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| 1 | 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 |
| 2 | Dielectric barrier discharge-based defect engineering method to assist flash sintering显示文摘Oxygen vacancy OV plays an important role in a flash sintering (FS) process. In defect engineering, the methods of creating oxygen vacancy defects include doping, heating, and etching, and all of them often have complex processes or equipment. In this study, we used dielectric barrier discharge (DBD) as a new defect engineering technology to increase oxygen vacancy concentrations of green billets with different ceramics (ZnO, TiO_(2), and 3 mol% yttria-stabilized zirconia (3YSZ)). With an alternating current (AC) power supply of 10 kHz, low-temperature plasma was generated, and a specimen could be treated in different atmospheres. The effect of the DBD treatment was influenced by atmosphere, treatment time, and voltage amplitude of the power supply. After the DBD treatment, the oxygen vacancy defect concentration in ZnO samples increased significantly, and a resistance test showed that conductivity of the samples increased by 2–3 orders of magnitude. Moreover, the onset electric field (E) of ZnO FS decreased from 5.17 to 0.86 kV/cm at room temperature (RT);while in the whole FS, the max power dissipation decreased from 563.17 to 27.94 W. The defect concentration and conductivity of the green billets for TiO_(2) and 3YSZ were also changed by the DBD, and then the FS process was modified. It is a new technology to treat the green billet of ceramics in very short time, applicable to other ceramics, and beneficial to regulate the FS process. | Xinhao Zhao Nianping Yan Yueji Li Zikui Shen Rongxia Huang Chen Xu Xuetong Zhao Xilin Wang Ruobing Zhang Zhidong Jia | 2023 | Journal of Advanced Ceramics2023，12，5： | 0 |
| 3 | Author Correction: Cryo-EM structures of PAC1 receptor reveal ligand binding mechanism显示文摘We noticed the missing structure deposition information in our manuscript published online on February 11,2020,which are the PDB codes and EMDB map entries of the structure PACAP38-PAC1R-GS(PDB code:6M1I and EMDB entry:EMD-30048)and maxadilan-PAC1R-Gs(PDB code:6M1H and EMDB entry:EMD-30047).We apologize for any inconvenience this missing information has caused.This correction does not affect the description of the results or the conclusion of this work. | 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： | 0 |
| 4 | Reply to Comment by Lamy et al. on “Locating the source field lines of Jovian decametric radio emissions”显示文摘Locating the source of decametric(DAM)radio emissions is a key step in the use of remote radio observations to understand the Jovian magnetospheric dynamics and their interaction with the planet’s moons.Wang YM et al.(2020)presented a method by which recorded arc-shaped DAM emissions in the radio dynamic spectra can be used to locate the source of a DAM.An Io-related DAM event on March 14,2014 was used to demonstrate the method.A key parameter in the method is whether the DAM is emitted in the northern or the southern hemisphere;the hemisphere of origin can be determined definitively from the polarization of the emission.Unfortunately,polarization information for the emission on March 14,2014 event was not recorded.Our analysis assumed the source to be in the northern hemisphere.Lamy et al.(2022)argue convincingly that the source was probably in the southern hemisphere.We appreciate the helpful contribution of Lamy et al.(2022)to this discussion and have updated our analysis,this time assuming that the DAM source was in the southern hemisphere.We also explore the sensitivity of our method to another parameter-the height at which the value of fce,max,which is the maximal electron cyclotron frequency reached along the active magnetic flux tube,is adopted.Finally,we introduce our recent statistical study of 68 DAM events,which lays a more solid basis for testing the reliability of our method,which we continue to suggest is a promising tool by which remote radio observations can be used to locate the emission source of Jovian DAMs. | YuMing Wang RuoBing Zheng XianZhe Jia ChuanBing Wang Shui Wang V.Krupar | 2022 | Earth and Planetary Physics2022，6，1： | 0 |
| 5 | Extrachromosomal circular DNA: biogenesis, structure, functions and diseases显示文摘Extrachromosomal circular DNA(eccDNA),ranging in size from tens to millions of base pairs,is independent of conventional chromosomes.Recently,eccDNAs have been considered an unanticipated major source of somatic rearrangements,contributing to genomic remodeling through chimeric circularization and reintegration of circular DNA into the linear genome.In addition,the origin of eccDNA is considered to be associated with essential chromatin-related events,including the formation of super-enhancers and DNA repair machineries.Moreover,our understanding of the properties and functions of eccDNA has continuously and greatly expanded.Emerging investigations demonstrate that eccDNAs serve as multifunctional molecules in various organisms during diversified biological processes,such as epigenetic remodeling,telomere trimming,and the regulation of canonical signaling pathways.Importantly,its special distribution potentiates eccDNA as a measurable biomarker in many diseases,especially cancers.The loss of eccDNA homeostasis facilitates tumor initiation,malignant progression,and heterogeneous evolution in many cancers.An in-depth understanding of eccDNA provides novel insights for precision cancer treatment.In this review,we summarized the discovery history of eccDNA,discussed the biogenesis,characteristics,and functions of eccDNA.Moreover,we emphasized the role of eccDNA during tumor pathogenesis and malignant evolution.Therapeutically,we summarized potential clinical applications that target aberrant eccDNA in multiple diseases. | Ludi Yang Ruobing Jia Tongxin Ge Shengfang Ge Ai Zhuang Peiwei Chai Xianqun Fan | 2022 | Signal Transduction and Targeted Therapy2022，7，11： | 0 |
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