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Shuilin Shen,Zimeng Zhang,Haixiao Huang,Jing Yang,Xinyue Tao,Zhengjie Meng,Hao Ren,Xueming Li 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00
Background Immunogenic cell death (ICD) induced by different cancer treatments has been widely evaluated to recruit immune cells and trigger the specific antitumor immunity. However, cancer associated fibroblasts (CAFs) can hinder the invasion of immune cells and polarize the recruited monocytes to M2-type macrophages, which greatly restrict the efficacy of immunotherapy (IT). Methods In this study, an injectable hydrogel induced by copper (Cu) has been designed to contain antibody of PD-L1 and nitric oxide (NO) donor. The therapeutic efficacy of hydrogel was studied in 4T1 cells and CAFs in vitro and 4T1 tumor-bearing mice in vivo. The immune effects on cytotoxic T lymphocytes, dendritic cells (DCs) and macrophages were analyzed by flow cytometry. Enzyme-linked immunosorbent assay, immunofluorescence and transcriptome analyses were also performed to evaluate the underlying mechanism. Results Due to the absorbance of Cu with the near-infrared laser irradiation, the injectable hydrogel exhibits persistent photothermal effect to kill cancer cells. In addition, the Cu of hydrogel shows the Fenton-like reaction to produce reactive oxygen species as chemodynamic therapy, thereby enhancing cancer treatment and amplifying ICD. More interestingly, we have found that the released NO can significantly increase depletion of CAFs and reduce the proportion of M2-type macrophages in vitro. Furthermore, due to the amplify of ICD, injectable hydrogel can effectively increase the infiltration of immune cells and reverse the immunosuppressive tumor microenvironment (TME) by regulating CAFs to enhance the therapeutic efficacy of anti-PD-L1 in vivo. Conclusions The ion induced self-assembled hydrogel with NO could enhance immunotherapy via amplifying ICD and regulating CAFs. It provides a novel strategy to provoke a robust antitumor immune response for clinical cancer immunotherapy.
Hao Han,Jingming Hou,Zongxue Xu,Haixiao Jing,Jiahui Gong,Depeng Zuo,Bingyao Li,Shaoxiong Yang,Yongde Kang,Run Wang 대한토목학회 2022 KSCE JOURNAL OF CIVIL ENGINEERING Vol.26 No.3
Frequent urban rainstorm inundations can cause serious damages to human life and social economy. Reliable simulation of urban rainstorm inundation is an effective approach for performing flood risk analysis to reduce losses. In this work, a full 2D high-performance hydrodynamic model for urban rainstorm inundation simulation based on Graphic Processing Unit (GPU) was developed. The idealized V-shape catchment and sponge city district of Fengxi New City were selected as the study areas to assess performance of the model. The model was validated against analytical benchmark results of the idealized V-catchment test which show good agreement between the modelled flow and analytical solutions. The model was then applied to simulate actual urban rainstorm inundation process under measured rainfall. The results indicated that the model can be applied to high-resolution urban region simulations. Specifically, the validation results indicated that the proposed model had a good performance, with an accepted error of less than 15%. When applied to compute the Fengxi New city under design rainstorms with different annual return periods of 1, 5, 10, 20, 50, and 100 years, it was found that the model effectively evaluated the temporal and spatial variation process of urban inundation, and quantitatively investigated flood risks according to the water depth change. The model has been substantially accelerated on GPU to quickly predict urbaninundation. The accuracy and rapid simulation speed of the model were verified based on the actual study area. Therefore, the proposed model can help to predict the dynamic processes of urban flood inundation and thus reduce flood inundation disasters. This is essential for future optimal sponge urban construction planning in China.