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Targeting the CD146/Galectin-9 axis protects the integrity of the blood-brain barrier in experimental cerebral malaria

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Cellular & Molecular Immunology 2021年第10期18卷 2443-2454页

作者： Hongxia Duan Shuai Zhao jianquan xiang Chenhui Ju Xuehui Chen Irene Gramaglia Xiyun Yan Key Laboratory of Protein and Peptide Pharmaceutical Institute of BiophysicsChinese Academy of SciencesBeijing 100101China Laboratory of Biochemistry and Molecular Biology School of Basic Medical SciencesSouthwest Medical UniversityLuzhou 646000 SichuanChina La Jolla Infectious Disease Institute San DiegoCAUSA Joint Laboratory of Nanozymes in Zhengzhou University School of Basic Medical SciencesZhengzhou UniversityZhengzhou 450001 HenanChina

Cerebral malaria(CM)is a life-threatening diffuse encephalopathy caused by Plasmodium falciparum,in which the destruction of the blood–brain barrier(BBB)is the main cause of ***,increasing evidence has shown that antimalarial drugs,the current treatment for CM,do little to protect against CM-induced BBB ***,a means to alleviate BBB dysfunction would be a promising adjuvant therapy for *** adhesion molecule CD146 has been reported to be expressed in both endothelial cells and proinflammatory immune cells and mediates ***,we demonstrate that CD146 expressed on BBB endothelial cells but not immune cells is a novel therapeutic target in a mouse model of experimental cerebral malaria(eCM).Endothelial CD146 is upregulated during eCM development and facilitates the sequestration of infected red blood cells(RBCs)and/or proinflammatory lymphocytes in CNS blood vessels,thereby promoting the disruption of BBB *** studies showed that the interaction of CD146 and Galectin-9 contributes to the aggregation of infected RBCs and *** of endothelial CD146 or treatment with the anti-CD146 antibody AA98 prevents severe signs of eCM,such as limb paralysis,brain vascular leakage,and *** addition,AA98 combined with the antiparasitic drug artemether improved the cognition and memory of mice with *** together,our findings suggest that endothelial CD146 is a novel and promising target in combination with antiparasitic drugs for future CM therapies.

关键词： CD146 BBB experimental cerebral malaria

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A subpopulation of CD146^(+) macrophages enhances antitumor immunity by activating the NLRP3 inflammasome

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Cellular & Molecular Immunology 2023年第8期20卷 908-923页

作者： Lin Jing Yunhe An Tanxi Cai jianquan xiang Baoming Li Jiang Guo Xinran Ma Ling Wei Yanjie Tian Xiaoyan Cheng Xuehui Chen Zheng Liu Jing Feng Fuquan Yang Xiyun Yan Hongxia Duan Key Laboratory of Protein and Peptide Pharmaceutical Institute of BiophysicsChinese Academy of SciencesBejing 100101China Institute of Analysis and Testing Beijing Academy of Science and Technology(Bejing Center for Physical and Chemical Analysis)No.7 Fengxian Middle StreetHaidian DistrictBeijing 100094China Sino-Danish College University of Chinese Academy of SciencesBeijing100049China Laboratory of Proteomics Institute of BiophysicsChinese Academy of SciencesBeijingChina College of Life Sciences University of Chinese Academy of SciencesBeijing100049China Department of Interventional Oncology Beijing Ditan HospitalCapital Medical UniversityNo.8 Jingshun East StreetChaoyang DistrictBeijing100015China Joint Laboratory of Nanozymes in Zhengzhou University School of Basic Medical SciencesZhengzhou UniversityZhengzhou450001China

As one of the main tumor-infiltrating immune cell types, tumor-associated macrophages (TAMs) determine the efficacy of immunotherapy. However, limited knowledge about their phenotypically and functionally heterogeneous nature restricts their application in tumor immunotherapy. In this study, we identified a subpopulation of CD146+ TAMs that exerted antitumor activity in both human samples and animal models. CD146 expression in TAMs was negatively controlled by STAT3 signaling. Reducing this population of TAMs promoted tumor development by facilitating myeloid-derived suppressor cell recruitment via activation of JNK signaling. Interestingly, CD146 was involved in the NLRP3 inflammasome-mediated activation of macrophages in the tumor microenvironment, partially by inhibiting transmembrane protein 176B (TMEM176B), an immunoregulatory cation channel. Treatment with a TMEM176B inhibitor enhanced the antitumor activity of CD146+ TAMs. These data reveal a crucial antitumor role of CD146+ TAMs and highlight the promising immunotherapeutic approach of inhibiting CD146 and TMEM176B.

关键词： Tumor-associated macrophages CD146 Inflammasome TMEM176B Tumor immunotherapy

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Tectonic modes of mantle convection and their implications for Earth's tectonic evolution based on three-dimensional numerical simulations

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Science China Earth Sciences 2025年第1期68卷 270-296页

作者： Song xiang Jinshui HUANG Bingcheng WU School of Earth and Space Sciences University of Science and Technology of China CAS Center of Excellence in Comparative Planetary Studies

Five tectonic modes of mantle convection are obtained and analyzed with three-dimensional numerical models in a spherical shell domain. The five tectonic convective modes are non-plate mobile-lid, plate-like mobile-lid, episodic plate-like mobile-lid, episodic stagnant-lid, and stagnant-lid convective modes, respectively. The typical characteristics of these five tectonic modes and their numerical classification criteria based on plateness, mobility, and their standard deviations are presented and discussed. The results show that the yield stress of the lithosphere has profound effects on the tectonic convective *** the gradual increase of yield stress, the tectonic mode of mantle convection changes from one to another sequentially through the aforementioned five modes. Additionally, as the Rayleigh number increases, the range of yield stress for the platelike mobile-lid convective mode decreases, and the dimensionless transition stress between different tectonic modes ***, the dimensional transition stress between the non-plate mobile-lid convective mode and plate-like mobile-lid convective mode increases with the increase of Rayleigh number, but decreases between other tectonic modes. Furthermore, we find that the transition stress between different tectonic modes is inversely proportional to the internal heating rate, with the transition stress decreasing as the internal heating rate increases. The fitting analysis of the transition stress between tectonic modes shows that Earth's current plate tectonics correspond to a lithospheric yield stress of 150–250 MPa, which aligns with the strength of serpentinized mantle rock determined by experimental petrography. If the Archean mantle was 300°C warmer than it is today, then the Earth was in an episodic stagnant-lid convective mode. The tectonic evolution of the Earth's surface is closely related to the lithospheric strength and the process of thermal evolution. If the lithospheric strength w

关键词： Tectonic mode of mantle convection Plate-like mobile-lid convection Episodic plate-like mobile-lid convection Episodic stagnant-lid convection Plate tectonics and tectonic evolution of the Earth

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铁蛋白装载“铁-阿霉素”新策略

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中国科学：生命科学 2021年第7期51卷 871-878页

作者：向建全周彩玉张若飞曾凡才范克龙西南医科大学基础医学院生物化学与分子生物学教研室泸州646000 中国科学院生物物理研究所中国科学院纳米酶工程实验室北京100101

铁蛋白具备独特的笼状结构、自组装特性、内在的肿瘤靶向性、良好的生物相容性以及易于规模化生产等优势,是一种具有良好转化前景的纳米药物载体.目前,关于铁蛋白装载抗肿瘤药物阿霉素(doxorubicin,Dox)的研究较多,装载策略包括被动装... 详细信息

铁蛋白具备独特的笼状结构、自组装特性、内在的肿瘤靶向性、良好的生物相容性以及易于规模化生产等优势,是一种具有良好转化前景的纳米药物载体.目前,关于铁蛋白装载抗肿瘤药物阿霉素(doxorubicin,Dox)的研究较多,装载策略包括被动装载和主动内化两类,其中,预先螯合金属离子形成"金属-阿霉素"复合物以促进其主动进入铁蛋白内腔的装载方法具有装载量高、杀伤效应强等特点,然而,此类方法仍存在铁蛋白回收率低、蛋白完整性受损等缺陷.为此,本文结合温度孵育法,利用人重组重链铁蛋白(human heavy chain ferritin,human HFn)发展了一种基于铁离子的"金属-阿霉素"装载新策略,成功构建了"铁蛋白-铁-阿霉素"(HFn(Fe-Dox),HFeD)药物递送系统,该系统具有高装载量(80-100个/HFn)、高包封率(50%-63%)和高蛋白回收率(80%-90%)的特点.同时,该策略很好地保留了铁蛋白的结构完整性、肿瘤靶向性和药物释放可控性,因而保证了HFeD对肿瘤细胞的特异靶向和杀伤.该方法的报道有望增加HFeD成药的可能性,推动铁蛋白药物载体的发展与应用.

关键词：铁蛋白铁-阿霉素药物递送肿瘤

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Mitophagy in acute central nervous system injuries:regulatory mechanisms and therapeutic potentials

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Neural Regeneration Research 2025年第9期20卷 2437-2453页

作者： Siyi Xu Junqiu Jia Rui Mao xiang Cao Yun Xu Department of Neurology Nanjing Drum Tower HospitalClinical College of Jiangsu UniversityNanjingJiangsu ProvinceChina Department of Neurology Nanjing Drum Tower HospitalChinese Academy of Medical Science&Peking Union Medical CollegeNanjingJiangsu ProvinceChina Department of Neurology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsu ProvinceChina State Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical Diseases Nanjing UniversityNanjingJiangsu ProvinceChina Jiangsu Key Laboratory for Molecular Medicine Medical School of Nanjing UniversityNanjingJiangsu ProvinceChina Nanjing Neurology Medical Center NanjingJiangsu ProvinceChina

Acute central nervous system injuries,including ischemic stro ke,intracerebral hemorrhage,subarachnoid hemorrhage,traumatic brain injury,and spinal co rd injury,are a major global health *** optimal therapies and improving the long-term neurological functions of patients with acute central nervous system injuries are urgent *** are susceptible to damage after acute central nervous system injury,and this leads to the release of toxic levels of reactive oxygen species,which induce cell ***,a selective form of autophagy,is crucial in eliminating redundant or damaged mitochondria during these *** evidence has highlighted the significant role of mitophagy in acute central nervous system *** this review,we provide a comprehensive overview of the process,classification,and related mechanisms of *** also highlight the recent developments in research into the role of mitophagy in various acute central nervous system injuries and drug therapies that regulate *** the final section of this review,we emphasize the potential for treating these disorders by focusing on mitophagy and suggest future research paths in this area.

关键词： autophagy intracerebral hemorrhage ischemic stroke mitochondria mitochondrial biogenesis mitochondrial quality control mitophagy spinal cord injury subarachnoid hemorrhage traumatic brain injury

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Investigation of bubbles escape behavior from low basicity mold flux for high-Mn high-Al steels using 3D X-ray microscope

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International Journal of Minerals,Metallurgy and Materials 2025年第1期32卷 102-110页

作者： Qiang Liu xiang Li Shen Du Ming Gao Yanbin Yin Jiongming Zhang State Key Laboratory of Advanced Metallurgy University of Science and Technology BeijingBeijing 100083China

During the continuous casting process of high-Mn high-Al steels,various types of gases such as Ar need to escape through the top of the *** which,the behavior of bubbles traversing the liquid slag serves as a restrictive link,closely associated with viscosity and the thickness of liquid *** contrast to two-dimensional surface observation,three-dimensional(3D)analysis method can offer a more intuitive,accurate,and comprehensive ***,this study employs a 3D X-ray microscope(3D-XRM)to obtained spatial distribution and 3D morphological characteristics of residual bubbles in mold flux under different basicity of liquid slag,different temperatures,and different holding *** results indicate that as basicity of slag increases from 0.52 to 1.03,temperature increases from 1423 to 1573 K,the viscosity of slag decreases,the floating rate of bubbles *** addition,when holding time increases from 10 to 30 s,the bubbles floating distance increases,and the volume fraction and average equivalent sphere diameter of the bubbles solidified in the mold flux gradually *** one word,increasing the basicity,temperature,and holding time leading to an increase in the removal rate of bubbles especially for the *** findings of bubbles escape behavior provide valuable insights into optimizing low basicity mold flux for high-Mn high-Al steels.

关键词： mold flux low basicity bubbles three-dimensional X-ray microscope viscosity

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Laser image refractive index sensor based on the combination of a coreless optical fiber and a digital camera

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Optoelectronics Letters 2025年第2期21卷 65-68页

作者： GUO Jingzhong LAN Feng CHEN xiang LIU Haifeng Xi'an Institute of Space Radio Technology Key Laboratory of Optoelectronic Sensor and Sensing Network Technology College of Electronic Information and Optical Engineering Nankai University

As a laser passes through a scattering medium,the light interacts with the irregular reflections within the medium,resulting in light scattering and the formation of *** this paper,an image sensor based on the combination of a coreless optical fiber and a digital camera is proposed for liquid refractive index sensing *** coreless fiber is used as a sensing unit,and the change in the speckle pattern is measured using the digital correlation method to detect the magnitude of the liquid's refractive *** experimental results indicate that the laser image sensing technique is capable of effectively distinguishing liquid samples with refractive indices ranging from 1.332 8 to1.390 8,with a sensing sensitivity of-1.306 ***,the laser image sensing technique,with its advantages of high experimental reproducibility,simple system design,remote over-control,holds great research significance and potential application in laser communication and sensor integration.

关键词： Digital cameras

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Mainchain conformation ordering self-assembly tailored room temperature phosphorescence emission

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Science China Chemistry 2025年第1期68卷 329-336页

作者： Yuzhu Li Yumeng Gao Feng Tian Yu Wang Yuan Yao Shaoliang Lin xiang Ma Binbin Xu Shanghai Key Laboratory of Advanced Polymeric Materials Key Laboratory for Ultrafine Materials of Ministry of Education School of Materials Science and Engineering East China University of Science and Technology Shanghai Synchrotron Radiation Facility Shanghai Advanced Research Institute Chinese Academy of Sciences Key Laboratory for Advance Materials and Feringa Noble Prize Scientist Joint Research Centre Frontiers Science for Materiobiology and Dynamic Chemistry School of Chemistry and Molecular Engineering East China University of Science & Technology

Developing organic room-temperature phosphorescence （RTP） materials with a wide range of tunable-emission is significant in expanding the applications of RTP ***,we rationally designed amphiphilic alternating copolymers poly(1,2-bis（4-alkoxyphenyl）ethane-1,2-dione-alt-（ethylene glycol）x)(P（Bz-alt-EGx）) that combined the advantage of alternating benzil and EGxskeleton,and tunable mainchain *** a mainchain conformation ordering assembly （COA） process,P（Bz-alt-EGx） self-assembled into well-defined platelets,and such assemblies emitted blue RTP at ca.425 nm due to the ordered folded-chain conformation and confined *** contrast,traditional self-assembly （TA） of P（Bz-alt-EGx） obtained less ordered aggregates,such as asymmetric worms,vesicles,and rod-like *** resultant less ordered aggregates exhibited yellow-green RTP at ca.550 *** wide-tuning RTP emission in solution （between blue and yellow-green,over125 nm） is realized using the P（Bz-alt-EGx） alternating copolymers under the treatment of different self-assembly *** study uncovers a new strategy to tailor the RTP emission through different self-assembly pathways and holds great promise for the fabrication of advanced optical materials.

关键词： self-assembly conformation ordering alternating copolymer phosphorescence emission

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Decentralized fault diagnosis of discrete-event systems with unreliable sensors using linear temporal logic

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Science China(Information Sciences) 2025年第1期68卷 322-341页

作者： Weijie DONG Shaoyuan LI xiang YIN Key Laboratory of System Control and Information Processing Ministry of EducationDepartment of Automation Shanghai Jiao Tong University

In this paper,we investigate a decentralized diagnosis problem of a discrete-evnt system(DES) subject to unreliable sensors,where the sensor observations of local diagnosers may be non-deterministic as a result of possible *** studies on decentralized robust diagnosis can only deal with different types of sensor failures separately,e.g.,all sensors suffer from the same type of sensor failures such as intermittent sensor failures or permanent sensor ***,since sensors of different local diagnosers may face different external environments and have different internal characteristics,sensors corresponding to different local diagnosers may also have their own fault *** this paper,we propose a flexible framework of decentralized diagnosis for DES subject to unreliable sensors such that sensors of different local diagnosers are permitted to have different types of sensor *** this end,we extend the existing decentralized diagnosis framework to the case where there exist common sensors broadcasting their observations to all local *** apply linear temporal logic(LTL) to constrain infinite behaviors of private sensors of local diagnosers and common ***,a new notion of φ-codiagnosability is proposed as the necessary and sufficient condition for the existence of a decentralized diagnoser that works correctly under sensors,satisfying LTL-based sensor ***,we provide an effective approach to verify the φ-codiagnosability.

关键词： discrete event systems decentralized diagnosis codiagnosability automata

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AZD1775 synergizes with SLC7A11 inhibition to promote ferroptosis

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Science China Life Sciences 2025年第1期68卷 204-218页

作者： Chen Xiong Hong Ling Yingdan Huang Hanzhi Dong Bangxiang Xie Qian Hao xiang Zhou Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences Fudan University Department of Oncology Shanghai Medical CollegeFudan University Department of Breast Surgery Fudan University Shanghai Cancer CenterFudan University Department of Oncology First Affiliated Hospital of Nanchang University Beijing Institute of Hepatology Beijing Youan HospitalCapital Medical University Beijing Engineering Research Center for Precision Medicine and Transformation of Hepatitis and Liver Cancer Key Laboratory of Breast Cancer in Shanghai Fudan University Shanghai Cancer CenterFudan University Shanghai Key Laboratory of Medical Epigenetics International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology)Institutes of Biomedical SciencesFudan University

Tumor suppressor p53-mediated cell cycle arrest and DNA damage repair may exert cytoprotective effects against cancer therapies, including WEE1 inhibition. Considering that p53 activation can also lead to multiple types of cell death, the role of this tumor suppressor in WEE1 inhibitor-based therapies remains disputed. In this study, we reported that nucleolar stress-mediated p53 activation enhanced the WEE1 inhibitor AZD1775-induced ferroptosis to suppress lung cancer growth. Our findings showed that AZD1775 promoted ferroptosis by blocking cystine uptake, an action similar to that of Erastin. Meanwhile, inhibition of WEE1 by the WEE1 inhibitors or si RNAs induced compensatory upregulation of SLC7A11, which conferred resistance to ferroptosis. Mechanistically, AZD1775 prevented the enrichment of H3K9me3, a histone marker of transcriptional repression, on the SLC7A11 promoter by repressing the expression of the histone methyltransferase SETDB1, thereby enhancing NRF2-mediated SLC7A11 transcription. This finding was also validated using the H3K9me3 inhibitor BRD4770. Remarkably, we found that the nucleolar stress-inducing agent Actinomycin D(Act. D) inhibited SLC7A11 expression by activating p53, thus augmenting AZD1775-induced ferroptosis. Moreover, the combination of AZD1775 and Act. D synergistically suppressed wild-type p53-harboring lung cancer cell growth both in vitro and in vivo. Altogether, our study demonstrates that AZD1775 promotes ferroptosis by targeting cystine uptake but also mediates the adaptive activation of SLC7A11 through the WEE1-SETDB1 cascade and NRF2-induced transcription, and inhibition of SLC7A11 by Act. D boosts the anti-tumor efficacy of AZD1775 by enhancing ferroptosis in cancers with wild-type p53.

关键词： p53 NRF2 SLC7A11 WEE1 AZD1775 ferroptosis nucleolar stress

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