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Background: Mycobacterium abscessus is an emerging pathogen causing severe pulmonary infections, particularly in individuals with underlying conditions, such as cystic fibrosis or chronic obstructive pulmonary disease. Macrolides, such as clarithromycin (CLR) or azithromycin (AZM), represent the cornerstone of antibiotherapy against the M. abscessus species. However, prolonged exposure to these macrolides can induce of Erm(41)-mediated resistance, limiting their spectrum of activity and leading to therapeutic failure. Therefore, inhibiting Erm(41) could thwart this resistance mechanism to maintain macrolide susceptibility, thus increasing the rate of treatment success. In our previous study, the Erm(41) methyltransferase was identified as a possible target enzyme of Cyclipostins and Cyclophostin compounds (CyC)., Methods: Herein, we exploited this feature to evaluate the in vitro activity of CLR and AZM in combination with different CyC via the checkerboard assay on macrolide-susceptible and induced macrolide-resistant M. abscessus strains selected in vitro following exposure CLR and AZM., Results: Our results emphasize the use of the CyC to prevent/overcome Erm(41)‑induced resistance and to restore macrolide susceptibility., Conclusion: This work should expand our therapeutic arsenal in the fight against a antibioticresistant mycobacterial species and could provide the opportunity to revisit the therapeutic regimen for combating M. abscessus pulmonary infections in patients, and particularly in erm(41)-positive strains., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication and references: Not applicable. Competing interests: The authors declare that they have no competing interests. Not applicable., (© 2024. The Author(s).)

The Cell-Assembled extracellular Matrix (CAM) is an attractive biomaterial because it provided the backbone of vascular grafts that were successfully implanted in patients, and because it can now be assembled in "human textiles". For future clinical development, it is important to consider key manufacturing questions. In this study, the impact of various storage conditions and sterilization methods were evaluated. After 1 year of dry frozen storage, no change in mechanical nor physicochemical properties were detected. However, storage at 4 °C and room temperature resulted in some mechanical changes, especially for dry CAM, but physicochemical changes were minor. Sterilization modified CAM mechanical and physicochemical properties marginally except for hydrated gamma treatment. All sterilized CAM supported cell proliferation. CAM ribbons were implanted subcutaneously in immunodeficient rats to assess the impact of sterilization on the innate immune response. Sterilization accelerated strength loss but no significant difference could be shown at 10 months. Very mild and transient inflammatory responses were observed. Supercritical CO 2 sterilization had the least effect. In conclusion, the CAM is a promising biomaterial since it is unaffected by long-term storage in conditions available in hospitals (hydrated at 4 °C), and can be sterilized terminally (scCO 2 ) without compromising in vitro nor in vivo performance. STATEMENT OF SIGNIFICANCE: In the field of tissue engineering, the use of extracellular matrix (ECM) proteins as a scaffolding biomaterial has become very popular. Recently, many investigators have focused on ECM produced by cells in vitro to produce unprocessed biological scaffolds. As this new kind of "biomaterial" becomes more and more relevant, it is critical to consider key manufacturing questions to facilitate future transition to the clinic. This article presents an extensive evaluation of long-term storage stability and terminal sterilization effects on an extracellular matrix assembled by cells in vitro. We believe that this article will be of great interest to help tissue engineers involved in so-called scaffold-free approaches to better prepare the translation from benchtop to bedside., 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. Published by Elsevier Ltd.)

In July 2013, a fatal train derailment led to an explosion and fire in the town of Lac-Mégantic (LM), Quebec, and the crude oil contamination of regional surface water, soil, and sediment in the adjacent Lake Mégantic. This study investigated the degradation potential of the spilled crude oil by using the sediments from the incident site as the source of microorganisms. Two light crude oils (LM source oil and Alberta Sweet Mixed Blend (ASMB)) were tested at 22 °C for 4 weeks and 4 °C for 8 weeks, respectively. The post-incubation biological and chemical information of the samples were analysed. There was no marked difference in degradation efficacy and biological activities for both the LM and ASMB oils, although the biodegradation potential differed between the two incubations. Higher temperature favoured the growth of microorganisms, thus for the degradation of all petroleum hydrocarbons, except for some conservative biomarkers. The degradation of both oils followed the order of resolved components > total saturated hydrocarbons (TSH) > unresolved complex mixture (UCM) >total aromatic hydrocarbons (TAH). Normal alkanes were generally degraded more significantly than branched ones, and polycyclic aromatic hydrocarbons (PAHs). Degradation of polycyclic aromatic hydrocarbons (PAHs) and their alkylated congeners (APAHs) for both incubations generally decreased as the number of aromatic rings, and the degree of alkylation increased. This study showed that the LM sediments can biodegrade the petroleum hydrocarbons efficaciously if appropriate ambient temperatures are generated to favour the growth of autochthonous microorganisms., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Pyramidal metamaterials are currently developed for ultra-broadband absorbers. They consist of periodic arrays of alternating metal/dielectric layers forming truncated square-based pyramids. The metallic layers of increasing lengths play the role of vertically and, to a less extent, laterally coupled plasmonic resonators. Based on detailed numerical simulations, we demonstrate that plasmon hybridization between such resonators helps in achieving ultra-broadband absorption. The dipolar modes of individual resonators are shown to be prominent in the electromagnetic coupling mechanism. Lateral coupling between adjacent pyramids and vertical coupling between alternating layers are proven to be key parameters for tuning of plasmon hybridization. Following optimization, the operational bandwidth of Au/Ge pyramids, i.e. the bandwidth within which absorption is higher than 90%, extends over a 0.2-5.8 µm wavelength range, i.e. from UV-visible to mid-infrared, and total absorption (integrated over the operational bandwidth) amounts to 98.0%. The omni-directional and polarization-independent high-absorption properties of the device are verified. Moreover, we show that the choice of the dielectric layer material (Si versus Ge) is not critical for achieving ultra-broadband characteristics, which confers versatility for both design and fabrication. Realistic fabrication scenarios are briefly discussed. This plasmon hybridization route could be useful in developing photothermal devices, thermal emitters or shielding devices that dissimulate objects from near infrared detectors.

The functional patterns of microbial communities (microbial respiration, enzyme activities, functional diversity) and the relevant physico-chemical characteristics of rhizospheric soils were studied during the process of mudflat colonization by mangrove. The study site is a fringe mangrove stand located in Montabo Bay at Cayenne (French Guiana). It is characterized by different vegetation development stages dominated by an assemblage of Avicennia germinans and Laguncularia racemosa. Rhizospheric and surface soils were collected from three stations based on successional stages of mangrove colonization: pioneer (P), coppice (C), and young forest (F). The microbial functional patterns showed significant progressive shifts along the mangrove vegetation profile. The P stages, those most influenced by tide currents, were macroscopically characterized by hydro-sedimentary instability and micro-phytobenthic colonization of mudflat. This stage, characterized by low total organic carbon (TOC) content and quality, showed the lowest extracellular enzymatic activities and the highest functional metabolic diversities. TOC quality analyses by (13)C CPMAS NMR provided evidence of progressive TOC enrichment and an increasing imprint of aboveground vegetation on C quality as succession occurs. These differences in the origin, amount, and quality of soil organic matter (SOM) of older stages exerted both a quantitative and qualitative control over microbial functional responses. This indicated the enhancement of aboveground-belowground functional linkages, leading to the expression of high decomposition activities and a functional loss and specialization of rhizospheric microbial communities.

Because of the temporal incoherence of sunlight, solar cells efficiency should depend on the degree of coherence of the incident light. However, numerical computation methods, which are used to optimize these devices, fundamentally consider fully coherent light. Hereafter, we show that the incoherent efficiency of solar cells can be easily analytically calculated. The incoherent efficiency is simply derived from the coherent one thanks to a convolution product with a function characterizing the incoherent light. Our approach is neither heuristic nor empiric but is deduced from first-principle, i.e. Maxwell's equations. Usually, in order to reproduce the incoherent behavior, statistical methods requiring a high number of numerical simulations are used. With our method, such approaches are not required. Our results are compared with those from previous works and good agreement is found.

In this paper the design, fabrication and characterization of a bioinspired overlayer deposited on a GaN LED is described. The purpose of this overlayer is to improve light extraction into air from the diode's high refractive-index active material. The layer design is inspired by the microstructure found in the firefly Photuris sp. The actual dimensions and material composition have been optimized to take into account the high refractive index of the GaN diode stack. This two-dimensional pattern contrasts other designs by its unusual profile, its larger dimensions and the fact that it can be tailored to an existing diode design rather than requiring a complete redesign of the diode geometry. The gain of light extraction reaches values up to 55% with respect to the reference unprocessed LED.

Introduction: Hospital re-admissions for patients with congestive heart failure (CHF) are relatively common and costly occurrences within the US health infrastructure, including the Veterans Affairs (VA) healthcare system. Little is known about CHF re-admissions among rural veteran patients, including the effects of socio-demographics and follow-up outpatient visits on these re-admissions., Purpose: To examine socio-demographics of US veterans with CHF who had 30 day potentially preventable re-admissions and compare the effect of 30 day VA post-discharge service use on these re-admissions for rural- and urban-dwelling veterans., Methods: The 2005-2007 VA data were analyzed to examine patient characteristics and hospital admissions for 36 566 veterans with CHF. The CHF patients who were and were not re-admitted to a VA hospital within 30 days of discharge were identified. Logistic regression was used to examine and compare the effect of VA post-acute service use on re-admissions between rural- and urban-dwelling veterans., Results: Re-admitted veterans tended to be older (p=.002), had disability status (p=.024) and had longer hospital stays (p<.001). Veterans Affairs follow-up visits were negatively associated with re-admissions for both rural and urban veterans with CHF (ORs 0.16-0.76). Rural veterans aged 65 years and older who had VA emergency room visits following discharge were at high risk for re-admission (OR=2.66)., Conclusions: Post-acute follow-up care is an important factor for promoting recovery and good health among hospitalized veterans with CHF, regardless of their rural or urban residence. Older, rural veterans with CHF are in need of special attention for VA discharge planning and follow up with primary care providers.

The toxicity and bioavailability of metals were assessed to verify the efficiency of a new chemical leaching process (METIX-AC) to minimize the risk of metals found in municipal sewage sludge. For this purpose, sludge samples were spiked with cadmium, copper and/or zinc before being treated using METIX-AC. The sludge decontamination resulted in a removal of spiked metals (79-89%), in a decrease of the more labile fractions, and in a corresponding increase of the residual fraction. The toxicity observed after exposure of two plant species, barley (Hordeum vulgare) and ryegrass (Lolium perenne), and a terrestrial invertebrate, Eisenia andrei, to sludge-soil mixtures, disappeared after treatment, although the adverse effects were minor before treatment. The sludge treatment also significantly decreased the bioaccumulation of cadmium, copper, and zinc in the exposed species. For cadmium, maximum tissue concentrations of 0.45+/-0.08 mg/kg in barley, 0.79+/-0.27 mg/kg in ryegrass, and 21.82+/-1.85 mg/kg in earthworm exposed to sludge before treatment decreased after treatment to values similar to those observed with negative controls.

In normal colon epithelium, cell proliferation is followed by cell differentiation. The purpose of this work was to investigate, in the HT29-D4 colon adenocarcinoma cell line, the occurrence of a temporal sequence of changes in cell proliferation and differentiation, the role of autocrine EGF family ligands and to determine which transduction pathway(s) are involved in these processes. In a medium lacking both growth factor and serum, HT29-D4 cells secreted amphiregulin (AR), which was shown to be strongly involved in cell adhesion, growth and differentiation. In the main, integrins alpha2beta1 and alphavbeta6 intervened in these processes. Using tyrphostins, it was demonstrated that AR involvement was mediated through the ErbB1/ERK1,2 and ErbB1/FAK pathways. These signalling molecules were directly involved in pRb inhibition and, thus, in cyclin A expression. Concomitantly, colon differentiation markers were also expressed. Furthermore, terminal cell maturation resulted in a colon absorptive cell with strong polarisation, the growth of which was inhibited by tyrphostin and an ERK1,2 inhibitor. It was concluded that in a colon adenocarcinoma, cell proliferation and differentiation can occur concomitantly and that these deregulated processes are controlled by autocrine secretion through the ErbB1/ERK1,2 and FAK pathways.

The toxicities of 2,4,6-trinitrotoluene (TNT), 1,3,5-trinitrobenzene (TNB), 2,4-dinitrotoluene (2,4-DNT), and 2,6-dinitrotoluene (2,6-DNT) to terrestrial plants alfalfa (Medicago sativa L.), Japanese millet (Echinochloa crusgalli L.), and perennial ryegrass (Lolium perenne L.) were determined in Sassafras sandy loam soil using seedling emergence, fresh shoot, and dry mass measurement endpoints. A 13-week weathering and aging of energetic materials in soils, which included wetting and drying cycles, and exposure to sunlight of individual soil treatments, was incorporated into the study design to better reflect the soil exposure conditions in the field than toxicity determinations in freshly amended soils. Definitive toxicity tests showed that dinitrotoluenes were more phytotoxic for all plant species in freshly amended treatments based on EC20 values for dry shoot ranging from 3 to 24mgkg(-1) compared with values for TNB or TNT ranging from 43 to 62mgkg(-1). Weathering and aging of energetic materials (EMs) in soil significantly decreased the toxicity of TNT, TNB or 2,6-DNT to Japanese millet or ryegrass based on seedling emergence, but significantly increased the toxicity of all four EMs to all three plant species based on shoot growth. Exposure of the three plant species to relatively low concentrations of the four compounds initially stimulated plant growth before the onset of inhibition at greater concentrations (hormesis).

Explosives are released into the environment at production and processing facilities, as well as through field use. These compounds may be toxic at relatively low concentrations to a number of ecological receptors. A toxicity assessment was carried out on soils from an explosive-contaminated site at a Canadian Forces Area Training Center. Toxicity studies on soil organisms using endpoints such as microbial processes (potential nitrification activity, dehydrogenase activity, substrate-induced respiration, basal respiration), plant seedling and growth (Lactuca sativa and Hordeum vulgare), and earthworm (Eisenia andrei) growth and reproduction were carried out. Results showed that 1,3,5,7-tetranitro-1,3,5,7-tetrazacyclooctane (HMX) was the principal polynitro-organic compound measured in soils. Soils from the contaminated site decreased microbial processes and earthworm reproduction; whereas plant growth was not significantly reduced. Toxicity to aquatic organisms and genotoxicity were also assessed on soil elutriates using Microtox (Vibrio fischeri), growth inhibition of algae (Selenastrum capricornutum), and SOS Chromotest (Escherichia coli). Results indicated that soil elutriates were generally not toxic to bacteria (Microtox) and algae. However, genotoxicity was found in a number of soil elutriate samples. Thus, the explosive-contaminated soils from the antitank firing range may represent a hazard for the soil organisms. Nevertheless, the global toxicity might have partially resulted from HMX as well as from other (not identified) contaminants such as heavy metals.

Soils contaminated with 2,4,6-trinitrotoluene (TNT) and TNT primary reduction products have been found to be toxic to certain soil invertebrates, such as earthworms. The mechanism of toxicity of TNT and of its by-products is still not known. To ascertain if one of the TNT reduction products underlies TNT toxicity, we tested the toxicity and bioaccumulation of TNT reduction products. 2-Amino-4,6-dinitrotoluene (2-ADNT), 4-amino-2,6-dinitrotoluene (4-ADNT), 2,4-diamino-6-nitrotoluene (2,4-DANT) and 2,6-diamino-4-nitrotoluene (2,6-DANT) were tested separately in adult earthworms (Eisenia andrei) following a 14-d exposure to amended sandy loam forest soil. TNT, 4-ADNT, and 2-ADNT were lethal to earthworms (14-d LC(50) were: 580, 531 and 1088 micromol kg(-1), or 132, 105 and 215 mgkg(-1) dry soil, respectively) and gave the following order of toxicity: 4-ADNT>TNT>2-ADNT. Exposure to 2,4-DANT and to 2,6-DANT caused no mortality at 600 micromol kg(-1) or 100 mgkg(-1) dry soil. We found that all four TNT reduction products accumulated in earthworm tissues and 2-ADNT reached the highest levels at 3.0+/-0.3 micromol g(-1) tissue. The 14-d bioaccumulation factors were 5.1, 6.4, 5.1 and 3.2 for 2-ADNT, 4-ADNT, 2,4-DANT and 2,6-DANT, respectively. Results also suggest that some TNT metabolites are at least as toxic as TNT and should be considered when evaluating the overall toxicity of TNT-contaminated soil to earthworms.

The acetonitrile-sonication extraction method (US EPA SW-846 Method 8330) and aquatic-based toxicity tests were used on laboratory and field samples, to characterize the ecotoxicity of soils contaminated with energetic substances. Spiked soil studies indicated that 2,4, 6-trinitrotoluene (TNT)-dependent soil toxicity could be measured in organic extracts and aqueous leachates using the 15-min Microtox (Vibrio fischeri, IC50=0.27 to 0.94 mg TNT/liter incubation medium) and 96-h Selenastrum capricornutum growth inhibition (IC50=0.62 to 1. 14 mg/liter) toxicity tests. Analyses of leachates of composite soil samples [containing TNT and some TNT metabolites, 1,3,5-trinitro-1,3, 5-triazacyclohexane (RDX), and 1,3,5,7-tetranitro-1,3,5, 7-tetrazacyclooctane (HMX)] from an explosives manufacturing facility, indicated toxicities similar to those found in the TNT-spiked soil studies and pure TNT in solution, and suggested that TNT was the major toxicant. Using TNT as a model toxicant in soils having different moisture contents (20% vs dry) and textures (sandy vs clayey-sandy) but similar organic matter content (3-4%), multi-factorial analyses of Microtox test data revealed that these soil factors significantly influenced the TNT extractability from soil and subsequent toxicity measurements. Taken together, data indicate that the modified Method 8330 may be used in conjunction with ecotoxicity tests to reflect the toxic potential of soils contaminated with energetic substances., (Copyright 1999 Academic Press.)

The human colon adenocarcinoma HT29-D4 cell line is an interesting model for studies on epithelial cell differentiation. Undifferentiated cells are malignant proliferating cells, whereas differentiated cells act like epithelial polarized cells. In the present study, we first characterized the action of taxoids on the microtubular network of HT29-D4 cells according to the state of differentiation. Microtubular bundles were found in undifferentiated cells but not in differentiated cells, even with 500-fold higher taxoid concentrations for 96 h. This finding led us to study changes in microtubules according to the polarity status of the cell. E-MAP-115 was expressed only in differentiated cells; expression of beta-tubulin isotypes was altered in them relative to undifferentiated cells. Classes I, II, III, IVa and IVb isotypes were expressed in both phenotypes; however, differentiated epithelial cells displayed a specific increase in class III beta-tubulin. Thus, the increase in expression of this beta-tubulin isotype in differentiated cells is not restricted to neuronal cells. Moreover, these expression changes may reflect a higher stability of microtubular network in differentiated cells, which may explain the lower activity of anti-microtubule agents, independently of the mitotic process. These results indicate that the composition of microtubules should be considered as one of the criteria involved in the response of tumour cells to chemotherapy with anti-microtubule agents.

The acetonitrile-sonication extraction method (US EPA Method 8330) associated with aquatic-based toxicity tests was examined to study the ecotoxicity of energetic substances in soil. Three studies were carried out: (1) toxicological characterization of different energetic substances to select a representative toxicant and to validate the choice of bioassays; (2) choice of an appropriate solvent to transfer acetonitrile extracts to the bioassay incubation media; and (3) optimization of Method 8330 using soil samples spiked with the toxicant. Initial studies indicated that pure 2,4,6-trinitrotoluene (TNT) was toxic to Vibrio fischeri [Microtox; IC50 (15 min) of 4.2 microM], whereas RDX was less toxic (IC20 = 181 microM) and HMX was not toxic up to its limit of water solubility (< 22 microM). Selected pure TNT metabolites were less toxic than TNT. Similar results were found using the 96-h Selenastrum capricornutum growth inhibition test. The toxicity of pure TNT in different solvents (acetonitrile, acetone, and DMSO) and that from Method 8330-extracted TNT-spiked soil samples were compared to TNT dissolved in water. Data indicated that DMSO was the most appropriate solvent to transfer the acetonitrile extracts. A modified Method 8330 may be used in conjunction with bioassays and chemical analyses to examine the ecotoxicity of soils contaminated with energetic substances.

We have characterized the binding of trans-1-(2,5-dimethoxyphenyl)-3-[4-(dimethylamino)phenyl]-2-methyl-2- propen- 1-one (MDL 27048) to purified procine brain tubulin, and the inhibition of microtubule assembly by this compound in vitro and using cultured cells. Binding measurements were performed by difference absorption and fluorescence spectroscopy. MDL 27048 binds to one site/tubulin heterodimer with an apparent equilibrium constant Kb = (2.8 +/- 0.8) X 10(6) M-1 (50 mM 2-(N-morpholino)ethanesulfonic acid, 1 mM [ethylenebis(oxyethylenenitrilo)]tetraacetic acid, 0.5 mM MgCl2, 0.1 mM GTP buffer, pH 6.7, at 25 degrees C). Podophyllotoxin displaced the binding of MDL 27048, suggesting an overlap with the colchicine-binding site. Assembly of purified tubulin into microtubules was inhibited by substoichiometric concentrations of MDL 27048, which also induced a slow depolymerization of preassembled microtubules. The cytoplasmic microtubules of PtK2 cells were disrupted in a concentration and time-dependent manner by MDL 27048, as observed by indirect immunofluorescence microscopy. Maximal depolymerization took place with 2 X 10(-6) M MDL 27048 in 3 h. When the inhibitor was washed off from the cells, fast microtubule assembly (approximately 8 min) and complete reorganization of the cytoplasmic microtubule network (15-30 min) were observed. MDL 27048 also induced mitotic arrest in SV40-3T3 cell cultures. Due to all these properties, this anti-tumor drug constitutes a new and potent microtubule inhibitor, characterized by its specificity and reversibility.