Mcdougallortiz4088

In the SoluAirway™, most of the biocides decreased cell viability even within the approved limits, except for PE, IPBC, and deltamethrin, suggesting that the airway may be more vulnerable to biocides than the skin. Taken together, our result indicates that some biocides can induce toxicity in skin and airway. Further studies on the dermal and inhalational toxicity of biocides are warranted.Elution of Ni ions from medical devices induces inflammation and toxicity. We previously reported that elution of Ni ions from Ni wires induced COX-2 expression and increased lactate production, but whether lactate is involved in the further elution of Ni ions remains unclear. In this study, using KMST-6, a human fibroblast cell line, we examined the molecular mechanisms by which Ni ions increase lactate release and the role of lactate in enhancing the elution of Ni ions. When KMST-6 cells were incubated on a Ni plate or stimulated with NiCl2 (1 mM), the expression of glucose transporter 1 (GLUT1), hexokinase 2 (HK2), and lactate dehydrogenase A (LDHA), and the release of lactate were enhanced. The NiCl2 (1 mM)-induced expression of these genes was inhibited by a hypoxia-inducible factor-1α (HIF-1α) inhibitor, PX-478 (10-25 μM). Stimulation of cells with a prolyl hydroxylase domain (PHD) inhibitor, roxadustat, increased the expression of these genes, lactate release, and elution of Ni ions at 10 μM. A monocarboxylate transporter-4 (MCT4) inhibitor, syrosingopine, inhibited lactate release from roxadustat-treated cells and reduced the elution of Ni ions by the cells at 10 μM. Finally, syrosingopine (10 μM) reduced the elution of Ni ions by the cells from the Ni plate. These results suggest that elution of Ni ions from metals promotes the production of lactate via HIF-1α-mediated gene expression and causes further Ni elution. Thus, Ni ions show a positive feedback mechanism of Ni elution, and this step may be potentially targeted to protect against metal elution from metal devices.Metribuzin is a herbicide that inhibits photosynthesis and has been used for over 40 years. Its main target organ is the liver and to some extent the kidney in rats, dogs, and rabbits. Metribuzin shows a specific thyroxine (T4) profile in rat studies with T4 increases at low doses and T4 decreases at higher doses. Only the T4 decreases occur together with histopathological changes in the thyroid and weight changes of liver and thyroid. A set of experiments was conducted to investigate metribuzin's endocrine disruptor potential according to European guidance and regulations. The results indicate that a liver enzyme modulation, i.e. PGE2 of the uridine 5'-diphospho-glucuronosyltransferase (UDPGT, UGT), is most likely responsible for both increased and decreased plasma thyroxine level and for thyroid histopathological observations. Animals with high T4 levels show low UGT activity, while animals with low T4 levels show high UGT activity. A causal relationship was inferred, since other potentially human-relevant mode of action (MOA) pathways were excluded in dedicated studies, i.e. inhibition of deiodinases (DIO), inhibition of thyroid peroxidase (TPO) or of the sodium importer system (NIS). This liver metabolism-associated MOA is considered not relevant for human hazard assessment, due to species differences in thyroid homeostasis between humans and rats and, more importantly, based on experimental data showing that metribuzin affects UGT activity in rat but not in human hepatocytes. Further, we discuss whether or not increased T4 levels in the rat, in the absence of histopathological changes, should be considered as adverse and therefore used as an appropriate hazard model for humans. Based on a weight of evidence approach, metribuzin should not be classified as an endocrine disruptor with regard to the thyroid modality.In this paper, a year-old stalk of Glycyrrhiza glabra was used as the research object. The electronic universal testing machine was used to test the mechanical properties of shearing and bending. The microstructure of the stalk of Glycyrrhiza glabra was observed with a microscope. Mechanical test research indicated that the shearing process included an elastic phase, a yield phase, and a plastic deformation phase. The bending process was divided into elastic deformation stage and plastic deformation stage. In addition, the shearing force, shearing energy, bending force and bending energy all increased with the increase in diameter. As the water content increased, the shearing force and bending force decreased at first, reached the minimum when the water content was about 45%, and then had an upward trend. The shearing energy increased with the water content, and the bending energy, decreased with the water content. The two test factors were statistically significant for both shearing and bending properties. The microscopic test results showed that the phloem, fiber, and pith constitute the microstructure of the licorice stalk. The linear regression model could reflect the correlation between the cross-sectional area of each part and the shearing force and bending force (P less then 0.05). Through analysis, it was concluded that the change of the cross-sectional area of the stalk microstructure had an important influence on the mechanical properties of shearing and bending. The results can provide theoretical basis for the design of Glycyrrhiza Glabra stalk harvesting, crushing and processing equipment.Succinyl-CoA3-oxoacid coenzyme A transferase deficiency (SCOTD) is a rare autosomal recessive disorder of ketone body utilization caused by mutations in OXCT1. We performed a systematic literature search and evaluated clinical, biochemical and genetic data on 34 previously published and 10 novel patients with SCOTD. Structural mapping and in silico analysis of protein variants is also presented. All patients presented with severe ketoacidotic episodes. Age at first symptoms ranged from 36 h to 3 years (median 7 months). About 70% of patients manifested in the first year of life, approximately one quarter already within the neonatal period. Two patients died, while the remainder (95%) were alive at the time of the report. Almost all the surviving patients (92%) showed normal psychomotor development and no neurologic abnormalities. A total of 29 missense mutations are reported. Analysis of the published crystal structure of the human SCOT enzyme, paired with both sequence-based and structure-based methods to predict variant pathogenicity, provides insight into the biochemical consequences of the reported variants.