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Journal of Genetics and Genomics 2009年第2期36卷 99-107页

作者： Yunfei Zhang Guangyu Cao Li-Jia Qu Hongya Gu National Laboratory of Protein Engineering and Plant Genetic Engineering College of Life Sciences Peking University Beijing 100871 China

MYB transcription factors compose one of the largest transcription factor families in Arabidopsis, which play important roles in vari- ous developmental processes as well as defense responses against environmental stresses. In this study, we report the characterization of AtMYB17 gene, a putative R2R3 type MYB gene family member in Arabidopsis. AtMYB17 was found exclusively localized in nuclear, with an activation domain at its C-terminus. AtMYBI7 was highly expressed in inflorescences and siliques, especially at early flower developmental stages. The level of AtMYB17 transcripts was also found to increase after imbibition during seed germination and gradually concentrate to the shoot apex. Bioinformatics analysis identified several binding sites of LEAFY （LFY） and AGL15 in the promoter re- gion of AtMYB17. Promoter-GUS fusion analysis showed that the LFY binding sites were important in fine-tuning regulation of the spatio-temporal expression ofAtMYB17 in transgenic plants. Moreover, AtMYB17 was up-regulated in 35S：：AGL15 plants. Taken together, our data suggest that LFY may be involved in the regulation of AtMYB17, possibly together with AGL 15, and thereafter in early inflores- cence development and seed germination.

关键词： AtMYB17 transcription factor Arabidopsis LEAFY AGL 15

DELLA proteins interact with FLC to repress flowering transition

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Journal of Integrative Plant Biology 2016年第7期58卷 642-655页

作者： Mingzhe Li Fengying An Wenyang Li Mengdi Ma Ying Feng Xing Zhang Hongwei Guo State Key Laboratory of Protein and Plant Gene Research College of Life Sciences Peking-Tsinghua Center for Life Sciences Peking University

Flowering is a highly orchestrated and extremely ct critical process in a plant＇s life cycle. Previous study has ademonstrated that SUPPRESSOR OF OVEREXPRESSION OF pCONSTANS 1（SOC1） and FLOWERING LOCUS T（FT） integrate m^-1 the gibberellic acid（GA） signaling pathway and vernalization higpathway in regulating flowering time, but detailed molecular Hmechanisms remain largely unclear. In GA signaling pathway,DELLA proteins are a group of master transcriptional regulators, while in vernalization pathway FLOWERING LOCUS C（FLC） is a core transcriptional repressor that down-regulates the expression of SOC1 and FT. Here, we report that DELLA proteins interact with FLC in vitro and in vivo, and the LHRI domains of DELLAs and the C-terminus of MADS domain of FLC are required for these *** and gene expression analysis showed that mutation of FLC reduces while over-expression of FLC enhances the GA response in the flowering process. Further,DELLA-FLC interactions promote the repression ability of FLC on its target genes. In summary, these findings report that the interaction between MADS box transcription factor FLC and GRAS domain regulator DELLAs may integrate various signaling inputs in flowering time control, and shed new light on the regulatory mechanism both for FLC and DELLAs in regulating gene expression.

关键词： Arabidopsis co-repressor DELLAs FLC flowering

Histone modifications in DNA damage response

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Science china(Life Sciences) 2016年第3期59卷 257-270页

作者： Lin-Lin Cao Changchun Shen Wei-Guo Zhu Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) State Key Laboratory of Natural and BiomimeticDrugs Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function Department of Biochemistry and Molecular Biology Peking University Health Science Center Beijing 100191 China peking university-Tsinghua university Joint Center for Life Sciences Beijing 100084 China Shenzhen university School of Medicine Shenzhen 518060 China Department of Clinical Laboratory peking university People's Hospital Beijing 100044 China

DNA damage is a relatively common event in eukaryotic cell and may lead to genetic mutation and even cancer. DNA damage induces cellular responses that enable the cell either to repair the damaged DNA or cope with the damage in an appropriate way. Histone proteins are also the fundamental building blocks of eukaryotic chromatin besides DNA, and many types of post-translational modifications often occur on tails of histones. Although the function of these modifications has remained elusive, there is ever-growing studies suggest that histone modifications play vital roles in several chromatin-based processes, such as DNA damage response. In this review, we will discuss the main histone modifications, and their functions in DNA damage response.

关键词： DNA damage response histone modifications chromatin DNA repair

Polycyclic aromatic hydrocarbons in ambient air,surface soil and wheat grain near a large steel-smelting manufacturer in northern china

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Journal of Environmental Sciences 2017年第7期29卷 93-103页

作者： Weijian Liu Yilong Wang Yuanchen Chen Shu Tao Wenxin Liu Laboratory for Earth Surface Processes College of Urban and Environmental SciencesPeking UniversityBeijing 100871China

The total concentrations and component profiles of polycyclic aromatic hydrocarbons（PAHs） in ambient air,surface soil and wheat grain collected from wheat fields near a large steel-smelting manufacturer in Northern china were *** on the specific isomeric ratios of paired species in ambient air,principle component analysis and multivariate linear regression,the main emission source of local PAHs was identified as a mixture of industrial and domestic coal combustion,biomass burning and traffic *** total organic carbon（TOC） fraction was considerably correlated with the total and individual PAH concentrations in surface *** total concentrations of PAHs in wheat grain were relatively low,with dominant low molecular weight constituents,and the compositional profile was more similar to that in ambient air than in *** with more significant results from partial correlation and linear regression models,the contribution from air PAHs to grain PAHs may be greater than that from soil PAHs.

关键词： PAHs Ambient air Surface soil Wheat grain Steel-smelting activity

Evaluating cost and benefit of air pollution control policies in china:A systematic review

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Journal of Environmental Sciences 2023年第1期123卷 140-155页

作者： Xinyuan Liu Chaoyi Guo Yazhen Wu Chen Huang Keding Lu Yuanhang Zhang Lei Duan Miaomiao Cheng Fahe Chai Fengqiao Mei Hancheng Dai Laboratory of Energy&Environmental Economics and Policy College of Environmental Sciences and EngineeringPeking UniversityBeijing 100871China School of Environment Tsinghua UniversityBeijing 100084China Chinese Research Academy of Environmental Sciences Beijing 100012China

china has put great efforts into air pollution control over the past years and recently committed to its most ambitious climate *** and benefit analysis has been widely used to evaluate the control policies in terms of past performance,future reduction potential,and direct and indirect *** understand the cost and benefit analysis for air pollution control in china,we conducted a bibliometric review of more than 100 studies published over the past two decades,including the current research progress,most commonly adopted methods,and core *** control target in cost and benefit analysis has shifted in three stages,from individual and primary pollution control,moving to joint prevention of multiple and secondary pollutants,and then towards synergistic control of air pollution and *** the expansion of the research scope,the integrated assessment model has gradually demonstrated the necessity for long-term ex-anti policy simulation,especially for dealing with complex *** ensure long-term air quality,climate,public health,and sustainable economic development,substantial evidence from published studies has suggested that china needs to continue its efforts in the upstream adjustment of the energy system and industrial structure with multi-regional and-sector *** cost and benefit review paper provides decision-makers with the fundamental information and knowledge gaps in air pollution control strategies in china,and direction for facing future challenges.

关键词： Air pollution control policy Cost and benefit analysis Climate policy Health co-benefit Economic impact

Depletion of Kindlin-2 induces cardiac dysfunction in mice

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Science china(Life Sciences) 2016年第11期59卷 1123-1130页

作者： Lihua Qi Yu Yu Xiaochun Chi Danyu Lu Yao Song Youyi Zhang Hongquan Zhang Department of Human Anatomy Histology and Embryology and Key Laboratory of Carcinogenesis and Translational Research Ministry of Education Peking University Health Science and State Key Laboratory of Natural and Biomimetic Drugs Peking University Health Science Center Institute of Vascular Medicine Peking University Third Hospital and Key Laboratory of Molecular Cardiovascular Sciences Ministry of Education Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides Ministry of Health Peking University Health Science

Kindlin-2, a member of the Kindlin family focal adhesion proteins, plays an important role in cardiac development. It is known that defects in the Z-disc proteins lead to hypertrophic cardiomyopathy(HCM) or dilated cardiomyopathy(DCM). Our previous investigation showed that Kindlin-2 is mainly localized at the Z-disc and depletion of Kindlin-2 disrupts the structure of the Z-Disc. Here, we reported that depletion of Kindlin-2 leads to the disordered myocardial fibers, fractured and vacuolar degeneration in myocardial fibers. Interestingly, depletion of Kindlin-2 in mice induced cardiac myocyte hypertrophy and increased the heart weight. Furthermore, decreased expression of Kindlin-2 led to cardiac dysfunction and also markedly impairs systolic function. Our data indicated that Kindlin-2 not only maintains the cardiac structure but also is required for cardiac function.

关键词： Kindlin-2 depletion myocardial hypertrophy cardiac dysfunction mouse

Differential expression of Kindlin-1 and Kindlin-2 correlates with esophageal cancer progression and epidemiology

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Science china(Life Sciences) 2017年第11期60卷 1214-1222页

作者： peng wang jun zhan jiagui song yunling wang weigang fang zhihua liu hongquan zhang department of anatomy histology and embryologykey laboratory of carcinogenesis and translational researchministry of educationand state key laboratory of natural and biominelic drugspeking university health science centerBeijing 100191China department of pathology peking university health science centerBeijing 100191China institute of cardiovascular research peking university health science centerBeijing 100191China state key laboratory of motecular oncology national cancer center/cancer hospitalchinese academy of medical sciences and peking union medical collegeBeijing 100121China

Esophageal cancer （EC） is one of the most lethal malignancies in china, but the etiology and risk factors remain unclear. The integrin-interacting proteins Kindlin-1 and Kindlin-2 are focal adhesion molecules that activate transmembrane receptor integrins and regulate tumor cell growth, invasion, and metastasis. Here, we report that Kindlin-1 and Kindlin-2 are differentially expressed among Chinese EC patients. For this, Kindlin-1 and Kindlin-2 expression was evaluated in 220 EC patients by immunohistochemistry （IHC） and found to be correlated with the EC progression, along with a variety of epidemiologic parameters, including smoking, family EC history, and EC invasion status. Moreover, data downloaded from the Oncomine database revealed that both Kindlin- 1 and Kindlin-2 were upregulated in ECs compared with normal esophageal tissues; although Kindlin-1 was highly expressed in well-differentiated tumors, whereas Kindlin-2 was more prevalent in poorly differentiated tumors. Collectively, these data suggest that Kindlin-1 may inhibit, while Kindlin-2 may promote, EC progression. This study, for the first time, linked the expression of Kindlin-1 and Kindlin-2 with EC family genetic background and living habits, which may help further our understanding of the various causes of EC.

关键词： Kindlin-l Kindlin-2 esophageal cancer epidemiology

Enhanced YOLOv5 network-based object detection(BALFilter Reader)promotes PERFECT filter-enabled liquid biopsy of lung cancer from bronchoalveolar lavage fluid(BALF)

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Microsystems & Nanoengineering 2023年第5期9卷 177-189页

作者： Zheng Liu Jixin Zhang Ningyu Wang Yun’ai Feng Fei Tang Tingyu Li Liping Lv Haichao Li Wei Wang Yaoping Liu School of Software and Microelectronics Peking UniversityBeijing 100871China Department of Pathology Peking University First HospitalBeijing 100034China School of Integrated Circuits Peking UniversityBeijing 100871China Department of Respirology and Critical Care Medicine Peking University First HospitalBeijing 100034China Department of Interventional Lung Disease and Center of Endoscopic Diagnosis and Treatment Anhui Chest HospitalHefeiAnhui 230022China National Key Laboratory of Advanced Micro and Nano Manufacture Technology Beijing 100871China Frontiers Science Center for Nano-optoelectronics Peking UniversityBeijing 100871China AntiMicrobial Resistance(AMR)and Critical Analytics for Manufacturing Personalized-Medicine(CAMP)IRGs Singapore-MIT Alliance for Research and Technology(SMART)CenterSingapore 138602Singapore

Liquid biopsy of cancers,detecting tumor-related information from liquid samples,has attracted wide attentions as an emerging *** previously reported large-area PERFECT(Precise-Efficient-Robust-Flexible-Easy-ControllableThin)filter has demonstrated competitive sensitivity in recovering rare tumor cells from clinical ***,it is time-consuming and easily biased to manually inspect rare target cells among numerous background cells distributed in a large area(Φ≥13 mm).This puts forward an urgent demand for rapid and bias-free ***,this paper implemented deep learning-based object detection for the inspection of rare tumor cells from large-field images of PERFECT filters with hematoxylin-eosin(HE)-stained cells recovered from bronchoalveolar lavage fluid(BALF).CenterNet,EfficientDet,and YOLOv5 were trained and validated with 240 and 60 image blocks containing tumor and/or background cells,***5 was selected as the basic network given the highest mAP@0.5 of 92.1%,compared to those of CenterNet and EfficientDet at 85.2%and 91.6%,***,tricks including CIoU loss,image flip,mosaic,HSV augmentation and TTA were applied to enhance the performance of the YOLOv5 network,improving mAP@0.5 to 96.2%.This enhanced YOLOv5 network-based object detection,named as BALFilter Reader,was tested and cross-validated on 24 clinical *** overall diagnosis performance(~2 min)with sensitivity@66.7%±16.7%,specificity@100.0%±0.0%and accuracy@75.0%±12.5%was superior to that from two experienced pathologists(10–30 min)with sensitivity@61.1%,specificity@16.7%and accuracy@50.0%,with the histopathological result as the gold *** AUC of the BALFilter Reader is 0.84±***,a customized Web was developed for a user-friendly interface and the promotion of wide *** current results revealed that the developed BALFilter Reader is a rapid,bias-free and easily accessible AI-enabled tool to promote the transplantation

关键词： specificity network consuming

Kindler syndrome protein Kindlin-1 is mainly expressed in adult tissues originating from ectoderm/endoderm

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Science china(Life Sciences) 2015年第5期58卷 432-441页

作者： ZHAN Jun YANG Mei ZHANG Jing GUO YongQing LIU Wei ZHANG HongQuan Key Laboratory of Carcinogenesis and Translational Research Ministry of Education State Key Laboratory of Natural and Biomimetic Drugs Peking University Health Science Center Laboratory of Molecular Cell Biology and Tumor Biology Department of Anatomy Histology and Embryology Peking University Health Science Center Department of Thoracic Surgery Sino-Japan Friendship Hospital Department of Immunology Third Military Medical University

Mutations of integrin-interacting protein Kindlin-1 cause Kindler syndrome and deregulation of Kindlin-1 is implicated in human cancers. The Kindlin-1-related diseases are confined in limited tissue types. However, Kindlin-1 tissue distribution and the dogma that governs Kindlin-1 expression in normal human body are elusive. This study examined Kindlin-1 expression in normal human adult organs, human and mouse embryonic organs by immunohistochemical analyses. We identified a general principle that the level of Kindlin-1 expression in tissues is tightly correlated with the corresponding germ layers from which these tissues originate. We compared the expression of Kindlin-1 with Kindlin-2 and found that Kindlin-1 is highly expressed in epithelial tissues derived from ectoderm and endoderm, whereas Kindlin-2 is mainly expressed in mesoderm-derived tissues. Likewise, Kindlin-1 was also found highly expressed in endoderm/ectoderm-derived tissues in human and mouse embryos. Our findings indicate that Kindlin-1 may play an importance role in the development of endoderm/ectoderm related tissues.

关键词： Kindlin- 1 epithelial tissue ectoderm endoderm embryo

C1orf106, an innate immunity activator, is amplified in breast cancer and is required for basal-like/luminal progenitor fate decision

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Science china(Life Sciences) 2019年第9期62卷 1229-1242页

作者： Ji Ma Cheng Liu Decao Yang Jiagui Song Jing Zhang Tianzhuo Wang Mengyuan Wang Weizhi Xu Xueying Li Shigang Ding Jun Zhan Hongquan Zhang Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of AnatomyHistology and Embryologyand State Key Laboratory of Natural and Biomimetic DrugsPeking University Health Science CenterBeijing 100191China Department of Gastroenterology Peking University Third HospitalBeijing 100191China

Basal-like breast cancer with a luminal progenitor gene expression profile is an aggressive subtype of breast cancer with a poorer prognosis compared with other ***,genes that specifically promote basal-like breast cancer development remain largely ***,we report that a novel gene C1orf106 plays an important role in maintaining the feature of basal-like/luminal progenitors.C1orf106 is frequently amplified and overexpressed in basal-like breast cancer and is associated with a poor outcome in *** human TCGA database,C1orf106 expression was correlated with upregulation of ELF5 and downregulation of GATA3,two transcription factors that regulate mammary gland stem cell *** expression of C1orf106 promotes tumor progression and expression of basal-like/luminal progenitor marker ELF5;depletion of C1orf106 suppresses tumorigenesis and expression of basal-like/luminal progenitor marker *** findings suggest that C1orf106 maintains the basal-like/luminal progenitor character through balancing the expression of ELF5 and *** together,we demonstrated that C1orf106 is an important regulator for basal-like/luminal progenitors and targeting C1orf106 is of therapeutic value for breast cancer.

关键词： C1orf106 basal-like luminal progenitor breast cancer ELF5 GATA3