Platelets favor the outgrowth of established metastases.

Despite abundant evidence demonstrating that platelets foster metastasis, anti-platelet agents have low therapeutic potential due to the risk of hemorrhages. In addition, whether platelets can regulate metastasis at the late stages of the disease remains unknown. In this study, we subject syngeneic models of metastasis to various thrombocytopenic regimes to show that platelets provide a biphasic contribution to metastasis. While potent intravascular binding of platelets to tumor cells efficiently promotes metastasis, platelets further support the outgrowth of established metastases via immune suppression. Genetic depletion and pharmacological targeting of the glycoprotein VI (GPVI) platelet-specific receptor in humanized mouse models efficiently reduce the growth of established metastases, independently of active platelet binding to tumor cells in the bloodstream. Our study demonstrates therapeutic efficacy when targeting animals bearing growing metastases. It further identifies GPVI as a molecular target whose inhibition can impair metastasis without inducing collateral hemostatic perturbations.

A sustainable activated carbon fiber/TiO2 cathode for the photoelectro-Fenton treatment of pharmaceutical pollutant enalapril.

In this work, a TiO2-decorated electrode was fabricated by dip coating activated carbon fibers (ACF) with TiO2, which were then used as a cathode for the photoelectro-Fenton (PEF) treatment of the pharmaceutical enalapril, an angiotensin-converting enzyme inhibitor that has been detected in several waterways. The TiO2 coating was found to principally improve the electrocatalytic properties of ACF for H2O2 production via the 2-e- O2 reduction, in turn increasing enalapril degradation by PEF. The effect of the current density on the mineralization of enalapril was evaluated and the highest TOC removal yield (80.5% in 3 h) was obtained at 8.33 mA cm-2, in the presence of 0.5 mmol L-1 of Fe2+ catalyst. Under those conditions, enalapril was totally removed within the first 10 min of treatment with a rate constant k = 0.472 min-1. In contrast, uncoated ACF only achieved 60% of TOC removal in 3 h at 8.33 mA cm-2. A degradation pathway for enalapril mineralization is proposed, based on the degradation by-products identified during treatment. Overall, the results demonstrate the promises of TiO2 cathodes for PEF, a strategy that has often been overlooked in favor of photoelectrocatalysis (PEC) based on TiO2-modified photoanodes.

A new approach of simultaneous adsorption and regeneration of activated carbon to address the bottlenecks of pharmaceutical wastewater treatment.

This study proposes a sustainable approach for hard-to-treat wastewater using sintered activated carbon (SAC) both as an adsorption filter and as an electrode, allowing its simultaneous electrochemical regeneration. SAC improves the activated carbon (AC) particle contact and thus the conductivity, while maintaining optimal liquid flow. The process removed 87 % of total organic carbon (TOC) from real high-load (initial TOC of 1625 mg/L) pharmaceutical wastewater (PWW), generated during the manufacturing of azithromycin, in 5 h, without external input of chemicals other than catalytic amounts of Fe(II). Kinetic modelling indicated that adsorption was the dominant process, while concomitant electrochemical degradation of complex organics first converted them to short-chain acids, followed by their full mineralization. In-situ electrochemical regeneration of SAC, taking place at the same time as the treatment, is a key feature of our process, enhancing its performance and ensuring its stable operation over time, while eliminating cleaning downtimes altogether. The energy consumption of this innovative process was remarkably low at 8.0×10-3 kWh gTOC-1. This study highlights the potential of SAC for treating hard-to-treat effluents by concurrent adsorption and mineralization of organics.

Blood flow diverts extracellular vesicles from endothelial degradative compartments to promote angiogenesis.

Extracellular vesicles released by tumors (tEVs) disseminate via circulatory networks and promote microenvironmental changes in distant organs favoring metastatic seeding. Despite their abundance in the bloodstream, how hemodynamics affect the function of circulating tEVs remains unsolved. We demonstrated that efficient uptake of tEVs occurs in venous endothelial cells that are subjected to hemodynamics. Low flow regimes observed in veins partially reroute internalized tEVs toward non-acidic and non-degradative Rab14-positive endosomes, at the expense of lysosomes, suggesting that endothelial mechanosensing diverts tEVs from degradation. Subsequently, tEVs promote the expression of pro-angiogenic transcription factors in low flow-stimulated endothelial cells and favor vessel sprouting in zebrafish. Altogether, we demonstrate that low flow regimes potentiate the pro-tumoral function of circulating tEVs by promoting their uptake and rerouting their trafficking. We propose that tEVs contribute to pre-metastatic niche formation by exploiting endothelial mechanosensing in specific vascular regions with permissive hemodynamics.

Hybrid TiO2/Carbon quantum dots heterojunction photoanodes for solar photoelectrocatalytic wastewater treatment.

The modification of titanium dioxide (TiO2) is a strategy to maximize the utilization of sunlight. Carbon quantum dots (CQDs) are carbon nanomaterials with outstanding optical and electronic properties that are suitable for that purpose. In this work, three types of hybrid TiO2/CQD photoelectrodes were synthesized following different methods: 1) deposition of a CQD layer on top of TiO2 (labelled as TiO2-CQD); 2) deposition of a TiO2 layer on top of CQDs (labelled as CQD-TiO2) and; 3) deposition of a mixed CQD + TiO2 layer (labelled as CQD + TiO2). The photoelectrodes were investigated for the photoelectrocatalytic degradation of phenol as model pollutant under simulated solar light and TiO2-CQD showed the highest apparent reaction rate constant of kapp = 0.0117 min-1 with 40% of TOC removal in 6 h of treatment. CQDs were found to enhance photon absorption in the visible region of the electromagnetic spectrum and in turn phenol degradation by promoting the separation of photogenerated charge carriers through electron transfer via the Ti-O-C bonds formed at the TiO2-CQD interface. Finally, the performance of the TiO2-CQD photoanode was evaluated for the treatment of real wastewater from the membrane fabrication sector, confirming its photoelectrocatalytic efficiency under solar radiation with 93% of TOC removal in 8 h of treatment and kapp = 0.0058 min-1.

Electro-Fenton treatment of contaminated mine water to decrease thiosalts toxicity to Daphnia magna.

Treatment of organic contaminants using the electro-Fenton (EF) process is efficient but generates toxic by-products. The aim of the present study was to assess the residual toxicity associated to the treatment of real mine effluents using EF and to perform a preliminary techno-economic analysis to compare the costs of different techniques. Two mine effluents from northern Quebec with different concentrations of thiosalts (MElow and MEhigh) were tested for acute toxicity to Daphnia magna, before and after EF treatment. The higher toxicity of untreated MElow compared to MEhigh, despite its lower thiosalts content (58 vs 199 mg/L), suggests the presence of an unidentified toxic species, which was removed during EF treatment, or that higher thiosalts concentrations mitigate the toxicity of other toxicants. EF treatment of MEhigh, initially non-acutely toxic (50% mortality), resulted in the elimination of D. magna mortality. A preliminary techno-economic analysis conducted for northern Quebec vs the rest of Canada and the USA showed that energy consumption was the main contributor (52-95%) to the total operating costs. Electricity-related costs nearly doubled (55%) for northern Quebec relative to the rest of Canada. These findings provide new insights for the potential application of the EF for the treatment of thiosalts in mine water, for operations in central jurisdictions and in remote northern areas.

Impairing flow-mediated endothelial remodeling reduces extravasation of tumor cells.

Tumor progression and metastatic dissemination are driven by cell-intrinsic and biomechanical cues that favor the growth of life-threatening secondary tumors. We recently identified pro-metastatic vascular regions with blood flow profiles that are permissive for the arrest of circulating tumor cells. We have further established that such flow profiles also control endothelial remodeling, which favors extravasation of arrested CTCs. Yet, how shear forces control endothelial remodeling is unknown. In the present work, we aimed at dissecting the cellular and molecular mechanisms driving blood flow-dependent endothelial remodeling. Transcriptomic analysis of endothelial cells revealed that blood flow enhanced VEGFR signaling, among others. Using a combination of in vitro microfluidics and intravital imaging in zebrafish embryos, we now demonstrate that the early flow-driven endothelial response can be prevented upon specific inhibition of VEGFR tyrosine kinase and subsequent signaling. Inhibitory targeting of VEGFRs reduced endothelial remodeling and subsequent metastatic extravasation. These results confirm the importance of VEGFR-dependent endothelial remodeling as a driving force of CTC extravasation and metastatic dissemination. Furthermore, the present work suggests that therapies targeting endothelial remodeling might be a relevant clinical strategy in order to impede metastatic progression.

Cost comparison of advanced oxidation processes for wastewater treatment using accumulated oxygen-equivalent criteria.

Advanced oxidation processes (AOPs) have received a lot of attention over the years as advanced physico-chemical polishing wastewater treatments to remove biorefractory pollutants. Additionally, many studies report their excellent degradation and mineralization performance as stand-alone technologies too, demonstrating the versatility of these processes; however, there is a lack of suitable methods to compare the performance (in terms of removal efficiency and operating costs) of different AOPs in the same conditions. In this context, the goal of this paper is to propose a systematic investigation by introducing a novel criterion, namely the accumulated oxygen-equivalent chemical-oxidation dose (AOCD), to systematically compare the diverse AOPs available: ozonation, H2O2 photolysis, Fenton, photo-Fenton, electro-Fenton and photoelectro-Fenton (paired with anodic oxidation, for the latter two). For each of these, the cost efficiency was determined by optimizing the operating conditions for the removal of phenol, selected as a model pollutant (1.4 mM, equivalent to 100 mg-C L-1). The operating costs considered sludge management, chemical use and electricity consumption. Among all AOPs, electro-Fenton was the most cost-effective (108 - 125 € m-3), notwithstanding the mineralization target (50%, 75% and 99%), owing to its electrocatalytic behavior. Chemical Fenton proved competitive too up to 50% of mineralization, meaning that it could also be considered as a cost-effective pre-treatment solution. AOCD was the lowest for electro-Fenton, which could be attributed to its excellent faradaic yield, while UV-based processes generally required the highest dose. The AOCD criterion could serve as a baseline for AOP comparison and prove useful for the legislator to determine the "best available techniques" as defined by the Industrial Emissions European Union Directive 2010/75/EU.

A comparison of visible-light photocatalysts for solar photoelectrocatalysis coupled to solar photoelectro-Fenton: Application to the degradation of the pesticide simazine.

Three different visible-light photocatalysts (hematite (α-Fe2O3), bismuth vanadate (BiVO4) and Mo-doped bismuth vanadate (BiMoVO4)) deposited on transparent fluorine-doped SnO2 (FTO) were evaluated for the solar-driven photoelectrocatalytic treatment of emerging pollutants. BiMoVO4 was found to be the most effective photoanode, yielding the fastest degradation rate constant and highest mineralization efficiency using phenol as the oxidation probe. The BiMoVO4 photoanode was then used to degrade the herbicide simazine in a photoelectrolytic cell combining photoelectrocatalysis (PEC) with photoelectron-Fenton (PEF) under solar light (SPEC-SPEC). Total simazine removal was achieved within 1 min of treatment (kapp = 4.21 min-1) at the optimum electrode potential of 2.5 V vs Ag/AgCl, with complete TOC removal in 2 h. The analysis of anionic species in solution during treatment showed that most of the nitrogen heteroatoms in the simazine structure were converted into NO3- following •OH addition to organic N. This innovative process combining BiMoVO4-PEC with PEF using solar light as a sustainable source of energy (SPEC-SPEF) achieved the highest degradation/mineralization efficiency ever reported for simazine treatment. Besides, this is the first work reporting the photo(electrochemical) degradation of this toxic herbicide.

Fluorescent nanocarriers targeting VCAM-1 for early detection of senescent endothelial cells.

Endothelial senescence has been identified as an early event in the development of endothelial dysfunction, a hallmark of cardiovascular disease. This study developed theranostic nanocarriers (NC) decorated with VCAM-1 antibodies (NC-VCAM-1) in order to target cell surface VCAM-1, which is overexpressed in senescent endothelial cells (ECs) for diagnostic and therapeutic purposes. Incubation of Ang II-induced premature senescent ECs or replicative senescent ECs with NC-VCAM-1 loaded with lipophilic fluorescent dyes showed higher fluorescence signals than healthy EC, which was dependent on the NC size and VCAM-1 antibodies concentration, and not observed following masking of VCAM-1. NC loaded with omega 3 polyunsaturated fatty acid (NC-EPA:DHA6:1) were more effective than native EPA:DHA 6:1 to prevent Ang II-induced VCAM-1 and p53 upregulation, and SA-ß-galactosidase activity in coronary artery segments. These theranostic NC might be of interest to evaluate the extent and localization of endothelial senescence and to prevent pro-senescent endothelial responses.

Electro-Fenton beyond the Degradation of Organics: Treatment of Thiosalts in Contaminated Mine Water.

Electro-Fenton (EF) is an emerging technology with well-known outstanding oxidation power; yet, its application to the treatment of inorganic contaminants has been largely disregarded. Thiosalts are contaminants of emerging concern in mine water, responsible for delayed acidity in natural waterways. In this study, EF was used to treat thiosalts in synthetic and real mine water. Thiosulfate (S2O32-) solutions were first used to optimize the main parameters affecting the process, namely, the current density (2.08-6.25 mA cm-2), temperature (4 vs 20 °C), and S2O32- concentration (0.25-2 g L-1). S2O32- was almost completely removed in 2 h of treatment at 6.25 mA cm-2, while temperature played no important role in the process efficiency. The optimal conditions were then applied to treat a real sample of contaminated mine water, resulting in complete S2O32- and S4O62- oxidation to SO42- in 90 min at 6.25 mA cm-2 (95% removal in only 60 min). The reaction mechanisms were investigated in detail based on the quantification of the main degradation byproducts. This study opens new possibilities for EF application to the treatment of thiosalt-contaminated mine water and other oxidizable inorganic-impacted wastewaters.

Ral GTPases promote breast cancer metastasis by controlling biogenesis and organ targeting of exosomes.

Cancer extracellular vesicles (EVs) shuttle at distance and fertilize pre-metastatic niches facilitating subsequent seeding by tumor cells. However, the link between EV secretion mechanisms and their capacity to form pre-metastatic niches remains obscure. Using mouse models, we show that GTPases of the Ral family control, through the phospholipase D1, multi-vesicular bodies homeostasis and tune the biogenesis and secretion of pro-metastatic EVs. Importantly, EVs from RalA or RalB depleted cells have limited organotropic capacities in vivoand are less efficient in promoting metastasis. RalA and RalB reduce the EV levels of the adhesion molecule MCAM/CD146, which favors EV-mediated metastasis by allowing EVs targeting to the lungs. Finally, RalA, RalB, and MCAM/CD146, are factors of poor prognosis in breast cancer patients. Altogether, our study identifies RalGTPases as central molecules linking the mechanisms of EVs secretion and cargo loading to their capacity to disseminate and induce pre-metastatic niches in a CD146-dependent manner.

[Influence of fluid mechanics on metastasis formation]. / Influence de la mécanique des fluides sur la formation des métastases.

Metastases are the main cause of cancer-related deaths. The chain of events leading to their development is called "the metastatic cascade". The biological and biochemical aspects of this process have been well studied but the importance of biomechanical parameters only recently became a focus in the field. Studies have shown the biological fluids (blood, lymph and interstitial fluid) to play a key role in the metastatic cascade. These fluids participate in the transport of circulating tumor cells (CTCs) as well as the factors that they secrete, while at the same time influencing the events of the metastatic cascade through the forces that they generate. The hemodynamic properties and topological constraints of the vascular architecture control the formation of metastatic niches and the metastatic potential of tumor cells. In this review, we discuss the importance of these mechanical forces and highlight the novel questions and research avenues that they open.

TITLE: Influence de la mécanique des fluides sur la formation des métastases. ABSTRACT: La suite d'évènements menant à l'apparition de métastases est appelée « cascade métastatique ¼. L'étude récente de la composante biomécanique de cette cascade a révélé le rôle central des liquides biologiques dans la dissémination métastatique. Tout en participant au transport des cellules tumorales circulantes et des facteurs qu'elles sécrètent, ces liquides circulants influencent cette cascade par les forces mécaniques qu'ils génèrent. Les propriétés hémodynamiques et les contraintes topologiques de l'architecture vasculaire contrôlent la formation de niches métastatiques et le potentiel métastatique des cellules tumorales.

Intrauterine Pressures Adjusted by Reichert's Membrane Are Crucial for Early Mouse Morphogenesis.

Mammalian embryogenesis proceeds in utero with the support of nutrients and gases from maternal tissues. However, the contribution of the mechanical environment provided by the uterus to embryogenesis remains unaddressed. Notably, how intrauterine pressures are produced, accurately adjusted, and exerted on embryos are completely unknown. Here, we find that Reichert's membrane, a specialized basement membrane that wraps around the implanted mouse embryo, plays a crucial role as a shock absorber to protect embryos from intrauterine pressures. Notably, intrauterine pressures are produced by uterine smooth muscle contractions, showing the highest and most frequent periodic peaks just after implantation. Mechanistically, such pressures are adjusted within the sealed space between the embryo and uterus created by Reichert's membrane and are involved in egg-cylinder morphogenesis as an important biomechanical environment in utero. Thus, we propose the buffer space sealed by Reichert's membrane cushions and disperses intrauterine pressures exerted on embryos for egg-cylinder morphogenesis.

Unconventional electro-Fenton process operating at a wide pH range with Ni foam cathode and tripolyphosphate electrolyte.

We propose an unconventional electro-Fenton (EF) system with a nickel-foam (Ni-F) cathode and tripolyphosphate (3-PP) electrolyte at near-neutral pH (EF/Ni-F-3-PP) to overcome pH restrictions in EF while preventing Ni-F corrosion. Response surface modelling was used to optimize the main operating parameters with a model prediction analysis (R2 = 0.99): pH = 5.8, Fe2+ = 3.0 mM and applied current = 349.6 mA. Among the three variables, the pH exerted the highest influence on the process. Under optimal conditions, 100 % of phenol removal was achieved in 25 min with a pseudo-first-order apparent rate constant (kapp) of 0.2 min-1, 3.2-fold higher than the kapp of EF/Ni-F with SO42- electrolyte at pH 3. A mineralization yield of 81.5 % was attained after 2 h; furthermore, it was found that 3-PP enhanced H2O2 accumulation by preventing bulk H2O2 decomposition. Finally, toxicity evaluation revealed the formation of toxic by-products at the early stages of treatment, which were totally depleted after 2 h, demonstrating the detoxifying capacity of the system. In conclusion, this study shows for the first time the potential of Ni-F as a cathode for EF under near-neutral conditions, rendered possible by the 3PP electrolyte. Under these conditions, the Ni-F corrosion issue could be alleviated.

Reusable Embedded Microcoils for Magnetic Nano-Beads Trapping in Microfluidics: Magnetic Simulation and Experiments.

In this study, a microfluidic chip with integrated coil was designed and fabricated for the aim of effectively trapping magnetic nanobeads (Adembeads®, 300 nm) and measuring the chip's temperature during the working time. In addition, a reversible technique of bonding Polydimethylsiloxane (PDMS) channels was presented. This bonding process used a coating layer of CYTOPproduct as a protection, insulation and low-adhesion layer. The reversible packaging technique allows the bottom substrate to be reused, possibly equipped with sensors, and to use a disposable microchannels network. The FE method was employed to calculate the magnetic field and power consumption by the ANSYS® version 12.1 software. Merit factors were defined in order to synthetically represent the ability of the simulated coil to trap beads for a unit power consumption, i.e. a given heat generation. The simulation results propose a new approach to optimize the design criteria in fabricating planar microcoils. The optimal microcoils were fabricated and then used to realize a magnetic immunoassay in a microfluidic chip. The aim was to integrate these microcoils into a lab-on-chip and obtain a fast and highly sensitive biological element detection.

Prediction of Drug Efficacy in Colon Cancer Preclinical Models Using a Novel Ranking Method of Gene Expression.

The presence of stromal cells in tumors is altering the significance of molecular profiling when using standard methods of gene expression quantification. We developed a novel normalization method to rank target gene expression in tumor samples by comparisons with reference samples representing the different cell types found in a tumor. The score for each target gene obtained after normalization, is aimed to be predictive of targeted therapies efficiency. We performed this qPCR analysis on human colorectal cancers to demonstrate the importance of reference samples to obtain accurate data and on a collection of patient-derived xenografted (PDX) colon tumors treated with Cetuximab (anti-EGFR) to demonstrate that the calculated EGFR score is predictive of Cetuximab efficacy. Interestingly, the score allowed to select an efficient treatment in a PDX model refractory to standard of care. This method is opening a novel way to predict targeted therapy efficiency which could be extended to several tumor types, and to unlimited target genes.

Effect of the electrocoagulation process on the toxicity of gold mine effluents: A comparative assessment of Daphnia magna and Daphnia pulex.

Mine effluents must meet discharge criteria for both physicochemical parameters and toxicity. While chemical precipitation is efficient for the treatment of metallic elements in mine effluents, the removal of sulfates, as a source of salinity and potential toxicity, is limited by gypsum solubility. This study evaluated the efficiency of electrocoagulation (EC), an emerging process to treat mine water, in removing sulfates and acute toxicity in two gold mine effluents (E1 and E2), before and after treatment (Fe-electrodes, 30 min at 20 mA/cm2, and pH near neutrality). Standard toxicity tests were conducted on two daphnia species, Daphnia magna (standard test species) and Daphnia pulex (more common in cold climate). Four uncontaminated surface waters (S#1 to S#4), which originated from different watershed lithologies, were also used as dilution media with E1 to assess water quality effect on toxicity response. Statistical analyses using the Student's t-test showed no significant difference in immobility or mortality caused by surface waters on either D. magna or D. pulex species (p > 0.05). However, higher toxicity was observed with both daphnia when reconstituted hard water was used for testing of the treated effluent E2. The present study highlights the toxicity effect added by EC despite a sulfates-related salinity decrease of >7.5%. Further research should identify and confirm the potential sources of observed toxicity.

[Access to rights, access to care: what obstacles for migrants ?] / Accès aux droits, accès aux soins : quels obstacles pour les migrants ?

Language barrier remains the number one obstacle in accessing health care and rights. Even though seeking for a professional interpreter assistance should be top priority, it is not yet a usual action among the health workers community. Foreign nationals are ruled by special immigration laws, thus facing specific legal challenges. According to health coverage laws (public social security system), every needy person living in France (regardless to his/her nationality or immigration status) should be granted a free of charge public health coverage to deal with health care expenses. Nevertheless, foreign nationals face long and recurring periods of time in which health coverage is over or in stand by (due to their precarious immigration status). It is recommended to anticipate those breakdown periods. Furthermore, an increasing range of medical certificates are demanded by administrations. Doctors dealing with the requests of their patients need to gain new dedicated skills. Asylum process (to qualify for an international protection) and access to a medical residence permit are two very different administrative actions which respectively involve two different kinds of officials and judges. The granting of a medical residence permit is a key concern for any doctor since he is in charge with ensuring his patient's continuity of care. The medical staff of OFII (the French authority in charge with the reception and integration of new incoming migrants and asylum seekers) tightened its assessment practices.

ACCÈS AUX DROITS, ACCÈS AUX SOINS : QUELS OBSTACLES POUR LES MIGRANTS ? Le premier obstacle dans l'accès aux droits et aux soins des étrangers est celui de la langue pour les patients allophones et le recours encore trop faible à l'interprétariat professionnel par les acteurs de la santé. Du fait de leur statut juridique particulier, les étrangers se trouvent confrontés à des difficultés spécifiques essentiellement dues à des difficultés d'accès aux droits. Alors que toute personne démunie résidant en France a droit à une protection maladie, les étrangers traversent des périodes longues et récurrentes de rupture de ces droits qu'il convient d'anticiper. De plus, la multiplication des types de certificats médicaux exigés des patients étrangers par les administrations impose aux médecins des connaissances spécifiques. La procédure d'asile et la procédure de titre de séjour pour soins sont deux procédures distinctes impliquant des administrations et des juges distincts. La procédure de titre de séjour pour soins est un outil permettant au médecin traitant d'assurer la continuité des soins de son patient. Le service médical de l'Office français de l'immigration et de l'intégration en a durci l'attribution en pratique.