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This review focuses on melatonin’s role in advancing Parkinson’s disease (PD) pathogenesis by inhibiting synaptic dysfunction and neuroinflammation. The early pathological changes in PD, caused by SNCA/ PARK1 and LRRK2/PARK8-mediated synaptic vesicle endocytosis during the early pathogenesis of PD, are briefly reviewed. The pathological changes related to synaptic plasticity and dendrites caused by synaptic dysfunction in neurotoxin 6-hydroxydopamine (6-OHDA) and 1-methl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP)-induced PD models are also discussed. The molecular mechanisms of pathological changes in PD, caused by the activation of microglia, astrocytes, and inflammatory vesicles, are discussed. The effectiveness of melatonin (MLT) in the restoration of dopaminergic neurons in the substantia nigra (SNc) has been established. MLT can upregulate dendritic numbers and restore synaptic plasticity by inhibiting alpha-synuclein aggregation and neurotoxicity. These functions of MLT improve sleep patterns in PD patients and suppresses synaptic dysfunction by inhibiting the overactivation of the PKA/CREB/ BDNF signaling pathway and reactive oxygen species (ROS) production. MLT can maintain the typical transport and release of neurotransmitters. MLT also reduces neuroinflammation by promoting microglia 2 (M2) polarization, which reduces the expression of inflammatory cytokines. Additionally, MLT stimulates the activation of the retinoic acid receptor-related orphan receptor α (RORα) ligand and inhibits the activation of the Recombinant Sirtuin 1 (SIRT1)-dependent pathway, the NLR family pyridine structure domain 3 (NLRP3) inflammasome. By integrating the latest advances in synaptic dysfunction and neuroinflammation-related PD, researchers can develop clinical interventions for treating PD and further explore the pathological hallmarks of prodromal PD. [ABSTRACT FROM AUTHOR]

Context. Penumbral filaments and light bridges are prominent structures inside sunspots and are important for understanding the nature of sunspot magnetic fields and magneto-convection underneath. Aims. We investigate an interesting event where several penumbral filaments intrude into a sunspot light bridge. In doing so we aim to gain further insight into the magnetic fields of the sunspot penumbral filament and light bridge, as well as their interaction. Methods. Combining data from the New Vacuum Solar Telescope, Solar Dynamics Observatory, and Interface Region Imaging Spectrograph, we study the emission, kinematic, and magnetic topology characteristics of the penumbral filaments intruding into the light bridge and the resultant jets. Results. At the west part of the light bridge, the intruding penumbral filaments penetrate into the umbrae on both sides of the light bridge, and two groups of jets are also detected. The jets share the same projected morphology with the intruding filaments and are accompanied by intermittent footpoint brightenings. Simultaneous spectral imaging observations provide convincing evidence for the presences of magnetic-reconnection-related heating and bidirectional flows near the jet bases and contribute to measuring the vector velocities of the jets. Additionally, nonlinear force-free field extrapolation results reveal strong and highly inclined magnetic fields along the intruding penumbral filaments, highly consistent with the results deduced from the vector velocities of the jets. Therefore, we propose that the jets could be caused by magnetic reconnections between emerging fields within the light bridge and the nearly horizontal fields of intruding filaments. The jets are then ejected outward along the stronger filament fields. Conclusions. Our study indicates that magnetic reconnection could occur between the penumbral filament fields and emerging fields within the light bridge and produce jets along the stronger filament fields. These results further complement the study of magnetic reconnection and dynamic activities within the sunspot. [ABSTRACT FROM AUTHOR]

Aims: We aimed to investigate the heterogeneity of seasonal suicide patterns among multiple geographically, demographically and socioeconomically diverse populations. Methods: Weekly time-series data of suicide counts for 354 communities in 12 countries during 1986–2016 were analysed. Two-stage analysis was performed. In the first stage, a generalised linear model, including cyclic splines, was used to estimate seasonal patterns of suicide for each community. In the second stage, the community-specific seasonal patterns were combined for each country using meta-regression. In addition, the community-specific seasonal patterns were regressed onto community-level socioeconomic, demographic and environmental indicators using meta-regression. Results: We observed seasonal patterns in suicide, with the counts peaking in spring and declining to a trough in winter in most of the countries. However, the shape of seasonal patterns varied among countries from bimodal to unimodal seasonality. The amplitude of seasonal patterns (i.e. the peak/trough relative risk) also varied from 1.47 (95% confidence interval [CI]: 1.33–1.62) to 1.05 (95% CI: 1.01–1.1) among 12 countries. The subgroup difference in the seasonal pattern also varied over countries. In some countries, larger amplitude was shown for females and for the elderly population (≥65 years of age) than for males and for younger people, respectively. The subperiod difference also varied; some countries showed increasing seasonality while others showed a decrease or little change. Finally, the amplitude was larger for communities with colder climates, higher proportions of elderly people and lower unemployment rates (p-values < 0.05). Conclusions: Despite the common features of a spring peak and a winter trough, seasonal suicide patterns were largely heterogeneous in shape, amplitude, subgroup differences and temporal changes among different populations, as influenced by climate, demographic and socioeconomic conditions. Our findings may help elucidate the underlying mechanisms of seasonal suicide patterns and aid in improving the design of population-specific suicide prevention programmes based on these patterns. [ABSTRACT FROM AUTHOR]