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Effectiveness of colorectal cancer screening integrating non-genetic and genetic risk: a prospective study based on UK Biobank data

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Cancer Biology & Medicine 2024年第8期21卷 712-723页

作者： Yu Zhang Chao Sheng Zhangyan Lyu Hongji Dai Fangfang Song Fengju Song Yubei Huang Kexin Chen Department of epidemiology and Biostatistics Key Laboratory of Molecular Cancer Epidemiology Key Laboratory of Prevention and Control of Human Major Diseases Ministry of Education National Clinical Research Center for Cancer Tianjin Medical University Cancer Institute and Hospital Tianjin Medical University

Objective: Few studies have evaluated the benefits of colorectal cancer(CRC) screening integrating both non-genetic and genetic risk factors. Here, we aimed to integrate an existing non-genetic risk model(QCancer-10) and a 139-variant polygenic risk score to evaluate the effectiveness of screening on CRC incidence and ***: We applied the integrated model to calculate 10-year CRC risk for 430,908 participants in the UK Biobank, and divided the participants into low-, intermediate-, and high-risk groups. We calculated the screening-associated hazard ratios(HRs) and absolute risk reductions(ARRs) for CRC incidence and mortality according to risk ***: During a median follow-up of 11.03 years and 12.60 years, we observed 5,158 CRC cases and 1,487 CRC deaths, respectively. CRC incidence and mortality were significantly lower among screened than non-screened participants in both the intermediateand high-risk groups [incidence: HR: 0.87, 95% confidence interval(CI): 0.81±0.94; 0.81, 0.73±0.90; mortality: 0.75, 0.64±0.87; 0.70, 0.58±0.85], which composed approximately 60% of the study population. The ARRs(95% CI) were 0.17(0.11±0.24) and 0.43(0.24±0.61), respectively, for CRC incidence, and 0.08(0.05±0.11) and 0.24(0.15±0.33), respectively, for mortality. Screening did not significantly reduce the relative or absolute risk of CRC incidence and mortality in the low-risk group. Further analysis revealed that screening was most effective for men and individuals with distal CRC among the intermediate to high-risk ***: After integrating both genetic and non-genetic factors, our findings provided priority evidence of risk-stratified CRC screening and valuable insights for the rational allocation of health resources.

关键词： Colorectal cancer incidence mortality polygenic risk score screening

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Innovative computational tools provide new insights into the polyploid wheat genome

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aBIOTECH 2024年第1期5卷 52-70页

作者： Yongming Chen Wenxi Wang Zhengzhao Yang Huiru Peng Zhongfu Ni Qixin Sun Weilong Guo Frontiers Science center for molecular Design Breeding Key Laboratory of Crop Heterosis and UtilizationBeijing Key Laboratory of Crop Genetic ImprovementChina Agricultural UniversityBeijing 100193China

Bread wheat(Triticum aestivum)is an important crop and serves as a significant source of protein and calories for humans,***,its large and allopolyploid genome poses constraints on genetic *** complex reticulate evolutionary history and the intricacy of genomic resources make the deciphering of the functional genome considerably more ***,we have developed a comprehensive list of versatile computational tools with the integration of statistical models for dissecting the polyploid wheat ***,we summarize the methodological innovations and applications of these tools and databases.A series of step-by-step examples illustrates how these tools can be utilized for dissecting wheat germplasm resources and unveiling functional genes associated with important agronomic ***,we outline future perspectives on new advanced tools and databases,taking into consideration the unique features of bread wheat,to accelerate genomic-assisted wheat breeding.

关键词： Polyploid wheat Genome complexity Functional genomics Tool development

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Maternal Preconception Serum Alanine Aminotransferase Levels and Risk of Preterm Birth among Reproductive-Aged Women—China,2013-2017

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China CDC weekly 2024年第10期6卷 181-188,I0001页

作者： Chuanyu Zhao Jiajing Jia Hanbin Wu Qin Xu Xinyi Lyu Meiya Liu Xuan Hu Jueming Lei Yuzhi Deng Yuan He Yuanyuan Wang Zuoqi Peng Ya Zhang Hongguang Zhang Qiaomei Wang Haiping Shen Yiping Zhang Donghai Yan Ying Yang Xu Ma National Research Institute for Family Planning BeijingChina National Human genetic Resources center BeijingChina Graduate School of Peking Union Medical College BeijingChina Department of epidemiology Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Summary What is already known about this topic?The significance of maternal liver health concerning preterm birth(PTB)is well recognized;however,there is a gap in understanding the precise influence of preconception s... 详细信息

关键词： Serum precise concerning

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Immunobiology of COVID-19: Mechanistic and therapeutic insights from animal models

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Zoological Research 2024年第4期45卷 747-766页

作者： Hong-Yi Zheng Tian-Zhang Song Yong-Tang Zheng State Key Laboratory of genetic Evolution&Animal Models KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesCenter for Biosafety Mega-ScienceKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China National Resource center for Non-Human Primates National Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility)Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650107China

The distribution of the immune system throughout the body complicates in vitro assessments of coronavirus disease 2019(COVID-19)immunobiology,often resulting in a lack of reproducibility when extrapolated to the whole ***,developing animal models is imperative for a comprehensive understanding of the pathology and immunology of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)*** review summarizes current progress related to COVID-19 animal models,including non-human primates(NHPs),mice,and hamsters,with a focus on their roles in exploring the mechanisms of immunopathology,immune protection,and long-term effects of SARS-CoV-2 infection,as well as their application in immunoprevention and immunotherapy of SARS-CoV-2 *** among these animal models and their specific applications are also highlighted,as no single model can fully encapsulate all aspects of *** effectively address the challenges posed by COVID-19,it is essential to select appropriate animal models that can accurately replicate both fatal and non-fatal infections with varying courses and *** animal model libraries and associated research tools is key to resolving the global COVID-19 pandemic,serving as a robust resource for future emerging infectious diseases.

关键词： SARS-CoV-2 COVID-19 Animal models Infection immunology Immunotherapy

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Doubled haploid technology and synthetic apomixis:Recent advances and applications in future crop breeding

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molecular Plant 2024年第7期17卷 1005-1018页

作者： Yanzhi Qu Alisdair R.Fernie Jie Liu Jianbing Yan National Key Laboratory of Crop genetic Improvement Huazhong Agricultural UniversityWuhan 430070China Hubei Hongshan Laboratory Wuhan 430070China Department of molecular Physiology Max-Planck-Institute of Molecular Plant Physiology14476 Potsdam-GolmGermany center of Plant Systems Biology and Biotechnology 4000 PlovdivBulgaria azhouwan National Laboratory Sanya 572024China

Doubled haploid(DH)technology and synthetic apomixis approaches can considerably shorten breeding cycles and enhance breeding *** with traditional breeding methods,DH technology offers the advantage of rapidly generating inbred lines,while synthetic apomixis can effectively fix hybrid *** this review,we focus on(i)recent advances in identifying and characterizing genes responsible for haploid induction(Hl),(ii)the molecular mechanisms of Hl,(ili)spontaneous haploid genome doubling,and(iv)crop synthetic *** also discuss the challenges and potential solutions for future crop breeding programs utilizing DH technology and synthetic ***,we provide our perspectives about how to integrate DH and synthetic apomixis for precision breeding and de novo domestication.

关键词： maize doubled haploid technology haploid induction synthetic apomixis precision breeding

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IbNIEL-mediated degradation of IbNAC087 regulates jasmonic acid-dependent salt and drought tolerance in sweet potato

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Journal of Integrative Plant Biology 2024年第2期66卷 176-195页

作者： Xu Li Zhen Wang Sifan Sun Zhuoru Dai Jun Zhang Wenbin Wang Kui Peng Wenhao Geng Shuanghong Xia Qingchang Liu Hong Zhai Shaopei Gao Ning Zhao Feng Tian Huan Zhang Shaozhen He Key Laboratory of Sweet Potato Biology and Biotechnology Ministry of Agriculture and Rural Affairs/Beijing Key Laboratory of Crop Genetic Improvement/Laboratory of Crop Heterosis&Utilization and Joint Laboratory for International Cooperation in Crop Molecular BreedingMinistry of EducationCollege of Agronomy&BiotechnologyChina Agricultural UniversityBeijing 100193China Sanya Institute of China Agricultural University Sanya 572025China State Key Laboratory of Plant Physiology and Biochemistry National Maize Improvement CenterKey Laboratory of Biology and Genetic Improvement of MaizeBeijing Key Laboratory of Crop Genetic ImprovementChina Agricultural UniversityBeijing 100193China

Sweet potato(Ipomoea batatas[L.]Lam.)is a crucial staple and bioenergy *** abiotic stress tolerance holds significant importance in fully utilizing marginal *** processes regulate abiotic stress responses,yet the molecular regulatory mechanisms in sweet potato remain *** this study,a NAC(NAM,ATAF1/2,and CUC2)transcription factor,IbNAC087,was identified,which is commonly upregulated in salt-and drought-tolerant *** of IbNAC087 increased salt and drought tolerance by increasing jasmonic acid(JA)accumulation and activating reactive oxygen species(ROS)scavenging,whereas silencing this gene resulted in opposite ***-rich IbNAC087-OE(overexpression)plants exhibited more stomatal closure than wild-type(WT)and IbNAC087-Ri plants under NaCl,polyethylene glycol,and methyl jasmonate ***087 functions as a nuclear transcriptional activator and directly activates the expression of the key JA biosynthesisrelated genes lipoxygenase(IbLOX)and allene oxide synthase(IbAOS).Moreover,IbNAC087 physically interacted with a RING-type E3 ubiquitin ligase NAC087-INTERACTING E3 LIGASE(IbNIEL),negatively regulating salt and drought tolerance in sweet *** ubiquitinated IbNAC087 to promote 26S proteasome degradation,which weakened its activation on IbLOX and *** findings provide insights into the mechanism underlying the IbNIEL-IbNAC087 module regulation of JA-dependent salt and drought response in sweet potato and provide candidate genes for improving abiotic stress tolerance in crops.

关键词： abiotic tolerance IbNAC087 IbNIEL JA sweet potato

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A k-mer-based pangenome approach for cataloging seed-storage-protein genes in wheat to facilitate genotype-to-phenotype prediction and improvement of end-use quality

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molecular Plant 2024年第7期17卷 1038-1053页

作者： Zhaoheng Zhang Dan Liu Binyong Li Wenxi Wang Jize Zhang Mingming Xin Zhaorong Hu Jie Liu Jinkun Du Huiru Peng Chenyang Hao Xueyong Zhang Zhongfu Ni Qixin Sun Weilong Guo Yingyin Yao Frontiers Science center for molecular Design Breeding Key Laboratory of Crop Heterosis and Utilization(MOE)and Bejing Key Laboratory of Crop Genetic ImprovementChina Agricultural UniversityBeijing100193China Key Laboratory of Crop Gene Resources and Breeding Institute of Crop ScienceChinese Academy of Agricultural SciencesBejingChina

Wheat is a staple foodfor more than 35%of the world's population,with wheatflourused to make hundreds of baked *** end-use quality is a major breeding target;however,improving it is especially time-consuming and ***,genes encoding seed-storage proteins(ssPs)form multigene families and are repetitive,with gaps commonplace in several genome *** overcome these barriers and efficiently identify superior wheat SSP alleles,we developed"PanSK"(Pan-SSP k-mer)for genotype-to-phenotype prediction based on an SsP-based pangenome *** uses 29-mer sequences that represent each ssP gene at the pangenomic level to reveal untapped diversity across landraces and modern ***-wide association studies with k-mers identified 23 Ssp genes associated with end-use quality that represent novel targets for *** evaluated the effect of rye secalin genes on end-use quality and found that removal of w-secalins from 1BL/1RS wheat translocation lines is associated with enhanced end-use ***,using machine-learning-based prediction inspired by PanSK,we predicted the quality phenotypes with high accuracy from genotypes *** study provides an effective approach for genome design based on ssP genes,enabling the breeding of wheat varieties with superior processing capabilities and improved end-use quality.

关键词： wheat seed-storage protein end-use quality k-mer pangenome genomic prediction

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DNA-delivered monoclonal antibodies targeting the p53 R175H mutant epitope inhibit tumor development in mice

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Genes & Diseases 2024年第4期11卷 368-380页

作者： Dafei Chai Xu Wang Praveen Neeli Shan Zhou Xingfang Yu Kanaga Sabapathy Yong Li Department of Medicine Section of Epidemiology and Population SciencesDan L Duncan Comprehensive Cancer CenterBaylor College of MedicineHoustonTX 77030USA Division of Cellular&molecular Research Humphrey Oei Institute of Cancer ResearchNational Cancer Centre SingaporeSingapore 168583Singapore

tThe tumor suppressor p53 is the most common mutated gene in cancer,with the R175H as the most frequent p53 missense ***,there are currently no approved targeted therapies or immunotherapies against mutant ***,we characterized and inves-tigated a monoclonal antibody(mAb)that recognizes the mutant p53-R175H for its affinity,specificity,and activity against tumor cells in *** then delivered DNA plasmids expres-sing the anti-R175H mAb or a bispecific antibody(BsAb)into mice to evaluate their therapeutic *** results showed that the anti-R175H mAb specifically bound to the p53-R175H an-tigen with a high affinity and recognized the human mutant p53-R175H antigen expressed on HEK293T or MC38 cells,with no cross-reactivity with wild-type *** cultured cells,the anti-R175H mAb showed higher cytotoxicity than the control but did not induce antibody-dependent cellular *** made a recombinant MC38 mouse cell line(MC38-p53-R175H)that overexpressed the human p53-R175H after knocking out the endogenous mutant p53 *** vivo,administration of the anti-R175H mAb plasmid elicited a robust anti-tumor effect against MC38-p53-R175H in *** administration of the anti-R175H BsAb plasmid showed no therapeutic effects,yet potent anti-tumor activity was observed in combination with the anti-PD-1 *** results indicate that targeting specific mutant epitopes using DNA-delivered mAbs or BsAbs presents a form of improved natural immunity derived from tumor-infiltrating B cells and plasma cells against intracellular tumor antigens.

关键词： BsAb Cytotoxicity mAb Mutant p53 PD-1 R175H

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Fine mapping and characterization of a major QTL for grain length,***-2D.1,that has pleiotropic effects in synthetic allohexaploid wheat

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Journal of Integrative Agriculture 2024年第9期23卷 2911-2922页

作者： Mingming Wang Jia Geng Zhe Zhang Zihan Zhang Lingfeng Miao Tian Ma Jiewen Xing Baoyun Li Qixin Sun Yufeng Zhang Zhongfu Ni Frontiers Science center for molecular Design Breeding/Key Laboratory of Crop Heterosis and Utilization Ministry of Education/Beijing Key Laboratory of Crop Genetic ImprovementChina Agricultural UniversityBeijing 100193China National Plant Gene Research Centre Beijing 100193China

Grain size is one of the determinants of grain yield,and identifying the genetic loci that control grain size will be helpful for increasing grain *** our previous study,a quantitative trait locus(QTL)for grain length(GL),***-2D.1,was identified from an F2 population developed from the cross between the natural(TAA10)and synthetic(XX329)allohexaploid *** the present study,we mainly fine mapped and validated its genetic *** this end,multiple near-isogenic lines(NILs)were obtained through marker-assisted selection with TAA10 as the recurrent *** secondary populations derived from 25 heterozygous recombinants were used for fine mapping of ***-2D.1,and the allele from XX329 significantly increased GL,thousand-grain weight(TGW),total spikelet number per spike(TSN)and spike compactness(SC).Using NILs for XX329(2D+)and TAA10(2D−),we determined the genetic and pleiotropic effects of *** target sequences were aligned with the wheat reference genome RefSeq v2.1 and spanned an~0.9 Mb genomic ***2D03G0114900(ortholog of Os03g0594700)was predicted as the candidate gene based on whole-genome re-sequencing and expression *** summary,the map-based cloning of ***-2D.1 will be useful for improving grain weight with enhanced GL and TSN.

关键词： grain length total spikelet number per spike spike compactness near-isogenic lines QTL wheat

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Simultaneously quantifying hundreds of acylcarnitines in multiple biological matrices within ten minutes using ultrahigh-performance liquid-chromatography and tandem mass spectrometry

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Journal of Pharmaceutical Analysis 2024年第1期14卷 140-148页

作者： Jingxian Zhang Qinsheng Chen Lianglong Zhang Biru Shi Men Yu Qingxia Huang Huiru Tang State Key Laboratory of genetic Engineering School of Life SciencesHuman Phenome InstituteZhangjiang Fudan International Innovation CenterMetabonomics and Systems Biology Laboratory at Shanghai International Centre for Molecular PhenomicsZhongshan HospitalFudan UniversityShanghai200032China Wuhan Laboratory for Shanghai Metabolome Institute(SMI)Ltd. Wuhan430000China

Acylcarnitines are metabolic intermediates of fatty acids and branched-chain amino acids having vital biofunctions and pathophysiological significances. Here, we developed a high-throughput method for quantifying hundreds of acylcarnitines in one run using ultrahigh performance liquid chromatography and tandem mass spectrometry (UPLC-MS/MS). This enabled simultaneous quantification of 1136 acylcarnitines (C0–C26) within 10-min with good sensitivity (limit of detection 0.992), accuracy (relative error 0.998) for predicting retention time (tR) of acylcarnitines with no standards and built a database of their multiple reaction monitoring parameters (tR, ion-pairs, and collision energy). Furthermore, we quantified 514 acylcarnitines in human plasma and urine, mouse kidney, liver, heart, lung, and muscle. This provides a rapid method for quantifying acylcarnitines in multiple biological matrices.

关键词： Acylcarnitine UPLC-MS/MS Quantitative structure-retention relationship molecular phenotype

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