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Bionic immunoactivator copresenting autophagy promoting and costimulatory molecules for synergistic cancer immunotherapy

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Nano Research 2024年第3期17卷 1710-1724页

作者： yiwei peng Yiliang Yang Zhenzhen Yang Datong Gao Jiajia Li Qi Sun Yitian Du Meng Lin Xianrong Qi Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System School of Pharmaceutical SciencesPeking UniversityBeijing 100191China

Immunotherapy has great promise in improving malignant tumor treatment.However,the efficacy of existing strategies is often limited by the immunosuppressive environment.Here,we demonstrate an in situ bionic immunoactivator,PLT-Bec1/DTA-1,with possessed natural advantages of platelets for tumor recruitment and activation,on which DTA-1(CD357 monoclonal antibody)and Bec1 were tethered as combined immune boosters.PLT-Bec1/DTA-1,as a self-triggered release repository,can deliver the pre-tethered Bec1 and DTA-1 deeply through the secretion of platelet microparticles(PMPs),thereby cooperate tacitly and exhibit superiority in immune activation of dendritic cells(DCs)and T cells via autophagy inducibility,coupled with glucocorticoid-induced tumor necrosis factor receptor(GITR)-triggered T_(Reg) suppression,remodeled the immunosuppressive network of tumor microenvironment.PLT-Bec1/DTA-1 promoted antigen presentation and T cell proliferation,and alleviated the low activity state of bone marrow-derived dendritic cells(BMDCs)in tumor suppressive environment.PLT-Bec1/DTA-1 inhibited tumor recurrence(5-and 13-fold lower of control group in tumor volume)and CD8^(+)T/T_(Reg) ratio(6.3-and 8.8-fold vs.control group)in mouse tumor model after intravenous or subcutaneous administration.Also,PLT-Bec1/DTA-1 prevented tumor colonization in lung through in situ immune activation,and was slightly superior to the combined of Bec1 and PD-L1.Our findings highlight the promise of delivering immunostimulatory payloads via bionic carriers,eliciting automatic in situ activation of effector immune cells in tumor microenvironment for tumor eradication.All these results provide promising prospects into the application of immunoactivator in improving cancer synergistic immunotherapy to overcome the bottlenecks in clinic.

关键词： in situ bionic immunoactivator autophagy glucocorticoid-induced tumor necrosis factor receptor(GITR)agonist platelets and platelet microparticles cancer immunotherapy

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Mechanisms of enhanced sub-bandgap absorption in high-speed all-silicon avalanche photodiodes

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Photonics Research 2023年第2期11卷 337-346页

作者： YUAN YUAN WAYNE V.SORIN DI LIANG STANLEY CHEUNG yiwei peng MUDIT JAIN ZHIHONG HUANG MARCO FIORENTINO RAYMOND G.BEAUSOLEIL Hewlett Packard Labs Hewlett Packard EnterpriseMilpitasCalifornia 95035USA

All-silicon (Si) photodiodes have drawn significant interest due to their single and simple material system and perfect compatibility with complementary metal-oxide semiconductor photonics. With the help from a cavity enhancement effect, many of these photodiodes have shown considerably high responsivity at telecommunication wavelengths such as 1310 nm, yet the mechanisms for such high responsivity remain unexplained. In this work,an all-Si microring is studied systematically as a photodiode to unfold the various absorption mechanisms.At-6.4 V, the microring exhibits responsivity up to0.53 A∕W with avalanche gain, a 3 dB bandwidth of25.5 GHz, and open-eye diagrams up to 100 Gb/s. The measured results reveal the hybrid absorption mechanisms inside the device. A comprehensive model is reported to describe its working principle, which can guide future designs and make the all-Si microring photodiode a promising building block in Si photonics.

关键词： Gb/s avalanche absorption

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Temperature dependence of the ionization coefficients of InAlAs and AlGaAs digital alloys

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Photonics Research 2018年第8期6卷 794-799页

作者： YUAN YUAN JIYUAN ZHENG YAOHUA TAN yiwei peng ANN-KATHRYN ROCKWELL SETH R. BANK AVIK GHOSH JOE C. CAMPBELL Electrical and Computer Engineering Department University of Virginia 351 McCormick Rd. Charlottesville Virginia 22904 USA Electrical and Computer Engineering Department University of Texas at Austin 1616 Guadalupe St. Austin Texas 78758 USA

Digital alloy In_(0.52)Al_(0.48) As avalanche photodiodes exhibit lower excess noise than those fabricated from random alloys. This paper compares the temperature dependence, from 203 to 323 K, of the impact ionization characteristics of In_(0.52)Al_(0.48) As and Al_(0.74)Ga_(0.26) As digital and random alloys. These results provide insight into the low excess noise exhibited by some digital alloy materials, and these materials can even obtain lower excess noise at low temperature.

关键词：超额噪声通讯技术发展现状技术创新

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Redetermination of the Depositional Age of the Haerdaban Group in the Northern Margin of the Yili Block,Western Tianshan,NW China:Implications for Regional Tectonics and Pb-Zn Mineralization

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Acta Geologica Sinica(English Edition) 2023年第2期97卷 404-417页

作者： WANG Jialin GU Xuexiang XU Jingchi ZHANG Yongmei peng yiwei LU Liangtao State Key Laboratory of Processes and Mineral Resources China University of Geosciences(Beijing)Beijing 100083China School of Earth Sciences and Resources China University of Geosciences(Beijing)Beijing 100083China Development Research Center of the China Geological Survey Beijing 100037China Mineral Exploration Technical Guidance Center of the Ministry of Natural Resources Beijing 100083China State Key Laboratory of Tectonic Controls on Mineralization and Hydrocarbon Accumulation of the Ministry of Natural Resources Chengdu University of TechnologyChengdu 610059China

The Yili Block in the Western Tianshan orogen is a key area for understanding the early crustal formation and evolution of the Central Asian orogenic belt,due to the widely-distributed Precambrian rocks.Also,it hosts a lot of medium–to large-scale sedimentary exhalative(SEDEX)Pb-Zn deposits that mainly occur in Proterozoic metamorphosed clasticcarbonate rocks.In this study,LA-ICP-MS U-Pb analyses were carried out on detrital zircons in siltstones of the Precambrian Haerdaban Group in the Haerdaban Pb-Zn deposit and magmatic zircons in the diorite dyke that cuts through the strata and orebodies.The maximum depositional age of the siltstones was determined to be about 604 Ma,the diorite having formed at approximately 500 Ma.As such,the Haerdaban Group was most likely formed in the Neoproterozoic Sinian,rather than the previously considered Mesoproterozoic Changchengian.Detrital materials of the Haerdaban Group were mostly derived from the Nanhua–Sinian mafic dykes and granitic rocks around Lake Sayram at the northern margin of the Yili Block.It is proposed that the Yili Block,together with the Kazakhstan and Central Tianshan blocks and the Tarim Craton,might all pertain to the same Rodinia supercontinent,which has great potential for targeting large to super-large SEDEX Pb-Zn deposits.

关键词： Haerdaban Group zircon U-Pb dating SEDEX Pb-Zn mineralization Neoproterozoic Yili Block Western Tianshan

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Transcriptomic analysis identifies the neuropeptide cortistatin (CORT) as an inhibitor of temozolomide (TMZ) resistance by suppressing the NF-kB-MGMT signaling axis in human glioma

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Genes & Diseases 2024年第3期11卷 385-399页

作者： Zongze He Bo peng Qi Wang Jie Tian Ping Liu Jie Feng yiwei Liao Longyi Chen Ping Jia Jian Tang Department of Neurosurgery Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan 610072China Department of Rehabilitation Medicine Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan 610072China Department of Neurosurgery Xiangya HospitalCentral South UniversityChangshaHunan 410008China

Glioma is a common tumor originating in the brain that has a high mortality rate.Temozolomide(TMZ)is the first-line treatment for high-grade gliomas.However,a large pro-portion of gliomas are resistant to TMZ,posing a great challenge to their treatment.In the study,the specific functions and mechanism(s)by which cortistatin(CORT)regulates TMZ resis-tance and glioma progression were evaluated.The decreased expression of CoRT was detected in glioma tissues,and highly expressed CORT was associated with a better survival rate in pa-tients with glioma.CORT overexpression notably decreased the capacity of glioma cells to pro-liferate and migrate in vitro and to form tumors in vivo.CORT overexpression also markedly suppressed the viability and enhanced the apoptosis of TMZ-resistant U251 cells by regulating MGMT,p21,and Puma expression.Importantly,CORT overexpression reduced the resistance of gliomas to TMZ in vivo.CORT expression Was negatively correlated with MGMT expression in both glioma tissues and cells,and it was found that CORT inhibited NF-kB pathway activation in glioma cells,thereby inhibiting MGMT expression.In conclusion,CORT regulates glioma cell growth,migration,apoptosis,and TMZ resistance by weakening the activity of NF-kB/p65 and thereby regulating MGMT expression.The CORT/NF-kB/MGMT axis might be regarded as a molecular mechanism contributing to the resistance of glioma to TMZ.Our data also suggest that CORT regulates the viability and metastatic potential of glioma cells,independent of its effects on TMZ resistance,providing evidence of novel therapeutic targets for glioma that should be evaluated infurther studies.

关键词： Cortistatin Glioma MGMT NF-kB pathway Temozolomide

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Amorphous hybrid tungsten oxide–nickel hydroxide nanosheets used as a highly efficient electrocatalyst for hydrogen evolution reaction

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Nano Research 2024年第4期17卷 2499-2508页

作者： Chao Lyu Chenghai Dai yiwei Tan State Key Laboratory of Materials-Oriented Chemical Engineering School of Chemistry and Chemical EngineeringNanjing Tech UniversityNanjing 211816China

There are more challenges for alkaline hydrogen evolution reaction(HER)via simultaneously expediting the electron-coupled water dissociation process(Volmer step)and the following electrochemical H_(2) desorption(Heyrovsky step).Hybrid amorphous electrocatalysts are highly desirable for efficient hydrogen evolution from water-alkali electrolyzers due to the bifunctionality for the different elementary steps of HER and optimal interactions with water molecules and the reactive hydrogen intermediates(Had).Herein,the synthesis of amorphous hybrid ultrathin(tungsten oxide/nickel hydroxide)hydrate(a-[WO_(3)/Ni(OH)_(2)]·0.2H_(2)O)nanosheets on nickel foam(NF)for efficient alkaline HER is described.The structural and composition features of a-[WO_(3)/Ni(OH)_(2)]·0.2H_(2)O are characterized in detailed.The resulting a-[WO_(3)/Ni(OH)_(2)]·0.2H_(2)O/NF electrocatalyst with the synergistic effect of both hybrid components for the HER elementary steps shows greatly improved the activity and durability for the HER with a low overpotential of-41 and-163 mV at-10 and-500 mA·cm^(-2),respectively,a Tafel slope as low as-72.9 mV·dec^(-1),and long-term stability of continuous electrolysis for at least 150 h accompanying by inappreciable overpotential change in 1 M KOH.In the hybrid a-[WO_(3)/Ni(OH)_(2)]·0.2H_(2)O,Ni(OH)_(2) and WO_(3) moieties are separately responsible for accelerating dissociative adsorption of water and weakening Had adsorption strength,which is beneficial to the improvement of the alkaline HER activity.

关键词： amorphous nanomaterial bimetallic electrocatalyst tungsten oxide ultrathin nanosheet hydrogen evolution reaction

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聚合物-脂质纳米粒用于增强酪氨酸血症I型治疗性碱基编辑器质粒的肝靶向递送研究

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Journal of Chinese Pharmaceutical Sciences 2024年第3期33卷 189-200页

作者：高达同林萌彭祎玮李嘉嘉杨宜靓滕雨璐陈思宇孙雯吴子楠袁泉仰浈臻周艳霞李馨儒齐宪荣北京大学药学院药剂学系分子药剂学与新释药系统北京市重点实验室北京100191 四川大学华西医院药剂科四川成都610041 北京大学第三医院医学创新研究所药物临床试验中心北京100191

酪氨酸血症I型是一种罕见的常染色体隐性遗传病,目前尚无有效的治疗方法。近年来,以碱基编辑器为代表的基因编辑技术已被报道用于酪氨酸血症I型的治疗。然而,由于生理屏障的存在,碱基编辑器递送困难。在本研究中,我们构建了一种靶向去... 详细信息

酪氨酸血症I型是一种罕见的常染色体隐性遗传病,目前尚无有效的治疗方法。近年来,以碱基编辑器为代表的基因编辑技术已被报道用于酪氨酸血症I型的治疗。然而,由于生理屏障的存在,碱基编辑器递送困难。在本研究中,我们构建了一种靶向去唾液酸糖蛋白受体的聚合物-脂质纳米递送系统,用于改善酪氨酸血症I型治疗性核酸药物的递送效率。我们首先合成了一种生物可降解性丙烯酸酯-氨基醇共聚物用于递送碱基编辑器质粒,其转染效率显著优于市售转染试剂Hieff Trans^(TM)。随后,共聚物纳米粒与DOPE-PEG-Gal NAc自组装形成聚合物-脂质纳米粒,用于增强纳米粒的肝脏递送效率。在体外转染实验中,包载Fah-p CMV-ABE6.3-EGFP碱基编辑器质粒的聚合物-脂质纳米粒表现出了良好的肝细胞选择性,其转染效率是游离质粒的70倍以上。研究表明,携带肝靶向配体的聚合物-脂质纳米递送系统能够有效增强治疗性碱基编辑器质粒的肝靶向递送效率并为酪氨酸血症I型的基因治疗提供了一种潜在的递送载体。

关键词：酪氨酸血症I型碱基编辑器聚合物-脂质纳米粒转染效率基因递送

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“卓越工程师教育培养计划”创新实验班设立10年的成效与思考——以成都理工大学地球科学学院资源勘查工程专业为例

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中国地质教育 2024年第1期33卷 34-40页

作者：邹灏陈翠华郎兴海施泽明李晨伟丁枫霍艳黎文徐争启彭义伟成都理工大学地球科学学院四川成都610059

资源勘查工程专业是成都理工大学历史最悠久的工科专业之一,也是国家级特色专业、中国工程教育专业认证专业、国家级一流本科专业。自2011年获批教育部“卓越工程师教育培养计划”专业以来,设立创新实验班,并进行了10年的教育教学探索... 详细信息

资源勘查工程专业是成都理工大学历史最悠久的工科专业之一,也是国家级特色专业、中国工程教育专业认证专业、国家级一流本科专业。自2011年获批教育部“卓越工程师教育培养计划”专业以来,设立创新实验班,并进行了10年的教育教学探索、改革和创新,取得了一定的成效,同时也存在一些不足。从思政引领、制度创新、师资建设、机制改革等方面对“卓越工程师教育培养计划”创新实验班的实施措施进行了梳理和总结,也对创新实验班建设10年来所取得的成效进行了归纳,并提出了思考与建议,以期为新形势下我国地学人才培养的发展探索新思路,对推动地学创新人才培养模式改革具有借鉴作用。

关键词：卓越计划资源勘查工程创新实验班

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Multi-scale physics-informed neural networks for solving high Reynolds number boundary layer flows based on matched asymptotic expansions

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Theoretical & Applied Mechanics Letters 2024年第2期14卷 76-81页

作者： Jianlin Huang Rundi Qiu Jingzhu Wang yiwei Wang Key Laboratory for Mechanics in Fluid Solid Coupling Systems Institute of MechanicsChinese Academy of SciencesBeijing 100190China School of Future Technology University of Chinese Academy of SciencesBeijing 100049China School of Engineering Science University of Chinese Academy of SciencesBeijing 100049China Guangdong Aerospace Research Academy Guangzhou 511458China

Multi-scale system remains a classical scientific problem in fluid dynamics,biology,etc.In the present study,a scheme of multi-scale Physics-informed neural networks is proposed to solve the boundary layer flow at high Reynolds numbers without any data.The flow is divided into several regions with different scales based on Prandtl's boundary theory.Different regions are solved with governing equations in different scales.The method of matched asymptotic expansions is used to make the flow field continuously.A flow on a semi infinite flat plate at a high Reynolds number is considered a multi-scale problem because the boundary layer scale is much smaller than the outer flow scale.The results are compared with the reference numerical solutions,which show that the msPINNs can solve the multi-scale problem of the boundary layer in high Reynolds number flows.This scheme can be developed for more multi-scale problems in the future.

关键词： Physics-informed neural networks(PINNs) Multi-scale Fluid dynamics Boundary layer

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The burgeoning importance of PIWI-interacting RNAs in cancer progression

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Science China(Life Sciences) 2024年第4期67卷 653-662页

作者： Xinpei Deng Tianle Liao Jindong Xie Da Kang yiwei He Yuying Sun Zhangling Wang Yongluo Jiang Xuan Miao Yixuan Yan Hailin Tang Lewei Zhu Yutian Zou peng Liu State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060China School of Medicine Sun Yat-sen UniversityShenzhen 518107China Key Laboratory of Cardiovascular and Cerebrovascular Medicine Nanjing Medical UniversityNanjing 211166China Guanghua School of Stomatology Sun Yat-sen UniversityGuangzhou 510062China The First People’s Hospital of Foshan Foshan 528000China

PIWI-interacting RNAs(pi RNAs)are a class of small noncoding RNA molecules that specifically bind to piwi protein family members to exert regulatory functions in germ cells.Recent studies have found that pi RNAs,as tissue-specific molecules,both play oncogenic and tumor suppressive roles in cancer progression,including cancer cell proliferation,metastasis,chemoresistance and stemness.Additionally,the atypical manifestation of pi RNAs and PIWI proteins in various malignancies presents a promising strategy for the identification of novel biomarkers and therapeutic targets in the diagnosis and management of tumors.Nonetheless,the precise functions of pi RNAs in cancer progression and their underlying mechanisms have yet to be fully comprehended.This review aims to examine current research on the biogenesis and functions of pi RNA and its burgeoning importance in cancer progression,thereby offering novel perspectives on the potential utilization of pi RNAs and piwi proteins in the management and treatment of advanced cancer.

关键词： PIWI-interacting RNAs/piRNAs cancer progression metastasis chemoresistance stemness

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