Perspectives in multilevel decision-making in the process industry

Decisions in supply chains are hierarchically organized. Strategic decisions involve the long-term planning of the structure of the supply chain network.Tactical decisions are mid-term plans to allocate the production and distribution of materials, while operational decisions are related to the daily planning of the execution of manufacturing operations. These planning processes are conducted independently with minimal exchange of information between them. Achieving a better coordination between these processes allows companies to capture benefits that are currently out of their reach and improve the communication among their functional areas. We propose a network representation for the multilevel decision structure and analyze the components that are involved in finding integrated solutions that maximize the sum of the benefits of all nodes of the decision network.Although such task is very challenging, significant research progress has been made in each component of this structure. An overview of strategic models, mid-term planning models, and scheduling models is presented to address the solution of each node in the decision network.Coordination mechanisms for converging the integrated solutions are also analyzed, including solving large-scale models, multiobjective optimization, bi-level programming, and decomposition. We conclude by summarizing the challenges that hinder the full integration of multilevel decision making in supply chain management.

Deep tumor-penetrating nano-delivery strategy to improve diagnosis and therapy in patient-derived xenograft(PDX)oral cancer model and patient tissue

Nanoprodrugs that are directly assembled by prodrugs attract considerable attention with high anticancer potentials.However,their stability and efficiency of tumor-targeted delivery remain a major challenge in practical biomedical applications.Here,we report a new deep tumor-penetrating nano-delivery strategy to achieve enhanced anti-cancer performance by systematic optimization of a porphyrin-doxorubicin-based nanoprodrug using various PEGylations/crosslinks and co-administration of targeting peptide iRGD.Polyethylene glycols(PEGs)with different molecular weights and grafts are employed to crosslink the nanoprodrug and optimize size,charge,tumor accumulation and penetration,and anti-cancer efficiency,etc.The tumor penetration was validated in syngeneic oral cancer mouse models,patient-derived xenograft(PDX)models,and oral cancer tissue from patients.The optimized nanoprodrug co-administrated with iRGD remarkably enhances the accumulation and penetration both in tumor vascular and PDX tumor tissue.It is effective and safe to improve in vivo therapeutic efficacy via the passive tumor targeting dependent and independent mode.Our tumor-penetrating nano-delivery strategy is promising to strengthen the nanoprodrugs in clinical implementation.