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CRL2^(APPBP2)-mediated TSPYL2 degradation counteracts human mesenchymal stem cell senescence

Science China(Life Sciences) 2024年第3期67卷 460-474页

作者： Daoyuan huang Qian Zhao Kuan Yang Jinghui Lei Ying Jing Hongyu Li Chen Zhang Shuai Ma Shuhui Sun Yusheng Cai Guibin Wang Jing Qu weiqi Zhang Si Wang Guang-Hui Liu Advanced Innovation Centerfor Human Brain Protection National Clinical Research Centerfor Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Translational MedicineCenter International Centerfor Aging and CancerBejing Municipal GeriatricMedical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Beijing Institute for Stem Cell and Regenerative Medicine Beijing100101China CAS Key Laboratory of Genomic and Precision Medicine Bejing Institute of Genomics and China National Center for BioinformationChinese Academy of SciencesBeijing 100101China Institute for Stem Cell and Regeneration CASBeijing 100101China The Fifth People's Hospital of Chongqing Chongqing 400062China Sino-Danish Cllege University of Chinese Academy of SciencesBeijing101408China National Laboratory of Biomacromolecules CAS Center for Excelence in BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing100101China State Key Laboratory of Proteomics Beijing Proteome Research CenterNational Center for Protein Sciences(Beijing)Beijing Institute of LifeomicsBeijing 102206China

Cullin-RING E3 ubiquitin ligases(CRLs),the largest family of multi-subunit E3 ubiquitin ligases in eukaryotic cells,represent core cellular machinery for executing protein degradation and maintaining ***,we asked what roles Cullin proteins play in human mesenchymal stem cell(hMSC)homeostasis and *** this end,we conducted a comparative aging phenotype analysis by individually knocking down Cullin members in three senescence models:replicative senescent hMSCs,Hutchinson-Gilford Progeria Syndrome hMSCs,and Werner syndrome *** all family members,we found that CUL2 deficiency rendered hMSCs the most susceptible to *** investigate CUL2-specific underlying mechanisms,we then applied CRISPR/Cas9-mediated gene editing technology to generate CUL2-deficient human embryonic stem cells(hESCs).When we differentiated these into h MSCs,we found that CUL2 deletion markedly accelerates hMSC ***,we identified that CUL2 targets and promotes ubiquitin proteasome-mediated degradation of TSPYL2(a known negative regulator of proliferation)through the substrate receptor protein APPBP2,which in turn downregulates one of the canonical aging marker-P21^(waf1/cip1),and thereby delays *** work provides important insights into how CRL2^(APPBP2)-mediated TSPYL2 degradation counteracts hMSC senescence,providing a molecular basis for directing intervention strategies against aging and aging-related diseases.

关键词： Cullins stem cell senescence aging proteostasis ubiquitination APPBP2 TSPYL2

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Unraveling brain aging through the lens of oral microbiota

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Neural Regeneration Research 2025年第7期20卷 1930-1943页

作者： Qinchao Hu Si Wang weiqi Zhang Jing Qu Guang-Hui Liu State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Hospital of Stomatology Guanghua School of StomatologyGuangdong Provincial Key Laboratory of StomatologySun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric Disorders Xuanwu HospitalCapital Medical UniversityBeijingChina Aging Translational Medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijingChina CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijingChina University of Chinese Academy of Sciences BeijingChina Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijingChina Aging Biomarker Consortium BeijingChina State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Beijing Institute for Stem Cell and Regenerative Medicine BeijingChina

The oral cavity is a complex physiological community encompassing a wide range of *** of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative *** studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention *** this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and *** also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.

关键词： Alzheimer's disease brain aging multiple sclerosis neurodegeneration neurodegenerative diseases oral microbiota Parkinson's disease periodontitis bacteria Porphyromonas gingivalis

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泊松克里金算法在核辐射场重构中的应用研究

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原子能科学技术 2022年第8期56卷 1690-1699页

作者：王振宇黄伟奇孙健彭广宇陆军防化学院北京102205 湖南交通职业技术学院湖南长沙410132

为验证泊松克里金法在核辐射场重构中的应用效果,本文对泊松克里金算法在辐射场剂量率插值计算中的计算原理进行了研究,结合代理模型对泊松克里金算法进行了求解。通过SuperMC软件建立虚拟辐射场,对泊松克里金算法的参数影响进行了分析... 详细信息

为验证泊松克里金法在核辐射场重构中的应用效果,本文对泊松克里金算法在辐射场剂量率插值计算中的计算原理进行了研究,结合代理模型对泊松克里金算法进行了求解。通过SuperMC软件建立虚拟辐射场,对泊松克里金算法的参数影响进行了分析,筛选出二次多项式基函数和GAUSS误差相关模型。采用6150AD-b闪烁体探测器对实际放射源进行测量,并利用实测辐射场剂量率数据和福岛周边空间剂量率数据对泊松克里金算法在核辐射场重构中的可行性进行了验证。结果表明:小范围简单辐射场中,样本数据量为网格点数的1/10时,平均相对误差在10%以内;大范围辐射场中,辐射热点区域略有偏移,平均相对误差为141.69%。以上结果表明,该方法在快速、低成本解决未知放射源辐射场的重构问题中有一定的潜力。

关键词：辐射场重构插值算法克里金插值算法泊松克里金算法

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MAVS Antagonizes Human Stem Cell Senescence as a Mitochondrial Stabilizer

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Research 2024年第2期2023卷 239-257页

作者： Cui Wang Kuan Yang Xiaoqian Liu Si Wang Moshi Song Juan Carlos Izpisua Belimonte Jing Qu Guang-Hui Liu weiqi Zhang CAS Key Laboratory of Genomic and Precision Medicine Beijng Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Institute for Stem Cell and Regeneration Chinese Academy of Sciences Beijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Bejing 100101China Advanced Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Altos Labs Inc.San DiegoCA 94022USA

Mitochondrial dysfunction is a hallmark feature of cellular senescence and organ ***,we asked whether the mitochondrial antiviral signaling protein(MAVS),which is essential for driving antiviral response,also regulates human stem cell *** answer this question,we used CRISPR/Cas9-mediated gene editing and directed differentiation techniques to generate various MAVS-knockout human stem cell *** found that human mesenchymal stem cells(hMSCs)were sensitive to MAVS deficiency,as manifested by accelerated senescence *** uncovered that the role of MAVS in maintaining mitochondrial structural integrity and functional homeostasis depends on its interaction with the guanosine triphosphatase optic atrophy type 1(OPA1).Depletion of MAVS or OPA1 led to the dysfunction of mitochondria and cellular senescence,whereas replenishment of MAVS or OPA1 in MAVS-knockout hMSCs alleviated mitochondrial defects and premature senescence *** together,our data underscore an uncanonical role of MAVS in safeguarding mitochondrial homeostasis and antagonizing human stem cell senescence.

关键词： CRISPR/Cas9 homeostasis Mitochondrial

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路径依赖、市场导向与升学志愿选择--澳门保送生内地升学影响因素研究

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高教探索 2022年第4期 113-121页

作者：黄伟棋霍伟东中山大学粤港澳发展研究院广州510275

基于2020年和2021年澳门保送生的录取结果、内地高校和专业信息数据,本研究探讨澳门保送生内地升学志愿选择的影响因素。研究发现,学校和专业在往届的收生人数、学校排名、学校的主校区在一线城市都会对本届专业收生人数的提升产生显著... 详细信息

基于2020年和2021年澳门保送生的录取结果、内地高校和专业信息数据,本研究探讨澳门保送生内地升学志愿选择的影响因素。研究发现,学校和专业在往届的收生人数、学校排名、学校的主校区在一线城市都会对本届专业收生人数的提升产生显著的积极作用。结合澳门人才供需情况,路径依赖与市场导向是澳门高中毕业生内地升学志愿选择的动力机制。为了吸引港澳青年到内地学习融入国家发展大局,应该从资源调拨、精准匹配和就业支持三方面提升相关政策效能。

关键词：澳门保送生政策内地升学路径依赖市场导向升学志愿选择

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A Study on Artistic Treatment in Vocal Works

Journal of Social Science Development Research

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Journal of Social Science Development Research 2024年第1期2卷 25-35页

作者： weiqi Pu Geely University of China ChengduChina.

The singing of a vocal work is far more than a simple series of notes,but a delicate artistic process that requires the performer to skillfully use sound,emotion,and *** process is not just about performing music,but also about transmitting emotions,a spiritual dialogue resonating with the *** the wonderful stage of artistic treatment,the performer becomes the second creator of the song,infusing the work with new life through their unique personality and insightful *** the clever concatenation of notes,the performer can unfold the layers of emotion contained within the song,making it richer and deeper.

关键词： Vocal music works Artistic treatment Singing skill

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Elucidating the anti-obesity phytochemicals in Chenpi and their molecular mechanisms

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Food Science and Human Wellness 2024年

作者： Jinhai Luo weiqi Yan Zhi Chen Baojun Xu Guangdong Provincial Key Laboratory IRADS and Department of Life Sciences BNU-HKBU United International College Centre for Cancer and Inflammation Research School of Chinese Medicine Hong Kong Baptist University Faculty of Biochemistry and Molecular Medicine University of Oulu

Obesity has become a significant global public health issue. Previous studies have found that the Chenpi has the anti-obesity activity. However， the anti-obesity phytochemicals and their mechanisms are still unclear. This study investigated the anti-obesity phytochemicals and molecular mechanisms involved in treating obesity by Chenpi through network pharmacology and molecular docking. Seventeen bioactive phytochemicals from Chenpi and its 475 related anti-obesity targets have been identified. The KEGG pathway analysis showed that the PI3K/Akt signaling pathway， MAPK signaling pathway， AMPK signaling pathway， and NF-kappa B signaling pathway are the main signaling pathways involved in the anti-obesity effect of Chenpi. According to molecular docking analysis， the phytochemicals of Chenpi can bind to central anti-obesity targets. Based on the ADMET analysis and network pharmacology results， tangeretin exhibited the lowest predicted toxicity and the highest potential for anti-obesity effects. In the in vitro lipid accumulation model， tangeretin effectively suppressed the FFA-induced lipid in HepG2 cells by upregulating the PI3K/Akt/GSK3β signaling pathway based on the result of q-PCR and Western Blotting. The outcomes of this research give insights for future research on the anti-obesity phytochemicals and molecular mechanisms derived from Chenpi， also providing the theoretical basis for developing anti-obesity functional foods based on Chenpi.

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MMP-9在非小细胞肺癌转移中作用及其机制的研究进展

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中国肿瘤生物治疗杂志 2022年第9期29卷 846-850页

作者：刘小婷(综述) 江高峰黄炜祺(审阅) 武汉市第三医院肾内科湖北武汉430000 武汉科技大学附属天佑医院中心实验室湖北武汉430000 华中科技大学协和江北医院呼吸与危重症医学科湖北武汉430000

基质金属蛋白酶-9(MMP-9)是一种关键的基质金属蛋白酶,它能够降解细胞外基质,在肿瘤的侵袭和转移中发挥重要作用。MMP-9已被国内外多项研究证实在非小细胞肺癌(NSCLC)组织中呈高表达,而与此相关的信号通路有很多,如PI3K/AKT信号通路、AP... 详细信息

基质金属蛋白酶-9(MMP-9)是一种关键的基质金属蛋白酶,它能够降解细胞外基质,在肿瘤的侵袭和转移中发挥重要作用。MMP-9已被国内外多项研究证实在非小细胞肺癌(NSCLC)组织中呈高表达,而与此相关的信号通路有很多,如PI3K/AKT信号通路、AP-1/NF-κB信号通路、TGF-β1/SIRT1/AMPK信号通路,Wnt/β-catenin信号通路等,其中PI3K/AKT信号通路起主要作用。高表达的MMP-9可降解细胞外基质,促进肿瘤细胞从原发瘤体脱离,穿过血管内皮细胞进入血液或淋巴并游走至体循环,最终外渗至新的解剖部位形成转移灶。MMP-9还与免疫逃逸有关,促使机体形成肿瘤适宜的微环境。在NSCLC患者中,MMP-9的高表达与淋巴结及远处转移相关,还意味着更低的生存率及不良预后。因此,MMP-9有望成为该肿瘤诊治及预后评估的重要指标。已开发出多种人工合成MMP抑制剂,但极少数已应用于临床诊治,相信在不久的将来,MMP抑制剂或可成为治疗NSCLC的一种新方式。

关键词：基质金属蛋白酶-9 非小细胞肺癌表达调控转移机制

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Application of Heavy Solvent Deasphalting in Sour Resid Processing

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China Petroleum Processing & Petrochemical Technology 2003年第3期5卷 1-7页

作者： Long Jun Wang Zijun huang weiqi Zu Deguang(SINOPEC Research Institute of Petroleum Processing, Beijing 100083) SINOPEC Res. Inst. of Petroleum Processing Beijing 100083 China

Complete conversion of resid into light oil needs to consume large amount of hydrogen, because the light oil has higher hydrogen content. The conversion of whole resid into light oil is not economic at the normal price gap between the light and heavy oils. Hence a combination of hydrogenation process with carbon removal process is generally *** heavy solvent deasphalting can selectively remove the asphaltenes and metals contained in resid while providing a large amount of easily convertible deasphalted oil for the down-stream *** article refers to the characteristics of heavy solvent deasphalting and its application in sour resid processing, along with various routes for utilization of deoiled asphalt.

关键词：脱沥青残油处理精制处理加氢精制

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Colony-stimulating factor-1 receptor inhibition combined with paclitaxel exerts effective antitumor effects in the treatment of ovarian cancer

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Genes & Diseases 2024年第3期11卷 400-416页

作者： Meijia Yu Yiming Wu Qingfang Li weiqi Hong Yang Yang Xiaoyi Hu Yanfei Yang Tianqi Lu Xia Zhao Xiawei Wei Laboratory of Aging Research and Cancer Drug Target State Key Laboratory of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengduSichuan 610041China Department of Gynecology and Obstetrics Development and Related Disease of Women and Children Key Laboratory of Sichuan ProvinceKey Laboratory of Birth Defects and Related Diseases of Women and ChildrenMinistry of EducationWest China Second HospitalSichuan UniversityChengduSichuan 610041China Department of Obstetrics and Gynecology The First Affiliated HospitalArmy Medical UniversityChongqing 400038China

Ovarian cancer is the tumor with the highest mortality among gynecological *** have confirmed that paclitaxel chemoresistance is associated with increased infiltration of tumor-associated macrophages(TAMs)in the ***-stimu-lating factor 1(CSF-1)receptor(CSF-1R)plays a key role in regulating the number and differ-entiation of macrophages in certain solid *** are few reports on the effects of targeted inhibition of CSF-1R in combination with chemotherapy on ovarian cancer and the tu-mor ***,we explored the antitumor efficacy and possible mechanisms of the CSF-1R inhibitor pexidartinib(PLX3397)when combined with the first-line chemothera-peutic agent paclitaxel in the treatment of ovarian *** found that CSF-1R is highly ex-pressed in ovarian cancer cells and correlates with poor *** by PLX3397 in combination with paclitaxel significantly inhibited the growth of ovarian cancer both in vitro and in *** of CSF-1R altered the macrophage phenotype and reprogrammed the immunosuppressive cell population in the tumor microenvironment.

关键词： CSF-1R Ovariancancer Paclitaxel PLX3397 Targeted therapy Tumor-associated macrophages

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