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| 1 | 5-Hydroxymethylcytosine signatures in circulating cell-free DNA as diagnostic biomarkers for human cancers显示文摘象 5-methylcytosine (5mC ) 和 5-hydroxymethylcytosine (5hmC ) 那样的 DNA 修正是知道在哺乳动物影响全球基因表示的 epigenetic 标记。在人的染色体,与基因表示的靠近的关联和高化学的稳定性给他们的流行,这些 DNA epigenetic 标记能为癌症用作理想的 biomarkers 诊断。利用一种高度敏感、选择的化学标记技术,我们这里报导在传播没有房间的 DNA ( cfDNA )并且在从最近与 colorectal 诊断的 260 个病人的一个队收集的配对的肿瘤和邻近的纸巾的 genomic DNA ( gDNA )的 5hmC 的染色体宽的介绍,胃,胰腺,从 90 个健康个人的肝或甲状腺癌症和正常纸巾。5hmC 主要在与开的染色质和容许的 histone 修正重合的 transcriptionally 活跃的区域被散布。柔韧的联系癌症的 5hmC 签名在 cfDNA 被识别为特定的癌症类型是特征的。传播 cfDNA 的 5hmC 底 biomarkers colorectal 和胃的癌症是高度预兆的并且比常规 biomarkers 优异并且比得上从织物活体检视的 5hmC biomarkers。因此,这新策略能从血样品的分析为癌症的诊断和预后导致有效、最低限度地侵略的方法的发展。 | Wenshuai Li Xu Zhang Xingyu Lu Lei You Yanqun Song Zhongguang Luo Jun Zhang Ji Nie Wanwei Zheng Diannan Xu Yaping Wang Yuanqiang Dong Shulin Yu Jun Hong Jianping Shi Hankun Hao Fen Luo Luchun Hua Peng Wang Xiaoping Qian Fang Yuan Lianhuan Wei Ming Cui Taiping Zhang Quan Liao Menghua Dai Ziwen Liu Ge Chen Katherine Meckel Sarbani Adhikari Guifang Jia Marc B Bissonnette Xinxiang Zhang Yupei Zhao Wei Zhang Chuan He Jie Liu | 2017 | Cell Research2017，27，10： | 30 |
| 2 | L-3-n-butylphthalide protects against vascular dementia via activation of the Akt kinase pathway显示文摘As a neuroprotective drug for the treatment of ischemic stroke, 3-n-butylphthalide, a celery seed extract, has been approved by the State Food and Drug Administration of China as a clinical therapeutic drug for ischemic stroke patients. L-3-n-butylphthalide possesses significant efficacy in the treatment of acute ischemic stroke. The activated Akt kinase pathway can prevent the death of nerve cells and exhibit neuroprotective effects in the brain after stroke. This study provides the hypothesis that l-3-n-butylphthalide has a certain therapeutic effect on vascular dementia, and its mechanism depends on the activation of the Akt kinase pathway. A vascular dementia mouse model was established by cerebral repetitive ischemia/reperfusion, and intragastrically administered l-3-n-butylphthalide daily for 28 consecutive days after ischemia/reperfusion, or 7 consecutive days before ischemia/reperfusion. The Morris water maze test showed significant impairment of spatial learning and memory at 4 weeks after operation, but intragastric administration of l-3-n-butylphthalide, especially pretreatment with l-3-n-butylphthalide, significantly reversed these changes. Thionine staining and western blot analylsis showed that preventive and therapeutic application of l-3-n-butylphthalide can reduce loss of pyramidal neurons in the hippocampal CA1 region and alleviate nerve damage in mice with vascular demen-tia. In addition, phosphorylated Akt expression in hippocampal tissue increased significantly after l-3-n-butylphthalide treatment. Experimental findings demonstrate that l-3-n-butylphthalide has preventive and therapeutic effects on vascular dementia, and its mechanism may be mediated by upregulation of phosphorylated Akt in the hippocampus. | Yaping Huai Yanhong Dong Jing Xu Nan Meng Chunfeng Song Wenbin Li Peiyuan Lv | 2013 | Neural Regeneration Research2013，8，19： | 17 |
| 3 | A New Species of the Genus Thermophis(Serpentes: Colubridae) from Shangri-La, Northern Yunnan, China, with a Proposal for an Eclectic Rule for Species Delimitation显示文摘The hot-spring snakes, Thermophis, were previously known only from the Tibet Autonomous Region and Western Sichuan, China. During the past two years, three adult hot-spring snakes(2 females, 1 male) were sampled in Shangri-La, northern Yunnan, China, thus expanding their known distribution region towards the southeast. This site is the southeastern-most corner of the Tibetan Plateau and the southernmost tip of the Hengduan Mountains(Mts.). Phylogenetic analysis of mitochondrial(mt) and nuclear(n) DNA segments suggested that the three specimens belong to the genus of Thermophis. Morphologically, the new species is more similar to T. zhaoermii. However, it is distinguished from T. zhaoermii in the number of maxillary teeth(15), distance between the two eyes/head width, rostral width/height, mental width/height, in one character limited to female: head width/length, and in four characters restricted to male: occurrence of the reduction from 10 to 8(8 to 6, 6 to 4) scales in each dorsal row on the tail. There are differences in morphology, genetics(mt DNA, n DNA), and geography between the putative new species and T. zhaoermii, the new species meets our proposed eclectic and feasible 'four-differences' rule. | Lifang PENG Changhu LU Song HUANG Peng GUO Yaping ZHANG | 2014 | Asian Herpetological Research2014，5，4： | 4 |
| 4 | Introduction of a multicenter online database for non-metastatic breast cancer in China显示文摘Dear Editor,Breast cancer is now the most frequently diagnosed cancer and is the fifth leading cause of cancer-related death in Chinese women. Therefore, the burden of breast cancer in China is gradually increasing. According to figures released by the Chinese Cancer Center in 2018, the number of newly diagnostic breast cancer is about 278,900 cases, accounting for 16.51%of all women who were diagnosed with the first primary malignant tumors;and 66,000 cases of breast cancer died in 2014 (Chen et al., 2016). | Yaping Yang Jieqiong Liu Min Peng Fengxi Su Xiaoming Xie Zhenzhen Liu Jundong Wu Wei Wei Dongxian Zhou Weiwen Li Ailing Zhang Guosen Su Weixiong Yang Jishang Chen Dekui Ma Yongguang Cai Kai Chen Liling Zhu Qiang Liu Erwei Song | 2020 | Science China(Life Sciences)2020，63，9： | 4 |
| 5 | Enhancing the catalytic efficiency of the Heck coupling reaction by forming 5 nm Pd octahedrons using kinetic control显示文摘异构的催化作用通过界面的反应的一个过程发生;因此,表面方面和尺寸控制能增加催化效率。八面的 Pd nanocrystals,围住由 { 111 } 方面,应该是理想的几何形状为哎呀联合反应;然而,综合是挑战性的有用存在帽子代理人技术的相对一致的尺寸分布的 5 nm Pd 八面体。这里,我们把钯用作一个模型系统调查原子增加的动力学怎么能精确用注射泵被控制。作为结果,我们的方法生产了象 5 nm 一样小的 Pd 八面体,它增加了催化效率哎呀当减少使用的催化剂的重量时,联合反应。 | Ran Long Di Wu Yaping Li Yu Bai Chengming Wang Li Song Yujie Xiong | 2015 | Nano Research2015，8，6： | 4 |
| 6 | Telmisartan prevents high-fat diet-induced hypertension and decreases perirenal fat in rats显示文摘We sought to investigate the effects of telmisartan on high-fat diet-induced hypertension and to explore the possible underlying mechanisms.Rats receiving high-fat diet were randomly divided into two groups,the telmisartan group(n = 9) and the high-fat diet group(n = 10).The control group consisted of age-matched rats on a regular diet(n = 10).At the end of the treatment,the body weight,blood pressure,insulin sensitivity and serum adiponectin levels of all rats were examined,and their visceral fat was extracted and weighed.Our results showed that telmisartan improved insulin resistance and dyslipidemia and increased serum adiponectin levels.Telmisartan also lowered both systolic blood pressure and diastolic blood pressure,and decreased the accumulation of perirenal fat associated with high-fat diet.Furthermore,telmisartan increased adiponectin mRNA expression in the perirenal fat.Correlation analysis showed that both systolic blood pressure and diastolic blood pressure were positively correlated with perirenal fat.These effects of telmisartan may be mediated through decreases in perirenal fat and contributed to the improvement of perirenal fat function.Our findings suggested a strong link between perirenal fat and high-fat diet-induced hypertension,and identified telmisartan as a potential drug for the treatment of obesity-related hypertension. | Yaping Wang Yan Song Meng Suo Xin Jin Gang Tian | 2012 | The Journal of Biomedical Research2012，26，3： | 3 |
| 7 | First principle calculation of lithiation/delithiation voltage in Li-ion battery materials显示文摘A first principle method, based on the density functional theory, was used to investigate the average voltage of lithiation/delithiation for Li-ion battery materials across 7 categories and 18 series, including LiMO 2 , LiMn 2 O 4 , LiMPO 4 , Li 2 MSiO 4 and graphite. The average voltage of lithiation/delithiation in the relevant electrode materials was obtained by comparing the total-energy difference, before and after an electrochemical reaction. The calculated values were in good agreement with experimental data. The systematic difference between the simulated and experimental values could be explained in terms of the binding energy on the surface of the lithium electrode. This type of calculation method could be applied as an easy and effective tool for predicting the potential performance of new lithiation/delithiation materials. | ZHU XiaoHui CHEN Ning LIAN Fang SONG YaPing LI Yang | 2011 | Chinese Science Bulletin2011，56，30： | 3 |
| 8 | Beclin-1/LC3-II dependent macroautophagy was uninfluenced in ischemia-challenged vascular endothelial cells显示文摘Autophagy has been extensively studied and occurs in many biological settings.However,a question remains as to whether ischemia enhances Beclin-1/LC3-II-dependent macroautophagy in vascular endothelial cells,as has been previously thought.Furthermore,the effect of the level of autophagy on cell or skin flap survival still requires elucidation.We created a lethal ischemia model in human umbilical vascular endothelial cells(HUVECs),performed quantitative proteomics and bioinformatics analyses,and verified the autophagic status and effect both in vitro and in vivo.The significantly upregulated proteins encoded by autophagy-related genes(ATGs)included ATG2A,ATG3,ATG4B,ATG5,ATG7,ATG9A,ATG12,ATG16,and ATG101.The significantly enhanced lysosomal proteins were cathepsin B,cathepsin D,lysosome-associated membrane protein 1(LAMP1),and LAMP2.However,the differentially expressed proteins excluded Beclin-1,microtubule-associated protein light chain 3(LC3)-I,and LC3-II.Western blot analyses verified that the protein expression levels of Beclin-1,LC3-I,and LC3-II were neither upregulated nor downregulated in ischemia-challenged HUVECs.The autophagic status was not enhanced by rapamycin in ischemic HUVECs but appeared to be inhibited by chloroquine.Our in vivo study on rats showed that a downregulation in autophagic status jeopardized skin flap survival.In conclusion,Ischemia neither enhanced nor inhibited Beclin-1/LC3-II-dependent canonical macroautophagy both in vitro and in vivo,in contradiction to previous studies.An appropriate autophagic homeostasis can minimize cell or skin flap damage. | Yaping Ma Chaofan Li Yan He Tiwei Fu Li Song Qingsong Ye Fugui Zhang | 2022 | Genes & Diseases2022，9，2： | 3 |
| 9 | Distribution of Borehole Temperature at Four High-altitude Alpine Glaciers in Central Asia显示文摘在四条高高度的高山的冰河的地上凿穿温度的分发被调查。结果证明温度从 −13.4 ° C 到 −1.84 ° C,显示冰河在整个地上凿穿是冷的。否定坡度(即,与增加深度减少的温度)由于冰的移流并且温暖的气候,和向下移动的否定坡度联系到温暖的气候,为移动在韦斯特中国与以前调查的大陆人冰核心地上凿穿温度相比在 Gyabrag 冰河和 Miaoergou 冰河的地上凿穿降低深度的观察最小的温度可能负责。在 10 m 深度的地上凿穿温度在阿尔泰山范围在 Tsabagarav 冰河在中央喜马拉雅山脉在 Gyabrag 冰河从 −8.0 ° C 到 −12.9 ° C。在 10 m 深度的地上凿穿温度比冰河的表面上的计算吝啬的年度空气温度高是 3 ∼4 度并且更高, 10 m 深度温度被潜伏的热的生产主要由于融化水过滤和 refreezing 引起。基础温度在融化的点下面是远的,显示冰河被冻结到基岩。基岩附近的低温度坡度建议基础温度上的地热的流动和冰流动的影响是很弱的。低温度和冰河的冰流动的小速度为在冰核心的化学、同位素的信息的保藏是有益的。 | LIU Yaping HOU Shugui WANG Yetang SONG Linlin | 2009 | Journal of Mountain Science2009，6，3： | 3 |
| 10 | Microsatellite DNA analysis proves nucleus of interspecies reconstructed blastocyst coming from that of donor giant panda显示文摘A method for DNA isolation from early development of blastocyst and further analysis of nuclear and mitochondrial DNA was developed in present study. Total DNA was prepared from interspecies reconstructed blastocyst and a giant panda specific microsatellite locus g010 was successfully amplified. DNA sequencing of the PCR product showed that two sequences of reconstructed blastocysts are the same as that of positive control giant panda. Our results prove that the nucleus of interspecies reconstructed blastocyst comes from somatic nucleus of donor giant panda. | DING Bo SHI Peng XIANGYU Jinggong ZHANG Yaping CHEN Dayuan SUN Qingyuan LI Guangpeng WANG Minkang LIU Yilong KANG Li HAN Zhiming SONG Xiangfen LI Jingsong CHEN Yuchun | 2000 | Chinese Science Bulletin2000，45，20： | 3 |
| 11 | A 10-miRNA risk score-based prediction model for pathological complete response to neoadjuvant chemotherapy in hormone receptor-positive breast cancer显示文摘Patients with hormone receptor(HR)-positive tumors breast cancer usually experience a relatively low pathological complete response(p CR)to neoadjuvant chemotherapy(NAC).Here,we derived a 10-micro RNA risk score(10-mi RNA RS)-based model with better performance in the prediction of p CR and validated its relation with the disease-free survival(DFS)in 755 HRpositive breast cancer patients(273,265,and 217 in the training,internal,and external validation sets,respectively).This model,presented as a nomogram,included four parameters:the 10-mi RNA RS found in our previous study,progesterone receptor(PR),human epidermal growth factor receptor 2(HER2)status,and volume transfer constant(K).Favorable calibration and discrimination of 10-mi RNA RS-based model with areas under the curve(AUC)of 0.865,0.811,and 0.804 were shown in the training,internal,and external validation sets,respectively.Patients who have higher nomogram score(>92.2)with NAC treatment would have longer DFS(hazard ratio=0.57;95%CI:0.39–0.83;P=0.004).In summary,our data showed the 10-mi RNA RS-based model could precisely identify more patients who can attain p CR to NAC,which may help clinicians formulate the personalized initial treatment strategy and consequently achieves better clinical prognosis for patients with HRpositive breast cancer. | Chang Gong Ziliang Cheng Yaping Yang Jun Shen Yingying Zhu Li Ling Wanyi Lin Zhigang Yu Zhihua Li Weige Tan Chushan Zheng Wenbo Zheng Jiajie Zhong Xiang Zhang Yunjie Zeng Qiang Liu RStephanie Huang Andrzej LKomorowski Eddy SYang François Bertucci Francesco Ricci Armando Orlandi Gianluca Franceschini Kazuaki Takabe Suzanne Klimberg Naohiro Ishii Angela Toss Mona PTan Mathew A Cherian Erwei Song | 2022 | Science China(Life Sciences)2022，65，11： | 3 |
| 12 | Electrochemical hydrogen storage performance of AB_(5-)CoB composites synthesized by a simple mixing method显示文摘AB5 (MlNi4.0Al0.3Cu0.5Zn0.2) alloy and CoB alloy were prepared by arc melting. AB5-CoB composites were synthesized by simple mixing of AB5 alloy powders and CoB alloy powders, and their electrochemical hydrogen storage properties were studied as negative electrodes in KOH aqueous solution. The maximum discharge capacity of the AB5-CoB(50%) composite (the content of CoB in the composite is 50 wt.%) reached 365.3 mAh·g-1. After 100 charge-discharge cycles, the discharge capacity of the AB5-CoB(50%) composite was still much higher than that of the AB5 alloy. The high rate discharge capability (HRD) and potentiodynamic polarization were also tested. | SONG Dawei WANG Yijing WANG Yaping JIAO Lifang YUAN Huatang | 2009 | Rare Metals2009，28，6： | 2 |
| 13 | Using a conceptual Bayesian network to investigate environmental management of vegetable production in the Lake Taihu region of China显示文摘 | David Nash David Waters Andres Buldu Yuming Wu Yaping Lin Weiqiu Yang Yuzhi Song Jianhua Shu Wei Qin Murray Hannah | 2013 | Environmental Modelling and Software2013，，： | 1 |
| 14 | High Performance Work System and Collective OCB : A Collective Social Exchange Perspective显示文摘 | Yaping Gong Song Chang Siu Yin Cheung | 2010 | Human Resource Management Journal2010，20，2： | 1 |
| 15 | Analysis of electromagnetic scattering problems by means of a VSIE- ODDM- MLFMA method显示文摘 | CHEN JIALIN LI SHANGSHENG SONG YAPING | 2012 | Applied Computational Electromagnetic Society Journal2012，27，8： | 1 |
| 16 | Identification of liver metastasis-associated genes in human colon carcinoma by mRNA profiling显示文摘Objective: Liver metastasis,which contributes substantially to high mortality,is the most common recurrent mode of colon carcinoma.Thus,it is necessary to identify genes implicated in metastatic colonization of the liver in colon carcinoma.Methods: We compared mRNA profiling in 18 normal colon mucosa(N),20 primary tumors(T) and 19 liver metastases(M) samples from the dataset GSE49355 and GSE62321 of Gene Expression Omnibus(GEO) database.Gene ontology(GO) and pathways of the identified genes were analyzed.Co-expression network and proteinprotein interaction(PPI) network were employed to identify the interaction relationship.Survival analyses based on The Cancer Genome Atlas(TCGA) database were used to further screening.Then,the candidate genes were validated by our data.Results: We identified 22 specific genes related to liver metastasis and they were strongly associated with cell migration,adhesion,proliferation and immune response.Simultaneously,the results showed that C-X-C motif chemokine ligand 14(CXCL14) might be a favorable prediction factor for survival of patients with colon carcinoma.Importantly,our validated data further suggested that lower CXCL14 represented poorer outcome and contributed to metastasis.Gene set enrichment analysis(GSEA) showed that CXCL14 was negatively related to the regulation of stem cell proliferation and epithelial to mesenchymal transition(EMT).Conclusions: CXCL14 was identified as a crucial anti-metastasis regulator of colon carcinoma for the first time,and might provide novel therapeutic strategies for colon carcinoma patients to improve prognosis and prevent metastasis. | Jianling Liu Dan Wang Chaoqi Zhang Zhen Zhang Xinfeng Chen Jingyao Lian Jinbo Liu Guixian Wang Weitang Yuan Zhenqiang Sun Weijia Wang Mengjia Song Yaping Wang Qian Wu Ling Cao Dong Wang Yi Zhang | 2018 | Chinese Journal of Cancer Research2018，30，6： | 1 |
| 17 | Engineering white blood cell membrane-camouflaged nanocarriers for inflammation-related therapeutics显示文摘White blood cells(WBCs)play essential roles against inflammatory disorders,bacterial infections,and cancers.Inspired by nature,WBC membrane-camouflaged nanocarriers(WBC-NCs)have been developed to mimic the“dynamic”functions of WBCs,such as transendothelial migration,adhesion to injured blood vessels,etc,which make them promising for diverse medical applications.WBC-NCs inherit the cell membrane antigens of WBCs,while still exhibiting the robust inflammation-related therapeutic potential of synthetic nanocarriers with excellent(bio)physicochemical performance.This review summarizes the proposed concept of cell membrane engineering,which utilizes physical engineering,chemical modification,and biological functionalization technologies to endow the natural cell membrane with abundant functionalities.In addition,it highlights the recent progress and applications of WBC-NCs for inflammation targeting,biological neutralization,and immune modulation.Finally,the challenges and opportunities in realizing the full potential of WBC-NCs for the manipulation of inflammation-related therapeutics are discussed. | Wanli Song Pengfei Jia Yaping Ren Junmiao Xue Bingqian Zhou Xinkai Xu Yansheng Shan Jing Deng Qihui Zhou | 2023 | Bioactive Materials2023，，5： | 1 |
| 18 | Novel mutation c.1210-3C>G in cis with a poly-T tract of 5T affects CFTR mRNA splicing in a Chinese patient with cystic fibrosis显示文摘Cystic fibrosis(CF)is a rare autosomal recessive disease with only one pathogenic gene cystic fibrosis transmembrane conductance regulator(CFTR).To identify the potential pathogenic mutations in a Chinese patient with CF,we conducted Sanger sequencing on the genomic DNA of the patient and his parents and detected all 27 coding exons of CFTR and their flanking intronic regions.The patient is a compound heterozygote of c.2909G>A,p.Gly970Asp in exon 18 and c.1210-3C>G in cis with a poly-T of 5T(T5)sequence,3 bp upstream in intron 9.The splicing effect of c.1210-3C>G was verified via minigene assay in vitro,indicating that wild-type plasmid containing c.1210-3C together with T7 sequence produced a normal transcript and partial exon 10-skipping-transcript,whereas mutant plasmid containing c.1210-3G in cis with T5 sequence caused almost all mRNA to skip exon 10.Overall,c.1210-3C>G,the newly identified pathogenic mutation in our patient,in combination with T5 sequence in cis,affects the CFTR gene splicing and produces nearly no normal transcript in vitro.Moreover,this patient carries a p.Gly970Asp mutation,thus confirming the high-frequency of this mutation in Chinese patients with CF. | Xinyue Zhao Keqiang Liu Wenshuai Xu Meng Xiao Qianli Zhang Jiaxing Song Keqi Chen Yaping Liu Xinlun Tian Kai-Feng Xu Xue Zhang | 2022 | Frontiers of Medicine2022，16，1： | 1 |
| 19 | Electron-ion collider in China显示文摘Lepton scattering is an established ideal tool for studying inner structure of small particles such as nucleons as well as nuclei.As a future high energy nuclear physics project,an Electron-ion collider in China(EicC)has been proposed.It will be constructed based on an upgraded heavy-ion accelerator,High Intensity heavy-ion Accelerator Facility(HIAF)which is currently under construction,together with a new electron ring.The proposed collider will provide highly polarized electrons(with a po-larization of 80%)and protons(with a polarization of 70%)with variable center of mass energies from 15 to 20 GeV and the luminosity of(2–3)×1033 cm^(−2)·s^(−1).Polarized deuterons and Helium-3,as well as unpolarized ion beams from Carbon to Uranium,will be also available at the EicC.The main foci of the EicC will be precision measurements of the structure of the nucleon in the sea quark region,including 3D tomography of nucleon;the partonic structure of nuclei and the parton interaction with the nuclear environment;the exotic states,especially those with heavy flavor quark contents.In addition,issues fundamental to understanding the origin of mass could be addressed by measurements of heavy quarkonia near-threshold production at the EicC.In order to achieve the above-mentioned physics goals,a hermetical detector system will be constructed with cutting-edge technologies.This document is the result of collective contributions and valuable inputs from experts across the globe.The EicC physics program complements the ongoing scientific programs at the Jefferson Laboratory and the future EIC project in the United States.The success of this project will also advance both nuclear and particle physics as well as accelerator and detector technology in China. | Daniele PAnderle Valerio Bertone Xu Cao Lei Chang Ningbo Chang Gu Chen Xurong Chen Zhuojun Chen Zhufang Cui Lingyun Dai Weitian Deng Minghui Ding Xu Feng Chang Gong Longcheng Gui Feng-Kun Guo Chengdong Han Jun He Tie-Jiun Hou Hongxia Huang Yin Huang KrešImir KumeričKi LPKaptari Demin Li Hengne Li Minxiang Li Xueqian Li Yutie Liang Zuotang Liang Chen Liu Chuan Liu Guoming Liu Jie Liu Liuming Liu Xiang Liu Tianbo Liu Xiaofeng Luo Zhun Lyu Boqiang Ma Fu Ma Jianping Ma Yugang Ma Lijun Mao Cédric Mezrag HervéMoutarde Jialun Ping Sixue Qin Hang Ren Craig DRoberts Juan Rojo Guodong Shen Chao Shi Qintao Song Hao Sun PawełSznajder Enke Wang Fan Wang Qian Wang Rong Wang Ruiru Wang Taofeng Wang Wei Wang Xiaoyu Wang Xiaoyun Wang Jiajun Wu Xinggang Wu Lei Xia Bowen Xiao Guoqing Xiao Ju-Jun Xie Yaping Xie Hongxi Xing Hushan Xu Nu Xu Shusheng Xu Mengshi Yan Wenbiao Yan Wencheng Yan Xinhu Yan Jiancheng Yang Yi-Bo Yang Zhi Yang Deliang Yao Zhihong Ye Peilin Yin C-PYuan Wenlong Zhan Jianhui Zhang Jinlong Zhang Pengming Zhang Yifei Zhang Chao-Hsi Chang Zhenyu Zhang Hongwei Zhao Kuang-Ta Chao Qiang Zhao Yuxiang Zhao Zhengguo Zhao Liang Zheng Jian Zhou Xiang Zhou Xiaorong Zhou Bingsong Zou Liping Zou | 2021 | Frontiers of physics2021，16，6： | 1 |
| 20 | Cryo-EM structures of PAC1 receptor reveal ligand binding mechanism显示文摘The pituitary adenylate cyclase-activating polypeptide type I receptor(PAC1R)belongs to the secretin receptor family and is widely distributed in the central neural system and peripheral organs.Abnormal activation of the receptor mediates trigeminovascular activation and sensitization,which is highly related to migraine,making PAC1R a potential therapeutic target.Elucidation of PAC1R activation mechanism would benefit discovery of therapeutic drugs for neuronal disorders.PAC1R activity is governed by pituitary adenylate cyclase-activating polypeptide(PACAP),known as a major vasodilator neuropeptide,and maxadilan,a native peptide from the sand fly,which is also capable of activating the receptor with similar potency.These peptide ligands have divergent sequences yet initiate convergent PAC1R activity.It is of interest to understand the mechanism of PAC1R ligand recognition and receptor activity regulation through structural biology.Here we report two near-atomic resolution cryo-EM structures of PAC1R activated by PACAP38 or maxadilan,providing structural insights into two distinct ligand binding modes.The structures illustrate flexibility of the extracellular domain(ECD)for ligands with distinct conformations,where ECD accommodates ligands in different orientations while extracellular loop 1(ECU)protrudes to further anchor the ligand bound in the orthosteric site.By structureguided molecular modeling and mutagenesis,we tested residues in the ligand-binding pockets and identified clusters of residues that are critical for receptor activity.The structures reported here for the first time elucidate the mechanism of specificity and flexibility of ligand recognition and binding for PACT R,and provide insights toward the design of therapeutic molecules targeting PAC1R. | Jia Wang Xianqiang Song Dandan Zhang Xiaoqing Chen Xun Li Yaping Sun Cui Li Yunpeng Song Yao Ding Ruobing Ren Essa Hu Harrington Liaoyuan AHu Wenge Zhong Cen Xu Xin Huang Hong-Wei Wang Yingli Ma | 2020 | Cell Research2020，30，5： | 1 |
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