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At 50 mg/kg, the content of glutamate was increased by 11-fold, whereas glutamine was decreased by 99% with respect to controls. Interestingly, eight metabolic pathways were disturbed at 50 mg/kg, but none at 500 mg/kg. This metabolic reprogramming at the lower dose represented potential risks to the health of exposed plants, which could be particularly important although no phenotypic impacts were noted. Overall, metabolites analysis provides a deeper understanding at the molecular level of plant response to nZVI and is a powerful tool for full characterization of risk posed to crop species as part of food safety assessment.Moving towards safe and sustainable innovations is an international policy ambition. In the on-hand manuscript, a concept combining safe by design and sustainability was implemented through the integration of human and environmental risk assessment, life cycle assessment as well as an assessment of the economic viability. The result is a nested and iterative process in form of a decision tree that integrates these three elements in order to achieve sustainable, safe and competitive materials, products or services. This approach, embedded into the stage-gate-model for safe by design, allows to reduce the uncertainty related to the assessment of risks and impacts by improving the quality of the data collected along each stage. In the second part of the manuscript, the application is shown for a case study dealing with the application of nanoparticles for Li-Ion batteries. One of the general conclusions out of this case study is that data gaps are a key aspect in view of the reliability of the results.Graphene quantum dots (GQDs) are an excellent tool for theranostics, and are widely used in nanomedical applications. The biosafety of GQDs has received abundant attention, but their latent toxicological mechanisms remain inadequately understood. To investigate the cellular and molecular mechanisms underlying graphene-mediated changes, quantitative proteomics and untargeted lipidomics were integrated. We discovered that glutathione peroxidase 4 as a key regulator of ferroptosis, was down-regulated at the protein level by GQDs. ML390 inhibitor Lipidomics profiling with features of ferroptosis was identified in GQDs-treated RAW264.7 macrophages. Furthermore, GQDs exposure was associated with reduced levels of GSH and increased lipid peroxidation. Overexpression of GPX4 in RAW264.7 cells and pre-treatment of a ferroptosis inhibitor Ferrostatin-1 (Fer-1) not only suppressed cell death, but also alleviated lipid peroxidation. Taken together, our results indicated that GQDs exposure induced ferroptosis in RAW264.7 macrophages, and provided essential data for biosafety evaluations of GQDs.Tubular nanomaterials (NMs), such as multi-walled carbon nanotubes (MWCNTs) and halloysite nanotubes (HNTs), may be used in biomedicine, but previous studies showed that MWCNTs induced toxicity to endothelial cells (ECs). However, the influence of tubular NMs on EC lipid profiles has gained little attention, probably because ECs are not traditionally considered to be involved in regulating lipid homeostasis. This study compared the different effects of MWCNTs and HNTs on lipid profile changes in human umbilical vein ECs (HUVECs). The results showed that MWCNTs but not HNTs of the same mass concentrations induced cytotoxicity, ultrastuctural changes and intracellular thiol depletion. Meanwhile, only MWCNTs promoted lipid accumulation due to the induction of ER stress leading to up-regulation of fatty acid synthase (FASN). Interestingly, lipidomics results showed that the main lipid classes induced by MWCNTs but not HNTs were ceramide (Cer) and phosphatidylinositol (PI), with most of the lipid classes unaltered or even decreased after NM exposure. Then, extra Cer and PI were added to explore the implications of increase of these lipids. Adding Cer promoted the cytotoxicity of MWCNTs to HUVECs, indicating the lipotoxic role of Cer. Whereas adding PI partially increased intracellular NO and decreased interleukin-6 (IL-6) release due to MWCNT exposure, indicating the signaling role of PI. These results indicated novel roles of lipid dysfunction in NM-induced toxicity to ECs, even though ECs are not the professional cells for controlling lipid homeostasis.Carbon dots (CDs) are carbon-based nanomaterials with advantageous luminescent properties, making them promising alternatives to other molecular and nanosized fluorophores. However, the development of CDs is impaired by the low synthesis yield of standard fabrication strategies, making high-yield strategies essential. To help future studies to focus on cleaner production strategies, we have employed a Life Cycle Assessment (LCA) to compare and understand the environmental impacts of available routes for the high-yield synthesis of carbon dots. These routes were (1) production of hydrochar, via hydrothermal treatment of carbon precursors, and its alkaline-peroxide treatment into high-yield carbon dots; (2) thermal treatment of carbon precursors mixed in a eutectic mixture of salts. Results show that the first synthesis route is associated with the lowest environmental impacts. This is attributed to the absence of the mixture of salts in the first synthesis route, which offsets its higher electricity consumption. Sensitivity analysis showed that the most critical parameter in the different synthetic strategies is the identity of the carbon precursor, with electricity being also relevant for the first synthesis route. Nevertheless, the use of some carbon precursors (as citric acid) with higher associated environmental impacts may be justified by their beneficial role in increasing the luminescent performance of carbon dots. Thus, the first synthesis route is indicated to be the most environmental benign and should be used as a basis in future studies aimed to the cleaner and high-yield production of carbon dots.The empirical necessity for integrating informatics throughout the experimental process has become a focal point of the nano-community as we work in parallel to converge efforts for making nano-data reproducible and accessible. The NanoInformatics Knowledge Commons (NIKC) Database was designed to capture the complex relationship between nanomaterials and their environments over time in the concept of an 'Instance'. Our Instance Organizational Structure (IOS) was built to record metadata on nanomaterial transformations in an organizational structure permitting readily accessible data for broader scientific inquiry. By transforming published and on-going data into the IOS we are able to tell the full transformational journey of a nanomaterial within its experimental life cycle. The IOS structure has prepared curated data to be fully analyzed to uncover relationships between observable phenomenon and medium or nanomaterial characteristics. Essential to building the NIKC database and associated applications was incorporating the researcher's needs into every level of development. We started by centering the research question, the query, and the necessary data needed to support the question and query. The process used to create nanoinformatic tools informs usability and analytical capability. In this paper we present the NIKC database, our developmental process, and its curated contents. We also present the Collaboration Tool which was built to foster building new collaboration teams. Through these efforts we aim to 1) elucidate the general principles that determine nanomaterial behavior in the environment; 2) identify metadata necessary to predict exposure potential and bio-uptake; and 3) identify key characterization assays that predict outcomes of interest.Given the wide variety of potential applications of graphene oxide (GO), its consequent release into the environment poses serious concerns on its safety. The future production and exploitation of graphene in the years to come should be guided by its specific chemical-physical characteristics. The unparalleled potential of single-cell mass cytometry (CyTOF) to dissect by high-dimensionality the specific immunological effects of nanomaterials, represents a turning point in nanotoxicology. It helps us to identify the safe graphene in terms of physical-chemical properties and therefore to direct its future safe production. Here we present a high-dimensional study to evaluate two historically indicated as key parameters for the safe exploitation functionalization and dimension. The role of lateral dimension and the amino-functionalization of GO on their immune impact were here evaluated as synergistic players. To this end, we dissected the effects of GO, characterized by a large or small lateral size (GO 1.32 μm , but a proper surface functionalization is the dominant characteristic in its immune effects. In particular, the amino-functionalization can critically modify graphene impact dampening the immune cell activation. Our study can serve as a guide for the future broad production and use of graphene in our everyday life.The majority of published research on the effect of engineered nanoparticles on terrestrial plant species is focused on inorganic nanoparticles, with the effects of organic polymeric nanoparticles (NP) on plants remaining largely unexplored. It is critical to understand the impact of polymeric NPs on plants if these particles are to be used as agrochemical delivery systems. This study investigates the effect of biodegradable polymeric lignin-based nanoparticles (LNPs) and zein nanoparticles (ZNP) on soybean plant health. The LNPs (114 ± 3.4 nm, -53.8 ± 6.9 mV) were synthesized by emulsion evaporation from lignin-graft-poly(lactic-co-glycolic) acid, and ZNPs (142 ± 3.9 nm and + 64.5 ± 4.7 mV) were synthesized by nanoprecipitation. Soybeans were grown hydroponically and treated with 0.02, 0.2, and 2 mg/ml of LNPs or ZNPs at 28 days after germination. Plants were harvested after 1, 3, 7 and 14 days of particle exposure and analyzed for root and stem length, chlorophyll concentration, dry biomass of roots and stem, nutrient uptake and plant ROS. Root and stem length, chlorophyll and stem biomass did not differ significantly between treatments and controls for LNPs-treated plants at all concentrations, and at low doses of ZNPs. At 2 mg/ml ZNPs, the highest concentration tested, after 7 days of treatment chlorophyll levels and root biomass increased and stem length was reduced in comparison to the control. Nutrient uptake was largely unaffected at 0.02 and 0.2 mg/ml NPs. A concentration-dependent increase in the oxidative stresss was detected, especially in the ZNP treated plants. Overall, LNPs and ZNPs had a minimum impact on soybean health especially at low and medium doses. To our knowledge this is the first study to show the effect of zein and lignin based polymeric NPs designed for agrochemical delivery on soybean plant health.The enhancement in reactivity of the antioxidant functionalized gold nanoparticles is closely related to the rate constant and activation energy, which were significantly affected by the chain length of the PEG ligands that capped the gold nanoparticles. Meanwile, the enhancement could be attributed to the π-π stacking interaction between the adjacent phenol groups coated on gold nanoparticles' surface.

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