488 research outputs found

    An Exploration of Spatial and Social Inequalities of Urban Sports Facilities in Nanning City, China

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    Health and well-being have become important dimensions of urban sustainability, particularly in countries with rapid urbanization and aging populations. As such, providing opportunities for physical activity and exercise has become a priority in the planning and governance of Healthy City in these countries. Relatively little research has investigated the provision of sports facilities in developing countries. This paper seeks to address this gap by exploring the spatial and social inequality of sports facilities at the urban scale using Nanning City in South China as a case study. Spatial aggregate analyses, including an allocation index, accessibility, diversity, and geographically weighted regression, were applied to mixed data sets from primary and secondary sources from 2018. The results confirmed a strong inequality of sports facilities provision across the study area and between age groups. This study suggests that the reduction of inequality and the improvement of equity and social justice should consider the spatial and social matches between demand and supply, through increasing sports facilities investment intensity and road network density

    Nickel pyrithione induces apoptosis in chronic myeloid leukemia cells resistant to imatinib via both Bcr/Abl-dependent and Bcr/Abl-independent mechanisms

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    Abstract Background Acquired imatinib (IM) resistance is frequently characterized by Bcr-Abl mutations that affect IM binding and kinase inhibition in patients with chronic myelogenous leukemia (CML). Bcr-Abl-T315I mutation is the predominant mechanism of the acquired resistance to IM. Therefore, it is urgent to search for additional approaches and targeting strategies to overcome IM resistance. We recently reported that nickel pyrithione (NiPT) potently inhibits the ubiquitin proteasome system via targeting the 19S proteasome-associated deubiquitinases (UCHL5 and USP14), without effecting on the 20S proteasome. In this present study, we investigated the effect of NiPT, a novel proteasomal deubiquitinase inhibitor, on cell survival or apoptosis in CML cells bearing Bcr-Abl-T315I or wild-type Bcr-Abl. Methods Cell viability was examined by MTS assay and trypan blue exclusion staining assay in KBM5, KBM5R, K562, BaF3-p210-WT, BaF3-p210-T315I cells, and CML patients’ bone marrow samples treated with NiPT. Cell apoptosis in CML cells was detected with Annexin V-FITC/PI and rhodamine-123 staining followed by fluorescence microscopy and flow cytometry and with western blot analyses for apoptosis-associated proteins. Expression levels of Bcr-Abl in CML cells were analyzed by using western blotting and real-time PCR. The 20S proteasome peptidase activity was measured using specific fluorogenic substrate. Active-site-directed labeling of proteasomal DUBs, as well as the phosphorylation of USP14 was used for evaluating the inhibition of the DUBs activity by NiPT. Mouse xenograft models of KBM5 and KBM5R cells were analyzed, and Bcr-Abl-related proteins and protein biomarkers related to proliferation, differentiation, and adhesion in tumor tissues were detected by western blots and/or immunohistological analyses. Results NiPT induced apoptosis in CML cells and inhibited the growth of IM-resistant Bcr-Abl-T315I xenografts in nude mice. Mechanistically, NiPT induced decreases in Bcr-Abl proteins, which were associated with downregulation of Bcr-Abl transcription and with the cleavage of Bcr-Abl protein by activated caspases. NiPT-induced ubiquitin proteasome system inhibition induced caspase activation in both IM-resistant and IM-sensitive CML cells, and the caspase activation was required for NiPT-induced Bcr-Abl downregulation and apoptotic cell death. Conclusions These findings support that NiPT can overcome IM resistance through both Bcr-Abl-dependent and Bcr-Abl-independent mechanisms, providing potentially a new option for CML treatment

    Lupus Erythematosus: Dermatologic Perspectives on the Diversity

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    Lupus is one of the complex autoimmune disease, which is difficult to diagnose and consists of few subtypes that are required to be classified. During our clinical work, we found out that the dermoscopy can be of great benefit to diagnose discoid lupus erythematosus (DLE). The histopathological examination is very important to confirm the diagnosis. The cases of infant LE patients, may derive the autoimmune antibodies from their mothers in order to diagnose the neonatal lupus erythematosus. Thus, it is very important to examine the antibodies of the mother, who may also be a subclinical LE patient and need continuous follow-ups or even treatment managements. Here, we present the cases of lupus with particular characteristics including linear cutaneous lupus erythematosus, DLE, and neonatal lupus erythematosus

    GJB2 mutation spectrum in 2063 Chinese patients with nonsyndromic hearing impairment

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    Background: Mutations in GJB2 are the most common molecular defects responsible for autosomal recessive nonsyndromic hearing impairment (NSHI). The mutation spectra of this gene vary among different ethnic groups. Methods: In order to understand the spectrum and frequency of GJB2 mutations in the Chinese population, the coding region of the GJB2 gene from 2063 unrelated patients with NSHI was PCR amplified and sequenced. Results: A total of 23 pathogenic mutations were identified. Among them, five (p.W3X, c.99delT, c.155_c.158delTCTG, c.512_c.513insAACG, and p.Y152X) are novel. Three hundred and seven patients carry two confirmed pathogenic mutations, including 178 homozygotes and 129 compound heterozygotes. One hundred twenty five patients carry only one mutant allele. Thus, GJB2 mutations account for 17.9% of the mutant alleles in 2063 NSHI patients. Overall, 92.6% (684/739) of the pathogenic mutations are frame-shift truncation or nonsense mutations. The four prevalent mutations; c.235delC, c.299_c.300delAT, c.176_c.191del16, and c.35delG, account for 88.0% of all mutantalleles identified. The frequency of GJB2 mutations (alleles) varies from 4% to 30.4% among different regions of China. It also varies among different sub-ethnic groups. Conclusion: In some regions of China, testing of the three most common mutations can identify at least one GJB2 mutant allele in all patients. In other regions such as Tibet, the three most common mutations account for only 16% the GJB2 mutant alleles. Thus, in this region, sequencing of GJB2 would be recommended. In addition, the etiology of more than 80% of the mutant alleles for NSHI in China remains to be identified. Analysis of other NSHI related genes will be necessary.Version of Recor

    Diffusion-Augmented Depth Prediction with Sparse Annotations

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    Depth estimation aims to predict dense depth maps. In autonomous driving scenes, sparsity of annotations makes the task challenging. Supervised models produce concave objects due to insufficient structural information. They overfit to valid pixels and fail to restore spatial structures. Self-supervised methods are proposed for the problem. Their robustness is limited by pose estimation, leading to erroneous results in natural scenes. In this paper, we propose a supervised framework termed Diffusion-Augmented Depth Prediction (DADP). We leverage the structural characteristics of diffusion model to enforce depth structures of depth models in a plug-and-play manner. An object-guided integrality loss is also proposed to further enhance regional structure integrality by fetching objective information. We evaluate DADP on three driving benchmarks and achieve significant improvements in depth structures and robustness. Our work provides a new perspective on depth estimation with sparse annotations in autonomous driving scenes.Comment: Accepted by ACM MM'202

    [N-(3-Meth­oxy-2-oxidobenzyl­idene-κO 2)threoninato-κ2 O 1,N](1,10-phenanthroline-κ2 N,N′)copper(II) hemihydrate

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    In the title complex, [Cu(C12H13NO5)(C12H8N2)]·0.5H2O, the CuII ion is five-coordinated by one N atom and two O atoms from a tridentate Schiff base ligand, derived from the condensation of l-threonine and o-vanillin, and two N atoms from a 1,10-phenanthroline ligand in a distorted square-pyramidal geometry. In the crystal, inter­molecular O—H⋯O hydrogen bonds form a one-dimensional left-handed helical structureextending parallel to [001]. The water molecule of crystallization shows half-occupancy

    A common variant near TGFBR3 is associated with primary open angle glaucoma

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    This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited.Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution.We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10−33), we observed one SNP showing significant association to POAG (CDC7–TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10−8). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis

    Comprehensive molecular etiology analysis of nonsyndromic hearing impairment from typical areas in China

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    <p>Abstract</p> <p>Background</p> <p>Every year, 30,000 babies are born with congenital hearing impairment in China. The molecular etiology of hearing impairment in the Chinese population has not been investigated thoroughly. To provide appropriate genetic testing and counseling to families, we performed a comprehensive investigation of the molecular etiology of nonsyndromic deafness in two typical areas from northern and southern China.</p> <p>Methods</p> <p>A total of 284 unrelated school children with hearing loss who attended special education schools in China were enrolled in this study, 134 from Chifeng City in Inner Mongolia and the remaining 150 from Nangtong City in JiangSu Province. Screening was performed for <it>GJB2</it>, <it>GJB3</it>, <it>GJB6</it>, <it>SLC26A4</it>, <it>12S rRNA</it>, <it>and tRNA</it><sup><it>ser</it>(<it>UCN</it>) </sup>genes in this population. All patients with <it>SLC26A4 </it>mutations or variants were subjected to high-resolution temporal bone CT scan to verify the enlarged vestibular aqueduct.</p> <p>Results</p> <p>Mutations in the <it>GJB2 </it>gene accounted for 18.31% of the patients with nonsyndromic hearing loss, 1555A>G mutation in mitochondrial DNA accounted for 1.76%, and <it>SLC26A4 </it>mutations accounted for 13.73%. Almost 50% of the patients with nonsyndromic hearing loss in these typical Chinese areas carried <it>GJB2 </it>or <it>SLC26A4 </it>mutations. No significant differences in mutation spectrum or prevalence of <it>GJB2 </it>and <it>SLC26A4 </it>were found between the two areas.</p> <p>Conclusion</p> <p>In this Chinese population, 54.93% of cases with hearing loss were related to genetic factors. The <it>GJB2 </it>gene accounted for the etiology in about 18.31% of the patients with hearing loss, <it>SLC26A4 </it>accounted for about 13.73%, and <it>mtDNA </it>1555A>G mutation accounted for 1.76%. Mutations in <it>GJB3, GJB6</it>, and <it>mtDNA tRNA</it><sup><it>ser</it>(<it>UCN</it>) </sup>were not common in this Chinese cohort. Conventionally, screening is performed for <it>GJB2</it>, <it>SLC26A4</it>, and mitochondrial <it>12S rRNA </it>in the Chinese deaf population.</p

    Observation of Viruses, Bacteria, and Fungi in Clinical Skin Samples under Transmission Electron Microscopy

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    The highlight of this chapter is the description of the clinical manifestation and its pathogen and the host tissue damage observed under the transmission electron microscopy, which helps the clinician understand the pathogen’s ultrastructure, the change of host sub-cell structure, and helps the laboratory workers understand the pathogen-induced human skin lesions’ clinical characteristics, to establish a two-way learning exchange database with vivid images
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