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Journal of Integrative Plant Biology 2011年第1期53卷 54-62页

作者： Xianhui Hou Sainan Liu Florencia Pierri Xinhua Dai Li-jia qu Yunde Zhao National Laboratory for Protein Engineering and Plant Genetic Engineering Peking-Yale Joint Research Center for Plant Molecular Genetics and AgroBiotechnology College of Life Sciences Peking University Beijing 100871 China Section of Cell and Developmental Biology University of California at San Diego La Jolla California 92093-0116 USA

Flavin monooxygenases （FMOs） play critical roles in plant growth and development by synthesizing auxin and other signaling molecules. However, the structure and function relationship within plant FMOs is not understood. Here we defined the important residues and domains of the Arabidopsis YUC1 FMO, a key enzyme in auxin biosynthesis. We previously showed that simultaneous inactivation of YUC1 and its homologue YUC4 caused severe defects in vascular and floral development. We mutagenized the yuc4 mutant and screened for mutants with phenotypes similar to those of yucl yuc4 double mutants. Among the isolated mutants, five of them contained mutations in the YUC1 gene. Interestingly, the mutations identified in the new yucl alleles were concentrated in the two GXGXXG motifs that are highly conserved among the plant FMOs. One such motif presumably binds to flavin adenine dinucleotide （FAD） cofactor and the other binds to nicotinamide adenine dinucleotide phosphate （NADPH）. We also identified the Ser139 to Phe conversion in yucl, a mutation that is located between the two nucleotide-binding sites. By analyzing a series of yucl mutants, we identified key residues and motifs essential for the functions of YUC1 FMO.

关键词： Auxins Residues Plants Planting Adenine Mutation Mutants

TRANSLUCENT GREEN, an ERF Family Transcription Factor, Controls Water Balance in Arabidopsis by Activating the Expression of Aquaporin Genes

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Molecular Plant 2014年第4期7卷 601-615页

作者： Danling Zhu Zhe Wu Guangyu Cao Jigang Li jia Wei Tomohiko Tsuge Hongya Gua Takashi Aoyama Li-jia qu State Key Laboratory of Protein and Plant Gene Research Peking-Tsinghua Center for Life Sciences College of Life Sciences Peking University Beijing 100871 China State Key Laboratory of Plant Physiology and Biochemistry College of Biological Sciences China Agricultural University Beijing 100193 China Institute for Chemical Research Kyoto University Gokasho Uji Kyoto 611-0011 Japan The National Plant Gene Research Center (Beijing) Beijing 100101 China

Water is the most abundant molecule in almost all living organisms. Aquaporins are channel proteins that play critical roles in controlling the water content of cells. Here, we report the identification of an AP2/EREBP family transcription factor in Arabidopsis thaliana, TRANSLUCENT GREEN （TG）, whose overexpression in transgenic plants gave enhanced drought tolerance and vitrified leaves. TG protein is localized in the nucleus, binds DRE and GCC elements in vitro, and acts as a transcriptional activator in yeast cells. Microarray analysis revealed a total of 330 genes regulated by TG, among which five genes encode aquaporins. A transient expression assay showed that TG directly binds to the promoters of three aquaporin genes, such as AtTIP1;1, AtTIP2;3, and AtPIP2;2, indicating that TG directly regulates the expression of these genes. Moreover, overexpression of AtTIP1;1 resulted in vitrified phenotypes in transgenic Arabidopsis plants, similar to those observed in TG overexpression lines. Water injection into wild-type leaves recapitulated the vitrified leaf phenotypes, which was reversed by cutting off the water supply from vascular bundles. Taken together, our data support that TG controls water balance in Arabidopsis through directly activating the expression of aquaporin genes.

关键词： AP2/EREBP TRANSLUCENT GREEN vitrified leaf transcriptional regulation aquaporin.

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健康医疗数据治理体系建构的困境及对策

医学与社会 2023年第12期36卷 7-13,32页

作者：屈佳浙江大学光华法学院浙江杭州310008

健康医疗数据是一种具有高商业价值和强人身属性的宝贵资源,开发与利用健康医疗数据带来了可观的数据红利,同时也导致数据泄漏风险显著提升。为了更好地利用数据造福社会,各国都致力于健康医疗数据治理体系的建构。然而,数据权利主体不... 详细信息

健康医疗数据是一种具有高商业价值和强人身属性的宝贵资源,开发与利用健康医疗数据带来了可观的数据红利,同时也导致数据泄漏风险显著提升。为了更好地利用数据造福社会,各国都致力于健康医疗数据治理体系的建构。然而,数据权利主体不明、对数据处理者监管不严与数据要素流通受阻这3大关键问题阻碍了健康医疗数据治理体系的建构。虽然健康医疗数据基本源于个人,但不宜将数据归属于个人所有,并进行绝对化与排他性的权利保障。健康医疗数据治理体系的建构应兼顾公共利益与个人权益,以多学科人员参与的全程监管系统为基础,以促进数据安全有序共享为目标,增强健康医疗数据处理的透明度,打破数据共享壁垒,推动我国医疗卫生事业的创新和进步。

关键词：健康医疗数据医疗信息化数据安全数据治理

Plant Hormones:Metabolism,Signaling and Crosstalk

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Journal of Integrative Plant Biology 2011年第6期53卷 410-411页

作者： Li-jia qu Issue Editor Yunde Zhao Issue Editor School of Life Sciences Peking University Beijing China Section of Cell and Developmental Biology University of California at San Diego USA

Plants synthesize various hormones in response to environ- mental cues and developmental signals to ensure their proper growth and development. Elucidation of the molecular mech- anisms by which plant hormones control growth and devel- opment contributes to our understanding of fundamental plant biology and provides tools to improve crops. Because of their critical roles in plant growth and development, plant hormones have been studied extensively since the early days of plant biology.

关键词： Metabolism Signaling Crosstalk

Capturing the opportunities to initiate an in-depth integration of traditional Chinese medicine and western medicine

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Frontiers of Medicine 2014年第3期8卷 268-271页

作者： jia-Hua qu Bing Liu Zhu-Qin Zhang De-Pei Liu State Key Laboratory of Medical Molecular Biology Department of Biochemistry and Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical Sciences and Peking Union Medical College Beijing 100005 China

Medicine is mainly categorized into traditional Chinese medicine （TCM） from the east and western medicine from the west. The abundant practical experiences and classical medical theories in ancient China show that TCM not only studies the diagnosis, therapy, and prognosis of diseases but also focuses on prevention before disease onset and rehabilitation after therapy. These factors are characterized by the application of treatment methods, including prescription, acupuncture, and moxibustion. By comparison, western medicine utilizes modern instruments and standardized index analytical tools to evaluate diseases and perform quantitative and qualitative research in biological mor- phology and local positioning of life and disease. Therefore, TCM and western medicine are two different medical systems with respective advantages.

关键词： Capturing opportunities initiate in-depth integration

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周期性矩形管浮筏结构的振动分析

哈尔滨工程大学学报 2022年第9期43卷 1277-1282页

作者：朱自强李爽曲嘉哈尔滨工程大学航天与建筑工程学院黑龙江哈尔滨150001 哈尔滨工程大学青岛创新发展基地山东青岛266400

为减小舰船动力设备机械振动的传播,提高舰船减振能力,本文设计了一种在压缩载荷下具备负泊松比特性的周期性矩形管浮筏结构。通过数值模拟分析了矩形管层数、梯度排列方式和矩形管单胞壁厚对结构振动传递特性的影响。结果表明:矩形管... 详细信息

为减小舰船动力设备机械振动的传播,提高舰船减振能力,本文设计了一种在压缩载荷下具备负泊松比特性的周期性矩形管浮筏结构。通过数值模拟分析了矩形管层数、梯度排列方式和矩形管单胞壁厚对结构振动传递特性的影响。结果表明:矩形管层数和矩形管单胞厚度对结构的固有频率影响较大。在相同面密度下,梯度排列的矩形管可改变结构的共振频率,同时对减振效果有一定程度的提升。此外随着矩形管壁厚的增加,结构的固有频率逐渐增高,同时结构整体的减振效果呈现先增强后减弱的趋势。

关键词：周期性结构位移振级落差浮筏数值模拟负泊松比梯度排列矩形管共振频率减振效果

A positive feedback inhibition of isocitrate dehydrogenase 3βon paired-box gene 6 promotes Alzheimer-like pathology

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2324-2340页

作者： Xin Wang Qian Liu Hai-tao Yu jia-zhao Xie Jun-ning Zhao Zhi-ting Fang Min qu Yao Zhang Ying Yang jian-Zhi Wang Department of Pathophysiology School of Basic MedicineKey Laboratory of Education Ministry of China/Hubei Province for Neurological DisordersTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Department of Fundamental Medicine Wuxi School of MedicineJiangnan UniversityWuxiJiangsu 214122China Hubei Provincial Key Laboratory for Applied Toxicology Hubei Provincial Center for Disease Control and PreventionHubei Provincial Academy of Preventive MedicineWuhan 430000China Endocrine Department of Liyuan Hospital Key Laboratory of Ministry of Education of China for Neurological DisordersTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430077China Co-innovation Center of Neuroregeneration Nantong UniversityNantong 226000China

Impaired brain glucose metabolism is an early indicator of Alzheimer’s disease(AD);however,the fundamental mechanism is unknown.In this study,we found a substantial decline in isocitrate dehydrogenase 3β(IDH3β)levels,a critical tricarboxylic acid cycle enzyme,in AD patients and AD-transgenic mice’s brains.Further investigations demonstrated that the knockdown of IDH3βinduced oxidation-phosphorylation uncoupling,leading to reduced energy metabolism and lactate accumulation.The resulting increased lactate,a source of lactyl,was found to promote histone lactylation,thereby enhancing the expression of paired-box gene 6(PAX6).As an inhibitory transcription factor of IDH3β,the elevated PAX6 in turn inhibited the expression of IDH3β,leading to tau hyperphosphorylation,synapse impairment,and learning and memory deficits resembling those seen in AD.In AD-transgenic mice,upregulating IDH3βand downregulating PAX6 were found to improve cognitive functioning and reverse AD-like pathologies.Collectively,our data suggest that impaired oxidative phosphorylation accelerates AD progression via a positive feedback inhibition loop of IDH3β-lactate-PAX6-IDH3β.Breaking this loop by upregulating IDH3βor downregulating PAX6 attenuates AD neurodegeneration and cognitive impairments.

关键词： metabolism Alzheimer impaired

The assembly of a composite based on nano-sheet graphene oxide and montmorillonite

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Petroleum Science 2018年第2期15卷 366-374页

作者： Yu-Xiu An Wei-jia qu Pei-Zhi Yu jian-Guo Lu School of Engineering and Technology China University of Geosciences(Beijing)Beijing 100083China

Graphene oxide （GO） nano-sheets were synthesized using a modified Hummers＇ method from graphite powder. The Raman spectrum of GO displayed a D-band at 1359 cm-1 and a G-band at 1594 cm-l. The ID/IG value of GO was calculated to be 0.97, suggesting the formation of new sp2 clusters upon reduction. A method was designed to investigate the assembly of the GO/montmorillonite （MMT） composite. After the addition of GO, the typical peaks of montmorillonite in FT-IR spectra shifted, indicating the assembly between GO and MMT. The D-band and G-band reduced sharply in the GO/MMT composite. More importantly, the D-band （1344 cm-1） and G-band （1574 cm 1） shifted significantly and the ID/ IG value of the GO/MMT composite was calculated to be 1.13, showing a change in the GO structure. In the addition of 0.04 wt% GO to MMT, the value of interlayer space （d） was up to 13.0 Ameasured by XRD due to the insertion of GO into MMT. The evident increases in contents of carbon atoms （26.59%） and nitrogen atoms （3.44%） indicate that GO was successfully combined with MMT. The nano-pores and clay sheets were not observed in the SEM image of GO/clay, but obvious wrinkles, while flexible sheets were observed in the typical scanning electron microscopy images of GO. This further proves that GO was combining with clay. The TEM image shows that the GO nano-sheets were tiled on the surface of MMT sheets. This observation suggests that a stable assembly structure was formed between GO sheets and MMT sheets. The change in particle size of MMT with the addition of GO shows that interaction occurred between GO sheets and MMT sheets, which was further confirmed by the results of zeta potential. Adsorption and insertion were the main mechanisms to assemble GO and MMT.

关键词： Drilling fluid Graphene oxide Montmorillonite Wellbore stability

Detection of Novel BEST1 Variations in Autosomal Recessive Bestrophinopathy Using Third-generation Sequencing

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Current Medical Science 2024年第2期44卷 419-425页

作者： jia-xun LI Ling-rui MENG Bao-ke HOU Xiao-lu HAO Da-jiang WANG Ling-hui qu Zhao-hui LI Lei ZHANG Xin JIN Department of Senior Ophthalmology the Third Medical Center of PLA General HospitalBeijing 100853China Department of Ophthalmology the 74th Army Group HospitalGuangzhou 510318China

Objective:Autosomal recessive bestrophinopathy(ARB),a retinal degenerative disease,is characterized by central visual loss,yellowish multifocal diffuse subretinal deposits,and a dramatic decrease in the light peak on electrooculogram.The potential pathogenic mechanism involves mutations in the BEST1 gene,which encodes Ca2+-activated Cl−channels in the retinal pigment epithelium(RPE),resulting in degeneration of RPE and photoreceptor.In this study,the complete clinical characteristics of two Chinese ARB families were summarized.Methods:Pacific Biosciences(PacBio)single-molecule real-time(SMRT)sequencing was performed on the probands to screen for disease-causing gene mutations,and Sanger sequencing was applied to validate variants in the patients and their family members.Results:Two novel mutations,c.202T>C(chr11:61722628,p.Y68H)and c.867+97G>A,in the BEST1 gene were identified in the two Chinese ARB families.The novel missense mutation BEST1 c.202T>C(p.Y68H)resulted in the substitution of tyrosine with histidine in the N-terminal region of transmembrane domain 2 of bestrophin-1.Another novel variant,BEST1 c.867+97G>A(chr11:61725867),located in intron 7,might be considered a regulatory variant that changes allele-specific binding affinity based on motifs of important transcriptional regulators.Conclusion:Our findings represent the first use of third-generation sequencing(TGS)to identify novel BEST1 mutations in patients with ARB,indicating that TGS can be a more accurate and efficient tool for identifying mutations in specific genes.The novel variants identified further broaden the mutation spectrum of BEST1 in the Chinese population.

关键词： autosomal recessive bestrophinopathy BEST1 gene third-generation sequencing mutation

The Arabidopsis Anaphase-Promoting Complex/Cyclosome Subunit 1 is Critical for Both Female Gametogenesis and Embryogenesis

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Journal of Integrative Plant Biology 2013年第1期55卷 64-74页

作者： Yanbing Wang Yingnan Hou Hongya Gu Dingming Kang Zhang-Liang Chen Jingjing Liu Li-jia qu State Key Laboratory of Protein and Plant Gene Research College of Life Sciences Peking University College of Agronomy and Biotechnology China Agricultural University The National Plant Gene Research Center

Anaphase-promoting complex/cyclosome （APC/C）, a multisubunit E3 ligase, plays a critical role in cell cycle control, but the functional characterization of each subunit has not yet been completed. To investigate the function of APC1 in Arabidopsis, we analyzed four mutant alleles of APC1, and found that mutation in APC1 resulted in significantly reduced plant fertility, accumulation of cyclin B, and disrupted auxin distribution in embryos. The three mutant alleles apcl-1, apcl-2 and apcl-3 shared variable defects in female gametogenesis including degradation, abnormal nuclear number, and disrupted polarity of nuclei in the embryo sac as well as in embryogenesis, in which embryos were arrested at multiple stages. All of these defects are similar to those previously identified in apc4. The mutant apcl-4, in which the T-DNA was inserted after the transmembrane domain at the C-terminus, showed much more severe phenotypes; that is, most of the ovules were arrested at the one-nucleate female gametophyte stage （stage FG1）. In the apcl apc4 double mutants, the fertility was further reduced by one-third in apcl-ll＋ apc4-1/＋, and in some cases no ovules even survived in siliques of apcl-4/＋ apc4-1/＋. Our data thus suggest that APC1, an essential component of APC/C, plays a synergistic role with APC4 both in female gametogenesis and in embryogenesis.

关键词： Arabidopsis anaphase-promoting complex/cyclosome （APC/C） APC1 APC4 female gametogenesis embryogenesis synergistic role