Rivers are important ecosystems under continuous anthropogenic stresses. The hyporheic zone is a ubiquitous, reactive interface between the main channel and its surrounding sediments along the river network. We elaborate on the main physical, biological, and biogeochemical drivers and processes within the hyporheic zone that have been studied by multiple scientific disciplines for almost half a century. These previous efforts have shown that the hyporheic zone is a modulator for most metabolic stream processes and serves as a refuge and habitat for a diverse range of aquatic organisms. It also exerts a major control on river water quality by increasing the contact time with reactive environments, which in turn results in retention and transformation of nutrients, trace organic compounds, fine suspended particles, and microplastics, among others. The paper showcases the critical importance of hyporheic zones, both from a scientific and an applied perspective, and their role in ecosystem services to answer the question of the manuscript title. It identifies major research gaps in our understanding of hyporheic processes. In conclusion, we highlight the potential of hyporheic restoration to efficiently manage and reactivate ecosystem functions and services in river corridors.

A series of 5-aryl-2-amino- i midazo t hia d iazole (ITD) derivatives were identified by a phenotype-based high-throughput screening using a blood stage Plasmodium falciparum ( Pf ) growth inhibition assay. A lead optimization program focused on improving antiplasmodium potency, selectivity against human kinases, and absorption, distribution, metabolism, excretion, and toxicity properties and extended pharmacological profiles culminated in the identification of INE963 ( 1 ), which demonstrates potent cellular activity against Pf 3D7 (EC 50 = 0.006 μM) and achieves “artemisinin-like” kill kinetics in vitro with a parasite clearance time of <24 h. A single dose of 30 mg/kg is fully curative in the Pf -humanized severe combined immunodeficient mouse model. INE963 ( 1 ) also exhibits a high barrier to resistance in drug selection studies and a long half-life ( T 1/2 ) across species. These properties suggest the significant potential for INE963 ( 1 ) to provide a curative therapy for uncomplicated malaria with short dosing regimens. For these reasons, INE963 ( 1 ) was progressed through GLP toxicology studies and is now undergoing Ph1 clinical trials.

Xenobiotic organic compounds can be discharged from contaminated groundwater inflow and may seep into streams from multiple pathways with very different dynamics, some not fully understood. In this study, we investigated the spatio‐temporal variation of chlorinated ethenes discharging from a former industrial site (with two main contaminant sources, A and B) into a stream system in a heterogeneous clay till setting in eastern Denmark. The investigated reach and near‐stream surroundings are representative of peri‐urban settings, with a mix of high channel alteration and more natural stream environment. We therefore propose an approach for risk assessing impacts arising from such complex contamination patterns, accounting for potential spatio‐temporal fluctuations and presence of multiple pathways. Our study revealed substantial variations in pathway contributions and overall contaminant mass discharge to the stream. Variable contaminant contributions arising from both groundwater seepage and urban drains were identified in the channelized part of the north stream, primarily from source A. Furthermore, variations in the hyporheic and shallow groundwater flows were found to enhance contaminant transport from source B. These processes result in an increase of the overall mass of contaminant discharged, correlating with the channels' flow. Thus, an in‐stream control plane approach was found to be an effective method for integrating multiple and variable discharge contributions quantitatively, although information on specific contaminant sources is lost. This study highlights the complexity and variability of contaminant fluxes occurring at the interface between groundwater and peri‐urban streams, and calls for the consideration of these variations when designing monitoring programs and remedial actions for contaminated sites with the potential to impact streams.