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Metabolic responses to cellular stress are pivotal in cell ferroptosis, with mitophagy serving as a crucial mechanism in both metabolic processes and ferroptosis. This study aims to elucidate the effects of high glucose on cardiomyocytes (CMs) and cardiac fibroblasts (CFs) regarding ferroptosis and to uncover the underlying mechanisms involved. We examined alterations in glycolysis, mitochondrial oxidative phosphorylation (OXPHOS), and mitophagy, which are essential for metabolic adaptations and ferroptosis. High glucose exposure induced ferroptosis specifically in CMs, while CFs exhibited resistance to ferroptosis, increased glycolytic activity, and no change in OXPHOS. Moreover, high glucose treatment enhanced mitophagy and upregulated mitochondrial ferritin (FTMT). Notably, the combination of FTMT and the autophagy-related protein nuclear receptor coactivator 4 (NCOA4) increased under high glucose conditions. Silencing FTMT significantly impeded mitophagy and eliminated ferroptosis resistance in CFs cultured under high glucose conditions. The transcription factor forkhead box A1 (FOXA1) was upregulated in CFs upon high glucose exposure, playing a crucial role in the increased expression of FTMT. Within the 5'-flanking sequence of the FTMT mRNA, approximately -500 nt from the transcription initiation site, three putative FOXA1 binding sites were identified. High glucose augmented the binding affinity between FOXA1 and these sequences, thereby promoting FTMT transcription. In summary, high glucose upregulated FOXA1 expression and stimulated FTMT promoter activity in CFs, thereby promoting FTMT-dependent mitophagy and conferring ferroptosis resistance in CFs.
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The current study performs the thermodynamic and life-cycle assessments (LCA) of a novel charging station in two system designs. The goal is to design an efficient charging station for electric vehicles with high efficiencies and low environmental impacts using Solid Oxide Fuel Cell (SOFC) technology. SOFC is considered a sustainable and environmentally friendly technology to generate electricity compared to combustion engines. To ameliorate the performance, the exhaust heat of the SOFC stacks will be recovered for hydrogen production in an electrolyzer. The system uses four SOFCs to charge the electric vehicles while the output heat is recovered by an Organic Rankine Cycle (ORC) to generate further electricity for hydrogen production in an electrolyzer. In the first design, it is assumed that the SOFC stacks will work full-load during the 24 h of the day, while the second design considers full-load operation for 16 h and part-load (30%) operation for 8 h. The second design of the system analyzes the possibility of integrating a [Formula: see text] lithium-ion battery stores the excessed electricity once the power load is low and acts as a backup in high power demands. Results of the thermodynamic analysis calculated the overall efficiencies of 60.84% and 60.67% for the energy and exergy, respectively, with the corresponding power and hydrogen production of 284.27 kWh and 0.17 g/s. It was observed that higher current density would increase the output of SOFC while reducing the overall energy and exergy efficiencies. In dynamic operation, the use of the batteries can well balance the change of the power loads and improve the dynamic response of the system to the simultaneous changes in the power demand. LCA results also showed that the 284.27kWh system leads to global warming (kg [Formula: see text] eq) of 5.17E+05, 4.47E+05, and 5.17E+05 using Solid Oxide Electrolyzer (SOE), Proton Exchange Membrane Electrolyzer (PEME), and Alkaline Electrolyzer (ALE), respectively. In this regard, the usage of PEME has the lowest impact on the environment in comparison to SOEC, and ALE. A comparison between the environmental impacts of different ORC's working fluids also suggested against the usage of R227ea while R152a showed promising results to be used in the system. The size and weight study also revealed that the battery benefits from the lowest volume and weight in comparison to the other components. Among the considered components in this study, the SOFC unit and the PEME have by far the highest volume.
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Biodegradable electrospun sponges are of interest for various applications including tissue engineering, drug release, dental therapy, plant protection, and plant fertilization. Biodegradable electrospun poly(l-lactide)/poly(ε-caprolactone) (PLLA/PCL) blend fiber-based sponge with hierarchical pore structure is inherently hydrophobic, which is disadvantageous for application in tissue engineering, fertilization, and drug delivery. Contact angles and model studies for staining with a hydrophilic dye for untreated, plasma-treated, and surfactant-treated PLLA/PCL sponges are reported. Thorough hydrophilization of PLLA/PCL sponges is found only with surfactant-treated sponges. The MTT assay on the leachates from the sponges does not indicate any cell incompatibility. Furthermore, the cell proliferation and penetration of the hydrophilized sponges are verified by in vitro cell culture studies using MG63 and human fibroblast cells.
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Poliésteres , Engenharia Tecidual , Humanos , Poliésteres/farmacologia , Poliésteres/química , Tensoativos , Alicerces Teciduais/químicaRESUMO
The enzymatic degradation of aliphatic polyesters offers unique opportunities for various use cases in materials science. Although evidently desirable, the implementation of enzymes in technical applications of polyesters is generally challenging due to the thermal lability of enzymes. To prospectively overcome this intrinsic limitation, we here explored the thermal stability of proteinase K at conditions applicable for polymer melt processing, given that this hydrolytic enzyme is well established for its ability to degrade poly(l-lactide) (PLLA). Using assorted spectroscopic methods and enzymatic assays, we investigated the effects of high temperatures on the structure and specific activity of proteinase K. Whereas in solution, irreversible unfolding occurred at temperatures above 75-80 °C, in the dry, bulk state, proteinase K withstood prolonged incubation at elevated temperatures. Unexpectedly little activity loss occurred during incubation at up to 130 °C, and intermediate levels of catalytic activity were preserved at up to 150 °C. The resistance of bulk proteinase K to thermal treatment was slightly enhanced by absorption into polyacrylamide (PAM) particles. Under these conditions, after 5 min at a temperature of 200 °C, which is required for the melt processing of PLLA, proteinase K was not completely denatured but retained around 2% enzymatic activity. Our findings reveal that the thermal processing of proteinase K in the dry state is principally feasible, but equally, they also identify needs and prospects for improvement. The experimental pipeline we establish for proteinase K analysis stands to benefit efforts directed to this end. More broadly, our work sheds light on enzymatically degradable polymers and the thermal processing of enzymes, which are of increasing economical and societal relevance.
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Poliésteres , Polímeros , Endopeptidase K/metabolismo , Poliésteres/química , Polímeros/química , TemperaturaRESUMO
The effects of microplastic (MP) pollution on organisms are gaining increasing attention. To date, a variety of polymers of different shapes and sizes are used in ecotoxicology. Although polystyrene (PS) is the predominant polymer type used in effect studies, it is still unclear whether the observed effects derive from the polymer itself or from a certain particle shape and size. To elucidate whether the effects are polymer specific, we conducted a systematic study on Daphnia magna by comparing various PS-MPs to nonplastic control particles with similar properties. In chronic exposure experiments, we used PS beads (6 µm; 20 µm), fibers (Ø 3 µm, length: 75.5 µm), and fragments (5.7 µm; 17.7 µm) in two different size classes and two different concentrations (500 and 5000 particles ml-1) and in-house-produced control particles of comparable size, shape, concentration and, if possible, density. Although most PS properties did not elicit effects on the tested endpoints, we observed sublethal effects on D. magna life history and morphology for small PS beads and fragments. Interestingly, no adverse effects were detected for any of the control particles. Hence, the observed effects are polymer-specific, related to the size and shape of the polymer, and do not result from particle exposure per se.
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Microplásticos , Poluentes Químicos da Água , Animais , Daphnia , Plásticos/toxicidade , Polímeros/toxicidade , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidadeRESUMO
This work focuses on the development of a responsive sponge made of an anionic cellulose nanocrystal (CNC) skeleton that is electrostatically crosslinked by a pH-responsive poly(allylamine hydrochloride) (PAH) and poly(acrylic acid) (PAA) polyelectrolyte complex (PEC). The results prove the formation of a global percolated network comprised of disordered CNC rods crosslinked by PEC clusters. The bulk density of the freeze-dried CNC-PEC sponges increases from 35 to 93 mg/cm3 with PEC concentration, while the compression modulus of dry specimens increases from 7 up to 62 kPa. At the lowest PEC concentration of 1 wt%, at pH 2.0, the compression modulus decreases to 0.9 kPa, whereas at pH 5.5, it increases to 42 kPa. The intensive complexation between sponge constituents is also reflected in a reduced ability to bind charged dyes at neutral pH values. Decreasing the pH results in an increased adsorption efficiency for anionic dyes, while raising the pH improves the cationic dye adsorption.
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Prolonged endoplasmic reticulum (ER) stress is the key driving force behind diabetic cardiomyopathy (DCM). Autophagy is extensively implicated in adaptive mechanisms for cell survival. Interleukin-33 (IL-33) is known to be a potent cardiac protector, but its roles in DCM, ER stress, and autophagy are currently unknown. We aimed to explore the effects of IL-33 on DCM and characterize the roles that ER stress and autophagy play in DCM. The effects of IL-33 on DCM, ER stress, and autophagy were characterized both in db/db mice and in palmitic acid (PA)-treated cardiomyocytes. The manipulators of ER stress and autophagy were used to clarify their roles in DCM remittance conferred by IL-33. Gene expression analysis was used to identify IL-33-dependent regulators of ER stress and autophagy. Both db/db mice and PA-treated cells presented with enhanced levels of ER stress, apoptosis, and lipid deposition, as well as impaired autophagy, all of which could be reversed by IL-33. Treatment with IL-33 improved the cardiac diastolic function of diabetic mice. Nonselective autophagy inhibitors, such as 3-methyladenine (3-MA) or wortmannin, abolished the protective effects of IL-33, resulting in an increase in both ER stress and apoptosis. Strikingly, insulin-like growth factor-binding protein 3 (IGFBP3) was identified as the gene most significantly differentially expressed between IL-33 and control groups. Knockdown of IGFBP3 expression, similar to the effect of nonselective autophagy inhibitors, resulted in high levels of ER stress, impaired autophagy, and apoptosis that were not rescued upon treatment with IL-33. IL-33 abates DCM by alleviating ER stress and promoting autophagy. IGFBP3 is essential for IL-33-induced ER stress resolution and autophagic enhancement during DCM.