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GAC filtration of municipal wastewater was optimized and intensified, making its implementation and operation directly after secondary clarification possible and relevant. GAC was first selected based on laboratory tests. Performances on organic micropollutants were linked to the repartition of BET surface between micropores and meso/macropores. At pilot scale, in order to limit the impact of head loss, downflow declogging sequences (DCS) were implemented and upflow filtration tested. 6 to 12 DCS per day led to a 4.7-5.5-fold increase of particles retention capacity between backwashes (cycle duration of 20-120 h), and upflow operations improved head loss evolution profile with only a slight GAC (<15 %) expansion. DCS allows backwash frequency reduction, enabling significant water savings. Both adaptations maintained high organic micropollutants removals compared to a review of 16 GAC studies at pilot or full-scale, results being in the upper range. A specific dose of 2.0-2.5 g GAC/gC was necessary to obtain an average removal of pharmaceuticals and benzotriazole of 80 % at 20 min contact time, which is comparable to PAC and low granulometry GAC. Higher doses are needed for PFAS but >80 % removals are achievable. Particles, TKN, particulate phosphorus and organic matter are well removed by GAC filtration in both configurations. Biological activity is observed through nitrogen transformation in the GAC bed. Heavy metals are greatly removed in GAC filtration, in particular Cd, Cu, Ni and Pb, probably through biosorption onto the biofilm, developed within the GAC bed. For wastewater reuse applications, GAC filtration has an added value through physicochemical quality improvement and fecal contamination indicators removal of 1 log, facilitating the implementation and optimizing the design of a post-disinfection. Antibiotic resistant bacteria and antibiotic resistance genes are also partially retained in GAC filtration. Finally, biological wastewater treatments combined to GAC filtration is a good solution to effectively treat organic micropollutants together with heavy metals and preparing post-disinfection for reuse., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Romain Mailler has patent pending to SUEZ. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: We have previously demonstrated the significant reliance of pancreatic Cancer Stem Cells (PaCSCs) on mitochondrial oxidative phosphorylation (OXPHOS), which enables versatile substrate utilization, including fatty acids (FAs). Notably, dysregulated lipid scavenging and aberrant FA metabolism are implicated in PDAC progression., Methods & Results: Our bioinformatics analyses revealed elevated expression of lipid metabolism-related genes in PDAC tissue samples compared to normal tissue samples, which correlated with a stemness signature. Additionally, PaCSCs exhibited heightened expression of diverse lipid metabolism genes and increased lipid droplet accumulation compared to differentiated progenies. Treatment with palmitic, oleic, and linolenic FAs notably augmented the self-renewal and chemotherapy resistance of CD133 + PaCSCs. Conversely, inhibitors of FA uptake, storage and metabolism reduced CSC populations both in vitro and in vivo. Mechanistically, inhibition of FA metabolism suppressed OXPHOS activity, inducing energy depletion and subsequent cell death in PaCSCs. Importantly, combining a FAO inhibitor and Gemcitabine treatment enhanced drug efficacy in vitro and in vivo, effectively diminishing the CSC content and functionality., Conclusion: Targeting FAO inhibition represents a promising therapeutic strategy against this highly tumorigenic population., (© 2024. The Author(s).)

Mitochondrial diseases are genetic disorders impairing mitochondrial functions. Here we describe a patient with a neurodegenerative condition associated with myopia, bilateral sensorineural hearing loss and motor disorders. Brain MRIs showed major cortico-subcortical and infra-tentorial atrophies, as well as intracerebral iron accumulation and central calcifications, compatible with a NBIA-like phenotype. Mitochondrial DNA analysis revealed an undescribed variant: m.8091G>A in the MT-CO2 gene, associated with a complex IV deficiency and a decrease of the mitochondrial respiratory chain capabilities. We report here this pathogenic variant, associated with a NBIA-like phenotype., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Pediatric forms of multiple sclerosis are more active than those in adults. Yet, the effectiveness of different therapeutic approaches is not well studied in this population. Our objective was to compare the effectiveness of the early use of high efficacy therapies (HETs) with the effectiveness of moderate efficacy therapies (METs) in children with MS., Methods: This observational study included patients diagnosed with pediatric MS, at 4 hospital centers in France, during a 10-year period. METs included: interferon β-1a, glatiramer acetate, dimethyl fumarate, teriflunomide; HETs included: fingolimod, natalizumab, ocrelizumab, alemtuzumab. The primary endpoint was the occurrence of a new relapse, the secondary endpoint was EDSS worsening., Results: Sixty-four patients were included in the analysis (80% women; mean age 15.5 years, 81% treated with MET) with a median follow-up of 22.5 months. At baseline, 52 patients were on MET (interferon β-1a, glatiramer acetate, dimethyl fumarate, teriflunomide) and 12 patients were on HET (natalizumab, ocrelizumab). The cumulative probability of being relapse-free at 6.5 years was 23.3% on MET, vs 90.9% on HET (p = 0.013). The cumulative probability of no EDSS worsening did not differ between the 2 groups., Conclusion: Patients starting with METs had much higher clinical disease activity than those starting early with HETs. Rapid initiation of more aggressive treatment may allow better disease control; however, the data on EDSS worsening are not conclusive., Competing Interests: Declaration of Competing Interest A. Moreau reports no disclosure relevant to the manuscript; I. Kolitsi reports no disclosure relevant to the manuscript; L. Kremer reports no disclosure relevant to the manuscript; M.-C. Fleury reports no disclosure relevant to the manuscript; L. Lanotte reports no disclosure relevant to the manuscript; F. Sellal reports no disclosure relevant to the manuscript; C. Gaultier reports no disclosure relevant to the manuscript; G. Ahle reports grants from Biogen, grants from Novartis, grants from Roche, grants from Sanofi, grants from Abbvie, grants from Pfizer, grants from CSL Behring, outside the submitted work; S. Courtois reports no disclosure relevant to the manuscript; A. Fickl reports no disclosure relevant to the manuscript; S. Mostoufizadeh reports no disclosure relevant to the manuscript; C. Dentel reports no disclosure relevant to the manuscript; N. Collongues reports no disclosure relevant to the manuscript; J. de Seze reports no disclosure relevant to the manuscript; K. Bigaut has received lecturing fees and travel grants from Biogen, Celgene-BMS, Novartis, Roche, and Sanofi-Genzyme., (Copyright © 2023. Published by Elsevier B.V.)

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive disease characterized by its metastatic potential and chemoresistance. These traits are partially attributable to the highly tumorigenic pancreatic cancer stem cells (PaCSCs). Interestingly, these cells show unique features in order to sustain their identity and functionality, some of them amenable for therapeutic intervention. Screening of phospho-receptor tyrosine kinases revealed that PaCSCs harbored increased activation of anaplastic lymphoma kinase (ALK). We subsequently demonstrated that oncogenic ALK signaling contributes to tumorigenicity in PDAC patient-derived xenografts (PDXs) by promoting stemness through ligand-dependent activation. Indeed, the ALK ligands midkine (MDK) or pleiotrophin (PTN) increased self-renewal, clonogenicity and CSC frequency in several in vitro local and metastatic PDX models. Conversely, treatment with the clinically-approved ALK inhibitors Crizotinib and Ensartinib decreased PaCSC content and functionality in vitro and in vivo, by inducing cell death. Strikingly, ALK inhibitors sensitized chemoresistant PaCSCs to Gemcitabine, as the most used chemotherapeutic agent for PDAC treatment. Consequently, ALK inhibition delayed tumor relapse after chemotherapy in vivo by effectively decreasing the content of PaCSCs. In summary, our results demonstrate that targeting the MDK/PTN-ALK axis with clinically-approved inhibitors impairs in vivo tumorigenicity and chemoresistance in PDAC suggesting a new treatment approach to improve the long-term survival of PDAC patients., Competing Interests: Conflict of Interest Statement The authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Exit strategy after natalizumab cessation in multiple sclerosis (MS) is a crucial point because the risk of disease reactivation is high during this period. The objective of this observational study was to compare ocrelizumab to fingolimod after natalizumab cessation in patients with relapsing-remitting multiple sclerosis (RRMS)., Methods: All RRMS patients starting fingolimod or ocrelizumab within 6 weeks after natalizumab cessation were included. The primary endpoint was the annualized relapse rate (ARR) at 1 year., Results: We included 54 patients receiving fingolimod and 48 patients receiving ocrelizumab after natalizumab cessation. In multivariate analysis, ARR at 1 year was significantly lower in the ocrelizumab group than in the fingolimod group (0.12 ± 0.39 versus 0.41 ± 0.71, p = 0.026), i.e. a 70.7% lower relapse rate. The cumulative probability of relapses at 1 year was 31.5% (17/54 patients) with fingolimod and 10.4% (5/48 patients) with ocrelizumab, corresponding to a hazard ratio of 3.4 (95% confidence interval: 1.1-11, p = 0.04)., Conclusions: Our results suggest ocrelizumab is potentially a better exit strategy than fingolimod after natalizumab cessation., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

SARS-CoV-2 RNA quantification in wastewater has emerged as a relevant additional means to monitor the COVID-19 pandemic. However, the concentration can be affected by black water dilution factors or movements of the sewer shed population, leading to misinterpretation of measurement results. The aim of this study was to evaluate the performance of different indicators to accurately interpret SARS-CoV-2 in wastewater. Weekly/bi-weekly measurements from three cities in France were analysed from February to September 2021. The concentrations of SARS-CoV-2 gene copies were normalised to the faecal-contributing population using simple sewage component indicators. To reduce the measurement error, a composite index was created to combine simultaneously the information carried by the simple indicators. The results showed that the regularity (mean absolute difference between observation and the smoothed curve) of the simple indicators substantially varied across sampling points. The composite index consistently showed better regularity compared to the other indicators and was associated to the lowest variation in correlation coefficient across sampling points. These findings suggest the recommendation for the use of a composite index in wastewater-based epidemiology to compensate for variability in measurement results.

The level of evidence of expert recommendations for starting extracorporeal cardiopulmonary resuscitation (ECPR) in refractory out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA) is low. Therefore, we reported our experience in the field to identify factors associated with hospital mortality. We conducted a retrospective cohort study of all consecutive patients treated with ECPR for refractory cardiac arrest without return to spontaneous circulation, regardless of cause, at the Caen University Hospital. Factors associated with hospital mortality were analyzed. Eighty-six patients (i.e., 35 OHCA and 51 IHCA) were included. The overall hospital mortality rate was 81% (i.e., 91% and 75% in the OHCA and IHCA groups, respectively). Factors independently associated with mortality were: sex, age > 44 years, and time from collapse until extracorporeal life support (ECLS) initiation. Interestingly, no-shockable rhythm was not associated with mortality. The receiver operating characteristic-area under the curve values of pH value (0.75 [0.60-0.90]) and time from collapse until ECLS initiation over 61 minutes (0.87 [0.76-0.98]) or 74 minutes (0.90 [0.80-1.00]) for predicting hospital mortality showed good discrimination performance. No-shockable rhythm should not be considered a formal exclusion criterion for ECPR. Time from collapse until ECPR initiation is the cornerstone of success of an ECPR strategy in refractory cardiac arrest., Competing Interests: Disclosures: The authors have no conflicts of interest to report., (Copyright © ASAIO 2021.)

Previously regarded as simple fat storage particles, new evidence suggests that lipid droplets (LDs) are dynamic and functional organelles involved in key cellular processes such as membrane biosynthesis, lipid metabolism, cell signalling and inflammation. Indeed, an increased LD content is one of the most apparent features resulting from lipid metabolism reprogramming necessary to support the basic functions of cancer cells. LDs have been associated to different cellular processes involved in cancer progression and aggressiveness, such as tumorigenicity, invasion and metastasis, as well as chemoresistance. Interestingly, all of these processes are controlled by a subpopulation of highly aggressive tumoral cells named cancer stem cells (CSCs), suggesting that LDs may be fundamental elements for stemness in cancer. Considering the key role of CSCs on chemoresistance and disease relapse, main factors of therapy failure, the design of novel therapeutic approaches targeting these cells may be the only chance for long-term survival in cancer patients. In this sense, their biology and functional properties render LDs excellent candidates for target discovery and design of combined therapeutic strategies. In this review, we summarise the current knowledge identifying LDs and CSCs as main contributors to cancer aggressiveness, metastasis and chemoresistance., Competing Interests: Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other co-authors who contributed their efforts in this manuscript., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is shed in the feces of infected people. As a consequence, genomic RNA of the virus can be detected in wastewater. Although the presence of viral RNA does not inform on the infectivity of the virus, this presence of genetic material raised the question of the effectiveness of treatment processes in reducing the virus in wastewater and sludge. In this work, treatment lines of 16 wastewater treatment plants were monitored to evaluate the removal of SARS-CoV-2 RNA in raw, processed waters and sludge, from March to May 2020. Viral RNA copies were enumerated using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) in 5 different laboratories. These laboratories participated in proficiency testing scheme and their results demonstrated the reliability and comparability of the results obtained for each one. SARS-CoV-2 RNA was found in 50.5% of the 101 influent wastewater samples characterized. Positive results were detected more frequently in those regions with a COVID-19 incidence higher than 100 cases per 100,000 inhabitants. Wastewater treatment plants (WWTPs) significantly reduced the occurrence of virus RNA along the water treatment lines. Secondary treatment effluents showed an occurrence of SARS-CoV-2 RNA in 23.3% of the samples and no positive results were found after MBR and chlorination. Non-treated sludge (from primary and secondary treatments) presented a higher occurrence of SARS-CoV-2 RNA than the corresponding water samples, demonstrating the affinity of virus particles for solids. Furthermore, SARS-CoV-2 RNA was detected in treated sludge after thickening and anaerobic digestion, whereas viral RNA was completely eliminated from sludge only when thermal hydrolysis was applied. Finally, co-analysis of SARS-CoV-2 and F-specific RNA bacteriophages was done in the same water and sludge samples in order to investigate the potential use of these bacteriophages as indicators of SARS-CoV-2 fate and reduction along the wastewater treatment., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Glutamoptosis is the induction of apoptotic cell death as a consequence of the aberrant activation of glutaminolysis and mTORC1 signaling during nutritional imbalance in proliferating cells. The role of the bioenergetic sensor AMPK during glutamoptosis is not defined yet. Here, we show that AMPK reactivation blocks both the glutamine-dependent activation of mTORC1 and glutamoptosis in vitro and in vivo. We also show that glutamine is used for asparagine synthesis and the GABA shunt to produce ATP and to inhibit AMPK, independently of glutaminolysis. Overall, our results indicate that glutamine metabolism is connected with mTORC1 activation through two parallel pathways: an acute alpha-ketoglutarate-dependent pathway; and a secondary ATP/AMPK-dependent pathway. This dual metabolic connection between glutamine and mTORC1 must be considered for the future design of therapeutic strategies to prevent cell growth in diseases such as cancer., (© 2021. The Author(s).)

Metformin is widely prescribed to treat type 2 diabetes. Diabetes patients treated with metformin have a decreased risk of cancers, including gastric cancer. Among the factors influencing digestive carcinogenesis, gut microbiota interactions have been intensively studied. Metformin exhibits direct antimicrobial activity toward Helicobacter pylori , which plays a crucial role in gastric carcinogenesis. Mice were infected with H. pylori and treated for 12 days with either metformin or phosphate-buffered saline (PBS) as a control. At the end of the treatment period, the mice were euthanized and cecal and intestinal contents and stool were collected. The gut microbiota of the three different digestive sites (stool, cecal, and intestinal contents) were characterized through 16S RNA gene sequencing. In mice infected with H. pylori , metformin significantly decreased alpha diversity indices and led to significant variation in the relative abundance of some bacterial taxa including Clostridium and Lactobacillus , which were directly inhibited by metformin in vitro. PICRUSt analysis suggested that metformin modifies functional pathway expression, including a decrease in nitrate reducing bacteria in the intestine. Metformin significantly changed the composition and predicted function of the gut microbiota of mice infected with H. pylori ; these modifications could be implicated in digestive cancer prevention.

Background: Data are needed on long-term effect of natalizumab (NTZ) in relapsing-remitting multiple sclerosis (RRMS)., Objectives: To evaluate the time of onset of secondary progressive phase in patients with an RRMS treated with NTZ and to investigate predictive factors., Methods: TYSTEN is an observational study. Patients starting NTZ between 2007 and 2012 were included and followed up until October 2018. Relapses, Expanded Disability Status Scale (EDSS) scores, and results of brain magnetic resonance imaging (MRI) were collected each year. Data were used to estimate the cumulative probability of several poor outcomes such as secondary progressive multiple sclerosis (SPMS) conversion, EDSS worsening, EDSS 4.0, and EDSS 6.0., Results: 770 patients were included. The mean follow-up duration was 97 months and the mean time exposure to NTZ was 66 months. At 10 years, the cumulative probability of SPMS was 27.7%. Predictive factors for poor outcomes were a ⩾1-point increase in EDSS score from baseline, new T2 lesion or T1 gadolinium-enhancing lesion, the occurrence of relapse at 1 or 2 years and No Evidence of Disease Activity (NEDA-3; no relapse, no new T2 or T1 gadolinium-enhancing lesions, no progression) was a protective factor., Conclusion: In our cohort of patients treated with NTZ, poor outcomes were infrequent and are driven by disease activity.

The aim of the present study was to develop a simple, sensitive, and specific approach to quantifying the SARS-CoV-2 genome in wastewater and to evaluate this approach as a means of epidemiological surveillance. Twelve wastewater samples were collected from a metropolitan area in north-eastern France during April and May 2020. In addition to the quantification of the SARS-CoV-2 genome, F-specific RNA phages of genogroup II (FRNAPH GGII), naturally present in wastewater, were used as an internal process control for the viral concentration and processing of RT-PCR inhibitors. A concentration method was required to allow the quantification of the SARS-CoV-2 genome over the longest possible period. A procedure combining ultrafiltration, phenol-chloroform-isoamyl alcohol purification, and the additional purification of the RNA extracts was chosen for the quantification of the SARS-CoV-2 genome in 100-mL wastewater samples. At the same time, the COVID-19 outbreak was evaluated through patients from the neighbouring University Hospital of Nancy, France. A regular decrease in the concentration of the SARS-CoV-2 genome from ~10 4 gc/L to ~10 2 gc/L of wastewater was observed over the eight weeks of the study, during which the population was placed under lockdown. The SARS-CoV-2 genome was even undetectable during one week in the second half of May and present but non-quantifiable in the last sample (28 May). A concordant circulation in the human community was highlighted by virological diagnosis using respiratory samples, which showed a decrease in the number of COVID-19 cases from 677 to 52 per week over the same period. The environmental surveillance of COVID-19 using a reliable viral quantification procedure to test wastewater is a key approach. The real-time detection of viral genomes can allow us to predict and monitor the circulation of SARS-CoV-2 in clinical settings and survey the entire urban human population., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest tumors, partly due to its intrinsic aggressiveness, metastatic potential, and chemoresistance of the contained cancer stem cells (CSCs). Pancreatic CSCs strongly rely on mitochondrial metabolism to maintain their stemness, therefore representing a putative target for their elimination. Since mitochondrial homeostasis depends on the tightly controlled balance between fusion and fission processes, namely mitochondrial dynamics, we aim to study this mechanism in the context of stemness. In human PDAC tissues, the mitochondrial fission gene DNM1L (DRP1) was overexpressed and positively correlated with the stemness signature. Moreover, we observe that primary human CSCs display smaller mitochondria and a higher DRP1/MFN2 expression ratio, indicating the activation of the mitochondrial fission. Interestingly, treatment with the DRP1 inhibitor mDivi-1 induced dose-dependent apoptosis, especially in CD133 + CSCs, due to the accumulation of dysfunctional mitochondria and the subsequent energy crisis in this subpopulation. Mechanistically, mDivi-1 inhibited stemness-related features, such as self-renewal, tumorigenicity, and invasiveness and chemosensitized the cells to the cytotoxic effects of Gemcitabine. In summary, mitochondrial fission is an essential process for pancreatic CSCs and represents an attractive target for designing novel multimodal treatments that will more efficiently eliminate cells with high tumorigenic potential.

Background: The main cause of gastric cancer is the infection by the bacterium Helicobacter pylori which induces a chronic inflammation and an epithelial-to-mesenchymal transition (EMT) leading to the emergence of cells with cancer stem cell (CSC) properties. However, the underlying mechanisms have not been fully characterized. Moreover, H. pylori modulates the host cell autophagic process, but a few studies have investigated the role of this process in tumoral transformation. The aim of this study was to determine whether H. pylori-induced autophagy has a role in CSC emergence., Methods: Autophagic flux in response to H. pylori infection was characterized in AGS cell line expressing the tandem-tagged mCherry-GFP-LC3 protein and using a ratiometric flow cytometry analysis. Then, AGS and MKN45 cell lines were treated with bafilomycin or chloroquine, two pharmaceutical well-known inhibitors of autophagy, and different EMT and CSC characteristics were analyzed., Results: First, a co-expression of the gastric CSC marker CD44 and the autophagic marker LC3 in mice and human stomach tissues infected with H. pylori was observed. Then, we demonstrated in vitro that H. pylori was able to activate the autophagy process with a reduced autophagic flux. Finally, infected cells were treated with autophagy inhibitors, which reduced (i) appearance of mesenchymal phenotypes and migration ability related to EMT and (ii) CD44 expression as well as tumorsphere formation capacities reflecting CSC properties., Conclusion: In conclusion, all these data show that H. pylori-induced autophagy is implicated in gastric CSC emergence and could represent an interesting therapeutic target.

Pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, is an extremely lethal disease due to late diagnosis, aggressiveness and lack of effective therapies. Considering its intrinsic heterogeneity, patient stratification models based on transcriptomic and genomic signatures, with partially overlapping subgroups, have been established. Besides molecular alterations, PDAC tumours show a strong desmoplastic response, resulting in profound metabolic reprogramming involving increased glucose and amino acid consumption, as well as lipid scavenging and biosynthesis. Interestingly, recent works have also revealed the existence of metabolic subtypes with differential prognosis within PDAC, which correlated to defined molecular subclasses in patients: lipogenic subtype correlated with a classical/progenitor signature, while glycolytic tumours associated with the highly aggressive basal/squamous profile. Bioinformatic analyses have demonstrated that the representative genes of each metabolic subtype are up-regulated in PDAC samples and predict patient survival. This suggests a relationship between the genetic signature, metabolic profile, and aggressiveness of the tumour. Considering all this, defining metabolic subtypes represents a clear opportunity for patient stratification considering tumour functional behaviour independently of their mutational background.

Renal cell carcinoma (RCC) represents the main renal tumors and are highly metastatic. They are heterogeneous tumors and are subdivided in 12 different subtypes where clear cell RCC (ccRCC) represents the main subtype. Tumor extracellular matrix (ECM) is composed, in RCC, mainly of different fibrillar collagens, fibronectin, and components of the basement membrane such as laminin, collagen IV, and heparan sulfate proteoglycan. Little is known about the role of these ECM components on RCC cell behavior. Analysis from The Human Protein Atlas dataset shows that high collagen 1 or 4A2, fibronectin, entactin, or syndecan 3 expression is associated with poor prognosis whereas high collagen 4A3, syndecan 4, or glypican 4 expression is associated with increased patient survival. We then analyzed the impact of collagen 1, fibronectin 1 or Matrigel on three different RCC cell lines (Renca, 786-O and Caki-2) in vitro . We found that all the different matrices have little effect on RCC cell proliferation. The three cell lines adhere differently on the three matrices, suggesting the involvement of a different set of integrins. Among the 3 matrices tested, collagen 1 is the only component able to increase migration in the three cell lines as well as MMP-2 and 9 activity. Moreover, collagen 1 induces MMP-2 mRNA expression and is implicated in the epithelial to mesenchymal transition of two RCC cell lines via Zeb2 (Renca) or Snail 2 (Caki-2) mRNA expression. Taken together, our results show that collagen 1 is the main component of the ECM that enhances tumor cell invasion in RCC, which is important for the metastasic process., (Copyright © 2020 Majo, Courtois, Souleyreau, Bikfalvi and Auguste.)

Metformin is a biguanide molecule used since 1957 to treat type 2 diabetes patients. In addition to its hypoglycemic effects, epidemiological studies have shown that metformin can be associated with a decrease in cancer development risk in diabetic populations. Thus, since 2005 this molecule is largely studied for its antitumoural properties in different types of cancer. The potential antitumoural effect of metformin in gastric cancer has been poorly studied. Here, we detailed the different described mechanisms implicated in the antitumoural effect of metformin in gastric cancer, from the signalling pathways to the functional effects on gastric cancer cell lines and gastric cancer stem cells.

To quantify the impact of fecal pollution on the microbiological bathing water quality, predictive modeling is being increasingly used in which the decay rate of the fecal indicators plays an important role. The decay of sewage-sourced enterococci and Escherichia coli culturable cells and their associated molecular markers (16SrRNA) quantified by Quantitative Reverse transcription PCR were measured in controlled microcosms as well in in situ conditions using different water types, from marine waters to fresh waters with intermediate salinity. All bacterial decays were fitted to a first order decay model. In the laboratory study, the light radiation was the most influent factor affecting E. coli and enterococci survival by culture methods although environmental conditions weakly impacted the decay of molecular markers. The results also indicated differential persistence of genetic markers and culturable organisms of fecal indicator bacteria in different water systems. For each bacteria indicator and analytical method, four equations were obtained to predict the time required to have a 90% reduction (T90) according irradiance, salinity and temperature parameters. The weighted model RMSE (Root Mean Square Error) calculated for all field experiments showed that quantification obtained with the equations defined by laboratory-based study compared reasonably well with in-situ observed quantification (0.4 and 0.2 log by standard culture methods for E. coli and Enterococcus spp. and 0.6 and 0.3 log by RT-qPCR for E. coli and Enterococcus spp. respectively). The modeling tool can be used to predict the presence of fecal pollution in marine and fresh waters in combination with either culture based- or rapid molecular methods., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

The United Nations' Sustainable Development Goals initiated in 2016 reiterated the need for safe water and healthy lives across the globe. The tenth anniversary meeting of the International Water and Health Seminar in 2018 brought together experts, students, and practitioners, setting the stage for development of an inclusive and evidence-based research agenda on water and health. Data collection relied on a nominal group technique gathering perceived research priorities as well as underlying drivers and adaptation needs. Under a common driver of public health protection, primary research priorities included the socioeconomy of water, risk assessment and management, and improved monitoring methods and intelligence. Adaptations stemming from these drivers included translating existing knowledge to providing safe and timely services to support the diversity of human water needs. Our findings present a comprehensive agenda of topics at the forefront of water and health research. This information can frame and inform collective efforts of water and health researchers over the coming decades, contributing to improved water services, public health, and socioeconomic outcomes., (Copyright © 2019 Elsevier GmbH. All rights reserved.)