. Tagging SNPs in the HOTAIR gene are associated with bladder cancer risk in a Chinese population
- Author
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Haiyan Chu, Zhengdong Zhang, Ke Zhang, Da-min Gu, Xu Lv, Qiang Zhang, Weida Gong, Bin Xu, Lin Yuan, Xiang Wang, Yuqiu Ge, Wenying Wang, Mulong Du, and Meilin Wang
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Male ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Genotyping Techniques ,Single-nucleotide polymorphism ,Biology ,Real-Time Polymerase Chain Reaction ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,0302 clinical medicine ,Asian People ,Risk Factors ,Internal medicine ,Genotype ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,3' Untranslated Regions ,Aged ,Bladder cancer ,Incidence ,Case-control study ,HOTAIR ,Sequence Analysis, DNA ,General Medicine ,Odds ratio ,Middle Aged ,medicine.disease ,Long non-coding RNA ,Confidence interval ,030104 developmental biology ,Urinary Bladder Neoplasms ,Case-Control Studies ,030220 oncology & carcinogenesis ,Female ,RNA, Long Noncoding - Abstract
Background The HOX transcript antisense intergenic RNA (HOTAIR) is a well-known long noncoding RNA (lncRNA) that plays a critical role in biological processes in most cancers. However, the function of HOTAIR in bladder cancer remains largely unknown. In this study, we hypothesize that tag single nucleotide polymorphisms (tagSNPs) in HOTAIR are associated with bladder cancer (BCa) risk. Methods We performed a hospital-based case-control study of 1050 cases and 1407 controls to investigate the associations between tagSNPs and the risk of BCa in a Chinese population. Results We found that individuals with the rs874945 AG/AA genotype had a significantly increased risk of BCa compared with those carrying the GG genotype, with an odds ratio (OR) of 1.23 [95% confidence interval (CI) = 1.04–1.46, P = 0.014]. The subsequently stratified analyses showed that the increased risk was more pronounced in subgroups of older subjects (age > 60 years), never smokers and subjects without pack-years of smoking. Interactive analysis showed that there was no interaction effect between smoking status and rs874945. Conclusion Our study showed that rs874945 in HOTAIR was associated with BCa risk in a Chinese population.
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- 2018
24. S-CUDA: Self-cleansing unsupervised domain adaptation for medical image segmentation
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Shuai Li, Yefeng Zheng, Zhengdong Zhang, Kai Ma, and Luyan Liu
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Radiological and Ultrasound Technology ,Computer science ,business.industry ,Deep learning ,Optic Disk ,Health Informatics ,Pattern recognition ,Image segmentation ,Computer Graphics and Computer-Aided Design ,Convolutional neural network ,Domain (software engineering) ,Margin (machine learning) ,Image Processing, Computer-Assisted ,Code (cryptography) ,Humans ,Radiology, Nuclear Medicine and imaging ,Segmentation ,Neural Networks, Computer ,Computer Vision and Pattern Recognition ,Artificial intelligence ,business ,Algorithms ,Test data - Abstract
Medical image segmentation tasks hitherto have achieved excellent progresses with large-scale datasets, which empowers us to train potent deep convolutional neural networks (DCNNs). However, labeling such large-scale datasets is laborious and error-prone, which leads the noisy (or incorrect) labels to be an ubiquitous problem in the real-world scenarios. In addition, data collected from different sites usually exhibit significant data distribution shift (or domain shift). As a result, noisy label and domain shift become two common problems in medical imaging application scenarios, especially in medical image segmentation, which degrade the performance of deep learning models significantly. In this paper, we identify a novel problem hidden in medical image segmentation, which is unsupervised domain adaptation on noisy labeled data, and propose a novel algorithm named "Self-Cleansing Unsupervised Domain Adaptation" (S-CDUA) to address such issue. S-CUDA sets up a realistic scenario to solve the above problems simultaneously where training data (i.e., source domain) not only shows domain shift w.r.t. unsupervised test data (i.e., target domain) but also contains noisy labels. The key idea of S-CUDA is to learn noise-excluding and domain invariant knowledge from noisy supervised data, which will be applied on the highly corrupted data for label cleansing and further data-recycling, as well as on the test data with domain shift for supervised propagation. To this end, we propose a novel framework leveraging noisy-label learning and domain adaptation techniques to cleanse the noisy labels and learn from trustable clean samples, thus enabling robust adaptation and prediction on the target domain. Specifically, we train two peer adversarial networks to identify high-confidence clean data and exchange them in companions to eliminate the error accumulation problem and narrow the domain gap simultaneously. In the meantime, the high-confidence noisy data are detected and cleansed in order to reuse the contaminated training data. Therefore, our proposed method can not only cleanse the noisy labels in the training set but also take full advantage of the existing noisy data to update the parameters of the network. For evaluation, we conduct experiments on two popular datasets (REFUGE and Drishti-GS) for optic disc (OD) and optic cup (OC) segmentation, and on another public multi-vendor dataset for spinal cord gray matter (SCGM) segmentation. Experimental results show that our proposed method can cleanse noisy labels efficiently and obtain a model with better generalization performance at the same time, which outperforms previous state-of-the-art methods by large margin. Our code can be found at https://github.com/zzdxjtu/S-cuda.
- Published
- 2021
25. Genomic expansion of Aldh1a1 protects beavers against high metabolic aldehydes from lipid oxidation
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M. Reza Jabalameli, Jan Vijg, Joydeep Mitra, Jhih Rong Lin, Lei Zhang, Zhengdong Zhang, Quanwei Zhang, Vadim N. Gladyshev, Vera Gorbunova, Zachary J. Smith, Alus M. Xiaoli, Zhen Wang, Yang Zhao, Nha Nguyen, Andrei Seluanov, Julia Ablaeva, Xuming Zhou, and Gregory Tombline
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Male ,Tumor suppressor gene ,DNA repair ,media_common.quotation_subject ,Longevity ,Rodentia ,Biology ,Aldehyde Dehydrogenase 1 Family ,Article ,General Biochemistry, Genetics and Molecular Biology ,Mice ,Lipid oxidation ,parasitic diseases ,Gene expression ,otorhinolaryngologic diseases ,Animals ,Humans ,Genes, Tumor Suppressor ,Gene ,Phylogeny ,media_common ,Aldehydes ,Genome ,Lipid metabolism ,Lipids ,eye diseases ,Cell biology ,ALDH1A1 ,biology.protein ,Female - Abstract
SUMMARY The North American beaver is an exceptionally long-lived and cancer-resistant rodent species. Here, we report the evolutionary changes in its gene coding sequences, copy numbers, and expression. We identify changes that likely increase its ability to detoxify aldehydes, enhance tumor suppression and DNA repair, and alter lipid metabolism, potentially contributing to its longevity and cancer resistance. Hpgd, a tumor suppressor gene, is uniquely duplicated in beavers among rodents, and several genes associated with tumor suppression and longevity are under positive selection in beavers. Lipid metabolism genes show positive selection signals, changes in copy numbers, or altered gene expression in beavers. Aldh1a1, encoding an enzyme for aldehydes detoxification, is particularly notable due to its massive expansion in beavers, which enhances their cellular resistance to ethanol and capacity to metabolize diverse aldehyde substrates from lipid oxidation and their woody diet. We hypothesize that the amplification of Aldh1a1 may contribute to the longevity of beavers., Graphical Abstract, In brief Zhang et al. examine the genome of North American beavers and find evolutionary changes that could contribute to beavers’ longevity. In particular, Aldh1a1, encoding an enzyme for aldehyde detoxification, is massively expanded in the beaver genome, protecting them against exposure to aldehydes from lipid oxidation and their woody diet.
- Published
- 2021
26. RETRACTED: Nested Inversion Polymorphisms Predispose Chromosome 22q11.2 to Meiotic Rearrangements
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Wolfram Demaerel, Matthew S. Hestand, Elfi Vergaelen, Ann Swillen, Marcos López-Sánchez, Luis A. Pérez-Jurado, Donna M. McDonald-McGinn, Elaine Zackai, Beverly S. Emanuel, Bernice E. Morrow, Jeroen Breckpot, Koenraad Devriendt, Joris R. Vermeesch, Kevin Antshel, Celso Arango, Marco Armando, Anne Bassett, Carrie Bearden, Erik Boot, Marta Bravo-Sanchez, Elemi Breetvelt, Tiffany Busa, Nancy Butcher, Linda Campbell, Miri Carmel, Eva Chow, T. Blaine Crowley, Joseph Cubells, David Cutler, Maria Cristina Digilio, Sasja Duijff, Stephan Eliez, Beverly Emanuel, Michael Epstein, Rens Evers, Luis Fernandez Garcia-Moya, Ania Fiksinski, David Fraguas, Wanda Fremont, Rosemarie Fritsch, Sixto Garcia-Minaur, Aaron Golden, Doron Gothelf, Tingwei Guo, Ruben Gur, Raquel Gur, Damian Heine-Suner, Matthew Hestand, Stephen Hooper, Wendy Kates, Leila Kushan, Alejandra Laorden-Nieto, Johanna Maeder, Bruno Marino, Christian Marshall, Kathryn McCabe, Donna McDonald-McGinn, Elena Michaelovosky, Bernice Morrow, Edward Moss, Jennifer Mulle, Declan Murphy, Kieran Murphy, Clodagh Murphy, Maria Niarchou, Claudia Ornstein, Michael Owen, Nicole Philip, Gabriela Repetto, Maude Schneider, Vandana Shashi, Tony Simon, Flora Tassone, Marta Unolt, Therese van Amelsvoort, Marianne van den Bree, Esther Van Duin, Joris Vermeesch, Stefano Vicari, Claudia Vingerhoets, Jacob Vorstman, Steve Warren, Ronnie Weinberger, Omri Weisman, Abraham Weizman, Zhengdong Zhang, and Michael Zwick
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0301 basic medicine ,Genetics ,Chromosome ,Low copy repeats ,Biology ,Structural variation ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Gene duplication ,Human genome ,Homologous recombination ,030217 neurology & neurosurgery ,Genetics (clinical) ,Chromosomal inversion ,Segmental duplication - Abstract
Inversion polymorphisms between low-copy repeats (LCRs) might predispose chromosomes to meiotic non-allelic homologous recombination (NAHR) events and thus lead to genomic disorders. However, for the 22q11.2 deletion syndrome (22q11.2DS), the most common genomic disorder, no such inversions have been uncovered as of yet. Using fiber-FISH, we demonstrate that parents transmitting the de novo 3 Mb LCR22A–D 22q11.2 deletion, the reciprocal duplication, and the smaller 1.5 Mb LCR22A–B 22q11.2 deletion carry inversions of LCR22B–D or LCR22C–D. Hence, the inversions predispose chromosome 22q11.2 to meiotic rearrangements and increase the individual risk for transmitting rearrangements. Interestingly, the inversions are nested or flanking rather than coinciding with the deletion or duplication sizes. This finding raises the possibility that inversions are a prerequisite not only for 22q11.2 rearrangements but also for all NAHR-mediated genomic disorders.
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- 2017
27. METTL3 regulates PM2.5-induced cell injury by targeting OSGIN1 in human airway epithelial cells
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Haiyan Chu, Meilin Wang, Huanhuan Zhu, Zhengdong Zhang, Qi Yuan, and Hanting Liu
- Subjects
A549 cell ,021110 strategic, defence & security studies ,Gene knockdown ,Environmental Engineering ,Chemistry ,Immunoprecipitation ,Health, Toxicology and Mutagenesis ,Autophagy ,0211 other engineering and technologies ,02 engineering and technology ,010501 environmental sciences ,Cell cycle ,medicine.disease_cause ,complex mixtures ,01 natural sciences ,Pollution ,Cell biology ,MRNA Sequencing ,Apoptosis ,medicine ,Environmental Chemistry ,Waste Management and Disposal ,Oxidative stress ,0105 earth and related environmental sciences - Abstract
N6-methyladenosine (m6A) is implicated in alteration of cellular biological processes caused by exogenous environmental factors. However, little is known about the role of m6A in airborne fine particulate matter (PM2.5)-induced adverse effects. Thus, we investigated the role of m6A modification in PM2.5-induced airway epithelial cell injury. We observed a methyltransferase-like 3 (METTL3)-dependent induction of m6A modification after PM2.5 treatment in HBE and A549 cells. METTL3 knockdown attenuated PM2.5-induced apoptosis and arrest of cell cycle. mRNA sequencing and RNA N6-methyladenosine binding protein immunoprecipitation (Me-RIP) assay identified m6A-modified oxidative stress induced growth inhibitor 1 (OSGIN1) as the target gene of METTL3. Knockdown of METTL3 resulted a shorter mRNA half-life of OSGIN1 by catalyzing its m6A modification. Knockdown of METTL3 or OSGIN1 attenuated cell apoptosis, arrest of cell cycle and autophagy induced by PM2.5. In conclusion, METTL3 may mediate PM2.5-induced cell injury by targeting OSGIN1 in human airway epithelial cells. Our work uncovered a critical role of METTL3 in PM2.5-induced airway epithelial cell injury and provided insight into the vital role of m6A modification in PM2.5-induced human hazards.
- Published
- 2021
28. Sorption and desorption of petroleum hydrocarbons on biodegradable and nondegradable microplastics
- Author
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Cuijie Shi, Xiaowei Song, Xiaofeng Wu, Xiaoping Song, and Zhengdong Zhang
- Subjects
Microplastics ,Environmental Engineering ,Health, Toxicology and Mutagenesis ,0208 environmental biotechnology ,02 engineering and technology ,010501 environmental sciences ,01 natural sciences ,chemistry.chemical_compound ,Polylactic acid ,Desorption ,Polyethylene terephthalate ,Environmental Chemistry ,0105 earth and related environmental sciences ,Public Health, Environmental and Occupational Health ,Sorption ,General Medicine ,General Chemistry ,Polyethylene ,Pollution ,020801 environmental engineering ,Polyvinyl chloride ,Petroleum ,chemistry ,Chemical engineering ,Adsorption ,Polystyrene ,Plastics ,Water Pollutants, Chemical - Abstract
Both biodegradable and nondegradable plastics are widely used. However, their interactions with petroleum hydrocarbons (PHs) have not been sufficiently studied. In this study, a type of biodegradable [polylactic acid (PLA)] and five types of nondegradable microplastics [polyamide (PA), polyethylene (PE), polyethylene terephthalate (PET), polystyrene (PS), and polyvinyl chloride (PVC)] were selected to investigate the sorption and desorption mechanisms of PHs. The sorption kinetics of the six types of microplastics followed a pseudo-second-order kinetics model (R2 ranged from 0.956 to 0.999) and indicated that chemical sorption dominated the sorption process. The key rate-controlling steps of the sorption of PHs on microplastics were intraparticle diffusion and liquid film diffusion. The sorption capacity of PHs on microplastics followed the order of PA > PE > PS > PET > PLA > PVC. The difference in sorption capacity might be due to the crystallinity, and rubber or glass state of the microplastics. In addition, all types of microplastics exhibited reversible sorption without noticeable desorption hysteresis. No obvious differences were observed in the sorption and desorption of PHs between biodegradable and nondegradable microplastics. Both biodegradable and nondegradable microplastics could sorb/desorb PHs and serve as transportation vectors.
- Published
- 2021
29. Effect of PM2.5 exposure on circulating fibrinogen and IL-6 levels: A systematic review and meta-analysis
- Author
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Huanhuan Zhu, Zheng Guo, Yanling Wu, Dafei Wang, Hanting Liu, Haiyan Chu, Jing Qian, Zhengdong Zhang, Meilin Wang, Weida Gong, and Xingya Kuang
- Subjects
medicine.medical_specialty ,Environmental Engineering ,Fine particulate ,Health, Toxicology and Mutagenesis ,0208 environmental biotechnology ,Subgroup analysis ,02 engineering and technology ,010501 environmental sciences ,Fibrinogen ,complex mixtures ,01 natural sciences ,Gastroenterology ,Internal medicine ,medicine ,Environmental Chemistry ,Interleukin 6 ,Adverse effect ,0105 earth and related environmental sciences ,biology ,business.industry ,Respiratory disease ,Public Health, Environmental and Occupational Health ,General Medicine ,General Chemistry ,Publication bias ,medicine.disease ,Pollution ,020801 environmental engineering ,Meta-analysis ,biology.protein ,business ,medicine.drug - Abstract
Background Ambient fine particulate matter (PM2.5) pollution poses a great threat on global health. Previous studies have reported that PM2.5 regulates circulating fibrinogen and IL-6 levels in the development of cardiovascular and respiratory disease. However, the correlation between PM2.5 exposure and both biomarkers remains inconsistent. Methods We searched related articles through PubMed, Web of Science and ScienceDirect. Random effects model was used to obtain a pooled estimate effect of both biomarkers as PM2.5 concentration increased by every 10 μg/m3. Meta-regression analysis, sensitivity analysis and publication bias test were conducted to evaluate the heterogeneity, stability and reliability of this meta-analysis. Results A total of 22 articles were included. Each 10 μg/m3 increase in PM2.5 concentration was significantly correlated with a 1.76% increase in circulating fibrinogen level (95% CI: 0.38%–3.14%, P = 0.013) and a 4.66% increase in IL-6 level (95% CI: 1.14%–8.18%, P = 0.010). Subgroup analysis revealed that high-level PM2.5 exposure had a more significant association with circulating IL-6 level (11.67%, 95% CI: 0.66%–22.69%, P = 0.038) than low-level exposure, but this association was not observed in fibrinogen (2.50%, 95% CI: −0.78%–5.77%, P = 0.135). Sensitivity analysis and publication bias test confirmed the stability of the results. Conclusion Circulating fibrinogen and IL-6 significantly increased with exposure to PM2.5, may serve as promising biomarkers for PM2.5-related adverse effects.
- Published
- 2021
30. Exome Array Analysis Identifies Variants in SPOCD1 and BTN3A2 That Affect Risk for Gastric Cancer
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Zhaoming Wang, Shouyu Wang, Meng Zhu, Meilin Wang, Zhengdong Zhang, Juncheng Dai, Tongtong Huang, Yue Jiang, Hongxia Ma, Chuanli Ren, Yongyong Shi, Yong Gao, Jiangbo Du, Guozhong Ji, Hongbing Shen, Jinfei Chen, Yong Ji, Xiaodan Huang, Jianwei Zhou, Xun Zhu, Ming Yang, Zhibin Hu, Caiwang Yan, Xiaoping Miao, Guangfu Jin, and Haiyong Gu
- Subjects
Male ,0301 basic medicine ,Candidate gene ,Time Factors ,Genome-wide association study ,Exosomes ,medicine.disease_cause ,Gene Frequency ,Cell Movement ,Risk Factors ,Odds Ratio ,Stomach cancer ,Exome ,Regulation of gene expression ,Mice, Inbred BALB C ,Mutation ,Gastroenterology ,Middle Aged ,Tumor Burden ,Phenotype ,Female ,RNA Interference ,China ,Mice, Nude ,Biology ,Transfection ,03 medical and health sciences ,Stomach Neoplasms ,Cell Line, Tumor ,Biomarkers, Tumor ,medicine ,Animals ,Humans ,Genetic Predisposition to Disease ,Neoplasm Invasiveness ,Genetic Association Studies ,Aged ,Cell Proliferation ,Butyrophilins ,Hepatology ,Genetic Variation ,Cancer ,medicine.disease ,Molecular biology ,Logistic Models ,030104 developmental biology ,Case-Control Studies ,Multivariate Analysis ,Cancer cell ,CRISPR-Cas Systems - Abstract
Background & Aims Several genetic variants have been associated with gastric cancer risk, although these account for only a fraction of cases of gastric cancer. We aimed to identify low-frequency and other genetic variants that determine gastric cancer susceptibility. Methods We performed exome array analysis of DNA in blood samples from 1113 patients with gastric cancer, collected at hospitals from 2006 to 2010 in China, and 1848 individuals without cancer (controls) undergoing physical examinations. Among 71,290 variants analyzed (including 25,784 common variants), 24 variants were selected and replicated in an analysis of DNA in blood samples from 4687 additional cases of gastric cancer and 5780 controls. We compared expression of candidate genes in tumor vs normal gastric tissues using data from TCGA and performed functional annotation analyses. An immortalized human gastric epithelial cell line (GES1) and 7 human gastric cancer lines were used to express transgenes, knock down gene expression (with small interfering RNAs), disrupt genes (using the CRISPR/Cas9 system), or assess expression of reporter constructs. We measured cell proliferation, colony formation, invasion, and migration, and assessed growth of xenograft tumors in nude mice. Results A low-frequency missense variant rs112754928 in the SPOC domain containing 1 gene ( SPOCD1 ; encoding p.Arg71Trp), at 1p35.2, was reproducibly associated with reduced risk of gastric cancer (odds ratio, 0.56; P = 3.48 × 10 –8 ). SPOCD1 was overexpressed in gastric tumors, and knockout of SPOCD1 reduced gastric cancer cell proliferation, invasive activity, and migration, as well as growth of xenograft tumors in nude mice. We also associated the variant rs1679709 at 6p22.1 with reduced risk for gastric cancer (odds ratio, 0.80; P = 1.17 × 10 –13 ). The protective allele rs1679709-A correlated with the surrounding haplotype rs2799077-T–rs2799079-C, which reduced the enhancer activity of this site to decrease expression of the butyrophilin subfamily 3 member A2 gene ( BTN3A2 ). BTN3A2 is overexpressed in gastric tumors, and deletion of BTN3A2 inhibited proliferation, migration, and invasion of gastric cancer cells. Conclusions We have associated variants at 1p35.2 and 6p22.1 with gastric cancer risk, indicating a role for SPOCD1 and BTN3A2 in gastric carcinogenesis.
- Published
- 2017
31. A 12-month longitudinal study of Listeria monocytogenes contamination and persistence in pork retail markets in China
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Yimao Miao, Lijuan Luo, Jianping Deng, Pengfei Wang, Yang Zhou, Xiang Liu, Ling Zhang, Jianguo Xu, Qun Li, Yi Wang, Ruiting Lan, Yan Wang, Songsong Sun, Xi Chen, Hong Wang, Zhengdong Zhang, and Changyun Ye
- Subjects
0301 basic medicine ,Serotype ,Veterinary medicine ,Longitudinal study ,business.industry ,030106 microbiology ,Biology ,Contamination ,Sequence types ,medicine.disease_cause ,Biotechnology ,Persistence (computer science) ,03 medical and health sciences ,030104 developmental biology ,Listeria monocytogenes ,Pulsed-field gel electrophoresis ,medicine ,Multilocus sequence typing ,business ,Food Science - Abstract
Listeria monocytogenes is a foodborne pathogen frequently isolated from raw pork meat. This study was designed to investigate the prevalence and molecular characteristics of L. monocytogenes in raw pork from open markets in China. The survey was conducted monthly over a 12-month period in Zigong, China. L. monocytogenes was isolated from 262 of 1641 samples collected (16.0%) including minced meat samples (131/608, 21.5%), pork pieces samples (111/857, 13.0%) and environmental swabs (20/176, 11.4%). The isolation rates in spring and winter were significantly higher than those in summer and autumn ( X 2 = 68.85, P AscI pulsed-field gel electrophoresis (PFGE). The 262 isolates were subtyped into five serotypes: 1/2b (43.1%), 1/2c (35.5%), 1/2a (19.1%), 4b (1.1%), 3a (1.1%); 20 sequence types (STs) with four most frequent STs, being ST9 (35.9%), ST87 (19.8%), ST3 (16.0%) and ST8 (14.1%); and 39 pulsotypes (PTs) with PT4 (26.3%), PT30 (14.5%) and PT11 (12.6%) being most frequent. Two primary pulsotypes from pork pieces were previously isolated from clinical listeriosis cases in the local hospitals. The six markets from different districts differed in the level of contamination and strain types. Persistent contamination of L. monocytogenes was found in the markets especially in meat mincers, which were found to be one likely source of continuous cross contamination. These findings will help develop strategies to reduce L. monocytogenes contamination in open markets for better public health control and prevention of foodborne L. monocytogenes infections.
- Published
- 2017
32. Cyclin C regulates adipogenesis by stimulating transcriptional activity of CCAAT/enhancer-binding protein α
- Author
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Sven Wang, Rui Chang, Ellen S.T. Yang, Randy Strich, Yi Zhang, Quanwei Zhang, Jeffrey E. Pessin, Alus M. Xiaoli, Fajun Yang, Ziyi Song, Zhengdong Zhang, and Gongshe Yang
- Subjects
Transcriptional Activation ,0301 basic medicine ,Cellular differentiation ,Peroxisome proliferator-activated receptor ,Biology ,Biochemistry ,Mice ,03 medical and health sciences ,Transactivation ,chemistry.chemical_compound ,Cyclin C ,3T3-L1 Cells ,Adipocyte ,Gene expression ,Animals ,Humans ,Molecular Biology ,Mice, Knockout ,chemistry.chemical_classification ,Regulation of gene expression ,Adipogenesis ,Ccaat-enhancer-binding proteins ,Cell Differentiation ,Cell Biology ,Cell biology ,PPAR gamma ,Adipocytes, Brown ,Metabolism ,030104 developmental biology ,chemistry ,CCAAT-Enhancer-Binding Proteins - Abstract
Brown adipose tissue is important for maintaining energy homeostasis and adaptive thermogenesis in rodents and humans. As disorders arising from dysregulated energy metabolism, such as obesity and metabolic diseases, have increased, so has interest in the molecular mechanisms of adipocyte biology. Using a functional screen, we identified cyclin C (CycC), a conserved subunit of the Mediator complex, as a novel regulator for brown adipocyte formation. siRNA-mediated CycC knockdown (KD) in brown preadipocytes impaired the early transcriptional program of differentiation, and genetic KO of CycC completely blocked the differentiation process. RNA sequencing analyses of CycC-KD revealed a critical role of CycC in activating genes co-regulated by peroxisome proliferator activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα). Overexpression of PPARγ2 or addition of the PPARγ ligand rosiglitazone rescued the defects in CycC-KO brown preadipocytes and efficiently activated the PPARγ-responsive promoters in both WT and CycC-KO cells, suggesting that CycC is not essential for PPARγ transcriptional activity. In contrast, CycC-KO significantly reduced C/EBPα-dependent gene expression. Unlike for PPARγ, overexpression of C/EBPα could not induce C/EBPα target gene expression in CycC-KO cells or rescue the CycC-KO defects in brown adipogenesis, suggesting that CycC is essential for C/EBPα-mediated gene activation. CycC physically interacted with C/EBPα, and this interaction was required for C/EBPα transactivation domain activity. Consistent with the role of C/EBPα in white adipogenesis, CycC-KD also inhibited differentiation of 3T3-L1 cells into white adipocytes. Together, these data indicate that CycC activates adipogenesis in part by stimulating the transcriptional activity of C/EBPα.
- Published
- 2017
33. Genetic variants, PM2.5 exposure level and global DNA methylation level: A multi-center population-based study in Chinese
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Zhengdong Zhang, Jiahui Zhang, Jia Liu, Yuzhuo Wang, Kaipeng Xie, Meng Zhu, Juncheng Dai, Yang Cheng, Wei Shen, Jiangbo Du, Hongxia Ma, Hongbing Shen, Guangfu Jin, Zhihua Li, Weihong Chen, Meilin Wang, Liguo Geng, Zhibin Hu, Tangchun Wu, and Jing Yuan
- Subjects
0301 basic medicine ,Genetics ,Genetic variants ,Chromosome ,General Medicine ,Methylation ,Biology ,Joint analysis ,Toxicology ,Population based study ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Exposure level ,030220 oncology & carcinogenesis ,DNA methylation ,Exome - Abstract
Global DNA methylation levels can be determined by environmental and genetic factors. There are emerging evidences that methylation status can be modified as exposed to environmental factors such as PM2.5, but the genetic determinants are still largely unknown. To explore whether genetic variants contribute to global DNA methylation levels with consideration of environmental exposures, we systematically evaluated the association between genetic variants and global DNA methylation levels in 301 subjects from three cities in southern, central and northern China with different PM2.5 exposure levels (Zhuhai, Wuhan and Tianjin, respectively). Personal 24-h PM2.5 exposure levels and global DNA methylation levels for each subject were evaluated. Using Illumina Human Exome BeadChip, 241,305 SNVs was genotyped and assessed for their association with global DNA methylation levels. We found that after adjusting for age, gender, PM2.5 exposure level, pack-years of smoking and BMI, 14 SNVs were consistently associated with global DNA methylation levels with pooled P≤1.00×10-4 after meta-analysis of three cohorts, in which 8 SNVs together with age were independent factors modifying global DNA methylation levels. Joint analysis of these identified SNVs showed a significant allele-dosage association between the number of variants and global DNA methylation levels (P=1.82×10-23). In particular, we detected a significant multiplicative interaction between rs4344916 on chromosome 2p22.3 and PM2.5 exposure on global DNA methylation level (P=0.0095). Our findings indicate that genetic variants alone or in combination with PM2.5 play an important role in modifying individual global DNA methylation levels.
- Published
- 2017
34. Genetic Variants in CircTUBB Interacting Smoking Enhance Colorectal Cancer Risk
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Shuai Ben, Kaili Xu, Shuwei Li, Mulong Du, Yixuan Meng, Dongying Gu, Meilin Wang, Junyi Xin, Rui Zheng, Yongqian Shu, Ke Zhang, Zhengdong Zhang, Haiyan Chu, and Lingxiang Liu
- Subjects
Oncology ,medicine.medical_specialty ,Colorectal cancer ,business.industry ,Single-nucleotide polymorphism ,Genome-wide association study ,Odds ratio ,medicine.disease ,Institutional review board ,medicine.disease_cause ,Internal medicine ,microRNA ,medicine ,1000 Genomes Project ,business ,Carcinogenesis - Abstract
Background: Circular RNAs (circRNAs) are an intriguing class of regulatory RNAs involved in the tumorigenesis of many cancers, including colorectal cancer. Mechanistically, circRNAs sponge microRNAs (miRNAs) with specific miRNA response elements (MREs) and compete for regulatory target genes downstream. However, the genetic effects of MREs on colorectal cancer susceptibility remain unclear. Methods: The MREs of colorectal cancer-specific circRNAs (CRC-circRNAs) and corresponding single nucleotide polymorphisms (SNPs) were identified by the transcriptome of cancer cells and the 1000 Genomes Project. The association between candidate SNPs and colorectal cancer risk was evaluated in a Chinese population (1,150 cases and 1,342 controls) and two European populations (9,023 cases and 386,896 controls) using logistic regression analysis. Findings: Among the 197 candidate SNPs within MREs of 186 CRC-circRNAs, rs25497 in circTUBB was significantly associated with colorectal cancer risk in a Chinese population after false discovery rate (FDR) correction [odds ratio (OR) = 1.78, 95% confidence interval (CI) = 1.44-2.21, P = 1.42×10-7, PFDR = 2.80×10-5] and even reached significance in a genomewide association study (GWAS) under the dominant model (P = 1.28×10-8). Similar results were found in the European populations (ORmeta = 1.30, 95% CI = 1.10-1.53). Both stratified and interaction analyses revealed that rs25497 interacting with smoking affected the colorectal cancer risk (Pinteraction = 1.48×10-2). Interpretation: We first comprehensively identified genetic variants in MREs of colorectal cancer-associated circRNAs (CRC-circRNAs) and evaluated their effects on colorectal cancer risk in both Chinese and European populations. These findings provide basis for comprehensive understanding of colorectal cancer etiology. Funding Statement: This study was partly supported by National Natural Science Foundation of China (81703307, 21575064) and the Natural Science Foundation of Jiangsu Province (BK20181371) and the project of National Key Research and Development Plan of China (2017YFC1309201). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: This study was approved by the Institutional Review Board of Nanjing Medical University.
- Published
- 2019
35. Genetic variants in multisynthetase complex genes are associated with DNA damage levels in Chinese populations
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Yuzhuo Wang, Hongxia Ma, Yang Cheng, Kaipeng Xie, Juncheng Dai, Hongbing Shen, Zhibin Hu, Jiangbo Du, Weihong Chen, Jing Yuan, Meilin Wang, Zhengdong Zhang, Jia Liu, Guangfu Jin, Tangchun Wu, Wei Shen, Meng Zhu, and Liguo Geng
- Subjects
Lysine-tRNA Ligase ,0301 basic medicine ,China ,DNA Repair ,Genotyping Techniques ,DNA repair ,DNA damage ,Health, Toxicology and Mutagenesis ,Biology ,Polymorphism, Single Nucleotide ,Amino Acyl-tRNA Synthetases ,03 medical and health sciences ,0302 clinical medicine ,Asian People ,Gene Frequency ,Databases, Genetic ,Genetic variation ,Genetics ,Humans ,Lymphocytes ,Allele ,Molecular Biology ,Gene ,Allele frequency ,Alleles ,Tumor Suppressor Proteins ,Genetic Variation ,Peptide Elongation Factors ,EPRS ,Molecular biology ,Comet assay ,030104 developmental biology ,030220 oncology & carcinogenesis ,Comet Assay ,DNA Damage - Abstract
Aminoacyl-tRNA synthetases (ARSs) and ARS-interacting multi-functional proteins (AIMPs) form a multisynthetase complex (MSC) and play an important role in the process of DNA damage repair. We hypothesized that genetic variants in key ARSs and AIMPs might regulate the DNA damage response. Therefore, we systematically screened 23 potentially functional polymorphisms in MSC genes and evaluated the association between the genetic variants and DNA damage levels in 307 subjects from three cities in southern, central and northern China (Zhuhai, Wuhan and Tianjin, respectively). We examined personal 24-h PM2.5 exposure levels and DNA damage levels in peripheral blood lymphocytes for each subject. We found that the variant allele of rs12199241 in AIMP3 was significantly associated with DNA damage levels (β=0.343, 95%CI: 0.133-0.554, P=0.001). Meanwhile, the results of rs5030754 in EPRS and rs3784929 in KARS indicated their suggestive roles in DNA damage processes (β=0.331, 95%CI: 0.062-0.599, P=0.016 for rs5030754; β=0.192, 95%CI: 0.016-0.368, P=0.033 for rs3784929, respectively). After multiple testing, rs12199241 was still significantly associated with DNA damage levels. Combined analysis of these three polymorphisms showed a significant allele-dosage association between the number of risk alleles and higher DNA damage levels (Ptrend
- Published
- 2016
36. Sex hormones and genetic variants in hormone metabolic pathways associated with the risk of colorectal cancer
- Author
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Lingjun Zhu, Shuwei Li, Haiyan Chu, Meilin Wang, Dongying Gu, Yixuan Meng, Mulong Du, Lisheng Xie, Chen Yehua, and Zhengdong Zhang
- Subjects
Male ,010504 meteorology & atmospheric sciences ,Colorectal cancer ,Cell ,010501 environmental sciences ,01 natural sciences ,Sex hormone-binding globulin ,Tandem Mass Spectrometry ,Humans ,Medicine ,Clinical significance ,Allele ,Gonadal Steroid Hormones ,lcsh:Environmental sciences ,0105 earth and related environmental sciences ,General Environmental Science ,lcsh:GE1-350 ,biology ,business.industry ,Cell growth ,Cell cycle ,medicine.disease ,medicine.anatomical_structure ,biology.protein ,Cancer research ,Colorectal Neoplasms ,business ,Metabolic Networks and Pathways ,Chromatography, Liquid ,Hormone - Abstract
Objective: The different incidence of colorectal cancer between the sexes suggests that sex hormones may be involved in the susceptibility to colorectal cancer. The association between sex hormones and genetic variants in hormone metabolic pathways and the colorectal cancer risk remains unclear. Methods: We detected sex hormone levels in plasma from colorectal cancer patients and controls in males by ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). We evaluated the clinical significance of sex hormones on colorectal cancer diagnosis with the area under the receiver operating characteristic curve (AUC). The role of genetic variants in hormone metabolic pathways in the colorectal cancer risk was assessed by a logistic regression model. The biological functions were detected by luciferase reporter assays and cell behavior experiments. Results: We found that 2-methoxyestrone (2-MeO-E1) was highly expressed in cases (PFDR = 3.48 × 10−19). The expression of 2-MeO-E1 in plasma showed improved accuracy for predicting colorectal cancer (AUC = 0.88). In the 2-MeO-E1 metabolic pathway, rs165599 in COMT was significantly associated with an increased risk of colorectal cancer (P = 0.009). Mechanistically, we found that the rs165599 G allele could decrease the binding ability of miR-22-3p to the COMT 3′-UTR. Furthermore, knockdown of COMT inhibited cell proliferation, induced cell apoptosis and arrested the cell cycle in the G1 phase. Conclusion: This is the first study to show that 2-MeO-E1 and a genetic variant in COMT contribute to the susceptibility to colorectal cancer. These results shed light on the different incidence of colorectal cancer between the sexes. Keywords: Sex hormone, UPLC-MS/MS, Colorectal cancer, Genetic variants
- Published
- 2020
37. The Association Study of CpG-SNPs in Gastric Acid Secretion Pathway Genes and Gastric Cancer Risk
- Author
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Shuwei Li, Zhengdong Zhang, Mengting Liu, Wang Meilin, Chu Haiyan, and Mulong Du
- Subjects
CpG site ,Gastric Acid Secretion Pathway ,Genetic variation ,Cancer research ,Single-nucleotide polymorphism ,Methylation ,Biology ,Cancer risk ,Gene - Published
- 2018
38. Genetic Variants in m6A-Switches Among hnRNP C Binding Sites are Associated with Bladder Cancer Risk
- Author
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Zheng Guo, Haiyan Chu, Chao Qin, Qiang Lv, Zhengdong Zhang, Meilin Wang, Yu Jin, Mulong Du, Lin Yuan, Hanting Liu, Yuqiu Ge, Yadi Lin, and Qi Yuan
- Subjects
Oncology ,medicine.medical_specialty ,Bladder cancer ,business.industry ,Cancer ,medicine.disease ,Institutional review board ,Internal medicine ,Genetic variation ,Expression quantitative trait loci ,medicine ,Personalized medicine ,Allele ,business ,Preventive healthcare - Abstract
Objective: N6-Methyladenosine (m6A), an abundant and prevalent chemical modification on RNA, is involved in multiple biological processes. Recent reports have identified that m6A guides the interaction of RNA-binding proteins such as hnRNP C and their target RNAs, which is termed as m6A-switches. Here we aim to investigate the contribution of genetic variants in m6A-switches to the development of bladder cancer. Methods: A two-stage case-control study was performed to systematically evaluate the association of genetic variants in m6A-switches with bladder cancer risk in 3,997 subjects (discovery stage: 578 cases and 1,006 controls; validation stage: 1,026 cases and 1,387 controls). The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), GTEx Portal and m6AVar were used to conduct bioinformatics analysis. The real-time PCR (RT-PCR) was conducted to detect the relative SOD2 mRNA expression level. Results: We identified that rs5746136 (G>A) in m6A-switches was significantly associated with the reduced risk of bladder cancer (addictive model in discovery stage: adjusted OR = 0.80, 95%CI = 0.69-0.93, P = 3.6—10-3; validation stage: adjusted OR = 0.88, 95%CI= 0.79-0.99, P = 3.0—10-2). In combined analysis, the P value for the association between rs5746136 and bladder cancer reached 4.0—10-4 (adjusted OR = 0.85, 95%CI = 0.78-0.93). Using expression quantitative trait locus (eQTL) analysis and public database, we observed that rs5746136 A allele reduced the expression level of SOD2 in bladder tissues. SOD2 was abnormally expressed in bladder cancer and correlated to m6A modifying enzymes. Conclusion: Our findings uncovered the important role of genetic variants in m6A-switches in bladder cancer susceptibility and indicated that the aberrant expression of SOD2 may be biologically relevant to bladder carcinogenesis. Funding: National Natural Science Foundation of China (81473050), Jiangsu Provincial 333 project, Collaborative Innovation Center for Cancer Personalized Medicine, and the Priority Academic Program Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine). Declaration of Interest: The authors declare no competing financial interests. Ethical Approval: This study was approved by the Institutional Review Board of Nanjing Medical University.
- Published
- 2018
39. Personal exposure to PM2.5, genetic variants and DNA damage: A multi-center population-based study in Chinese
- Author
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Minjie Chu, Tangchun Wu, Meilin Wang, Jing Yuan, Zhengdong Zhang, Meng Zhu, Jianhang Gong, Xiaojie Ding, Yankai Xia, Chongqi Sun, Zhibin Hu, Guangfu Jin, Juncheng Dai, Weihong Chen, Haidong Kan, Hongbing Shen, Yuanchao Song, Xuejiang Guo, Yun Pan, and Mulong Du
- Subjects
Male ,China ,Genotype ,DNA damage ,Genome-wide association study ,Biology ,Toxicology ,complex mixtures ,Asian People ,Genetic variation ,Humans ,Particle Size ,Gene ,Genotyping ,Exome ,Aged ,Genetics ,Mutagenesis ,Genetic Variation ,General Medicine ,Middle Aged ,Comet assay ,Mutation ,Female ,Particulate Matter ,DNA Damage - Abstract
Exposure to particulate matter (e.g., PM2.5) may result in DNA damage, a major culprit in mutagenesis and environmental toxicity. DNA damage levels may vary among individuals simultaneously exposed to PM2.5, however, the genetic determinants are still unclear. To explore whether PM2.5 exposure and genetic variants contribute to the alteration in DNA damage, we recruited 328 subjects from three independent cohorts (119 from Zhuhai, 123 from Wuhan and 86 from Tianjin) in southern, central and northern China with different PM2.5 exposure levels. Personal 24-h PM2.5 exposure levels and DNA damage levels of peripheral blood lymphocytes were evaluated. Genotyping were performed using Illumina Human Exome BeadChip with 241,305 single nucleotide variants (SNVs). The DNA damage levels are consistent with the PM2.5 exposure levels of each cohort. A total of 35 SNVs were consistently associated with DNA damage levels among the three cohorts with pooled P values less than 1.00 × 10 −3 after adjustment for age, gender, smoking status and PM2.5 exposure levels, of which, 18 SNVs together with gender and PM2.5 exposure levels were independent factors contributing to DNA damage. Gene-based test revealed 3 genes significantly associated with DNA damage levels ( P = 5.11 × 10 −3 for POLH , P = 2.88 × 10 −3 for RIT2 and P = 2.29 × 10 −2 for CNTN4 ). Gene ontology (GO) analyses indicated that the identified variants were significantly enriched in DNA damage response pathway. Our findings highlight the importance of genetic variation as well as personal PM2.5 exposure in modulating individual DNA damage levels.
- Published
- 2015
40. A miR-29c binding site genetic variant in the 3′-untranslated region of LAMTOR3 gene is associated with gastric cancer risk
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Peng Song, Guoquan Tao, Haiyan Chu, Weida Gong, Qinghong Zhao, Jianwei Zhou, Weizhi Wang, Meilin Wang, Dongmei Wu, Na Tong, Zhengdong Zhang, Haixia Zhu, and Baolin Wang
- Subjects
Male ,WWOX ,Oncology ,medicine.medical_specialty ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Metastasis ,Risk Factors ,Stomach Neoplasms ,Internal medicine ,medicine ,Genetic predisposition ,Humans ,Genetic Predisposition to Disease ,Stomach cancer ,3' Untranslated Regions ,Genetic Association Studies ,Adaptor Proteins, Signal Transducing ,Aged ,Demography ,Pharmacology ,Three prime untranslated region ,General Medicine ,Odds ratio ,Middle Aged ,medicine.disease ,Molecular biology ,MicroRNAs ,Tumor progression ,Female - Abstract
Single nucleotide polymorphisms (SNPs) in the 3′-untranslated regions (UTRs) targeted by putative mircoRNAs (miRNAs) could influence the susceptibility of cancer. Recently, miR-29c has been reported to be down-regulated in gastric cancer (GC) and serve as a tumor suppressor that regulated tumor progression. The present study was aimed at investigating whether the miR-29c binding site SNPs within the 3′-UTRs of target genes affected the gastric cancer risk. Using bioinformatics tools, we chose three SNPs (IGHMBP2 rs3750980, LAMTOR3 rs11944405 and WWOX rs2288035) located in miR-29c binding sites. We genotyped these three SNPs to assess their associations with GC risk in a case-control study comprising 753 GC cases and 950 controls. Among these three SNPs, we found a significantly decreased risk of GC associated with the LAMTOR3 rs11944405 T > C polymorphism [TC vs. TT, adjusted odds ratio (OR) = 0.79, 95% confidence interval (CI) = 0.63–0.99; TC/CC vs. TT, adjusted OR = 0.81, 95% CI = 0.65–1.00]. The significant association was also presented in the subgroup analysis by age (≤ 65), sex (female), depth of invasion (T3/T4), lymph node metastasis (N1-3), distant metastasis (M0) and TNM stage (III/IV). However, no significant association was detected for IGHMBP2 rs3750980 and WWOX rs2288035. Our results suggested that the LAMTOR3 rs11944405 polymorphism may be a potential biomarker for genetic susceptibility to GC.
- Published
- 2015
41. Hsa-miR-196a2 polymorphism increases the risk of acute lymphoblastic leukemia in Chinese children
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Zhengdong Zhang, Mulong Du, Xin Li, Na Tong, Meilin Wang, Jie Li, Danni Shi, Dongmei Wu, Bin Xu, Xiaojing Sheng, Haiyan Chu, and Yongjun Fang
- Subjects
Male ,Risk ,Oncology ,medicine.medical_specialty ,Health, Toxicology and Mutagenesis ,Single-nucleotide polymorphism ,Biology ,medicine.disease_cause ,Bioinformatics ,Polymorphism, Single Nucleotide ,Internal medicine ,Genotype ,Genetics ,medicine ,Genetic predisposition ,Humans ,SNP ,Child ,Molecular Biology ,Heterozygote advantage ,Environmental Exposure ,Odds ratio ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Confidence interval ,MicroRNAs ,Case-Control Studies ,Child, Preschool ,Female ,Carcinogenesis - Abstract
Acute lymphoblastic leukemia (ALL) is a major cause of mortality and morbidity in childhood, and the causes of ALL are not completely understood. microRNAs (miRNAs) regulate various biological processes including organ development, cell growth regulation, cell differentiation, apoptosis, and tumorigenesis. We performed a case–control study with 570 childhood ALL cases and 673 cancer-free controls to investigate the association between hsa-miR-196a2 rs11614913 T > C polymorphism and ALL risk. The bioinformatics was used to estimate the potential target of hsa-miR-196a2. In the present study, the hsa-miR-196a2 variant TC heterozygote, and CC/TC genotypes were found to be associated with a significantly increased childhood ALL risk, compared with the TT wild-type homozygote (adjusted OR = 1.50, 95% CI = 1.15–1.95 for TC and OR = 1.40, 95% CI = 1.09–1.79 for CC/TC). Further, the difference was pronounced in younger (≤6) subjects or parental non-drinker. The significance of the increased risk is more obvious than the higher treatment branch. Additionally, we found that the rs11614913 TC genotype can increase B-phenotype ALL risk (OR = 1.37, 95% CI = 1.07–1.76). Finally, combination of three bioinformatics approaches revealed that HOXC8 may be the target gene of hsa-miR-196a2. Taken together, our finding suggested that hsa-miR-196a2 rs11614913 T > C may increase the risk of childhood ALL. Large studies with the function of hsa-miR-196a2 are needed in the further study.
- Published
- 2014
42. Tagging SNPs in the ERCC4 gene are associated with gastric cancer risk
- Author
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Qinghong Zhao, Yongfei Tan, Dongmei Wu, Ming Xu, Haiyan Chu, Dewei Luo, Zhengdong Zhang, Shizhi Wang, Weida Gong, Meilin Wang, and Yan Gao
- Subjects
Male ,medicine.medical_specialty ,Single-nucleotide polymorphism ,Biology ,Bioinformatics ,Polymorphism, Single Nucleotide ,Gastroenterology ,Asian People ,Stomach Neoplasms ,Internal medicine ,Genotype ,Odds Ratio ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Aged ,Multifactor dimensionality reduction ,Smoking ,Haplotype ,Cancer ,General Medicine ,Odds ratio ,Middle Aged ,medicine.disease ,DNA-Binding Proteins ,Minor allele frequency ,Logistic Models ,Haplotypes ,Case-Control Studies ,Female ,Gene-Environment Interaction ,ERCC4 - Abstract
ERCC4 plays an essential role in the nucleotide excision repair (NER) pathway, which is involved in the removal of a wide variety of DNA lesions. To determine whether the ERCC4 tagging SNPs (tSNPs) are associated with risk of gastric cancer, we conducted a hospital-based case-control study of 350 cases and 468 cancer-free controls. In the logistic regression (LR) analysis, we found a significantly decreased risk of gastric cancer associated with the rs744154 GC/CC genotypes [adjusted odds ratio (OR) = 0.56, 95% confidence interval (CI) = 0.42–0.75, false discovery rate (FDR) P = 0.003] compared with the wild-type GG genotype. Haplotype-based association study revealed that the CGC haplotype that containing the rs744154 C allele can decrease the risk of gastric cancer compared with the most common haplotype GGT (adjusted OR = 0.61, 95% CI = 0.46–0.81). Using the multifactor dimensionality reduction (MDR) analysis, we identified that the SNP rs744154 and smoking status were the best two predictive factors for gastric cancer with a testing accuracy of 55.76% and a perfect cross-validation consistency (CVC) of 10 (P = 0.001). Furthermore, the smokers with the rs744154 GC/CC genotypes showed a decreased risk of gastric cancer (adjusted OR = 0.55, 95% CI = 0.35–0.85) compared with the smokers with the GG genotype using multivariate LR analysis. The above findings consistently suggested that genetic variants in the ERCC4 gene may play a protective role in the etiology of gastric cancer, even in the smokers.
- Published
- 2013
43. Levels of phthalate esters in settled house dust from urban dwellings with young children in Nanjing, China
- Author
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Xiaomei Lu, Renzheng Zhao, Qi Zhang, Bingling Wang, Zhengdong Zhang, Xiaoling Zhang, Dong-Mei Zhu, and Yong-Gang Sun
- Subjects
Atmospheric Science ,Wax ,Environmental engineering ,Phthalate ,Plastic materials ,chemistry.chemical_compound ,chemistry ,Benzyl butyl phthalate ,visual_art ,Environmental chemistry ,visual_art.visual_art_medium ,Environmental science ,Gas chromatography ,Detection rate ,General Environmental Science - Abstract
To investigate the levels and possible determinants of phthalate esters (PEs) in settled house dust from urban dwellings with young children, dust was collected from 215 urban houses in Nanjing, China, and 145 outdoor settled dust samples were collected nearby. Six PEs were measured by gas chromatography/mass spectrometry. All PEs were detected in the dust from approximately 90% of the houses, with the exception of dioctyl phthalate (DOP), which had only a 59% detection rate. Di-2-ethylhexyl phthalate (DEHP) and di-n-butyl phthalate (DBP) were the most abundant PEs, with geometric means of 110 and 16.4 μg g−1, respectively, and maximal concentrations 9950 and 2150 μg g−1. Factor analysis showed that DBP, DEHP and benzyl butyl phthalate (BBP) might come from the same source and were significantly influenced by the use of solid-wood floor wax. High BBP, DEHP, DOP and total PE levels were associated with indices of dampness, and high DOP was associated with humidifier use. In conclusion, six PEs are ubiquitous in urban settled house dust in Nanjing, China, and both plastic materials and cosmetic and personal care products are important sources. Flooring material, dampness and humidifier use potentially influence house dust PE levels.
- Published
- 2013
44. Regioselective nucleophilic addition of 3-aryl-5-difluoromethyl-isoxazoles to aldehydes
- Author
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Fanhong Wu, Dong Zhang, Xiang Fang, Xueyan Yang, Zhengdong Zhang, and Yanlin Yu
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Steric effects ,Nucleophilic addition ,Aryl ,Organic Chemistry ,Regioselectivity ,Biochemistry ,Nucleophilic abstraction ,Inorganic Chemistry ,chemistry.chemical_compound ,chemistry ,Nucleophile ,Environmental Chemistry ,Organic chemistry ,Acid hydrolysis ,Physical and Theoretical Chemistry - Abstract
A series of 5-difluoromethyl-isoxazoles 2 were prepared, and their regioselective nucleophilic addition to aldehydes was investigated. It was found that the nucleophilic difluoromethylation of aldehydes with 5-difluoromethyl-isoxazoles could be efficiently and uniquely achieved in the presence of LDA as a base that provides a large steric hindrance. In contrast, 3,4,5-trisubstituted 5-difluoromethyl isoxazoles were alternatively afforded as the sole product in moderate yields when n -BuLi was used as the base.
- Published
- 2013
45. Polymorphisms in the IL-13 and IL-4R genes are associated with the development of renal cell carcinoma
- Author
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Dongyan Zhong, Xuping Pan, Lan Ma, Fu Yan, Chao Qin, Haiyan Chu, Changjun Yin, Danni Shi, Meilin Wang, and Zhengdong Zhang
- Subjects
Male ,Oncology ,medicine.medical_specialty ,Genotype ,urologic and male genital diseases ,Polymorphism, Single Nucleotide ,Immune system ,Renal cell carcinoma ,Polymorphism (computer science) ,Internal medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,Receptor ,Carcinoma, Renal Cell ,Interleukin 4 ,Interleukin-13 ,business.industry ,Interleukin-4 Receptor alpha Subunit ,Cancer ,Hematology ,Middle Aged ,medicine.disease ,Kidney Neoplasms ,Case-Control Studies ,Immunology ,Interleukin 13 ,Female ,business - Abstract
Background Cytokines are the important modulators that bind to their relevant receptors in response to some stimuli to mediate the homeostasis. It has been suggested that the imbalance of immune system of the host might affect the generation of diseases, including cancers. Patients and methods We investigated the association between six functional polymorphisms of IL-4, IL-13, and IL-4R genes and susceptibility to renal cell cancer in a hospital-based study, including 620 renal cell carcinoma (RCC) patients and 623 controls. Logistic regression model was used to assess the genetic effects on the development of RCC. Results Overall, individuals with IL-4R Ile50Val CT/TT genotypes had a 0.34-fold significantly decreased RCC risk (CT/TT versus CC), and the T variant allele was associated with a decreased risk of RCC in a dose–response manner (Ptrend = 0.009). In addition, we also observed that IL-13 C-1055T and Arg130Gln polymorphisms could decrease the risk of RCC [TT versus CC/CT: odds ratio = 0.36, 95% confidence interval (CI) = 0.16–0.78; AA versus GG/GA: 0.66, 0.44–0.97, respectively]. Furthermore, a multiplicative interaction association between the combined IL-4R Ile50Val and IL-13 C-1055T genotypes was observed to decrease the risk of RCC (P = 0.036). Conclusion IL-13 and IL-4R may play an important role in the etiology of RCC.
- Published
- 2012
46. The polymorphisms in the VHL and HIF1A genes are associated with the prognosis but not the development of renal cell carcinoma
- Author
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Xiaoxin Meng, Meilin Wang, Xiaobing Ju, Changjun Yin, Chao Qin, Wei Zhang, Jian Zhu, Fu Yan, Qiang Cao, Pu Li, Qi Ding, Min Gu, Jianchun Chen, and Zhengdong Zhang
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Genotype ,Tumor suppressor gene ,Single-nucleotide polymorphism ,Kaplan-Meier Estimate ,urologic and male genital diseases ,Bioinformatics ,Polymorphism, Single Nucleotide ,Gene Frequency ,Renal cell carcinoma ,Internal medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,Allele ,Carcinoma, Renal Cell ,neoplasms ,Genetic Association Studies ,Aged ,Proportional Hazards Models ,Proportional hazards model ,business.industry ,Hematology ,Middle Aged ,Hypoxia-Inducible Factor 1, alpha Subunit ,Prognosis ,medicine.disease ,Kidney Neoplasms ,female genital diseases and pregnancy complications ,HIF1A ,Von Hippel-Lindau Tumor Suppressor Protein ,Case-Control Studies ,Multivariate Analysis ,Cohort ,Female ,business - Abstract
Background The von Hippel–Lindau (VHL) tumor suppressor gene and hypoxia-inducible factor-1α (HIF1A) play a pivotal role in renal carcinogenesis. This study was aimed to clarify the influence of VHL and HIF1A polymorphisms on renal cell cancer (RCC) susceptibility and survival. Subjects and methods We genotyped four potentially functional single-nucleotide polymorphisms (rs779805 in VHL and rs11549465, rs11549467, and rs2057482 in HIF1A) and assessed their associations with RCC risk, clinicopathologic parameters in a case–control study of 620 patients and 623 controls, and the prognosis of RCC in a cohort of 311 patients. Results No significant differences in VHL or HIF1A genotypes were observed between RCC cases and controls. However, individuals with ≥2 variant alleles of the four polymorphisms were associated with less frequent lymph node metastasis and lower clinical stage (P = 0.032 and P = 0.041, respectively). And the number of variant alleles was associated with improved survival in a dose–response manner (Ptrend = 0.013). Furthermore, multivariate Cox regression analysis showed that the number of variant alleles (≥1 versus 0) was an independent prognostic factor for RCC survival (P = 0.036) together with clinical stage and tumor grade. Conclusion The VHL and HIF1A polymorphisms may not influence RCC susceptibility but may jointly influence RCC progression and survival.
- Published
- 2012
47. Impact of genotypic and phenotypic resistance to second-line anti-tuberculosis drugs on treatment outcomes in multidrug-resistant tuberculosis in China
- Author
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Xubin Zheng, Sven Hoffner, Qun Li, Zhu Ning, Yi Hu, and Zhengdong Zhang
- Subjects
0301 basic medicine ,Microbiology (medical) ,Drug ,medicine.medical_specialty ,China ,Tuberculosis ,Multidrug resistant tuberculosis ,media_common.quotation_subject ,030106 microbiology ,lcsh:QR1-502 ,Drug resistance ,Pharmacology ,Gene mutation ,lcsh:Microbiology ,03 medical and health sciences ,Internal medicine ,medicine ,Culture conversion ,media_common ,business.industry ,Pyrazinamide ,medicine.disease ,Multiple drug resistance ,Treatment ,Infectious Diseases ,PncA ,Molecular diagnosis ,business ,medicine.drug - Abstract
Background Despite the strong association between drug resistance and genetic mutations, the value of molecular diagnosis of drug resistance to guide the treatment of multidrug-resistant tuberculosis (MDR-TB) remains unclear. This is particularly relevant in resource-limited areas, in which it is difficult to implement the drug susceptibility test. Here, we focused on the association of drug susceptibility phenotype and genotype with treatment outcomes in patients with MDR-TB. Methods In a prospective cohort study, we enrolled 252 consecutive patients with confirmed MDR-TB between 2010 and 2013, and outcomes were followed-up over the 24-month treatment course in terms of clinical manifestation and sputum conversion. All the isolates were tested for phenotypic susceptibility to second-line drugs in the Mycobacteria Growth Indicator Tube based system, and genotypic mutations were assessed by DNA sequencing. Results Among the 252 MDR-TB isolates, 88 (34.9%) were resistant to fluoroquinolones and/or second-line injectable drugs, of which 65 (73.9%) harbored a mutation in drug resistance-related genes ( gyrA , rrs and eis ). In addition, 85 individuals (33.7%) were also resistant to pyrazinamide, with 87.1% containing the pncA mutation. Of 252 MDR-TB patients, 207 (82.1%) had known outcomes and 45 (17.9%) were lost to follow-up. Among those with known outcomes, treatment succeeded in 85.8% with plain MDR-TB, 69.7% with initial resistance to either a fluoroquinolone or second-line injective drugs, 37.5% with initial resistance to pyrazinamide, 29.3% with initial extensively drug resistance. In contrast, among those with known outcomes, treatment success and culture conversion depends on the susceptibility to drug especially for pyrazinamide and fluoroquinolones. In multivariate analysis, pyrazinamide resistance and its related pncA gene mutation were independently associated with a lower risk of culture conversion on at 8 weeks and treatment success, while fluoroquinolone resistance was negatively correlated with treatment success. Besides, specific treatment, patient and program variables were also associated with treatment outcome. Conclusion Drug susceptibility testing for pyrazinamide and fluoroquinolones together with genetic information appears to provide a clinically useful indicator of the treatment outcome of MDR-TB in China.
- Published
- 2016
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48. Retraction Notice to: Nested Inversion Polymorphisms Predispose Chromosome 22q11.2 to Meiotic Rearrangements
- Author
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Wolfram Demaerel, Matthew S. Hestand, Elfi Vergaelen, Ann Swillen, Marcos López-Sánchez, Luis A. Pérez-Jurado, Donna M. McDonald-McGinn, Elaine Zackai, Beverly S. Emanuel, Bernice E. Morrow, Jeroen Breckpot, Koenraad Devriendt, Joris R. Vermeesch, Kevin Antshel, Celso Arango, Marco Armando, Anne Bassett, Carrie Bearden, Erik Boot, Marta Bravo-Sanchez, Elemi Breetvelt, Tiffany Busa, Nancy Butcher, Linda Campbell, Miri Carmel, Eva Chow, T. Blaine Crowley, Joseph Cubells, David Cutler, Maria Cristina Digilio, Sasja Duijff, Stephan Eliez, Beverly Emanuel, Michael Epstein, Rens Evers, Luis Fernandez Garcia-Moya, Ania Fiksinski, David Fraguas, Wanda Fremont, Rosemarie Fritsch, Sixto Garcia-Minaur, Aaron Golden, Doron Gothelf, Tingwei Guo, Ruben Gur, Raquel Gur, Damian Heine-Suner, Matthew Hestand, Stephen Hooper, Wendy Kates, Leila Kushan, Alejandra Laorden-Nieto, Johanna Maeder, Bruno Marino, Christian Marshall, Kathryn McCabe, Donna McDonald-McGinn, Elena Michaelovosky, Bernice Morrow, Edward Moss, Jennifer Mulle, Declan Murphy, Kieran Murphy, Clodagh Murphy, Maria Niarchou, Claudia Ornstein, Michael Owen, Nicole Philip, Gabriela Repetto, Maude Schneider, Vandana Shashi, Tony Simon, Flora Tassone, Marta Unolt, Therese van Amelsvoort, Marianne van den Bree, Esther Van Duin, Joris Vermeesch, Stefano Vicari, Claudia Vingerhoets, Jacob Vorstman, Steve Warren, Ronnie Weinberger, Omri Weisman, Abraham Weizman, Zhengdong Zhang, and Michael Zwick
- Subjects
Genetics ,DNA Copy Number Variations ,Notice ,Chromosome ,Locus (genetics) ,Inversion (meteorology) ,Biology ,Polymorphism, Single Nucleotide ,Genome ,Human genetics ,Retraction ,Meiosis ,Polymorphism (computer science) ,Report ,Chromosome Inversion ,DiGeorge Syndrome ,Humans ,Genetic Predisposition to Disease ,Chromosome Deletion ,Homologous Recombination ,In Situ Hybridization, Fluorescence ,Genetics (clinical) - Abstract
(The American Journal of Human Genetics 101, 616–622; October 5, 2017) This article has been retracted at the request of the authors. In this article, we claimed the presence of nested inversion polymorphisms, spanning the LCR22-B/D or LCR22-C/D locus. We detected an increased frequency of inversions in the chromosomes of the parental genome in which the 22qll.2 rearrangement occurred. Since this publication, we have continued working on an improved map of the 22qll Iocus. During these efforts, we were unable to confirm the presence of the inversion polymorphism. We proved the polymorphism to be absent and the original data to be biased. Absence of a double-blinded control left complex observations open to interpretation and hampered objective analysis. With this crucial flaw uncovered, we no longer support these data and are retracting the article. We apologize to the scientific community, the readers of AJHG, and the families who were involved in this research.
- Published
- 2018
49. Polymorphisms in the FOXP3 gene in Han Chinese psoriasis patients
- Author
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Lin Gao, Ling Liu, Tianwen Gao, Zhengdong Zhang, Kai Li, Fang Li, Hong Li, Yufeng Liu, and Lin Wang
- Subjects
Adult ,CD4-Positive T-Lymphocytes ,Male ,China ,medicine.medical_specialty ,Adolescent ,Single-nucleotide polymorphism ,Dermatology ,Biology ,Polymorphism, Single Nucleotide ,Biochemistry ,Gastroenterology ,Autoimmune Diseases ,Asian People ,Psoriasis ,Internal medicine ,Genotype ,medicine ,Humans ,Allele ,Child ,Molecular Biology ,Polymorphism, Single-Stranded Conformational ,Polymorphism, Genetic ,Interleukin-2 Receptor alpha Subunit ,Case-control study ,Forkhead Transcription Factors ,Middle Aged ,medicine.disease ,Genotype frequency ,Case-Control Studies ,Immunology ,Female ,Gene polymorphism ,Restriction fragment length polymorphism ,Polymorphism, Restriction Fragment Length - Abstract
Background Psoriasis is a common dermatological disorder, in which autoimmunity plays an important role. CD4+CD25+ regulatory T cells (T-regs) have been suggested to be involved in the pathogenesis of some autoimmune diseases. T-regs express the fork head/winged helix transcription factor, FOXP3, which appears to be of key importance in the development and function of T-regs. Studies have found that single-nucleotide polymorphisms (SNPs) in the FOXP3 gene contribute to susceptibility to some autoimmune disorders. However, information about FOXP3 gene in psoriasis is limited. Objective This study evaluated the association between FOXP3 gene SNPs and susceptibility to psoriasis in a Han Chinese population. Methods In a hospital-based case–control study, 524 patients with psoriasis and 549 psoriasis-free controls were recruited according to age and gender. We investigated four SNPs in the FOXP3 gene (-6054, deletion/ATT; -3279, A/C; -924, A/G; IVS9+459, A/G) in psoriatic patients, and assessed allele and genotype frequencies in psoriatic patients (237 females, 287 males) and normal controls (272 females, 277 males). The polymorphisms were genotyped using the PCR sequence-specific primer (PCR-SSP) technique and PCR-restriction fragment length polymorphism (RFLP) analysis. Results We found that increased risk of psoriasis was associated with the FOXP3 -3279 AC genotype (adjusted OR, 1.32; 95% CI, 1.01–1.74) and the combined AC + AA genotype (adjusted OR, 1.38; 95% CI, 1.07–1.78), compared with the -3279 CC genotype. We also found that an increased risk of psoriasis was associated with the FOXP3 IVS9+459 GG genotype (adjusted OR, 2.24; 95% CI, 1.41–3.58). However, the combined GA + GG genotype showed no such tendency (adjusted OR = 1.28; 95% CI, 1.00–1.64), compared with the IVS9+459 AA genotype. There was no evidence of an increased risk associated with the FOXP3-6054 deletion/ATT or FOXP3-924 A/G genotype. In combined genotype analyses, the FOXP3-3279 AC + AA genotype was more obviously associated in males (adjusted OR = 1.60, 95% CI = 1.11–2.31) and severe psoriasis patients (PASI score >20; adjusted OR = 1.97, 95% CI = 1.41–2.75). Meanwhile, the FOXP3 IVS9+459 GA + GG genotype was also associated with severe psoriasis patients (adjusted OR = 1.69, 95% CI = 1.21–2.36). Conclusions FOXP3 polymorphisms appear to contribute to the risk of psoriasis in a Han Chinese population. Larger studies are needed to confirm these findings.
- Published
- 2010
50. Systematic inflammatory response markers (SIRs) factors associated with pain prevalence and other characteristics in advanced cancer patients
- Author
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Xiao Li Gu, Wenwu Cheng, Menglei Cheng, Ming Hui Liu, Zhengdong Zhang, and W. Zhao
- Subjects
Pathology ,medicine.medical_specialty ,Oncology ,business.industry ,Inflammatory response ,Internal medicine ,medicine ,Hematology ,business ,Advanced cancer - Published
- 2017
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