The low overall survival rate of patients with pancreatic cancer has driven research to seek a new therapeutic protocol. Radiotherapy (RT) is frequently an option in the neoadjuvant or palliative settings for pancreatic cancer treatment. This study explored the effect of RT protocols on the tumor microenvironment (TME) and their consequent impact on anti-programmed cell death ligand-1 (PD-L1) therapy. Using a murine orthotopic pancreatic tumor model, UN-KC-6141, RT-disturbed TME was examined by immunohistochemical staining. The results showed that ablative RT is more effective than fractionated RT at recruiting T cells. On the other hand, fractionated RT induces more myeloid-derived suppressor cell infiltration than ablative RT. The RT-disturbed TME presents a higher perfusion rate per vessel. The increase in vessel perfusion is associated with a higher amount of anti-PD-L1 antibody being delivered to the tumor. Animal survival is increased by anti-PD-L1 therapy after ablative RT, with 67% of treated animals surviving more than 30 days after tumor inoculation compared to a median survival time of 16.5 days for the control group. Splenocytes isolated from surviving animals were specifically cytotoxic for UN-KC-6141 cells. We conclude that the ablative RT-induced TME is more suited than conventional RT-induced TME to combination therapy with immune checkpoint blockade. 相似文献
The aim of this exploratory study has been to investigate the fire properties and environmental aspects of different upholstery material combinations, mainly for domestic applications. An analysis of the sustainability and circularity of selected textiles, along with lifecycle assessment, is used to qualitatively evaluate materials from an environmental perspective. The cone calorimeter was the primary tool used to screen 20 different material combinations from a fire performance perspective. It was found that textile covers of conventional fibres such as wool, cotton and polyester, can be improved by blending them with fire resistant speciality fibres. A new three‐dimensional web structure has been examined as an alternative padding material, showing preliminary promising fire properties with regard to ignition time, heat release rates and smoke production. 相似文献
Polymer‐grafted inorganic particles (PGIPs) are attractive building blocks for numerous chemical and material applications. Surface‐initiated controlled radical polymerization (SI‐CRP) is the most feasible method to fabricate PGIPs. However, a conventional in‐batch reaction still suffers from several disadvantages, including time‐consuming purification processes, low grafting efficiency, and possible gelation problems. Herein, a facile method is demonstrated to synthesize block copolymer–grafted inorganic particles, that is, poly(poly(ethylene glycol) methyl ether methacrylate) (PPEGMEMA)‐b‐poly(N‐isopropylacrylamide) (PNIPAM)–grafted silica micro‐particles using continuous flow chemistry in an environmentally friendly aqueous media. Immobilizing the chain transfer agent and subsequent SI‐CRP can be accomplished sequentially in a continuous flow system, avoiding multi‐step purification processes in between. The chain length (MW) of the grafted polymers is tunable by adjusting the flow time or monomer concentration, and the narrower molar mass dispersity (Ð < 1.4) of the grafted polymers reveals the uniform polymer chains on the particles. Moreover, compared with the in‐batch reaction at the same condition, the continuous system also suppresses possible gelation problems. 相似文献
Reconstructing gene regulatory networks (GRNs) plays an important role in identifying the complicated regulatory relationships, uncovering regulatory patterns in cells, and gaining a systematic view for biological processes. In order to reconstruct large-scale GRNs accurately, in this paper, we first use fuzzy cognitive maps (FCMs), which are a kind of cognition fuzzy influence graphs based on fuzzy logic and neural networks, to model GRNs. Then, a novel hybrid method is proposed to reconstruct GRNs from time series expression profiles using memetic algorithm (MA) combined with neural network (NN), which is labeled as MANNFCM-GRN. In MANNFCM-GRN, the MA is used to determine regulatory connections in GRNs and the NN is used to determine the interaction strength of the regulatory connections. In the experiments, the performance of MANNFCM-GRN is validated on both synthetic data and the benchmark dataset DREAM3 and DREAM4. The experimental results demonstrate the efficacy of MANNFCM-GRN and show that MANNFCM-GRN can reconstruct GRNs with high accuracy without expert knowledge. The comparison with existing algorithms also shows that MANNFCM-GRN outperforms ant colony optimization, non-linear Hebbian learning, and real-coded genetic algorithms.