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Immunostimulatory gene therapy combined with checkpoint blockade reshapes tumor microenvironment and enhances ovarian cancer immunotherapy

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Acta Pharmaceutica Sinica B 2024年第2期14卷 854-868页

作者： Yunzhu Lin Xiang Wang Shi He Zhongxin Duan yunchu zhang Xiaodong Sun Yuzhu Hu Yuanyuan zhang Zhiyong Qian Xiang Gao Zhirong zhang Key Laboratory of Drug Targeting and Drug Delivery Systems Ministry of EducationWest China School of PharmacySichuan UniversityChengdu 610041China Department of Pharmacy Evidence-based Pharmacy CenterWest China Second University HospitalKey Laboratory of Birth Defects and Related Diseases of Women and ChildrenSichuan UniversityChengdu 610041China Department of Neurosurgery and Institute of Neurosurgery State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalWest China Medical SchoolSichuan University and Collaborative Innovation Center for BiotherapyChengdu 610041China Department of Radiation Oncology State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalWest China Medical SchoolSichuan University and Collaborative Innovation Center for BiotherapyChengdu 610041China West China School of Basic Medical Sciences&Forensic Medicine Sichuan UniversityChengdu 610041China

Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN-γ release and subsequently upregulate PDL-1 expression on tumor cells. Therefore, the tumor-targeting folate-modified delivery system F-DPC is constructed for concurrent delivery of IL-12 encoding gene and small molecular PDL-1 inhibitor(i PDL-1) to reduce immune escape and boost anti-tumor immunity. The physicochemical characteristics, gene transfection efficiency of the F-DPC nanoparticles in ovarian cancer cells are analyzed. The immune-modulation effects of combination therapy on different immune cells are also studied. Results show that compared with non-folate-modified vector, folate-modified F-DPC can improve the targeting of ovarian cancer and enhance the transfection efficiency of p IL-12. The underlying anti-tumor mechanisms include the regulation of T cells proliferation and activation, NK activation,macrophage polarization and DC maturation. The F-DPC/p IL-12/i PDL-1 complexes have shown outstanding antitumor effects and low toxicity in peritoneal model of ovarian cancer in mice. Taken together, our work provides new insights into ovarian cancer immunotherapy. Novel F-DPC/p IL-12/i PDL-1 complexes are revealed to exert prominent anti-tumor effect by modulating tumor immune microenvironment and preventing immune escape and might be a promising treatment option for ovarian cancer treatment.

关键词： IL-12encodinggene Checkpointblocker Nanoparticles Targeted delivery Tumormicroenvironment Immune escape Ovarian cancer Immunotherapy

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改进YOLOv7的轧钢车间安全帽佩戴检测算法

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计算机测量与控制 2024年第7期32卷 15-22页

作者：张欣毅张运楚王菲刘一铭山东建筑大学信息与电气工程学院济南250101 山东省智能建筑技术重点实验室济南250101

佩戴安全帽能够保护生产工作者头部免受坠物撞击带来的伤害;轧钢车间存在空间跨度大、作业设备繁多、环境杂乱、昼夜光照差别大、炫光、监控目标尺度变化范围大等问题,增加了安全帽佩戴检测难度;针对上述问题,设计了基于改进YOLOv7模型... 详细信息

佩戴安全帽能够保护生产工作者头部免受坠物撞击带来的伤害;轧钢车间存在空间跨度大、作业设备繁多、环境杂乱、昼夜光照差别大、炫光、监控目标尺度变化范围大等问题,增加了安全帽佩戴检测难度;针对上述问题,设计了基于改进YOLOv7模型的轧钢车间安全帽佩戴检测方案;算法基于NWD方法改进损失函数以提高目标检测精度,并在SPPCSPC模块上增加了BiFormer模块,使模型对小目标具有更好的检测精度,同时不会增加运算负担,优于其他注意力机制;在自建安全帽数据集上对改进的YOLOv7模型进行训练,实验表明,改进的YOLOv7模型平均精度均值为99.3%,检测速度达82FPS,与其他主流算法、改进算法对比,改进YOLOv7的mAP指标最高,大大超过了其他模型的指标,同时检测速度基本与改进模型前相差不大,并没有因为精度提高而明显降低检测速度,有较好效果。

关键词：轧钢车间安全帽检测 YOLOv7 NWD BiFormer

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Co-delivery of doxorubicin and curcumin via cRGD-peptide modified PEG-PLA self-assembly nanomicelles for lung cancer therapy

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Chinese Chemical Letters 2022年第5期33卷 2507-2511页

作者： yunchu zhang Tingting Li Yuzhu Hu Jing Chen Yihong He Xiang Gao Yan zhang Department of Thoracic Oncology Cancer CenterState Key Laboratory of BiotherapyWest China HospitalWest China Medical SchoolSichuan University and Collaborative Innovation Center for BiotherapyChengdu 610041China Department of Neurosurgery and Institute of Neurosurgery State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalWest China Medical SchoolSichuan University and Collaborative Innovation Center for BiotherapyChengdu 610041China

Lung cancer is the most common malignancy in the world, with a high mortality rate. Nevertheless,therapies to act effectively against lung cancer remain elusive. So far, chemotherapy is still the frontline treatment of lung cancer. Doxorubicin(DOX) is a broad-spectrum anti-tumor drug. However, DOX often has serious side effects and causes multi-drug resistance, which greatly limits its clinical *** this work, biodegradable methoxy poly(ethylene glycol)-poly(lactic acid)(MPEG-PLA) and cyclo(ArgGly-Asp-D-Phe-Lys)(c RGD) polypeptide modified PEG-PLA(c RGD-PEG-PLA) copolymers were used for the co-delivery of curcumin(CUR) and DOX(CUR-DOX/c RGD-M). The particle size of the self-assembled drugloaded nanomicelle approximately was 27.4 nm and the zeta potential was -2.7mV. Interestingly, CUR can enhance the uptake of DOX by Lewis lung carcinoma(LL/2) cells. The experimental results in vivo and in vitro showed that CUR-DOX/c RGD-M combination therapy could promote apoptosis of lung cancer cells, and conspicuously inhibit the tumor growth. Our data indicate that CUR-DOX/c RGD-M will be biodegradable and sustainable, which may have potential clinical application value in the treatment of lung cancer.

关键词： Doxorubicin Curcumin Lung cancer Nanomicelle Co-delivery

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基于改进YOLOv5s的焦炉烟火识别算法

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计算机测量与控制 2024年第5期32卷 186-192,200页

作者：刘一铭张运楚周燕菲张欣毅山东建筑大学信息与电气工程学院济南250101 山东省智能建筑技术重点实验室济南250101

针对炼焦厂烟火排放全天候环保监测的要求,提出了基于改进YOLOv5s的焦炉烟火识别算法;该算法以YOLOv5s为基础网络,在主干网络Backbone中添加CBAM注意力机制模块,使网络更加关注重要的特征,提升目标检测的准确率;新增FReLU激活函数代替S... 详细信息

针对炼焦厂烟火排放全天候环保监测的要求,提出了基于改进YOLOv5s的焦炉烟火识别算法;该算法以YOLOv5s为基础网络,在主干网络Backbone中添加CBAM注意力机制模块,使网络更加关注重要的特征,提升目标检测的准确率;新增FReLU激活函数代替SiLU激活函数,提高激活空间的灵敏度,改善烟火图像视觉任务;在自建数据集中烟、火样本标签基础上,增加灯光标签来解决强灯光对火焰识别的干扰,并通过分流训练、检测的方式来解决昼夜场景的烟火检测问题;在自建数据集上做对比实验,更换激活函数后,联合CBAM模块的YOLOv5s模型效果最佳;实验结果显示,与原始YOLOv5s模型相比,在白天场景下的烟火识别mAP值提升了6.7%,在夜间场景下的烟火识别mAP值高达97.4%。

关键词：烟火识别 YOLOv5s 注意力机制激活函数目标检测

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架空线路绝缘子破损视觉检测研究

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高技术通讯 2005年第8期15卷 35-38页

作者：张运楚梁自泽谭民中国科学院自动化研究所复杂系统与智能科学重点实验室北京100080

研究了架空线路瓷绝缘子破损视觉检测问题.基于瓷绝缘子局部区域特征,采用三层BP神经元网络从复杂背景中识别出目标绝缘子并定位,然后采用扫描分析绝缘子图像窗口纵向剖线模式的方法,判定绝缘子的完好状态,最后进行了仿真和实验.实验验... 详细信息

研究了架空线路瓷绝缘子破损视觉检测问题.基于瓷绝缘子局部区域特征,采用三层BP神经元网络从复杂背景中识别出目标绝缘子并定位,然后采用扫描分析绝缘子图像窗口纵向剖线模式的方法,判定绝缘子的完好状态,最后进行了仿真和实验.实验验证了绝缘子破损视觉检测方法的可行性.

关键词：巡线机器人视觉检测目标识别绝缘子线路绝缘子架空线路破损 BP神经元网络瓷绝缘子区域特征

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N-doped graphene quantum dot-decorated N-TiO2/P-doped porous hollow g-C_(3)N_(4) nanotube composite photocatalysts for antibiotic photodegradation and H2 production

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International Journal of Minerals,Metallurgy and Materials 2024年第1期31卷 165-178页

作者： Jingshu Yuan Yao zhang Xiaoyan zhang Junjie zhang Shen’gen zhang Institute for Advanced Materials and Technology University of Science and Technology BeijingBeijing 100083China Xi’an Fanyi University Xi’an 710105China Shunde Graduate School of University of Science and Technology Beijing Foshan 528399China State Key Laboratory of Lunar and Planetary Sciences Macao University of Science and TechnologyMacao SAR 820000China

Exclusive responsiveness to ultraviolet light (~3.2 eV) and high photogenerated charge recombination rate are the two primary drawbacks of pure TiO_(2). We combined N-doped graphene quantum dots (N-GQDs), morphology regulation, and heterojunction construction strategies to synthesize N-GQD/N-doped TiO_(2)/P-doped porous hollow g-C_(3)N_(4) nanotube (PCN) composite photocatalysts (denoted as G-TPCN). The optimal sample (G-TPCN doped with 0.1wt% N-GQD, denoted as 0.1% G-TPCN) exhibits significantly enhanced photoabsorption, which is attributed to the change in bandgap caused by elemental doping (P and N), the improved light-harvesting resulting from the tube structure, and the upconversion effect of N-GQDs. In addition, the internal charge separation and transfer capability of0.1% G-TPCN are dramatically boosted, and its carrier concentration is 3.7, 2.3, and 1.9 times that of N-TiO_(2), PCN, and N-TiO_(2)/PCN(TPCN-1), respectively. This phenomenon is attributed to the formation of Z-scheme heterojunction between N-TiO_(2) and PCNs, the excellent electron conduction ability of N-GQDs, and the short transfer distance caused by the porous nanotube structure. Compared with those of N-TiO_(2), PCNs, and TPCN-1, the H2 production activity of 0.1%G-TPCN under visible light is enhanced by 12.4, 2.3, and 1.4times, respectively, and its ciprofloxacin (CIP) degradation rate is increased by 7.9, 5.7, and 2.9 times, respectively. The optimized performance benefits from excellent photoresponsiveness and improved carrier separation and migration efficiencies. Finally, the photocatalytic mechanism of 0.1% G-TPCN and five possible degradation pathways of CIP are proposed. This study clarifies the mechanism of multiple modification strategies to synergistically improve the photocatalytic performance of 0.1% G-TPCN and provides a potential strategy for rationally designing novel photocatalysts for environmental remediation and solar energy conversion.

关键词： N-doped TiO_(2) N-doped graphene quantum dots P-doped g-C_(3)N_(4) porous hollow nanotube heterojunction photocatalysis

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Reversing free-electron transfer of sulfide cocatalyst for exceptional photocatalytic H_(2)evolution

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Journal of Materials Science & Technology 2024年第4期171卷 147-149页

作者： Yanfeng zhang Zhenyi zhang National Experimental Chemistry Teaching Center Hebei Key Laboratory of Inorganic Nano-materialsCollege of Chemistry and Materials ScienceHebei Normal UniversityShijiazhuang 050024China Key Laboratory of New Energy and Rare Earth Resource Utilization of State Ethnic Affairs Commission Key Laboratory of Photosensitive Materials and Devices of Liaoning ProvinceSchool of Physics and Materials EngineeringDalian Minzu UniversityDalian 116600China

Recently,Yu and co-workers deeply explore the potential impact of free electron transfer between co-catalysts and photocatalyst carriers on H_(2)evolution efficiency of active sites over MoS_(2+x).They pro-pose an electron-reversal tactics to evade the unexpected electron transfer and synchronously regulate the above transfer in a beneficial orientation for weakening hydrogen adsorption on S ***,this highlight not only discusses and summarizes the essences of electron reversal and the optimized H ad-sorption/desorption mechanism,but also emphasizes the significance of femtosecond transient absorp-tion spectroscopy(fs-TAS)and in-situ irradiated X-ray photoelectron spectroscopy(ISI-XPS)for revealing charge transfer dynamics and *** anticipate that this highlight can disseminate a new per-spective on the roles of photocatalyst carriers in improving cocatalytic H_(2)-production kinetics.

关键词： Photocatalysis Cocatalyst Electron reversal Antibonding-orbital occupancy S–H bonds

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Deep Guided Attention Network for Joint Denoising and Demosaicing in Real Image

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Chinese Journal of Electronics 2024年第1期33卷 303-312页

作者： Tao zhang Ying FU Jun zhang School of Computer Science and Technology Beijing Institute of Technology Advanced Reasearch Institute of Multidisciplinary Science Beijing Institute of Technology

Denoising(DN) and demosaicing(DM) are the first crucial stages in the image signal processing pipeline. Recently, researches pay more attention to solve DN and DM in a joint manner, which is an extremely undetermined inverse problem. Existing deep learning methods learn the desired prior on synthetic dataset, which limits the generalization of learned network to the real world data. Moreover, existing methods mainly focus on the raw data property of high green information sampling rate for DM, but occasionally exploit the high intensity and signalto-noise(SNR) of green channel. In this work, a deep guided attention network(DGAN) is presented for real image joint DN and DM(JDD), which considers both high SNR and high sampling rate of green information for DN and DM, respectively. To ease the training and fully exploit the data property of green channel, we first train DN and DM sub-networks sequentially and then learn them jointly, which can alleviate the error accumulation. Besides, in order to support the real image JDD, we collect paired raw clean RGB and noisy mosaic images to conduct a realistic dataset. The experimental results on real JDD dataset show the presented approach performs better than the state-of-the-art methods, in terms of both quantitative metrics and qualitative visualization.

关键词： Training Visualization Inverse problems Green products Noise reduction Pipelines Signal processing

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Value Iteration-Based Cooperative Adaptive Optimal Control for Multi-Player Differential Games With Incomplete Information

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IEEE/CAA Journal of Automatica Sinica 2024年第3期11卷 690-697页

作者： Yun zhang Lulu zhang Yunze Cai the Department of Automation Shanghai Jiao Tong UniversityShanghai 200240 the Key Laboratory of System Control and Information Processing Ministry of Education of ChinaShanghai 200240China

This paper presents a novel cooperative value iteration(VI)-based adaptive dynamic programming method for multi-player differential game models with a convergence *** players are divided into two groups in the learning process and adapt their policies *** method removes the dependence of admissible initial policies,which is one of the main drawbacks of the PI-based ***,this algorithm enables the players to adapt their control policies without full knowledge of others’ system parameters or control *** efficacy of our method is illustrated by three examples.

关键词： Adaptive dynamic programming incomplete information multi-player differential game value iteration

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Host plant traits play a crucial role in shaping the composition of epiphytic microbiota in the arid desert,Northwest China

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Journal of Arid Land 2024年第5期16卷 699-724页

作者： zhang Jun zhang Yuanming zhang Qi State Key Laboratory of Desert and Oasis Ecology Key Laboratory of Ecological Safety and Sustainable Development in Arid LandsXinjiang Institute of Ecology and GeographyChinese Academy of SciencesUrumqi 830011China Xinjiang Key Laboratory of Biodiversity Conservation and Application in Arid Lands Xinjiang Institute of Ecology and GeographyChinese Academy of SciencesUrumqi 830011China Xinjiang Field Scientific Observation Research Station of Tianshan Wild Fruit Forest Ecosystem Yili Botanical GardenXinjiang Institute of Ecology and GeographyChinese Academy of SciencesUrumqi 830011China College of Life Sciences Shihezi UniversityShihezi 832003China

Phyllosphere microorganisms are a crucial component of environmental microorganisms,highly influenced by host characteristics,and play a significant role in plant health and ***,the impact of host characteristics on shaping phyllosphere microbial communities of plants with different life forms remains *** high-throughput sequencing technology,this study analyzed the diversity and community composition of phyllosphere epiphytic microorganisms(e.g.,bacteria and fungi)of various plant life forms in the hinterland of the Gurbantunggut Desert,Northwest *** annotation of prokaryotic taxa(FAPROTAX)and fungi function guild(FUNGuild)were employed to assess the ecological functions of microorganisms and to investigate the role of stochastic and deterministic processes in shaping phyllosphere microbial *** showed a diverse array of phyllosphere epiphytic microorganisms in the desert plants,with Proteobacteria,Cyanobacteria,and Actinobacteriota dominating bacterial community,while Ascomycota and Basidiomycota were prevalent in fungal *** across different plant life forms highlighted distinct microbial communities,indicating strong filtering effects by plant *** prediction identified intracellular parasites(accounting for 27.44%of bacterial community abundance),chemoheterotrophy(10.12%),and phototrophy(17.41%)as the main functions of epiphytic bacteria on leaves of different life form *** prediction indicated that phyllosphere epiphytic fungi primarily served as Saprotrophs(81.77%),Pathotrophs(17.41%),and Symbiotrophs(0.82%).Co-occurrence network analysis demonstrated a predominance of positive correlations among different microbial ***-Crick dissimilarity index analysis revealed that deterministic processes predominantly influenced phyllosphere bacterial and fungal community *** partitioning analysis and random forest modeling suggested that pla

关键词： phyllosphere epiphytic bacteria phyllosphere epiphytic fungi community structure community diversity functional diversity plant life form plant functional traits

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