Buckwalker6850

The rat immediate implant model indicated that the SP-ALN dual-delivery system could present the promoted peri‑implant osteogenic property and osseointegration through modulating the osteogenesis-osteoclastogenesis balance. This work highlights the sequential dual delivery of SP and ALN has a promising potential of achieving enhanced osseointegration for immediate implant placement.In order to develop optimum microneedle designs, researchers must first develop robust, repeatable and adaptable test methods which are representative of in vivo conditions. However, there is a lack of experimental tools which can accurately comparatively interrogate functional microneedle penetration of tissue. In this study, we seek to develop a state of the art finite element model of microneedle insertion into and penetration of human skin. The developed model employs a 3D hyperelastic, anisotropic pre-stressed multi-layered material which more accurately reflects in vivo skin conditions, while the microneedle is modeled as an array, which can capture the influence of adjacent microneedles on the overall response. Using the developed finite element model, we highlight the importance of accurate computational modeling which can decipher the mechanics of microneedle insertion, including the influence of its position within an array and how it correlates well with experimental observations. In particular, we functional assessment of production batches and ultimately the likelihood of clinical translation are challenging to predict. Here, we have develop the most sophisticated in silico model of MNA insertion into pre-tensioned human skin to predict the extent of MNA penetration and therefore the likelihood of successful therapeutic delivery. Researchers can customise this model to predict the penetration efficiency of any MNA design.As the driving force of tumor progression, cancer stem cells (CSCs) hold much lower cellular stiffness than bulk tumor cells across many cancer types. However, it remains unclear whether low cell stiffness can be harnessed in nanoparticle-based therapeutics for CSC targeting. We report that breast CSCs exhibit much lower stiffness but considerably higher uptake of nitrogen-doped graphene quantum dots (N-GQDs) than bulk tumor cells. Softening/stiffening cells enhances/suppresses nanoparticle uptake through activating/inhibiting clathrin- and caveolae-mediated endocytosis, suggesting that low cell stiffness mediates the elevated uptake in soft CSCs that may lead to the specific elimination. Further, soft CSCs enhance drug release, cellular retention, and nuclear accumulation of drug-loaded N-GQDs by reducing intracellular pH and exocytosis. Remarkably, drug-loaded N-GQDs specifically eliminate soft CSCs both in vitro and in vivo, inhibit tumor but not animal growth, and reduce the tumorigenicity of xenograft cells. Our findings unveil a new mechanism by which low cellular stiffness can be harnessed in nanoparticle-based strategies for specific CSC elimination, opening a new paradigm of cancer mechanomedicine. STATEMENT OF SIGNIFICANCE Low cell stiffness is associated with high malignancy of tumor cells and thus serves as a mechanical hallmark of CSCs. However, it remains unclear whether cellular stiffness can be exploited for specific targeting of soft CSCs. This work reports that soft CSCs exhibit high N-GQD uptake compared to stiff tumor cells, which is regulated by cellular stiffness. Further, soft CSCs have enhanced drug release, cellular retention, and nuclear accumulation of drug-loaded N-GQDs, which enable the specific elimination of malignant CSCs both in vitro and in vivo with minimal side effect. In summary, our study demonstrates that CSC's low stiffness can be harnessed as a mechanical target for specific eradication, which provides a new paradigm of cancer mechanomedicine.

To compare the performance of agar dilution and broth microdilution by commercial and in-house prepared plates for the Bacteroides fragilis group. The cost analysis was performed to demonstrate that in-house prepared BMD plates were a suitable alternative to agar dilution given the high cost and low feasibility of incorporating commercial BMD plates in routine, particularly in the tertiary care institutes of many low- and middle-income countries.

Thirty B.fragilis group isolates were tested against six antibiotics, frequently used as empirical therapy for anaerobic infections including metronidazole, clindamycin, imipenem, piperacillin-tazobactam, cefoxitin, and chloramphenicol. The running consumable expenditure for all methodologies was calculated.

The results demonstrated essential and categorical agreement of >90% for all antibiotics except cefoxitin, which showed <90% categorical agreement. No major or very major errors were observed. We observed a high agreement and strong concordance for MIemployed for susceptibility testing of the B. fragilis group.Rhodolith beds increase the seabed complexity and are hotspots of biodiversity. Despite the crucial ecosystem services provided by rhodoliths, they are threatened by global change and local anthropogenic impacts. In this study, conducted on one of the largest beds of calcareous algae in the world located on the continental shelf of eastern Brazil, we tested whether the higher complexity of the seabed within rhodolith beds could explain the spatial biodiversity patterns of free-living nematodes. Our results show that beds with the highest densities of rhodoliths are associated with higher sedimentary organic matter (OM) contents and by a different biochemical composition. The higher OM nutritional quantity and nutritional quality, as shown by higher biopolymeric C contents and higher values of the protein to carbohydrate ratio, respectively, were associated with higher abundance, biomass, and diversity of nematode genera, thus supporting our hypothesis. Though based on a correlative approach, the results of this study suggest that a decrease in density of rhodoliths caused by human impacts may affect benthic biodiversity and, consequently, the range of ecosystem services they provide.North Atlantic zooplankton communities vary in terms of abundance, biomass and species composition depending on various environmental factors. In this study we analyzed the influence of hydrological factors (water temperature, salinity and density) on mesoplankton and retrieve boundaries between mesoplankton assemblages across the Subpolar North Atlantic. The material was collected in July 2013 with the use of Juday plankton net vertical hauls (0-300 m layer) at 55 stations arranged along a longitudinal transect along 59.5° N during the 41-th expedition of R/V "Akademik Ioffe". Both total abundance and biomass were higher in the eastern part of the transect and greatly decreased in the western part except the Greenland shelf and slope where the values were high. Four mesoplankton assemblages were retrieved by cluster analysis two of them (above the Rockall Plateau and the Island Basin) were associated with warm Atlantic waters, the other two assemblages (in the Irminger Basin and above the Greenland slope and shelf) inhabited cold Arctic waters. The major biogeographic boundary was linked to the Subarctic Front above the Reykjanes Ridge. The best correlations of zooplankton characteristics with the surface chlorophyll a amount were obtained when averaging the surface chlorophyll data over May and 3 latitudinal and longitudinal degrees around each station. This can be connected to the main spring phytoplankton bloom, occurring during May in this area. The exception was the western-most part of the transect above the Greenland shelf and slope that harbored separate mesoplankton assemblages with high abundance and biomass, dominated by early mesoplankton stages (e.g. young copepodites and nauplii). These assemblages were likely supported by summer subsurface phytoplankton bloom caused by a water discharge from the melting Greenland Ice Shield.Microplastics (MPs) have become a ubiquitous emerging pollutant in the global marine environment. The potential toxic effects of MPs and interactions of MP pollution with other stressors such as food limitation on marine organisms' health are not yet well understood. This study investigated the effects of three-week exposure to different MPs and food shortage on the physical defense mechanisms (byssus production and properties) of Mytilus coruscus. Starvation significantly reduced the number of byssus threads, and combined exposure to MPs and food shortage suppressed the adhesion ability and condition index of mussels. The length of the byssus threads was not affected by all experimental exposures. Transcript levels of genes encoding key proteins involved in byssus formation (the mussel foot proteins mfp-1, -2, -3, -4, -5 and -6, and prepolymerized collagen proteins preCOL-D, -P and -NG) were altered by interactions between the MPs and food shortage. These findings show that insufficient food supply can exacerbate the adverse effects of MPs on mussel defense which might have implications for survival and fitness of mussels under food limited conditions (e.g. in winter) in polluted coastal habitats.Cyanobacteria are a potential threat to aquatic ecosystems and human health because of their ability to produce cyanotoxins, such as microcystins (MCs). MCs are regularly monitored in fresh waters, but rarely in estuarine and marine waters despite the possibility of their downstream export. Over a period of two years, we monthly analyzed intracellular (in phytoplankton) and extracellular (dissolved in water) MCs at five stations along a river continuum from a freshwater reservoir with ongoing cyanobacterial blooms to the coast of Brittany, France. MCs were quantified using two integrative samplers placed at each site solid phase adsorption toxin tracking (SPATT) samplers for collecting extracellular MCs and caged mussels (Anodonta anatina and Mytilus edulis) filter-feeding on MC-producing cyanobacteria. The MC transfer was demonstrated each year during five months at estuarine sites and sporadically at the marine outlet. SPATT samplers integrated extracellular MCs, notably at low environmental concentrations (0.2 µg/L) and with the same variant profile as in water. The mussel A. anatina highlighted the presence of MCs including at intracellular concentrations below 1 µg/L. M. edulis more efficiently revealed the MC transfer at estuarine sites than water samplings. Bivalves showed the same MC variant profile as phytoplankton samples, but with differential accumulation capacities between the variants and the two species. Using SPATT or bivalves can give a more accurate assessment of the contamination level of a freshwater-marine continuum, in which the MC transfer can be episodic. MC content in M. edulis represents a potent threat to human health if considering updated French guideline values, and particularly the total (free and protein-bound) MC content, highlighting the necessity to include cyanotoxins in the monitoring of seafood originating from estuarine areas.Fluorescence spectroscopy has become a fundamental tool for the qualitative and quantitative fingerprinting of dissolved organic matter. Due to the inherent sensitivity of the technique, a strict sampling protocol should be followed to ensure sample integrity. A literature survey conducted as part of this research determined that 27% of fluorescence sampling has been conducted in polymeric containers, while 52% did not report. Given the potential for fluorescence leachates to arise from plastics commonly used in sampling bottles, a systematic laboratory investigation was undertaken to assess the likelihood of leachate contamination and consequent interferences. It was observed that characteristic fluorescent dissolved organic matter (FDOM) leachates from standard polypropylene sampling containers were produced at environmentally relevant peaks, Peak T (λEx/λEm 250/349 nm) and B (λEx/λEm 250/306 nm), commonly attributed to tryptophan-like and tyrosine-like molecular origins. FTO inhibitor Leachate fluorescence and concentration generally increased with elevated storage temperatures (>4 °C), sample acidification, container steam sterilisation and in new containers, with variability across different manufactured batches.