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Inducing mitochondriopathy-like damages by transformable nucleopeptide nanoparticles for targeted therapy of bladder cancer

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National Science Review 2024年第4期11卷 216-227页

作者： Da-Yong Hou Ni-Yuan Zhang Lu Wang Mei-Yu Lv Xiang-Peng Li Peng Zhang Yue-Ze Wang Lei Shen Xiu-Hai Wu Bo Fu Peng-Yu Guo Zi-Qi Wang Dong-Bing Cheng Hao Wang wanhai xu NHC and CAMS Key Laboratory of Molecular Probe and Targeted Theranostics Heilongjiang Key Laboratory of Scientific Research in Urology Harbin Medical University Department of Urology Harbin Medical University Cancer Hospital CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology(NCNST) School of Chemistry Chemical Engineering & Life Science Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases Wuhan University of Technology

Mitochondriopathy inspired adenosine triphosphate(ATP) depletions have been recognized as a powerful way for controlling tumor growth. Nevertheless, selective sequestration or exhaustion of ATP under complex biological environments remains a prodigious challenge. Harnessing the advantages of in vivo self-assembled nanomaterials, we designed an Intracellular ATP Sequestration(IAS) system to specifically construct nanofibrous nanostructures on the surface of tumor nuclei with exposed ATP binding sites,leading to highly efficient suppression of bladder cancer by induction of mitochondriopathy-like damages.Briefly, the reported transformable nucleopeptide(NLS-FF-T) self-assembled into nuclear-targeted nanoparticles with ATP binding sites encapsulated inside under aqueous conditions. By interaction with KPNA2, the NLS-FF-T transformed into a nanofibrous-based ATP trapper on the surface of tumor nuclei,which prevented the production of intracellular energy. As a result, multiple bladder tumor cell lines(T24,EJ and RT-112) revealed that the half-maximal inhibitory concentration(IC50) of NLS-FF-T was reduced by approximately 4-fold when compared to NLS-T. Following intravenous administration, NLS-FF-T was found to be dose-dependently accumulated at the tumor site of T24 xenograft mice. More significantly, this IAS system exhibited an extremely antitumor efficacy according to the deterioration of T24 tumors and simultaneously prolonged the overall survival of T24 orthotopic xenograft mice. Together, our findings clearly demonstrated the therapeutic advantages of intracellular ATP sequestration-induced mitochondriopathy-like damages, which provides a potential treatment strategy for malignancies.

关键词： self-assembly nucleopeptide nanomaterial bladder cancer mitochondriopathy

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Coronavirus transmissible gastroenteritis virus antagonizes the antiviral effect of the microRNA miR-27b via the IRE1 pathway

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Science China(Life Sciences) 2022年第7期65卷 1413-1429页

作者： Changlin Wang Mei xue Peng Wu Honglei Wang Zhongqing Liu Guangzheng Wu Pinghuang Liu Keliang Wang wanhai xu Li Feng Department of Urology the Fourth Affiliated Hospital of Harbin Medical UniversityHarbin 150001China State Key Laboratory of Veterinary Biotechnology Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy Harbin Medical UniversityHarbin 150001China

Although the functional parameters of micro RNAs(mi RNAs)have been explored to some extent,the roles of these molecules in coronavirus infection and the regulatory mechanism of mi RNAs in virus infection are still unclear.Transmissible gastroenteritis virus(TGEV)is an enteropathgenic coronavirus and causes high morbidity and mortality in suckling piglets.Here,we demonstrated that microRNA-27b-3p(miR-27b-3p)suppressed TGEV replication by directly targeting porcine suppressor of cytokine signaling 6(SOCS6),while TGEV infection downregulated miR-27b-3p expression in swine testicular(ST)cells and in piglets.Mechanistically,the decrease of miR-27b-3p expression during TGEV infection was mediated by the activated inositolrequiring enzyme 1(IRE1)pathway of the endoplasmic reticulum(ER)stress.Further studies showed that when ER stress was induced by TGEV,IRE1 acted as an RNase activated by autophosphorylation and unconventionally spliced m RNA encoding a potent transcription factor,X-box-binding protein 1(Xbp1s).Xbp1s inhibited the transcription of miR-27 and ultimately reduced the production of miR-27b-3p.Therefore,our findings indicate that TGEV inhibits the expression of an anti-coronavirus micro RNA through the IRE1 pathway and suggest a novel way in which coronavirus regulates the host cell response to infection.

关键词： coronavirus transmissible gastroenteritis coronavirus(TGEV) micro RNA inositol-requiring enzyme 1(IRE1) immune evasion

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柱体流激振动能量俘获理论与技术研究若干进展

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力学学报 2024年第3期56卷 524-539页

作者：徐万海马烨璇天津大学水利工程智能建设与运维全国重点实验室天津300072 中国科学院力学研究所北京100190

潮流能分布广泛,且储量巨大,具备巨大的规模化开发利用价值.流激振动是一种常见的流固耦合现象,通过柱体流激振动能够在流速较低时实现有效的能量转换,基于柱体流激振动的能量俘获技术在未来具备广阔的工程应用前景.近年来,针对柱体结... 详细信息

潮流能分布广泛,且储量巨大,具备巨大的规模化开发利用价值.流激振动是一种常见的流固耦合现象,通过柱体流激振动能够在流速较低时实现有效的能量转换,基于柱体流激振动的能量俘获技术在未来具备广阔的工程应用前景.近年来,针对柱体结构流激振动特性和能量俘获性能,出现了大量的实验和数值仿真研究工作.文章全面阐述了多种截面形式的单个柱体、柱群结构流激振动能量俘获理论与技术方面的研究进展:对于单个圆柱流激振动能量俘获,目前已基本揭示了被动湍流控制器参数、系统阻尼、雷诺数和边界条件等因素对能量俘获性能的影响规律,基本完成了理论和技术积累;对于非圆截面柱体流激振动能量俘获,已初步明确特定来流攻角、系统质量比、系统阻尼、系统刚度和雷诺数条件下三角形、四边形、多边形与异形等多种截面形式柱体的流激振动作用机理和能量俘获能力;对于柱群的流激振动能量俘获,各柱体振子之间存在流场干涉,需要合理设计柱体排布形式、柱体间距和系统阻尼等参数,实现流体能量俘获最大化.通过综述国内外流激振动能量俘获理论和技术方面的研究进展,对今后该问题的研究进行了力所能及的展望,期望促进流激振动能量俘获理论的发展和流激振动能量转换装置的工程应用.

关键词：流激振动驰振潮流能能量俘获柱体结构

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Boosting image-guiding radiation therapy through W_(18)O_(49) nanospheres and the second near-infrared light irradiation

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Nano Research 2022年第3期15卷 2315-2323页

作者： Nannan Zheng Shouhao Zhang Lu Wang Zhilin Qi Qiang Peng Lingrui Jian Yang Bai Yue Feng Jiachen Shen Ranxu Wang Jia Jiao wanhai xu Shaoqin Liu School of Life Science and Technology MOE Key Laboratory of Micro-systems and Micro-structures ManufacturingHarbin Institute of TechnologyHarbin 150080China NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy Harbin Medical UniversityHarbin 150001China The First Affiliated Hospital Department of EndodonticsHarbin Medical UniversityHarbin 150080China Department of Gynecological Radiotherapy Harbin Medical University Cancer HospitalHarbin 150081China

More than 60%of cancer patients receive radiation therapy(RT)during their anticancer treatment.However,there is a huge challenge to improve the therapeutic efficacy of RT in less radioresponsive tumors and decrease damages dealt to the surrounding healthy tissues.Herein,we have reported the development of an efficacious RT treatment of relatively radio-resistant breast cancer using W_(18)O_(49)nanospheres and the second near-infrared(NIR)light irradiation.Featuring the X-ray attenuation ability and photothermal effect,together with ability to generate intracellular singlet oxygen and·OH,W_(18)O_(49)nanospheres can significantly increase radiation-induced DNA damage and decrease the mitochondrial membrane potential of cancer cells during RT,causing in nearby three-times improvement in inhibiting the proliferation of 4T1 cells.The in vivo evaluations verify that a rather effective therapeutic outcome is achieved by treatment of 4T1 tumor xenograft with NIR-enhanced RT using W_(18)O_(49)nanospheres.Moreover,the X-ray attenuation ability and the strong near-infrared absorption of W_(18)O_(49)nanospheres have enabled highly resolved in vivo computer tomography(CT)/photoacoustic(PA)imaging.This work presents an“all-in-one”synergistic platform to improve the therapeutic efficacy of RT in less radioresponsive tumors,therefore opening a new door for multimodal cancer therapy.

关键词： W_(18)O_(49) tumor metastasis radiosensitizer phototherapy singlet oxygen

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流固耦合力学专题序

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力学学报 2024年第3期56卷 521-523页

作者：徐万海赖姜马烨璇天津大学水利工程智能建设与运维全国重点实验室天津300072 电子科技大学航空航天学院成都611731 中国科学院力学研究所北京100190

流固耦合力学是流体力学与固体力学交叉而成的力学分支,以两相介质之间的相互作用为重要特征,研究可变形固体在流场作用下的行为及固体变形对流场影响的相互作用.流固耦合现象存在于海洋工程、航空航天、石油化工、核能工程、土木工程... 详细信息

流固耦合力学是流体力学与固体力学交叉而成的力学分支,以两相介质之间的相互作用为重要特征,研究可变形固体在流场作用下的行为及固体变形对流场影响的相互作用.流固耦合现象存在于海洋工程、航空航天、石油化工、核能工程、土木工程等几乎所有涉及国计民生的重大领域中,并会诱发结构静发散、载荷重新分布、颤振、极限环振荡及涡激振动等诸多工程问题.

关键词：极限环振荡航空航天固体力学流固耦合石油化工两相介质流体力学土木工程

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An activated excretion-retarded tumor imaging strategy towards metabolic organs

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Bioactive Materials 2022年第8期7卷 110-119页

作者： Da-Yong Hou Man-Di Wang Xing-Jie Hu Zhi-Jia Wang Ni-Yuan Zhang Gan-Tian Lv Jia-Qi Wang Xiu-Hai Wu Lu Wang Hao Wang wanhai xu Department of Urology The Fourth Hospital of Harbin Medical UniversityHeilongjiang Key Laboratory of Scientific Research in UrologyHarbin150001China NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy Harbin Medical UniversityHarbin150001China CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology(NCNST)Beijing100190China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesNo.19A Yuquan Road100049 BeijingChina Henan Institute of Advanced Technology Zhengzhou UniversityZhengzhou450052China

Intraoperative fluorescence-based tumor imaging plays a crucial role in performing the oncological safe tumor resection with the advantage of differentiating tumor from normal tissues.However,the application of these fluorescence contrast agents in renal cell carcinoma(RCC)and hepatocellular carcinoma(HCC)was dramatically hammered as a result of lacking active targeting and poor retention time in tumor,which limited the Signal to Noise Ratio(SNR)and narrowed the imaging window for complicated surgery.Herein,we reported an activated excretion-retarded tumor imaging(AERTI)strategy,which could be in situ activated with MMP-2 and self-assembled on the surface of tumor cells,thereby resulting in a promoted excretion-retarded effect with an extended tumor retention time and enhanced SNR.Briefly,the AERTI strategy could selectively recognize the Integrin α_(v)β_(3).Afterwards,the AERTI strategy would be activated and in situ assembled into nanofibrillar structure after specifically cleaved by MMP-2 upregulated in a variety of human tumors.We demonstrated that the AERTI strategy was successfully accumulated at the tumor sites in the 786-O and HepG2 xenograft models.More importantly,the modified modular design strategy obviously enhanced the SNR of AERTI strategy in the imaging of orthotopic RCC and HCC.Taken together,the results presented here undoubtedly confirmed the design and advantage of this AERTI strategy for the imaging of tumors in metabolic organs.

关键词： Self-assembly Biomaging Peptide Probe Tumor

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浅海高压立管涡激振动及疲劳特性分析工艺

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西南石油大学学报（自然科学版） 2024年第3期46卷 102-108页

作者：姜玉峰徐万海中海油能源发展股份有限公司上海工程技术分公司上海长宁200335 天津大学水利工程仿真与安全国家重点实验室天津南开300072

随着东海油气资源的不断开发,开发成本较低的自升式平台将得到广泛应用。立管所在海洋环境复杂多变,其结构长度与直径比值较大,在海流作用下会发生涡激振动。采用尾流振子模型对高压立管涡激振动响应进行预报,并基于DNV规范,根据S-N曲... 详细信息

随着东海油气资源的不断开发,开发成本较低的自升式平台将得到广泛应用。立管所在海洋环境复杂多变,其结构长度与直径比值较大,在海流作用下会发生涡激振动。采用尾流振子模型对高压立管涡激振动响应进行预报,并基于DNV规范,根据S-N曲线法对结构疲劳进行计算。模型通过有限差分法进行离散求解。研究重点关注顶张力对立管的涡激振动及疲劳特性影响。结果表明,顶张力会影响立管的涡激振动响应,并进一步改变结构的疲劳寿命,影响结构安全性。

关键词：自升式平台高压立管涡激振动疲劳损伤尾流振子有限差分法

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基于Hertz模型的海洋立管束碰撞力计算方法研究

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振动与冲击 2024年第13期43卷 248-253,314页

作者：徐万海李航贺子琪天津大学水利工程智能建设与运维全国重点实验室天津300072

立管是海洋油气开采的关键设备之一,其在流致振动作用下,相邻立管可能会发生振动碰撞损伤。基于Hertz模型,针对不同夹角下的两根立管碰撞的碰撞力计算开展研究。借助有限元方法探讨海洋立管局部碰撞过程,立管的直径选取为工程应用较为... 详细信息

立管是海洋油气开采的关键设备之一,其在流致振动作用下,相邻立管可能会发生振动碰撞损伤。基于Hertz模型,针对不同夹角下的两根立管碰撞的碰撞力计算开展研究。借助有限元方法探讨海洋立管局部碰撞过程,立管的直径选取为工程应用较为广泛的30.48 cm,截取长度基于相关碰撞参与长度来确定,径厚比范围为16~60,分别设置立管碰撞时的速度为0.25 m/s、1.5 m/s、2.4 m/s和3 m/s,分析两根立管夹角和立管径厚比等对于Hertz模型计算精度的影响。研究发现:两根立管夹角越小和径厚比越小,Hertz模型得到的碰撞力误差越大;通过在Hertz模型中添加与径厚比相关的系数,对Hertz模型进行了修正,最终得到了关于立管束碰撞力的精确计算方法。

关键词：立管碰撞 Hertz模型有限元模拟接触力法

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Clinical practice guideline on bladder cancer(Part Ⅰ)

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UroPrecision 2023年第3期1卷 20-30页

作者： Xiying Dong Gang Song Kaopeng Guan Tie Wang Xiaoli Feng Yulin Liu Min Liu Zhigang Ji Xiao Li Jiongming Li Yong Zhang Fangjian Zhou Aiping Zhou wanhai xu Tao xu Xianshu Gao Qing Zhai Qiang Wei Nianzeng Xing Department of Urology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Nuclear Medicine Beijing Chaoyang Hospital Affiliated with Capital Medical UniversityBeijingChina Department of Pathology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Imaging Diagnosis Department Hubei Cancer HospitalAffiliated Cancer Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Department of Pharmacy National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Urology Peking Union Medical College HospitalBeijingChina Department of Interventional Therapy National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Urology The Second Affiliated Hospital of Kunming Medical UniversityKunmingChina Department of Urology Sun Yat-Sen University Cancer CenterGuangzhouChina Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Urology Harbin Medical University Cancer HospitalHarbinChina Department of Urology Peking University People's HospitalBeijingChina Department of Radiotherapy Peking University First HospitalBeijingChina Department of Pharmacy Fudan University Shanghai Cancer CenterShanghaiChina Department of Urology West China School of Medicine/West China Hospital of Sichuan UniversityChengduChina

Bladder cancer represents one of the most prevalent malignant tumors affecting the urinary system.As per data disclosed by the National Cancer Registration Center of China in 2019,the incidence of bladder cancer was 5.80 per 100,000 in 2015,placing it as the thirteenth most common systemic malignancy.Bladder cancer poses a substantial threat to public health in China,underlining the critical importance of standardizing diagnosis and treatment to enhance clinical outcomes.This clinical practice guideline for bladder cancer centers on the etiologies,clinical presentations,and diagnostic procedures for suspected bladder cancer,in addition to the histopathology and staging of urothelial bladder cancer.

关键词： bladder cancer guideline precision urology

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深海采矿柔性管力学性能及加工工艺研究综述

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力学与实践 2024年第3期46卷 532-547页

作者：徐万海沙沐王莹莹马烨璇天津大学水利工程智能建设与运维全国重点实验室中国石油大学(北京)安全与海洋工程学院中国科学院力学研究所

海洋蕴藏着储量丰富的矿产资源，深海矿产资源开发逐渐成为学术界和工程界的研究热点。管道提升式开采方案是目前公认的最具商业前景的海洋矿产开发方案。矿产输运管道作为连接海底中继舱和海上采矿平台的纽带，需要承受恶劣的风、浪、... 详细信息

海洋蕴藏着储量丰富的矿产资源，深海矿产资源开发逐渐成为学术界和工程界的研究热点。管道提升式开采方案是目前公认的最具商业前景的海洋矿产开发方案。矿产输运管道作为连接海底中继舱和海上采矿平台的纽带，需要承受恶劣的风、浪、流环境载荷和复杂作业工况的工作载荷，其设计制造和力学性能分析一直备受关注。相比于刚性管道，柔性管道的弯曲刚度小、便于安装与回收、使用寿命较长。然而，柔性管道的结构复杂，各层之间相互影响，金属柔性管道由于自身结构的限制，在深海采矿行业中难以广泛应用，人们开始把目光放在非金属柔性管的设计与应用上。本文回顾了柔性管的发展历程，总结阐述了柔性管设计及加工制造中的力学性能分析方法和力学特性，并对柔性管设计制造的未来发展提供力所能及的展望。

关键词：柔性管管道设计管道加工深海采矿

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