Table_1_Combination of Radiofrequency Ablation With Resiquimod to Treat Hepatocellular Carcinoma Via Inflammation of Tumor Immune Microenvironment and Suppression of Angiogenesis.docx

BackgroundRadiofrequency ablation (RFA) destroys tumors through hyperthermic injury, which induces the release of immunogenic intracellular substrates and damages associated molecular patterns (DAMPs) to evoke a systemic immune response, but its therapeutic effect is limited. This study aimed to combine RFA with an immunomodulator, resiquimod (R848), to enhance the RFA-induced antitumor immunity.MethodsWe performed RFA on subcutaneous tumors in immunocompetent mice and intraperitoneally injected R848 to observe the efficacy of the combination therapy. Our research investigated changes in the composition of tumor-infiltrating immune cells in primary and distant tumors by flow cytometry. Natural killer (NK) cell depletion experiment was applied to confirm the role of NK cell in the combination therapy. The expression levels of cytokines and chemokines were detected by real-time quantitative PCR. Immunohistochemical test was conducted to reveal tumor angiogenesis, tumor proliferation, and apoptosis after the different treatments.Results and ConclusionCompared with RFA or R848 monotherapy, the combination therapy significantly slowed the tumor growth, prolonged the survival time, and shrank the tumor-draining lymph nodes of tumor-bearing mice. The flow cytometry results showed that tumor-infiltrating immune cells, total T cells, the ratio of CD8+ T and NK cells to CD45+ cells, and functional NK cells were obviously increased after the combined treatment. Distal tumor growth was also suppressed, and the profile of tumor-infiltrating immune cells was remodeled, too. In addition, the additive effect of the combination therapy disappeared after NK cell depletion. Furthermore, immunohistochemical results verified that R848 inhibited tumor angiogenesis in murine liver cancer, and the combination therapy promoted tumor cell apoptosis. In conclusion, our data suggest that RFA combined with R848 stimulated a stronger antitumor immune response and effectively inhibited liver cancer progression in a NK cell-dependent manner. Meanwhile, we confirmed that R848 inhibited tumor angiogenesis and promoted apoptosis in murine liver cancer. Overall, this is a promising therapeutic strategy to improve the efficacy of RFA in the treatment of liver cancer and provides a novel option for combined thermal ablation and immunotherapy.</p

Image_5_Combination of Radiofrequency Ablation With Resiquimod to Treat Hepatocellular Carcinoma Via Inflammation of Tumor Immune Microenvironment and Suppression of Angiogenesis.tif

BackgroundRadiofrequency ablation (RFA) destroys tumors through hyperthermic injury, which induces the release of immunogenic intracellular substrates and damages associated molecular patterns (DAMPs) to evoke a systemic immune response, but its therapeutic effect is limited. This study aimed to combine RFA with an immunomodulator, resiquimod (R848), to enhance the RFA-induced antitumor immunity.MethodsWe performed RFA on subcutaneous tumors in immunocompetent mice and intraperitoneally injected R848 to observe the efficacy of the combination therapy. Our research investigated changes in the composition of tumor-infiltrating immune cells in primary and distant tumors by flow cytometry. Natural killer (NK) cell depletion experiment was applied to confirm the role of NK cell in the combination therapy. The expression levels of cytokines and chemokines were detected by real-time quantitative PCR. Immunohistochemical test was conducted to reveal tumor angiogenesis, tumor proliferation, and apoptosis after the different treatments.Results and ConclusionCompared with RFA or R848 monotherapy, the combination therapy significantly slowed the tumor growth, prolonged the survival time, and shrank the tumor-draining lymph nodes of tumor-bearing mice. The flow cytometry results showed that tumor-infiltrating immune cells, total T cells, the ratio of CD8+ T and NK cells to CD45+ cells, and functional NK cells were obviously increased after the combined treatment. Distal tumor growth was also suppressed, and the profile of tumor-infiltrating immune cells was remodeled, too. In addition, the additive effect of the combination therapy disappeared after NK cell depletion. Furthermore, immunohistochemical results verified that R848 inhibited tumor angiogenesis in murine liver cancer, and the combination therapy promoted tumor cell apoptosis. In conclusion, our data suggest that RFA combined with R848 stimulated a stronger antitumor immune response and effectively inhibited liver cancer progression in a NK cell-dependent manner. Meanwhile, we confirmed that R848 inhibited tumor angiogenesis and promoted apoptosis in murine liver cancer. Overall, this is a promising therapeutic strategy to improve the efficacy of RFA in the treatment of liver cancer and provides a novel option for combined thermal ablation and immunotherapy.</p

Image_1_Combination of Radiofrequency Ablation With Resiquimod to Treat Hepatocellular Carcinoma Via Inflammation of Tumor Immune Microenvironment and Suppression of Angiogenesis.tif

BackgroundRadiofrequency ablation (RFA) destroys tumors through hyperthermic injury, which induces the release of immunogenic intracellular substrates and damages associated molecular patterns (DAMPs) to evoke a systemic immune response, but its therapeutic effect is limited. This study aimed to combine RFA with an immunomodulator, resiquimod (R848), to enhance the RFA-induced antitumor immunity.MethodsWe performed RFA on subcutaneous tumors in immunocompetent mice and intraperitoneally injected R848 to observe the efficacy of the combination therapy. Our research investigated changes in the composition of tumor-infiltrating immune cells in primary and distant tumors by flow cytometry. Natural killer (NK) cell depletion experiment was applied to confirm the role of NK cell in the combination therapy. The expression levels of cytokines and chemokines were detected by real-time quantitative PCR. Immunohistochemical test was conducted to reveal tumor angiogenesis, tumor proliferation, and apoptosis after the different treatments.Results and ConclusionCompared with RFA or R848 monotherapy, the combination therapy significantly slowed the tumor growth, prolonged the survival time, and shrank the tumor-draining lymph nodes of tumor-bearing mice. The flow cytometry results showed that tumor-infiltrating immune cells, total T cells, the ratio of CD8+ T and NK cells to CD45+ cells, and functional NK cells were obviously increased after the combined treatment. Distal tumor growth was also suppressed, and the profile of tumor-infiltrating immune cells was remodeled, too. In addition, the additive effect of the combination therapy disappeared after NK cell depletion. Furthermore, immunohistochemical results verified that R848 inhibited tumor angiogenesis in murine liver cancer, and the combination therapy promoted tumor cell apoptosis. In conclusion, our data suggest that RFA combined with R848 stimulated a stronger antitumor immune response and effectively inhibited liver cancer progression in a NK cell-dependent manner. Meanwhile, we confirmed that R848 inhibited tumor angiogenesis and promoted apoptosis in murine liver cancer. Overall, this is a promising therapeutic strategy to improve the efficacy of RFA in the treatment of liver cancer and provides a novel option for combined thermal ablation and immunotherapy.</p

Image_4_Combination of Radiofrequency Ablation With Resiquimod to Treat Hepatocellular Carcinoma Via Inflammation of Tumor Immune Microenvironment and Suppression of Angiogenesis.tif

BackgroundRadiofrequency ablation (RFA) destroys tumors through hyperthermic injury, which induces the release of immunogenic intracellular substrates and damages associated molecular patterns (DAMPs) to evoke a systemic immune response, but its therapeutic effect is limited. This study aimed to combine RFA with an immunomodulator, resiquimod (R848), to enhance the RFA-induced antitumor immunity.MethodsWe performed RFA on subcutaneous tumors in immunocompetent mice and intraperitoneally injected R848 to observe the efficacy of the combination therapy. Our research investigated changes in the composition of tumor-infiltrating immune cells in primary and distant tumors by flow cytometry. Natural killer (NK) cell depletion experiment was applied to confirm the role of NK cell in the combination therapy. The expression levels of cytokines and chemokines were detected by real-time quantitative PCR. Immunohistochemical test was conducted to reveal tumor angiogenesis, tumor proliferation, and apoptosis after the different treatments.Results and ConclusionCompared with RFA or R848 monotherapy, the combination therapy significantly slowed the tumor growth, prolonged the survival time, and shrank the tumor-draining lymph nodes of tumor-bearing mice. The flow cytometry results showed that tumor-infiltrating immune cells, total T cells, the ratio of CD8+ T and NK cells to CD45+ cells, and functional NK cells were obviously increased after the combined treatment. Distal tumor growth was also suppressed, and the profile of tumor-infiltrating immune cells was remodeled, too. In addition, the additive effect of the combination therapy disappeared after NK cell depletion. Furthermore, immunohistochemical results verified that R848 inhibited tumor angiogenesis in murine liver cancer, and the combination therapy promoted tumor cell apoptosis. In conclusion, our data suggest that RFA combined with R848 stimulated a stronger antitumor immune response and effectively inhibited liver cancer progression in a NK cell-dependent manner. Meanwhile, we confirmed that R848 inhibited tumor angiogenesis and promoted apoptosis in murine liver cancer. Overall, this is a promising therapeutic strategy to improve the efficacy of RFA in the treatment of liver cancer and provides a novel option for combined thermal ablation and immunotherapy.</p

Modeling and Simulation of Borstar Bimodal Polyethylene Process Based on a Rigorous PC-SAFT Equation of State Model

This work aims to develop a rigorous model for industrial successive supercritical slurry-phase and gas-phase catalytic polymerization reactors of the Borstar bimodal polyethylene process. The model consists of thermodynamic modeling, multisite Ziegler–Natta polymerization kinetics, and reactor modeling. The perturbed-chain statistical associating fluid theory equation of state (PC-SAFT EOS) with updated parameters allows an accurate description of the phase equilibria of the supercritical slurry-phase and gas-phase system in a wide range of temperatures and pressures. The model predictions of the process variables (i.e., residence time, molar ratio of H2/C2H4 and H2/1-C4H8 of each reactor) and polymer properties (i.e., molecular weight, comonomer content, molecular weight distribution (MWD)) agree well with the industrial plant data under multi-steady-state operation conditions. The model is also capable of simulating the effects on the MWD of bimodal polyethylene resulting from the hydrogen inflow rate in a supercritical slurry-phase loop reactor (SLR) and a gas-phase fluidized bed reactor (FBR), as well as the supercritical solvent propane inflow rate of the SLR

Image_6_Combination of Radiofrequency Ablation With Resiquimod to Treat Hepatocellular Carcinoma Via Inflammation of Tumor Immune Microenvironment and Suppression of Angiogenesis.jpeg

BackgroundRadiofrequency ablation (RFA) destroys tumors through hyperthermic injury, which induces the release of immunogenic intracellular substrates and damages associated molecular patterns (DAMPs) to evoke a systemic immune response, but its therapeutic effect is limited. This study aimed to combine RFA with an immunomodulator, resiquimod (R848), to enhance the RFA-induced antitumor immunity.MethodsWe performed RFA on subcutaneous tumors in immunocompetent mice and intraperitoneally injected R848 to observe the efficacy of the combination therapy. Our research investigated changes in the composition of tumor-infiltrating immune cells in primary and distant tumors by flow cytometry. Natural killer (NK) cell depletion experiment was applied to confirm the role of NK cell in the combination therapy. The expression levels of cytokines and chemokines were detected by real-time quantitative PCR. Immunohistochemical test was conducted to reveal tumor angiogenesis, tumor proliferation, and apoptosis after the different treatments.Results and ConclusionCompared with RFA or R848 monotherapy, the combination therapy significantly slowed the tumor growth, prolonged the survival time, and shrank the tumor-draining lymph nodes of tumor-bearing mice. The flow cytometry results showed that tumor-infiltrating immune cells, total T cells, the ratio of CD8+ T and NK cells to CD45+ cells, and functional NK cells were obviously increased after the combined treatment. Distal tumor growth was also suppressed, and the profile of tumor-infiltrating immune cells was remodeled, too. In addition, the additive effect of the combination therapy disappeared after NK cell depletion. Furthermore, immunohistochemical results verified that R848 inhibited tumor angiogenesis in murine liver cancer, and the combination therapy promoted tumor cell apoptosis. In conclusion, our data suggest that RFA combined with R848 stimulated a stronger antitumor immune response and effectively inhibited liver cancer progression in a NK cell-dependent manner. Meanwhile, we confirmed that R848 inhibited tumor angiogenesis and promoted apoptosis in murine liver cancer. Overall, this is a promising therapeutic strategy to improve the efficacy of RFA in the treatment of liver cancer and provides a novel option for combined thermal ablation and immunotherapy.</p

Life Cycle Assessment and Multiobjective Optimization for Steam Cracking Process in Ethylene Plant

With energy savings and emission reduction becoming national policies in recent years, the environmental impacts of industrial production are more and more critical. Most of the studies have concentrated on the environmental effects of the industrial production process. Little attention has been paid to the energy consumption and pollution emission in extracting, processing, and transporting the feedstock and other secondary materials. An integrated multiobjective optimization framework is proposed for the steam cracking process on the basis of a life cycle assessment and data-driven modeling methods. A multiobjective economic–environmental optimization model is developed on the basis of industrial and simulated data. A multiobjective optimization model combined with energy cost is also developed for comparative study. The nondominated sorting genetic algorithm-II is utilized to solve the problems, and the Pareto front is obtained. An industrial case study is carried out to indicate the effectiveness of the proposed method. The results show that the LCA-based method can better represent the environmental impacts in comparison with the standard energy cost model. Therefore, the proposed method can achieve a better tradeoff between economic benefits and environmental impacts for guiding ethylene production

DataSheet_1_Combination of Radiofrequency Ablation With Resiquimod to Treat Hepatocellular Carcinoma Via Inflammation of Tumor Immune Microenvironment and Suppression of Angiogenesis.zip

BackgroundRadiofrequency ablation (RFA) destroys tumors through hyperthermic injury, which induces the release of immunogenic intracellular substrates and damages associated molecular patterns (DAMPs) to evoke a systemic immune response, but its therapeutic effect is limited. This study aimed to combine RFA with an immunomodulator, resiquimod (R848), to enhance the RFA-induced antitumor immunity.MethodsWe performed RFA on subcutaneous tumors in immunocompetent mice and intraperitoneally injected R848 to observe the efficacy of the combination therapy. Our research investigated changes in the composition of tumor-infiltrating immune cells in primary and distant tumors by flow cytometry. Natural killer (NK) cell depletion experiment was applied to confirm the role of NK cell in the combination therapy. The expression levels of cytokines and chemokines were detected by real-time quantitative PCR. Immunohistochemical test was conducted to reveal tumor angiogenesis, tumor proliferation, and apoptosis after the different treatments.Results and ConclusionCompared with RFA or R848 monotherapy, the combination therapy significantly slowed the tumor growth, prolonged the survival time, and shrank the tumor-draining lymph nodes of tumor-bearing mice. The flow cytometry results showed that tumor-infiltrating immune cells, total T cells, the ratio of CD8+ T and NK cells to CD45+ cells, and functional NK cells were obviously increased after the combined treatment. Distal tumor growth was also suppressed, and the profile of tumor-infiltrating immune cells was remodeled, too. In addition, the additive effect of the combination therapy disappeared after NK cell depletion. Furthermore, immunohistochemical results verified that R848 inhibited tumor angiogenesis in murine liver cancer, and the combination therapy promoted tumor cell apoptosis. In conclusion, our data suggest that RFA combined with R848 stimulated a stronger antitumor immune response and effectively inhibited liver cancer progression in a NK cell-dependent manner. Meanwhile, we confirmed that R848 inhibited tumor angiogenesis and promoted apoptosis in murine liver cancer. Overall, this is a promising therapeutic strategy to improve the efficacy of RFA in the treatment of liver cancer and provides a novel option for combined thermal ablation and immunotherapy.</p

Image_3_Combination of Radiofrequency Ablation With Resiquimod to Treat Hepatocellular Carcinoma Via Inflammation of Tumor Immune Microenvironment and Suppression of Angiogenesis.tif

BackgroundRadiofrequency ablation (RFA) destroys tumors through hyperthermic injury, which induces the release of immunogenic intracellular substrates and damages associated molecular patterns (DAMPs) to evoke a systemic immune response, but its therapeutic effect is limited. This study aimed to combine RFA with an immunomodulator, resiquimod (R848), to enhance the RFA-induced antitumor immunity.MethodsWe performed RFA on subcutaneous tumors in immunocompetent mice and intraperitoneally injected R848 to observe the efficacy of the combination therapy. Our research investigated changes in the composition of tumor-infiltrating immune cells in primary and distant tumors by flow cytometry. Natural killer (NK) cell depletion experiment was applied to confirm the role of NK cell in the combination therapy. The expression levels of cytokines and chemokines were detected by real-time quantitative PCR. Immunohistochemical test was conducted to reveal tumor angiogenesis, tumor proliferation, and apoptosis after the different treatments.Results and ConclusionCompared with RFA or R848 monotherapy, the combination therapy significantly slowed the tumor growth, prolonged the survival time, and shrank the tumor-draining lymph nodes of tumor-bearing mice. The flow cytometry results showed that tumor-infiltrating immune cells, total T cells, the ratio of CD8+ T and NK cells to CD45+ cells, and functional NK cells were obviously increased after the combined treatment. Distal tumor growth was also suppressed, and the profile of tumor-infiltrating immune cells was remodeled, too. In addition, the additive effect of the combination therapy disappeared after NK cell depletion. Furthermore, immunohistochemical results verified that R848 inhibited tumor angiogenesis in murine liver cancer, and the combination therapy promoted tumor cell apoptosis. In conclusion, our data suggest that RFA combined with R848 stimulated a stronger antitumor immune response and effectively inhibited liver cancer progression in a NK cell-dependent manner. Meanwhile, we confirmed that R848 inhibited tumor angiogenesis and promoted apoptosis in murine liver cancer. Overall, this is a promising therapeutic strategy to improve the efficacy of RFA in the treatment of liver cancer and provides a novel option for combined thermal ablation and immunotherapy.</p

Image_2_Combination of Radiofrequency Ablation With Resiquimod to Treat Hepatocellular Carcinoma Via Inflammation of Tumor Immune Microenvironment and Suppression of Angiogenesis.tif

BackgroundRadiofrequency ablation (RFA) destroys tumors through hyperthermic injury, which induces the release of immunogenic intracellular substrates and damages associated molecular patterns (DAMPs) to evoke a systemic immune response, but its therapeutic effect is limited. This study aimed to combine RFA with an immunomodulator, resiquimod (R848), to enhance the RFA-induced antitumor immunity.MethodsWe performed RFA on subcutaneous tumors in immunocompetent mice and intraperitoneally injected R848 to observe the efficacy of the combination therapy. Our research investigated changes in the composition of tumor-infiltrating immune cells in primary and distant tumors by flow cytometry. Natural killer (NK) cell depletion experiment was applied to confirm the role of NK cell in the combination therapy. The expression levels of cytokines and chemokines were detected by real-time quantitative PCR. Immunohistochemical test was conducted to reveal tumor angiogenesis, tumor proliferation, and apoptosis after the different treatments.Results and ConclusionCompared with RFA or R848 monotherapy, the combination therapy significantly slowed the tumor growth, prolonged the survival time, and shrank the tumor-draining lymph nodes of tumor-bearing mice. The flow cytometry results showed that tumor-infiltrating immune cells, total T cells, the ratio of CD8+ T and NK cells to CD45+ cells, and functional NK cells were obviously increased after the combined treatment. Distal tumor growth was also suppressed, and the profile of tumor-infiltrating immune cells was remodeled, too. In addition, the additive effect of the combination therapy disappeared after NK cell depletion. Furthermore, immunohistochemical results verified that R848 inhibited tumor angiogenesis in murine liver cancer, and the combination therapy promoted tumor cell apoptosis. In conclusion, our data suggest that RFA combined with R848 stimulated a stronger antitumor immune response and effectively inhibited liver cancer progression in a NK cell-dependent manner. Meanwhile, we confirmed that R848 inhibited tumor angiogenesis and promoted apoptosis in murine liver cancer. Overall, this is a promising therapeutic strategy to improve the efficacy of RFA in the treatment of liver cancer and provides a novel option for combined thermal ablation and immunotherapy.</p