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Biomolecular condensates and disease pathogenesis

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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k-dominant Skyline query algorithm for dynamic datasets

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Frontiers of Computer Science 2021年第1期15卷 213-221页

作者： Zhiyun ZHENG ke ruan Mengyao YU Xingjin ZHANG Ning WANG Dun LI School of Information Engineering Zhengzhou UniversityZhengzhou 450001China

At present,most k-dominant Skyline query algorithms are oriented to static datasets,this paper proposes a k-dominant Skyline query algorithm for dynamic *** algorithm is recursive ***,we compute the dominant ability of each object and sort objects in descending order by dominant ***,we maintain an inverted index of the dominant index by k-dominant Skyline point calculation *** the data changes,it is judged whether the update point will afect the k dominant Skyline point *** the k-dominant Skyline point of the new data set is obtained by inserting and deleting *** proposed algorithm resolves maintenance isue of a frequently updated database by dynamically updating the data *** experimental results show that the query algorithm can efectively improve query eficiency.

关键词： multi-objective decision Skyline queries k-dominant Skyline queries dynamic datasets

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重庆春见和沃柑果园叶片黄化原因分析

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中国南方果树 2024年第5期53卷 37-42页

作者：李群贞阮科朱礼乾曹婷婷凌丽俐彭良志淳长品西南大学柑桔研究所/国家柑桔工程技术研究中心重庆400712 四川省南充市顺庆区农业农村局四川南充637002 四川省眉山市东坡区农业农村局四川眉山620010 云阳县农业农村委员会重庆404100

重庆忠县、长寿和铜梁等地由甜橙高接换种的春见和沃柑,存在叶片黄化问题。为找出叶片黄化的主要原因,采集高换春见和沃柑正常园和黄化园的土壤和叶片样品,比较土壤理化性状、叶片矿质元素含量及叶片SPAD值,并对土壤理化性状、叶片SPAD... 详细信息

重庆忠县、长寿和铜梁等地由甜橙高接换种的春见和沃柑,存在叶片黄化问题。为找出叶片黄化的主要原因,采集高换春见和沃柑正常园和黄化园的土壤和叶片样品,比较土壤理化性状、叶片矿质元素含量及叶片SPAD值,并对土壤理化性状、叶片SPAD值与叶片矿质营养的关系进行分析。结果表明,春见黄化园土壤pH均值(8.09)比正常园(6.89)显著高出17.42%,土壤有效铁含量(均值)显著低于正常园,交换性钙含量显著高于正常园,叶片铁含量显著低于正常园。沃柑黄化园土壤交换性钙含量高于正常园,有效铁含量显著低于正常园,叶片氮、硫、铁含量均值显著低于正常园。叶片SPAD值分别与叶片氮和叶片铁含量呈显著正相关,增强回归树分析显示叶片铁含量对叶片SPAD的贡献度最高(35.23%),其次为氮(22.29%)。排除自然灾害或病害等因素后,认为高换杂柑叶片黄化是因为土壤pH值和交换性钙较高,导致土壤有效铁含量降低,并抑制树体对Fe的吸收,最终引起叶片缺Fe黄化;另外,叶片N含量较低是导致沃柑黄化的因素之一。

关键词：高换杂柑叶片黄化矿质营养诊断土壤重庆

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Stromal cell-derived factor-1α promotes recruitment and differentiation of nucleus pulposus-derived stem cells

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World Journal of Stem Cells 2019年第3期11卷 196-211页

作者： Jin-Wei Ying Tian-Yong Wen Shi-Shen Pei Ling-Hao Su Di-ke ruan The Second School of Clinical Medicine Southern Medical University Department of Orthopedic Surgery Navy General Hospital

BACKGROUND Intervertebral disc(IVD) degeneration is a condition characterized by a reduction in the water and extracellular matrix content of the nucleus pulposus(NP) and is considered as one of the dominating contributing factors to low back pain. Recent evidence suggests that stromal cell-derived factor 1α(SDF-1α) and its receptor CX-C chemokine receptor type 4(CXCR4) direct the migration of stem cells associated with injury repair in different musculoskeletal *** To investigate the effects of SDF-1α on recruitment and chondrogenic differentiation of nucleus pulposus-derived stem cells(NPSCs).METHODS We performed real-time RT-PCR and enzyme-linked immunosorbent assay to examine the expression of SDF-1α in nucleus pulposus cells after treatment with pro-inflammatory cytokines in vitro. An animal model of IVD degeneration was established using annular fibrosus puncture in rat coccygeal discs. Tissue samples were collected from normal control and degeneration *** in the expression of SDF-1α between the normal and degenerative IVDs were analyzed by immunohistochemistry. The migration capacity of NPSCs induced by SDF-1α was evaluated using wound healing and transwell migration assays. To determine the effect of SDF-1α on chondrogenic differentiation of NPSCs, we conducted cell micromass culture and examined the expression levels of Sox-9, aggrecan, and collagen II. Moreover, the roles of SDF-1/CXCR4 axis in the migration and chondrogenesis differentiation of NPSCs were analyzed by immunofluorescence, immunoblotting, and real-time *** SDF-1α was significantly upregulated in the native IVD cells cultured in vitro with pro-inflammatory cytokines, such as interleukin-1β and tumor necrosis factor-α, mimicking the degenerative settings. Immunohistochemical staining showed that the level of SDF-1α was also significantly higher in the degenerative group than in the normal group. SDF-1α enhanced the migration capacity of NPSCs in a dose-depende

关键词： Stromal cell-derived factor 1α CXC chemokine receptor 4 Nucleus pulposusderived stem cells Intervertebral disc degeneration Endogenous regeneration

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Ultrathin nanosheets of Mn3O4： A new two-dimensional ferromagnetic material with strong magnetocrystalline anisotropy

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Frontiers of physics 2018年第3期13卷 29-35页

作者： Jun-Chi Wu Xu Peng Yu-Qiao Guo Hao-Dong Zhou Ji-Yin Zhao ke-Qin ruan Wang-Sheng Chu Changzheng Wu Hefei National Laboratory for Physical Sciences at the Microscale iChEM (Collaborative Innovation Center of Chemistry for Energy Materials) CAS Center for Excellence in Nanoscience and CAS Key Laboratory of Mechanical Behavior and Design of Materials University of Science and Technology of China Hefei 230026 China National Synchrotron Radiation Laboratory University fff Science and Technology of China Hefei 230026 China

Two-dimensional （2D） materials with robust ferromagnetism have played a key role in realizing next- generation spin-electronic devices, but many challenges remain, especially the lack of intrinsic ferro- magnetic behavior in almost all 2D materials. Here, we highlight ultrathin Mn3O4 nanosheets as a new 2D ferromagnetic material with strong magnetocrystalline anisotropy. Magnetic measurements along the in-plane and out-of-plane directions confirm that the out-of-plane direction is the easy axis. The 2D-confined environment and Rashba-type spin-orbit coupling are thought to be responsible for the magnetocrystaUine anisotropy. The robust ferromagnetism in 2D MnaO4 nanosheets with magne- tocrystalline anisotropy not only paves a new way for realizing the intrinsic ferromagnetic behavior in 2D materials but also provides a novel candidate for building next-generation spin-electronic devices.

关键词： 2D ferromagnetic material topochemical conversion magnetocrystalline anisotropy

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Dominant negative effect as a novel mechanism of SPAST gene mutation in a large family with hereditary spastic paraplegia

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Genes & Diseases 2024年第5期11卷 74-77页

作者： ke Deng Haibo ruan Feifei Yu Zhenle Pei Congjian Xu Shuo Zhang Shanghai Ji Ai Genetics&IVF Institute Obstetrics and Gynecology Hospital of Fudan UniversityShanghai 200000China Shanghai key Laboratory of Female Reproductive Endocrine Related Diseases Shanghai 200000China The First People’s Hospital of Wenling WenlingZhejiang 317500China Rushan Hospital of Traditional Chinese Medicine RushanShandong 264599China Department of Obstetrics and Gynecology Fudan UniversityShanghai 200000China.

Hereditary spastic paraplegia(HSP)is a group of disorders with genetic heterogeneity,lower-extremity weakness,and spasticity are the most common signs and *** is the most frequently disease-causing *** is a microtubule-severing enzyme encoded by SPAST that cleaves long microtubules into short fragments by interacting with other proteins or *** spastic paraplegia type 4(SPG4),which is autosomal dominant,is the clinical subtype associated with SPAST ***4 accounts for up to one-third of all HSP cases and usually presents with isolated lower extremity spasticity,with or without bladder or sensory dysfunction.1 The main cause of SPG4 is believed to be spastin haploinsufficiency,which results from mutations in the SPAST gene.

关键词： bladder insufficiency clinical

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Driving force of biomolecular liquid–liquid phase separation probed by nuclear magnetic resonance spectroscopy

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Biophysics Reports 2022年第2期8卷 90-99页

作者： Hanyu Zhang Weiwei Fan Gilbert Nshogoza Yaqian Liu Jia Gao Jihui Wu Yunyu Shi Xiaoming Tu Jiahai Zhang ke ruan Ministry of Education key Laboratory for Membraneless Organelles & Cellular Dynamics Hefei National Laboratory for Physical Sciences at the Microscale School of Life SciencesDivision of Life Sciences and Medicine University of Science and Technology of China Department of Applied Chemistry College of Science and Technology University of Rwanda

The assembly of biomolecular condensates is driven by liquid–liquid phase separation. To understand the structure and functions of these condensates, it is essential to characterize the underlying driving forces, e.g., protein–protein and protein–RNA interactions. As both structured and low-complexity domains are involved in the phase separation process, NMR is probably the only technique that can be used to depict the binding topology and interaction modes for the structured and nonstructured domains simultaneously. Atomic-resolution analysis for the intramolecular and intermolecular interactions between any pair of components sheds light on the mechanism for phase separation and biomolecular condensate assembly and disassembly. Herein, we describe the procedures used for the most extensively employed NMR techniques to characterize key interactions for biomolecular phase separation.

关键词： Membraneless organelles Liquid–liquid phase separation NMR spectroscopy Chemical shift perturbation Paramagnetic relaxation enhancement

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Recent progress in fragment-based drug discovery facilitated by NMR spectroscopy

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Magnetic Resonance Letters 2022年第2期2卷 107-118,I0003页

作者： Lei Wang Jia Gao Rongsheng Ma Yaqian Liu Mingqing Liu Fumei Zhong Jie Hu Shuju Li Jihui Wu Hualiang Jiang Jiahai Zhang ke ruan The First Affiliated Hospital of USTC Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei230001China Ministry of Education key Laboratory for Membraneless Organelles&Cellular Dynamics Hefei National Laboratory for Physical Sciences at the MicroscaleSchool of Life SciencesDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei230027China Drug Discovery and Design Center State Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of Sciences555 Zuchongzhi RoadShanghai201203China

Considerable developments have been observed in fragment-based lead/drug discovery(FBLD/FBDD)recently,with four drugs approved and many others under *** magnetic resonance(NMR)has gained increasing popularity in FBLD due to its intrinsic capability in characterizing protein-ligand interactions in a large dynamic range of affinity,from weak hits to highly potent ***,we summarize NMR applications in fragment-based hit-to-lead evolution,including the construction of a fragment library,screening methods,spectra processing,and the delineation of the protein-ligand binding *** state-of-the-art NMR techniques have been exemplified in the discovery of inhibitors against multiple targets over the past five years,and they are expected to continue to provide new insights in the future.

关键词： Fragment-based lead/drug discovery NMR spectroscopy Protein-ligand interaction Complex structure Hit-to-lead evolution

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Automated NMR Fragment Based Screening Hits a Novel Interface Blocker to the LARG/RhoA Complex

Automated NMR Fragment Based Screening Hits a Novel Interfac...

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第四届中国结构生物学学术讨论会

作者： Jia Gao Rongsheng Ma ke ruan Hefei National Laboratory for Physical Science at Microscale School of Life Science University of Science and Technology of China

The deregulation of the small GTPase RhoA can cause an uncontrolled phosphorylation of downstream kinase and eventually tumor cell growth and metastasis1, however, direct targeting RhoA may render severe side effects due to its extensive roles in normal cells. Inhibition of the upstream Guanine Exchange Factors（GEFs） by small molecules has been proved to be a fruitful route2,3. We therefore select Leukemia Associated RhoGEF（LARG） as our target, which has the largest catalytic activity to promote RhoA from the inactive GDP binding form to the active GTP binding form, aimed to find a blocker to the interaction between LARG catalytic domain DH and RhoA. We have applied our recently accomplished NMR fragment based screening to find the chemical probes to block the DH/RhoA complex formation. The whole screening facility has been highly automated by the 96 well autosampler and home-made data processing scripts to process thousands of NMR spectra in real time. Our fragment library of 1008 compounds has been first filtered by their drug like physiochemical properties, and aqueous solubility measured by the automated quantitative NMR, where 893 compounds have passed the solubility criteria. Those compounds were prepared in 10 compounds each well, with optimized aromatic peak overlapping for better deconvolution. The primary NMR fragment screening over DH/RhoA complex for compounds in cocktails has harvested seven compounds, which were then interrogated by a secondary screening for those hits individually. Two reconfirmed hits were validated by the following HSQC titration of small molecules to DH and RhoA, respectively, to determine their binding cavity formed by the switch I and switch II of RhoA, and at the interface of DH/RhoA complex as well. The native gel electrophoresis and the signal intensity variation of RhoA titrated to 15 N DH demonstrate the fragment hit as a blocker to the complex formation, thus a potential ligand to inhibit the RhoA activation by DH. We are n

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Assembly regulation of the heat-induced G3BP1 stress granule

Assembly regulation of the heat-induced G3BP1 stress granule

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2021年全国生物相分离和相变学术研讨会

作者： Weiwei Fan Shonghong Guang ke ruan National Hefei National Laboratory for Physical Sciences at the Microscale School of Life SciencesUniversity of Science and Technology of China

G3BP1 is the nucleating protein of stress-induced liquid-liquid phase separation（LLPS）.Here,we found that the RNA recognition motif（RRM） domain of G3 BP1 facilitates LLPS of the RGG *** methylation catalyzed by PRMT1 suppressed the phase separation of G3 BP1 RRM-RGG,which is promoted by the addition of total *** RNA binding topology was hence mapped by using NMR chemical shift perturbations of the 15 N-labeled G3 BP1 RRM-RGG upon titration of various RNA sequences,e.g.,poly（A）,poly（C）,poly（U） and *** reversible formation of G3 BP1 foci was observed in *** upon treatment of heat *** are currently working on the regulatory roles of arginine methylation in the assembly of heat-induced G3 BP 1 stress granule.

关键词： Stress Granule G3BP1 post-translational modification protein-RNA interaction

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