Globally, many rivers are experiencing declining water quality, for example, with altered levels of sediments, salts, and nutrients. Effective water quality management requires a sound understanding of how and why water quality differs across space, both within and between river catchments. Land cover, land use, land management, atmospheric deposition, geology and soil type, climate, topography, and catchment hydrology are the key features of a catchment that affect:(1) the amount of suspended sediment, nutrient, and salt concentrations in catchments (i.e., the source), (2) the mobilization ,and (3) the delivery of these constituents to receiving waters. There are, however, complexities in the relationship between landscape characteristics and stream water quality. The strength of this relationship can be influenced by the distance and spatial arrangement of constituent sources within the catchment, cross correlations between landscape characteristics, and seasonality. A knowledge gap that should be addressed in future studies is that of interactions and cross correlations between landscape characteristics. There is currently limited understanding of how the relationships between landscape characteristics and water quality responses can shift based on the other characteristics of the catchment. Understanding the many forces driving stream water quality and the complexities and interactions in these forces is necessary for the development of successful water quality management strategies. This knowledge could be used to develop predictive models, which would aid in forecasting of riverine water quality.

Understanding the factors that influence temporal variability in water quality is critical for designing water quality management strategies. In this study, we explore the key factors that affect temporal variability in stream water quality across multiple catchments using a Bayesian hierarchical model. We apply this model to a case study data set consisting of monthly water quality measurements obtained over a 20‐year period from 102 water quality monitoring sites in the state of Victoria (Southeast Australia). We investigate six water quality constituents: total suspended solids, total phosphorus, filterable reactive phosphorus, total Kjeldahl nitrogen, nitrate‐nitrite (NOx), and electrical conductivity. We find that same‐day streamflow has the greatest effect on water quality variability for all constituents. Additional important predictors include soil moisture, antecedent streamflow, vegetation cover, and water temperature. Overall, the models do not explain a large proportion of temporal variation in water quality, with Nash‐Sutcliffe coefficients lower than 0.49. However, when considering performance on a site‐by‐site basis, we see high model performance in some locations, with Nash‐Sutcliffe coefficients of up to 0.8 for NOx and electrical conductivity. The effect of the temporal predictors on water quality varies between sites, which should be explored further for potential spatial patterns in future studies. There is also potential for further extension of these temporal variability models into a predictive spatiotemporal model of riverine constituent concentrations, which will be a useful tool to inform decision making for catchment water quality management.

This study uses water‐quality data collected over 20 years, from 102 predominantly rural sites across Victoria, Australia, to further our understanding of spatial variability in riverine water quality. We focus on concentrations of total suspended solids, total phosphorus, filterable reactive phosphorus, total Kjeldahl nitrogen, nitrate/nitrite (NOx), and electrical conductivity. We used an exhaustive search approach to identify the linear models that best link catchment characteristics to time‐averaged constituent concentrations. We ran additional analyses to (1) assess the performance of these models under drought conditions, and (2) understand the key drivers of site‐level variability (standard deviations) of constituent concentrations. Natural catchment characteristics appear to have a greater effect on spatial differences in average constituent concentrations. Performance of the statistical models of time‐averaged constituent concentrations varied, and spatial variability in mean electrical conductivity levels could be more readily explained by catchment characteristics compared to more reactive nutrients. Notwithstanding, the models performed relatively well under varying hydrologic conditions for most constituents. As such, these models provide an insight into the key factors affecting spatial variability in average stream water‐quality conditions. We also identified that hydrologic, climatic, and topographic characteristics of the catchment helped explain the spatial variability in temporal changes in constituents. After calibration and validation, these models of both average water quality and variability in water quality could be used to forecast stream water‐quality responses to future land use, climate, or soil and land management changes.

BackgroundInterleukin (IL) 1 released from monocytes/macrophages is one of the critical determinants in mediating the adverse events of chimeric antigen receptor T cell (CAR-T) therapy, including cytokine release syndrome and neurotoxicity. However, the molecular mechanisms of IL-1 production during CAR-T therapy remain unknown.MethodsThe roles of AIM2 and α1-adrenergic receptor (α1-AR) in CAR-T treatment-induced IL-1β release were evaluated by gene silencing, agonist or antagonist treatment. The phenotype switch of macrophages in response to CAR-T treatment was analyzed concerning cytotoxicity of CAR-T cells and proliferation of activated T cells.ResultsThis study provided the experimental evidence that CAR-T treatment-induced activation of AIM2 inflammasome of macrophages resulted in the release of bioactive IL-1β. CAR-T treatment-induced α1-AR-mediated adrenergic signaling augmented the priming of AIM2 inflammasome by enhancing IL-1β mRNA and AIM2 expression. Meanwhile, tumor cell DNA release triggered by CAR-T treatment potentiated the activation of AIM2 inflammasome in macrophages. Interestingly, an apparent phenotypic switch in macrophages occurred after interacting with CAR-T/tumor cells, which greatly inhibited the cytotoxicity of CAR-T cells and proliferation of activated T cells through upregulation of programmed cell death-ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase (IDO) in the macrophages. Blockade of AIM2 inflammasome or α1-AR reversed the upregulation of PD-L1 and IDO and the phenotypic switch of the macrophages.ConclusionOur study implicates that CAR-T therapy combined with the blockade of AIM2 inflammasome or α1-AR may relieve IL-1β-related toxic side effects of CAR-T therapy and ensure antitumor effects of the treatment.

For effective water quality management and policy development, spatial variability in the mean concentrations and dynamics of riverine water quality needs to be understood. Using water chemistry (calcium, electrical conductivity, nitrate‐nitrite, soluble reactive phosphorus, total nitrogen, total phosphorus and total suspended solids) data for up to 578 locations across the Australian continent, we assessed the impact of climate zones (arid, Mediterranean, temperate, subtropical, tropical) on (i) inter‐annual mean concentration and (ii) water chemistry dynamics as represented by constituent export regimes (ratio of the coefficients of variation of concentration and discharge) and export patterns (slope of the concentration‐discharge relationship). We found that inter‐annual mean concentrations vary significantly by climate zones and that spatial variability in water chemistry generally exceeds temporal variability. However, export regimes and patterns are generally consistent across climate zones. This suggests that intrinsic properties of individual constituents rather than catchment properties determine export regimes and patterns. The spatially consistent water chemistry dynamics highlights the potential to predict riverine water quality across the Australian continent, which can support national riverine water quality management and policy development.