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SUB1 promotes colorectal cancer metastasis by activating NF-κB signaling via UBR5-mediated ubiquitination of UBXN1

Science China(Life Sciences) 2024年第6期67卷 1199-1211页

作者： Hao wang Wenwen Chen yanting wang Yuzhen Gao Zizhen Zhang Shuyi Mi Liangjing wang Meng Xue Department of Gastroenterology The Second Affiliated Hospital of Zhejiang University School of MedicineHangzhou 310009China Institution of Gastroenterology Zhejiang UniversityHangzhou 310058China Department of Clinical Laboratory Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China Department of Gastrointestinal Oncology Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing)Peking University Cancer Hospital and InstituteBeijing 100142China

Metastasis accounts for the major cause of colorectal cancer(CRC)related mortality due to the lack of effective treatments.In this study,we integrated the single-cell RNA-seq(sc RNA-seq)and bulk RNA-seq data and identified the transcriptional coactivator SUB1 homolog(SacSaccharomyces cerevisiae)/PC4(positive cofactor 4)associated with CRC metastasis.Elevated SUB1 expression was correlated with advanced tumor stage and poor survival in CRC.In vivo and vitro assays showed that SUB1 depletion could inhibit the invasive and metastatic abilities of CRC cells.SUB1 activated NF-κB signaling and its transcriptional target genes CXCL1 and CXCL3 to drive CRC metastasis.Mechanistically,SUB1 integrated with the E3 ubiquitin-protein ligase UBR5 and increased its protein level in CRC cells.Subsequently,the increased UBR5mainly mediated Lys11-linked polyubiquitination and degradation of NF-κB negative regulator UBXN1,thus to activate the NF-κB signaling.Overall,our study demonstrated that SUB1 promoted CRC progression by modulating UBR5/UBXN1 and activating NF-κB signaling,providing a new therapeutic strategy for treating metastatic CRC through targeting SUB1.

关键词： colorectal cancer Metastasis SUB1 UBR5 NF-κB signaling

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Asymmetric nucleation processes in spontaneous mode switch of active matter

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Communications in Theoretical Physics 2024年第5期76卷 154-158页

作者：杨冰王延颋 CAS Key Laboratory of Theoretical Physics Institute of Theoretical Physics Chinese Academy of Sciences Beijing 100190 China School of Physical Sciences University of Chinese Academy of Sciences Beijing 100049 China

Flocking and vortical are two typical motion modes in active matter.Although it is known that the two modes can spontaneously switch between each other in a finite-size system,the switching dynamics remain elusive.In this work,by computer simulation of a two-dimensional Vicsek-like system with 1000 particles,we find from the perspective of the classical nucleation theory that the forward and backward switching dynamics are asymmetric:going from flocking to vortical is a one-step nucleation process,while the opposite is a two-step nucleation process,with the system staying in a metastable state before reaching the final flocking state.

关键词： active matter dynamics classical nucleation theory

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Stability of inner dump slope under coal pillar support:case study in an open‑pit coal mine

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International Journal of Coal Science & Technology 2022年第2期9卷 193-210页

作者： Guanghe Li Xiaoxu Yang Dong wang yanting wang Xiangyu Yu College of Mining Liaoning Technical UniversityFuxin 123000LiaoningChina

The stability of an inner dump slope was investigated under the efect of coal pillar support considering the development position of dumping.Based on the instability mechanism and load distribution characteristics of the supporting coal pillar,the three-dimensional mechanical efects of the supporting coal pillar are characterized.Using the two-dimensional equivalent principle and the residual thrust method,the stability of the inner dump slope was analyzed under the efect of pillar support at diferent dump development positions.The quantitative efects of various factors on the inner dump slope stability were revealed,and the coal pillar shape parameters were optimized through numerical simulations.The results indicate that the slope stability coefcient is linearly related to the top width and height of the coal pillar,slope angle,and base inclination angle,and has an exponential relation with the coal pillar strike length and slope height increment.There are quadratic and absolute value relations with the coal pillar outer and the inner bottom angle,respectively.The top width of the coal pillar in the inner dump of Shengli East No.2 open-pit coal mine should be at a level of+824 m,and the optimal top width and height are 15 and 36.7 m,respectively.The instability mechanism of the supporting and retaining coal pillar obtained by numerical simulations and the stability of the inner dump are in good agreement with the theoretical analysis.Our results provide a theoretical basis for the design,treatment,and safe implementation of similar open-pit mine slope engineering.

关键词： Inner dump Supporting coal pillar Slope stability Numerical simulation Morphological parameters

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IQGAP3 promotes the progression of glioma as an immune and prognostic marker

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Oncology Research 2024年第4期32卷 659-678页

作者： XIAOFENG GAO JUANJUAN GE XUZHENG GAO NA MEI yanting SU SHIGANG SHAN WENBIN QIAN JIANGHENG GUAN ZHENwang ZHANG LONG wang Hubei Provincial Key Laboratory of Diabetic Cardiovascular Diseases Xianning Medical CollegeHubei University of Science and TechnologyXianning437100China School of Stomatology and Ophthalmology Xianning Medical CollegeHubei University of Science and TechnologyXianning437100China School of Basic Medical Sciences Xianning Medical CollegeHubei University of Science and TechnologyHubei University of Science and TechnologyXianning437100China School of Pharmacy Xianning Medical CollegeHubei University of Science and TechnologyXianning437100China Department of Neurosurgery The General Hospital of Chinese PLA Central Theater CommandWuhan430070China

Background:IQGAP3 plays a crucial role in regulating cell proliferation,division,and cytoskeletal organization.Abnormal expression of IQGAP3 has been linked to various tumors,but its function in glioma is not well understood.Methods:Various methods,including genetic differential analysis,single-cell analysis,ROC curve analysis,Cox regression,Kaplan-Meier analysis,and enrichment analysis,were employed to analyze the expression patterns,diagnostic potential,prognostic implications,and biological processes involving IQGAP3 in normal and tumor tissues.The impact of IQGAP3 on immune infiltration and the immune microenvironment in gliomas was evaluated using immunofluorescence.Additionally,the cBioPortal database was used to analyze copy number variations and mutation sites of IQGAP3.Experimental validation was also performed to assess the effects of IQGAP3 on glioma cells and explore underlying mechanisms.Results:High IQGAP3 expression in gliomas is associated with an unfavorable prognosis,particularly in wild-type IDH and 1p/19q non-codeleted gliomas.Enrichment analysis revealed that IQGAP3 is involved in regulating the cell cycle,PI3K/AKT signaling,p53 signaling,and PLK1-related pathways.Furthermore,IQGAP3 expression may be closely related to the immunosuppressive microenvironment of glioblastoma.BRD-K88742110 and LY-303511 are potential drugs for targeting IQGAP3 in anti-glioma therapy.In vitro experiments showed that downregulation of IQGAP3 inhibits the proliferation and migration of glioma cells,with the PLK1/PI3K/AKT pathway potentially playing a crucial role in IQGAP3-mediated glioma progression.Conclusion:IQGAP3 shows promise as a valuable biomarker for diagnosis,prognosis,and immunotherapeutic strategies in gliomas.

关键词： IQGAP3 Tumor immune infiltration Prognosis Glioma Biomarker

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A novel preimplantation genetic testing strategy for a subtelomeric genetic disorder:A case study

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Genes & Diseases 2024年第4期11卷 13-15页

作者： Songchang Chen Li Wanng Luting Chen Weihui Shi Junyu Zhang Yuting Hu Yinyu wang Li Jin Jianzhong Sheng Feng Zhang yanting Wu Hefeng Huang Chenming Xu Obstetrics and Gynecology Hospital Institute of Reproduction and DevelopmentFudan UniversityShanghai 200090China The International Peace Maternity and Child Health Hospital School of MedicineShanghai Jiao Tong UniversityShanghai 200030China Research Units of Embryo Original Diseases Chinese Academy of Medical SciencesShanghai 200030China Key Laboratory of Reproductive Genetics(Ministry of Education) Department of Reproductive EndocrinologyWomen's HospitalZhejiang University School of MedicineHangzhouZhejiang 310058China Shanghai Key Laboratory of Embryo Original Diseases Shanghai 200030China Shanghai First Maternity and Infant Hospital Tongji University School of MedicineShanghai 200030China

Preimplantation genetic testing(PGT)is a precise and effective technique for detecting inherited pathogenic mutations to prevent birth defects.However,there are few reports on PGT for pseudo-autosomal genetic diseases.

关键词： implantation testing precise

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Nutrient enrichment driven by canopy rainfall redistribution:Mechanism,quantification,and pattern

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Science China Earth Sciences 2024年第5期67卷 1529-1544页

作者： Chuan YUAN Xiaoping YUE Yafeng ZHANG Yu ZHANG yanting HU Qiang TANG Li GUO Shuai wang Xingwu DUAN Wenhua XIANG Xiaohua WEI Xiaoyan LI College of Forestry and Biotechnology Zhejiang A&F UniversityHangzhou 311300China Chongqing Jinfo Mountain Karst Ecosystem National Observation and Research Station School of Geographical SciencesSouthwest UniversityChongqing 400715China Shapotou Desert Research and Experiment Station Northwest Institute of Eco-Environment and ResourcesChinese Academy of SciencesLanzhou 730000China School of Geographical Sciences Hebei Normal UniversityShijiazhuang 050024China Faculty of Life Science and Technology Central South University of Forestry and TechnologyChangsha 410004China State Key Laboratory of Hydraulics and Mountain River Engineering College of Water Resource and HydropowerSichuan UniversityChengdu 610065China State Key Laboratory of Earth Surface Processes and Resource Ecology Faculty of Geographical ScienceBeijing Normal UniversityBeijing 100875China Yunnan Key Laboratory of Soil Erosion Prevention and Green Development Institute of International Rivers and Eco-securityYunnan UniversityKunming 650091China Department of Earth Environmental and Geographic SciencesUniversity of British Columbia(Okanagan)KelownaBritish Columbia V1V 1V7Canada

Vegetation canopies intercept and redistribute rainfall into throughfall and stemflow,which transfer substantial amounts of elements into the soil,influencing soil microbial community,plant survival,and plant community succession.Despite advancements in ecohydrological research,the implication of nutrient enrichment resulting from this redistribution of rainfall by canopies remains largely unexplored.To address this gap,we conducted a systematic review of 1020 papers published between 2000 and 2022,gathering data on nutrient concentration and enrichment for critical ions(including K^(+),Na^(+),Ca^(2+),Mg^(2+),NH_(4)^(+),Cl^(-),NO_(3)^(-)and SO_(4)^(2-))from the Web of Science and Chinese Knowledge Infrastructure databases.We aimed to synthesize the mechanisms,quantify the enrichments,and identify global patterns of nutrient enrichment in stemflow and throughfall across climate zones,and vegetation types and ecosystems.The results of this study indicate that stemflow exhibits,on average,2.1times greater ion concentration(6.13 mg L^(-1))compared to throughfall.In particular,among the investigated ions,SO_(4)^(2-)(12.45and 6.32 mg L^(-1))for stemflow and throughfall,respectively,and Cl^(-)(9.21 and 4.81 mg L^(-1))exhibit the highest concentrations in both rainfall redistribution components,while K^(+)(13.7 and 5.8)and Mg^(2+)(5.6 and 2.8)have the highest enrichment factors.Across climate zones,throughfall and stemflow show the lowest ion concentrations but the highest enrichment factors in extremely humid regions.Along the temperature gradient,ion concentrations are the highest in cold climates with no clear patterns observed for enrichment factors with increasing temperature.In addition,shrubs,conifers,mixed forests,and artificial ecosystems demonstrate enrichment factors 1.1 to 3.0 times greater than those of trees,broad-leaved plants,pure forests,and natural ecosystems.These findings emphasize the need for increased attentions to artificial ecosystems,such as urban and agricultural ecosystems,which often received

关键词： Ecohydrology Rainfall redistribution Nutrients transport Enrichment characteristics Climate zones

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FGF7 enhances the expression of ACE2 in human islet organoids aggravating SARS-CoV-2 infection

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2260-2274页

作者： Hao Meng Zhiying Liao yanting Ji Dong wang Yang Han Chaolin Huang Xujuan Hu Jingyi Chen Hengrui Zhang Zonghong Li Changliang wang Hui Sun Jiaqi Sun Lihua Chen Jiaxiang Yin Jincun Zhao Tao Xu Huisheng Liu School of Biomedical Engineering Guangzhou Medical UniversityGuangzhou 511495 GuangdongChina Guangzhou National Laboratory Guangzhou 510320 GuangdongChina State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China Center for Translational Medicine Wuhan Jinyintan HospitalWuhan 430023 HubeiChina School of Biomedical Sciences and Engineering South China University of TechnologyGuangzhou 510006 GuangdongChina

The angiotensin-converting enzyme 2(ACE2)is a primary cell surface viral binding receptor for SARS-CoV-2,so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against COVID-19.In the current study,we utilized islet organoids derived from human embryonic stem cells(hESCs),animal models and COVID-19 patients to discover that fibroblast growth factor 7(FGF7)enhances ACE2 expression within the islets,facilitating SARS-CoV-2 infection and resulting in impaired insulin secretion.Using hESC-derived islet organoids,we demonstrated that FGF7 interacts with FGF receptor 2(FGFR2)and FGFR1 to upregulate ACE2 expression predominantly inβcells.This upregulation increases both insulin secretion and susceptibility ofβcells to SARS-CoV-2 infection.Inhibiting FGFR counteracts the FGF7-induced ACE2 upregulation,subsequently reducing viral infection and replication in the islets.Furthermore,retrospective clinical data revealed that diabetic patients with severe COVID-19 symptoms exhibited elevated serum FGF7 levels compared to those with mild symptoms.Finally,animal experiments indicated that SARS-CoV-2 infection increased pancreatic FGF7 levels,resulting in a reduction of insulin concentrations in situ.Taken together,our research offers a potential regulatory strategy for ACE2 by controlling FGF7,thereby protecting islets from SARS-CoV-2 infection and preventing the progression of diabetes in the context of COVID-19.

关键词： ACE2 FGF7 islet

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Differential distribution of PINK1 and Parkin in the primate brain implies distinct roles

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Neural Regeneration Research 2025年第4期20卷 1124-1134页

作者： yanting Liu Wei Huang Jiayi Wen Xin Xiong Ting Xu Qi wang Xiusheng Chen Xianxian Zhao Shihua Li Xiaojiang Li Weili Yang Guangdong Key Laboratory of Non-human Primate Research Key Laboratory of CNS Regeneration(Ministry of Education)Guangdong-Hongkong-Macao CNS Regeneration Institute of Jinan UniversityJinan UniversityGuangzhouGuangdong ProvinceChina

The vast majority of in vitro studies have demonstrated that PINK1 phosphorylates Parkin to work together in mitophagy to protect against neuronal degeneration.However,it remains largely unclear how PINK1 and Parkin are expressed in mammalian brains.This has been difficult to address because of the intrinsically low levels of PINK1 and undetectable levels of phosphorylated Parkin in small animals.Understanding this issue is critical for elucidating the in vivo roles of PINK1 and Parkin.Recently,we showed that the PINK1 kinase is selectively expressed as a truncated form(PINK1–55)in the primate brain.In the present study,we used multiple antibodies,including our recently developed monoclonal anti-PINK1,to validate the selective expression of PINK1 in the primate brain.We found that PINK1 was stably expressed in the monkey brain at postnatal and adulthood stages,which is consistent with the findings that depleting PINK1 can cause neuronal loss in developing and adult monkey brains.PINK1 was enriched in the membrane-bound fractionations,whereas Parkin was soluble with a distinguishable distribution.Immunofluorescent double staining experiments showed that PINK1 and Parkin did not colocalize under physiological conditions in cultured monkey astrocytes,though they did colocalize on mitochondria when the cells were exposed to mitochondrial stress.These findings suggest that PINK1 and Parkin may have distinct roles beyond their well-known function in mitophagy during mitochondrial damage.

关键词： neurodegeneration Parkin Parkinson’s disease PINK1 subcellular distribution

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Decoding the Puzzle of Late Ediacaran Glaciation(s)

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Journal of Earth Science 2024年第3期35卷 1049-1052页

作者： Bin Wen yanting Lin Fuyun Shen Junyuan Zhou School of Earth Sciences China University of GeosciencesWuhan 430074China State Key Laboratory of Biogeology and Environmental Geology China University of GeosciencesWuhan 430078China

INTRODUCTION In the Earth’s history,the Late Ediacaran to Early Cambrian period witnessed a series of profound changes in both Earth’s interior and surficial systems which may have made this planet more habitable for the first radiation of early animals(known as the global occurrence of Ediacaran biota;Xiao and Narbonne,2020).Among those changes,the Late Ediacaran glaciation,soon followed and accompanied by the early complex life of Ediacaran biota,attracted much attention of scientists and may have provided a good opportunity to investigate the interactions between the Earth’s surficial environment and the biosphere(e.g.,Xu et al.,2024;Zhang et al.,2023;Hoffman et al.,2017).To achieve this goal,the nature of the glaciation itself needs to be understood first.Until now,32 or more Ediacaran glacial deposits have been documented on almost all the existing continents(Niu et al.,2024;wang et al.,2023a,b,c),showing a similar distribution pattern to the two Cryogenian(Sturtian and Marinoan)Snowball Earth glaciations if plotted in one single paleogeographic map(Figure 1;Niu et al.,2024;Li et al.,2013).But further compared to the Cryogenian Snowball Earth glaciations,the Late Ediacaran glaciation has some fundamentally different characteristics:(1)as shown in Figure 1,most glacial deposits are not stratigraphically overlain by the typical cap carbonate while it usually happened in the aftermath of a Snowball Earth glaciation and represented an abrupt climatic switch from extreme icehouse(global freezing)to greenhouse(global warming)condition(Hoffman et al.,2017).

关键词： Earth glacial Cambrian

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基于科学思维进阶培养的“细胞的结构”复习课教学设计

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生物学教学 2024年第3期49卷 38-41页

作者：王妍婷华东师范大学附属东昌中学上海200120

围绕“细胞的结构”这一主题,通过创设真实的情境贯穿整节课,设计渐进的任务,为学生科学思维的发展提供阶梯,帮助学生在建构概念的同时,逐步提升科学思维能力,切实提高学科核心素养。

关键词：思维进阶细胞结构情境贯穿高中生物学

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