2022 Vol. 13, No. 9

New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Liu et al. identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes β-coronavirus lineage B (β-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Their findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against β-CoV-B and newly emerging SARS-CoV-2 variants of concern.

Recollection
Academician Qi-Yi Xing (Chi-Yi Hsing): pioneer organic chemist of synthetic insulin
Ming-Hua Qiu
2022, 13(9): 627-630. doi: 10.1007/s13238-021-00891-2
Abstract:
Review
The mini player with diverse functions: extracellular vesicles in cell biology, disease, and therapeutics
Abhimanyu Thakur, Xiaoshan Ke, Ya-Wen Chen, Pedram Motallebnejad, Kui Zhang, Qizhou Lian, Huanhuan Joyce Chen
2022, 13(9): 631-654. doi: 10.1007/s13238-021-00863-6
Abstract:
Extracellular vesicles (EVs) are tiny biological nanovesicles ranging from approximately 30–1000 nm in diameter that are released into the extracellular matrix of most cell types and in biofluids. The classification of EVs includes exosomes, microvesicles, and apoptotic bodies, dependent on various factors such as size, markers, and biogenesis pathways. The transition of EV relevance from that of being assumed as a trash bag to be a key player in critical physiological and pathological conditions has been revolutionary in many ways. EVs have been recently revealed to play a crucial role in stem cell biology and cancer progression via intercellular communication, contributing to organ development and the progression of cancer. This review focuses on the significant research progress made so far in the role of the crosstalk between EVs and stem cells and their niche, and cellular communication among different germ layers in developmental biology. In addition, it discusses the role of EVs in cancer progression and their application as therapeutic agents or drug delivery vehicles. All such discoveries have been facilitated by tremendous technological advancements in EV-associated research, especially the microfluidics systems. Their pros and cons in the context of characterization of EVs are also extensively discussed in this review. This review also deliberates the role of EVs in normal cell processes and disease conditions, and their application as a diagnostic and therapeutic tool. Finally, we propose future perspectives for EV-related research in stem cell and cancer biology.
Research Article
An ultrapotent pan-β-coronavirus lineage B (β-CoV-B) neutralizing antibody locks the receptor-binding domain in closed conformation by targeting its conserved epitope
Zezhong Liu, Wei Xu, Zhenguo Chen, Wangjun Fu, Wuqiang Zhan, Yidan Gao, Jie Zhou, Yunjiao Zhou, Jianbo Wu, Qian Wang, Xiang Zhang, Aihua Hao, Wei Wu, Qianqian Zhang, Yaming Li, Kaiyue Fan, Ruihong Chen, Qiaochu Jiang, Christian T. Mayer, Till Schoofs, Youhua Xie, Shibo Jiang, Yumei Wen, Zhenghong Yuan, Kang Wang, Lu Lu, Lei Sun, Qiao Wang
2022, 13(9): 655-675. doi: 10.1007/s13238-021-00871-6
Abstract:
New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes β-coronavirus lineage B (β-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional “down” conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD “up”. Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against β-CoV-B and newly emerging SARS-CoV-2 variants of concern.
Letters
mTORC2/RICTOR exerts differential levels of metabolic control in human embryonic, mesenchymal and neural stem cells
Qun Chu, Feifei Liu, Yifang He, Xiaoyu Jiang, Yusheng Cai, Zeming Wu, Kaowen Yan, Lingling Geng, Yichen Zhang, Huyi Feng, Kaixin Zhou, Si Wang, Weiqi Zhang, Guang-Hui Liu, Shuai Ma, Jing Qu, Moshi Song
2022, 13(9): 676-682. doi: 10.1007/s13238-021-00898-9
Abstract:
Modeling hepatoblastoma development with human fetal liver organoids reveals YAP1 activation is sufficient for tumorigenesis
Li Yang, Jin Chen, Jianqing Liang, Yufeng Zhang, Qingzhe Wang, Xiaojun Ren, Jinsong Wei, Qianchun Gong, Jiting Zhang, Ning Jiang, Xinhua Lin, Jin Li, Bing Zhao
2022, 13(9): 683-688. doi: 10.1007/s13238-021-00893-0
Abstract:
Crystal structure of SARS-CoV-2 main protease in complex with protease inhibitor PF-07321332
Yao Zhao, Chao Fang, Qi Zhang, Ruxue Zhang, Xiangbo Zhao, Yinkai Duan, Haofeng Wang, Yan Zhu, Lu Feng, Jinyi Zhao, Maolin Shao, Xiuna Yang, Leike Zhang, Chao Peng, Kailin Yang, Dawei Ma, Zihe Rao, Haitao Yang
2022, 13(9): 689-693. doi: 10.1007/s13238-021-00883-2
Abstract:
Correction
Correction to: Potentiating CD8+ T cell antitumor activity by inhibiting PCSK9 to promote LDLR-mediated TCR recycling and signaling
Juanjuan Yuan, Ting Cai, Xiaojun Zheng, Yangzi Ren, Jingwen Qi, Xiaofei Lu, Huihui Chen, Huizhen Lin, Zijie Chen, Mengnan Liu, Shangwen He, Qijun Chen, Siyang Feng, Yingjun Wu, Zhenhai Zhang, Yanqing Ding, Wei Yang
2022, 13(9): 694-700. doi: 10.1007/s13238-021-00833-y
Abstract: