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Microenvironmental signals strongly influence chronic lymphocytic leukemia (CLL) cells through the activation of distinct membrane receptors, such as B-cell receptors, and inflammatory receptors, such as Toll-like receptors (TLRs). Inflammatory pathways downstream of these receptors lead to NF-κB activation, thus protecting leukemic cells from apoptosis. Dimethyl fumarate (DMF) is an anti-inflammatory and immunoregulatory drug used to treat patients with multiple sclerosis and psoriasis in which it blocks aberrant NF-κB pathways and impacts the NRF2 antioxidant circuit. Our in vitro analysis demonstrated that increasing concentrations of DMF reduce ATP levels and lead to the apoptosis of CLL cells, including cell lines, splenocytes from Eµ-TCL1-transgenic mice, and primary leukemic cells isolated from the peripheral blood of patients. DMF showed a synergistic effect in association with BTK inhibitors in CLL cells. DMF reduced glutathione levels and activated the NRF2 pathway; gene expression analysis suggested that DMF downregulated pathways related to NFKB and inflammation. In primary leukemic cells, DMF disrupted the TLR signaling pathways induced by CpG by reducing the mRNA expression of NFKBIZ, IL6, IL10 and TNFα. Our data suggest that DMF targets a vulnerability of CLL cells linked to their inflammatory pathways, without impacting healthy donor peripheral blood mononuclear cells., (© 2024. The Author(s).)

Urbanization is characterized by rapid environmental changes such as an increase in building surface, in pollution, or a decrease in invertebrate abundance. For many bird species, morphological and physiological differences have been observed between urban and rural individuals that seem to reflect a negative impact of urban life on the health and fitness of individuals. Studies on passerine birds also showed important differences between populations and species in their responses to the urban environment. We propose to test physiological differences between urban and forest individuals over 3 years to understand whether the observed patterns are constant or subject to variations across years. For this purpose, we assessed the health parameters of adults and fledgling of great tits, Parus major, living in an urban and in a forest site in the Eurometropole of Strasbourg, for three years. Bird health was estimated with morphological parameters (body condition and size) and also with physiological parameters (oxidative status and telomere length). Our results showed lower body condition of urban fledglings regardless of the year, but no site effects on telomere length. On the contrary, for adult breeders, urban individuals had longer telomeres than forest ones except for one year which coincide with bad weather conditions during reproduction where no difference was detected. Urban birds also had higher antioxidant capacity whatever the years. These results suggest that cities act as a filter in which only good quality individuals survive and achieve successful reproduction regardless of year, whereas in the forest the selection occurs only during harsh weather years., 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 Inc. All rights reserved.)

The interaction between tumor cells and activated fibroblasts determines malignant features of desmoplastic carcinomas such as rapid growth, progression towards a metastatic phenotype, and resistance to chemotherapy. On one hand, tumor cells can activate normal fibroblasts and even reprogram them into CAFs through complex mechanisms that also involve soluble factors. Among them, transforming growth factor beta (TGF-β) and Platelet-Derived Growth Factor (PDGF) have an established role in the acquisition of pro-tumorigenic phenotypes by fibroblasts. On the other hand, activated fibroblasts release Interleukin-6 (IL-6), which increases tumor-cell invasiveness and chemoresistance. However, the interplay between breast cancer cells and fibroblasts, as well as the modes of action of TGF-β, PDGF, and IL-6, are difficult to investigate in vivo. Here, we validated the usage of advanced cell culture models as tools to study the interplay between mammary tumor cells and fibroblasts, taking mouse and human triple-negative tumor cells and fibroblasts as a case study. We employed two different settings, one permitting only paracrine signaling, the other both paracrine and cell-contact-based signaling. These co-culture systems allowed us to unmask how TGF-β, PDGF and IL-6 mediate the interplay between mammary tumor cells and fibroblasts. We found that the fibroblasts underwent activation induced by the TGF-β and the PDGF produced by the tumor cells, which increased their proliferation and IL-6 secretion. The IL-6 secreted by activated fibroblasts enhanced tumor-cell proliferation and chemoresistance. These results show that these breast cancer avatars possess an unexpected high level of complexity, which resembles that observed in vivo. As such, advanced co-cultures provide a pathologically relevant tractable system to study the role of the TME in breast cancer progression with a reductionist approach.

Functional materials are challenging to characterize because of the presence of small structures and inhomogeneous materials. If interference microscopy was initially developed for use for the optical profilometry of homogeneous, static surfaces, it has since been considerably improved in its capacity to measure a greater variety of samples and parameters. This review presents our own contributions to extending the usefulness of interference microscopy. For example, 4D microscopy allows real-time topographic measurement of moving or changing surfaces. High-resolution tomography can be used to characterize transparent layers; local spectroscopy allows the measurement of local optical properties; and glass microspheres improve the lateral resolution of measurements. Environmental chambers have been particularly useful in three specific applications. The first one controls the pressure, temperature, and humidity for measuring the mechanical properties of ultrathin polymer films; the second controls automatically the deposition of microdroplets for measuring the drying properties of polymers; and the third one employs an immersion system for studying changes in colloidal layers immersed in water in the presence of pollutants. The results of each system and technique demonstrate that interference microscopy can be used for more fully characterizing the small structures and inhomogeneous materials typically found in functional materials., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Trace metal elements are significant stressors in urban areas. Their harmful effects on physiological parameters are demonstrated, but current laboratory studies are not representative of wild chronic exposure to a trace metal cocktail. Calcium can reduce the accumulation and toxicity of several metals, but soil acidification in cities leads to a decrease in bioavailability of this element. The objective of this study was to investigate the accumulation and toxicity of a trace metal cocktail representative of urban exposure on passerine birds, and test the importance of calcium availability on these toxic effects. We exposed zebra finches (Taeniopygia guttata) to a cocktail of seven metals and one metalloid in drinking water, with or without calcium supplementation. We monitored the concentration of metals in the blood and feathers, and their effects on oxidative status and telomere length. The metal cocktail led to higher concentration of all elements in the feathers, and of arsenic and lead in the blood. Birds with a higher concentration of cadmium, arsenic and lead in the feathers had shorter telomeres, but no impact of the cocktail was detected on oxidative status. Birds of the 'calcium' group and the 'calcium and metal' group accumulated higher concentrations of zinc, chromium and nickel in feathers. The 'calcium and metal' group also accumulated lower concentrations of arsenic and lead in feathers compared to the 'metal' group. Our results suggest that chronic exposure to a cocktail of metals at low concentrations has deleterious effects on birds, which can be limited through calcium intake., (Copyright © 2020 Elsevier Inc. All rights reserved.)

We addressed here, by means of electrospray ionization mass spectrometry (ESI-MS) with ultrahigh resolution, the molecular level fractionation of a reference fulvic acid (SRFA) during its sorption at an alumina surface, taken as a model for surfaces of natural aluminum oxide hydrates. Examination of ESI-MS spectra of a native SRFA solution and of supernatants collected in sorption experiments at acidic pH showed that the ∼5700 compounds identified in the native solution were partitioned between the solution and alumina surface to quite varying degrees. Compounds showing the highest affinity for the surface were aromatic compounds with multiple oxygenated functionalities, polycyclic aromatic compounds depleted of hydrogen and carrying few oxygenated groups, and aliphatic compounds with very high O/C values, highlighting the fact that SRFA constituents were sorbed mainly via chemical sorption involving their oxygenated functionalities. We observed an inverse correlation between the degree of sorption of a molecule within a CH2 series and its number of CH2 groups and a positive correlation between the degree of sorption and the number of CO2 groups in a COO series, which was remarkable. These correlations provide evidence at the molecular scale that molecule acidity is the key parameter governing fulvic acid (FA) sorptive fractionation, and they are useful for predicting sorption of FA at a natural oxide surface.

The complexation of U(VI) by organic P-containing ligands in humic substances (HS) is an important issue of uranyl mobility in soil. We have investigated the complexation of uranyl by a model ligand for aromatic phosphorus functionalities in HS, phenylphosphonic acid, by using ultrahigh resolution electrospray ionization-mass spectrometry (ESI-MS). The high sensitivity permitted to investigate the complexation of trace level uranyl and to explore directly in the native aqueous solutions the nature of the uranyl-phenylphosphonate complexes. Positive identification of the complexes coexisting in solutions with low pH and varying ligand-to-metal ratio was achieved thanks to the high resolving power, high mass accuracy, and reliability of ion abundance of the technique. The positively charged and neutral uranyl species were detected simultaneously on negative ion mass spectra, evidencing formation of three types of U(VI)-phenylphosphonate complexes. Two complexes with a metal-to-ligand stoichiometry of 1:1 (in the monoprotonated and nonprotonated forms) existed in solutions at pH 3-5, and a 1:2 complex was additionally formed at relatively high ligand-to-metal ratio. A strategy based on the use of uranyl-phosphate solution complexes as internal standards was developed to determine from the ESI(-)MS results the stability constants of the complexes, which were calculated to be log K111 = 3.4 ± 0.2 for UO2(HPhPO3)(+), log K101 = 7.1 ± 0.1 for UO2PhPO3, and log K112 = 7.2 ± 0.2 for UO2(HPhPO3)2. The speciation model presented here suggests that organic P existing at low concentration in HS is involved significantly in binding by humic and fulvic acids of trace level uranyl in soil.

We studied the ligand-enhanced sorption of uranyl ions (1-12 μM) on α-alumina colloids suspended in (and pre-equilibrated with) solutions at various concentrations of phosphate ions (P(T) = 0-900 μM). A highly sensitive technique, time resolved laser-induced fluorescence spectroscopy (TRLFS), was used to examine the chemical speciation of uranyl sorbed at trace concentrations (0.4-4 μmol U·g⁻¹). The suspensions with P(T) ≥ 100 μM exhibited high uranyl adsorption, and a very high intensity of fluorescence that increased with the sorbed amounts of phosphate and uranyl. These samples exhibited similar spectral and temporal characteristics of fluorescence emission, evidencing a uniform speciation pattern and a single coordination environment for sorbed U, despite large variation in parameters such as aqueous uranyl speciation, U loading, and extent of coverage of alumina by secondary Al phosphates precipitating on the surface. The results pointed formation of surface precipitates of uranyl phosphates, which are characterized by high quantum yield, peak maxima at positions similar to those of U(VI) phosphate minerals and four lifetimes indicating distortions, in-homogeneities or varying number of water molecules in the lattice. The findings have major implications for our understanding of the mechanisms of immobilization of U at trace levels on surfaces of oxides submitted to phosphated solutions in soils with low pH.

This study presents new in situ electrophoretic and ATR-FTIR data on the surface species controlling the cosorption of uranyl and phosphate ions in alpha-Al(2)O(3) suspensions at acidic pH (3.3). It was shown that the uranyl sorption (i) was promoted in the presence of phosphate, (ii) induced significant changes in zeta potential of P-loaded alumina, and (iii) was governed by two mechanisms, surface complexation and surface precipitation, with the predominant species being mainly dependent on phosphate surface coverage. Formation of surface precipitates of uranyl phosphate at high phosphate surface coverage was inferred from the high negative charges imparted to the surface by uranyl and phosphate (co)sorption, and from assignments of IR bands at 1107, 1024, and 971 cm(-1) to P-O-stretching vibrations for phosphate coordinated to uranyl, at the alumina surface. The ATR-FTIR study showed that the precipitates of uranyl phosphate formed at the surface of alpha-Al(2)O(3) for aqueous concentrations of uranyl at trace levels. It also evidenced that formation of surface precipitates of U(VI)-phosphate was occurring along with the transformation of alumina into secondary surface precipitates of Al-phosphate, at very high phosphate concentrations. These findings are relevant to the mechanisms of adsorption of trace uranyl on naturally occurring oxide surfaces, in soils with low pH where cosorption of phosphate and uranyl ions is known to play a crucial role in the long-term retention of U., (Copyright 2010 Elsevier Inc. All rights reserved.)

We have investigated the effect of solution parameters on the adsorption of phosphate ions and on charges and structures, i.e., on the nature of species, at the alpha-Al(2)O(3) colloid/solution interface by using the batch method, zeta potential measurements, and in situ ATR-FTIR spectroscopy. The uptake of phosphate decreases with the extent of surface deprotonation (i.e., pH), imparts negative charges to the colloid surface, and induces IEP shifts showing chemical sorption. Use of complementary techniques provides evidence that phosphate is sorbed at low pH (3.3) by a combination of surface reactions of complexation and precipitation, whose relative contributions depend on phosphate loading. Surface complexation includes fast reactions of ligand exchange with single coordinated hydroxyls, and electrostatic attraction of H(2)PO(4)(-) ions at positively charged surface sites. This is supported by experiments at low coverage showing sharp and linear decrease of zeta potential (i.e., surface charge) with amount of phosphate sorbed. At high coverage, zeta potential values are low and independent of phosphate loading. Formation of surface precipitates of Al-phosphate is inferred from the assignment of the ATR-FTIR absorption band at 1137cm(-1), whose intensity increases with phosphate solution content and reaction time, to the P-O-stretching vibration mode for phosphate sorbed at high concentrations on alpha-Al(2)O(3). In situ ATR-FTIR spectroscopy reveals also structural reorganizations of surface hydroxyls with time, due to surface hydration and to surface precipitation continuing over extended periods along alumina dissolution., (Copyright 2009 Elsevier Inc. All rights reserved.)

Purpose: Using a simulated perfusion system, the intent was to determine: 1) the sealing ability of eight restorative materials (five composite resins and three compomers) used together with their corresponding dentin bonding systems, 2) their tensile bond strength, and 3) the correlation (if any) between both parameters., Materials and Methods: Permeability in crown segments from sound human third molars (n = 140) subjected to simulated perfusion (32 cm of distilled water) was measured before and after restoring with each material, and the percentage of decrease in permeability (PPD) was recorded. Specimens were later subjected to tensile tests to determine the tensile bond strength (TBS) of the interface. Finally, parameters were analyzed for correlation., Results: For the eight adhesive systems, the percentage of reduction in permeability was relatively high [mean in %, (SD)]: F2000 93.6 (5.7), SB1 88.6 (11.3), SSC 86.0 (5.7), PB20 81.1 (15.9), COM 77.5 (10.8), OPTS 75.3 (20.6), DYR 73.7 (12.7), SSPR 65.5 (19.8). TBS values were relatively low [mean (SD)], in MPa: F2000 1.8 (0.7), SB1 4.9 (1.4), SSC 2.6 (1.4), PB20 4.3 (1.2), COM 2.4 (1.1), OPTS 4.5 (1.7), DYR 1.6 (0.6), SSPR 4.2 (1.5). We could not demonstrate any statistically significant correlation between both parameters for these results (maximum significance [F2000]: r = 0.39, p = 0.206)., Conclusion: No material completely ceased to filtrate through the interface. The low TBS values were probably due to the large size of adhesive areas. No significant correlation was found between PPD and TBS for the materials tested. There was a statistically significant relationship (r2 = 0.063, p = 0.018) between TBS and TBA (total bonded area), described by the equation TBS = 5.9 - 0.03.TBA.

The objectives of this research were (1) to analyze the variations of the permeability of dentin after restoration with two polyacid-modified resin composites (Compoglass, Dyract) and four single-bottle adhesives (Prime & Bond 2.0, Syntac Single Component, OptiBond Solo, and Single Bond--Scotch Bond 1 in Europe--immediately (approximately 1 hour) after insertion. A perfusion system with distilled water was used at a pressure of 32.5 cm of water; (2) to study the bond strength of their interfaces; and (3) to find the correlation, if any, between both parameters. None of the materials used produced a complete cessation in fluid filtration. Tensile bond strengths were very low (maximum: P&B = 3.96 MPa) probably because of the very large bonding surfaces used (mean bonded surface area = 88.8 mm2). No significant correlation was found between tensile bond strength and the sealing ability for any material.

Assay of glycosylated hemoglobin provides reliable information on metabolic control in diabetes mellitus over a period of about 90 days. This is why it is currently used as a parameter of blood glucose control in diabetic patients. However, at present little is known about the kinetics of stable glycosylated hemoglobin variations as a result of circadian changes in blood glucose level. The authors describe a mathematical model which allows to foresee glycosylated hemoglobin variability as a result of alterations of blood glucose equilibrium.