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Nature computational science 2025年 2025 May 27页

作者： Juntian Qi Zhengchao Luo Chuan-Yun Li Jinzhuo Wang Wanqiu Ding State Key Laboratory of Gene Function and Modulation Research Laboratory of Bioinformatics and Genomic Medicine Institute of Molecular Medicine College of Future Technology Peking University Beijing China. Institute of Genetics and Developmental Biology Chinese Academy of Sciences Beijing China. University of Chinese Academy of Sciences Beijing China. Department of Big Data and Biomedical AI College of Future Technology Peking University Beijing China. State Key Laboratory of Gene Function and Modulation Research Laboratory of Bioinformatics and Genomic Medicine Institute of Molecular Medicine College of Future Technology Peking University Beijing China. chuanyunli@***. Institute of Genetics and Developmental Biology Chinese Academy of Sciences Beijing China. chuanyunli@***. University of Chinese Academy of Sciences Beijing China. chuanyunli@***. Department of Big Data and Biomedical AI College of Future Technology Peking University Beijing China. wangjinzhuo@***. State Key Laboratory of Gene Function and Modulation Research Laboratory of Bioinformatics and Genomic Medicine Institute of Molecular Medicine College of Future Technology Peking University Beijing China. dingwq@***. Bioinformatics Core Facility College of Future Technology Peking University Beijing China. dingwq@***.

Cell‒cell communication (CCC) is a fundamental biological process for the harmonious functioning of biological systems. Increasing evidence indicates that cells of the same type or cluster may exhibit different interaction patterns under varying niches, yet most prevailing methods perform CCC inference at the cell type or cluster level while disregarding niche heterogeneity. Here we introduce the Spatial Transcriptomics-based cell‒cell Communication And Subtype Exploration (STCase) tool, which can describe CCC events at the single-cell/spot level based on spatial transcriptomics (ST). STCase includes an interpretable multi-view graph neural network via CCC-aware attention to identify niches for each cell type and uncover niche-specific CCC events. We show that STCase outperforms state-of-the-art approaches and accurately captures reported immune-related CCC events in human bronchial glands. We also identify three distinct niches of oral squamous cell carcinoma that may be obscured by agglomerative methods, and discover niche-specific CCC events that could influence tumor prognosis.

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Chitosan microspheres loaded with WJMSCs facilitate the restoration of ovarian function in CTX-induced premature ovarian failure mice

MedComm - Biomaterials and Applications

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MedComm - Biomaterials and Applications 2023年第4期2卷

作者： Jiao, Yiren Niu, Yongxia Luo, Mingxun Qiu, Yanling Gao, Min Chen, Xiaolin Huang, Sunxing Zhu, Jing Xiao, Lin Liu, Haiying Huang, Junjiu MOE Key Laboratory of Gene Function and Regulation State Key Laboratory of Biocontrol School of Life Sciences Sun Yat-sen University Guangzhou China Zhejiang Engineering Research Center for Tissue Repair Materials Wenzhou Institute University of Chinese Academy of Sciences Wenzhou China Key Laboratory of Reproductive Medicine of Guangdong Province the First Affiliated Hospital and School of Life Sciences Sun Yat-sen University Guangzhou China School of Biomedical Engineering Sun Yat-sen University Guangzhou China

Premature ovarian failure (POF) is a complex disease affecting an increasing number of young women. Traditional treatments are limited in low efficacy and side effects. Wharton's jelly mesenchymal stem cells (WJMSCs) therapy holds promise in the treatment of POF. However, the clinical application of WJMSCs is hindered by challenges such as low cell viability, significant loss, and poor survival rates. In this study, we prepared three-dimensional chitosan microspheres (CSM). CSM loading substantial improved the proliferative ability and cell viability of WJMSCs. Furthermore, transplantation of CSM loaded with WJMSCs into ovaries of POF mice increased serum levels of Estradiol (E2) and Anti-Müllerian hormone (AMH), alongside decreased levels of follicle-stimulating hormone (FSH). CSM+WJMSCs transplantation enhanced the number of growth follicles while reduced atresia follicles, and effective alleviated the ovarian fibrosis and apoptosis within the ovarian cortex. CSM also prolonged the residence time of WJMSCs in the ovarian capsule. Moreover, superovulation experiments illustrated that CSM+WJMSCs transplantation enhanced the total number of oocytes and reduced oocyte abnormality rates. Overall, CSM+WJMSCs transplantation promotes follicle development and regeneration, restoring ovarian function by inhibiting ovarian cell apoptosis and reducing levels of fibrosis. This study presents a novel therapeutic strategy that combines biomaterial and mesenchymal stem cells for the clinical treatment of premature ovarian failure. © 2023 The Authors. MedComm – Biomaterials and Applications published by John Wiley & Sons Australia, Ltd on behalf of Sichuan International Medical Exchange & Promotion Association (SCIMEA).

关键词： chitosan microspheres follicular development premature ovarian failure Wharton's jelly mesenchymal stem cells

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Expanding the σ54-dependent transcription process with orthogonal designs

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Nucleic acids research 2025年第10期53卷 gkaf442页

作者： Yiheng Liu Shuyi Cai Ziyi Zhang Zhuoting Xie Chenyue Guo Yi-Ping Wang Jianguo Yang State Key Laboratory of Gene Function and Modulation Research School of Advanced Agricultural Sciences Peking University Beijing 100871 China. Academy for Advanced Interdisciplinary Studies Peking University Beijing 100871 China. Yazhouwan National Laboratory Sanya 572025 Hainan China. School of Life Sciences Peking University Beijing 100871 China.

The significance of orthogonal gene expression lies in its ability to ensure consistent and predictable operation of genetic pathways in synthetic biology. In bacteria, σ factors are responsible for promoter recognition, where the recognition pattern of σ54 is distinct from that of σ70. Moreover, σ54-dependent promoters require bacterial enhancer-binding proteins (bEBPs) for transcription initiation, which are stringently regulated and strongly activated. Thus, σ54 appears to be a promising candidate for orthogonal designs. In this study, through knowledge-based screening and rewiring of the RpoN box in σ54, together with its partnered promoter, we identified three sets of orthogonal expression systems based on σ54-R456H, R456Y, and R456L, with different promoter preferences and ideal mutual orthogonality toward each other and the native σ54. The orthogonality is transferable, as specific transcription via σ54-R456H was demonstrated in three non-model bacteria. When combined with different bEBPs, the system can be employed to control orthogonal downstream output in response to environmental or chemical signals. The orthogonal σ54 factors proved to be capable of orthogonalizing complex biological pathways and genetic circuits. Therefore, the orthogonal transcription system will contribute to the expansion of synthetic biology toolkits, thereby providing reliable and diversified gene expression in a wide range of hosts.

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Epitranscriptomic technologies and analyses

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Science China(Life Sciences) 2020年第4期63卷 501-515页

作者： Xiaoyu Li Qiao-Xia Liang Jin-Ran Lin Jinying Peng Jian-Hua Yang Chengqi Yi Yang Yu Qiangfeng Cliff Zhang Ke-Ren Zhou State Key Laboratory of Protein and Plant Gene Research School of Life SciencesPeking UniversityBeijing 100871China MOE Key Laboratory of Gene Function and Regulation State Key Laboratory for BiocontrolSchool of Life SciencesSun Yat-Sen UniversityGuangzhou 510275China The Fifth Affiliated Hospital Sun Yat-Sen UniversityZhuhai 519000China Department of Chemical Biology and Synthetic and Functional Biomolecules Center College of Chemistry and Molecular EngineeringPeking UniversityBeijing 100871China Key Laboratory of RNA Biology CAS Center for Excellence in BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing 100101 China MOE Key Laboratory of Bioinformatics Beijing Advanced Innovation Center for Structural BiologyCenter for Synthetic and Systems BiologyTsinghua-Peking Joint Center for Life SciencesSchool of Life SciencesTsinghua UniversityBeijing 100084China

RNA can interact with RNA-binding proteins(RBPs),mRNA,or other non-coding RNAs(ncRNAs)to form complex regulatory ***-throughput CLIP-seq,degradome-seq,and RNA-RNA interactome sequencing methods represent powerful approaches to identify biologically relevant ncRNA-target and protein-ncRNA ***,assigning ncRNAs to their regulatory target genes or interacting RNA-binding proteins(RBPs)remains technically *** modifications to mRNA also play important roles in regulating gene *** of the functional roles of these modifications relies highly on the detection methods *** structure is also critical at nearly every step of the RNA life *** this review,we summarize recent advances and limitations in CLIP technologies and discuss the computational challenges of and bioinformatics tools used for decoding the functions and regulatory networks of *** also summarize methods used to detect RNA modifications and to probe RNA structure.

关键词： ncRNA bioinformatics CLIP-seq RNA modification quantification and locus-specific detection methods transcriptome-wide sequencing technologies RNA structuromes RNA structure probing methods

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Author Correction: The rapid proximity labeling system PhastID identifies ATP6AP1 as an unconventional GEF for Rheb

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Cell research 2025年第4期35卷 317页

作者： Ran Feng Feng Liu Ruofei Li Zhifen Zhou Zhuoheng Lin Song Lin Shengcheng Deng Yingying Li Baoting Nong Ying Xia Zhiyi Li Xiaoqin Zhong Shuhan Yang Gang Wan Wenbin Ma Su Wu Zhou Songyang MOE Key Laboratory of Gene Function and Regulation State Key Laboratory of Biocontrol Guangzhou Key Laboratory of Healthy Aging Research School of Life Sciences Institute of Healthy Aging Research Sun Yat-sen University Guangzhou Guangdong China. Sun Yat-sen Memorial Hospital Sun Yat-sen University Guangzhou Guangdong China. MOE Key Laboratory of Gene Function and Regulation State Key Laboratory of Biocontrol Guangzhou Key Laboratory of Healthy Aging Research School of Life Sciences Institute of Healthy Aging Research Sun Yat-sen University Guangzhou Guangdong China. liufeng23@***. Sun Yat-sen Memorial Hospital Sun Yat-sen University Guangzhou Guangdong China. wusu5@***. MOE Key Laboratory of Gene Function and Regulation State Key Laboratory of Biocontrol Guangzhou Key Laboratory of Healthy Aging Research School of Life Sciences Institute of Healthy Aging Research Sun Yat-sen University Guangzhou Guangdong China. songyanz@***. Sun Yat-sen Memorial Hospital Sun Yat-sen University Guangzhou Guangdong China. songyanz@***.

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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 1-15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 Center for Protein Science Peking University Beijing 100871 P.R. China

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 inEscherichia coli, we show that the extreme N-terminal intrinsically disordered region (N-IDR) of FtsZ acts as acisdisassembly 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 certaintrans-acting factors (such as theE. coliMinC protein).

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Clinical biomarkers of perioperative neurocognitive disorder:initiation and recommendation

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Science China Life Sciences 2025年

作者： Jianhui Liu Cheng Li Junyan Yao Lei Zhang Xuan Zhao Xin Lv Zhiqiang Liu Changhong Miao Yingwei Wang Hong Jiang Weifeng Yu Tianlong Wang Dongxin Wang E Wang Xiaoping Gu Hailong Dong Junli Cao Yuan Shen Weihong Song Shengdi Chen Yanjiang Wang Guanghui Liu Zhongcong Xie Lize Xiong Jialin C.Zheng Department of Anesthesiology Shanghai Ninth People’s Hospital School of Medicine Shanghai Jiao Tong University Department of Anesthesiology Shanghai Renji Hospital Shanghai Jiao Tong University School of Medicine Department of Anesthesiology Xuanwu Hospital Capital Medical University Department of Anesthesiology and Critical Care Medicine Peking University First Hospital Department of Anesthesiology Xiangya Hospital of Central South University Department of Anesthesiology Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School Department of Anesthesiology Xijing Hospital Fourth Military Medical University Jiangsu Province Key Laboratory of Anesthesiology Xuzhou Medical University Department of Anesthesiology The Affiliated Hospital of Xuzhou Medical University Shanghai Mental Health Center of Shanghai Jiao Tong University Department of Anesthesiology Tongji Hospital School of Medicine Tongji University Anesthesia and Brain Research Institute Tongji University Oujiang Laboratory Key Laboratory of Alzheimer’s Disease of Zhejiang Province Zhejiang Provincial Clinical Research Center for Mental Disorders Institute of Aging School of Mental Health Affiliated Kangning Hospital The Second Affiliated Hospital Yuying Children’s Hospital Wenzhou Medical University Department of Neurology Ruijin Hospital Shanghai Jiao Tong University School of Medicine Department of Neurology Daping Hospital Third Military Medical University State Key Laboratory of Membrane Biology Institute of Zoology Chinese Academy of Sciences Geriatric Anesthesia Research Unit Department of Anesthesia Critical Care and Pain Medicine Massachusetts General Hospital Harvard Medical School Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation Clinical Research Center for Anesthesiology and Perioperative Medicine Translational Research Institute of Brain and Brain-Like Intelligence Shanghai Fourth People’s Hospital School of Medicine Tongji University Center for Tr

Perioperative neurocognitive disorder(PND) is a significant neurological complication in aging perioperative patients that impacts postoperative cognition. PND is currently diagnosed through cognitive function testing, which is limited by its subjectivity and time requirements. Thus, the identification of biomarkers to assess PND onset is a priority to identify at-risk individuals and enable interventions and treatments to patient outcomes. This article synthesizes expert perspectives on brain aging and PND, presents the latest clinical evidence on PND biomarkers(imaging, electroencephalography, and molecular biomarkers), and delves into the relationship between PND and other age-related cognitive disorders. Thorough review of PND research identified several biomarkers with high sensitivity and specificity,offering a solid scientific foundation to predict and diagnose PND. These biomarkers not only enhance diagnostic accuracy for clinicians but also provide opportunities for earlier intervention and more effective treatment, potentially enhancing patient outcomes and quality of life.

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A multisensor high-temperature signaling framework for triggering daytime thermomorphogenesis in Arabidopsis

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Nature Communications 2025年第1期16卷 1-15页

作者： De Fan Nan Xu Ethan R. Seto Xuemei Chen Meng Chen Wei Hu John Clark Lagarias Department of Botany and Plant Sciences Institute for Integrative Genome Biology University of California Riverside CA USA State Key Laboratory for Gene Function and Modulation Research Peking-Tsinghua Joint Center for Life Sciences College of Life Sciences Peking University Beijing China Beijing Advanced Center of RNA Biology (BEACON) Peking University Beijing China Department of Molecular and Cellular Biology University of California Davis CA USA

The phytochrome B (phyB) photoreceptor and EARLY FLOWERING 3 (ELF3) are two major plant thermosensors that monitor high temperatures primarily at night. However, high temperatures naturally occur during the daytime; the mechanism of daytime thermosensing and whether these thermosensors can also operate under intense sunlight remain ambiguous. Here, we show that phyB plays a substantial role in daytime thermosensing in Arabidopsis, and its thermosensing function becomes negligible only when the red light intensity reaches 50 μmol m−2s−1. Leveraging this restrictive condition for phyB thermosensing, we reveal that triggering daytime thermomorphogenesis requires two additional thermosensory pathways. High temperatures induce starch breakdown in chloroplasts and the production of sucrose, which stabilizes the central thermal regulator PHYTOCHROME-INTERACTING FACTOR 4 (PIF4) by antagonizing phyB-dependent PIF4 degradation. In parallel, high temperatures release the inhibition ofPIF4transcription and PIF4 activity by ELF3. Thus, our study elucidates a multisensor high-temperature signaling framework for understanding diverse thermo-inducible plant behaviors in daylight.

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Cost-effective generation of A-to-G mutant mice by zygote electroporation of adenine base editor ribonucleoproteins

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Journal of genetics and Genomics 2020年第6期47卷 337-340页

作者： Hongwei Sun Shengyao Zhi Guifang Wu Guanglan Wu Tianqi Cao Hu Hao Zhou Songyang Puping Liang Junjiu Huang MOE Key Laboratory of Gene Function and Regulation and Guangzhou Key Laboratory of Healthy Aging Research SYSU-BCM Joint Research CenterSchool of Life SciencesSun Yat-sen UniversityGuangzhou510275China Department of Paediatrics The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou510655China Key Laboratory of Reproductive Medicine of Guangdong Province School of Life Sciencesand the First Affiliated HospitalSun Yat-sen UniversityGuangzhou510275China State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangzhou510060China Verna and Marrs Mclean Department of Biochemistry and Molecular Biology Baylor College of MedicineOne Baylor PlazaHoustonTX77030USA

More than 32,000 pathogenic single nucleotide polymorphisms(SNPs)have been identified in the human genome(Gaudelli et al.,2017).genetically modified mice with pathogenic SNPs are good models for studies of disease pathogenesis and the development of new ***,an efficient,high-throughput method for the generation of mouse models with SNPs is needed.

关键词： al. editor pathogenesis

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

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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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