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DSCI: a database of synthetic biology components for innate immunity and cell engineering decision-making processes

Advanced biotechnology 2024年第3期2卷 29页

作者： Chenqiu Zhang Tianjian Chen Zhiyu Li Qing Lu Xiaotong Luo Sihui Cai Jie Zhou Jian Ren Jun Cui MOE Key Laboratory of Gene Function and Regulation Guangdong Province Key Laboratory of Pharmaceutical Functional Genes State Key Laboratory of Biocontrol School of Life Sciences Sun Yat-Sen University Guangzhou Guangdong 510275 China. State Key Laboratory of Oncology in South China Cancer Center Collaborative Innovation Center for Cancer Medicine School of Life Sciences Sun Yat-sen University Guangzhou 510275 China. State Key Laboratory of Membrane Biology & Frontier Research Center for Biological Structure School of Life Sciences Tsinghua University Beijing 100101 China. Tsinghua University-Peking University Joint Center for Life Sciences Beijing 100101 China. MOE Key Laboratory of Gene Function and Regulation Guangdong Province Key Laboratory of Pharmaceutical Functional Genes State Key Laboratory of Biocontrol School of Life Sciences Sun Yat-Sen University Guangzhou Guangdong 510275 China. renjian@***. State Key Laboratory of Oncology in South China Cancer Center Collaborative Innovation Center for Cancer Medicine School of Life Sciences Sun Yat-sen University Guangzhou 510275 China. renjian@***. MOE Key Laboratory of Gene Function and Regulation Guangdong Province Key Laboratory of Pharmaceutical Functional Genes State Key Laboratory of Biocontrol School of Life Sciences Sun Yat-Sen University Guangzhou Guangdong 510275 China. cuij5@***.

Although significant progress of clinical strategy has been made in gene editing and cell engineering in immunotherapy, it is now apparent that design and modification in terms of complex signaling pathways and motifs on medical synthetic biology are still full of challenges. Innate immunity, the first line of host defense against pathogens, is critical for anti-pathogens immune response as well as regulating durable and protective T cell-mediated anti-tumor responses. Here, we introduce DSCI (Database of Synthetic Biology Components for Innate Immunity, https://***/ ), a web-accessible and integrative database that provides better insights and strategies for innate immune signaling circuit design in biosynthesis. Users can interactively navigate comprehensive and carefully curated components resources that presented as visualized signaling motifs that participate in innate immunity. The current release of DSCI incorporates 1240 independent components and more than 4000 specific entries contextually annotated from public literature with experimental verification. The data integrated into DSCI includes the components of pathways, relationships between regulators, signal motifs based on regulatory cascades, and loop graphs, all of which have been comprehensively annotated to help guide modifications to gene circuits. With the support of DSCI, users can easily obtain guidance of gene circuits construction to make decision of cell engineering based on innate immunity. DSCI not only provides comprehensive and specialized resource on the biological components of innate immune synthesis, but also serves as a useful tool to offer modification or generation strategies for medical synthetic biology.

关键词： Database Innate immunity Interaction network Loop visualization Signal motif Synthetic biology

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The functional analysis of transiently upregulated miR-101 suggests a “braking” regulatory mechanism during myogenesis

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Science China(Life Sciences) 2021年第10期64卷 1612-1623页

作者： Shurong Liu Shujuan Xie Huafeng Chen Bin Li Zhirong Chen Yeya Tan Jianhua Yang Lingling Zheng Zhendong Xiao Qi Zhang Lianghu Qu MOE Key Laboratory of Gene Function and Regulation State Key Laboratory of BiocontrolSchool of Life SciencesSun Yat-sen UniversityGuangzhou 510275China Vaccine Research Institute of Sun Yat-sen University the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Cell-Gene Therapy Translational Medicine Research Center the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China

Skeletal muscle differentiation is a highly coordinated process that involves many cellular signaling pathways and microRNAs(miRNAs).A group of muscle-specific miRNAs has been reported to promote myogenesis by suppressing key signaling pathways for cell ***,the functional role and regulatory mechanism of most non-muscle-specific miRNAs with stage-specific changes during differentiation are largely ***,we describe the functional characterization of miR-101a/b,a pair of non-muscle-specific miRNAs that show the largest change among a group of transiently upregulated miRNAs during myogenesis in C2C12 *** overexpression of miR-101a/b inhibits myoblast differentiation by suppressing the p38/MAPK,Interferon Gamma,and Wnt pathways and enhancing the C/EBP ***2a,a key protein in the p38/MAPK pathway,was identified as a direct target of miR-101a/***,we found that the long non-coding RNA(lncRNA)Malat1,which promotes muscle differentiation,interacts with miR-101a/b,and this interaction competes with Mef2a mRNA to relieve the inhibition of the p38/MAPK pathway during *** results uncovered a“braking”role in differentiation of transiently upregulated miRNAs and provided new insights into the competing endogenous RNA(ceRNA)regulatory mechanism in myoblast differentiation and myogenesis.

关键词： miR-101a/b p38/MAPK signaling pathway Mef2a Malat1 skeletal muscle differentiation

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A two-step self-pollination mechanism maximizes fertility in Brassicaceae

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Cell 2025年第11期188卷 2845-2855.e8页

作者： Liu, Pu Quan, Xin Song, Zihan Li, Wenhao Wang, Yuan Gu, Hongya Xie, Daoxin Yang, Weicai Dresselhaus, Thomas Zhong, Sheng Qu, Li-Jia State Key Laboratory for Gene Function and Modulation Research Peking-Tsinghua Center for Life Sciences New Cornerstone Science Laboratory College of Life Sciences Peking University Beijing 100871 China Ministry of Education Key Laboratory of Bioinformatics Tsinghua-Peking Center for Life Sciences and School of Life Sciences Tsinghua University Beijing 100084 China Yazhouwan National Laboratory 8 Huanjing Road Yacheng Hainan Sanya 572025 China Cell Biology and Plant Biochemistry University of Regensburg Regensburg 93053 Germany

Self-pollination in self-compatible plant species often occurs prior to flower opening. By tracking the temporal progress of pollination in Arabidopsis, we observed that pollen predominantly targets the lateral region of the stigma in unopened flowers. Notably, approximately 7 h after flower opening, flowers close, thereby pressing anthers toward the central region of the stigma for a second self-pollination. This two-step self-pollination results in a doubling of pollen deposition, which significantly increases the ovule-targeting ratio and improves fertility under pollen-limiting conditions, as evident in the anther-dehiscence-defective mutant myb108 and under environmental stress conditions. Analysis using gamete-interaction-defective mutants hap2/gcs1 and dmp8 dmp9 revealed that the timely separation of both pollination events promotes fertilization recovery efficiency. A similar two-step pollination was observed in two other self-pollinating but not in outcrossing Brassicaceae species. This mechanism represents a reproductive assurance strategy in predominantly self-pollinating annuals to maximize fertility under unfavorable conditions. © 2025 The Author(s)

关键词： Arabidopsis Brassicaceae fertility fertilization recovery heat stress pollination reproduction stigma

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Biomolecular condensates and disease pathogenesis

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Science China(Life Sciences) 2024年第9期67卷 1792-1832页

作者： Ke Ruan Ge Bai Yanshan Fang Dan Li Tingting Li Xingguo Liu Boxun Lu Qing Lu Zhou Songyang Shuguo Sun Zheng Wang Xin Zhang Wen Zhou Hong Zhang The First Affiliated Hospital&School of Life Sciences Ministry of Education Key Laboratory for Membrane-less Organelles&Cellular DynamicsHefei National Research Center for Interdisciplinary Sciences at the MicroscaleCenter for Advanced Interdisciplinary Science and Biomedicine of IHMDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230027China Nanhu Brain-computer Interface Institute Hangzhou 311100China Department of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine Zhejiang University School of MedicineHangzhou 310058China Interdisciplinary Research Center on Biology and Chemistry Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai 201210China University of Chinese Academy of Sciences Beijing 100049China Bio-X Institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders(Ministry of Education)Shanghai Jiao Tong UniversityShanghai 200030China Department of Biomedical Informatics School of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China CAS Key Laboratory of Regenerative Biology Joint School of Life SciencesGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China Joint School of Life Sciences Guangzhou Medical UniversityGuangzhou 510000China Neurology Department at Huashan Hospital State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceInstitutes of Brain ScienceSchool of Life SciencesFudan UniversityShanghai 200433 China Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders Ministry of EducationBio-X InstitutesShanghai Jiao Tong UniversityShanghai 200030China State Key Laboratory of Biocontrol MOE Key Laboratory of Gene Function and Regulation and Guangzhou Key Laboratory of Healthy Aging ResearchSchool of Life SciencesSun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510275China Department of Human Anatomy Hist

Biomolecular condensates or membraneless organelles(MLOs)formed by liquid-liquid phase separation(LLPS)divide intracellular spaces into discrete compartments for specific *** of LLPS or aberrant phase transition that disturbs the formation or material states of MLOs is closely correlated with neurodegeneration,tumorigenesis,and many other pathological ***,we summarize the recent progress in development of methods to monitor phase separation and we discuss the biogenesis and function of MLOs formed through phase *** then present emerging proof-of-concept examples regarding the disruption of phase separation homeostasis in a diverse array of clinical conditions including neurodegenerative disorders,hearing loss,cancers,and immunological ***,we describe the emerging discovery of chemical modulators of phase separation.

关键词： liquid-liquid phase separation biomolecular condensate membraneless organelle

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Plant reproduction: Seed size gated by central cell fertilization

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Current biology : CB 2025年第10期35卷 R389-R391页

作者： Zijun Lan Sheng Zhong Li-Jia Qu State Key Laboratory for Gene Function and Modulation Research Peking-Tsinghua Center for Life Sciences New Cornerstone Science Laboratory College of Life Sciences Peking University Beijing 100871 People's Republic of China. State Key Laboratory for Gene Function and Modulation Research Peking-Tsinghua Center for Life Sciences New Cornerstone Science Laboratory College of Life Sciences Peking University Beijing 100871 People's Republic of China. Electronic address: shengshengzz@***. State Key Laboratory for Gene Function and Modulation Research Peking-Tsinghua Center for Life Sciences New Cornerstone Science Laboratory College of Life Sciences Peking University Beijing 100871 People's Republic of China. Electronic address: qulj@***.

Double fertilization produces the embryo and endosperm, the primary components of a seed. A recent study shows how central cell fertilization specifically initiates the opening of a vascular gate to ensure efficient a...

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PFOS and F–53B disrupted inner cell mass development in mouse preimplantation embryo

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Chemosphere 2024年 349卷 140948页

作者： Qiu, Yanling Gao, Min Cao, Tianqi Wang, Jingwen Luo, Mingxun Liu, Simiao Zeng, Xiaowen Huang, Junjiu MOE Key Laboratory of Gene Function and Regulation State Key Laboratory of Biocontrol School of Life Sciences Sun Yat-sen University Guangzhou510275 China Key Laboratory of Reproductive Medicine of Guangdong Province School of Life Sciences and the First Affiliated Hospital Sun Yat-sen University Guangzhou510275 China Guangdong Provincial Key Laboratory of Food Nutrition and Health Guangdong Provincial Engineering Technology Research Center of Environmental and Health Risk Assessment Department of Occupational and Environmental Health School of Public Health Sun Yat-sen University Guangzhou510275 China

Perfluorooctane sulfonic acid (PFOS) is a perfluoroalkyl and polyfluoroalkyl substance (PFAS) widely used in daily life. As its toxicity was confirmed, it has been gradually substituted by F–53B (chlorinated polyfluoroalkyl sulfonates, Cl-PFESAs) in China. PFOS exposure during prenatal development may hinder the development of preimplantation embryos, as indicated by recent epidemiological research and in vivo assays. However, the embryotoxicity data for F–53B are scarce. Furthermore, knowledge about the toxicity of F–53B and PFOS exposure to internal follicular fluid concentrations on early preimplantation embryo development remains limited. In this study, internal exposure concentrations of PFOS (10 nM) and F–53B (2 nM) in human follicular fluid were chosen to study the effects of PFAS on early mouse preimplantation embryo development. We found that both PFOS and F–53B treated zygotes exhibited higher ROS activity in 8-cell embryos but not in 2-cell stage embryos. PFOS and F–53B significantly affected the proportion and aggregation of the inner cell mass (ICM) in the blastocyst, but not the total cell number. Mouse embryonic stem cells (mESCs, isolated from the ICM) and embryoid body (EB) assays were employed to assess the toxicity of PFOS and F–53B on the development and differentiation of embryonic pluripotent cells. These results suggested that mESCs exhibited more DNA damage and abnormal germ layer differentiation after brief exposure to PFOS or F–53B. Finally, RNA-sequencing revealed that PFOS and F–53B exposure affected mESCs biosynthetic processes and chromatin-nucleosome assembly. Our results indicate that F–53B has potential risks as an alternative to PFOS, which disrupts ICM development and differentiation. © 2023 Elsevier Ltd

关键词： Toxicity

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Cranial irradiation impairs intrinsic excitability and synaptic plasticity of hippocampal CA1 pyramidal neurons with implications for cognitive function

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Neural Regeneration research 2022年第10期17卷 2253-2259页

作者： Min-Yi Wu Wen-Jun Zou Pei Yu Yuhua Yang Shao-Jian Li Qiang Liu Jiatian Xie Si-Qi Chen Wei-Jye Lin Yamei Tang Department of Neurology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina State Key Laboratory of Organ Failure Research Key Laboratory of Mental Health of the Ministry of EducationGuangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired IntelligenceKey Laboratory of Psychiatric Disorders of Guangdong ProvinceCollaborative Innovation Center for Brain ScienceDepartment of NeurobiologySouthern Medical UniversityGuangzhouGuangdong ProvinceChina Department of Anesthesiology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Guangdong-Hong Kong Joint Laboratory for RNA MedicineSun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Medical Research Center Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Guangdong Province Key Laboratory of Brain Function and Disease Zhongshan School of MedicineSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina

Radiation therapy is a standard treatment for head and neck ***,patients often exhibit cognitive impairments following radiation *** studies have revealed that hippocampal dysfunction,specifically abnormal hippocampal neurogenesis or neuroinflammation,plays a key role in radiation-induced cognitive ***,the long-term effects of radiation with respect to the electrophysiological adaptation of hippocampal neurons remain poorly *** found that mice exhibited cognitive impairment 3 months after undergoing 10 minutes of cranial irradiation at a dose rate of 3 Gy/***,we observed a remarkable reduction in spike firing and excitatory synaptic input,as well as greatly enhanced inhibitory inputs,in hippocampal CA1 pyramidal *** to the electrophysiological adaptation,we found reduced expression of synaptic plasticity marker VGLUT1 and increased expression of ***,in irradiated mice,long-term potentiation in the hippocampus was weakened and GluR1 expression was *** findings suggest that radiation can impair intrinsic excitability and synaptic plasticity in hippocampal CA1 pyramidal neurons.

关键词： GABA-mediated hyperfunction GluR intrinsic excitability long-term potentiation radiation-induced cognitive impairment spontaneous excitatory postsynaptic currents spontaneous inhibitory postsynaptic currents synaptic plasticity type I vesicular glutamate transporter vesicular GABA transporter whole-cell patch clamp recording

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Biomarkers of aging

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Science China(Life Sciences) 2023年第5期66卷 893-1066页

作者： Aging Biomarker Consortium Hainan Bao Jiani Cao Mengting Chen Min Chen Wei Chen Xiao Chen Yanhao Chen Yu Chen Yutian Chen Zhiyang Chen Jagadish K Chhetri Yingjie Ding Junlin Feng Jun Guo Mengmeng Guo Chuting He Yujuan Jia Haiping Jiang Ying Jing Dingfeng Li Jiaming Li Jingyi Li Qinhao Liang Rui Liang Feng Liu Xiaoqian Liu Zuojun Liu Oscar Junhong Luo Jianwei Lv Jingyi Ma Kehang Mao Jiawei Nie Xinhua Qiao Xinpei Sun Xiaoqiang Tang Jianfang Wang Qiaoran Wang Siyuan Wang Xuan Wang Yaning Wang Yuhan Wang Rimo Wu Kai Xia Fu-Hui Xiao Lingyan Xu Yingying Xu Haoteng Yan Liang Yang Ruici Yang Yuanxin Yang Yilin Ying Le Zhang Weiwei Zhang Wenwan Zhang Xing Zhang Zhuo Zhang Min Zhou Rui Zhou Qingchen Zhu Zhengmao Zhu Feng Cao Zhongwei Cao Piu Chan Chang Chen Guobing Chen Hou-Zao Chen Jun Chen Weimin Ci Bi-Sen Ding Qiurong Ding Feng Gao Jing-Dong JHan Kai Huang Zhenyu Ju Qing-Peng Kong Ji Li Jian Li Xin Li Baohua Liu Feng Liu Lin Liu Qiang Liu Qiang Liu Xingguo Liu Yong Liu Xianghang Luo Shuai Ma Xinran Ma Zhiyong Mao Jing Nie Yaojin Peng Jing Qu Jie Ren Ruibao Ren Moshi Song Zhou Songyang Yi Eve Sun Yu Sun Mei Tian Shusen Wang Si Wang Xia Wang Xiaoning Wang Yan-Jiang Wang Yunfang Wang Catherine CL Wong Andy Peng Xiang Yichuan Xiao Zhengwei Xie Daichao Xu Jing Ye Rui Yue Cuntai Zhang Hongbo Zhang Liang Zhang Weiqi Zhang Yong Zhang Yun-Wu Zhang Zhuohua Zhang Tongbiao Zhao Yuzheng Zhao Dahai Zhu Weiguo Zou Gang Pei Guang-Hui Liu Aging Biomarker Consortium(ABC) Beijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Department of Dermatology Xiangya HospitalCentral South UniversityChangsha 410008China Hunan Key Laboratory of Aging Biology Xiangya HospitalCentral South UniversityChangsha 410008China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangsha 410008China Clinic Center of Human Gene Research Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Hubei Clinical Research Center of Metabolic and Cardiovascular Disease Huazhong University of Science and TechnologyWuhan 430022China Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging Huazhong University of Science and TechnologyWuhan 430022China Stem Cell Translational Research Center Tongji HospitalTongji University School of MedicineShanghai 200065China Department of Nuclear Medicine Daping HospitalThird Military Medical UniversityChongqing 400042China CAS Key Laboratory of Nutrition Metabolism and Food SafetyShanghai Institute of Nutrition and HealthUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China Shanghai Key Laboratory of Maternal Fetal Medicine Clinical and Translational Research Center of Shanghai First Maternity and Infant HospitalFrontier Science Center for Stem Cell ResearchShanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China The Department of Endovascular Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Key Laboratory of Regenerative Medicine of Ministry of Education Institute of Ageing and Regenerative MedicineJ

Aging biomarkers are a combination of biological parameters to(i)assess age-related changes,(ii)track the physiological aging process,and(iii)predict the transition into a pathological *** a broad spectrum of aging biomarkers has been developed,their potential uses and limitations remain poorly *** immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research:How old are we?Why do we get old?And how can we age slower?This review aims to address this ***,we summarize our current knowledge of biomarkers developed for cellular,organ,and organismal levels of aging,comprising six pillars:physiological characteristics,medical imaging,histological features,cellular alterations,molecular changes,and secretory *** fulfill all these requisites,we propose that aging biomarkers should qualify for being specific,systemic,and clinically relevant.

关键词： aging senescence biomarker clock

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Noncoding RNA:from dark matter to bright star

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Science China(Life Sciences) 2020年第4期63卷 463-468页

作者： Yuanchao Xue Runsheng Chen Lianghu Qu Xiaofeng Cao Key Laboratory of RNA Biology Institute of BiophysicsChinese Academy of SciencesBeijing 100101China MOE Key Laboratory of Gene Function and Regulation State Key Laboratory for BiocontrolSchool of Life SciencesSun Yat-Sen UniversityGuangzhou 510275China State Key Laboratory of Plant Genomics and National Center for Plant Gene Research(Beijing) Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

The central dogma states that genes encoded in the DNA should be first transcribed into messenger RNA(mRNA)and then translated into functional proteins(Crick,1970).This dogma has been written in numerous textbooks and learned by myriad ***,along with the completion of the human genome project in June 2000,an astonishing fact was revealed:only 1.5%of the human genome encodes for proteins(Lander et al.,2001;Venter et al.,2001).This fact raised three fundamental questions:(i)why does the human genome have so few protein-coding genes?(ii)how to explain the apparent differences between humans and other species using the limited coding genes?(iii)what are the roles of the noncoding regions in our genome?

关键词： al. apparent raised

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A FtsZ cis disassembly element acts in Z-ring assembly during bacterial cell division

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Nature communications 2025年第1期16卷 5194页

作者： Huijia Yin Yang Liu Ying Zhao Pengyue Chen Zengyi Chang State Key Laboratory of Gene Function and Modulation Research School of Life Sciences Peking University Beijing 100871 P.R. China. Institute of Geriatrics National Clinical Research Center for Geriatric Diseases Second Medical Center of Chinese PLA General Hospital Beijing 100853 P.R. China. State Key Laboratory of Gene Function and Modulation Research School of Life Sciences Peking University Beijing 100871 P.R. China. changzy@***. Center for Protein Science Peking University Beijing 100871 P.R. China. changzy@***.

Bacterial cell division hinges on the Z-ring, an architecture built from the dynamical assembly and disassembly of FtsZ proteins. This delicate balance ensures not only apparent stability, but also continuous remodeling, both of which are required for Z-ring functioning. However, the molecular nature of such subcellular structures remains elusive. Here, by identifying all amino acid residues participating in FtsZ self-assembly in Escherichia coli, we show that the extreme N-terminal intrinsically disordered region (N-IDR) of FtsZ acts as a cis disassembly element that contacts and disrupts the longitudinal interface, tipping the balance more toward polymer disassembly. This previously unappreciated structural characteristic is indispensable for promoting Z-ring architecture condensation at midcell (rather than elsewhere) upon modulation by certain trans-acting factors (such as the E. coli MinC protein).

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