Parkinson’s disease (PD) is a gradually progressing neurodegenerative condition that is marked by a loss of motor coordination along with non-motor features. Although the precise cause of PD has not been determined, the disease condition is mostly associated with the exposure to environmental toxins, such as metals, and their abnormal accumulation in the brain. Heavy metals, such as iron (Fe), mercury (Hg), manganese (Mn), copper (Cu), and lead (Pb), have been linked to PD and contribute to its progression. In addition, the interactions among the components of a metal mixture may result in synergistic toxicity. Numerous epidemiological studies have demonstrated a connection between PD and either single or mixed exposure to these heavy metals, which increase the prevalence of PD. Chronic exposure to heavy metals is related to the activation of proinflammatory cytokines resulting in neuronal loss through neuroinflammation. Similarly, metals disrupt redox homeostasis while inducing free radical production and decreasing antioxidant levels in the substantia nigra. Furthermore, these metals alter molecular processes and result in oxidative stress, DNA damage, mitochondrial dysfunction, and apoptosis, which can potentially trigger dopaminergic neurodegenerative disorders. This review focuses on the roles of Hg, Pb, Mn, Cu, and Fe in the development and progression of PD. Moreover, it explores the plausible roles of heavy metals in neurodegenerative mechanisms that facilitate the development of PD. A better understanding of the mechanisms underlying metal toxicities will enable the establishment of novel therapeutic approaches to prevent or cure PD.

The mechanism of the electrical degradation in amorphous InGaZnO thin-film transistors under a positive gate and drain bias stress is investigated. The stress tests under various combinations of bias and temperature reveal that the negative shift of transfer curves accompanied by a hump is attributed to not an electric field or heating alone, but the simultaneous effect of them. Furthermore, the mitigated degradation under a pulsed stress of a reduced pulse period from 2 s to 0.1 ms and the difference in output characteristics between a dc sweep and a pulsed sweep measurements imply that self-heating with the high field could be the main cause of the degradation rather than hot-carrier effect.

Background/Objectives: Semaglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist, is a well-established pharmacologic agent for inducing weight loss in individuals with obesity and is prescribed regardless of type 2 diabetes mellitus (DM) status. However, it remains unclear whether the weight-lowering efficacy of semaglutide differs significantly between individuals with and without DM. To address this question, we conducted a systematic review and meta-analysis comparing the effects of once-weekly subcutaneous semaglutide at 2.4 mg on weight loss in adults with and without DM. Methods: A comprehensive literature search was performed using the PubMed database to identify randomized controlled trials (RCTs) involving overweight or obese adults receiving semaglutide at 2.4 mg weekly for 40 to 70 weeks. Using a random-effects model, we estimated the weighted mean differences in body weight reduction between the two groups. Nine RCTs met the inclusion criteria, among which two provided subgroup data for participants with and without DM within the same trial population. Registration number in PROSPERO: CRD420251077610. Results: In participants with DM (n = 4 studies), semaglutide was associated with a weighted mean body weight reduction of −6.34% (95% confidence interval: −6.98 to −5.69), with negligible heterogeneity across studies (I² = 0.0%). By contrast, among participants without DM (n = 7 studies), the weighted estimate of weight loss was −11.57% (95% confidence interval: −12.94 to −10.19), with moderate heterogeneity observed (I² = 63.6%). Conclusions: The observed difference in weight loss efficacy between the groups was clinically meaningful. While once-weekly semaglutide at 2.4 mg elicited significant weight loss in both populations, the magnitude of effect was notably greater in those without DM. This disparity may be explained by metabolic characteristics frequently present in individuals with DM, such as insulin resistance, hyperinsulinemia, and compensatory mechanisms related to glycemic control.

Background: Aluminum (Al), lead (Pb), and mercury (Hg) are major environmental pollutants, and a large population may be simultaneously exposed to these metals. However, studies on the potential neurobehavioral effects of mixed exposure to Al, Pb, and Hg are lacking. Objectives: This study aimed to evaluate neurobehavioral changes in mice following combined exposure to Al, Pb, and Hg and to investigate the effects of this exposure on dopaminergic neurotransmission within the striatum. Methods: In this study, C57BL/6 mice (n = 10 per group) were assigned to control and metal-treated groups. Changes in motor coordination and locomotor activity that occurred when mice were simultaneously exposed to these metals via drinking water for 28 days were measured using the rotarod and open field tests. In addition, dopamine content and key factors involved in dopaminergic neurotransmission in the striatum were evaluated using real-time PCR and Western blot analysis. Results: The mixed metal exposure decreased motor function and significantly reduced the content of dopamine in the striatum of the experimental mice (P < 0.001). Expression of tyrosine hydroxylase, vesicular monoamine transporter 2, and dopamine receptor D1, which are involved in dopaminergic neurotransmission in the striatum, was significantly decreased (P < 0.01), whereas expression of the dopamine transporter was significantly increased (P < 0.05). Dopamine receptor D2 expression was not significantly changed by the mixed metal exposure. Conclusions: These results suggest that mixed exposure to Al, Pb, and Hg inhibits normal dopaminergic neurotransmission, resulting in neurobehavioral disorders.