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Prioritization of risk genes in colorectal cancer by integrative analysis of multi-omics data and gene networks

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Science China(Life Sciences) 2024年第1期67卷 132-148页

作者： Ming Zhang Xiaoyang Wang Nan Yang Xu zhu Zequn Lu Yimin Cai Bin Li Ying zhu Xiangpan Li yongchang Wei Shaokai Zhang Jianbo Tian Xiaoping Miao Department of Epidemiology and Biostatistics School of Public HealthDepartment of Gastrointestinal OncologyZhongnan Hospital of Wuhan UniversityDepartment of Radiation OncologyRenmin Hospital of Wuhan UniversityTaiKang Center for Life and Medical SciencesWuhan UniversityWuhan 430071China Research Center of Public Health Renmin hospital of Wuhan UniversityWuhan UniversityWuhan 430060China Department of Cancer Epidemiology The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalHenan Engineering Research Center of Cancer Prevention and ControlHenan International Joint Laboratory of Cancer PreventionZhengzhou 450008China Department of Gastrointestinal Surgery Renmin Hospital of Wuhan UniversityWuhan 430060China Department of Radiation Oncology Renmin Hospital of Wuhan UniversityWuhan 430060China Department of Gastrointestinal Oncology Hubei Cancer Clinical Study CenterZhongnan Hospital of Wuhan UniversityWuhan 430062China Department of Epidemiology and Biostatistics School of Public HealthTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430073China Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine Nanjing Medical UniversityNanjing 211166China

Genome-wide association studies(GWASs)have identified over 140 colorectal cancer(CRC)-associated loci;however,target genes at the majority of loci and underlying molecular mechanisms are poorly understood.Here,we utilized a Bayesian approach,integrative risk gene selector(iRIGS),to prioritize risk genes at CRC GWAS loci by integrating multi-omics data.As a result,a total of 105 high-confidence risk genes(HRGs)were identified,which exhibited strong gene dependencies for CRC and enrichment in the biological processes implicated in CRC.Among the 105 HRGs,CEBPB,located at the 20q13.13 locus,acted as a transcription factor playing critical roles in cancer.Our subsequent assays indicated the tumor promoter function of CEBPB that facilitated CRC cell proliferation by regulating multiple oncogenic pathways such as MAPK,PI3K-Akt,and Ras signaling.Next,by integrating a fine-mapping analysis and three independent case-control studies in Chinese populations consisting of 8,039 cases and 12,775 controls,we elucidated that rs1810503,a putative functional variant regulating CEBPB,was associated with CRC risk(OR=0.90,95%CI=0.86–0.93,P=1.07×10^(−7)).The association between rs1810503 and CRC risk was further validated in three additional multi-ancestry populations consisting of 24,254 cases and 58,741 controls.Mechanistically,the rs1810503 A to T allele change weakened the enhancer activity in an allele-specific manner to decrease CEBPB expression via longrange promoter-enhancer interactions,mediated by the transcription factor,REST,and thus decreased CRC risk.In summary,our study provides a genetic resource and a generalizable strategy for CRC etiology investigation,and highlights the biological implications of CEBPB in CRC tumorigenesis,shedding new light on the etiology of CRC.

关键词： susceptibility genes gene screening models multi-omics GWAS CEBPB long-range promoter-enhancer interactions

A genetic variant in the immune-related gene ERAP1 affects colorectal cancer prognosis

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Chinese Medical Journal 2024年第4期137卷 431-440页

作者： Danyi Zou Yimin Cai Meng Jin Ming Zhang Yizhuo Liu Shuoni Chen Shuhui Yang Heng Zhang Xu zhu Chaoqun Huang Ying zhu Xiaoping Miao yongchang Wei Xiaojun Yang Jianbo Tian Department of Clinical Laboratory Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China Department of Epidemiology and Biostatistics School of Public HealthTaiKang Center for Life and Medical SciencesWuhan UniversityWuhanHubei 430071China Department of Gastrointestinal Oncology Zhongnan Hospital of Wuhan UniversityWuhanHubei 430071China Department of Oncology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China Department of Gastrointestinal Surgery Renmin Hospital of Wuhan UniversityWuhanHubei 430071China Department of Gastrointestinal Surgery Zhongnan Hospital of Wuhan UniversityWuhan UniversityWuhanHubei 430071China Department of Epidemiology and Biostatistics School of Public HealthTongji Medical CollegeHuazhong University of Sciences and TechnologyWuhanHubei 430030China Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine Nanjing Medical UniversityNanjingJiangsu 211166China

Background:Findings on the association of genetic factors and colorectal cancer(CRC)survival are limited and inconsistent,and revealing the mechanism underlying their prognostic roles is of great importance.This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism.Methods:We first systematically performed expression quantitative trait locus(eQTL)analysis using The Cancer Genome Atlas(TCGA)dataset.Then,the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets(TCGA and GSE39582 dataset from the Gene Expression Omnibus database).The seven most potentially functional eQTL single nucleotide polymorphisms(SNPs)associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data.The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments.Results:The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1(ERAP1)was significantly associated with the prognosis of CRC(additive model,hazard ratio[HR]:1.43,95%confidence interval[CI]:1.08-1.88,P=0.012).The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3(TCF3)and subsequently reduce the expression of ERAP1.The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and was significantly associated with severe survival outcomes.Conclusion:The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1.Trial Registration:No.NCT00454519(https://clinicaltrials.gov/)

关键词： Colorectal cancer Prognosis Genetic variation Quantitative trait loci TCF3 rs71630754 Single nucleotide polymorphisms

Leaching kinetics of fluorine during the aluminum removal from spent Li-ion battery cathode materials

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Journal of Environmental Sciences 2024年第4期138卷 312-325页

作者： Shengjie Li Jianxin zhu Research Center for Eco-Environmental Sciences Chinese Academy of SciencesBeijing 100085China University of Chinese Academy of Sciences Beijing 100049China

The high content of aluminum(Al)impurity in the recycled cathode powder seriously affects the extraction efficiency of Nickel,Cobalt,Manganese,and Lithium resources and the actual commercial value of recycled materials,so Al removal is crucially important to conform to the industrial standard of spent Li-ion battery cathode materials.In this work,we systematically investigated the leaching process and optimum conditions associated with Al removal from the cathode powder materials collected in a wet cathode-powder peeling and recycling production line of spent Li-ion batteries(LIBs).Moreover,we specifically studied the leaching of fluorine(F)synergistically happened along with the removal process of Al,which was not concerned about in other studies,but one of the key factors affecting pollution prevention in the recovery process.The mechanism of the whole process including the leaching of Al and F from the cathode powder was indicated by using NMR,FTIR,and XPS,and a defluoridation process was preliminarily investigated in this study.The leaching kinetics of Al could be successfully described by the shrinking core model,controlled by the diffusion process and the activation energy was 11.14 kJ/mol.While,the leaching of F was attributed to the dissolution of LiPF6and decomposition of PVDF,and the kinetics associated was described by Avrami model.The interaction of Al and F is advantageous to realize the defluoridation to some degree.It is expected that our investigation will provide theoretical support for the large-scale recycling of spent LIBs.

关键词： Al removal F leaching Cathode powder Heating alkali leaching Leaching kinetics

Electron beam lithography on nonplanar and irregular surfaces

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Microsystems & Nanoengineering 2024年第2期10卷 1-23页

作者： Chenxu zhu Huseyin Ekinci Aixi Pan Bo Cui Xiaoli zhu Department of Electrical and Computer Engineering and Waterloo Institute for Nanotechnology(WIN) University of WaterlooWaterlooONCanada

E-beam lithography is a powerful tool for generating nanostructures and fabricating nanodevices with fine features approaching a few nanometers in size.However,alternative approaches to conventional spin coating and development processes are required to optimize the lithography procedure on irregular surfaces.In this review,we summarize the state of the art in nanofabrication on irregular substrates using e-beam lithography.To overcome these challenges,unconventional methods have been developed.For instance,polymeric and nonpolymeric materials can be sprayed or evaporated to form uniform layers of electron-sensitive materials on irregular substrates.Moreover,chemical bonds can be applied to help form polymer brushes or self-assembled monolayers on these surfaces.In addition,thermal oxides can serve as resists,as the etching rate in solution changes after e-beam exposure.Furthermore,e-beam lithography tools can be combined with cryostages,evaporation systems,and metal deposition chambers for sample development and lift-off while maintaining low temperatures.Metallic nanopyramids can be fabricated on an AFM tip by utilizing ice as a positive resistor.Additionally,Ti/Au caps can be patterned around a carbon nanotube.Moreover,3D nanostructures can be formed on irregular surfaces by exposing layers of anisole on organic ice surfaces with a focused e-beam.These advances in e-beam lithography on irregular substrates,including uniform film coating,instrumentation improvement,and new pattern transferring method development,substantially extend its capabilities in the fabrication and application of nanoscale structures.

关键词： lithography beam coating

Wood of trees:Cellular structure,molecular formation,and genetic engineering

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Journal of Integrative Plant Biology 2024年第3期66卷 443-467页

作者： Yingying zhu Laigeng Li State Key Laboratory of Herbage Improvement and Grassland Agro-ecosystems and College of Ecology Lanzhou UniversityLanzhou 730000China National Key Laboratory of Plant Molecular Genetics CAS Center for Excellence in Molecular Plant SciencesChinese Academy of SciencesShanghai 200032China

Wood is an invaluable asset to human society due to its renewable nature,making it suitable for both sustainable energy production and material manufacturing.Additionally,wood derived from forest trees plays a crucial role in sequestering a significant portion of the carbon dioxide fixed during photosynthesis by terrestrial plants.Nevertheless,with the expansion of the global population and ongoing industrialization,forest coverage has been substantially decreased,resulting in significant challenges for wood production and supply.Wood production practices have changed away from natural forests toward plantation forests.Thus,understanding the underlying genetic mechanisms of wood formation is the foundation for developing high-quality,fast-growing plantation trees.Breeding ideal forest trees for wood production using genetic technologies has attracted the interest of many.Tremendous studies have been carried out in recent years on the molecular,genetic,and cell-biological mechanisms of wood formation,and considerable progress and findings have been achieved.These studies and findings indicate enormous possibilities and prospects for tree improvement.This review will outline and assess the cellular and molecular mechanisms of wood formation,as well as studies on genetically improving forest trees,and address future development prospects.

关键词： cambium cell wall Populus wood formation xylem

Compositional evolution for mixed aerosols containing gluconic acid and typical nitrate and the effect of multiply factors on hygroscopicity

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Journal of Environmental Sciences 2024年第5期139卷 206-216页

作者： Yue zhu Shufeng Pang Yunhong Zhang School of Chemistry and Chemical Engineering Beijing Institute of TechnologyBeijing 100081China

The aging process of atmospheric aerosols usually leads to a mixture of inorganic salts and organic compounds of anthropogenic origin.In organic compounds,polyhydroxy organic acids are important components,however,the study on composition and hygroscopic properties of the mixture containing inorganics and polyhydroxy organic acids is scanty.In this study,gluconic acid,the proxy of polyhydroxy organic acids,is mixed with the representative nitrate(Mg(NO_(3))_(2),Ca(NO_(3))_(2))to form aerosols.ATR-FTIR and optical microscopy are employed to study the component changes and hygroscopicity as a function of relative humidity.As relative humidity fluctuates,the FTIR-ATR spectra display that the internal mixed gluconic acid(CH_(2)(CH)_(4)(OH)_(5)COOH)and nitrate can react to release acidic gases,forming relevant gluconate and further affecting the hygroscopicity.The specific presentation is particles cannot be recovered to their original size after the dehydration-hydration process and there will be some disparities in GF for mixed particles.For the gluconic acid-Ca(NO_(3))_(2)/Mg(NO_(3))_(2)mixtures with molar ratios of 1:1,higher degree of reaction resulting in the production of large amounts of gluconate should be responsible to the lower hygroscopicity compared to ZSR model.For 1:2 gluconic acid-nitrate mixed systems(with higher nitrate content),the hygroscopicity of mixtures are higher than the ZSR prediction.A possible reason could be‘salt-promoting effect’on the organic fractions of the surplus inorganic salt in the mixture.These data can improve the chemical composition list evaluation,in turn hygroscopic properties and phase state of atmospheric aerosol,and then the climate effect.

关键词： Hygroscopicity Gluconic acid Reaction ZSR simulation Size growth factors

Controllable chemical redox reactions to couple microbial degradation for organic contaminated sites remediation:A review

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Journal of Environmental Sciences 2024年第5期139卷 428-445页

作者： Bin Chen Jiang Xu Lizhong zhu College of Environmental and Resource Sciences Zhejiang UniversityHangzhou 310058China Zhejiang Provincial Key Laboratory of Organic Pollution Process and Control Zhejiang UniversityHangzhou 310058China Zhejiang Agriculture&Forest University Lin'an 311300China

Global environmental concern over organic contaminated sites has been progressively conspicuous during the process of urbanization and industrial restructuring.While traditional physical or chemical remediation technologies may significantly destroy the soil structure and function,coupling moderate chemical degradation with microbial remediation becomes a potential way for the green,economic,and efficient remediation of contaminated sites.Hence,this work systematically elucidates why and how to couple chemical technology with microbial remediation,mainly focused on the controllable redox reactions of organic contaminants.The rational design of materials structure,selective generation of reactive oxygen species,and estimation of degradation pathway are described for chemical oxidation.Meanwhile,current progress on efficient and selective reductions of organic contaminants(i.e.,dechlorination,defluorination,-NO_(2) reduction)is introduced.Combined with the microbial remediation of contaminated sites,several consideration factors of how to couple chemical and microbial remediation are proposed based on both fundamental and practical points of view.This review will advance the understanding and development of chemical-microbial coupled remediation for organic contaminated sites.

关键词： Soil remediation Groundwater remediation Rational design Reactive species Environmental nanotechnology

Structure and ion transport properties of organic ionic compounds revealed by NMR

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Magnetic Resonance Letters 2024年第2期4卷 2-12页

作者： Haijin zhu Guangdong Provincial Key Laboratory of Materials and Technologies for Energy Conversion Guangdong Technion-Israel Institute of TechnologyShantou515063China

Organic ionic plastic crystals(OIPCs)are emerging as an important material family for solid-state electrolytes and many other applications.They have significant advantages over conventional electrolyte materials,such as high ionic conductivity,non-flammability,and plasticity.Various nuclear magnetic resonance(NMR)spectroscopy techniques including solid-state NMR,pulsed-field gradient(PFG)NMR,and magnetic resonance imaging(MRI)etc.,provide us a versatile toolkit to understand the fundamental level structures,molecular dynamics,and ionic interactions in these materials.This article reviews the commonly used NMR methods including solid-and solution-state NMR,PFG-NMR,dynamic nuclear polarization(DNP)and the application of these methods in revealing the microscopic level structures and ion-transport mechanisms in OIPC materials.

关键词： NMR Electrolyte Organic ionic plastic crystals Defects Diffusion Microstructure

Carbon Emission Effects Driven by Evolution of Chinese Dietary Structure from 1987 to 2020

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Chinese Geographical Science 2024年第1期34卷 181-194页

作者： zhu Yuanyuan ZHANG Yan zhu Xiaohua Key Laboratory of Geographic Process Analysis&Simulation Hubei Province Central China Normal UniversityWuhan430079China Institute of Geographic Sciences and Natural Resources Research Chinese Academy of SciencesBeijing100101China

Exploring carbon emission effects based on the evolution of residents’ dietary structure to achieve the carbon neutrality goal and mitigate climate change is an important task.This study took China as the research object(data excluding Hong Kong,Macao and Taiwan) and used the carbon emission coefficient method to quantitatively measure the food carbon emissions from 1987–2020,then analyzed the carbon emission effects under the evolution of dietary structure.The results showed that during the study period,the Chinese dietary structure gradually changed to a high-carbon consumption pattern.The dietary structure of urban residents developed to a balanced one,while that of rural residents developed to a high-quality one.During the study period,the per capita food carbon emissions and total food consumption of Chinese showed an increasing trend.The per capita food carbon emissions of residents in urban and rural showed an overall upward trend.The total food carbon emissions in urban increased significantly,while that in rural increased first and then decreased.The influence of beef and mutton on carbon emissions is the highest in dietary structure.Compared with the balanced dietary pattern,the food carbon emissions of Chinese residents had not yet reached the peak,but were evolving to a high-carbon consumption pattern.

关键词： dietary structure structural evolution carbon emission effects carbon neutrality China