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Tubeimoside-1 induces TFEB-dependent lysosomal degradation of PD-L1 and promotes antitumor immunity by targeting mTOR

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Acta Pharmaceutica Sinica B 2021年第10期11卷 3134-3149页

作者： Xiaojia Liu Mingxiao Yin Jingwen Dong Genxiang Mao Wenjian Min Zean Kuang Peng Yang Lu Liu Na zhang Hongbin Deng Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Zhejiang Provincial Key Lab of Geriatrics Department of GeriatricsZhejiang HospitalHangzhou 310013China State Key laboratory of Natural Medicines and jiang Su Key laboratory of Drug Design and Optimization China Pharmaceutical UniversityNanjing 210009China Qingdao Women and Children’s Hospital Qingdao UniversityQingdao 266034China

Programmed cell death ligand 1(PD-L1)/programmed cell death protein 1(PD-1)cascade is an effective therapeutic target for immune checkpoint blockade(ICB)*** PD-L1/PD-1 axis by small-molecule drug is an attractive approach to enhance antitumor *** flow cytometry-based assay,we identify tubeimoside-1(TBM-1)as a promising antitumor immune modulator that negatively regulates PD-L1 ***-1 disrupts PD-1/PD-L1 interaction and enhances the cytotoxicity of T cells toward cancer cells through decreasing the abundance of ***,TBM-1 exerts its antitumor effect in mice bearing Lewis lung carcinoma(LLC)and B16 melanoma tumor xenograft via activating tumor-infiltrating T-cell ***,TBM-1 triggers PD-L1 lysosomal degradation in a TFEB-dependent,autophagy-independent ***-1 selectively binds to the mammalian target of rapamycin(m TOR)kinase and suppresses the activation of m TORC1,leading to the nuclear translocation of TFEB and lysosome ***,the combination of TBM-1 and anti-CTLA-4 effectively enhances antitumor T-cell immunity and reduces immunosuppressive infiltration of myeloid-derived suppressor cells(MDSCs)and regulatory T(Treg)*** findings reveal a previously unrecognized antitumor mechanism of TBM-1 and represent an alternative ICB therapeutic strategy to enhance the efficacy of cancer immunotherapy.

关键词： PD-L1 Immune checkpoint blockade Transcription factor EB Lysosome mTOR

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Einstein Probe discovery of EP240408a: A peculiar X-ray transient with an intermediate timescale

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 222-240页

作者： Wenda zhang Weimin Yuan Zhixing Ling Yong Chen Nanda Rea Arne Rau Zhiming Cai Huaqing Cheng Francesco Coti Zelati Lixin Dai Jingwei Hu Shumei Jia Chichuan Jin Dongyue Li Paul O’Brien Rongfeng Shen Xinwen Shu Shengli Sun Xiaojin Sun Xiaofeng Wang Lei Yang Bing zhang Chen zhang Shuang-Nan zhang Yonghe zhang Jie An David Buckley Alexis Coleiro Bertrand Cordier Liming Dou Rob Eyles-Ferris Zhou Fan Hua Feng Shaoyu Fu Johan P.U.Fynbo Lluis Galbany Saurabh W.Jha Shuaiqing jiang Albert Kong Erik Kuulkers Weihua Lei Wenxiong Li Bifang Liu Mingjun Liu Xing Liu Yuan Liu Zhu Liu Chandreyee Maitra Alessio Marino Itumeleng Monageng Kirpal Nandra Jeremy Sanders Roberto Soria Lian Tao Junfeng Wang Song Wang Tinggui Wang Zhongxiang Wang Qingwen Wu Xuefeng Wu Dong Xu Yanjun Xu Suijian Xue Yongquan Xue Zijian zhang Zipei Zhu Hu Zou Congying Bao Fansheng Chen Houlei Chen Tianxiang Chen Wei Chen Yehai Chen Yifan Chen Chenzhou Cui Weiwei Cui Yanfeng Dai Dongwei Fan Ju Guan Dawei Han Dongjie Hou Haibo Hu Maohai Huang Jia Huo Zhenqing Jia Bowen jiang Ge Jin Chengkui Li Junfei Li Longhui Li Maoshun Li Wei Li Zhengda Li Tianying Lian Congzhan Liu Heyang Liu Huaqiu Liu Fangjun Lu Laidan Luo Jia Ma Xuan Mao Haiwu Pan Xin Pan Liming Song Hui Sun Yunyin Tan Qingjun Tang Yihan Tao Hao Wang Juan Wang Lei Wang Wenxin Wang Yilong Wang Yusa Wang Qinyu Wu Haitao Xu Jingjing Xu Xinpeng Xu Yunfei Xu Zhao Xu Changbin Xue Yulong Xue Ailiang Yan Haonan Yang Xiongtao Yang Yanji Yang Juan zhang Mo zhang Wenjie zhang Zhen zhang Zhen zhang Ziliang zhang Donghua Zhao Haisheng Zhao Xiaofan Zhao Zijian Zhao Hongyan Zhou Yilin Zhou Yuxuan Zhu Zhencai Zhu National Astronomical Observatories Chinese Academy of Sciences School of Astronomy and Space Sciences University of Chinese Academy of Sciences Key laboratory of Particle Astrophysics Institute of High Energy Physics Chinese Academy of Sciences Institute of Space Sciences (ICE) CSIC Institut d’Estudis Espacials de Catalunya (IEEC) Max Planck Institute for Extraterrestrial Physics Innovation Academy for Microsatellites Chinese Academy of Sciences Department of Physics University of Hong Kong School of Physics and Astronomy University of Leicester School of Physics and Astronomy Sun Yat-sen University Department of Physics Anhui Normal University Shanghai Institute of Technical Physics Chinese Academy of Sciences Physics Department Tsinghua University Nevada Center for Astrophysics University of Nevada Las Vegas Department of Physics and Astronomy University of Nevada Las Vegas South African Astronomical Observatory Department of Astronomy University of Cape Town Department of Physics University of the Free State Université Paris Cité CNRS Astroparticule et Cosmologie Université Paris Cité CEA Paris-Saclay IRFU/DAp-AIM Department of Astronomy Guangzhou University Cosmic Dawn Center (DAWN) Niels Bohr Institute University of Copenhagen Department of Physics and Astronomy Rutgers the State University of New Jersey Institute for Cosmic Ray Research The University of Tokyo ESA/ESTEC Department of Astronomy School of Physics Huazhong University of Science and Technology INAF-Osservatorio Astrofisico di Torino Sydney Institute for Astronomy School of Physics The University of Sydney Department of Astronomy Xiamen University Institute for Frontiers in Astronomy and Astrophysics Beijing Normal University Department of Astronomy University of Science and Technology School of Astronomy and Space Sciences University of Science and Technology of China Institute of Deep Space Sciences Deep Space Exploration laboratory Department of Astronomy School of Physics and Astronomy Yunnan University Shanghai Astronomical Observatory Chi

We report the discovery of a peculiar X-ray transient,EP240408a,by Einstein Probe （EP） and follow-up studies made with EP,Swift,NICER,GROND,ATCA and other ground-based multiwavelength *** new transient was first detected with Wide-field X-ray Telescope （WXT） on board EP on April 8th,2024,manifested in an intense yet brief X-ray flare lasting for *** flare reached a peak flux of 3.9×10-9erg cm-2s-1in 0.5-4 ke V,～300 times brighter than the underlying X-ray emission detected throughout the *** and more precise follow-up observations by EP/FXT,Swift and NICER confirmed the finding of this new *** X-ray spectrum is non-thermal in 0.5-10 ke V,with a power-law photon index varying *** X-ray light curve shows a plateau lasting for ～4 d,followed by a steep decay till becoming undetectable ～10 d after the initial *** on its temporal property and constraints from previous EP observations,an unusual timescale in the range of 7-23 d is found for EP240408a,which is intermediate between the commonly found fast and long-term *** counterparts have been found in optical and near-infrared,with the earliest observation at 17 h after the initial X-ray detection,suggestive of intrinsically weak emission in these *** demonstrate that the remarkable properties of EP240408a are inconsistent with any of the transient types known so far,by comparison with,in particular,jetted tidal disruption events,gamma-ray bursts,X-ray binaries and fast blue optical *** nature of EP240408a thus remains an *** suggest that EP240408a may represent a new type of transients with intermediate timescales of the order of～10 *** detection and follow-ups of more of such objects are essential for revealing their origin.

关键词： X-ray transients ${\bm~{Einstein~~Probe}}$

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Further New Highly Oxidative Cembranoids from the Hainan Soft Coral Sarcophyton trocheliophorum

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Natural Products and Bioprospecting 2016年第2期6卷 97-102页

作者： Wen-Ting Chen Lin-Fu Liang Xu-Wen Li Wei Xiao Yue-Wei Guo State Key laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of Sciences555 Zu Chong Zhi RoadZhang Jiang High-Tech ParkShanghai 201203People’s Republic of China College of Material Science and Engineering Central South University of Forestry and Technology498 South Shaoshan RoadChangsha 410004People’s Republic of China jiangsu Kanion Pharmaceutical Co. Ltd.Lianyungang 222001People’s Republic of China

Three new highly oxidative cembranoids,sarcophytrols D-F(1-3),were obtained from the South China Sea soft coral Sarcophyton trocheliophorum,along with two known related ones(4 and 5).Their structures were elucidated by extensive spectroscopic analyses and by comparison with literature *** discovery of these new secondary metabolites enriched the family of cembranoids deduced from the title animal.

关键词： Soft coral Sarcophyton trocheliophorum Cembranoids Sarcophytrol Structure elucidation

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A chemophotothermal and targeting multifunctional nanoprobe with a tumor-diagnosing ability

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Nano Research 2018年第8期11卷 4333-4347页

作者： Niannian Li Jiejun Cheng Ying zhang Jie Wang Gang Huang Jun Zhu Dannong He School of Materials Science and Engineerinq Shanqhai Jiao Tona University 800 Donachuan Road. Shanahai 2130240 Chinn Department of Radiology Renji Hospital School of Medicine Sh-anghai Jiao Tong University Shanghai200127 China Shanghai University of Medicine & Health Sciences 2 79 Zhou Zhu highway Shanghai 201318 China National Engineering Research Center for Nanotechnology 28 East Jiang Chuan Road Shanghai20024 I China Niannian Li Jiejun Cheng and Ying Zhang contributed equally to this work.

The development of multifunctional nanoparticles for diagnosis and therapy of cancer has been a focus of research in recent years. Owing to excellent properties of chemophotothermal therapy and tumor targeting accompanied by magnetic resonance （MR） or computed tomography （CT） imaging, mesoporous silica has been widely applied to tumor diagnosing carriers. However, previous research focused more on chemotherapy combined with photothermal therapeutic strategies but ignored intuitive assessment of tumors. In this work, we report a novel nanoprobe consisKng of hyaluronic-acid-modified gold nanorods@mSiO2@Mn@DOX （GNR@MMH@DOX） nanoparticles, which realize multifunctional integration of therapeutics and imaging. Au nanorods （GNRs） were synthesized without a seed precursor by a water bath method, then sequentially modified with mesoporous silica, doped with Mn2＋, and loaded with doxorubicin in a solution. In vitro and in vivo assays verified their great biocompatibility, good stability, and attractive specificity of targeting to receptor CD44, which is overexpressed on cancer cells. In addition, GNR@MMH nanoparticles proved to be a more distinguishable CT/MR imaging contrast compared to commercial contrast agents. The article demonstrates promising composition for CT/MR imaging and photothermal therapy of tumors, giving new insights into the diagnosis and therapy of different kinds of malignant tumors.

关键词： gold nanorods Mn doping magnetic resonance orcomputed tomography(MR/CT) imaging chemophotothermaltherapy

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Universally composable anonymous password authenticated key exchange

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Science China(Information Sciences) 2017年第5期60卷 153-168页

作者： Xuexian HU jiang zhang Zhenfeng zhang Jing XU Trusted Computing and Information Assurance laboratory Institute of SoftwareChinese Academy of Sciences State Key laboratory of Mathematical Engineering and Advanced Computing Science and Technology on Information Assurance laboratory State Key laboratory of Cryptology

Anonymous password authenticated key exchange(APAKE) is an important cryptographic primitive, through which a client holding a password can establish a session key with a server both authentically and anonymously. Although the server is guaranteed that the client in communication is from a pre-determined group, but the client’s actual identity is protected. Because of their convenience, APAKE protocols have been widely studied and applied to the privacy protection research. However, all existing APAKE protocols are handled in stand-alone models and do not adequately settle the problem of protocol composition, which is a practical issue for protocol implementation. In this paper, we overcome this issue by formulating and realizing an ideal functionality for APAKE within the well-known universal composability(UC) framework, which thus guarantees security under the protocol composition operations. Our formulation captures the essential security requirements of APAKE such as off-line dictionary attack resistance, client anonymity and explicit mutual authentication. Moreover, it addresses the arbitrary probabilistic distribution of passwords. The construction of our protocol, which utilizes SPHF-friendly commitments and CCA2-secure encryption schemes, can be instantiated and proven secure in the standard model, i.e., without random oracle heuristics.

关键词： anonymous password authentication key exchange universal composability provable security standard model

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Enhancing long-term stability of bio-photoelectrochemical cell by defect engineering of a WO_(3-x) photoanode

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Journal of Energy Chemistry 2023年第5期80卷 584-593,I0013页

作者： Cheng zhang Xuchao Zheng Yongyue Ning Zihan Li Zhongdong Wu Xiaoyu Feng Gangyong Li Zhongyuan Huang Zongqian Hu College of Textiles and Clothing Xin Jiang UniversityUrumqi 830046XinjiangChina Beijing Institute of Radiation Medicine Beijing 100850China State Key laboratory for Chemo/Biosensing and Chemometrics College of Chemistry and Chemical EngineeringHunan UniversityChangsha 410082HunanChina Department of Chemistry Northeast Normal UniversityChangchun 130024JilinChina Key laboratory of Polyoxometalate and Reticular Material Chemistry of Ministry of Education National&Local United Engineering Laboratory for Power BatteriesKey Laboratory of Nanobiosensing and Nanobioanalysis at Universities of Jilin ProvinceAnalysis and Testing CenterDepartment of ChemistryNortheast Normal UniversityChangchun 130024JilinChina Shanghai Key laboratory of Green Chemistry and Chemical Processes School of Chemistry and Molecular EngineeringEast China Normal UniversityShanghai 200241China Key laboratory of Hunan Province for Advanced Carbon-based Functional Materials School of Chemistry and Chemical EngineeringHunan Institute of Science and TechnologyYueyang 414006HunanChina

Bio-photoelectrochemical cells(BPECs)can further expand the use of conventional biofuel cells for renewable energy,but the poor stability of the photoelectrode still hinders their practical ***,a BPEC capable of long-term operating in a fuel-free model is fabricated by WO3-xphotoanode with oxygen vacancy(Ov)and bilirubin oxidase catalyzed *** construction of Ov on the WO3surface significantly suppresses the dissolution of W species into the electrolyte,and improves the charge separation efficiency and the reaction kinetics during the photoelectrochemical oxygen evolution process,thus enhancing the stability and power output performance of the *** a result,the assembled BPEC can output an open circuit voltage of 0.81 V and deliver a maximum output power of up to 283μW cm^(-2).Impressively,the BPECs maintain 97%of their original power after 36000 s of consecutive discharge under an enclosed *** fuel-free BPEC based on a robust WO3-xphotoanode shows excellent promise for accurate application.

关键词： WO_(3) Oxygen vacancy Oxygen reduction reaction Fuel-free Bio-photoelectrochemical cell

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A systematic survey of PRMT interactomes reveals the key roles of arginine methylation in the global control of RNA splicing and translation

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Science Bulletin 2021年第13期66卷 1342-1357,M0004页

作者： Huan-Huan Wei Xiao-Juan Fan Yue Hu Xiao-Xu Tian Meng Guo Miao-Wei Mao Zhao-Yuan Fang Ping Wu Shuai-Xin Gao Chao Peng Yun Yang Zefeng Wang CAS Key laboratory of Computational Biology Bio-Med Big Data CenterShanghai Institute of Nutrition and HealthCAS Center for Excellence in Molecular Cell ScienceUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China National Facility for Protein Science in Shanghai Zhang-Jiang LabShanghai Advanced Research InstituteChinese Academy of SciencesShanghai 201210China Xijing Hospital of Digestive Diseases Fourth Military Medical UniversityXi’an 710000China

Thousands of proteins undergo arginine methylation,a widespread post-translational modification catalyzed by several protein arginine methyltransferases(PRMTs).However,global understanding of their biological functions is limited due to the lack of a complete picture of the catalytic network for each ***,we systematically identified interacting proteins for all human PRMTs and demonstrated their functional importance in mRNA splicing and *** demonstrated significant overlapping of interactomes of human PRMTs with the known methylarginine-containing *** PRMTs are functionally redundant with a high degree of overlap in their substrates and high similarities between their putative methylation ***,RNA-binding proteins involved in regulating RNA splicing and translation contain highly enriched arginine methylation ***,inhibition of PRMTs globally alternates alternative splicing(AS)and suppresses *** particular,ribosomal proteins are extensively modified with methylarginine,and mutations in their methylation sites suppress ribosome assembly,translation,and eventually cell ***,our study provides a global view of different PRMT networks and uncovers critical functions of arginine methylation in regulating mRNA splicing and translation.

关键词： Post-translational modification Protein arginine methyltransferase RNA-binding protein Ribosomal proteins Alternative splicing mRNA translation

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Spectroscopic and electrochemical studies on molecular recognition of tetrathiafulvalene derivative with P-glycoprotein and drug-resistant leukemia cells

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Science China Chemistry 2015年第7期58卷 1193-1199页

作者： Yuanyuan zhang Changyu Wu Hui jiang Jinglin Zuo Xuemei Wang State Key laboratory of Bioelectronics (Chien-Shiung Wu laboratory) Southeast University State Key laboratory of Coordination Chemistry School of Chemistry and Chemical Engineering Nanjing University

Cancer is still one of the important diseases that threatens the health of people. Multidrug resistance(MDR) is the main factor that leads to the failure of cancer chemotherapy. Thus, MDR diagnosis could facilitate the monitoring of the therapy process and realization of efficient treatment of tumors. In this study, we have tried to use a new tetrathiafulvalene(TTF) derivative(TTF-(COONBu4)2) to sensitively recognize the MDR through the multi-signal responsive strategy. The relevant electrochemical and spectroscopic studies demonstrate the specific binding behavior of TTF-(COONBu4)2 with P-glycoprotein(P-gp) as well as drug-resistant leukemia cells. Especially due to the over-expression of specific components of P-gp on the plasma membranes of drug resistant cells, the electrochemical and hydrophilic/hydrophobic features of drug resistant-leukemia cells are apparently different from those of other kinds of leukemia cells. Meanwhile, Fourier transform infrared spectroscopic study illustrates that the most intense vibration band of TTF moieties in the 1400–1600 cm-1 range is almost smeared out upon binding to P-gp, and the binding of TTF-(COONBu4)2 to P-gp may also lead to changes in protein secondary structure and backbone. This observation may advance the development of the new TTF agent for the promising clinical diagnosis and monitoring of MDR of tumors with the aim of successful chemotherapy for human cancer.

关键词： tetrathiafulvalene derivative leukemia cell P-glycoprotein electrochemical detection Fourier transform infraredspectroscopy

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Effects of NO_(2) and SO_(2) on the secondary organic aerosol formation fromβ-pinene photooxidation

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Journal of Environmental Sciences 2024年第2期136卷 151-160页

作者： Xiangyu Zang Zhaoyan zhang Yingqi Zhao Gang Li Hua Xie Weiqing zhang Guorong Wu Xueming Yang Ling jiang zhang Dayu School of Chemistry Dalian University of TechnologyDalian 116024China State Key laboratory of Molecular Reaction Dynamics Dalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023China University of Chinese Academy of Sciences Beijing 100049China Department of Chemistry School of ScienceSouthern University of Science and TechnologyShenzhen 518055China

Elucidating the effects of anthropogenic pollutants on the photooxidation of biogenic volatile organic compounds is crucial to understanding the fundamental mechanisms of secondary organic aerosol(SOA)***,the impacts of NO_(2)and SO_(2)on SOA formation from the photooxidation of a representative monoterpene,β-pinene,were investigated by a number of laboratory *** results indicated NO_(2)enhanced the SOA mass concentrations and particle number concentrations under both low and highβ-pinene *** could be rationalized that the increased O_(3)concentrations upon the NO_(x)photolysis was helpful for the generation of more amounts of O_(3)-oxidized products,which accelerated the SOA nucleation and *** with NO_(2),the promotion of the SOA yield by SO_(2)was mainly reflected in the increase of mass concentration,which might be due to the elimination of the newly formed particles by the initially formed *** observed low oxidation degree of SOA might be attributed to the fast growth of SOA,resulting in the uptake of less oxygenated gas-phase species onto the particle *** present findings have important implications for SOA formation affected by anthropogenic–biogenic interactions in the ambient atmosphere.

关键词： Secondary organic aerosol Volatile organic compound Anthropogenic pollutant Beta-pinene Photooxidation

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The m^(6)A regulator KIAA1429 stabilizes RAB27B mRNA and promotes the progression of chronic myeloid leukemia and resistance to targeted therapy

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Genes & Diseases 2024年第2期11卷 993-1008页

作者： Fangyi Yao Fangmin Zhong Junyao jiang Ying Cheng Shuai Xu Jing Liu Jin Lin Jing zhang Shuqi Li Meiyong Li Yanmei Xu Bo Huang Xiaozhong Wang jiangxi Province Key laboratory of laboratory Medicine Jiangxi Provincial Clinical Research Center for Laboratory MedicineDepartment of Clinical LaboratoryThe Second Affiliated Hospital of Nanchang UniversityNanchangJiangxi 330006China

Chronic myeloid leukemia(CML)is a common adult *** the acute phase of the disease and the adverse effects of anti-cancer treatments can lead to a poor *** N6-methyladenine(m^(6)A)modification plays an important regulatory role in various physiological and pathological ***1429 is a known m^(6)A regulator,but the biological role of KIAA1429 in CML is *** this study,we observed that the m^(6)A levels and KIAA1429 expression were significantly up-regulated in patients with blast phase ***,KIAA1429 regulated the total level of RNA m^(6)A modification in the CML cells and promoted the malignant biological behaviors of CML cells,including proliferation,migration,and imatinib *** KIAA1429 in CML cells reduced the stability of RAB27B mRNA through the m^(6)A/YTHDF1 axis,consequently inhibiting CML proliferation and drug efflux,ultimately increasing the sensitivity of CML cells to ***,the knockdown of RAB27B also inhibited the proliferation and drug resistance of CML cells and promoted their ***,a recently developed anti-cancer agent,suppressed the expression of KIAA1429 and CML cell proliferation and promoted cell *** also inhibited the tumorigenesis of CML cells in *** combined use of rucaparib and imatinib enhanced the sensitivity of CML cells to *** study provides evidence that elevated KIAA1429 expression in the blast phase of CML enhances the stability of RAB27B mRNA through the m^(6)A/YTHDF1 axis to up-regulate RAB27B expression,thereby promoting CML *** exerts inhibitory effects on KIAA1429 expression and thus reduces CML progression.

关键词： Chronic myeloid leukemia KIAA1429 N6-methyladenine RAB27B Rucaparib YTHDF1

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