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The nexus of water, energy and ecosystems in the context of large-scale hydropower development is of worldwide concern; however, few quantitative studies have been conducted based on dynamic modeling. This study develops a system modeling approach to address the water-energy-ecosystem (WEE) nexus associated with the operation of cascade reservoirs. The approach couples multiobjective reservoir operation optimization with dynamic mass balance calculation of total phosphorus (TP). The approach was applied in the upper Mekong River Basin (i.e., the Lancang River Basin). The impacts of the cascade reservoirs on riverine TP transport were systematically investigated through a series of numerical experiments. The major study findings include the following. First, TP export from the Lancang River is closely related to characteristics of the cascade reservoirs, including the storage capacity and residence time of the reservoirs, as well as their locations. The two largest reservoirs demonstrate a much stronger retention effect than the other reservoirs. Second, although reservoir operations have significant impacts on the WEE nexus, the potential to enhance TP export is limited under traditional reservoir operations using total hydropower production and firm power as the objectives. Third, when TP export is incorporated as an environmental objective in the operation of the cascade reservoirs, strong tradeoffs among TP export and the two traditional objectives are revealed, and no synergetic effects are identified. Thus, a balance among the conflicting objectives must be carefully determined with compromise within the socioeconomic and political backgrounds of the complex nexus. Overall, this study establishes a general framework for quantifying the WEE nexus in the context of large-scale hydropower development and the results provide insights into the transboundary management of the Mekong River Basin. (C) 2019 Elsevier B.V. All rights reserved.d