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| 1 | Generation and characterization of stable pig pregastrulation epiblast stem cell lines显示文摘Pig epiblast-derived pluripotent stem cells are considered to have great potential and broad prospects for human therapeutic model developme nt and livestock breeding.Despite on going attempts since the 1990s,no stably defined pig epiblast-derived stem cell line has bee n established.Here,guided by in sights from a large-scale sin gle-cell tran scriptome an alysis of pig embryos from embryonic day(E)0 to E14,specifically,the tracing of pluripotency changes during epiblast development,we developed an in vitro culture medium for establishing and maintaining stable pluripotent stem cell lines from pig E10 pregastrulation epiblasts(pgEpiSCs).Enabled by chemical inhibition of WNT-related signaling in combination with growth factors in the FGF/ERK,JAK/STAT3,and Activin/Nodal pathways,pgEpiSCs maintain their pluripotency transcriptome features,similar to those of E10 epiblast cells,and normal karyotypes after more than 240 passages and have the potential to differentiate into three germ layers.Strikingly,ultradeep in situ Hi-C analysis revealed functional impacts of chromatin 3D-spatial associations on the transcriptional regulation of pluripote ncy marker genes in pgEpiSCs.I n practice,we con firmed that pgEpiSCs readily tolerate at least three rounds of successive gene editi ng and gene rated cloned gen e-edited live piglets.Our findings deliver on the long-a nticipated promise of pig pluripote nt stem cells and open new avenues for biological research,animal husbandry,and regenerative biomedicine. | Minglei Zhi Jinying Zhang Qianzi Tang Dawei Yu Shuai Gao Dengfeng Gao Pengliang Liu Jianxiong Guo Tang Hai Jie Gao Suying Cao Zimo Zhao Chongyang Li Xiaogang Weng Mengnan He Tianzhi Chen Yingjie Wang Keren Long Deling Jiao Guanglei Li Jiaman Zhang Yan Liu Yu Lin Daxin Pang Qianqian Zhu Naixin Chen Jingjing Huang Xinze Chen Yixuan Yao Jingcang Yang Zicong Xie Xianya Huang Mengxin Liu Ran Zhang Qiuyan Li Yiliang Miao Jianhui Tian Xingxu Huang Hongsheng Ouyang Bofeng Liu Wei Xie Qi Zhou Zhonghua Liu Caihong Zheng Mingzhou Li Jianyong Han | 2022 | Cell Research2022,32,4: | 3 |
| 2 | Merging PROTAC and molecular glue for degrading BTK and GSPT1 proteins concurrently显示文摘Dear Editor,Targeted protein degradation(TPD)represents a promising research field that has quickly attracted attention and efforts from both academia and pharmaceutical industry.TPD technology uses small molecules to induce the degradation of target proteins by harnessing the ubiquitin-proteasome system.PROTAC(PROteo-lysis Targeting Chimeras)1-3 and MG(Molecular Glue)4,5 are two major modes of TPD. | Zimo Yang Yonghui Sun Zhihao Ni Celi Yang Yan Tong Yujie Liu Haitao Li Yu Rao | 2021 | Cell Research2021,31,12: | 1 |
| 3 | Relative clock verifies endogenous bursts of human dynamics 显示文摘 | Zhou Tao Zhao Zhi-Dan Yang Zimo | 2012 | EPL ( Europhysics Letters)2012,97,1: | 1 |
| 4 | Global analysis of an SIS model with an infective vector on complex networks显示文摘 | Yi Wang Zhen Jin Zimo Yang Zi-Ke Zhang Tao Zhou Gui- Quan Sun | 2012 | Nonlinear Analysis: RealWorld Applica- tions2012,2012,: | 1 |
| 5 | Emergence of scaling in human-intere st dynamics显示文摘 | Zhi-Dan Zhao Zimo Yang Zike Zhang | 2013 | Scientific Report2013,,3: | 1 |
| 6 | A likely autotetraploidization event shaped the Chinese mahogany(Toona sinensis)genome显示文摘Chinese mahogany(Toona sinensis) is of considerable medical and economic importance, and its genome has been deciphered. However, the process underlying its polyploidy is unclear, and the chromosomal evolutionary trajectory is poorly understood. Here, by reanalysing the T.sinensis genome, we found evidence of a tetraploidization event(T. sinensis special tetraploidization, TST) that occurred approximately 15-17 million years ago(MYA) after the core eudicot-common hexaploidization(ECH or gamma) event. We characterized the synonymous nucleotide substitution rates(Ks values) of collinear genes and found that T. sinensis genes affected by the TST evolve at a slower rate than Acer yangbiense genes. Furthermore, we identified homologous genes related to polyploidization and speciation and constructed multiple alignments with different reference genomes. Notably, the significant balance of gene retention and loss characterized in the two TST-derived subgenomes suggests an autopolyploid nature of the TST. Moreover, we deduced the chromosomal karyotypes of the two subgenomes and identified 7chromosomal fusions that have shaped the T. sinensis genome;more information is available on a newly constructed karyotype platform(http://gffzze84c5b42976d4cd7h0xpoonfbuxkq6fuv.ffgz.tsg.suse.edu.cn/Toona_sinensis/index.html). The T. sinensis genome preserves the ancestral chromosome structure of dicotyledons well and could serve as a good reference for understanding genomic changes in other Meliaceae and Sapindales plants. In addition, we verified that tandem duplication and the ECH have promoted the expansion of terpene synthase(TPS) genes;conversely, the TST seems to have inhibited expansion of these genes. This present effort has clarified the polyploidy events of the T. sinensis genome, filled gaps in the history of karyotype evolution, and laid a solid foundation for further genomic studies in the Meliaceae research community and beyond. | Jianyu Wang Ziyi Yang Tianyu Lei Yan Zhang Qimeng Xiao Zijian Yu Jiaqi Zhang Sangrong Sun Qiang Xu Shaoqi Shen Zimo Yan Mengnan Fang Yue Ding Zihan Liu Qianwen Zhu Ke Ren Yuxin Pan Haibin Liu Jinpeng Wang | 2023 | Horticultural Plant Journal2023,9,2: | 0 |
| 7 | Synthesis of Quaternary Carbon-Centered Benzoindolizidinones via Novel Photoredox-Catalyzed Alkene Aminoarylation: Facile Access to Tylophorine and Analogues显示文摘Photoredox-catalyzed aminoarylation and thioami-nation of unactivated alkenes have been developed,providing novel synthetic routes to access synthe-tically challenging quaternary carbon-centered benzoindolizidinones and trifluoromethylthiolated piperidines using readily available starting materials.Notably,these transformations were enabled by merging amidyl radical generation from N-alkyl benzamides with oxidant incorporation.Density functional theory calculations were performed to understand the reaction mechanism and to rationa-lize the regioselectivities.Moreover,the newly deve-loped catalytic aminoarylation provided a convenient synthetic route for natural product tylophorine and its gem-dimethyl analogues with greatly improved drug-like properties such as enhanced solubility and stability. | Chao Zhang Yi Wang Yugang Song Hongying Gao Yonghui Sun Xiuyun Sun Yiqing Yang Ming He Zimo Yang Lingpeng Zhan Zhi-Xiang Yu Yu Rao | 2019 | CCS Chemistry2019,1,4: | 0 |
| 8 | Developing potent BTK^(C481S)PROTACs for ibrutinib-resistant malignant lymphoma显示文摘Ibrutinib is a first-line treatment drug for B-cell malignancies.However,resistance to ibrutinib has been reported due to BTKC481Smutation.Although PROTAC strategy is expected to overcome this clinical resistance,it has limitations such as large molecular weight and moderate bioactivity,which restrict its potential clinical application.Herein,we report a new type of potent BTKC481S-targeting PROTAC degrader.Through design,computer-assisted optimization and SAR studies,we have developed a representative BTKC481Sdegrader L6 with a much smaller molecular weight and improved solubility.Notably,L6 demonstrates better BTK degrading activity and lower IC50value in ibrutinib-resistant cell line than the first-generation BTK degrader P13I.Optimization strategy of L6 provides a general approach in the development of PROTACs targeting BTK and other proteins for future study. | Yonghui Sun Xin Luo Zimo Yang Wenxing Lv Lixia Chen Hua Li Yu Rao | 2023 | Chinese Chemical Letters2023,34,6: | 0 |