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Blockading a new NSCLC immunosuppressive target by pluripotent autologous tumor vaccines magnifies sequential immunotherapy

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Bioactive Materials 2022年第7期7卷 223-238页

作者： Hong Wu Hongyan Li Yiqiang Liu Jingchen Liang Qianshi Liu zhigang xu Zhongzhu Chen Xia Zhang Kun Zhang Chuan xu Integrative Cancer Center&Cancer Clinical Research Center Sichuan Cancer Hospital&InstituteSichuan Cancer Center School of MedicineUniversity of Electronic Science and Technology of ChinaNo.55Section 4South Ren-min RoadChengdu610042SichuanPR China Department of Medical Ultrasound and Central Laboratory Shanghai Tenth People’s HospitalUltrasound Research and Education InstituteTongji University School of MedicineNo.301 Yan-chang-zhong RoadShanghai200072PR China International Academy of Targeted Therapeutics and Innovation Chongqing University of Arts and SciencesNO.319Red River AvenueYong-chuan402160ChongqingPR China Institute of Pathology and Southwest Cancer Center Southwest HospitalThird Military Medical University(Army Medical University)NO.30Gao-tan-yan-zheng StreetChongqing400038PR China

The presence of multiple immunosuppressive targets and insufficient activation and infiltration of cytotoxic T lymphocytes(CTLs)allow tumor cells to escape immune surveillance and disable anti-PD-1/PD-L1 ***-engineered autologous tumor vaccines(ATVs)that were camouflaged by tumor cell membrane(TCM)were designed to activate and facilitate CTLs infiltration for killing the unprotected lung tumor cells,consequently realizing the sequential ***5 was firstly screened out as a new immunosuppressive target of lung cancer in clinical *** afterwards,phosphodiesterase-5(PDE5)and programmed cell death 1 ligand 1(PD-L1)dual-target co-inhibition was proposed to unfreeze the immunosuppressive microenvironment of *** studies validated that this ATVs-unlocked sequential immunotherapy after co-encapsulating PDE5 inhibitor and NO donor(i.e.,L-arginine)exerted robust anti-tumor effects through increasing inducible nitric oxide synthase(iNOS)expression,blockading PDE5 pathway and activating systematic immune responses,which synergistically eradicated local and abscopal lung cancers in either orthotopic or subcutaneous *** pluripotent ATVs that enable PDE5 inhibition and sequential immunotherapy provide a new avenue to mitigate immunosuppressive microenvironment and magnify anti-PD-1/PD-L1 immunotherapy.

关键词： Autologous tumor vaccines(ATVs) Sequential immunotherapy Immunosuppressive microenvironment Tumor tropism Immune escape target

The Systematic Evaluation of Physicochemical and Biological Properties In Vitro and In Vivo for Natural Silk Fibroin Nanoparticles

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Advanced Fiber Materials 2022年第5期4卷 1141-1152页

作者： Xinyi Li Mengjie Ye Yong‑E.Gao Shengxin Hou Peng Jia Peng xue Yuejun Kang zhigang xu State Key Laboratory of Silkworm Genome Biology School of Materials and Energy and Chongqing Engineering Research Center for Micro‑Nano Biomedical Materials and DevicesSouthwest UniversityChongqing 400715People’s Republic of China Chongqing Key Laboratory of Soft‑Matter Material Chemistry and Function Manufacturing Southwest UniversityChongqing 400715People’s Republic of China

Nanoparticle-based theranostics has served as a preferential technology for diagnosis and treatment of ***,there are still massive challenges in constructing the ideal platform,which hopefully integrate various characteristics such as easy preparation,multiple utilization,and high therapeutic effect and safety into a single ***,we reported a drug delivery system-based on natural silk fibroin(denoted as SF NPs),and systematically evaluated the physicochemi-cal properties,biological properties and the biosafety assessment of SF *** in vitro and in vivo experimental results confirmed that SF NPs showed high stability,low blood hemolysis and the universal delivery ability of ***,the SF NPs could rapidly enter into cells due to its nanoscale size,and had a weak cytotoxicity against MCF-7,4T1 and L929 ***,the SF NPs showed enhanced tumor permeability in a simulative model of multicellular spheroids,combined with excellent in vivo biosafety and the negligible organ injury,demonstrate that SF-based nanomedicine presents the utilization potentiality for drug delivery and may provide a new view for cancer treatment.

关键词： Silk fibroin Drug delivery Biocompatibility Cytotoxicity Nanotheranostics

Single color image super-resolution using sparse representation and color constraint

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Journal of Systems Engineering and Electronics 2020年第2期31卷 266-271页

作者： xu zhigang MA Qiang YUAN Feixiang School of Computer and Communication Lanzhou University of TechnologyLanzhou 730050China

Color image super-resolution reconstruction based on the sparse representation model usually adopts the regularization norm(e.g.,L1 or L2).These methods have limited ability to keep image texture detail to some extent and are easy to cause the problem of blurring details and color artifacts in color reconstructed *** paper presents a color super-resolution reconstruction method combining the L2/3 sparse regularization model with color channel *** method converts the low-resolution color image from RGB to *** L2/3 sparse regularization model is designed to reconstruct the brightness channel of the input low-resolution color *** the color channel-constraint method is adopted to remove artifacts of the reconstructed highresolution *** method not only ensures the reconstruction quality of the color image details,but also improves the removal ability of color *** experimental results on natural images validate that our method has improved both subjective and objective evaluation.

关键词： color image sparse representation super-resolution L2/3 regularization norm color channel constraint

Design, preparation and pharmacodynamics of ICG-Fe(Ⅲ) based HCPT nanocrystals against cancer

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Asian Journal of Pharmaceutical Sciences 2022年第4期17卷 596-609页

作者： Qiongzhe Ren xuefeng Tang Yi Lu Qing Li Zhiqian Liao Shinan Jiang Haoli Zhang zhigang xu Lei Luo College of Pharmaceutical Sciences Southwest UniversityChongqing 400715China Department of Pathology Chongqing General HospitalUniversity of Chinese Academy of SciencesChongqing 401120China School of Materials and Energy and Chongqing Engineering Research Center for Micro–Nano Biomedical Materials and Devices Southwest UniversityChongqing 400715China State Key Laboratory of Applied Organic Chemistry(SKLAOC) College of Chemistry and Chemical EngineeringKey Laboratory of Special Function Materials and Structure Design(MOE)Lanzhou UniversityLanzhou 730000China

The use of nanocrystal technology to manufacture drug delivery systems intended to enhance therapeutic efficacy has attracted the attention of the pharmaceutical ***,the clinical application of nanocrystal drugs for injection is restricted by Ostwald ripening and the large-scale use of stabilizers such as polysorbate and lecithin,which have potential toxicity risks including hemolysis and ***,we designed an amorphous nanocrystal drug complex(IHNC),which is stabilizer-free and composed of indocyanine green(ICG)framework loading with a chemotherapeutic agent of 10-hydroxycamptothecin(HCPT).Considering the possibility of industrial manufacturing,IHNC was simply prepared with the assistance of ferric ion(III)via supramolecular assembly *** theoretical result of Materials Studio simulation indicated that the prepared ICG-Fe(III)framework showed a stable spherical structure with the appropriate cavity for encapsulating the two drugs of HCPT and ICG with equal mass *** IHNC was stable at physiological pH,with excellent PTT/PDT efficacy,and in vivo probing *** nanoscale size and reductive stimuli-responsiveness can be conducive to drug accumulation into the tumor site and rapid unloading of ***,such combination therapy showed synergistic photo/chemotherapy effect against 4T1 breast cancer and its tumor inhibition rate even up to 79.4%.These findings demonstrated that the nanocrystal drug delivery strategy could avoid the use of stabilizers and provide a new strategy for drug delivery for combination therapy.

关键词： Nanocrystal Stabilizer-free Stimuli-responsive Drug delivery Combination therapy

Improving fatigue properties of normal direction ultrasonic vibration assisted face grinding Inconel 718 by regulating machined surface integrity

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International Journal of Extreme Manufacturing 2024年第3期6卷 458-475页

作者： Nianwei xu Renke Kang Bi Zhang Yuan Zhang Chenxu Wang Yan Bao zhigang Dong State Key Laboratory of High-Performance Precision Manufacturing Dalian University of TechnologyDalian 116024People’s Republic of China Department of Mechanical and Energy Engineering Southern University of Science and TechnologyShenzhen 518055People’s Republic of China

Fatigue properties are crucial for critical aero-engine components in extreme serviceenvironments,which are significantly affected by surface integrity(SI)indexes(especially surface topography,residual stressσ_(res),and microhardness)after machining ***-direction ultrasonic vibration-assisted face grinding(ND-UVAFG)has advantages in improving the machinability of Inconel 718,but there is a competitive relationship between higher compressiveσ_(res)and higher surface roughness R_(a)in affecting fatigue *** lack of a quantitative relationship between multiple SI indexes and fatigue strength makes theindeterminacy of a regulatory strategy for improving fatigue *** this work,a model of fatigue strength(σ_f)_(sur)considering multiple SI indexes was ***,high-cycle fatigue tests were carried out on Inconel 718 samples with different SI characteristics,and the influence of ND-UVAFG process parameters on SI was *** on SI indexes data,the(σ_f)_(sur)distribution in the grinding surface layer for ND-UVAFG Inconel 718 samples was determined using the developed model,and then the fatigue crack initiation(FCI)sites were *** predicted FCI sites corresponded well with the experimental results,therebyverifying this model.A strategy for improving the fatigue life was proposed in this work,which was to transfer the fatigue source from the machined surface to the bulk material by controlling the SI ***,a critical condition of SI indexes that FCI sites appeared on the surface or in bulk material was given by fitting the predicted *** to the critical condition,an SI field where FCI sites appeared in the bulk material could be *** this field,thefatigue life of Inconel 718 samples could be improved by approximately 140%.

关键词： surface integrity fatigue strength Inconel 718 ultrasonic assisted grinding

Synthesis of a novel Al foam with a periodic architecture by introducing hollow Al tubes and Al/Mg powders

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Journal of Materials Science & Technology 2023年第17期148卷 105-115页

作者： zhigang xu Dayong Shen Kai Wang Peng He Jian Zhang Hao Zhang Peng Cao Shangyu Huang Jian Peng Qiang Shen Chuanbin Wang Lianmeng Zhang Hubei Key Laboratory of Advanced Technology for Automotive Components Wuhan University of TechnologyWuhan 430070China State Key Lab of Advanced Technology for Materials Synthesis and Processing Wuhan University of TechnologyWuhan 430070China School of Materials Science and Engineering Wuhan University of TechnologyWuhan 430070China Wuhan Second Ship Design and Research Institute Wuhan 430205China Department of Chemical and Materials Engineering University of AucklandPrivate Bag 92019Auckland 1142New Zealand

In this work,we synthesized a brand-new Al foam with a periodic structure via a simple powder metallurgical *** periodic architecture consists of both hierarchical porous and bi-directional composition-graded *** results show that the hierarchical porous material includes large pores on millimeter scale inheriting from the hollow structure of the Al tubes,and small pores on mi-crometer scale produced by the sintering of Al/Mg *** bi-directional Mg concentration-graded structure is formed in the tube walls due to the condensation of Mg vapor in the inner tube *** addition of Mg powders achieves excellent metallurgical bonding between the Al powders and the hollow tubes at 550℃.The plateau stress and energy absorption capacity of the Al foam in y-axis compression are significantly higher than that in the x-axis due to their anisotropic *** general,the Al foam with Mg addition presents the most superior compression performance,and we believe that our find-ings could open up a unique strategy for developing high-performance metallic foams with the periodic architecture involving both hierarchical porous and bi-directional graded structure.

关键词： Al foam Hollow Al tube Mg evaporation Bi-directional composition-graded structure Compression properties Energy absorbing performance

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海上油田电泵连接螺栓断裂原因

理化检验（物理分册） 2024年第6期60卷 51-55页

作者：冯电稳何泽宇杨中娜杨阳徐志刚徐振东高海宾中海油(天津)管道工程技术有限公司天津300452 天津北海油人力资源咨询服务有限公司天津300452 中海石油(中国)有限公司天津分公司天津300459

某海上油田电泵连接螺栓发生断裂现象,采用宏观观察、断口分析、化学成分分析、硬度测试、金相检验等方法分析螺栓断裂的原因。结果表明:螺栓的断裂模式为疲劳断裂,在服役过程中,螺栓根部发生点腐蚀,进而引起应力腐蚀微裂纹,在电泵振动... 详细信息

某海上油田电泵连接螺栓发生断裂现象,采用宏观观察、断口分析、化学成分分析、硬度测试、金相检验等方法分析螺栓断裂的原因。结果表明:螺栓的断裂模式为疲劳断裂,在服役过程中,螺栓根部发生点腐蚀,进而引起应力腐蚀微裂纹,在电泵振动应力的作用下,腐蚀微裂纹进一步扩展,直至螺栓断裂。

关键词：点腐蚀微裂纹疲劳断裂表面锈蚀显微组织

Engineering prodrug nanomicelles as pyroptosis inducer for codelivery of PI3K/mTOR and CDK inhibitors to enhance antitumor immunity

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Acta Pharmaceutica Sinica B 2022年第7期12卷 3139-3155页

作者： Qichao Yang Xianbin Ma Yao Xiao Tian Zhang Leilei Yang Shaochen Yang Mengyun Liang Shuo Wang Zhizhong Wu zhigang xu Zhijun Sun The State Key Laboratory Breeding Base of Basic Science of Stomatology(Hubei-MOST)&Key Laboratory of Oral Biomedicine Ministry of Education School&Hospital of StomatologyWuhan UniversityWuhan 430079China Key Laboratory of Luminescence Analysis and Molecular Sensing(Southwest University) Ministry of EducationSchool of Materials and Energy&Chongqing Engineering Research Center for Micro-Nano Biomedical Materials and DevicesSouthwest UniversityChongqing 400715China

Aberrant activation of oncogenic signaling pathways in tumors can promote resistance to the antitumor immune ***,single blockade of these pathways is usually ineffective because of the complex crosstalk and feedback among oncogenic signaling *** enhanced toxicity of free small molecule inhibitor combinations is considered an insurmountable barrier to their clinical *** circumvent this issue,we rationally designed an effective tumor microenvironment-activatable prodrug nanomicelle(PNM)for cancer *** was engineered by integrating the PI3K/m TOR inhibitor PF-04691502(PF)and the broad spectrum CDK inhibitor flavopiridol(Flav)into a single nanoplatform,which showed tumor-specific accumulation,activation and deep penetration in response to the high glutathione(GSH)tumoral *** codelivery of PF and Flav could trigger gasdermin E(GSDME)-based immunogenic pyroptosis of tumor cells to elicit a robust antitumor immune ***,the combination of PNM-induced immunogenic pyroptosis with antiprogrammed cell death-1(a PD-1)immunotherapy further boosted the antitumor effect and prolonged the survival time of ***,these results indicated that the pyroptosis-induced nanoplatform codelivery of PI3K/m TOR and CDK inhibitors can reprogram the immunosuppressive tumor microenvironment and efficiently improve checkpoint blockade cancer immunotherapy.

关键词： Pyroptosis Prodrug Stimuli-responsive Immunotherapy Targeted therapy Tumor microenvironment

EEI反演技术在西非深水砂岩储层岩性预测中的应用

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石化技术 2024年第7期31卷 255-258页

作者：赵佳奇许志刚王嘉赵红岩武静孔令武中国海洋石油国际有限公司北京100028

扩展弹性阻抗(EEI)是对弹性阻抗(EI)的改进,融合了叠后声波阻抗(AI)和叠前AVO技术的优势。阐述了EEI方法的基本原理,介绍了关键的流程步骤,包括储层预测前的数据准备、EEI最优角度的确定、反演模型的建立与实施反演,并针对西非深水某研... 详细信息

扩展弹性阻抗(EEI)是对弹性阻抗(EI)的改进,融合了叠后声波阻抗(AI)和叠前AVO技术的优势。阐述了EEI方法的基本原理,介绍了关键的流程步骤,包括储层预测前的数据准备、EEI最优角度的确定、反演模型的建立与实施反演,并针对西非深水某研究区的浊积砂岩储层目标进行了实例应用,对EEI反演的效果进行了分析。根据研究区地层、岩性的特点,采用EEI方法,结合岩性敏感参数GR曲线,进行角度扫描求取最优岩性角度及EEI曲线,同时结合叠前地震道集反演的EEI体,预测岩性、刻画优势砂体平面展布特征,其结果实现了有利岩性圈闭和储层的预测,有效支持了勘探目标潜力评价和区块优选。

关键词：扩展弹性阻抗弹性阻抗最优角度储层预测

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