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The influences of perforating phase and bedding planes on the fracture deflection in laminated shale

Petroleum Science 2024年第2期21卷 1221-1230页

作者： Ming-Zhe Gu Mao sheng Xiao-Ying zhuang Xin-Yi Li Gen-sheng Li National Key Laboratory of Petroleum Resources and Engineering China University of PetroleumBeijing102249China College of Petroleum Engineering China University of PetroleumBeijing102249China College of Civil Engineering Tongji UniversityShanghai200092China

The perforating phase leads to complex and diverse hydraulic fracture propagation behaviors in laminated shale formations. In this paper, a 2D high-speed imaging scheme which can capture the interaction between perforating phase and natural shale bedding planes was proposed. The phase field method was used to simulate the same conditions as in the experiment for verification and hydraulic fracture propagation mechanism under the competition of perforating phase and bedding planes was discussed.The results indicate that the bedding planes appear to be no influence on fracture propagation while the perforating phase is perpendicular to the bedding planes, and the fracture propagates along the perforating phase without deflection. When the perforating phase algins with the bedding planes, the fracture initiation pressure reserves the lowest value, and no deflection occurs during fracture propagation. When the perforating phase is the angle 45°, 60°and 75°of bedding planes, the bedding planes begin to play a key role on the fracture deflection. The maximum deflection degree is reached at the perforating phase of75°. Numerical simulation provides evidence that the existence of shale bedding planes is not exactly equivalent to anisotropy for fracture propagation and the difference of mechanical properties between different shale layers is the fundamental reason for fracture deflection. The findings help to understand the intrinsic characteristics of shale and provide a theoretical basis for the optimization design of field perforation parameters.

关键词： Shale Propagation Perforating Bedding Structure

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Modularized viromimetic polymer nanoparticle vaccines(VPNVaxs) to elicit durable and effective humoral immune responses

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National Science Review 2024年第3期11卷 200-214页

作者： Zichao Huang Xinyu zhuang Liping Liu Jiayu Zhao sheng Ma Xinghui Si Zhenyi Zhu Fan Wu Ningyi Jin Mingyao Tian Wantong Song Xuesi Chen Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied ChemistryChinese Academy of Sciences School of Applied Chemistry and Engineering University of Science and Technology of China Changchun Veterinary Research Institute Chinese Academy of Agricultural Sciences Jilin Biomedical Polymers Engineering Laboratory State Key Laboratory of Polymer Physics and Chemistry Changchun Institute of Applied Chemistry Chinese Academy of Sciences

Virus-like particle(VLP) vaccines had shown great potential during the COVID-19 pandemic, and was thought to be the next generation of antiviral vaccine technology due to viromimetic structures. However,the time-consuming and complicated processes in establishing a current recombinant-protein–based VLP vaccine has limited its quick launch to the out-bursting pandemic. To simplify and optimize VLP vaccine design, we herein report a kind of viromimetic polymer nanoparticle vaccine(VPNVax), with subunit receptor-binding domain(RBD) proteins conjugated to the surface of polyethylene glycol-b-polylactic acid(PEG-b-PLA) nanoparticles for vaccination against SARS-CoV-2. The preparation of VPNVax based on synthetic polymer particle and chemical post-conjugation makes it possible to rapidly replace the antigens and construct matched vaccines at the emergence of different viruses. Using this modular preparation system, we identified that VPNVax with surface protein coverage of 20%–25% had the best immunostimulatory activity, which could keep high levels of specific antibody titers over 5 months and induce virus neutralizing activity when combined with an aluminum adjuvant. Moreover, the polymer nano-vectors could be armed with more immune-adjuvant functions by loading immunostimulant agents or chemical chirality design. This VPNVax platform provides a novel kind of rapidly producing and efficient vaccine against different variants of SARS-CoV-2 as well as other viral pandemics.

关键词： vaccine polymer nanomaterials SARS-CoV-2

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Seasonal variations of nonmotor symptoms in patients with Parkinson's disease in Southeast China

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Chinese Medical Journal 2023年第4期136卷 415-422页

作者： Jingyi Wang Kangping Xiong Jingyuan Chao sheng zhuang Jie Li Chunfeng Liu Department of Neurology and Clinical Research Center of Neurological Disease The Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu 215004China Sleep Center The Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu 215004China Institute of Neuroscience Soochow UniversitySuzhouJiangsu 215123China

Background:Studies suggest seasonal fluctuations of symptoms in Parkinson’s disease(PD)patients in Western countries.However,the association between seasonal change and variation in nonmotor symptoms(NMS)in Chinese PD patients is unclear.Here,we studied whether there is a change rule with annual cycle with severity of NMS for patients with PD in Southeast China.Methods:We studied 1005 PD patients between April 2008 and October 2020.Patients were classified into four seasons according to the 24 Chinese solar terms,based on assessment date.We compared comprehensive NMS scales and polysomnography parameters among groups and conducted further analysis of disease severity.Results:Among the 1005 patients studied,the mean age was 64.2±9.7 years and 569(56.6%)of them were men.Relative to the summer group,patients assessed during winter had higher Scales for Outcomes in Parkinson’s disease-Autonomic Dysfunction(SCOPA-AUT)scores(P=0.045).The sleep efficiency factor scores of Pittsburgh Sleep Quality Index in patients were higher during spring than summer(P=0.009).Among patients who completed polysomnography during the same period(n=135),compared with summer follow-ups,we observed a higher percentage of NREMS1 in winter and spring follow-ups(P=0.042,P=0.011),a higher NREMS1 time in spring follow-ups(P=0.0024),a lower NREMS2 time in winter follow-ups(P=0.007),and a higher percentage of phasic rapid eye movement(REM)-sleep without atonia in autumn and winter follow-ups(P=0.026 and P=0.020,respectively).In a subset of patients with PD and REM sleep behavior disorder(RBD;n=182),those visited during winter had higher scores for RBD questionnaire-Hong Kong and its factor 1(dream-related sub-score)than those visited during summer(P=0.034,P=0.020).We observed similar findings for SCOPA-AUT and sleep efficiency factor scores in early stage patients in subgroup analysis.Conclusions:PD patients assessed for follow-up during summer showed less severe symptoms of autonomic dysfunction and RBD symptoms than those assessed in winter,and l

关键词： Nonmotor symptoms Parkinson’s disease Seasonal variations

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Pien Tze Huang Inhibits Migration and Invasion of Hepatocellular Carcinoma Cells by Repressing PDGFRB/YAP/CCN2 Axis Activity

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Chinese Journal of Integrative Medicine 2024年第2期30卷 115-124页

作者： LUO Zhi-yi TIAN Qi CHENG Niang-mei LIU Wen-han YANG Ye CHEN Wei ZHANG Xiang-zhi ZHENG Xiao-yuan CHEN Ming-sheng zhuang Qiu-yu ZHAO Bi-xing LIU Cong-sheng LIU Xiao-long LI Qin WANG Ying-chao The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhou(350025)China Fujian Pien Tze Huang Enterprise Key Laboratory of Natural Medicine Research and Development Zhangzhou Pien Tze Huang Pharmaceutical Co.Ltd.ZhangzhouFujian Province(363099)China College of Biological Science and Engineering and Mengchao Med-X Center Fuzhou UniversityFuzhou(350116)China Department of Internal Medicine Mengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhou(350025)China

Objective:To investigate the effects of Pien Tze Huang(PZH) on the migration and invasion of HCC cells and underlying molecular mechanism.Methods:Cell counting kit-8(CCK-8) was applied to evaluate the cell viabilities of SMMC-7721,SK-Hep-1,C3A and HL-7702(6 × 10^(3)cells/well) co-incubated with different concentrations of PZH(0,0.2,0.4,0.6,0.8 mg/mL) for 24 h.Transwell,wound healing assay,CCK-8and Annexin V-FITC/PI staining were conducted to investigate the effects of PZH on the migration,invasion,proliferation and apoptosis of SK-Hep-1 and SMMC-7721 cells(650 μg/mL for SK-Hep-1 cells and 330 μg/mL for SMMC-7721 cells),respectively.In vivo,lung metastasis mouse model constructed by tail vein injection of HCC cells was used for evaluating the anti-metastasis function of PZH.SK-Hep-1 cells(10^(6)cells/200 μL per mice) were injected into B-NDG mice via tail vein.Totally 8 mice were randomly divided into PZH and control groups,4 mice in each group.After 2-d inoculation,mice in the PZH group were administered with PZH(250 mg/kg,daily) and mice in the control group received only vehicle(PBS) from the 2nd day after xenograft to day 17.Transcriptome analysis based on RNA-seq was subsequently used for deciphering anti-tumor mechanism of PZH.Quantitative real-time polymerase chain reaction(qRT-PCR) and Western blot were applied to verify RNA-seq results.Luciferase reporter assay was performed to examine the transcriptional activity of yes-associated protein(YAP).Results:PZH treatment significantly inhibited the migration,invasion,proliferation and promoted the apoptosis of HCC cells in vitro and in vivo(P<0.01).Transcriptome analysis indicated that Hippo signaling pathway was associated with anti-metastasis function of PZH.Mechanical study showed PZH significantly inhibited the expressions of platelet derived growth factor receptor beta(PDGFRB),YAP,connective tissue growth factor(CCN2),N-cadherin,vimentin and matrix metallopeptidase 2(MMP2,P<0.01).Meanwhile,the phosphorylation of YAP was also enhanced by PZH treatment in v

关键词： PienTzeHuang hepatocellular carcinoma RNA-seq Hippo yes-associated protein

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Cinobufotalin prevents bone loss induced by ovariectomy in mice through the BMPs/SMAD and Wnt/β-catenin signaling pathways

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Animal Models and Experimental Medicine 2024年第3期7卷 208-221页

作者： Da-zhuang Lu Li-jun Zeng Yang Li Ran-li Gu Meng-long Hu Ping Zhang Peng Yu Xiao Zhang Zheng-wei Xie Hao Liu Yong-sheng Zhou Department of Prosthodontics Peking University School and Hospital of StomatologyBeijingChina National Center of Stomatology BeijingChina National Clinical Research Center for Oral Diseases BeijingChina Beijing Key Laboratory of Digital Stomatology BeijingChina Department of Cariology and Endodontology Peking University School and Hospital of StomatologyBeijingChina Peking University International Cancer Institute Peking University Health Science CenterPeking UniversityBeijingChina Central Laboratory Peking University School and Hospital of StomatologyBeijingChina National Engineering Research Center of Oral Biomaterials and Digital Medical Devices BeijingChina

Background:Osteoporosis is a chronic bone disease characterized by bone loss and decreased bone strength.However,current anti-resorptive drugs carry a risk of various complications.The deep learning-based efficacy prediction system(DLEPS)is a forecasting tool that can effectively compete in drug screening and prediction based on gene expression changes.This study aimed to explore the protective effect and potential mechanisms of cinobufotalin(CB),a traditional Chinese medicine(TCM),on bone loss.Methods:DLEPS was employed for screening anti-osteoporotic agents according to gene profile changes in primary osteoporosis.Micro-CT,histological and morphological analysis were applied for the bone protective detection of CB,and the osteogenic differentiation/function in human bone marrow mesenchymal stem cells(hBMMSCs)were also investigated.The underlying mechanism was verified using qRT-PCR,Western blot(WB),immunofluorescence(IF),etc.Results:A safe concentration(0.25mg/kg in vivo,0.05μM in vitro)of CB could effectively preserve bone mass in estrogen deficiency-induced bone loss and promote osteogenic differentiation/function of hBMMSCs.Both BMPs/SMAD and Wnt/β-catenin signaling pathways participated in CB-induced osteogenic differentiation,further regulating the expression of osteogenesis-associated factors,and ultimately promoting osteogenesis.Conclusion:Our study demonstrated that CB could significantly reverse estrogen deficiency-induced bone loss,further promoting osteogenic differentiation/function of hBMMSCs,with BMPs/SMAD and Wnt/β-catenin signaling pathways involved.

关键词： BMPs/SMAD bone loss cinobufotalin hBMMSCs osteogenesis osteoporosis Wnt/β-catenin signaling pathways

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Molecular solid solution of lanthanide-titanium-oxo clusters with enhanced photocatalytic hydrogen evolution

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Science China Chemistry 2024年第2期67卷 529-535页

作者： Rong Chen Chao-Long Chen Hui Zhang Zi-Han Wang Fu-Li Sun Ming-Hao Du Gui-Lin zhuang Cheng Wang La-sheng Long Lan-Sun Zheng Xiang-Jian Kong Collaborative Innovation Centre of Chemistry for Energy Materials State Key Laboratory of Physical Chemistry of Solid Surfaces and Department of Chemistry College of Chemistry and Chemical EngineeringXiamen UniversityXiamen361005China College of Chemical Engineering Zhejiang University of TechnologyHangzhou310032China

Molecular solid solutions of metal clusters containing different metal centers with well-defined structures can accurately regulate the HOMO-LUMO gap,but are rarely available.Herein,a series of colorless lanthanide-titanium-oxo clusters Ln_(2)Ti_4(μ_(2)-O)_(2)(μ_(3)-O)_4(Piv)_(10)(THF)_(2)(Ln_(2)Ti_4,Ln = Eu,Gd,Tb,and Ce,HPiv = pivalic acid) were synthesized by the reaction of pivalic acid with Ln(Ac)_(3) and titanium isopropoxide.The light yellow crystal of cluster solid solutions Eu_(2)Ti_(4-x)Cd_(x),containing a mixture of Eu_(2)Ti_4 and Eu_(2)Ti_(3)Cd,was obtained by in situ doping Cd^(2+) and S^(2–).Eu_(2)Ti_(3.92)Cd_(0.08) displays efficient photocatalytic hydrogen evolution activity without a co-catalyst,which is up to 2.6 times that of Eu_(2)Ti_4.Femtosecond time-resolved transient absorption spectroscopy and spin-polarized density functional calculations showed that the enhanced photocatalytic performance of Eu_(2)Ti_(4-x)Cd_(x) can be attributed to the narrower HOMO-LUMO gap and lower LUMO position than that of Eu_(2)Ti_4.This studyprovides an in situ doping method to realize the simple preparation of cluster solid solution.

关键词： molecular solid solution lanthanide-titanium-oxo clusters photocatalytic hydrogen evolution

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A combined nanotherapeutic approach targeting farnesoid X receptor,ferroptosis,and fibrosis for nonalcoholic steatohepatitis treatment

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2228-2246页

作者： Jiangtao Fu Pingping Zhang Zhiguo Sun Guodong Lu Qi Cao Yiting Chen Wenbin Wu Jiabao Zhang Chunlin zhuang Chunquan sheng Jiajun Xu Ying Lu Pei Wang The Center for Basic Research and Innovation of Medicine and Pharmacy(MOE) School of PharmacyNaval Medical UniversityShanghai 200433China National Demonstration Center for Experimental Pharmaceutical Education Naval Medical University/Second Military Medical UniversityShanghai 200433China Department of Diving and Hyperbaric Medicine Naval Special Medical CenterNaval Medical UniversityShanghai 200433China

Obeticholic acid(OCA),a farnesoid X receptor(FXR)agonist with favorable effects on fatty and glucose metabolism,has been considered the leading candidate drug for nonalcoholic steatohepatitis(NASH)treatment.However,its limited effectiveness in resolving liver fibrosis and lipotoxicity-induced cell death remains a major drawback.Ferroptosis,a newly recognized form of cell death characterized by uncontrolled lipid peroxidation,is involved in the progression of NASH.Nitric oxide(NO)is a versatile biological molecule that can degrade extracellular matrix.In this study,we developed a PEGylated thiolated hollow mesoporous silica nanoparticles(MSN)loaded with OCA,as well as a ferroptosis inhibitor liproxsatin-1 and a NO donor S-nitrosothiol(ONL@MSN).Biochemical analyses,histology,multiplexed flow cytometry,bulk-tissue RNA sequencing,and fecal 16S ribosomal RNA sequencing were utilized to evaluate the effects of the combined nanoparticle(ONL@MSN)in a mouse NASH model.Compared with the OCA-loaded nanoparticles(O@MSN),ONL@MSN not only protected against hepatic steatosis but also greatly ameliorated fibrosis and ferroptosis.ONL@MSN also displayed enhanced therapeutic actions on the maintenance of intrahepatic macrophages/monocytes homeostasis,inhibition of immune response/lipid peroxidation,and correction of microbiota dysbiosis.These findings present a promising synergistic nanotherapeutic strategy for the treatment of NASH by simultaneously targeting FXR,ferroptosis,and fibrosis.

关键词： Nonalcoholic steatohepatitis Nanotherapy Farnesoid X receptor Ferroptosis Fibrosis Obeticholic acid S-Nitrosothiol Liproxstatin-1

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基于高阶剪切变形理论的功能梯度板自由振动分析简化模型

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振动工程学报 2024年第3期37卷 384-393页

作者：王壮壮王腾丁艳梅马连生潍坊科技学院建筑工程学院山东潍坊262700

基于高阶剪切变形理论提出了一种功能梯度板自由振动分析的简化模型,该简化模型最显著的特点是适用于功能梯度板的振动分析,且不需要剪切修正。相比于其他具有更多未知变量的剪切变形理论,本文提出的简化模型只包含一个控制方程,极大地... 详细信息

基于高阶剪切变形理论提出了一种功能梯度板自由振动分析的简化模型,该简化模型最显著的特点是适用于功能梯度板的振动分析,且不需要剪切修正。相比于其他具有更多未知变量的剪切变形理论,本文提出的简化模型只包含一个控制方程,极大地减少了计算量。基于该简化模型研究了功能梯度矩形板在简支边界条件下的自由振动,并与其他已有文献进行了比较。结果表明,本文提出的简化模型在分析功能梯度板的自由振动行为时简单且精确。此外,文中还通过多个数值算例分析讨论了不同的梯度指数、长宽比和边厚比对功能梯度板自由振动行为的影响。

关键词：自由振动功能梯度材料简化模型精化板理论固有频率

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Tanshinone ⅡA improves Alzheimer’s disease via RNA nuclearenriched abundant transcript 1/microRNA-291a-3p/member RAS oncogene family Rab22a axis

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World Journal of Psychiatry 2024年第4期14卷 563-581页

作者： Long-Xiu Yang Man Luo sheng-Yu Li Department of Neurology The First Affiliated Hospital of Guangxi Medical UniversityNanning 530000Guangxi Zhuang Autonomous RegionChina Department of Neurology Wuming Hospital of Guangxi Medical UniversityNanning 530199Guangxi Zhuang Autonomous RegionChina

BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has shown potential neuroprotective effects;however,the mechanisms underlying such a function remain unclear.AIM To investigate potential Tan-ⅡA neuroprotective effects in AD and to elucidate their underlying mechanisms.METHODS Hematoxylin and eosin staining was utilized to analyze structural brain tissue morphology.To assess changes in oxidative stress and neuroinflammation,we performed enzyme-linked immunosorbent assay and western blotting.Additionally,the effect of Tan-ⅡA on AD cell models was evaluated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Genetic changes related to the long non-coding RNA(lncRNA)nuclear-enriched abundant transcript 1(NEAT1)/microRNA(miRNA,miR)-291a-3p/member RAS oncogene family Rab22a axis were assessed through reverse transcription quantitative polymerase chain reaction.RESULTS In vivo,Tan-ⅡA treatment improved neuronal morphology and attenuated oxidative stress and neuroinflammation in the brain tissue of AD mice.In vitro experiments showed that Tan-ⅡA dose-dependently ameliorated the amyloid-beta 1-42-induced reduction of neural stem cell viability,apoptosis,oxidative stress,and neuroinflammation.In this process,the lncRNA NEAT1-a potential therapeutic target-is highly expressed in AD mice and downregulated via Tan-ⅡA treatment.Mechanistically,NEAT1 promotes the transcription and translation of Rab22a via miR-291a-3p,which activates nuclear factor kappa-B(NF-κB)signaling,leading to activation of the pro-apoptotic B-cell lymphoma 2-associated X protein and inhibition of the anti-apoptotic B-cell lymphoma 2 protein,which exacerbates AD.Tan-ⅡA intervention effectively blocked this process by inhibiting the NEAT1/miR-291a-3p/Rab22a axis and NF-κB signaling.CONCLUSION This study demonstrates that Tan-ⅡA exerts neuroprotective effects in AD by

关键词： TanshinoneⅡA Alzheimer’s disease Nuclear-enriched abundant transcript 1 Member of RAS oncogene family Rab22a Reactive oxygen species

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A human-specific insertion promotes cell proliferation and migration by enhancing TBC1D8B expression

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Science China(Life Sciences) 2024年第4期67卷 765-777页

作者： Hui Zhao Lin-Lin Liu Jian Sun Lian Jin Hai-Bing Xie Jian-Bo Li Hui Xu Dong-Dong Wu Xiao-Lin zhuang Min-sheng Peng Ya-Jun Guo Wei-Zhu Qian Newton OOtecko Wei-Jie Sun Liang-Hu Qu Jie He Zhao-Li Chen Rong Liu Ce-Shi Chen Ya-Ping Zhang State Key Laboratory for Conservation and Utilization of Bio-resource School of Life SciencesSchool of Ecology and Environmental ScienceYunnan UniversityKunming 650091China School of Forensic Medicine Kunming Medical UniversityKunming 650500China Academy of Biomedical Engineering Kunming Medical UniversityKunming 650500China The Third Affiliated Hospital Kunming Medical UniversityKunming 650118China Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650201China State Key Laboratory of Genetic Resources and Evolution Yunnan Laboratory of Molecular Biology of Domestic AnimalsKunming Institute of ZoologyChinese Academy of SciencesKunming 650201China The Key Laboratory of Gene Engineering of the Ministry of Education State Key Laboratory for BiocontrolSun Yat-sen UniversityGuangzhou 510275China National Engineering Research Center for Antibody Medicine and Shanghai Key Laboratory of Cell Engineering and Antibody Shanghai 201203China Department of Thoracic Surgery Cancer Institute and HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

Human-specific insertions play important roles in human phenotypes and diseases.Here we reported a 446-bp insertion(Insert-446)in intron 11 of the TBC1D8B gene,located on chromosome X,and traced its origin to a portion of intron 6 of the EBF1 gene on chromosome 5.Interestingly,Insert-446 was present in the human Neanderthal and Denisovans genomes,and was fixed in humans after human-chimpanzee divergence.We have demonstrated that Insert-446 acts as an enhancer through binding transcript factors that promotes a higher expression of human TBC1D8B gene as compared with orthologs in macaques.In addition,over-expression TBC1D8B promoted cell proliferation and migration through“a dual finger”catalytic mechanism(Arg538 and Gln573)in the TBC domain in vitro and knockdown of TBC1D8B attenuated tumorigenesis in vivo.Knockout of Insert-446 prevented cell proliferation and migration in cancer and normal cells.Our results reveal that the human-specific Insert-446 promotes cell proliferation and migration by upregulating the expression of TBC1D8B gene.These findings provide a significant insight into the effects of human-specific insertions on evolution.

关键词： human-specific insertion enhancer gene expression cell proliferation and migration

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