Lake ecosystems confront escalating challenges to their stability and resilience, most intuitively leading to biodiversity loss, necessitating effective preservation strategies to safeguard aquatic environments. However, the complexity of ecological processes governing lake biodiversity under multi-stressor interactions remains an ongoing concern, primarily due to insufficient long-term bioindicator data, particularly concerning macroinvertebrate biodiversity. Here we utilize a unique, continuous, and in situ biomonitoring dataset spanning from 2011 to 2019 to investigate the spatio-temporal variation of macroinvertebrate communities. We assess the impact of four crucial environmental parameters on Lake Dongting and Lake Taihu, i.e., water quality, hydrology, climate change, and land use. These two systems are representative of lakes with Yangtze-connected and disconnected subtropical floodplains in China. We find an alarming trend of declining taxonomic and functional diversities among macroinvertebrate communities despite improvements in water quality. Primary contributing factors to this decline include persistent anthropogenic pressures, particularly alterations in human land use around the lakes, including intensified nutrient loads and reduced habitat heterogeneity. Notably, river-lake connectivity is pivotal in shaping differential responses to multiple stressors. Our results highlight a strong correlation between biodiversity alterations and land use within a 2–5 km radius and 0.05–2.5 km from the shorelines of Lakes Dongting and Taihu, respectively. These findings highlight the importance of implementing land buffer zones with specific spatial scales to enhance taxonomic and functional diversity, securing essential ecosystem services and enhancing the resilience of crucial lake ecosystems.

Organophosphate esters (OPEs) are widespread in various environmental media, and can disrupt thyroid endocrine signaling pathways. Mechanisms by which OPEs disrupt thyroid hormone (TH) signal transduction are not fully understood. Here, we present in vivo-in vitro-in silico evidence establishing OPEs as environmental THs competitively entering the brain to inhibit growth of zebrafish via multiple signaling pathways. OPEs can bind to transthyretin (TTR) and thyroxine-binding globulin, thereby affecting the transport of TH in the blood, and to the brain by TTR through the blood–brain barrier. When GH3 cells were exposed to OPEs, cell proliferation was significantly inhibited given that OPEs are competitive inhibitors of TH. Cresyl diphenyl phosphate was shown to be an effective antagonist of TH. Chronic exposure to OPEs significantly inhibited the growth of zebrafish by interfering with thyroperoxidase and thyroglobulin to inhibit TH synthesis. Based on comparisons of modulations of gene expression with the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases, signaling pathways related to thyroid endocrine functions, such as receptor–ligand binding and regulation of hormone levels, were identified as being affected by exposure to OPEs. Effects were also associated with the biosynthesis and metabolism of lipids, and neuroactive ligand–receptor interactions. These findings provide a comprehensive understanding of the mechanisms by which OPEs disrupt thyroid pathways in zebrafish.