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Abstract Extracellular vesicles (EVs) exist throughout our bodies. We recently revealed the important role of intracardiac EVs induced by myocardial ischemia/reperfusion on cardiac injury and dysfunction. However, the role of EVs isolated from normal tissues remains unclear. Here we found that EVs, derived from murine heart, lung, liver and kidney have similar effects on macrophages and regulate the inflammation, chemotaxis, and phagocytosis of macrophages. Interestingly, EV‐treated macrophages showed LPS resistance with reduced expressions of inflammatory cytokines and enhanced phagocytic activity. Furthermore, we demonstrated that the protein content in EVs contributed to the activation of inflammation, while the RNA component mainly limited the excessive inflammatory response of macrophages to LPS. The enrichment of miRNAs, including miR‐148a‐3p, miR‐1a‐3p and miR‐143‐3p was confirmed in tissue EVs. These EV‐enriched miRNAs contributed to the inflammation remission in LPS induced macrophages through multiple pathways, including STAT3, P65 and SAPK/JNK. Moreover, administration of both EVs and EV‐educated macrophages attenuated septic injury and cytokine storm in murine CLP models. Taken together, the present study disclosed that EVs from normal tissues can orchestrate the homeostasis of macrophages and attenuate inflammatory injury of sepsis. Therefore, tissue derived EVs or their derivatives may serve as potential therapeutic strategies in inflammatory diseases.

This paper proposes an optimization model for the train operation scheme of the Airport Express Line (AEL) based on the expected arrival time of passengers by the introduction of the train departure time to cope with the time-dependent passenger flow and provide better prompt train service according to passengers’ demand. Considering factors such as train sections, station arrangement, passenger capacity, departure time windows, passenger flow conservation, and boarding and disembarkation processes, this paper also aims to find the optimal combination of the passengers’ total travel time and the train operation cost. A set of alternative train options is introduced to simplify the model and convert integer variables related to train pairs into 0-1 variables. The elaborately designed simulated annealing algorithm mainly focuses on the key elements of strategies like initial solution generation, neighborhood solution construction, and the allocation of passenger flows, tailored to the model’s unique features and the time-dependent passenger flow. Neighborhood solution strategies include the increase or haut of train operations and the adjustment of the number of stops, which refines the solution space and boosts the process efficiency of the heuristic algorithm. Additionally, the model and algorithm proposed in this paper are practiced during the peak hour of Nanjing Metro Line S1 for empirical validation. The research findings demonstrate that the optimized train operation scheme is better synchronized with the fluctuating number of time-dependent passenger flows and exhibits notable improvement in computational efficiency and convergence.

Abstract Extracellular vesicles (EVs) curb important biological functions. We previously disclosed that ischemia‐reperfusion (IR) induces increased release of EVs (IR‐EVs) in the heart. However, the role of IR‐EVs in IR pathological process remains poorly understood. Here we found that adoptive transfer of IR‐EVs aggravated IR induced heart injury, and EV inhibition by GW4869 reduced the IR injury. Our in vivo and in vitro investigations substantiated that IR‐EVs facilitated M1‐like polarization of macrophages with increased expression of proinflammatory cytokines. Further, we disclosed the miRNA profile in cardiac EVs and confirmed the enrichment of miRNAs, such as miR‐155‐5p in IR‐EVs compared to EVs from the sham heart (S‐EVs). In particular, IR‐EVs transferred miR‐155‐5p to macrophages and enhanced the inflammatory response through activating JAK2/STAT1 pathway. Interestingly, IR‐EVs not only boosted the local inflammation in the heart, but even triggered systemic inflammation in distant organs. Taken together, we newly identify an IR‐EVs–miR‐155‐5p–M1 polarization axis in the heart post IR. The EVs derived from IR‐injured heart contribute to both local and systemic inflammation. Importantly, EV inhibition by GW4869 is supposed to be a promising therapeutic strategy for IR injury.

The paper studies the coopetition of the downstream different carriers by providing complementary transport services in intermodal freight transport chain. Considering different information structure, a two-stage dynamic game model with simultaneous actions on investment and price is first formulated. Equilibria show both parties have motivation to select coopetition even if the agreement for cooperation investment is reached in advance. When both firms agree on the specific allocation, the new coopetition with higher efficiency would be emerged. Moreover, we analyze the complexity and evolution of coopetition by repeated pricing game with finitely and infinitely time horizon. In the finitely repeated pricing game, both firms have incentive to reach a tacit understanding to alternate choosing price cooperation and competition after setting suitable allocation scheme; the repeated periods t are then going to be an issue. In the infinitely repeated pricing game, the perfect cooperation is realized by designing the suitable trigger strategy.