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AbstractParkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra. Recently, disorders in metabolism of metals, including copper (Cu) and iron (Fe), have been reported to be linked to the pathogenesis of PD. We previously demonstrated that 6-hydoroxydopamine (6-OHDA), a neurotoxin used for the production of PD model animals, decreases Atox1, a Cu chaperone, and ATP7A, a Cu transporter, and disrupts intracellular Cu metabolism in human neuroblastoma SH-SY5Y cells. However, the exact mechanisms remain unclear. Meanwhile, intracellular Fe modulates 6-OHDA-induced cellular responses. In this study, we investigated whether Fe participates in 6-OHDA-induced abnormality in Cu metabolism. 6-OHDA-induced reactive oxygen species (ROS) production and cellular injury were suppressed by Fe chelators, deferoxamine and 2,2′-bipyridyl (BIP). These chelators also restored 6-OHDA-induced degradation of Atox1 and ATP7A proteins and subsequent Cu accumulation, indicating that intracellular Fe is involved in the disruption of Cu homeostasis associated with 6-OHDA. Atox1 has redox-sensitive cysteine (Cys) residues in its Cu-binding site. The Cys residues of Atox1 were oxidized by 6-OHDA, and BIP suppressed their oxidation. Moreover, the replacement of Cys with histidine in the Cu-binding site conferred resistance to 6-OHDA-induced Atox1 degradation. These results suggest that oxidized modification of Atox1 by 6-OHDA is likely to accelerate its degradation. Thus, we conclude that Fe and Cu metabolisms are closely related to each other in the pathogenesis of PD. [ABSTRACT FROM AUTHOR]

Zinc (Zn) is an essential metal in the body. It binds to many proteins and regulates their functions. In the immune system, it is known that administration of ZnSO 4 suppresses T cell activation, but its effects on allergies are still unknown. In this study, we investigated the effects of ZnSO 4 administration on allergic reactions using the rat basophilic leukemia cell line, RBL-2H3. ZnSO 4 treatment inhibited cell degranulation induced by antigen and IgE stimulation, as well as by A23187, a Ca 2+ ionophore. Antigen and IgE stimulation increased mRNA expression of IL-4, IL-13, and COX-2, and ZnSO 4 treatment inhibited this expression. The elevation of intracellular Zn concentration and depletion of Zn did not affect degranulation. Phosphorylation of the proteins spleen tyrosine kinase, p38, ERK1/2, JNK, and Akt was increased by antigen stimulation, but ZnSO 4 treatment did not inhibit this phosphorylation. ZnSO 4 treatment inhibited the elevation of intracellular Ca 2+ concentration induced by antigen and IgE stimulation, as well as by A23187. Additionally, ZnSO 4 treatment inhibited thapsigargin, a store-operated Ca 2+ entry stimulant, from inducing degranulation and increasing intracellular Ca 2+ concentration. These data indicate that exogenous Zn 2+ possesses a preventive effect on RBL-2H3 activation via inhibition of Ca 2+ influx. The effect of Zn may involve Ca 2+ release-activated channels. This study suggests that ZnSO 4 treatment is valuable in suppressing allergic responses., Competing Interests: Declaration of competing interest We declare that there are no conflicts of interest to disclose., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Transition metal dichalcogenides (TMDs) exhibit unique properties and potential applications when reduced to one-dimensional (1D) nanoribbons (NRs), owing to quantum confinement and high edge densities. However, effective growth methods for self-aligned TMD NRs are still lacking. We demonstrate a versatile approach for lattice-guided growth of dense, aligned MoS 2 NR arrays via chemical vapor deposition (CVD) on anisotropic sapphire substrates, without tailored surface steps. This method enables the synthesis of NRs with widths below 10 nanometers and longitudinal axis parallel to the zigzag direction, being also extensible to the growth of WS 2 NRs and MoS 2 -WS 2 heteronanoribbons. Growth is influenced by both substrate and CVD temperature, indicating the role of anisotropic precursor diffusion and substrate interaction. The 1D nature of the NRs was asserted by the observation of Coulomb blockade at low temperatures. Pronounced catalytic activity was observed at the edges of the NRs, indicating their promise for efficient catalysis.