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Branched glycopolymer prodrug-derived nanoassembly combined with a STING agonist activates an immuno-supportive status to boost anti-PD-L1 antibody therapy

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2194-2209页

作者： Zhilin Li Qianfeng Zhang Zhiqian Li Long Ren Dayi Pan Qiyong Gong Zhongwei Gu hao cai Kui Luo Department of Radiology Huaxi MR Research Center(HMRRC)Clinical Research Center for BreastDepartment of Breast SurgeryDepartment of Thoracic Surgery and Institute of Thoracic OncologyFrontiers Science Center for Disease-Related Molecular NetworkState Key Laboratory of BiotherapyWest China Hospital Sichuan UniversityChengdu 610041China Functional and Molecular Imaging Key Laboratory of Sichuan Province and Research Unit of PsychoradiologyChinese Academy of Medical SciencesChengdu 610041China Department of Radiology West China Xiamen Hospital of Sichuan UniversityXiamen 361021China Key Laboratory of Medicinal Chemistry for Natural Resource Ministry of EducationYunnan Key Laboratory of Research and Development for Natural ProductsSchool of PharmacyYunnan UniversityKunming 650500China

Despite the great potential of anti-PD-L1 antibodies for immunotherapy,their low response rate due to an immunosuppressive tumor microenvironment has hampered their application.To address this issue,we constructed a cell membrane-coated nanosystem(mB4S)to reverse an immunosuppressive microenvironment to an immuno-supportive one for strengthening the anti-tumor effect.In this system,Epirubicin(EPI)as an immunogenic cell death(ICD)inducer was coupled to a branched glycopolymer via hydrazone bonds and diABZI as a stimulator of interferon genes(STING)agonist was encapsulated into mB4S.After internalization of mB4S,EPI was acidic-responsively released to induce ICD,which was characterized by an increased level of calreticulin(CRT)exposure and enhanced ATP secretion.Meanwhile,diABZI effectively activated the STING pathway.Treatment with mB4S in combination with an anti-PD-L1 antibody elicited potent immune responses by increasing the ratio of matured dendritic cells(DCs)and CD8+T cells,promoting cytokines secretion,up-regulating M1-like tumor-associated macrophages(TAMs)and down-regulating immunosuppressive myeloid-derived suppressor cells(MDSCs).Therefore,this nanosystem for co-delivery of an ICD inducer and a STING agonist achieved promotion of DCs maturation and CD8+T cells infiltration,creating an immuno-supportive microenvironment,thus potentiating the therapy effect of the anti-PD-L1 antibody in both 4T1 breast and CT26 colon tumor mice.

关键词： Glycopolymer Polymer prodrug Immunogenic cell death Nanoassembly Epirubicin STING pathway Immuno-supportive microenvironment Immunotherapy

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Lysosome-targeted carbon dots with a light-controlled nitric oxide releasing property for enhanced photodynamic therapy

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Chinese Chemical Letters 2024年第4期35卷 420-425页

作者： hao cai Xiaoyan Wu Lei Jiang Feng Yu Yuxiang Yang Yan Li Xian Zhang Jian Liu Zijian Li Hong Bi School of Materials Science and Engineering Anhui UniversityHefei 230601China School of Chemistry and Chemical Engineering Anhui UniversityHefei 230601China School of Food and Biological Engineering Hefei University of TechnologyHefei 230009China

The reactive oxygen species(ROS) generation efficiency is always limited by the extreme tumor microenvironment(TME), leading to unsatisfactory antitumor effects in photodynamic therapy(PDT). As a promising gas therapy molecule, nitric oxide(NO) is independent of oxygen and could even synergize ROS to enhance the therapeutic effect. However, the short half-life, instability, and uncontrollable release of exogenous NO limited the application of tumor synergistic therapy. Herein, we reported a novel kind of red-emissive carbon dots(CDs) that was capable of lysosome-targeted and light-controlled NO delivery. The CDs were synthesized by using metformin and methylene blue(MB) via a hydrothermal method.The obtained metformin-MB CDs(MMCDs) exhibited a higher1O2quantum yield and NO generation efficiency under light emitting diode(LED) light irradiation. Noteworthily, the1O2could further in situ oxidize NO into peroxynitrite anions(ONOO-), which own the higher cytotoxicity against cancer cells.Cell experiments indicate that MMCDs could destruct lysosome membrane integrity and kill almost 80%of Hep G2 cells under light irradiation while very low cytotoxicity in the dark. Moreover, MMCDs significantly decreased tumor volume and weight after phototherapy in hepatoma Hep G2-bearing mice. Our study provides a new strategy for light-controlled NO generation as well as precise lysosome-targeting for enhancement of PDT efficiency.

关键词： Carbon dots Nitric oxide Lysosome-targeting Photodynamic therapy Cancer

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Encoding biological metaverse: Advancements and challenges in neural fields from macroscopic to microscopic

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The Innovation 2024年第3期5卷 30-32页

作者： Yantong cai Wenbo Hu Yao Pei hao Zhao Guangchuang Yu Dermatology Hospital Southern Medical UniversityGuangzhou 266003China Department of Bioinformatics School of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510515China Tencent AI Lab Shenzhen 518071China State Key Laboratory of Emerging Infectious Diseases School of Public HealthThe University of Hong KongHong Kong SARChina Laboratory of Data Discovery for Health(D24H) Hong Kong Science ParkHong Kong SARChina Institute for AI Industry Research Tsinghua UniversityBeijing 100000China

Neural fields can efficiently encode three-dimensional(3D)scenes,providing a bridge between two-dimensional(2D)images and virtual reality.This method becomes a trendsetter in bringing the metaverse into vivo life.It has initially captured the attention of macroscopic biology,as demonstrated by computed tomography and magnetic resonance imaging,which provide a 3D field of view for diagnostic biological images.Meanwhile,it has also opened up new research opportunities in microscopic imaging,such as achieving clearer de novo protein structure reconstructions.Introducing this method to the field of biology is particularly significant,as it is refining the approach to studying biological images.However,many biologists have yet to fully appreciate the distinctive meaning of neural fields in transforming 2D images into 3D perspectives.This article discusses the application of neural fields in both microscopic and macroscopic biological images and their practical uses in biomedicine,highlighting the broad prospects of neural fields in the future biological metaverse.We stand at the threshold of an exciting new era,where the advancements in neural field technology herald the dawn of exploring the mysteries of life in innovative ways.

关键词： neural bringing innovative

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New insights into the pre-lithiation kinetics of single-crystalline Ni-rich cathodes for long-life Li-ion batteries

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Green Energy & Environment 2024年第3期9卷 556-564页

作者： Qiang Han Lele cai Zhaofeng Yang Yanjie Hu hao Jiang Chunzhong Li Shanghai Engineering Research Center of Hierarchical Nanomaterials School of Chemical EngineeringEast China University of Science and TechnologyShanghai200237China Key Laboratory for Ultrafine Materials of Ministry of Education School of Materials Science and EngineeringEast China University of Science and TechnologyShanghai200237China

Developing single-crystalline Ni-rich cathodes is an effective strategy to improve the safety and cycle life of Li-ion batteries(LIBs).However,the easy-to-loss of Li and O in high-temperature lithiation results in unsatisfactory ordered layered structure and stoichiometry.Herein,we demonstrate the synthesis of highly-ordered and fully-stoichiometric single-crystalline LiNi_(0.83)Co_(0.12)Mn_(0.05)O_(2)(SC-NCM83)cathodes by the regulation of pre-lithiation kinetics.The well-balanced pre-lithiation kinetics have been proved to greatly improve the proportion of layered phase in the intermediate by inhibiting the formation of metastable spinel phase,which promoted the rapid transformation of the intermediate into highly-ordered layered SC-NCM83 in the subsequent lithiation process.After coating a layer of Li_(2)O–B_(2)O_(3),the resultant cathodes deliver superior cycling stability with 90.9%capacity retention at 1C after 300 cycles in pouch-type full batteries.The enhancement mechanism has also been clarified.These findings exhibit fundamental insights into the pre-lithiation kinetics process for guiding the synthesis of high-quality singlecrystalline Ni-rich cathodes.

关键词： Single-crystalline cathode Ni-rich oxides Pre-lithiation Li-ion batteries Surface modification

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Co_(3)O_(4)as an efficient passive NO_(x) adsorber for emission control during cold-start of diesel engines

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Chinese Journal of Chemical Engineering 2024年第2期66卷 1-7页

作者： Jinhuang cai Shijie hao Yun Zhang Xiaomin Wu Zhenguo Li Huawang Zhao Department of Environmental Science&Engineering College of Chemical EngineeringHuaqiao UniversityXiamen 361021China Wuxi Weifu Environmental Catalysts Co. LtdWuxi 214000China National Engineering Laboratory for Mobile Source Emission Control Technology China Automotive Technology&Research Center Co.Ltd.Tianjin 300300China

The Co_(3)O_(4)nanoparticles,dominated by a catalytically active(110)lattice plane,were synthesized as a low-temperature NO_(x) adsorbent to control the cold start emissions from vehicles.These nanoparticles boast a substantial quantity of active chemisorbed oxygen and lattice oxygen,which exhibited a NO_(x) uptake capacity commensurate with Pd/SSZ-13 at 100℃.The primary NO_(x) release temperature falls within a temperature range of 200-350℃,making it perfectly suitable for diesel engines.The characterization results demonstrate that chemisorbed oxygen facilitate nitro/nitrites intermediates formation,contributing to the NO_(x) storage at 100℃,while the nitrites begin to decompose within the 150-200℃range.Fortunately,lattice oxygen likely becomes involved in the activation of nitrites into more stable nitrate within this particular temperature range.The concurrent processes of nitrites decomposition and its conversion to nitrates results in a minimal NO_(x) release between the temperatures of 150-200℃.The nitrate formed via lattice oxygen mainly induces the NO_(x) to be released as NO_(2) within a temperature range of 200-350℃,which is advantageous in enhancing the NO_(x) activity of downstream NH_(3)-SCR catalysts,by boosting the fast SCR reaction pathway.Thanks to its low cost,considerable NO_(x) absorption capacity,and optimal release temperature,Co_(3)O_(4)demonstrates potential as an effective material for passive NO_(x) adsorber applications.

关键词： Emission control Cold-start Low-temperature adsorption Co_(3)O_(4) Nitrate formation

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Analysis and Optimization of the Electrohydraulic Forming Process of Sinusoidal Corrugation Tubes

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Fluid Dynamics & Materials Processing 2024年第4期20卷 873-887页

作者： Da cai Yinlong Song hao Jiang Guangyao Li Junjia Cui State Key Laboratory of Advanced Design and Manufacturing Technology for Vehicle Hunan UniversityChangsha410082China

Aluminum alloy thin-walled structures are widely used in the automotive industry due to their advantages related to light weight and crashworthiness.They can be produced at room temperature by the electrohydraulic forming process.In the present study,the influence of the related parameters on the forming quality of a 6063 aluminum alloy sinusoidal corrugation tube has been assessed.In particular,the orthogonal experimental design(OED)and central composite design(CCD)methods have been used.Through the range analysis and variance analysis of the experimental data,the influence degree of wire diameter(WD)and discharge energy(DE)on the forming quality was determined.Multiple regression analysis was performed using the response surface methodology.A prediction model for the attaching-die state coefficient was established accordingly.The following optimal arrangement of parameters was obtained(WD=0.759 mm,DE=2.926 kJ).The attaching-die state coefficient reached the peak value of 0.001.Better optimized wire diameter and discharge energy for a better attaching-die state could be screened by CCD compared with OED.The response surface method in CCD was more suitable for the design and optimization of the considered process parameters.

关键词： Electrohydraulic forming aluminum alloy tube process parameters attaching-die state 1 Introduction

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Mitigating set-stuck failure in 3D phase change memory: substituting square pulses with surge pulses

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Science China(Information Sciences) 2024年第5期67卷 295-301页

作者： Ninghua LI Wang cai Jun XIANG hao TONG Weiming CHENG Xiangshui MIAO School of Integrated Circuits Huazhong University of Science and Technology Hubei Yangtze Memory Laboratories Hubei Institute of Measurement and Testing Technology

In the devices that integrate phase change memory(PCM) and ovonic threshold switching(OTS),the OTS threshold voltage often surpasses the RESET operation voltage of PCM. The conventional application of square pulses hinders the successful completion of the SET operation in these integrated devices. To address this challenge, a novel pulse called the surge pulse is introduced, which comprises a high amplitude pulse for OTS activation and a low amplitude pulse for PCM operation. By employing COMSOL simulation,the operational effectiveness of both square pulses and surge pulses is validated. Test results reveal that using a square pulse to operate the integrated device accelerates the occurrence of SET-stuck failure(SSF).In contrast, the surge pulse enables the integrated device to operate for at least 1000 cycles while preserving the essential cyclic characteristics. Additionally, an investigation into the overshoot component of the surge pulse is conducted, revealing that an increase in overshoot amplitude and pulse width also accelerates the emergence of SSF. By applying the theory of ion migration induced by the electric field, the root cause of SSF in integrated devices is explained, and the accuracy of the theory is validated through the application of a reverse pulse. In summary, this study elucidates the rationality of replacing the square pulse with a surge pulse, presenting a superior approach for operating PCM and OTS integrated devices.

关键词： surge pulse phase change memory (PCM) integration SET-stuck failure (SSF) square pulse

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Status and trends of carbon emissions research at the county level in China

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Advances in Climate Change Research 2024年第2期15卷 338-352页

作者： Ang-Zu cai Ru GUO Yu-hao ZHANG Jiang WU College of Environmental Science and Engineering Institute of Environmental Planning and ManagementTongji UniversityShanghai 200092China Institute of Carbon Neutrality Tongji UniversityShanghai 200092China Shanghai Institute of Pollution Control and Ecological Security Shanghai 200092China College of Architecture and Urban Planning Tongji UniversityShanghai 200092China Megacity Elaborated Urban Governance Institute Tongji UniversityShanghai 200092China

This study provides a comprehensive overview of the challenges to achieving carbon neutrality at the county level in China and offers targeted recommendations,laying the groundwork for future specialized research in this area.A total of 283 relevant studies(2004-2023)were analyzed to assess county-level carbon emissions through three phases:bibliometric analysis,frontier analysis,and future prospects.Bibliometric findings reveal that publication trends were largely influenced by domestic and foreign policies.Keyword cluster discerns ten primary themes,ranging from conceptual frameworks to research methodologies.The frontier analysis of the literature highlights the leading research areas,which include carbon neutrality pathway,driving factors,spatiotemporal variation of carbon emissions,the co-effects of pollutants and carbon reduction,and carbon emissions in China's rural areas.Drawing from the results of bibliometric and frontier analyses,this study elucidates the recommendations for achieving carbon neutrality at the county level from three perspectives:effective regional policy guidance,emphasis on ecological conservation,and the deployment of advanced carbon reduction and sequestration technologies.This study enriches the body of knowledge on carbon emissions at the county level and holds significant implications for China's comprehensive push towards achieving its carbon neutrality objectives.

关键词： Carbon emissions Emission reduction County Carbon neutrality Sustainability

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Water modeling on fluid flow and mixing phenomena in a BOF steelmaking converter

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Journal of Iron and Steel Research(International) 2024年第3期31卷 595-607页

作者： Xin-yu cai hao-jian Duan Ding-han Li Anjun Xu Li-feng Zhang School of Metallurgical and Ecological Engineering University of Science and Technology Beijing(USTB)Beijing 100083China School of Mechanical and Materials Engineering North China University of TechnologyBeijing 100144China

A 1∶8 physical water model was constructed to investigate the fluid flow and mixing phenomena in the basic oxygen furnace(BOF)converter.The particle image velocimetry was employed to measure the velocity distribution of the bath and the high-speed camera was applied to capture the cavity shape in the combined blowing BOF converter.The mixing time for varied operating conditions was measured by the stimulus-response approach.The cavity depth increased with the decrease in the lance height and the increase in the top gas flow rate while the bottom blowing gas had little influence on the cavity depth.The minimum cavity depth was obtained under the condition of a 69.8 m^(3)/h top gas flow rate,a 287.5 mm lance height and a 0.93 m^(3)/h bottom blowing gas flow rate,which was 161.2 mm.The mixing time decreased as the lance height decreased and the top blowing gas flow rate increased.The mixing time was first decreased and then increased with the increase in the bottom gas flow rate.With the condition of 69.8 m^(3)/h gas flow rate of top blowing,the 287.5 mm lance height and the 0.93 m^(3)/h gas flow rate of bottom blowing,the mixing time in the converter was 48.65 s.The empirical formula between the stirring power and the mixing time in the converter was calculated.

关键词： Water model Fluid flow Particle image velocimetry Mixing time BOF converter

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New indole derivatives from endophytic fungus Colletotruchum sp. HK-08 originated from leaves of Nerium indicum

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Chinese Herbal Medicines 2024年第2期16卷 235-238页

作者： Huiqin Chen hao Zheng caihong cai hao Wang Cuijuan Gai Zhiqiong Tan haofu Dai Wenli Mei Hainan Key Laboratory of Research and Development of Natural Product from Li Folk Medicine Institute of Tropical Bioscience and BiotechnologyChinese Academy of Tropical Agricultural SciencesHaikou 571101China Hainan Institute for Tropical Agricultural Resources Haikou 571101China School of Life and Pharmaceutical Sciences Hainan UniversityHaikou 570228China

Objective: To study secondary metabolites from endophytic fungus Colletotruchum sp. HK-08 originated from the leaves of Nerium indicum.Methods: The compounds were isolated by various column chromatographic techniques, and their structures were elucidated by spectroscopic techniques [high resolution electrospray ionization mass spectroscopy(HRESIMS), one-dimensional(1D) and two-dimensional(2D) nuclear magnetic resonance spectroscopy(NMR)], as well as comparison with literature data. The Ellman method was used to determine the acetylcholinesterase(ACh E) inhibitory activity.Results: Four indole derivatives were identified from Colletotruchum sp. HK-08, including 6’-hydroxymonaspiloindole(1), 2-(2-oxoindolin-3-yl)ethyl 2-(4-hydroxyphenyl) acetate(2), 2-(2-oxoindolin-3-yl)ethyl 2-(2-hydroxyphenyl)acetate(3), and monaspiloindole(4). Compound 4 presented weak ACh E inhibitory activity with IC50value of(69.30 ± 6.27) μmol/L [tacrine as the positive control, with IC50value of(0.61 ± 0.07) μmol/L].Conclusion: Compounds 1–3 were new compounds, and compound 4 had weak ACh E inhibitory activity.

关键词： Colletotruchum sp. endophytic fungus indole derivatives Nerium indicum Mill. secondary metabolites

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