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PHARC syndrome is a rare neurodegenerative disorder caused by mutations in the ABHD12 gene. It is a genetically heterogeneous and clinically variable disease, which is characterized by demyelinating polyneuropathy, hearing loss, cerebellar ataxia, retinitis pigmentosa, and early-onset cataract and can easily be misdiagnosed as other neurologic disorders with a similar clinical picture, such as Charcot-Marie-Tooth disease and Refsum disease. We describe the genotype-phenotype correlation of two siblings with a novel genotype underlying PHARC syndrome. The genotype was identified using next-generation sequencing. We examined both patients by means of thorough history taking and clinical examination, nerve conduction studies (NCS), brain imaging, and optical coherence tomography to establish a genotype-phenotype correlation. We identified a novel homozygous point mutation (c.784C > T, p.Arg262*) in the ABHD12 gene. This mutation was detected in both siblings, who had bilateral hearing loss and cataracts, signs of cerebellar ataxia, and neuropathy with a primarily demyelinating pattern in NCS. In one case, retinitis pigmentosa was also evident. As PHARC syndrome is a rare autosomal recessive disorder, our findings highlight the importance of an interdisciplinary diagnostic workup with clinical and molecular genetic testing to avoid a misdiagnosis as Charcot-Marie-Tooth disease or Refsum disease. © 2020 Peripheral Nerve Society.Monoamine oxidases have two functionally distinct but structurally similar isoforms (MAO-A and MAO-B). The ability to differentiate them by using fluorescence detection/imaging technology is of significant biological relevance, but highly challenging with available chemical tools. Herein, we report the first MAO-A-specific two-photon fluorogenic probe (F1), capable of selective imaging of endogenous MAO-A enzymatic activities from a variety of biological samples, including MAO-A-expressing neuronal SY-SY5Y cells, the brain of tumor-bearing mice and human Glioma tissues by using two-photon fluorescence microscopy (TPFM) with minimal cytotoxicity. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.BACKGROUND We aimed to develop a time-resolved fluorescence immunoassay (TRFIA) for detecting soluble T-cell immunoglobulin and mucin domain 3 (sTim3) in serum samples and to demonstrate a preliminary application of this method in membranous nephropathy (MN). METHODS sTim3 TRFIA was developed, and the sTim3 concentration in the serum of patients with MN and healthy individuals was detected using a sandwich method. RESULTS The sensitivity of the developed sTim3 TRFIA was 0.66 ng/mL, higher than that of an enzyme-linked immunosorbent assay (ELISA) (1.11 ng/mL). The detection range was 0.66-40 ng/mL. The intra-assay coefficient of variation (CV) for sTim3 was 1.64%-4.68%, and the inter-assay CV was 5.72%-9.32%. The cross-reactivity to interleukin 6 (IL-6) and kidney injury molecule 1 (KIM-1) was 0.25% and 0.04%, respectively. The average recovery was 105.26%. AZD-5153 6-hydroxy-2-naphthoic The sTim3 concentration in patients with MN was considerably higher than that in healthy individuals (P  less then  .001). The sTim3 concentration in the serum of patients with MN was significantly increased from G1 to G4 based on the Jonckheere-Terpstra test (P  less then  .001). Thus, we used sTim3 as a diagnostic indicator for distinguishing between healthy individuals and patients with MN as well as between different stages of MN. CONCLUSION We successfully established TRFIA to detect sTim3 in serum. We then applied this method to patients with MN, demonstrating for the first time that TRFIA is a valid diagnostic tool to detect sTim3 in serum. © 2020 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals, Inc.Protein phosphatase 4 regulatory subunit 1 (PP4R1) has been shown to play a role in the regulation of centrosome maturation, apoptosis, DNA repair, and tumor necrosis factor signaling. However, the function of PP4R1 in non-small-cell lung cancer remains unclear. In this study, we identify PP4R1 as an oncogene through Oncomine database mining and immunohistochemical staining, and we showed that PP4R1 is upregulated in lung cancer tissues as compared with that in normal lung tissues and correlated with a poor prognosis in lung cancer patients. Furthermore, in vitro study by wound-healing and Transwell assay showed that PP4R1 could promote migration and invasion of lung cancer cells. Mechanistic investigations revealed that PP4R1 could cooperate with high mobility group AT-hook 2 and thereby promotes epithelial-mesenchymal transition via MAPK/extracellular receptor kinase activation. Taken together, our study provides a rich resource for understanding PP4R1 in lung cancer and indicates that PP4R1 may serve as a potential biomarker in lung cancer therapies. © 2020 Wiley Periodicals, Inc.Chemical architectures with an ordered porous backbone and high charge transfer are significant for fiber-shaped supercapacitors (FSCs). However, owing to the sluggish ion kinetic diffusion and storage in compacted fibers, achieving high energy density remains a challenge. An innovative magnetothermal microfluidic method is now proposed to design hierarchical carbon polyhedrons/holey graphene (CP/HG) core-shell microfibers. Owing to highly magnetothermal etching and microfluidic reactions, the CP/HG fibers maintain an open inner-linked ionic pathway, large specific surface area, and moderate nitrogen active site, facilitating more rapid ionic dynamic transportation and accommodation. The CP/HG FSCs show an ultrahigh energy density (335.8 μWh cm-2 ) and large areal capacitance (2760 mF cm-2 ). A self-powered endurance application with the integration of chip-based FSCs is designed to profoundly drive the durable motions of an electric car and walking robot. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.αβ-tubulin subunits cycle through a series of different conformations in the polymer lattice during microtubule growing and shrinking. How these allosteric responses to different tubulintubulin contacts contribute to microtubule dynamics, and whether the contributions are evolutionarily conserved, remains poorly understood. Here, we sought to determine whether the microtubule-stabilizing effects (slower shrinking) of the βT238A mutation we previously observed using yeast αβ-tubulin would generalize to mammalian microtubules. Using recombinant human microtubules as a model, we found that the mutation caused slow microtubule shrinking, indicating that this effect of the mutation is indeed conserved. However, unlike in yeast, βT238A human microtubules grew faster than wild-type and the mutation did not appear to attenuate the conformational change associated with guanosine 5'-triphosphate (GTP) hydrolysis in the lattice. We conclude that the assembly-dependent conformational change in αβ-tubulin can contribute to determine the rates of microtubule growing as well as shrinking.