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1.
Theranostics ; 10(9): 4150-4167, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32226545

RESUMO

E3 ubiquitin ligases play a critical role in cellular mechanisms and cancer progression. F-box protein is the core component of the SKP1-cullin 1-F-box (SCF)-type E3 ubiquitin ligase and directly binds to substrates by various specific domains. According to the specific domains, F-box proteins are further classified into three sub-families: 1) F-box with leucine rich amino acid repeats (FBXL); 2) F-box with WD 40 amino acid repeats (FBXW); 3) F-box only with uncharacterized domains (FBXO). Here, we summarize the substrates of F-box proteins, discuss the important molecular mechanism and emerging role of F-box proteins especially from the perspective of cancer development and progression. These findings will shed new light on malignant tumor progression mechanisms, and suggest the potential role of F-box proteins as cancer biomarkers and therapeutic targets for future cancer treatment.

2.
Sci Total Environ ; 721: 137740, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32163736

RESUMO

Recently, two-dimensional black phosphorus (BP) nanomaterial has captured much attention due to its superb physiochemical and electronic properties and various promising biomedical applications. However, relatively few studies have explored its antimicrobial properties, particularly for targeting antibiotic-resistant pathogens. A comprehensive understanding of the bactericidal mechanisms of BP is essential for application of this material as an antimicrobial. This review discusses the physicochemical and electronic properties of BP that are relevant for antimicrobial applications, especially the unique characteristics that may play a role in overcoming drug resistance. The literature is discussed in the context of what is known and what information is missing. We also highlight the differences and advantages of BP over other two-dimensional nanomaterials (i.e., graphene oxide and molybdenum disulfide) for bactericidal activity. Finally, we analyze existing challenges and note topics that require future investigation to overcome current inadequacies, aiming to assist the safe development of BP-based nanotechnology for pathogen control.

3.
Immunol Invest ; : 1-11, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32183599

RESUMO

Hepatitis B, caused by hepatitis B virus (HBV) infection, is one of the epidemic and infectious hepatitis diseases. The sigle-nucleotide polymorphisms were identified to associate with HBV infection in East Asian population by genome-wide association study (GWAS), but no study in Yunnan HBV population was reported. We recruited 493 HBV patients and 460 general controls to genotype 7 GWAS SNPs, and then, the association study was performed between these SNPs and biochemical features of HBV patients. The results showed that genotype and allele frequencies of SNPs in the HLA-DP (rs3077, 9277535, and 3128917) and HLA-DQ (rs2856718 and 7453920) genes were associated with HBV infection. Significantly different genotyping frequencies were investigated among three HBV subgroups. Genotype AA of rs3130542 (HLA-C) showed significantly higher frequency in subgroup #1 patients than the other two subgroups (#1 vs. #2, p = .02; #1 vs. #3, p = .03). Meanwhile, genotype frequencies of rs3077, rs9277535, and 3128917 (HLA-DP) were significantly different between patients in subgroup #2 and #3. The indirect bilirubin level was significantly lower in patients with genotype CT of rs3077 than patients with genotype CC (p = .009) or TT (p = .016), and it also showed lower level in patients with genotype GT of rs3128917 than patients with genotype GG (p = .015). The direct bilirubin level was higher in patients with genotype TT of rs4821116 (UBE2L3) than patients with genotype CT (p = .010). In summary, we identified the association between GWAS SNPs and HBV infection or biochemical features in Yunnan HBV population.

4.
Trials ; 21(1): 239, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32131886

RESUMO

BACKGROUND: Traditional Chinese medicine (TCM) usually involves syndrome differentiation and treatment. Acupuncture, one form of TCM, requires the selection of appropriate acupoints and needling techniques, but many clinical trials on acupuncture have used fixed acupuncture protocols without accounting for individual patient differences. We have designed a multicenter randomized controlled trial (RCT) to evaluate whether personalized or fixed acupuncture increases the likelihood of live births in infertile women with polycystic ovary syndrome (PCOS) compared with letrozole or placebo letrozole. We hypothesize that letrozole is more effective than personalized acupuncture, which in turn is more effective than fixed acupuncture, and that placebo letrozole is the least effective intervention. Moreover, we hypothesize that personalized acupuncture is more likely to reduce the miscarriage rate and the risk of pregnancy complications compared with letrozole. METHODS/DESIGN: The study is designed as an assessor-blinded RCT. A total of 1100 infertile women with PCOS will be recruited from 28 hospitals and randomly allocated to 4 groups: personalized acupuncture, fixed acupuncture, letrozole, or placebo letrozole. They will receive treatment for 16 weeks, and the primary outcome is live birth. Secondary outcomes include ovulation rate, conception rate, pregnancy rate, pregnancy loss rate, changes in hormonal and metabolic parameters, and changes in quality of life scores. Adverse events will be recorded throughout the trial. All statistical analyses will be performed using IBM SPSS Statistics version 21.0 software (IBM Corp., Armonk, NY, USA), and a P value < 0.05 will be considered statistically significant. DISCUSSION: This study will be the first multicenter RCT to compare the effect of personalized or fixed acupuncture with letrozole or placebo letrozole on live birth in infertile women with PCOS. The findings will inform whether personalized acupuncture therapy can be considered an alternative treatment to improve the live birth rate in infertile women with PCOS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03625531. Registered on July 13, 2018. Chinese Clinical Trial Registry, ChiCTR1800017304. Registered on July 23, 2018.

6.
Chemistry ; 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32212280

RESUMO

Extension of a fused aromatic ring core is beneficial for enhancing the intramolecular charge transfer and effective π-conjugation in A-D-A type non-fullerene acceptors (NFAs). In this work, a novel strategy involving extension of fused-ring core by symmetrically replicating core unit was developed, and a novel symmetric fused-12-ring NFA, LC81 was synthesized. When paired with the wide-bandgap polymer donor, PBT1-C, the corresponding organic solar cells (OSCs) showed a high-power conversion efficiency (PCE) of 12.71%, much higher than that of the device based on reference NFA, TPTT-4F. Moreover, the LC81-based OSC displayed a lower energy loss and a better ambient stability than the TPTT-4F-based device. Our results indicate that the extension of fused-ring core by symmetric replicating core unit is an effective strategy for promoting photovoltaic characteristics of A-D-A-type NFAs.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32050549

RESUMO

Background: Exposures to both ambient fine particulate matter (PM2.5) and extreme weather conditions have been associated with cardiovascular disease (CVD) deaths in numerous epidemiologic studies. However, evidence on the associations with CVD deaths for interaction effects between PM2.5 and weather conditions is still limited. This study aimed to investigate associations of exposures to PM2.5 and weather conditions with cardiovascular mortality, and further to investigate the synergistic or antagonistic effects of ambient air pollutants and synoptic weather types (SWTs). Methods: Information on daily CVD deaths, air pollution, and meteorological conditions between 1 January 2012 and 31 December 2014 was obtained in Shanghai, China. Generalized additive models were used to assess the associations of daily PM2.5 concentrations and meteorological factors with CVD deaths. A 15-day lag analysis was conducted using a polynomial distributed lag model to access the lag patterns for associations with PM2.5. Results: During the study period, the total number of CVD deaths in Shanghai was 59,486, with a daily mean of 54.3 deaths. The average daily PM2.5 concentration was 55.0 µg/m3. Each 10 µg/m3 increase in PM2.5 concentration was associated with a 1.26% (95% confidence interval (CI): 0.40%, 2.12%) increase in CVD mortality. No SWT was statistically significantly associated with CVD deaths. For the interaction between PM2.5 and SWT, statistically significant interactions were found between PM2.5 and cold weather, with risk for PM2.5 in cold dry SWT decreasing by 1.47% (95% CI: 0.54%, 2.39%), and in cold humid SWT the risk decreased by 1.45% (95% CI: 0.52%, 2.36%). In the lag effect analysis, statistically significant positive associations were found for PM2.5 in the 1-3 lag days, while no statistically significant effects were found for other lag day periods. Conclusions: Exposure to PM2.5 was associated with short-term increased risk of cardiovascular deaths with some lag effects, while the cold weather may have an antagonistic effect with PM2.5. However, the ecological study design limited the possibility to identify a causal relationship, so prospective studies with individual level data are warranted.

9.
Nanoscale ; 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32100778

RESUMO

A CoCrFeNiMn high entropy alloy with a novel nanostructure consisting of ultrafine grains, TiO(C) nanoparticles and nanotwins has been fabricated. It achieves an ultrahigh tensile yield strength of 1507 MPa by coupling multiple strengthening mechanisms, including grain boundary strengthening, twin boundary strengthening, nanoparticle strengthening and dislocation strengthening. The work hardening ability is also improved by coupling the interactions of dislocations with nanoparticles and nanotwins during plastic deformation, leading to a good tensile ductility with a uniform elongation of 4.7%.

10.
Brain Res ; 1733: 146680, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-31987731

RESUMO

INTRODUCTION: To explore the underlying mechanism of electroacupuncture (EA) treatment on central post-stroke pain (CPSP), and provide basic evidence for the EA treatment on CPSP. METHODS: Firstly, 40 male SD rats were successfully established with a model of CPSP, under the intervention of different EA frequencies (2 Hz and 15 Hz) and fluoxetine (5 ml/kg and 0.4 mg/ml), whose brain tissue was then removed for paraffin-embedded sectioning; secondly, LPS induced the primary brain cells in the hippocampus to cause inflammation model which were added NS398 (inhibitor of COX-2) and DKK-1 (inhibitor of ß-catenin) later. The lesion sites of brain tissue were observed by Nissl staining and Transmission Electron Microscope (TEM) and autophagy-related proteins (LC3B, p62, LAMP-1), COX-2 and ß-catenin were detected by Western Blot and immunohistochemical staining. Finally, the correlation between LC3B, COX-2, and ß-catenin was calculated by multispectral quantification. RESULTS: (1) In the EA group (15 Hz), the number of Nissl bodies increased, autophagy-related protein LC3B-Ⅱ/Ⅰ, LAMP-1, COX-2, and ß-catenin was lowly expressed, p62 was highly expressed; (2) COX-2, ß-catenin and LC3B are positively correlated with each other (COX-2 & ß-catenin: r = 0.923; COX-2 & LC3B: r = 0.818; ß-catenin & LC3B: r = 0.801); (3) Nissl bodies of primary brain cells of the hippocampus under LPS were like animal experiments; after addition of DKK-1, high expression of ß-catenin and COX-2 induced by LPS was significantly down-regulated, and LC3B-II/I was significantly down-regulated, and p62 protein only had up-regulation trend; after addition of NS398, COX-2 and LC3B-II/I was significantly down-regulated. CONCLUSION: EA may inhibit autophagy in the hippocampus by reducing ß-catenin/COX-2 protein expression and effectively alleviating CPSP. SIGNIFICANCE STATEMENT: Previous studies have found that EA can reduce the expression of NK-1R in damaged rats by inhibition of COX-2 and ß-catenin loops, which controls the activation of glial cells in the damaged area and the apoptosis of neuronal cells, and alleviated pain. In the male SD rat model, we evaluated this effect that EA inhibits autophagy in the hippocampus by reducing ß-catenin/COX-2 protein expression in the brain tissue. In addition, we assessed expression levels of autophagy-related proteins and genes on the inflammatory primary brain cells model. From the experiment, we found EA may inhibit autophagy in the hippocampus by reducing ß-catenin/COX-2 protein expression. These findings provide a foundation for the interpretation of the mechanism of EA on relieving CPSP in clinical practice.

11.
Clin Cancer Res ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31911545

RESUMO

BACKGROUND: Tumor genomic features have been of particular interest because of their potential impact on the tumor immune microenvironment and response to immunotherapy. Due to the substantial heterogeneity, an integrative approach incorporating diverse molecular features is needed to characterize immunological features underlying primary resistance to immunotherapy and for the establishment of novel predictive biomarkers. METHODS: We developed a pan-cancer deep machine-learning model integrating tumor mutation burden, microsatellite instability and somatic copy number alterations to classify tumors of different types into different genomic clusters, assessed the immune microenvironment in each genomic cluster and the association of each genomic cluster with response to immunotherapy. RESULTS: Our model grouped 8,646 tumors of 29 cancer types from the Cancer Genome Atlas into four genomic clusters. Analysis of RNA-sequencing data revealed distinct immune microenvironment in tumors of each genomic class. Furthermore, applying this model to tumors from two melanoma immunotherapy clinical cohorts demonstrated that patients with melanoma of different genomic classes achieved different benefit from immunotherapy. Interestingly, tumors in cluster 4 demonstrated a cold immune microenvironment and lack of benefit from immunotherapy despite high microsatellite instability burden. CONCLUSION: Our study provides a proof-for-principle that deep learning modeling may have the potential to discover intrinsic statistical cross-modality correlations of multifactorial input data to dissect the molecular mechanisms underlying primary resistance to immunotherapy, which likely involves multiple factors from both the tumor and host at different molecular levels.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31910714

RESUMO

With the rapid increase in electronic cigarette (e-cig) users worldwide, secondhand exposure to e-cig aerosols has become a serious public health concern. We summarize the evidence on the effects of e-cigs on indoor air quality, chemical compositions of mainstream and secondhand e-cig aerosols, and associated respiratory and cardiovascular effects. The use of e-cigs in indoor environments leads to high levels of fine and ultrafine particles similar to tobacco cigarettes (t-cigs). Concentrations of chemical compounds in e-cig aerosols are generally lower than those in t-cig smoke, but a substantial amount of vaporized propylene glycol, vegetable glycerin, nicotine, and toxic substances, such as aldehydes and heavy metals, have been reported. Exposures to mainstream e-cig aerosols have biologic effects but only limited evidence showing adverse respiratory and cardiovascular effects in humans. Long-term studies are needed to better understand the dosimetry and health effects of exposures to secondhand e-cig aerosols. Expected final online publication date for the Annual Review of Public Health, Volume 41 is April 1, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

13.
J Exp Clin Cancer Res ; 39(1): 21, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31987045

RESUMO

In the original publication of this article [1], the molecular weight of RBMS3 was incorrectly noted as 38 KDa within Fig 1A, Fig 2A and Fig 2B. The figures have been updated to list the correct molecular weight of RBMS3 as 41 KDa.

14.
ACS Nano ; 14(1): 877-890, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31891481

RESUMO

The liver is the primary organ to sequester nanodrugs, representing a substantial hurdle for drug delivery and raising toxicity concerns. However, the mechanistic details underlying the liver sequestration and effects on the liver are still elusive. The difficulty in studying the liver lies in its complexity, which is structured with stringently organized anatomical units called lobules. Graphene oxide (GO) has attracted attention for its applications in biomedicine, especially as a nanocarrier; however, its sequestration and effects in the liver, the major enrichment and metabolic organ, are less understood. Herein, we unveiled the differential distribution of GO in lobules in the liver, with a higher amount surrounding portal triad zones than the central vein zones. Strikingly, liver zonation patterns also changed, as reflected by changes in vital zonated genes involved in hepatocyte integrity and metabolism, leading to compromised hepatic functions. RNA-Seq and DNA methylation sequencing analyses unraveled that GO-induced changes in liver functional zonation could be ascribed to dysregulation of key signaling pathways governing liver zonation at not only mRNA transcriptions but also DNA methylation imprinting patterns, partially through TET-dependent signaling. Together, this study reveals the differential GO distribution pattern in liver lobules and pinpoints the genetic and epigenetic mechanisms in GO-induced liver zonation alterations.

15.
Carbohydr Polym ; 231: 115736, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31888822

RESUMO

A recently developed three-dimensional (3D) gel-printing technology, namely continuous liquid interface production (CLIP), was utilized to fabricate supramolecular shape memory hydrogels with high resolutions and complex 3D geometries. The UV-curable ink for CLIP was composed of hydrogel precursors (alginate and acrylamide) and a photo-initiator (ammonium persulfate). As expected, the double network formed from ionically crosslinked alginate and covalently crosslinked polyacrylamide endowed the printed hydrogels with excellent mechanical properties. Meanwhile, due to the reversible metal-ligand coordination interaction, the hydrogel could be temporarily immobilized into an optional shape after introducing calcium ions and return to its original shapes upon ion removal, exhibiting ion-triggered shape memory effect. Moreover, the presence of ions greatly improved the conductivity of the resultant hydrogels. Such 3D printed versatile hydrogels with complex geometries demonstrated the potential for selected applications, particularly in load-bearing materials and flexible electronic devices.

16.
Chem Rev ; 120(4): 2288-2346, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-31971371

RESUMO

As a novel member of the two-dimensional nanomaterial family, mono- or few-layer black phosphorus (BP) with direct bandgap and high charge carrier mobility is promising in many applications such as microelectronic devices, photoelectronic devices, energy technologies, and catalysis agents. Due to its benign elemental composition (phosphorus), large surface area, electronic/photonic performances, and chemical/biological activities, BP has also demonstrated a great potential in biomedical applications including biosensing, photothermal/photodynamic therapies, controlled drug releases, and antibacterial uses. The nature of the BP-bio interface is comprised of dynamic contacts between nanomaterials (NMs) and biological systems, where BP and the biological system interact. The physicochemical interactions at the nano-bio interface play a critical role in the biological effects of NMs. In this review, we discuss the interface in the context of BP as a nanomaterial and its unique physicochemical properties that may affect its biological effects. Herein, we comprehensively reviewed the recent studies on the interactions between BP and biomolecules, cells, and animals and summarized various cellular responses, inflammatory/immunological effects, as well as other biological outcomes of BP depending on its own physical properties, exposure routes, and biodistribution. In addition, we also discussed the environmental behaviors and potential risks on environmental organisms of BP. Based on accumulating knowledge on the BP-bio interfaces, this review also summarizes various safer-by-design strategies to change the physicochemical properties including chemical stability and nano-bio interactions, which are critical in tuning the biological behaviors of BP. The better understanding of the biological activity of BP at BP-bio interfaces and corresponding methods to overcome the challenges would promote its future exploration in terms of bringing this new nanomaterial to practical applications.

17.
Oncogene ; 39(3): 587-602, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31511647

RESUMO

Ubiquitin-specific-processing proteases (USPs), the largest deubiquitinating enzyme (DUB) subfamily, play critical roles in cancer. However, clinical utility of USPs is hindered by limited knowledge about their varied and substrate-dependent actions. Here, we performed a comprehensive investigation on pan-cancer impacts of USPs by integrating multi-omics data and annotated data resources, especially a deubiquitination network. Meaningful insights into the roles of 54 USPs in 29 types of cancers were generated. Although rare mutations were observed, a majority of USPs exhibited significant expressional alterations, prognostic impacts and strong correlations with cancer hallmark pathways. Notably, from our DUB-substrate interaction prediction model, additional USP-substrate interactions (USIs) were recognized to complement knowledge gap about cancer-relevant USIs. Intriguingly, expression signatures of the USIs revealed clinically meaningful cancer subtypes, where key USPs and substrates cooperatively contributed to significant prognosis differences among subtypes. Overall, this investigation provides a valuable resource to assist mechanism research and clinical utility about USPs.

18.
Eye (Lond) ; 34(3): 537-543, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31406357

RESUMO

PURPOSE: To describe the characteristics, outcomes and complications of eyes after silicone oil removal. METHODS: Retrospective case series of eyes that underwent oil removal between 2012 and 2016 at The Institute of Ophthalmology and Visual Science. Visual acuity (VA), intraocular pressure (IOP) and rates of retinal re-detachment, hypotony, ocular hypertension, corneal decompensation, cystoid macular edema (CME) and cataract progression were evaluated. RESULTS: Totally, 101 eyes of 99 patients (65% male, average age 47.2 years) were identified. Oil tamponade had been used for retinal detachment (RD) repair in all eyes; 15 eyes had also undergone an open globe repair previously. The most common vitreous substitutes used after oil removal were balanced salt solution (BSS) and air in 90% of eyes. The average time of oil tamponade before removal was 9.46 months. The average logMAR VA before oil removal was 1.7 which improved to an average of 1.4 post-operatively. The average IOP pre-operatively was 16.1 mm Hg, which decreased to an average of 14.8 mm Hg post-operatively. Complications after oil removal, included retinal re-detachment (6.9%), hypotony (7.9%), ocular hypertension (12.9%), corneal decompensation (9.9%), CME (2%) and cataract progression (68%). CONCLUSION: This study showed an overall improvement in VA and decrease in IOP after oil removal. Cataract progression was the most common complication.

19.
J Hazard Mater ; 384: 121239, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31574384

RESUMO

Incorporating bioaccessibility into human health risk assessment is recognized as a valid way to reduce the conservative properties of conventional results, where the total concentration of a contaminant analysed by exhaustive chemical extraction is applied. Taking a coke production site in Beijing as an example, a mild chemical extraction technology was employed to profile the bioaccessibility of benzo[a]pyrene (BaP), indeno[1,2,3-cd]pyrene (IcP) and dibenz[ah]anthracene (DBA) in soils. The results that were regressed using two bi-phase desorption models (Karickhoff and Weibull) revealed that the rapid desorption fractions of BaP, IcP and DBA, which are taken for bioaccessible fractions, were basically less than half of the total contents in the soils. Probabilistic analysis (PA) was carried out with pre-set distributions of the exposure parameters to characterize the uncertainty in the assessment. The results incorporating bioaccessibility and PA were several times higher than the generic remediation goals which equal to national screening levels, and orders of magnitude higher than the baselines of the region and nation. The results of the Weibull fit were finally recommended as site-specific remediation goals (SSRGs) (10.59 mg/kg, 95.48 mg/kg and 9.24 mg/kg). Over-remediation was avoided while contributing to considerable economic and environmental benefits.

20.
Injury ; 51(2): 466-472, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31839426

RESUMO

PURPOSE: To evaluate intraoperative and early postoperative clinical outcomes using the Nice knot as an auxiliary reduction technique in displaced comminuted patellar fractures. METHODS: Thirty-nine patients with unilateral closed displaced comminuted patellar fractures received open reduction and internal fixation (ORIF), utilizing either Nice knot (the NK group, 24 patients) or traditional reduction (the TR group, 23 patients) techniques, were retrospectively reviewed in this study. Intra-operative surgical time and peri-operative hemoglobin were recorded. Post-operative clinical outcomes were measured using visual analgesic score, range of motion of the knee joint and the Böstman scales, and radiographic outcomes were used to evaluate fracture healing. Complications including infection, bone non-union, implant loosening, fragment displacement and painful hardware were also assessed. RESULTS: In-hospital records indicated significantly shorter surgical duration (32.6 min) in the NK group than in the TR group (63.9 min). Intraoperative blood loss was also significantly decreased in the NK group (64.7 ml) compared to the TR group (189.1 ml). Patients in the NK and TR groups were followed for mean of 12.9 months and 12.5 months respectively. The union rate was 100% (24/24) in the NK group and 91.3% (21/23) in the TR group. In the TR group, there were two non-unions, including one infected non-union. There was no difference in the visual analgesic score, the range of motion of the knee joint or the Böstman scale at last follow-up between the two groups. CONCLUSION: The sliding, self-stabilizing Nice knot was associated with reduced surgical time, decreased intraoperative blood loss, and satisfactory postoperative outcomes in the treatment of displaced patellar fractures. Future studies are needed to ensure the generalizability of these findings to additional patient populations at other institutions.

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