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Glioma-derived ANXA1 suppresses the immune response to TLR3 ligands by promoting an anti-inflammatory tumor microenvironment

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Cellular & Molecular Immunology 2024年第1期21卷 47-59页

作者： Yu Zheng Haihui Jiang Naixue Yang Shaoping Shen Daosheng Huang Lemei Jia Jing ling Longchen Xu mingxiao li Kefu Yu Xiaohui Ren Yong Cui Xun Lan Song lin Xin lin Institute for Immunology and School of Medicine Tsinghua UniversityBeijing100084China Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityChina.National Clinical Research Center for Neurological DiseasesCenter of Brain TumorBeijing Institute for Brain Disorders and Beijing Key Laboratory of Brain TumorBeijing100070China Department of Neurosurgery Peking University Third HospitalPeking UniversityBeijing100191China Tsinghua-Peking Center for life Sciences Beijing100084China

A highly immunosuppressive tumor microenvironment(TME)and the presence of the blood‒brain barrier are the two major obstacles to eliciting an effective immune response in patients with high-grade glioma(HGG).Here,we tried to enhance the local innate immune response in relapsed HGG by intracranially injecting poly(I:C)to establish a robust antitumor immune response in this registered clinical trial(NCT03392545).During the follow-up,12/27(44.4%)patients who achieved tumor control concomitant with survival benefit were regarded as responders in our study.We found that the T-cell receptor(TCR)repertoire in the TME was reshaped after poly(I:C)treatment.Based on the RNA-seq analysis of tumor samples,the expression of annexin A1(ANXA1)was significantly upregulated in the tumor cells of nonresponders,which was further validated at the protein level.In vitro and in vivo experiments showed that ANXA1 could induce the production of M2-like macrophages and microglia via its surface receptor formyl peptide receptor 1(FPR1)to establish a Treg cell-driven immunosuppressive TME and suppress the antitumor immune response facilitated by poly(I:C).The ANXA1/FPR1 signaling axis can inhibit the innate immune response of glioma patients by promoting an anti-inflammatory and Treg-driven TME.Moreover,ANXA1 could serve as a reliable predictor of response to poly(I:C),with a notable predictive accuracy rate of 92.3%.In light of these notable findings,this study unveils a new perspective of immunotherapy for gliomas.

关键词： glioma ANXA1 TLR3 poly(I:C) immunotherapy

Characterization of whole genomes from recently emerging Mpox cases in several regions of China,2023

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Science China(life Sciences) 2024年第5期67卷 1079-1081页

作者： Changcheng Wu Lunbiao Cui Yang Pan Ziquan Lv mingxiao Yao Wenling Wang Fei Ye Weibang Huo li Zhao Baoying Huang Fengcai Zhu Roujian Lu Yao Deng Quanyi Wang Wenjie Tan NHC Key Laboratory of Biosafety National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China NHC Key Laboratory of Enteric Pathogenic Microbiology Jiangsu Provincial Medical Key Laboratory of Pathogenic Microbiology in Emerging Major Infectious DiseasesJiangsu Provincial Center for Disease Control and PreventionNanjing 210009China Beijing Center for Disease Prevention and Control Beijing 100013China Central Laboratory Shenzhen Center for Disease Control and PreventionShenzhen 518055China Shandong Center for Disease Control and Prevention Jinan 250014China

Dear Editor,Mpox(formerly known as monkeypox)is a zoonotic disease caused by infection with the monkeypox virus(MPXV).Mpox cases have been sporadic over the past few decades,with outbreaks occurring in only a limited ... 详细信息

关键词： cases primarily imported

Practices and Empirical Insights from the National Research Program for Key Issues in Air Pollution in Beijing-Tianjin-Hebei and Surrounding Areas

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Engineering 2023年第11期30卷 20-26页

作者： Haisheng li Xiaolin Hou Jie Xue Tianfeng Guo Tiansen Zou Hefeng Zhang Xiang Guo mingxiao li Jiming Hao Chinese Research Academy of Environmental Sciences Beijing 100012China School of Environment Tsinghua UniversityBeijing 100084China

1.Introduction The United States began implementing policies against air pollution in earnest starting in the early 1970s,taking several decades and an economic recession to achieve reductions in air pollution.In cont... 详细信息

关键词： pollution pollution starting

3D spiral channels combined with flexible micro-sieve for high-throughput rare tumor cell enrichment and assay from clinical pleural effusion samples

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Bio-Design and Manufacturing 2022年第2期5卷 358-370页

作者： Jie Cheng lina Zhang Yiran Zhang Yifei Ye Wenjie Zhao lingqian Zhang Yuang li Yang liu Wenchang Zhang Hongyan Guo mingxiao li Yang Zhao Chengjun Huang Institute of Microelectronics Chinese Academy of SciencesBeijing 100029China School of Future Technology University of Chinese Academy of SciencesBeijing 100049China Department of Cellular and Molecular Biology Beijing Chest HospitalCapital Medical UniversityBeijing Tuberculosis and Thoracic Tumor Research InstituteBeijing 101149China National Engineering Research Center for Beijing Biochip Technology Beijing 102206China

The sieving and enrichment of rare tumor cells from large-volume pleural effusion(PE)samples is a promising technique for cell-based lung tumor diagnosis and drug tests,which features high throughput and recovery,purification,as well as viability rates of rare target cells as the prerequisites for high sensitivity,specificity,and accuracy of tumor cell analysis.In this paper,we propose a three-dimensional(3 D)sieving method for rare tumor cell enrichment,which effectively eliminates the"dead zones"in traditional two-dimensional(2 D)cell filters with a dimension-raising strategy to satisfy the requirements mentioned above.The prototype device was combined with a funnel-shaped holder,a flexible micropore membrane in the middle,and a3 D spiral fluid channel covered on the membrane as a three-layer ice-creaming cone composite structure.Driven by gravity alone,the device performed as follows:(1)20-fold throughput compared with the 2 D commercial planee hich was up to 20 mL/min for a threefold dilution of whole blood sample;(2)high recovery rates of 84.5%±21%,86%±25%,83%±14%for 100,1000,and 10000 cells/mL,respectively,in 30 mL phosphate buffer saline(PBS)sample,and a 100%positive detection rate in the case of≤5 A549 cells in 1 mL PBS;(3)a typical purification rate of 85.5%±9.1%;and(4)a viability rate of>93%.In the demonstration application,this device effectively enriched rare target cells from large volumes(>25 mL)of clinical pleural effusions.The following results indicated that tumor cells were easy-to-discover in the enriched PE samples,and the proliferation capability of purified cells was(>4.6 times)significantly stronger than that of unprocessed cells in the subsequent 6-day culture.The above evaluation indicates that the proposed easily reproducible method for the effective execution of rare cell enrichments and assays is expected to become a practical technique for clinical cell-based tumor diagnosis.

关键词： Cell enrichment High throughput Pleural effusion liquid biopsy 3D printing

Preliminary report of the September 5,2022 M_(S) 6.8 Luding earthquake,Sichuan,China

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Earthquake Research Advances 2023年第1期3卷 1-10页

作者： Yanru An Dun Wang Qiang Ma Yueren Xu Yu li Yingying Zhang Zhumei liu Chunmei Huang Jinrong Su Jilong li mingxiao li Wenkai Chen Zhifan Wan Dengjie Kang Baoshan Wang China Earthquake Networks Center Beijing 100045China Badong National Observation and Research Station of Geohazards School of Earth SciencesChina University of Geosciences(Wuhan)Wuhan 430074China Key Laboratory of Earthquake Engineering and Engineering Vibration Institute of Engineering MechanicsChina Earthquake AdministrationHarbin 150080China Institute of Earthquake Forecasting China Earthquake AdministrationBeijing 100036China Hubei Key Laboratory of Earthquake Early Warning Hubei Earthquake AgencyWuhan 430064China Sichuan Earthquake Agency Chengdu 610044China Lanzhou Institute of Seismology China Earthquake AdministrationLanzhou 730030China School of Earth and Space Sciences University of Science and Technology of ChinaHefei 230026China

The 2022 M_(S)6.8 Luding earthquake is the strongest earthquake in Sichuan Province, Western China, since the 2017 M_(S)7.0 Jiuzhaigou earthquake. It occurred on the Moxi fault in the southeastern segment of the Xianshuihe fault, a tectonically active and mountainous region with severe secondary earthquake disasters. To better understand the seismogenic mechanism and provide scientific support for future hazard mitigation, we summarize the preliminary results of the Luding earthquake, including seismotectonic background, seismicity and mainshock source characteristics and aftershock properties, and direct and secondary damage associated with the mainshock.The peak ground displacements in the NS and EW directions observed by the nearest GNSS station SCCM are ~35 mm and ~55 mm, respectively, resulting in the maximum coseismic dislocation of 20 mm along the NWW direction, which is consistent with the sinistral slip on the Xianshuihe fault. Back-projection of teleseismic P waves suggest that the mainshock rupture propagated toward south-southeast. The seismic intensity of the mainshock estimated from the back-projection results indicates a Mercalli scale of Ⅷ or above near the ruptured area,consistent with the results from instrumental measurements and field surveys. Numerous aftershocks were reported, with the largest being M_(S)4.5. Aftershock locations(up to September 18, 2022) exhibit 3 clusters spanning an area of 100 km long and 30 km wide. The magnitude and rate of aftershocks decreased as expected, and the depths became shallower with time. The mainshock and two aftershocks show left-lateral strike-slip focal mechanisms. For the aftershock sequence, the b-value from the Gutenberg-Richter frequency-magnitude relationship, h-value, and p-value for Omori’s law for aftershock decay are 0.81, 1.4, and 1.21, respectively, indicating that this is a typical mainshock-aftershock sequence. The low b-value implies high background stress in the hypocenter region. Analysis from remote sensing satellite images and UAV data

关键词： Luding earthquake Moxi fault Aftershock statistics Earthquake disasters Intensity map

From the teapot effect to tap-triggered self-wetting: a 3D self-driving sieve for whole blood filtration

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Microsystems & Nanoengineering 2023年第2期9卷 283-293页

作者： Yuang li Xue li lina Zhang Xiaofeng Luan Jiahong jiang lingqian Zhang mingxiao li Jinghui Wang Jiangang Duan Haiping Zhao Yang Zhao Chengjun Huang Institute of Microelectronics of the Chinese Academy of Sciences Bejing 100029China University of Chinese Academy of Sciences Beijing 100049China institute of Cerebrovascular Disease Research Xuanwu Hospital of Capital Medical UniversityBeijing 100053China Department of Cellular and Molecular Biology Bejing Chest HospitalCapital Medical University/Bejing Tuberculosis and Thoracic Tumor Research InstituteBeijing 101149China

Achieving passive microparticle filtration with micropore membranes is challenging due to the capillary pinning effect of the membranes.Inspired by the teapot effect that occurs when liquid(tea)is poured from a teapot spout,we proposed a tap-triggered self-wetting strategy and utilized the method with a 3D sieve to flter rare cells.First,a 3D-printed polymer tap-trigger microstructure was implemented.As a result,the 3μm micropore membrane gating threshold(the pressure needed to open the micropores)was lowered from above 3000 to 80 Pa by the tap-trigger microstructure that facilated the liquid leakage and spreading to self-wet more membrane area in a positive feedback loop.Then,we implemented a 3D cone-shaped cell sieve with tap-trigger microstructures.Driven by gravity,the sieve performed at a high throughput above 20 mL/min(DPBS),while the micropore size and porosity were 3μm and 14.1%,respectively.We further filtered leukocytes from whole blood samples with the proposed new 3D sieve,and the method was compared with the traditional method of leukocyte isolation by chemically removing red blood cells.The device exhibited comparable leukocyte purity but a higher platelet removal rate and lower leukocyte simulation level,facilitating downstream single-cell analysis.The key results indicated that the tap-triggered self-wetting strategy could significantly improve the performance of passive microparticle filtration.

关键词： effect removing filtered

Si nanowire Bio-FET for electrical and label-free detection of cancer cell-derived exosomes

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Microsystems & Nanoengineering 2022年第3期8卷 141-152页

作者： Wenjie Zhao Jiawei Hu Jinlong liu Xin li Sheng Sun Xiaofeng Luan Yang Zhao Shuhua Wei mingxiao li Qingzhu Zhang Chengjun Huang Institute of Micoelectronics Chinese Academy of SciencesBeijing 100029People's Republic of China School of Future Technology University of Chingse Academy of SciencesBeijing 100049People's Republic of China School of Information Science and Technology North China University of TechnologyBeijing 100144People's Republic of China

Exosomes are highly important in clinical diagnosis due to their high homology with their parental cells.However,conventional exosome detection methods still face the challenges of expensive equipment,low sensitivity,and complex procedures.Field effect transistors(FETs)are not only the most essential electronic component in the modern microelectronics industry but also show great potential for biomolecule detection owing to the advantages of rapid response,high sensitivity,and label-free detection.In this study,we proposed a Si nanowire field-effect transistor(Si-NW Bio-FET)device chemically modified with specific antibodies for the electrical and label-free detection of exosomes.The Si-NW FETs were fabricated by standard microelectronic processes with 45 nm width nanowires and packaged in a polydimethylsiloxane(PDMS)microfluidic channel.The nanowires were further modified with the specific CD63 antibody to form a Si-NW Bio-FET.The use of the developed Si-NW Bio-FET for the electrical and labelfree detection of exosomes was successfully demonstrated with a limit of detection(LOD)of 2159 particles/mL.In contrast to other technologies,in this study,Si-NW Bio-FET provides a unique strategy for directly quantifying and realtime detecting exosomes without labeling,indicating its potential as a tool for the early diagnosis of cancer.

关键词： diagnosis electrical free

基于Transformer的宫颈异常细胞自动识别方法

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中国激光 2024年第3期51卷 85-95页

作者：张峥陈明销李新宇程逸申书伟姚鹏中国科学技术大学工程科学学院精密机械与精密仪器系安徽合肥230027 中国科学技术大学苏州高等研究院江苏苏州215123 中国科学技术大学微电子学院安徽合肥230027

宫颈异常细胞与正常细胞在形态上存在较大相似性且细胞尺寸变化较大,这使得宫颈异常细胞的精准检测变得非常困难。鉴于此,开发了一种基于Transformer模型的宫颈异常细胞自动识别模型,以帮助病理学家作出更准确的诊断。提出了两种创新性... 详细信息

宫颈异常细胞与正常细胞在形态上存在较大相似性且细胞尺寸变化较大,这使得宫颈异常细胞的精准检测变得非常困难。鉴于此,开发了一种基于Transformer模型的宫颈异常细胞自动识别模型,以帮助病理学家作出更准确的诊断。提出了两种创新性方法,一是一种改进的Transformer编码器结构,通过引入深度(DW)卷积来高效获取图像的特征,捕捉图像中的全局依赖信息;二是自适应的动态交并比(IOU)阈值,在模型训练的不同阶段使用不同的IOU阈值,实现尽可能多的有效检测,提升模型的收敛速度和检测精度。在宫颈异常细胞数据集上,通过消融实验,证明了改进的Transformer编码器和动态IOU阈值的有效性。此外,与已有的宫颈异常细胞识别方法相比,所提出的方法在平均精度指标上有明显的提高。实验结果表明,所提出的方法能够高效且准确地识别宫颈异常细胞,且能辅助病理专家提高诊断准确率和效率,具有应用到临床的潜力。

关键词：医用光学宫颈细胞病理图像目标检测医学图像处理

piRT-IFC:Physics-informed real-time impedance flow cytometry for the characterization of cellular intrinsic electrical properties

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微系统与纳米工程(英文) 2023年第3期9卷 347-356页

作者： Xiaofeng Luan Pengbin liu Di Huang Haiping Zhao Yuang li Sheng Sun Wenchang Zhang lingqian Zhang mingxiao li Tian Zhi Yang Zhao Chengjun Huang Institute of Microelectronics of the Chinese Academy of Sciences BeijingChina University of Chinese Academy of Sciences BeijingChina State Key Laboratory of Computer Architecture Institute of Computing TechnologyChinese Academy of SciencesBeijingChina Cerebrovascular Diseases Research Institute Xuanwu Hospital of Capital Medical UniversityBeijingChina

Real-time transformation was important for the practical implementation of impedance flow cytometry.The major obstacle was the time-consuming step of translating raw data to cellular intrinsic electrical properties(e.g.,specific membrane capacitance C_(sm) and cytoplasm conductivityσ_(cyto)).Although optimization strategies such as neural network-aided strategies were recently reported to provide an impressive boost to the translation process,simultaneously achieving high speed,accuracy,and generalization capability is still challenging.To this end,we proposed a fast parallel physical fitting solver that could characterize single cells’C_(sm)andσ_(cyto)within 0.62 ms/cell without any data preacquisition or pretraining requirements.We achieved the 27000-fold acceleration without loss of accuracy compared with the traditional solver.Based on the solver,we implemented physics-informed real-time impedance flow cytometry(piRT-IFC),which was able to characterize up to 100,902 cells’C_(sm) andσ_(cyto)within 50 min in a real-time manner.Compared to the fully connected neural network(FCNN)predictor,the proposed real-time solver showed comparable processing speed but higher accuracy.Furthermore,we used a neutrophil degranulation cell model to represent tasks to test unfamiliar samples without data for pretraining.After being treated with cytochalasin B and N-Formyl-Met-Leu-Phe,HL-60 cells underwent dynamic degranulation processes,and we characterized cell’s C_(sm)andσ_(cyto)using piRT-IFC.Compared to the results from our solver,accuracy loss was observed in the results predicted by the FCNN,revealing the advantages of high speed,accuracy,and generalizability of the proposed piRT-IFC.

关键词： impedance intrinsic flow