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Nanomedicine integrating the lipidic derivative of 5-fluorouracil,miriplatin and PD-L1 si RNA for enhancing tumor therapy

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Chinese Chemical Letters 2024年第6期35卷 385-391页

作者： An Lu yuhao guo Yi Yan Lin Zhai Xiangyu Wang Weiran Cao Zijie Li Zhixia Zhao Yujie Shi Yuanjun Zhu Xiaoyan Liu Huining He Zhiyu Wang Jian-Cheng Wang Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems State Key Laboratory of Natural and Biomimetic DrugsSchool of Pharmaceutical SciencesPeking UniversityBeijing 100191China Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics School of PharmacyTianjin Medical UniversityTianjin 300070China Department of Immuno-oncology The Fourth Hospital of Hebei Medical UniversityShijiazhuang 050011China Department of Pharmacy Clinical Trial Research CenterChina-Japan Friendship HospitalBeijing 100029China Laboratory of innovative formulations and pharmaceutical excipients Ningbo Institute of Marine MedicinePeking UniversityNingbo 315832China

Immunosuppressive microenvironments present critical problems in clinical chemotherapy.To regulate the tumor immune microenvironment for enhancing antitumor effect,a combination of immune checkpoint inhibitors(ICIs)with chemotherapeutics has been applied clinically.In this study,miriplatin(MiPt),the lipidic derivative of 5-fluorouracil(Fu-OA),as well as the programmed death ligand 1(PD-L1)target si RNA(siPD-L1)were integrated into Lip-Pt/Fu@siPD-L1 nanoparticles(NPs)for chemo-immunotherapy.In vitro results showed that Lip-Pt/Fu@siPD-L1 NPs could exhibit effective siRNA gene silencing and promote the phagocytosis of tumor cells by macrophages.Furthermore,in vivo results revealed that LipPt/Fu@siPD-L1 NPs showed significantly higher anti-tumor efficiency than that of the physical mixing of Mi Pt,5-fluorouracil,and Lip@siPD-L1 NPs(delivery of siPD-L1 by liposomes).The best anti-tumor efficiency of Lip-Pt/Fu@siPD-L1 NPs resulted from the synergistic immunotherapeutic effects of Mi Pt and siPD-L1 based on the inhibition of CD47 expression and the downregulation of PD-L1 in tumor cells,which elicited a robust anti-tumor immune response through the activation of macrophage phagocytosis and immune checkpoint inhibition.The Lip-Pt/Fu@siPD-L1 NPs provide a potential strategy for tumor chemo-immunotherapy.

关键词： Chemo-immunotherapy Immune checkpoint inhibition Gene silencing Miriplatin Macrophage phagocytosis Nanotechnology

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Six-hierarchy model of accident analysis and its application in coal mine accidents

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Journal of Safety Science and Resilience 2022年第1期3卷 61-71页

作者： Qiuju Ma Mengsai Wan Juncheng Shao Mingyu Zhong yuhao guo Wei Wang School of Emergency Management and Safety Engineering China University of Mining and TechnologyBeijing 100083China Shanghai Fire Science and Technology Research Institute of MEM Shanghai 200032China

Accident analysis models play a significant role in accident investigation and analysis.Most traditional models,usually based on a chain of events,have serious limitations when used for complex systems,especially for coal mine accident.HFACS is a widely accepted accident cause model with complex structure and content.Based on HFACS and accident investigation need in China,a new systemic accident analysis method“Six-hierarchy model”is proposed.And the index database of accident causal factors at each hierarchy of coal mine accidents is established.This model provides clear guidance for the prevention of accidents from six levels,which helps to the targeted rectification after accidents and the improvement of safety management level.The source,ap-plication scope,advantages and disadvantages of HFACS and six-hierarchy model are compared.The“2.14”gas explosion accident in Sunjiawan coal mine is analyzed by using HFACS and six-hierarchy model and the safety management suggestions are put forward.The study shows that the Six-hierarchy model provides a clear guide for the prevention of accidents from six levels.And it benefits the targeted rectification after accidents and the continuous improvement of safety management.

关键词： Accident Accident analysis Six-hierarchy Coal mine accident HFACS

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A simplified method for investigating the bending behavior of piles supporting embankments on soft ground

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Frontiers of Structural and Civil Engineering 2023年第7期17卷 1021-1032页

作者： Yu DIAO yuhao guo Zhenyang JIA Gang ZHENG Weiqiang PAN Dongfan SHANG Ying ZHANG Key Laboratory of Coastal Civil Engineering Structure and Safety of Ministry of Education Tianjin UniversityTianjin 300072China Department of Civil Engineering Tianjin UniversityTianjin 300072China Shanghai Tunnel Engineering Construction Co. Ltd.Shanghai 200032China Hebei Academy of Building Research Co. Ltd.Shijiazhuang 050000China Tianjin Municipal Engineering Design&Research Institute Tianjin 300392China

In recent years,concrete and reinforced concrete piles have been widely used to stabilize soft ground under embankments.Previous research has shown that bending failure,particularly during rapid filling on soft ground,is the critical failure mode for pile-supported embankments.Here,we propose an efficient two-stage method that combines a test-verified soil deformation mechanism and Poulos’solution for pile–soil interaction to investigate the bending behavior of piles supporting embankments on soft ground.The results reveal that there are three possible bending failure scenarios for such piles:at the interface between the soft and firm ground layers,at mid-depths of the fan zone,and at the boundary of the soil deformation mechanism.The location of the bending failure depends on the position and relative stiffness of the given pile.Furthermore,the effect of embedding a pile into a firm ground layer on the bending behavior was investigated.When the embedded length of a pile exceeded a critical value,the bending moment at the interface between the soft and firm ground layers reached a limiting value.In addition,floating piles that are not embedded exhibit an overturning pattern of movement in the soft ground layer,and a potential failure is located in the upper part of these piles.

关键词： bending behavior pile embankment soil−structure interaction failure mode

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A small microring array that performs large complex-valued matrix-vector multiplication

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Frontiers of Optoelectronics 2022年第2期15卷 1-15页

作者： Junwei Cheng Yuhe Zhao Wenkai Zhang Hailong Zhou Dongmei Huang Qing Zhu yuhao guo Bo Xu Jianji Dong Xinliang Zhang Wuhan National Laboratory for Optoelectronics School of Optical and Electronic InformationHuazhong University of Science and TechnologyWuhan 430074China Photonics Research Centre Department of Electronic and Information EngineeringThe Hong Kong Polytechnic UniversityHong Kong 999077China The Hong Kong Polytechnic University Shenzhen Research Institute Shenzhen 518057China Photonics Research Centre Department of Electrical EngineeringThe Hong Kong Polytechnic UniversityHong Kong 999077China Institute of Strategic Research Huawei TechnologiesShenzhen 518129China

As an important computing operation,photonic matrix-vector multiplication is widely used in photonic neutral networks and signal processing.However,conventional incoherent matrix-vector multiplication focuses on real-valued operations,which cannot work well in complex-valued neural networks and discrete Fourier transform.In this paper,we propose a systematic solution to extend the matrix computation of microring arrays from the real-valued field to the complex-valued field,and from small-scale(i.e.,4×4)to large-scale matrix computation(i.e.,16×16).Combining matrix decomposition and matrix partition,our photonic complex matrix-vector multiplier chip can support arbitrary large-scale and complex-valued matrix computation.We further demonstrate Walsh-Hardmard transform,discrete cosine transform,discrete Fourier transform,and image convolutional processing.Our scheme provides a path towards breaking the limits of complex-valued computing accelerator in conventional incoherent optical architecture.More importantly,our results reveal that an integrated photonic platform is of huge potential for large-scale,complex-valued,artificial intelligence computing and signal processing.

关键词： Photonic matrix-vector multiplication Complex-valued computing Microring array Signal/image processing

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深潜器钛合金耐压壳蠕变屈曲强度评估方法研究

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中国造船 2024年第2期65卷 25-36页

作者：郭育豪刘刚大连理工大学船舶工程学院大连116024 工业装备结构分析优化与CAE软件全国重点实验室大连116024

深潜器钛合金耐压壳存在室温蠕变现象,会减弱耐压壳结构的屈曲极限强度,发生蠕变屈曲破坏。论文以钛合金圆柱形耐压壳为研究对象,考虑结构初始缺陷幅值、蠕变载荷和蠕变时间的影响,通过数值模拟研究蠕变变形对耐压壳非线性屈曲强度的影... 详细信息

深潜器钛合金耐压壳存在室温蠕变现象,会减弱耐压壳结构的屈曲极限强度,发生蠕变屈曲破坏。论文以钛合金圆柱形耐压壳为研究对象,考虑结构初始缺陷幅值、蠕变载荷和蠕变时间的影响,通过数值模拟研究蠕变变形对耐压壳非线性屈曲强度的影响。研究表明:蠕变变形会加剧结构初始缺陷的幅值,减弱耐压壳结构的非线性屈曲强度。另外,钛合金耐压壳存在蠕变屈曲现象,蠕变屈曲的临界时间对结构初始缺陷幅值极为敏感。建立了钛合金耐压壳室温蠕变屈曲临界时间与蠕变载荷之间指数关系的模型,可以快速评估深潜器在指定作业时间下的最大下潜深度。对于不同临界时间下的蠕变载荷,该模型拟合结果与数值计算结果的相对误差均在±2%以内。

关键词：钛合金耐压壳室温蠕变蠕变屈曲极限强度数值模拟

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钛合金室温受压蠕变损伤本构模型

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哈尔滨工程大学学报 2024年第4期45卷 642-650页

作者：郭育豪刘刚宋育泽大连理工大学船舶工程学院辽宁大连116024 大连理工大学工业装备结构分析优化与CAE软件全国重点实验室辽宁大连116024

为了解决工程上在评估深潜器耐压壳体安全可靠性时不考虑拉压蠕变破坏机理产生的差异,会导致较大计算误差问题,本文提出了适用于室温蠕变的蠕变损伤本构模型。通过分析钛合金材料蠕变特性,考虑了室温环境下位错堆积造成的蠕变阻力,并且... 详细信息

为了解决工程上在评估深潜器耐压壳体安全可靠性时不考虑拉压蠕变破坏机理产生的差异,会导致较大计算误差问题,本文提出了适用于室温蠕变的蠕变损伤本构模型。通过分析钛合金材料蠕变特性,考虑了室温环境下位错堆积造成的蠕变阻力,并且位错堆积的现象与时间有关。基于微分自洽法提出了适用于室温环境下的钛合金蠕变本构模型,得到受压情况下TC4ELI的相关材料参数,并将该模型用USDFLD和CREEP子程序进行定义。研究表明:对于受压结构而言,使用通过拉伸蠕变实验得到的本构模型的计算结果会过于保守,对于含V型缺口平板受压时等效蠕变应变的相对误差为168.20%。本文所提出的模型适用于环肋耐压壳结构的蠕变损伤分析。

关键词：钛合金室温蠕变蠕变损伤本构模型拉压不同连续损伤力学有限元法耐压壳

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Self-calibrating microring synapse with dual-wavelength synchronization

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Photonics Research 2023年第2期11卷 347-356页

作者： JUNWEI CHENG ZHENMING HE yuhao guo BO WU HAILONG ZHOU TEYAN CHEN YIXIN WU WENWEI XU JIANJI DONG XINLIANG ZHANG Wuhan National Laboratory for Optoelectronics Huazhong University of Science and TechnologyWuhan 430074China Optics Valley Laboratory Wuhan 430074China Galileo Advanced Technology Lab Huawei TechnologiesShenzhen 518129China Institute of Strategic Research Huawei TechnologiesShenzhen 518129China

As a resonator-based optical hardware in analog optical computing, a microring synapse can be straightforwardly configured to simulate the connection weights between neurons, but it faces challenges in precision and stability due to cross talk and environmental perturbations. Here, we propose and demonstrate a self-calibration scheme with dual-wavelength synchronization to monitor and calibrate the synaptic weights without interrupting the computation tasks. We design and fabricate an integrated 4 × 4 microring synapse and deploy our self-calibration scheme to validate its effectiveness. The precision and robustness are evaluated in the experiments with favorable performance, achieving 2-bit precision improvement and excellent robustness to environmental temperature fluctuations(the weights can be corrected within 1 s after temperature changes 0.5°C). Moreover, we demonstrate matrix inversion tasks based on Newton iterations beyond 7-bit precision using this microring synapse. Our scheme provides an accurate and real-time weight calibration independently parallel from computations and opens up new perspectives for precision boost solutions to large-scale analog optical computing.

关键词： synchronization microring resonator

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考虑点蚀损伤的系泊锚链极限强度分析

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中国造船 2024年第1期65卷 75-85页

作者：刘德让刘刚唐鑫彤郭育豪大连理工大学船舶工程学院大连116024 中国船级社海洋工程技术中心天津300451

在系泊锚链外表面模拟点蚀损伤,建立系泊锚链点蚀损伤模型,并对点蚀损伤下的锚链极限强度进行评估,分析锚链的极限强度演变规律。数值计算结果表明,锚链极限强度随着点蚀程度的加剧逐渐下降,在同等腐蚀体积损失率下,点蚀损伤对极限强度... 详细信息

在系泊锚链外表面模拟点蚀损伤,建立系泊锚链点蚀损伤模型,并对点蚀损伤下的锚链极限强度进行评估,分析锚链的极限强度演变规律。数值计算结果表明,锚链极限强度随着点蚀程度的加剧逐渐下降,在同等腐蚀体积损失率下,点蚀损伤对极限强度的影响远大于均匀腐蚀损伤。结合不同损伤形式下的腐蚀体积损失率,建立了点蚀损伤与均匀腐蚀的等效关系。研究结果可为系泊锚链极限强度的快速评估提供参考。

关键词：锚链点蚀极限强度载荷-位移曲线等效关系

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Numerical simulation of smoke stratification in tunnel fires under longitudinal velocities

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Underground Space 2021年第2期6卷 163-172页

作者： yuhao guo Zhongyuan Yuan Yanping Yuan Xiaoling Cao Peng Zhao School of Mechanical Engineering Southwest Jiaotong University111Second Ring RoadChengdu CitySichuan Province 610031PR China

Use of the longitudinal critical velocity in tunnel fires may destroy the stratification of smoke downstream,which is not conducive to the evacuation of downstream tunnel users.Reducing the longitudinal velocity can maintain stratification,but the appropriate longitudinal velocity range is unknown.Stratification of smoke under the longitudinal velocity is studied using Fire Dynamics Simulator(FDS).The aims of this paper are to explore the relationship between the longitudinal velocity and smoke stratification and to obtain a proper velocity range that can maintain clear downstream stratification.Based on Newman's theory,the"stratification velocity"is proposed,which is the maximum velocity that maintains downstream smoke stratification.A good correspondence between the average Froude number within 200 m downstream and the longitudinal velocity and heat release rate(HRR)is found.The correlation between the temperature stratification and Froude number is obtained.Fr=0.49 can be used to distinguish whether the stratification is clear.The relationship between the critical velocity and the stratification velocity is also discussed.

关键词： Tunnel fire Longitudinal ventilation Smoke stratification

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Downregulation of ceramide synthase 1 promotes oral cancer through endoplasmic reticulum stress

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International Journal of Oral Science 2021年第1期13卷 108-116页

作者： Wen Chen Chenzhou Wu Yafei Chen yuhao guo Ling Qiu Zhe Liu Haibin Sun Siyu Chen Zijian An Zhuoyuan Zhang Yi Li Longjiang Li State Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases&Department of Head and Neck Oncology West China Hospital of StomatologySichuan UniversityChengduChina Department of Oral and Maxillofacial-Head and Neck Oncology Capital Medical University School of StomatologyBeijingChina

C18 ceramide plays an important role in the occurrence and development of oral squamous cell carcinoma.However,the function of ceramide synthase 1,a key enzyme in C18 ceramide synthesis,in oral squamous cell carcinoma is still unclear.The aim of our study was to investigate the relationship between ceramide synthase 1 and oral cancer.In this study,we found that the expression of ceramide synthase 1 was downregulated in oral cancer tissues and cell lines.In a mouse oral squamous cell carcinoma model induced by 4-nitroquinolin-1-oxide,ceramide synthase 1 knockout was associated with the severity of oral malignant transformation.Immunohistochemical studies showed significant upregulation of PCNA,MMP2,MMP9,and BCL2 expression and downregulation of BAX expression in the pathological hyperplastic area.In addition,ceramide synthase 1 knockdown promoted cell proliferation,migration,and invasion in vitro.Overexpression of CERS1 obtained the opposite effect.Ceramide synthase 1 knockdown caused endoplasmic reticulum stress and induced the VEGFA upregulation.Activating transcription factor 4 is responsible for ceramide synthase 1 knockdown caused VEGFA transcriptional upregulation.In addition,mild endoplasmic reticulum stress caused by ceramide synthase 1 knockdown could induce cisplatin resistance.Taken together,our study suggests that ceramide synthase 1 is downregulated in oral cancer and promotes the aggressiveness of oral squamous cell carcinoma and chemotherapeutic drug resistance.

关键词： endoplasmic cancer reticulum

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