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Cancer cells are highly dependent on bioenergetic processes to support their growth and survival. Disruption of metabolic pathways, particularly by targeting the mitochondrial electron transport chain complexes (ETC-I to V) has become an attractive therapeutic strategy. As a result, the search for clinically effective new respiratory chain inhibitors with minimized adverse effects is a major goal. Here, we characterize a new OXPHOS inhibitor compound called MS-L6, which behaves as an inhibitor of ETC-I, combining inhibition of NADH oxidation and uncoupling effect. MS-L6 is effective on both intact and sub-mitochondrial particles, indicating that its efficacy does not depend on its accumulation within the mitochondria. MS-L6 reduces ATP synthesis and induces a metabolic shift with increased glucose consumption and lactate production in cancer cell lines. MS-L6 either dose-dependently inhibits cell proliferation or induces cell death in a variety of cancer cell lines, including B-cell and T-cell lymphomas as well as pediatric sarcoma. Ectopic expression of Saccharomyces cerevisiae NADH dehydrogenase (NDI-1) partially restores the viability of B-lymphoma cells treated with MS-L6, demonstrating that the inhibition of NADH oxidation is functionally linked to its cytotoxic effect. Furthermore, MS-L6 administration induces robust inhibition of lymphoma tumor growth in two murine xenograft models without toxicity. Thus, our data present MS-L6 as an inhibitor of OXPHOS, with a dual mechanism of action on the respiratory chain and with potent antitumor properties in preclinical models, positioning it as the pioneering member of a promising drug class to be evaluated for cancer therapy. MS-L6 exerts dual mitochondrial effects: ETC-I inhibition and uncoupling of OXPHOS. In cancer cells, MS-L6 inhibited ETC-I at least 5 times more than in isolated rat hepatocytes. These mitochondrial effects lead to energy collapse in cancer cells, resulting in proliferation arrest and cell death. In contrast, hepatocytes which completely and rapidly inactivated this molecule, restored their energy status and survived exposure to MS-L6 without apparent toxicity.

Despite achieving high rates of complete remission with RCHOP immuno-chemotherapy, almost all patients with follicular lymphoma (FL) will experience multiple relapses after treatment. The lack of experimental model of FL limits our understanding of treatment response heterogeneity. Here we characterized a new model of FL patient-derived xenograft in avian embryos. Based on 20 biopsy samples, we observed that tumor volume reduction achieved with RCHOP treatment in ovo predicted progression free survival in multivariate analysis. To further explore the model, we used single-cell RNA sequencing to discover a signature of 21 genes upregulated after RCHOP exposure, with significant intratumoral heterogeneity. Among these genes, we functionally validated BAX as a critical effector of RCHOP which can be targeted with venetoclax in vitro and in ovo. Overall, the FL-AVI-PDX model is a platform for functional precision oncology in FL, which captures both interpatient and intrapatient heterogeneity, and opens an avenue for drug development

For a long time, limestone has been massively used in stone building and monuments because of its easy extraction and common presence in the landscape. On ancient monuments, mostly built in urban areas, it is exposed to urban-borne pollutants responsible for specific alteration mechanisms and weathering kinetics. Especially, the dissolution of calcite and the precipitation of new phases will affect the limestone pore network, modify the stones capillary properties, and influence the further alteration. In order to better understand these processes, an altered limestone sample from ‘Tribunal Administratif’ (TA) in Paris was studied. The main secondary phase was found to be syngenite, which can be explained by the location of the sample close to the soil, a potential source of K (fertilizers). This phase is more soluble than gypsum that is commonly found on altered limestone. In order to assess the reactivity of the system (limestone and new phases), oxygen and hydrogen isotopes were used to trace the transfer of water (D 2 18 O) and identify the location of the reactive areas (susceptible to alteration). For that, TA samples were exposed in a climatic chamber to relative humidity (RH) cycles (25% RH for 2.5 days and 85% RH for 4.5 days) for 2 months with a D 2 18 O vapor to simulate alteration occurring in conditions sheltered from the rain. Results have shown that the water vapor easily circulates deep in the sample and reacts preferentially with syngenite the most reactive phase (compared with calcite and quartz). This phase could evolve in gypsum when exposed to an environment different from the one resulting in its formation.

Buildings and monuments are often colonized by microorganisms that can result in colour change and aesthetical and physico-chemical damages. This bio-colonization is dependent of the material and on the environment. In order to better understand and correlate the microbial development at the surface of buildings with meteorological parameters, concentration of green algae and cyanobacteria have been measured using an in situ instrument on the wall of a private habitation in the Parisian region during two periods: spring and fall-winter. Different locations were also chosen to assess the influence of the position (horizontal or vertical) and of the situation (shaded vs. sunny microclimate). The results show that the microorganism development rapidly responds to rainfall events but the response is more intense in winter as temperature is lower and relative humidity (RH) higher. Cyanobacteria are less sensitive to this seasonal effect as they are more resistant to desiccation than green algae. Based on all the data, different dose-response functions have been established to correlate RH, rain and temperature to the green algae concentration. The influence of the microclimate is considered via specific fitting parameters. This approach has to be extended to new campaign measurements but could be very useful to anticipate the effect of climate change.

This work aims to investigate the role played by a model Mn-oxidizing bacterial strain and its exudates on the alteration of Mn-bearing potash-lime silicate glasses representative of medieval stained glass windows. Two model glasses, with or without manganese, were prepared and used for abiotic and Pseudomonas putida inoculated dissolution experiments. Results show that the presence of P. putida slows down the dissolution kinetics while changing the dissolution stoichiometry. In biotic experiments, the acidification of the solution at the beginning of the experiment favors the release of K. After a few days, a drop in Mn and P in solution is observed, retained by bacterial cells. Reciprocally, the amount of glass influences bacterial behavior. The more glass, the faster the bacterial population increases in size and produces siderophore. In the presence of the Mn-bearing glass, siderophore production is followed by the formation of brown phases, identified as Mn oxides.

This paper reports estimated maintenance-cleaning costs, cost savings and cleaning interval increases for structural surfaces and windows in Europe obtainable by reducing the air pollution. Methodology and data from the ICP-materials project were used. The average present (2018) cleaning costs for sheltered white painted steel surfaces and modern glass due to air pollution over background, was estimated to be ~2.5 Euro/m2∙year. Hypothetical 50% reduction in the air pollution was found to give savings in these cleaning costs of ~1.5 Euro/m2∙year. Observed reduction in the air pollution, from 2002–2005 until 2011–2014, have probably increased the cleaning interval for white painted steel with ~100% (from 12 to 24 years), representing reductions in the single intervention cleaning costs from 7 to 4%/year (= % of one cleaning investment, per year during the cleaning interval) and for the modern glass with ~65% (from 0.85 to 1.3 years), representing reductions in the cleaning cost from 124 to 95%/year. The cleaning cost reductions, obtainable by 50% reduction in air pollution, would have been ~3 %/year for white painted steel and ~60%/year for the modern glass, representing ~100 and 50% additional cleaning interval increases. These potential cleaning cost savings are significantly higher than previously reported for the weathering of Portland limestone ornament and zinc monuments.

Limestone buildings in urban areas are weathered due to climatic factors, to pollution but also to biological activity. Many studies have focused on microbially-mediated precipitation of calcite but few on their influence on limestone dissolution rates. In this study, a cultivable approach for studying bacterial dissolution of limestone is proposed. The results show, for the first time, that limestone has selected a specific structure in the bacterial communities and that each bacterial class has its own metabolism inducing a different efficiency on the alteration of limestone grains. Cultivable bacterial and fungal strains in our study permit to considerably increase (by 100 to 1,000,000 times) the chemical weathering rates compared to laboratory or field experiments. Individually, the results bring information on the ability to alter limestone by dissolution. Moreover, taken together, a functional ecological adaptation of bacterial and fungal classes to the alteration of the limestone monument has been highlighted. In order to release calcium into solution, these strains slightly acidify the medium and produce low molecular mass organic acids during experiments, especially lactic and oxalic acids.

Biological activity, climate and pollution are responsible for the degradation of building stones, especially limestone, which is widely used in the Paris region. In order to determine the respective contribution of physicochemical and biological processes to the degradation of limestone, limestone specimens from the Père-Lachaise cemetery (Paris, France) were exposed for five years under different conditions: sheltered from or exposed to rain and in horizontal or vertical position. After exposure, the collected samples were characterized by light and electron microscopy, X-Ray diffraction and ion chromatography after elution. The results showed an intense biocolonization of the samples exposed to rain, while the sheltered samples were more affected by the pollution (soiling). The characterization of the bacterial and fungal communities using Next Generation Sequencing Illumina 16S for bacteria and ITS for fungi highlighted that five main bacterial phyla were identified: Actinobacteriota, Bacteroidota, Cyanobacteria, Proteobacteria and Deinococcota (major genera Flavobacterium, Methylobacterium-Methylobacter, Sphingomonas, Roseomonas and Nocardiodes). Among the fungi, the phylum Ascomycota was predominant with the genera Cladosporium, Ramularia, Aureobasidium and Lecania. However, the alteration of the limestone is difficult to quantify at this stage. Potassium nitrate of rain origin has been found in the sheltered area, but no gypsum. Therefore, the biocolonization is a fast phenomenon on the stone and the physico-chemical processes derived from it, caused by climate and pollution, are slower. This is in agreement with the long-term observations made on old and unrestored graves of the cemetery described in the literature.

Stained glass windows are a precious heritage to pass on to future generations. However, medieval stained glass windows are particularly altered due to their chemical composition and the effects of climatic (mainly water and temperature), environmental (pollution) and biological factors. In this review, we present the alteration patterns observed on ancient Si-K-Ca stained glass windows. To better understand their formation mechanisms and determine the alteration rates, different exposure campaigns to the current atmosphere in a position sheltered from rain or not and laboratory experiments in aqueous medium or in gaseous phase have been conducted. Either model glass or ancient stained glass windows were studied. Isotopic tracers (D, 18 O, 29 Si) have been used as they constitute a powerful tool to elucidate the involved processes and to measure their kinetics. Thanks to all of these data, an alteration scenario of medieval stained glass alteration is proposed. Besides, the extrapolation of kinetic data based on several hypotheses over seven centuries gives very consistent results compared to the ancient stained glass samples.

Most stained-glass windows installed during the Middle Ages have deteriorated over time due to climate and pollution. To reconstruct their alteration history over the centuries, evaluate the current environmental risk, and predict their alteration in the future, two modelling methodologies have been used. First, based on the short-term exposure of medieval-type glass in different sites, dose–response functions (DRFs) were established. These DRFs correlate relevant environmental factors (temperature, rain quantity, rain pH, relative humidity, and SO2 concentration) with the response of the material in terms of alteration layer thickness. The second methodology consists of laboratory experiments that aim at parametrising kinetic laws as a function of specific parameters (temperature, rain pH, and relative humidity). These kinetic laws can be extrapolated over long periods, contrary to DRFs. In this study, we compared both methodologies to simulate the alteration of a model stained glass at different European sites or over different time periods. The results highlighted that the kinetic laws were able to closely represent the data, except for the polluted sites where the alteration was underestimated. This indicated that the dependence of the alteration rate on the pollutant concentrations should be included to improve the model.