A data-driven modeling approach for the sustainable remediation of persistent arsenic (As) groundwater contamination in a fractured rock aquifer through a groundwater recirculation well (IEG-GCW®).

Persistent arsenic (As) pollution sources from anthropogenic activities pose a serious threat to groundwater quality. This work aims to illustrate the application of an innovative remediation technology to remove As from a heavily contaminated fractured aquifer at a historically polluted industrial site. Groundwater circulation well (GCW) technology was tested to significantly increase and accelerate the mobilization and removal of As in the source area. The GCW extracts and re-injects groundwater at different depths of a vertical circulation well. By pumping out and reinjecting in different screen sections of the well, the resulting vertical hydraulic gradients create recirculation cells and affect and mobilize trapped contaminants that cannot be influenced by traditional pumping systems. The first 45-m deep IEG-GCW® system was installed in 2020, equipped with 4 screen sections at different depths and with an above-ground As removal system by oxidation and filtration on Macrolite (Enki). A geomodeling approach supports both remediation and multi-source data interpretation. The first months of operation demonstrate the hydraulic effectiveness of the IEG-GCW® system in the fractured rock aquifer and the ability to significantly enhance As removal compared to conventional pumping wells currently feeding a centralized treatment system. The recirculation flow rate amounts to about 2 m3/h. Water pumped and treated by the GCW system is reintroduced with As concentrations reduced by an average of 20%-60%. During the pilot test, the recirculating system removed 23 kg As whilst the entire central pump-and-treat (P&T) system removed 129 kg, although it treated 100 times more water volume. The P&T plant removed 259 mg As per m3 of pumped and treated groundwater while the GCW removed 4814 mg As per m3 of the treated groundwater. The results offer the opportunity for a more environmentally sustainable remediation approach by actively attacking the contamination source rather than containing the plume.

Energy metabolism characterization of a novel cancer stem cell-like line 3AB-OS.

Cancer stem cells (CSC) have a central role in driving tumor growth. Since metabolism is becoming an important diagnostic and therapeutic target, characterization of CSC line energetic properties is an emerging need. Embryonic and adult stem cells, compared to differentiated cells, exhibit a reduced mitochondrial activity and a stronger dependence on aerobic glycolysis. Here, we aimed to comparatively analyze bioenergetics features of the human osteosarcoma 3AB-OS CSC-like line, and the parental osteosarcoma MG63 cells, from which 3AB-OS cells have been previously selected. Our results suggest that 3AB-OS cells depend on glycolytic metabolism more strongly than MG63 cells. Indeed, growth in glucose shortage or in presence of galactose or pyruvate (mitochondrial specific substrates) leads to a significant reduction of their proliferation compared to MG63 cells. Accordingly, 3AB-OS cells show an increased expression of lactate dehydrogenase A (LDHA) and a larger accumulation of lactate in the culture medium. In line with these findings 3AB-OS cells as compared to MG63 cells present a reduced mitochondrial respiration, a stronger sensitivity to glucose depletion or glycolysis inhibition and a lessened sensitivity to oxidative phosphorylation inhibitors. Additionally, in contrast to MG63 cells, 3AB-OS display fragmented mitochondria, which become networked as they grow in glucose-rich medium, while almost entirely loose these structures growing in low glucose. Overall, our findings suggest that 3AB-OS CSC energy metabolism is more similar to normal stem cells and to cancer cells characterized by a glycolytic anaerobic metabolism.

Structure-activity studies on arylamides and arysulfonamides Ras inhibitors.

This paper reports the synthesis of a panel of small molecules with arylamides and arylsulfonamides groups and their biological activity in inhibiting nucleotide exchange on human Ras. The design of these molecules was guided by experimental and molecular modelling data previously collected on similar compounds. Aim of this work is the validation of the hypothesis that a phenyl hydroxylamine group linked to a second aromatic moiety generates a pharmacophore capable to interact with Ras and to inhibit its activation. In vitro experiments on purified human Ras clearly show that the presence of an aromatic hydroxylamine and a sulfonamide group in the same molecule is a necessary condition for Ras binding and nucleotide exchange inhibition. The inhibitor potency is lower in molecules in which either the hydroxylamine has been replaced by other functional groups or the sulfonamide has been replaced by an amide. In the case both these moieties, the hydroxylamine and sulfonamide are absent, inactive compounds are obtained.