The iron chelator deferoxamine has been shown to inhibit ferroptosis in spinal cord injury. However, it is unclear whether deferoxamine directly protects neurons from ferroptotic cell death. By ...comparing the survival rate and morphology of primary neurons and SH-SY5Y cells exposed to erastin, it was found that these cell types respond differentially to the duration and concentration of erastin treatment. Therefore, we studied the mechanisms of ferroptosis using primary cortical neurons from E16 mouse embryos. After treatment with 50 μM erastin for 48 hours, reactive oxygen species levels increased, and the expression of the cystine/glutamate antiporter system light chain and glutathione peroxidase 4 decreased. Pretreatment with deferoxamine for 12 hours inhibited these changes, reduced cell death, and ameliorated cellular morphology. Pretreatment with the apoptosis inhibitor Z-DEVD-FMK or the necroptosis inhibitor necrostain-1 for 12 hours did not protect against erastin-induced ferroptosis. Only deferoxamine protected the primary cortical neurons from ferroptosis induced by erastin, confirming the specificity of the in vitro ferroptosis model. This study was approved by the Animal Ethics Committee at the Institute of Radiation Medicine of the Chinese Academy of Medical Sciences, China (approval No. DWLL-20180913) on September 13, 2018.
Objective. The spectrum of UDP-glucuronyl transferase A1 (UGT1A1) variants in hereditary unconjugated hyperbilirubinemia varies markedly between different ethnic populations. This study evaluated the ...UGT1A1 genotypes in hyperbilirubinemia patients from southeastern China. Methods. We enrolled 60 patients from southeastern China (44 men and 16 women; age range: 3–76 years) with unconjugated hyperbilirubinemia and performed genetic analysis of the UGT1A1 gene by direct sequencing. Results. For patients with Gilbert syndrome, 85% (47/55) harbored pathogenic variants of UGT1A1⁎60. Both UGT1A1⁎28 and UGT1A1⁎81 were detected in the promoter region of UGT1A1. Additionally, 83% (20/24) of patients with Gilbert syndrome heterozygous for UGT1A1⁎60 had an association with heterozygous variation of UGT1A1⁎28 or UGT1A1⁎81, while 91% (21/23) of Gilbert syndrome patients homozygous for UGT1A1⁎60 had biallelic variations of UGT1A1⁎28 and UGT1A1⁎81. We detected 213 UGT1A1 allelic variants, including six novel variations, with the most frequent allele being the UGT1A1⁎60, followed by UGT1A1⁎28 and UGT1A1⁎6. All of the patients showed multiple sites of variants in UGT1A1; however, variation number was not associated with bilirubin levels (P>0.05). Conclusions. The spectrum of UGT1A1 variants in southeastern Chinese patients was distinct from other ethnic populations. Our findings broaden the knowledge concerning traits associated with UGT1A1 variants and help profile genotype–phenotype correlations in hyperbilirubinemia patients.
Abstract
We present a data-driven approach to automatically detect L dwarfs from Sloan Digital Sky Survey (SDSS) images using an improved Faster R-CNN framework based on deep learning. The ...established L-dwarf automatic detection (LDAD) model distinguishes L dwarfs from other celestial objects and backgrounds in SDSS field images by learning the features of 387 SDSS images containing L dwarfs. Applying the LDAD model to the SDSS images containing 93 labeled L dwarfs in the test set, we successfully detected 83 known L dwarfs with a recall rate of 89.25% for known L dwarfs. Several techniques are implemented in the LDAD model to improve its detection performance for L dwarfs, including the deep residual network and the feature pyramid network. As a result, the LDAD model outperforms the model of the original Faster R-CNN, whose recall rate of known L dwarfs is 80.65% for the same test set. The LDAD model was applied to detect L dwarfs from a larger validation set including 843 labeled L dwarfs, resulting in a recall rate of 94.42% for known L dwarfs. The newly identified candidates include L dwarfs, late M and T dwarfs, which were estimated from color (
i
−
z
) and spectral type relation. The contamination rates for the test candidates and validation candidates are 8.60% and 9.27%, respectively. The detection results indicate that our model is effective to search for L dwarfs from astronomical images.
Although light arenes such as benzene, toluene, and xylene in coal tar are widely used in industries, their amounts are relatively small. The catalytic cracking method for gaseous tar is one of the ...promising techniques for upgrading tar, and the amounts of light arenes are improved. Therefore, the catalytic upgrading of gaseous tar using two different catalysts is investigated in this study; the variations of light arenes before and after catalytic cracking are determined. More importantly, the variation of heavy compounds in gaseous tar is analyzed, and also the catalytic cracking mechanism is elucidated. The results show that the amount of benzene increases by 500% under the action of USY zeolite, and the amount of other compounds such as toluene, ethylbenzene, xylene, and naphthalene also increases by different degrees. However, Al/SBA-15 zeolite shows no obvious effect on gaseous tar upgrading. At the same time, the analysis results show that heavy compounds can be cracked over USY zeolite. Side chains are cleaved from aromatic rings, and aromatic rings are also cracked during the catalytic cracking reactions. Furthermore, light arenes are formed after the hydroxyl groups in phenols cleaved from the aromatic rings.
•USY zeolite significantly catalyzed the upgrading of gaseous tar to light arenes.•The cracking mechanism of heavy compounds in gaseous tars over USY zeolite is elucidated.
Tumor-associated lymphangiogenesis is considered significant in number of solid malignancies. However, its impact on prognosis of intrahepatic cholangiocarcinoma (ICC) after resection remains further ...confirmation. Herein, we conducted this study to evaluate prognostic impact of tumor-associated lymphangiogenesis in patients with ICC.
Extent of tumor-associated lymphangiogenesis of ICC was evaluated by quantifying microlymphatic vessel density (MLVD) from immunohistochemical staining of a lymphatic endothelial-specific antibody (podoplanin). Clinicopathological characteristics were comprehensively analyzed to identify MLVD-associated factors. The patients were stratified into high and low MLVD groups according to the distinctive correlation between the MLVD and overall survival using the Spearman's correlation test. Kaplan-Meier estimation was performed to confirm prognostic impact of MLVD in patients with ICC. Univariate and multivariate analyses were performed using the Cox proportional hazard model.
The MLVD between 4 to 12 counts showed inverse proportion to the overall survival (Spearman's r = - 0.66; 95% confidence interval CI, - 0.82 to - 0.39; p < 0.0001), which was set as a cut-off for the high MLVD group, whereas the MLVD between 13 to 25 showed no correlation to the overall survival (r = - 0.11; 95% CI, - 0.38 to 0.19; p = 0.4791). The high MLVD group showed more frequent lymph node metastasis (p < 0.001) and were more likely to suffer from recurrence of the tumor compared to the low MLVD group (p < 0.001). The high MLVD was found to be independently associated with reduced overall and recurrence-free survival. The 5-year overall survival of the patients with high MLVD was significantly lower compared to those with low MLVD (0% vs 48%).
Our study reveals that tumor-associated lymphangiogenesis is significantly associated with increased lymphatic metastasis, recurrence of the tumor, and reduced overall survival in patients with ICC, thus providing guidance when estimating postresection prognosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Accumulating evidence confirms that sleep insufficiency is a high risk factor for cognitive impairment, which involves inflammation and synaptic dysfunction. Resveratrol, an agonist of the Sirt1, has ...demonstrated anti‐inflammation and neuroprotective effects in models of Alzheimer's disease, Parkinson's disease, and schizophrenia. However, the beneficial effects of resveratrol on sleep deprivation‐induced cognitive deficits and its underlying molecular mechanisms are unclear. In the present study, thirty‐two male C57BL/6 J mice were randomly divided into a Control+DMSO group, Control+Resveratrol group, SD+DMSO group, and SD+Resveratrol group. The mice in the SD+Resveratrol group underwent 5 days of sleep deprivation after pretreatment with resveratrol (50 mg/kg) for 2 weeks, while the mice in the SD+DMSO group only underwent sleep deprivation. After sleep deprivation, we evaluated spatial learning and memory function using the Morris water maze test. We used general molecular biology techniques to detect changes in levels of pro‐inflammatory cytokines and Sirt1/miR‐134 pathway‐related synaptic plasticity proteins. We found that resveratrol significantly reversed sleep deprivation‐induced learning and memory impairment, elevated interleukin‐1β, interleukin‐6, and tumor necrosis factor‐α levels, and decreased brain‐derived neurotrophic factor, tyrosine kinase receptor B, postsynaptic density protein‐95, and synaptophysin levels by activating the Sirt1/miR‐134 pathway. In conclusion, resveratrol is a promising agent for preventing sleep deprivation‐induced cognitive dysfunction by reducing pro‐inflammatory cytokines and improving synaptic function via the Sirt1/miR‐134 pathway.
In chemistry, theory of aromaticity or π bond resonance plays a central role in intuitively understanding the stability and properties of organic molecules. Here we present an analogue theory for σ ...bond resonance in flat boron materials, which allows us to determine the distribution of two-center two-electron and three-center two-electron bonds without quantum calculations. Based on this theory, three rules are proposed to draw the Kekulé-like bonding configurations for flat boron materials and to explore their properties intuitively. As an application of the theory, a simple explanation of why neutral borophene with ~1/9 hole has the highest stability and the effect of charge doping on borophene's optimal hole concentration is provided with the assumption of σ and π orbital occupation balance. Like the aromaticity theory for carbon materials, this theory greatly deepens our understanding on boron materials and paves the way for the rational design of various boron-based materials.
ISG15 is an Interferon (IFN)-α/β—inducible, ubiquitin-like intracellular protein. Its conjugation to various proteins (ISGylation) contributes to antiviral immunity in mice. Here, we describe human ...patients with inherited ISG15 deficiency and mycobacterial, but not viral, diseases. The lack of intracellular ISG15 production and protein ISGylation was not associated with cellular susceptibility to any viruses that we tested, consistent with the lack of viral diseases in these patients. By contrast, the lack of mycobacterium-induced ISG15 secretion by leukocytes—granulocyte, in particular—reduced the production of IFN-γ by lymphocytes, including natural killer cells, probably accounting for the enhanced susceptibility to mycobacterial disease. This experiment of nature shows that human ISGylation is largely redundant for antiviral immunity, but that ISG15 plays an essential role as an IFN-γ-inducing secreted molecule for optimal antimycobacterial immunity.
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