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A naturally derived small molecule compound suppresses tumor growth and metastasis in mice by relieving p53-dependent repression of CDK2/Rb signaling and the Snail-driven EMT

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Chinese Journal of Natural Medicines 2024年第02期 112-126页

作者： REN Boxue li yang DI Lei cheng Ranran liU lijuan li Hongmei li Yi TANG Zhangrui yan Yongming LU Tao FU Rong cheng Yongxian WU Zhaoqiu State Key Laboratory of Natural Medicines Department of Pharmacology School of Pharmacy China Pharmaceutical University Institute for Inheritance-Based Innovation of Chinese Medicine School of Pharmaceutical Sciences Shenzhen University Health Science Center

The tumor suppressor protein p53 is central to cancer biology, with its pathway reactivation emerging as a promising therapeutic strategy in oncology. This study introduced LZ22, a novel compound that selectively inhibits the growth, migration, and metastasis of tumor cells expressing wild-type p53, demonstrating ineffectiveness in cells devoid of p53 or those expressing mutant p53. LZ22's mechanism of action involves a high-affinity interaction with the histidine-96 pocket of the MDM2 protein. This interaction disrupted the MDM2-p53 binding, consequently stabilizing p53 by shielding it from proteasomal degradation. LZ22 impeded cell cycle progression and diminished cell proliferation by reinstating the p53-dependent suppression of the CDK2/Rb signaling ***, LZ22 alleviated the p53-dependent repression of Snail transcription factor expression and its consequent EMT, effectively reducing tumor cell migration and distal metastasis. Importantly, LZ22 administration in tumor-bearing mice did not manifest notable side effects. The findings position LZ22 as a structurally unique reactivator of p53, offering therapeutic promise for the management of human cancers with wild-type TP53.

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Nanomedicine integrating the lipidic derivative of 5-fluorouracil,miriplatin and PD-L1 si RNA for enhancing tumor therapy

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Chinese Chemical Letters 2024年第6期35卷 385-391页

作者： An Lu Yuhao Guo Yi yan lin Zhai Xiangyu Wang Weiran Cao Zijie li Zhixia Zhao Yujie Shi Yuanjun Zhu Xiaoyan liu Huining He Zhiyu Wang Jian-cheng Wang Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems State Key Laboratory of Natural and Biomimetic DrugsSchool of Pharmaceutical SciencesPeking UniversityBeijing 100191China Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics School of PharmacyTianjin Medical UniversityTianjin 300070China Department of Immuno-oncology The Fourth Hospital of Hebei Medical UniversityShijiazhuang 050011China Department of Pharmacy Clinical Trial Research CenterChina-Japan Friendship HospitalBeijing 100029China Laboratory of innovative formulations and pharmaceutical excipients Ningbo Institute of Marine MedicinePeking UniversityNingbo 315832China

Immunosuppressive microenvironments present critical problems in clinical *** regulate the tumor immune microenvironment for enhancing antitumor effect,a combination of immune checkpoint inhibitors(ICIs)with chemotherapeutics has been applied *** this study,miriplatin(MiPt),the lipidic derivative of 5-fluorouracil(Fu-OA),as well as the programmed death ligand 1(PD-L1)target si RNA(siPD-L1)were integrated into lip-Pt/Fu@siPD-L1 nanoparticles(NPs)for *** vitro results showed that lip-Pt/Fu@siPD-L1 NPs could exhibit effective siRNA gene silencing and promote the phagocytosis of tumor cells by ***,in vivo results revealed that lipPt/Fu@siPD-L1 NPs showed significantly higher anti-tumor efficiency than that of the physical mixing of Mi Pt,5-fluorouracil,and lip@siPD-L1 NPs(delivery of siPD-L1 by liposomes).The best anti-tumor efficiency of lip-Pt/Fu@siPD-L1 NPs resulted from the synergistic immunotherapeutic effects of Mi Pt and siPD-L1 based on the inhibition of CD47 expression and the downregulation of PD-L1 in tumor cells,which elicited a robust anti-tumor immune response through the activation of macrophage phagocytosis and immune checkpoint *** lip-Pt/Fu@siPD-L1 NPs provide a potential strategy for tumor chemo-immunotherapy.

关键词： Chemo-immunotherapy Immune checkpoint inhibition Gene silencing Miriplatin Macrophage phagocytosis Nanotechnology

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含粗粒滑带土剪切带演化及空间展布规律研究

岩土力学 2024年第4期45卷 1067-1080页

作者：李泽闯张昊程培峰王艳丽东北林业大学土木与交通学院黑龙江哈尔滨150040 华汇工程设计集团股份有限公司浙江绍兴312000

对含不同强度粗颗粒的滑带土进行了可视化中型直剪试验,通过竖直置入铝丝观察剪切后铝丝变形情况获取剪切破坏带的空间信息,并建立了剪切带空间曲面方程。通过粒子图像测速(particle image velocimetry,PIV)技术对可视面处二维剪切带信... 详细信息

对含不同强度粗颗粒的滑带土进行了可视化中型直剪试验,通过竖直置入铝丝观察剪切后铝丝变形情况获取剪切破坏带的空间信息,并建立了剪切带空间曲面方程。通过粒子图像测速(particle image velocimetry,PIV)技术对可视面处二维剪切带信息进行提取,并与剪切试验得到的空间曲面方程的边界外推值进行对比,证明了空间曲面方程与PIV技术能够描述剪切带特征。然后通过PIV技术对不同剪切总位移与某一剪切位移下短时间内相对位移规律进行了分析。最后分析了预制损伤与粗颗粒强度对剪切带特征的影响。研究结果表明,剪切带形状为两端薄中间厚的带状,可采用高斯曲面方程对剪切带轮廓进行拟合。剪切带在发展过程中经历压密、自由损伤、损伤沿固定路径发展与剪切带贯通4个阶段,损伤使得剪切带发展各阶段前移,粗颗粒强度会对局部剪切带变形产生较大影响而对整体剪切带的变形影响较小。该研究成果对于揭示滑坡剪切带形成与演变规律从而设计合理的边坡防治方案具有重要意义。

关键词：含粗粒滑带土剪切带中型直剪试验可视化 PIV技术

Targeting PKM2 signaling cascade with salvianic acid A normalizes tumor blood vessels to facilitate chemotherapeutic drug delivery

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2077-2096页

作者： cheng Qian Yueke Zhou Teng Zhang Guanglu Dong Mengyao Song Yu Tang Zhonghong Wei Suyun Yu Qiuhong Shen Wenxing Chen Jaesung P.Choi Juming yan Chongjin Zhong li Wan Jia li Aiyun Wang Yin Lu yang Zhao Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica Nanjing University of Chinese MedicineNanjing 210023China school of Medicine&Holistic Integrative Medicine Nanjing University of Chinese MedicineNanjing 210023China Centre for Inflammation Faculty of ScienceCentenary InstituteSchool of Life SciencesUniversity of Technology SydneySydney NSW 2050Australia Jiangsu Key Laboratory of Immunity and Metabolism Department of Pathogenic Biology and ImmunologyNational Experimental Demonstration Center for Basic Medicine EducationXuzhou Laboratory of Infection and ImmunityXuzhou Medical UniversityXuzhou 221004China Department of General Surgery Jiangsu Province Hospital of Chinese MedicineAffiliated Hospital of Nanjing University of Chinese MedicineNanjing 210029China Macquarie Medical school Faculty of MedicineHuman Health SciencesMacquarie UniversitySydney NSW 2109Australia

Aberrant tumor blood vessels are prone to propel the malignant progression of tumors,and targeting abnormal metabolism of tumor endothelial cells emerges as a promising option to achieve vascular normalization and antagonize tumor ***,we demonstrated that salvianic acid A(SAA)played a pivotal role in contributing to vascular normalization in the tumor-bearing mice,thereby improving delivery and effectiveness of the chemotherapeutic *** was capable of inhibiting glycolysis and strengthening endothelial junctions in the human umbilical vein endothelial cells(HUVECs)exposed to ***,SAA was inclined to directly bind to the glycolytic enzyme PKM2,leading to a dramatic decrease in endothelial *** importantly,SAA improved the endothelial integrity via activating theβ-Catenin/Claudin-5 signaling axis in a PKM2-dependent *** findings suggest that SAA may serve as a potent agent for inducing tumor vascular normalization.

关键词： Salvianic acid A Tumor vascular normalization PKM2 β-Catenin Claudin-5 Endothelial glycolysis Tight junctions Doxorubicin

Extracellular Disintegration of Viral Proteins as an Innovative Strategy for Developing Broad-Spectrum Antivirals Against Coronavirus

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CCS Chemistry 2024年第2期6卷 487-496页

作者： Ke Sun Zhe Ding Xiaoying Jia Haonan cheng Yingwen li yan Wu Zhuoyu li Xiaohua Huang Fangxu Pu Entao li Guiyou Wang Wei Wang Yun Ding Gary Wong Sandra Chiu Jiaming Lan Aiguo Hu Shanghai Key Laboratory of Advanced Polymeric Materials School of Materials Science and EngineeringEast China University of Science and TechnologyShanghai 200237 CAS Key Laboratory of Molecular Virology&Immunology Chinese Academy of SciencesShanghai 200031 university of the Chinese Academy of sciences Beijing 100049 State Key Laboratory of Virology Center for Biosafety Mega-ScienceWuhan Institute of VirologyChinese Academy of SciencesWuhan 430071 Division of life sciences and Medicine University of Science and Technology of ChinaHefeiAnhui 230027 Department of Clinical Laboratory The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230001

The coronavirus disease 2019(COVID-19)pandemic,caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has claimedmillions of lives and caused innumerable economic losses ***,state-of-the-art treatments still lag behind the continual emergence of new *** to resolving this issue is developing antivirals to deactivate coronaviruses regardless of their structural ***,we report an innovative antiviral strategy involving extracellular disintegration of viral proteins with hyperanion-grafted enediyne(EDY)*** core EDY generates reactive radical species and causes significant damage to the spike protein of coronavirus,while the hyperanion groups ensure negligible cytotoxicity of the *** EDYs exhibit antiviral activity down to nanomolar concentrations,and the selectivity index of up to 20,000 against four kinds of human coronavirus,including the SARS-CoV-2 Omicron variant,suggesting the high potential of this new strategy in combating the COVID-19 pandemic and a future“disease X.”

关键词： enediyne broad spectrum antiviral protein disintegration coronavirus polyanions

“In-N-out” design enabling high-content triethyl phosphate-based non-flammable and high-conductivity electrolytes for lithium-ion batteries

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Science china Chemistry 2024年第2期67卷 724-731页

作者： Mengchuang liu Fenfen Ma Zicheng Ge Ziqi Zeng Qiang Wu Hui yan Yuanke Wu Sheng Lei yanli Zhu Shijie cheng Jia Xie State Key Laboratory of Advanced Electromagnetic Engineering and Technology School of Electrical and Electronic EngineeringHuazhong University of Science and TechnologyWuhan430074China school of Chemistry and Chemical Engineering Huazhong University of Science and TechnologyWuhan430074China GuSu Laboratory of Materials Suzhou215123China Institute of Metal Research Chinese Academy of SciencesShenyang110000China State Key Laboratory of Explosion Science and Technology Beijing Institute of TechnologyBeijing100081China

Safety issues related to flammable electrolytes in lithium-ion batteries(liBs) remain a major challenge for their extended *** use of non-flammable phosphate-based electrolytes has proved the validity in inhibiting the combustion of ***,the strong interaction between li^(+) and phosphate leads to a dominant solid electrolyte interphase(SEI) with limited electronic shielding,resulting in the poor li^(+) intercalation at the graphite(Gr) anode when using high-phosphate-content *** mitigate this issue and improve li^(+) insertion,we propose an “In-N-Out” strategy to render phosphates “noncoordinative”.By employing a combination of strongly polar solvents for a “block effect” and weakly polar solvents for a “drag effect”,we reduce the li^(+)–phosphate *** a result,phosphates remain in the electrolyte phase(“In”),minimizing their impact on the incompatibility with the Gr electrode(“Out”).We have developed a non-flammable electrolyte with high triethyl phosphate(TEP) content(>60 wt.%),demonstrating the excellent ion conductivity(5.94 mS cm^(-1) at 30 ℃) and reversible li^(+) intercalation at a standard concentration(~1 mol L^(-1)).This approach enables the manipulation of multiple electrolyte functions and holds the promise for the development of safe electrochemical energy storage systems using non-flammable electrolytes.

关键词： lithium-ion batteries graphite anode high-phosphate-content electrolytes non-flammable electrolyte excellent ion conductivity standard concentration

Potentiation of the lateral habenula-ventral tegmental area pathway underlines the susceptibility to depression in mice with chronic pain

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Science china(life sciences) 2024年第1期67卷 67-82页

作者： Chun-Kui Zhang Pan Wang Yuan-Yuan Ji Jian-Shuai Zhao Jun-Xiang Gu Xian-Xia yan Hong-Wei Fan Ming-Ming Zhang Yu Qiao Xiao-Die liu Bao-Juan li Ming-Hui Wang Hai-Long Dong Hao-Hong li Peng-cheng Huang Yun-Qing li Wu-Gang Hou Jin-lian li Tao Chen Department of Anatomy and K.K.Leung Brain Research Centre Fourth Military Medical UniversityXi’an 710032China Beijing Institute of Basic Medical sciences Beijing 100850China Key Laboratory of Ministry of Public Health for Forensic Science Xi’an Jiaotong UniversityXi’an 710061China Department of Anesthesiology Xijing HospitalFourth Military Medical UniversityXi’an 710032China Department of Neurosurgery the Second Affiliated Hospital of Xian Jiaotong UniversityXi’an 710004China school of Biomedical Engineering Fourth Military Medical UniversityXi’an 710032China Affiliated Mental Health Centre and Hangzhou Seventh People’s Hospital Zhejiang University School of MedicineHangzhou 310013China The MOE Frontier Research Center of Brain&Brain-machine Integration Zhejiang University School of Brain Science and Brain MedicineHangzhou 310058China Department of Neurology The First Affiliated Hospital of Nanchang UniversityNanchang 330006China Department of Anatomy School of MedicineNorthwest UniversityXi’an 710069China

Chronic pain often develops severe mood changes such as ***,how chronic pain leads to depression remains elusive and the mechanisms determining individuals’responses to depression are largely *** we found that depression-like behaviors could only be observed in 67.9%of mice with chronic neuropathic pain,leaving 32.1%of mice with depression *** determined that the spike discharges of the ventral tegmental area(VTA)-projecting lateral habenula(LHb)glutamatergic(Glu)neurons were sequentially increased in sham,resilient and susceptible mice,which consequently inhibited VTA dopaminergic(DA)neurons through a LHbGlu-VTAGABA-VTADA ***,the LHbGlu-VTADA excitatory inputs were dampened via GABAB receptors in a pre-synaptic *** of LHb-VTA pathway largely affected the development of depressive symptoms caused by chronic *** study thus identifies a pivotal role of the LHb-VTA pathway in coupling chronic pain with depression and highlights the activity-dependent contribution of LHbGlu-to-VTADA inhibition in depressive behavioral regulation.

关键词： chronic pain depression lateral habenula ventral tegmental area dopamine susceptibility

Characterization of a pangolin SARS-CoV-2-related virus isolate that uses the human ACE2 receptor

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Science china(life sciences) 2024年第7期67卷 1502-1513页

作者： Luo-Yuan Xia Xue-feng Wang Xiao-Ming Cui Yi-Ming Zhang Zhen-Fei Wang En-Tao li Chang-Fa Fan Ke Song Yuan-Guo li Run-Ze Ye Fang-Xu li Dai-Yun Zhu Jie Zhang Zhuang-Zhuang Shi Ming-Zhu Zhang liang-Jing li Shi-Jing Shen Song Jin Ya-Wei Zhang Wei-Guang Fu lin Zhao Wen-Hao Wang Tie-cheng Wang You-Chun Wang Jia-Fu Jiang yan-ling Hu Na Jia Yu-Wei Gao Wu-Chun Cao Institute of EcoHealth School of Public HealthCheeloo College of MedicineShandong UniversityJinan 250012China Changchun Veterinary Research Institute Changchun 130122China State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and EpidemiologyBeijing 100071China Division of Animal Model Research Institute for Laboratory Animal ResourcesNational Institutes for Food and Drug ControlBeijing 102629China National Institutes for Food and Drug Control Beijing 102629China life sciences Institute Guangxi Medical UniversityNanning 530020China College of life sciences Shandong Normal UniversityJinan 250014China Research Unit of Discovery and Tracing of Natural Focus Diseases Chinese Academy of Medical SciencesBeijing 100071China

Various SARS-CoV-2-related coronaviruses have been increasingly identified in pangolins,showing a potential threat to *** we report the infectivity and pathogenicity of the SARS-CoV-2-related virus,PCoV-GX/P2V,which was isolated from a Malayan pangolin(Manis javanica).PCoV-GX/P2V could grow in human hepatoma,colorectal adenocarcinoma cells,and human primary nasal epithelial *** replicated more efficiently in cells expressing human angiotensin-converting enzyme 2(hACE2)as SARS-CoV-2 *** intranasal inoculation to the hACE2-transgenic mice,PCoV-GX/P2V not only replicated in nasal turbinate and lungs,but also caused interstitial pneumonia,characterized by infiltration of mixed inflammatory cells and multifocal alveolar *** population immunity established by SARS-CoV-2 infection and vaccination may not protect people from PCoV-GX/P2V *** findings further verify the hACE2 utility of PCoV-GX/P2V by in vivo experiments using authentic viruses and highlight the importance for intensive surveillance to prevent possible cross-species transmission.

关键词： pangolin SARS-CoV-2-related virus infectivity pathogenicity human cell lines human ACE2 receptor hACE2-transgenic mice

Wearable and interactive multicolored photochromic fiber display

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light(Science & Applications) 2024年第3期13卷 454-465页

作者： Pan li Yuwei Wang Xiaoxian He Yuyang Cui Jingyu Ouyang Ju Ouyang Zicheng He Jiayu Hu Xiaojuan liu Hang Wei Yu Wang Xiaoling Lu Qian Ji xinyuan Cai li liu Chong Hou Ning Zhou Shaowu Pan Xiangru Wang Huamin Zhou cheng-Wei Qiu yan-Qing Lu Guangming Tao State Key Laboratory of Material Processing and Die&Mould Technology School of Materials Science and Engineering and Wuhan National Laboratory for OptoelectronicsHuazhong University of Science and TechnologyWuhan 430074China Key Laboratory of Vascular Aging(HUST) Ministry of EducationWuhan 430030China school of Optoelectronic Science and Engineering University of Electronic Science and Technology of ChinaChengdu 611731China Department of Electrical and Computer Engineering National University of SingaporeSingapore 117583Singapore National Laboratory of Solid State Microstructures Key Laboratory of Intelligent Optical Sensing and ManipulationCollege of Engineering and Applied Sciencesand Collaborative Innovation Center of Advanced MicrostructuresNanjing UniversityNanjing 210023China school of Performing Arts Wuhan Conservatory of MusicWuhan 430060China school of Mechanical Science and Engineering Huazhong University of Science and TechnologyWuhan 430074China school of Architecture and Urban Planning Huazhong University of Science and TechnologyWuhan 430074China school of Fashion Beijing Institute of Fashion TechnologyBeijing 100029China school of Optical and Electronic Information Huazhong University of Science and TechnologyWuhan 430074China Tongji Medical College Huazhong University of Science and TechnologyWuhan 430074China State Key Laboratory for Modification of Chemical Fibers and Polymer Materials College of Materials Science and EngineeringDonghua UniversityShanghai 201620China

Endowing flexible and adaptable fiber devices with light-emitting capabilities has the potential to revolutionize the current design philosophy of intelligent,wearable interactive ***,significant challenges remain in developing fiber devices when it comes to achieving uniform and customizable light effects while utilizing lightweight ***,we introduce a mass-produced,wearable,and interactive photochromic fiber that provides uniform multicolored light *** designed independent waveguides inside the fiber to maintain total internal reflection of light as it traverses the *** impact of excessive light leakage on the overall illuminance can be reduced by utilizing the saturable absorption effect of fluorescent materials to ensure light emission uniformity along the transmission *** addition,we coupled various fluorescent composite materials inside the fiber to achieve artificially controllable spectral radiation of multiple color systems in a single *** prepared fibers on mass-produced kilometer-long using the thermal drawing *** fibers can be directly integrated into daily wearable devices or clothing in various patterns and combined with other signal input components to control and display patterns as *** work provides a new perspective and inspiration to the existing field of fiber display interaction,paving the way for future human–machine integration.

关键词： fiber interactive colored