Multiplex imaging reveals the architecture of the tumor immune microenvironment

The tumor immune microenvironment(TME)is composed of a variety of components,such as tumor cells,immune cells,and the extracellular matrix.The TME has been studied through transcriptomic,proteomic,metabolomic,and phosphoproteomic approaches,which have provided researchers with a wealth of TME-related molecular information.

Synergetic treatment of oxygen microcapsules and lenvatinib for enhanced therapy of HCC by alleviating hypoxia condition and activating anti-tumor immunity

Hypoxia is a typical characteristic of hepatocellular carcinoma(HCC), which causes tremendous obstacles to tumor treatments. Current first-line treatment may further deteriorate tumor hypoxia. For example,Lenvatinib, a receptor tyrosine kinase inhibitor(RTKI), suppresses tumor growth via blocking vascular endothelial growth factor(VEGF) signaling, and can also inhibit angiogenesis, thus limiting oxygen supply to tumor sites. Therefore, alleviating tumor microenvironment(TME) hypoxia holds great potential for enhancing the therapeutic effect of RTKI. Here, nanoparticle-stabilized oxygen microcapsules, a stable and biocompatible oxygen-loaded delivery system, are successfully prepared through interfacial polymerization of polydopamine nanoparticles. The microcapsules with a large loading capacity of oxygen in the core show excellent bioavailability and dispersity, which could effectively improve the hypoxic TME when they serve as oxygen delivery vehicles. Synergetic treatments of Lenvatinib and oxygen microcapsules could induce the transition of “cold tumor” in an immune-suppressed state to “hot tumor” in an immune-activated state by improving tumor hypoxic TME and reducing angiogenesis in HCC. It is revealed that combined treatments of oxygen microcapsules and Lenvatinib could polarize tumor-associated macrophages(TAMs) to anti-tumor M1 cells and activate T cell-mediated anti-tumor immune responses.The results suggest that synergetic therapy using oxygen microcapsules and Lenvatinib could alleviate the hypoxic TME and enhance the therapeutic performance of RTKI, demonstrating a promising anti-tumor strategy for enhanced therapy of HCC.

Oxygen microcapsules improve immune checkpoint blockade by ameliorating hypoxia condition in pancreatic ductal adenocarcinoma

Rationale:Hypoxia in tumor microenvironment(TME)represents an obstacle to the efficacy of immunotherapy for pancreatic ductal adenocarcinoma(PDAC)through several aspects such as increasing the expression of immune checkpoints or promoting fibrosis.Reversing hypoxic TME is a potential strategy to improve the validity of immune checkpoint blockade(ICB).Methods:Here,we synthesized polydopamine-nanoparticle-stabilized oxygen microcapsules with excellent stabilization,bioavailability,and biocompatibility for direct oxygen delivery into tumor sites by interfacial polymerization.Results:We observed oxygen microcapsules enhanced the oxygen concentration in the hypoxia environment and maintained the oxygen concentration for a long period both in vitro and in vivo.We found that oxygen microcapsules could significantly improve the efficiency of ICB against PDAC in vivo.Mechanismly,combined treatments using oxygen microcapsules and ICB could reduce the infiltration of tumor-associated macrophages(TAMs)and polarized pro-tumor M2 macrophages into anti-tumor M1 macrophages.In addition,combined treatments could elevate the proportion of T helper subtype 1 cells(Th1 cells)and cytotoxic T lymphocytes cells(CTLs)to mediate anti-tumor immune response in TME.Conclusion:In summary,this pre-clinical study indicated that reversing hypoxia in TME by using oxygen microcapsules was an effective strategy to improve the performances of ICB on PDAC,which holds great potential for treating PDAC in the future.

Impact of the PV Location in Distribution Networks on Network Power Losses and Voltage Fluctuations with PSO Analysis

Increased grid integration of photovoltaic(PV)has aggravated the uncertainty of distribution network operations.For a distribution network with PV,the impact of the PV location on the network power losses and voltage fluctuations is investigated with analytical derivations reflected by the line impedance.Optimization approaches of the PV location with consideration of two aspects,i.e.,minimum network power losses and minimum voltage fluctuations,are analyzed.A particle swarm optimization(PSO)algorithm is used to synthesize an optimal compromised solution so as to determine the PV location.A 10 kV distribution network with one PV is established on the time-domain simulation environment PSCAD/EMTDC.The simulation results justify the theoretical analysis and indicate that when the active power of the PV is more/less than twice that of the overall loads/end loads,the network power losses and node voltage fluctuations are both minimum when the PV is integrated into the head/tail end of the network.When the active power of the PV is between the above two conditions,nodes t/f can be identified for the integration of the PV between the head/end nodes of the network to achieve the minimum network power losses/voltage fluctuations,respectively.The effectiveness of the proposed optimization approach is verified and can provide a reference for selecting the PV location in the distribution network.

Equivalent model of multi-type distributed generators under faults with fast-iterative calculation method based on improved PSO algorithm

There are various types of distributed generators (DGs) with different grid integration strategies. The transient characteristics of the fault currents provided by the DGs are different to those of conventional synchronous generators. In this paper, a distribution network with multi-type DGs is investigated, including consideration of DG low-voltage ride through (LVRT). The fault current characteristics of two typical DGs, i.e. an inverter-interfaced distributed generator (IIDG) and a doubly-fed induction generator (DFIG), are analyzed, considering the specific operation modes. Based on analysis of the fault characteristics, an equivalent model of the multi-type DGs under symmetrical/asymmetrical fault conditions is established. A fast-iterative fault calculation method for enhancing the calculation efficiency while avoiding local convergence is then proposed using an improved particle swarm optimization (PSO) algorithm. A simulation system of the distribution network with multi-type DGs is established in PSCAD/EMTDC. The simulation results validate the high accuracy and calculation efficiency of the proposed calculation method of the fault components. This can assist in the settings of the protection threshold.