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| 1 | Discriminated sgRNAs-Based SurroGate System Greatly Enhances the Screening Efficiency of Plant Base-Edited Cells显示文摘The development of CRISPR/Cas9-mediated base editing has made genomic modification more efficient. However, selection of genetically modified cells from millions of treated cells, especially plant cells, is still challenging. In this study, an efficient surrogate reporter system based on a defective hygromycin resistance gene was established in rice to enrich base-edited cells. After step-by-step optimization, the Discriminated sgRNAs-based SurroGate system (DisSUGs) was established by artificially differentiating the editing abilities of a wild-type single guide RNA (sgRNA) targeting the surrogate reporter gene and an enhanced sgRNA targeting endogenous sites. The DisSUGs enhanced the efficiency of screening base-edited cells by 3- to 5-fold for a PmCDA1-based cytosine-to-tyrosine base editor (PCBE), and 2.5- to 6.5-fold for an adenine base editor (ABE) at endogenous targets. These targets showed editing efficiencies of <25% in the conventional systems. The DisSUGs greatly enhanced the frequency of homozygous substitutions and expanded the activity window slightly for both a PCBE and an ABE. Analyses of the total number of single-nucleotide variants from whole-genome sequencing revealed that, compared with the no-enrichment PCBE strategy, the DisSUGs did not alter the frequency of genome-wide sgRNA-independent off-target mutations, but slightly increased the frequency of target-dependent off-target mutations. Collectively, the DisSUGs developed in this study greatly enhances the efficiency of screening plant base-edited cells and will be a useful system in future applications. | Wen Xu Yongxing Yang Ya Liu Guiting Kang Feipeng Wang Lu Li Xinxin Lv Si Zhao Shuang Yuan Jinling Song Ying Wu Feng Feng Xiaoqing He Chengwei Zhang Wei Song Jiuran Zhao Jinxiao Yang | 2020 | Molecular Plant2020，13，1： | 8 |
| 2 | Paclitaxel-induced stress granules increase LINE-1 mRNA stability to promote drug resistance in breast cancer cells显示文摘Abnormal expression of long interspersed element-1(LINE-1)has been implicated in drug resistance,while our previous study showed that chemotherapy drug paclitaxel(PTX)increased LINE-1 level with unknown mechanism.Bioinformatics analysis suggested the regulation of LINE-1 mRNA by drug-induced stress granules(SGs).This study aimed to explore whether and how SGs are involved in drug-induced LINE-1 increase and thereby promotes drug resistance of triple negative breast cancer(TNBC)cells.We demonstrated that SGs increased LINE-1 expression by recruiting and stabilizing LINE-1 mRNA under drug stress,thereby adapting TNBC cells to chemotherapy drugs.Moreover,LINE-1 inhibitor efavirenz(EFV)could inhibit drug-induced SG to destabilize LINE-1.Our study provides the first evidence of the regulation of LINE-1 by SGs that could be an important survival mechanism for cancer cells exposed to chemotherapy drugs.The findings provide a useful clue for developing new chemotherapeutic strategies against TNBCs. | Xiao Shi Xinxin Si Ershao Zhang Ruochen Zang Nan Yang He Cheng Zhihong Zhang Beijing Pan Yujie Sun | 2021 | The Journal of Biomedical Research2021，35，6： | 1 |
| 3 | Identification of thyroid receptor ant/agonists in water sources using mass balance analysis and monte carlo simulation 显示文摘 | Shi Wei Wei Si Hu Xinxin | 2013 | Thyroid Receptor Ant/Agonists Identification2013，8，： | 1 |
| 4 | Highly sensitive genotyping of MTHFR C677T polymorphisms using a novel RPA-LDR-qPCR assay显示文摘The 5,10-methylenetetrahydrofolate reductase(MTHFR)is an important enzyme involved in the metabolism of folic acid,synthesis of DNA,and DNA methylation.The genetic single nucleotide polymorphisms(SNPs)of MTHFR caused by the C677T mutation have become an important clinical indicator related to folic acid intake in relevant populations[1].The C677T mutation,replacing cytosine(C)by thymine(T)at the site,causes the change of encoded amino acid from alanine to valine,reducing the enzyme activity and heat resistance capacity.In the MTHFR polymorphism of the hybrid type(CT),the enzyme activity is reduced by 30%,while in the polymorphism of the homozygous type(TT),the activity is reduced by more than 65%,causing various degrees of folic acid metabolism disorders[2].Therefore,MTHFR polymorphisms are important information for clinicians to make personalized nutrition supplementation or treatment decisions. | Xinxin Si Qinghua Gu Chenjie Zhao Xiao Zhang Tingting Xiao Yu Li Wei Ying Song Gao | 2022 | Acta Biochimica et Biophysica Sinica2022，54，11： | 0 |
| 5 | The tRNA-derived fragment tRF-5022a positively regulates melanogenesis显示文摘The tRNA-derived fragments(tRFs)are small non-coding RNAs containing fewer than 50 nucleotides that are abundant in humans and have various biological functions.However,their roles and mechanisms in melanogenesis are unclear.In this study,we firstly investigated the change in the expres-sion profile of tRFs in melanocytes after UVB irradiation through tsRNA sequencing.UVB-induced melanogenesis led to the upregulation of 119 tRFs and the downregulation of 103 tRFs. | Si Li Lan Zhang Jing Chen Ling Jiang Chuhan Fu Ao Huang Xinxin Lei Siyu Yang Qinghai Zeng Ke Cao | 2023 | Genes & Diseases2023，10，4： | 0 |
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