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Enhanced reverse zoonotic potential and immune evasion by omicron JN.1 variant

iScience 2025年第7期28卷

作者： Jiaxin Hu fuwen Zan Yixin He Xiuyuan Ou Xiaolu Tang Yan Liu Xing Lu Pei Li Zhixia Mu Siwen Dong Yahan Chen lin Tan Mengmeng Cao Pinghuang Liu Terrence Tsz-Tai Yuen Jian Lu Zhaohui Qian NHC Key Laboratory of Systems Biology of Pathogens Institute of Pathogen Biology Chinese Academy of Medical Sciences & Peking Union Medical College Beijing China MOE Key Laboratory of Pathogen Infection Prevention and Control Peking Union Medical College Beijing China State Key Laboratory of Respiratory Health and Multimorbidity Chinese Academy of Medical Sciences & Peking Union Medical College Beijing China Department of Microbiology School of Clinical Medicine Li Ka Shing Faculty of Medicine The University of Hong Kong Pokfulam Hong Kong China Key Laboratory of Animal Epidemiology of the Ministry of Agriculture College of Veterinary Medicine China Agricultural University Beijing China College of Life Sciences Peking University Beijing China

SARS-CoV-2 infects not only humans but also animals, posing reverse zoonotic risks. As SARS-CoV-2 rapidly evolves, JN.1 has become dominant globally. In this study, we determined the susceptibility of XBB.1.16, EG.5.1, BA.2.86, and JN.1 to 27 different animal angiotensin-converting enzyme 2 (ACE2) orthologs using pseudoviruses, and found that JN.1 displayed substantially higher overall reverse zoonotic risk potential compared to other variants except for EG.5.1. Live virus infection experiments further confirmed higher infectivity of JN.1 than BA.2.86. Mechanistic analyses revealed that L455S might be responsible for substantial increase in overall fusogenecity and infectivity by lowering S protein thermostability. Additionally, we also found that L455S mutation enhanced immune evasion of SARS-CoV-2, and XBB breakthrough infection increased levels of neutralization antibodies against JN.1. Together, our findings offer a better mechanistic understanding of CoV entry, host range, evolution, and immunogenicity and highlight the importance of surveillance of susceptible hosts to prevent potential outbreaks.

关键词： Immunology Virology

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Novel Reversible-Binding PET Ligands for Imaging Monoacylglycerol Lipase Based on the Piperazinyl Azetidine Scaffold

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JOURNAL OF MEDICINAL CHEMISTRY 2021年第19期64卷 14283-14298页

作者： Rong, Jian Mori, Wakana Xia, Xiaotian Schafroth, Michael A. Zhao, Chunyu Van, Richard S. Yamasaki, Tomoteru Chen, Jiahui Xiao, Zhiwei Haider, Ahmed Ogasawara, Daisuke Hiraishi, Atsuto Shao, Tuo Zhang, Yiding Chen, Zhen Pang, fuwen Hu, Kuan Xie, lin Fujinaga, Masayuki Kumata, Katsushi Gou, Yuancheng Fang, Yang Gu, Shuyin Wei, Huiyi Bao, Liang Xu, Hao Collier, Thomas L. Shao, Yihan Carson, Richard E. Cravatt, Benjamin F. Wang, Lu Zhang, Ming-Rong Liang, Steven H. Massachusetts Gen Hosp Div Nucl Med & Mol Imaging Boston MA 02114 USA Harvard Med Sch Dept Radiol Boston MA 02114 USA Natl Inst Quantum & Radiol Sci & Technol Natl Inst Radiol Sci Dept Adv Nucl Med Sci Chiba 2638555 Japan Skaggs Inst Chem Biol La Jolla CA 92037 USA Scripps Res Inst Dept Chem Physiol La Jolla CA 92037 USA Univ Oklahoma Dept Chem & Biochem Norman OK 73019 USA Chemshuttle Inc Wuxi 214174 Jiangsu Peoples R China Jinan Univ Affiliated Hosp 1 Ctr Cyclotron & PET Radiopharmaceut Dept Nucl Med Guangzhou 510630 Peoples R China Jinan Univ Affiliated Hosp 1 PET CT MRI Ctr Guangzhou 510630 Peoples R China Yale Univ Sch Med Dept Radiol & Biomed Imaging New Haven CT 06520 USA

Monoacylglycerol lipase (MAGL) is a 33 kDa serine protease primarily responsible for hydrolyzing 2-arachidonoylglycerol into the proinflammatory eicosanoid precursor arachidonic acid in the central nervous system. Inhibition of MAGL constitutes an attractive therapeutic concept for treating psychiatric disorders and neurodegenerative diseases. Herein, we present the design and synthesis of multiple reversible MAGL inhibitor candidates based on a piperazinyl azetidine scaffold. Compounds 10 and 15 were identified as the best-performing reversible MAGL inhibitors by pharmacological evaluations, thus channeling their radiolabeling with fluorine-18 in high radiochemical yields and favorable molar activity. Furthermore, evaluation of [F-18]10 and [F-18]15 ([F-18]MAGL-2102) by autoradiography and positron emission tomography (PET) imaging in rodents and nonhuman primates demonstrated favorable brain uptakes, heterogeneous radioactivity distribution, good specific binding, and adequate brain kinetics, and [F-18]15 demonstrated a better performance. In conclusion, [F-18]15 was found to be a suitable PET radioligand for the visualization of MAGL, harboring potential for the successful translation into humans.

关键词： Peptides and proteins Ligands Central nervous system Rodent models Inhibitors

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Suppressing Exciton-Vibration Coupling to Prolong Exciton Lifetime of Nonfullerene Acceptors Enables High-Efficiency Organic Solar Cells

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Angewandte Chemie 2024年第8期136卷

作者： Yufan Zhu Dr. Dan He Chong Wang Xiao Han Zesheng Liu Ke Wang Prof. Jianqi Zhang Dr. Xingxing Shen Dr. Jie Li Prof. Yuze lin Prof. Chunru Wang Prof. Yuehui He Prof. fuwen Zhao State Key Laboratory of Powder Metallurgy Central South University Changsha 410083 P. R. China College of Chemistry and Chemical Engineering Central South University Changsha 410083 P. R. China University of Chinese Academy of Sciences Beijing 100190 P. R. China Beijing National Laboratory for Molecular Sciences CAS Key Laboratory of Organic Solids and Laboratory of Molecular Nanostructure and Nanotechnology Institute of Chemistry Chinese Academy of Sciences Beijing 100190 P. R. China CAS Key Laboratory of Nanosystem and Hierarchical Fabrication CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology Beijing 100190 P. R. China College of Chemical Engineering Hebei Normal University of Science & Technology Qinhuangdao 066004 P. R. China

The limited exciton lifetime ( τ , generally <1 ns) leads to short exciton diffusion length ( L D ) of organic semiconductors, which is the bottleneck issue impeding the further improvement of power conversion efficiencies (PCEs) for organic solar cells (OSCs). However, efficient strategies to prolong intrinsic τ are rare and vague. Herein, we propose a facile method to efficiently reduce vibrational frequency of molecular skeleton and suppress exciton-vibration coupling to decrease non-radiative decay rate and thus prolong τ via deuterating nonfullerene acceptors. The τ remarkably increases from 0.90 ns (non-deuterated L8-BO) to 1.35 ns (deuterated L8-BO-D), which is the record for organic photovoltaic materials. Besides, the inhibited molecular vibration improves molecular planarity of L8-BO-D for enhanced exciton diffusion coefficient. Consequently, the L D increases from 7.9 nm (L8-BO) to 10.7 nm (L8-BO-D). The prolonged L D of L8-BO-D enables PM6 : L8-BO-D-based bulk heterojunction OSCs to acquire higher PCEs of 18.5 % with more efficient exciton dissociation and weaker charge carrier recombination than PM6 : L8-BO-based counterparts. Moreover, benefiting from the prolonged L D , D18/L8-BO-D-based pseudo-planar heterojunction OSCs achieve an impressive PCE of 19.3 %, which is among the highest values. This work provides an efficient strategy to increase the τ and thus L D of organic semiconductors, boosting PCEs of OSCs.

关键词： Deuteration Exciton Diffusion Length Exciton Lifetime Exciton-Vibration Coupling Organic Solar Cells

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Molecular mechanisms and topological consequences of drastic chromosomal rearrangements of muntjac deer

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NATURE COMMUNICATIONS 2021年第1期12卷 6858-6858页

作者： Yin, Yuan Fan, Huizhong Zhou, Botong Hu, Yibo Fan, Guangyi Wang, Jinhuan Zhou, Fan Nie, Wenhui Zhang, Chenzhou Liu, lin Zhong, Zhenyu Zhu, Wenbo Liu, Guichun lin, Zeshan Liu, Chang Zhou, Jiong Huang, Guangping Li, Zihe Yu, Jianping Zhang, Yaolei Yang, Yue Zhuo, Bingzhao Zhang, Baowei Chang, Jiang Qian, Haiyuan Peng, Yingmei Chen, Xianqing Chen, Lei Li, Zhipeng Zhou, Qi Wang, Wen Wei, fuwen Northwestern Polytech Univ Sch Ecol & Environm Xian 710072 Peoples R China Chinese Acad Sci Inst Zool CAS Key Lab Anim Ecol & Conservat Biol Beijing 100101 Peoples R China Southern Marine Sci & Engn Guangdong Lab Guangzho Ctr Evolut & Conservat Biol Guangzhou 511458 Guangdong Peoples R China Chinese Acad Sci Ctr Excellence Anim Evolut & Genet Kunming 650223 Yunnan Peoples R China BGI Shenzhen BGI Qingdao Qingdao 266555 Peoples R China BGI Shenzhen Shenzhen 518083 Peoples R China BGI Shenzhen China Natl GeneBank Shenzhen 518120 Peoples R China Chinese Acad Sci Kunming Inst Zool State Key Lab Genet Resources & Evolut Kunming Cell Bank Kunming 650223 Yunnan Peoples R China Frasergen Bioinformat Co Ltd Wuhan 430074 Hubei Peoples R China Beijing Milu Ecol Res Ctr Beijing 100076 Peoples R China Qianjiangyuan Natl Pk Kaihua 324300 Peoples R China Tech Univ Denmark Dept Biotechnol & Biomed DK-2800 Lyngby Denmark Anhui Univ Sch Life Sci Hefei 230039 Peoples R China Chinese Res Inst Environm Sci State Key Lab Environm Criteria & Risk Assessment Beijing 100012 Peoples R China Jilin Agr Univ Colleague Anim Sci & Technol Changchun 130118 Peoples R China Chinese Acad Agr Sci Inst Special Anim & Plant Sci Changchun Peoples R China Zhejiang Univ Life Sci Inst MOE Lab Biosyst Homeostasis & Protect Hangzhou 310058 Peoples R China Zhejiang Univ Life Sci Inst Zhejiang Prov Key Lab Canc Mol Cell Biol Hangzhou 310058 Peoples R China Univ Vienna Dept Neurosci & Dev Biol A-1090 Vienna Austria Zhejiang Univ Affiliated Hosp 2 Ctr Reprod Med Sch Med Hangzhou 310052 Peoples R China

Muntjac deer have experienced drastic karyotype changes during their speciation, making it an ideal model for studying mechanisms and functional consequences of mammalian chromosome evolution. Here we generated chromosome-level genomes for Hydropotes inermis (2n = 70), Muntiacus reevesi (2n = 46), female and male M. crinifrons (2n = 8/9) and a contig-level genome for M. gongshanensis (2n = 8/9). These high-quality genomes combined with Hi-C data allowed us to reveal the evolution of 3D chromatin architectures during mammalian chromosome evolution. We find that the chromosome fusion events of muntjac species did not alter the A/B compartment structure and topologically associated domains near the fusion sites, but new chromatin interactions were gradually established across the fusion sites. The recently borne neo-Y chromosome of M. crinifrons, which underwent male-specific inversions, has dramatically restructured chromatin compartments, recapitulating the early evolution of canonical mammalian Y chromosomes. We also reveal that a complex structure containing unique centromeric satellite, truncated telomeric and palindrome repeats might have mediated muntjacs' recurrent chromosome fusions. These results provide insights into the recurrent chromosome tandem fusion in muntjacs, early evolution of mammalian sex chromosomes, and reveal how chromosome rearrangements can reshape the 3D chromatin regulatory conformations during species evolution. Muntjac deer underwent rapid species radiation and dramatic chromosome fusions within a short period of time. Here the authors reveal that repeat sequences likely mediated illegitimate recombination to result in chromosome fusions and that 3D chromatin architecture around fusion sites have no significant change, while significant interactions across fusion sites were gradually established after speciation.

关键词： Genome evolution Evolutionary genetics Epigenomics Comparative genomics

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分布式电磁法仪器系统设计及实现

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地球物理学报 2019年第10期62卷 3772-3784页

作者：郑采君刘昕卓林品荣孙夫文李勇李建华王珺璐中国地质科学院地球物理地球化学勘查研究所河北廊坊065000 国土资源部地球物理电磁法探测技术重点实验室河北廊坊065000 北华航天工业学院河北廊坊065000

本文介绍一种采用大功率稳流发射、低噪声测量、宽频带接收以及分布式同步等技术,自主研制的分布式多功能电磁法仪器系统.系统包括大功率电磁法发射机、分布式电磁法接收机、磁场传感器、整流源等设备.采用ARM芯片和FPGA芯片进行发射机... 详细信息

本文介绍一种采用大功率稳流发射、低噪声测量、宽频带接收以及分布式同步等技术,自主研制的分布式多功能电磁法仪器系统.系统包括大功率电磁法发射机、分布式电磁法接收机、磁场传感器、整流源等设备.采用ARM芯片和FPGA芯片进行发射机的整机控制和信号整形发射,采用PC104工控机和FPGA芯片进行接收机的整机控制和信号处理.在人工场源模式下实现了可控源音频大地电磁法(CSAMT)、谱激电法(SIP)和时域激电法(TDIP)等测量功能;在天然场源模式下实现了大地电磁法(MT)、音频大地电磁法(AMT)的测量功能.发射机在满功率发射的情况下连续可靠运行时间大于12h,接收机的动态范围大于120dB,接收机可接收信号频率范围是0.001Hz^32kHz.通过典型矿区的野外实验和应用,表明本系统的性能总体上达到了国际先进水平.

关键词：大功率发射机分布式接收机磁场传感器多参数测量

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Enhanced degradation of BDE209 in spiked soil by ferrous-activated persulfate process with chelating agents

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ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH 2017年第3期24卷 2442-2448页

作者： Peng, Hongjiang Xu, Liya Zhang, Wei Liu, lin Liu, fuwen lin, Kuangfei Lu, Qiang East China Univ Sci & Technol Sch Resource & Environm Engn State Environm Protect Key Lab Environm Risk Asse Shanghai 200237 Peoples R China

In order to maintain the quantity of ferrous ions, two eco-friendly chelating agents (CAs), i.e., sodium citrate (Citrate) and sodium gluconate (Glu), have been introduced into a traditional iron activated sodium persulfate (PS) system (Fe2+/PS). The results indicated that the PS/CA/Fe2+ oxidation could be an effective method for BDE209 removal. Effects of the chelating agents, reagents dosage, and pH were evaluated in batch experiments. Glu was observed to be more effective than citrate. In addition, the rate constants (k(1)) of BDE209 removal indicated a quadratic curve relationship with initial persulfate concentrations (k(1) = -0.019 x [PS](0)(2) + 0.031 x [PS](0) + 0.007, R-2 = 0.933, [PS](0) = 0.1-1.0 M) and a good linear relationship with initial ferrous contents (k(1) = 0.109 x [Fe2+](0) + 0.002, R-2 = 0.943). Furthermore, as a reducing agent, ascorbic acid (H(2)A) could enhance the degradation rate of BDE209, which might be because H(2)A accelerated the transformation process from Fe3+- to Fe2+-gluconate complexes.

关键词： BDE209 Sodium persulfate Chelating agent Reducing agent Ascorbic acid

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铬污染土壤稳定化处理对蚯蚓的毒性效应

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环境科学学报 2019年第3期39卷 952-957页

作者：刘馥雯罗启仕王漫莉冉雨灵陆强林匡飞崔长征华东理工大学资源与环境工程学院国家环境保护化工过程环境风险评价与控制重点实验室上海200237 永清环保股份有限公司上海分公司上海200051

浸出毒性测试是评价重金属污染土壤稳定化处理效果的主要方法,但该方法不能准确反映稳定化处理后土壤的生物毒性变化.本研究以多硫化钙(CPS)稳定化处理的电镀厂铬(Cr)污染土壤为对象,以赤子爱胜蚓为指示生物,研究评估土壤稳定化处理的... 详细信息

浸出毒性测试是评价重金属污染土壤稳定化处理效果的主要方法,但该方法不能准确反映稳定化处理后土壤的生物毒性变化.本研究以多硫化钙(CPS)稳定化处理的电镀厂铬(Cr)污染土壤为对象,以赤子爱胜蚓为指示生物,研究评估土壤稳定化处理的生物毒性效应.结果表明,在Cr污染土壤中,随着CPS投加量的增加,蚯蚓的毒性效应逐渐减弱随后增强.高浓度Cr污染土壤经过CPS稳定化处理后仍然具有明显的生物毒性,CPS与土壤中Cr(VI)投加比(物质的量比,下同)为3时土壤浸出毒性虽满足浸出标准,但对蚯蚓的7 d致死效应高达100%,且暴毒期间出现肉眼可见的外部形态变化,回避率为83.3%,在暴毒第5 d时蚯蚓体内总Cr含量为20.9 mg·kg^(-1).CPS对蚯蚓具有较强的生物毒性作用,在不含Cr污染的对照组土壤中,CPS投加量与稳定化处理Cr污染土壤中稳定化药剂投加比为5相同时,蚯蚓的7 d急性毒性致死率为100%.蚯蚓的致死率和外部形态变化可快速直观地反映重金属污染土壤的生物毒性,可为土壤稳定化处理的安全性与生物毒性评估提供参考依据.

关键词： Cr污染土壤稳定化 CPS 生物毒性赤子爱胜蚓

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Quantification of radioactivity by planar gamma-camera images, a promoted method of absorbed dose in the thyroid after iodine-131 treatment

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SCIENTIFIC REPORTS 2018年第1期8卷 10167-10167页

作者： Li, Yuhao Cai, Huawei Shen, Guohua Pang, fuwen Dong, Ping Li, lin Sichuan Univ West China Hosp Dept Nucl Med 37 Guoxue Lane Chengdu Sichuan Peoples R China

Iodine-131 (I-131) is an essential and widely used radioisotope in thyroid diseases and animal experiments. Planar imaging has been considered the most popular method for I-131 thyroid uptake radioactive activity quantification. The ROI defining section is essential and can affect the accuracy of quantitative results. However, a consistent method has not been proposed. In this study, a UC-ROI defining method based on ULWL setting and colour display grade was applied. Three steps were performed: image acquisition of five standard activity models and obtaining the exact value that the counts per radioactive activity contributes to the ROI;image acquisition of 20 rat thyroids and obtaining the counts of the ROI (thyroid);and calculating the rat thyroid radioactive activity and comparing these values with the true values. The accuracy of quantification activity of I-131 in rat thyroid reached 2.62% +/- 0.41%. The mean quantification within 5% could be achieved in 19 of 20 rat thyroids. No significant difference existed between calculated thyroid I-131 activity and true values with a paired matched-test (t = -0.384, P = 0.706 > 0.05). The results indicated that with the UC-ROI defining method, more accurate thyroid uptake I-131 radioactive activity quantification by SPECT planar imaging can be achieved in vivo rat study.

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Enhancing the performance of the electron acceptor ITIC-Th via tailoring its end groups

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MATERIALS CHEMISTRY FRONTIERS 2018年第3期2卷 537-543页

作者： Li, Zeyuan Dai, Shuixing Xin, Jingming Zhang, lin Wu, Yang Rech, Jeromy Zhao, fuwen Li, Tengfei Liu, Kuan Liu, Qiao Ma, Wei You, Wei Wang, Chunru Zhan, Xiaowei Peking Univ Coll Engn Dept Mat Sci & Engn Key Lab Polymer Chem & PhysMinist Educ Beijing 100871 Peoples R China Xi An Jiao Tong Univ State Key Lab Mech Behav Mat Xian 710049 Peoples R China Univ North Carolina Chapel Hill Dept Chem Chapel Hill NC 27599 USA Chinese Acad Sci Inst Chem Beijing 100190 Peoples R China

We choose the high-performance nonfullerene acceptor ITIC-Th as an example, and incorporate electron-donating methoxy and electron-withdrawing F groups onto the terminal group 1,1-dicyanomethylene-3-indanone (IC) to construct a small library of four fused-ring electron acceptors. With this series, we systematically investigate the effects of the substituents on the end-groups on the electronic properties, charge transport, film morphology, and photovoltaic properties of the ITIC-Th series. The electron-withdrawing ability increases from methoxylated to unsubstituted, fluorinated, and difluorinated IC, leading to a downshift of energy levels and a redshift of absorption spectra. Optimized organic solar cells based on the ITIC-Th series show power conversion efficiencies ranging from 8.88% to 12.1%.

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Different kinds of persulfate activation with base for the oxidation and mechanism of BDE209 in a spiked soil system

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SCIENCE OF THE TOTAL ENVIRONMENT 2017年 574卷 307-313页

作者： Peng, Hongjiang Xu, Liya Zhang, Wei Liu, fuwen Lu, Xin Lu, Wei Danish, Muhammad lin, Kuangfei East China Univ Sci & Technol State Environm Protect Key Lab Environm Risk Asse Shanghai 200237 Peoples R China East China Univ Sci & Technol Sch Resource & Environm Engn Shanghai 200237 Peoples R China

The feasibility of using base persulfate (PS) and coupled with other activation methods (heat, ultrasonic and Fe2+ gluconate) was first explored for the removal of decabromodiphenyl ether (BDE209) in a soil system, and various factors were also investigated. The results showed that the removal of BDE209 followed a pseudo first -order model. Interestingly, the rate constant (k1) indicated a good power exponential relationship with initial PS (k(1) = 0.018 x [PS](0.437)(0), R2 = 0.983, [PS](0) = 0.02-0.5 M) or BDE209 (k(1) = 0.029 x e(0)(-0.038x[BDE209]), R-2 = 0.999, [BDE209](0) = 10-50 mg kg(-1)) concentration, respectively. Additionally, k(1) well fitted the Arrhenius equation at the temperature range of 25 to 55 C, and the calculated activation energy (E-a) approximately was 41.2 kJ mol(-1). The removal efficiency could be enhanced in the presence of ultrasound due to increasing the amount of BDE209 molecules desorbed from soil and organic matters. Finally, nine intermediate products were identified during the heat and base co-activated PS oxidation process, and the possible reaction pathways were further proposed. (C) 2016 Elsevier B.V. All rights reserved.

关键词： BDE209 Persulfate Rate constant Free radical Degradation performance

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