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Background: Clinical diagnosis and monitoring of Parkinson's disease (PD) remain challenging because of the lack of an established biomarker. Neuromelanin-magnetic resonance imaging (NM-MRI) is an emerging biomarker of nigral depigmentation indexing the loss of melanized neurons but has unknown prospective diagnostic and tracking performance in multicenter settings. Objectives: The aim was to investigate the diagnostic accuracy of NM-MRI in early PD in a multiprotocol setting and to determine and compare serial NM-MRI changes in PD and controls. Methods: In this longitudinal case–control 3 T MRI study, 148 patients and 97 controls were included from six UK clinical centers, of whom 140 underwent a second scan after 1.5 to 3 years. An automated template-based analysis was applied for subregional substantia nigra NM-MRI contrast and volume assessment. A point estimate of the period of prediagnostic depigmentation was computed. Results: All NM metrics performed well to discriminate patients from controls, with receiver operating characteristic showing 85% accuracy for ventral NM contrast and 83% for volume. Generalizability using a priori volume cutoff was good (79% accuracy). Serial MRI demonstrated accelerated NM loss in patients compared to controls. Ventral NM contrast loss was point estimated to start 5 to 6 years before clinical diagnosis. Ventral nigral depigmentation was greater in the most affected side, more severe cases, and nigral NM volume change correlated with change in motor severity. Conclusions: We demonstrate that NM-MRI provides clinically useful diagnostic information in early PD across protocols, platforms, and sites. It provides methods and estimated depigmentation rates that highlight the potential to detect preclinical PD and track progression for biomarker-enabled clinical trials. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

There is accumulating evidence suggesting that an autoimmune component is involved in esophageal achalasia. An increase in immune cells, cytokines, chemokines, and autoimmune antibodies in serum and infiltration of immune cells in tissues support the view that immune-mediated inflammation is a crucial pathogenesis of inhibitory neuron degeneration in the lower esophageal sphincter. Infection of viruses such as the herpes virus family has been suspected of provoking the autoimmune reaction. Meanwhile, previous reports on immunogenetics have proposed that specific risk alleles on the human leukocyte antigen complex define the susceptible population to achalasia. In this study we reviewed current knowledge regarding the immune-related factors of achalasia, including immunology, viral infection and immunogenetic variations.

In contrast to the homeokinesis of mitosis, asymmetric division of cytoplasm is the conspicuous feature of meiosis in mammalian oocytes. Protein regulator of cytokinesis 1 (PRC1) is an important regulator during mitotic spindle assembly and cytoplasmic division, but its functions in oocyte meiosis and early embryo development have not been fully elucidated. In this study, we detected PRC1 expression and localization and revealed a nuclear, spindle midzone-related dynamic pattern throughout meiotic and mitotic progressions. Treatment of oocytes with the reagents taxol or nocodazole disturbed the distribution of PRC1 in metaphase II oocytes. Further, PRC1 depletion led to failure of first polar body (PB1) extrusion and spindle migration, aneuploidy and defective kinetochore-microtubule attachment and spindle assembly. Overexpression of PRC1 resulted in PB1 extrusion failure, aneuploidy and serious defects of spindle assembly. To investigate PRC1 function in early embryos, we injected Prc1 morpholino into zygotes and 2-cell stage embryos. Depletion of PRC1 in zygotes impaired 4-cell, morula and blastocyst formation. Loss of PRC1 in single or double blastomeres in 2-cell stage embryos significantly impaired cell division, indicating its indispensable role in early embryo development. Co-immunoprecipitation showed that PRC1 interacts with polo-like kinase 1 (PLK1), and functional knockdown and rescue experiments demonstrated that PRC1 recruits PLK1 to the spindle midzone to regulate cytoplasmic division during meiosis. Finally, kinesin family member 4 knockdown downregulates PRC1 expression and leads to PRC1 localization failure. Taken together, our data suggest PRC1 plays an important role during oocyte maturation and early embryonic development by regulating chromosome dynamics and cytoplasmic division.

Cisplatin, as one of the most effective chemotherapeutic agents, its clinical use is limited by serious side effect of nephrotoxicity. Cisplatin‐induced nephrotoxicity is closely related to apoptosis induction and activation of caspase. The present study aimed to explore the potential protective effect of ginsenoside Rk1 (Rk1), a rare ginsenoside generated during steaming ginseng, on cisplatin‐induced nephrotoxicity and the underlying mechanisms in human embryonic kidney 293 (HEK‐293) cells. Our results showed that the reduced cell viability induced by cisplatin could significantly recover by Rk1. Furthermore, glutathione (GSH) as an oxidative index, was elevated and the lipid peroxidation product malondialdehyde (MDA) was significantly decreased after Rk1 treatment compared to the cisplatin group. Additionally, Rk1 can also decrease the ROS fluorescence expression and increase the protein levels of nuclear factor erythroid 2‐related factor 2 (Nrf2) and heme oxygenase‐1 (HO‐1) compared to the cisplatin group, which suggested a suppression of oxidative response. More importantly, the cisplatin‐induced elevated protein levels of Bax, cleaved caspase‐3, cleaved caspase‐9, and decreased protein level of Bcl‐2 were reversed after treatment with Rk1. Our results elucidated the possible protective mechanism of Rk1 for the first time, which may involve in its anti‐oxidation and anti‐apoptosis effects.

BACKGROUND Achalasia is an esophageal motility disorder with unknown etiology. Previous findings indicate that immune-mediated inflammatory process causes inhibitory neuronal degeneration. This study was designed to evaluate levels of serological cytokines and chemokines in patients with achalasia. METHODS We collected information from forty-seven patients with achalasia who underwent peroral endoscopic myotomy. Control samples were collected from forty-seven age- and sex-matched healthy people. The concentrations of serological cytokines and chemokines were analyzed by Luminex xMAP immunoassay. Serological and clinical data were compared between groups. KEY RESULTS Compared with healthy controls, achalasia patients had significantly increased concentrations of eleven cytokines and chemokines, namely, TGF-s1 (P

The low performance and insufficient catalytic activity of perovskite anodes hinder their further application in intermediate-temperature solid-oxide fuel cells (IT-SOFCs). A novel La0.8 Sr0.2 Fe0.9 Nb0.1 Pd0.04 O3-δ (LSFNP) anode material has been developed with Fe-Pd co-exsolutions for IT-SOFCs. Fe0 and Pd0 metallic nanoparticles are confirmed to exsolve on the surface of the perovskite anode during operation under a hydrogen atmosphere. The introduced Pd exsolutions promote the charge-transfer process slightly and the H2 -adsorption ability of the La0.8 Sr0.2 Fe0.9 Nb0.1 O3-δ (LSFN) parent anode significantly, as metallic Pd is a conductor with excellent catalytic activity and an absorber of hydrogen that can absorb a large amount of H2 by forming unstable chemical bonds. A single cell with the LSFNP anode exhibits high output performance (maximum power density of 287.6 mW cm-2 at T=800 °C by using humidified H2 as the fuel), excellent redox stability, and considerable coking and sulfur tolerances. After the introduction of Pd exsolutions, the increase in the electrochemical performance is more significant under low H2 concentrations and at low temperatures with a maximum power density ratio of the LSFNP anode cell/LSFN anode cell reaching 18 under 5 % H2 /argon at T=650 °C. Pd-decorated LSFNP is a high-performance, redox-stable, coking-tolerant, and sulfur-tolerant anode material for IT-SOFCs, making Pd exsolution a reliable nanodecoration strategy to improve the low kinetics of perovskite anodes.

Background: Neuromelanin is a pigment with strong iron-chelating properties preferentially found in dopaminergic neurons of the substantia nigra, pars compacta (SNpc). Parkinson's disease is characterized by pronounced, MRI detectable neuromelanin loss, but the neuroprotective or neurotoxic role of neuromelanin remains debated. Histological studies demonstrated neuromelanin increases with age, but this has not been confirmed in vivo and there is uncertainty whether neuromelanin declines, stabilizes or increases from middle age.Methods: This study aimed to establish physiological changes of pigmentation of the SNpc using a pooled dataset of neuromelanin-sensitive 3T MRI from 134 healthy individuals, aged 5~83 years. Neuromelanin-related brightness (regional contrast-to-ratio) and calibrated hyperintense volumes were analyzed using linear and non-linear regression models to characterize age effects. Laterality, sex, and subregional effects were also assessed.Results: For brightness, age effects were best described as a quadratic trajectory explaining 81.5% of the observed variance in SNpc showing a strong increase from childhood to adolescence, with plateauing in middle age and a decline in older age. Similar but less pronounced effects were seen in hyperintense volumes. We also show an anteriorposterior gradient in SNpc contrast, larger normalized NM-rich volume in women >47 of age, but no laterality effect.Conclusions: Using optimized neuromelanin-MRI in a lifespan sample, we demonstrate a strong age effect with an inverted U-shape of SNpc pigmentation-related contrast from childhood to old age. This age trajectory of physiological SNpc pigmentation needs to be taken into account for diagnostic applications of depigmentation. The study also paves the way for systematic investigations of the mechanisms of neuromelanin in healthy and pathological brain development and aging.