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1.
Neural Plast ; 2020: 6872508, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32399026

RESUMO

Diabetic retinopathy (DR) patients are at an increased risk of cognitive decline and dementia. There is accumulating evidence that specific functional and structural architecture changes in the brain are related to cognitive impairment in DR patients. However, little is known regarding whether the functional architecture of resting-state networks (RSNs) changes in DR patients. The purpose of this study was to investigate the intranetwork functional connectivity (FC) and functional network connectivity (FNC) of RSN changes in DR patients using independent component analysis (ICA). Thirty-four DR patients (18 men and 16 women; mean age, 53.53 ± 8.67 years) and 38 nondiabetic healthy controls (HCs) (15 men and 23 women; mean age, 48.63 ± 11.83 years), closely matched for age, sex, and education, underwent resting-state magnetic resonance imaging scans. ICA was applied to extract the nine RSNs. Then, two-sample t-tests were conducted to investigate different intranetwork FCs within nine RSNs between the two groups. The FNC toolbox was used to assess interactions among RSNs. Pearson correlation analysis was conducted to explore the relationship between intranetwork FCs and clinical variables in the DR group. A receiver operating characteristic (ROC) curve was conducted to assess the ability of the intranetwork FCs of RSNs in discriminating between the two groups. Compared to the HC group, DR patients showed significant decreased intranetwork FCs within the basal ganglia network (BGN), visual network (VN), ventral default mode network (vDMN), right executive control network (rECN), salience network (SN), left executive control network (lECN), auditory network (AN), and dorsal default mode network (dDMN). In addition, FNC analysis showed increased VN-BGN, VN-vDMN, VN-dDMN, vDMN-lECN, SN-BGN, lECN-dDMN, and AN-BGN FNCs in the DR group, relative to the HC group. Furthermore, altered intranetwork FCs of RSNs were significantly correlated with the glycosylated hemoglobin (HbA1c) level in DR patients. A ROC curve showed that these specific intranetwork FCs of RSNs discriminated between the two groups with a high degree of sensitivity and specificity. Our study highlighted that DR patients had widespread deficits in both low-level perceptual and higher-order cognitive networks. Our results offer important insights into the neural mechanisms of visual loss and cognitive decline in DR patients.

2.
Anal Chim Acta ; 1118: 52-62, 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32418604

RESUMO

We have designed and synthesized a new luminescent mononuclear samarium (III) complex Sm-2h based on the [1 + 1] Schiff-base macrocycle H2L2h, derived from the cyclocondensation reaction between dialdehyde and diamine precursors, and its exact architecture is determined to be [Sm(HL2h) (NO3)2]. The sensing ability of complex Sm-2h is carefully evaluated for various common inorganic ions in solution. It is shown that complex Sm-2h is a multi-responsive fluorimetric sensor with high selectivity for F- and PO43- anions together with Zn2+ cation. The sensing process is rapid within 60 s for F- and PO43- ions and 300 s for Zn2+ ion. Further detailed responsive investigations suggest that its sensing behavior has excellent linear relationship between the fluorescence intensity (or absorption value) and ion concentration. The limit of detection (LOD) for sensing F-, PO43- and Zn2+ ions are as low as 2.61 µM (2.94 µM), 1.92 µM (1.64 µM) and 5.67 µM (3.53 µM), respectively, verified by fluorimetric (or colorimetric) titration experiments. ESI mass spectra prove that these efficient detections originate from the structure collapse of sensor Sm-2h because of the ion-induced imine bond breakage. Moreover, sensor Sm-2h shows excellent sensing performances for F-, PO43- and Zn2+ ions in real water samples, and we also have developed a convenient method to detect these three ions by use of the sensor impregnated test paper strips, providing rapid and distinguishable fluorimetric color changes. Therefore, the macrocyclic Sm(III) complex Sm-2h could be regarded as a valuable candidate for monitoring F-, PO43- and Zn2+ ions in practical applications.

3.
Biosci Rep ; 40(5)2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32364220

RESUMO

Choroideremia is a complex form of blindness-causing retinal degeneration. The aim of the present study was to investigate the pathogenic variant and molecular etiology associated with choroideremia in a Chinese family. All available family members underwent detailed ophthalmological examinations. Whole exome sequencing, bioinformatics analysis, Sanger sequencing, and co-segregation analysis of family members were used to validate sequencing data and confirm the presence of the disease-causing gene variant. The proband was diagnosed with choroideremia on the basis of clinical manifestations. Whole exome sequencing showed that the proband had a hemizygous variant in the CHM gene, c.22delG p. (Glu8Serfs*4), which was confirmed by Sanger sequencing and found to co-segregate with choroideremia. The variant was classified as likely pathogenic and has not previously been described. These results expand the spectrum of variants in the CHM gene, thus potentially enriching the understanding of the molecular basis of choroideremia. Moreover, they may provide insight for future choroideremia diagnosis and gene therapy.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32428290

RESUMO

In December 2019, an outbreak of a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in Wuhan, Hubei Province, China. This virus strain causes the respiratory illness coronavirus disease 2019 (COVID-19). Despite significant research efforts in this field, there is limited data on COVID-19 in pregnancy. This article presents a case of a pregnant woman from Wuhan infected with SARS-CoV-2, including her symptoms, pregnancy outcome, and treatment strategy.

5.
Nat Struct Mol Biol ; 27(4): 382-391, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32251414

RESUMO

The bestrophin family of calcium (Ca2+)-activated chloride (Cl-) channels, which mediate the influx and efflux of monovalent anions in response to the levels of intracellular Ca2+, comprises four members in mammals (bestrophin 1-4). Here we report cryo-EM structures of bovine bestrophin-2 (bBest2) bound and unbound by Ca2+ at 2.4- and 2.2-Å resolution, respectively. The bBest2 structure highlights four previously underappreciated pore-lining residues specifically conserved in Best2 but not in Best1, illustrating the differences between these paralogs. Structure-inspired electrophysiological analysis reveals that, although the channel is sensitive to Ca2+, it has substantial Ca2+-independent activity for Cl-, reflecting the opening at the cytoplasmic restriction of the ion conducting pathway even when Ca2+ is absent. Moreover, the ion selectivity of bBest2 is controlled by multiple residues, including those involved in gating.

6.
PLoS One ; 15(4): e0228760, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32348304

RESUMO

Accurate RNA quantification at the single-cell level is critical for understanding the dynamics of gene expression and regulation across space and time. Single molecule FISH (smFISH), such as RNAscope, provides spatial and quantitative measurements of individual transcripts, therefore, can be used to explore differential gene expression among a heterogeneous cell population if combined with cell identify information. However, such analysis is not straightforward, and existing image analysis pipelines cannot integrate both RNA transcripts and cellular staining information to automatically output cell type-specific gene expression. We developed an efficient and customizable analysis method, Single-Molecule Automatic RNA Transcription Quantification (SMART-Q), to enable the analysis of gene transcripts in a cell type-specific manner. SMART-Q efficiently infers cell identity information from multiplexed immuno-staining and quantifies cell type-specific transcripts using a 3D Gaussian fitting algorithm. Furthermore, we have optimized SMART-Q for user experiences, such as flexible parameters specification, batch data outputs, and visualization of analysis results. SMART-Q meets the demands for efficient quantification of single-molecule RNA and can be widely used for cell type-specific RNA transcript analysis.

7.
Diabetes Metab Res Rev ; : e3319, 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32233013

RESUMO

BACKGOUND: To figure out whether diabetes is a risk factor influencing the progression and prognosis of 2019 novel coronavirus disease (COVID-19). METHODS: A total of 174 consecutive patients confirmed with COVID-19 were studied. Demographic data, medical history, symptoms and signs, laboratory findings, chest computed tomography (CT) as well the treatment measures were collected and analysed. RESULTS: We found that COVID-19 patients without other comorbidities but with diabetes (n = 24) were at higher risk of severe pneumonia, release of tissue injury-related enzymes, excessive uncontrolled inflammation responses and hypercoagulable state associated with dysregulation of glucose metabolism. Furthermore, serum levels of inflammation-related biomarkers such as IL-6, C-reactive protein, serum ferritin and coagulation index, D-dimer, were significantly higher (P < .01) in diabetic patients compared with those without, suggesting that patients with diabetes are more susceptible to an inflammatory storm eventually leading to rapid deterioration of COVID-19. CONCLUSIONS: Our data support the notion that diabetes should be considered as a risk factor for a rapid progression and bad prognosis of COVID-19. More intensive attention should be paid to patients with diabetes, in case of rapid deterioration.

9.
Sci Adv ; 6(11): eaay3240, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32195345

RESUMO

Seeds of the desert shrub, jojoba (Simmondsia chinensis), are an abundant, renewable source of liquid wax esters, which are valued additives in cosmetic products and industrial lubricants. Jojoba is relegated to its own taxonomic family, and there is little genetic information available to elucidate its phylogeny. Here, we report the high-quality, 887-Mb genome of jojoba assembled into 26 chromosomes with 23,490 protein-coding genes. The jojoba genome has only the whole-genome triplication (γ) shared among eudicots and no recent duplications. These genomic resources coupled with extensive transcriptome, proteome, and lipidome data helped to define heterogeneous pathways and machinery for lipid synthesis and storage, provided missing evolutionary history information for this taxonomically segregated dioecious plant species, and will support efforts to improve the agronomic properties of jojoba.

10.
Mol Genet Genomic Med ; 8(3): e1131, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31960602

RESUMO

BACKGROUND: This study aimed to identify the gene variants and molecular etiologies in 76 unrelated Chinese families with retinitis pigmentosa (RP). METHODS: In total, 76 families with syndromic or nonsyndromic RP, diagnosed on the basis of clinical manifestations, were recruited for this study. Genomic DNA samples from probands were analyzed by targeted panels or whole exome sequencing. Bioinformatics analysis, Sanger sequencing, and available family member segregation were used to validate sequencing data and confirm the identities of disease-causing genes. RESULTS: The participants enrolled in the study included 62 families that exhibited nonsyndromic RP, 13 that exhibited Usher syndrome, and one that exhibited Bardet-Biedl syndrome. We found that 43 families (56.6%) had disease-causing variants in 15 genes, including RHO, PRPF31, USH2A, CLRN1, BBS2, CYP4V2, EYS, RPE65, CNGA1, CNGB1, PDE6B, MERTK, RP1, RP2, and RPGR; moreover, 12 families (15.8%) had only one heterozygous variant in seven autosomal recessive RP genes, including USH2A, EYS, CLRN1, CERKL, RP1, CRB1, and SLC7A14. We did not detect any variants in the remaining 21 families (27.6%). We also identified 67 potential pathogenic gene variants, of which 24 were novel. CONCLUSION: The gene variants identified in this study expand the variant frequency and spectrum of RP genes; moreover, the identification of these variants supplies foundational clues for future RP diagnosis and therapy.

11.
Curr Med Chem ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31942844

RESUMO

1-Deoxynojirimycin (1-DNJ) is a naturally occurred sugar analogue with unique bioactivities. It was found in mulberry leaves and silkworms, as well as in the metabolites of certain microorganisms, including Streptomyces and Bacillus. 1-DNJ is a potent α-glucosidase inhibitor and it possesses anti-hyperglycemic, anti-obese, anti-viral and anti-tumor features. Some derivatives of 1-DNJ, like miglitol, miglustat and migalastat, were applied clinically to treat diseases such as diabetes and lysosomal storage disorders. The present review focused on the extraction, determination, pharmacokinetics and bioactivity of 1-DNJ, as well as the clinical application of 1-DNJ derivatives.

12.
Nucleic Acids Res ; 48(1): 86-95, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31777938

RESUMO

Clustering is an essential step in the analysis of single cell RNA-seq (scRNA-seq) data to shed light on tissue complexity including the number of cell types and transcriptomic signatures of each cell type. Due to its importance, novel methods have been developed recently for this purpose. However, different approaches generate varying estimates regarding the number of clusters and the single-cell level cluster assignments. This type of unsupervised clustering is challenging and it is often times hard to gauge which method to use because none of the existing methods outperform others across all scenarios. We present SAME-clustering, a mixture model-based approach that takes clustering solutions from multiple methods and selects a maximally diverse subset to produce an improved ensemble solution. We tested SAME-clustering across 15 scRNA-seq datasets generated by different platforms, with number of clusters varying from 3 to 15, and number of single cells from 49 to 32 695. Results show that our SAME-clustering ensemble method yields enhanced clustering, in terms of both cluster assignments and number of clusters. The mixture model ensemble clustering is not limited to clustering scRNA-seq data and may be useful to a wide range of clustering applications.

13.
Ann Hum Genet ; 84(2): 177-184, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31674661

RESUMO

OBJECTIVE: The aim of this study was to investigate pathogenic variants and molecular etiologies of Stargardt disease (STGD) in a cohort of Chinese families. MATERIALS AND METHODS: A cohort of 12 unrelated STGD families diagnosed on the basis of clinical manifestations underwent analysis by targeted exome or whole-exome sequencing. Bioinformatics analysis, Sanger sequencing, and cosegregation analysis of available family members were used to validate sequencing data and confirm the presence of disease-causing genes. RESULTS: Using targeted exome and whole-exome sequencing, we found that eight families had disease-causing variants in the ABCA4 gene, one family had only one heterozygous variant in the ABCA4 gene, and the remaining three families have not been identified with any disease-causing variants for STGD. We identified 15 variants in the ABCA4 gene; of these, five variants have not been previously described for STGD. CONCLUSION: The findings in this study expand the data regarding the frequency and spectrum of variants in the ABCA4 gene, thus potentially enriching our understanding of the molecular basis of STGD. Moreover, they constitute clues for future STGD diagnosis and therapy.

14.
Cell Death Dis ; 10(12): 905, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31787761

RESUMO

Progressive degeneration of retinal ganglion cells (RGCs) will cause a blinding disease. Most of the study is focusing on the RGCs itself. In this study, we demonstrate a decline of the presynaptic rod bipolar cells (RBCs) response precedes RGCs loss and a decrease of protein kinase Cα (PKCα) protein expression in RBCs dendrites, using whole-cell voltage-clamp, electroretinography (ERG) measurements, immunostaining and co-immunoprecipitation. We present evidence showing that N-methyl D-aspartate receptor subtype 2B (NR2B)/protein interacting with C kinase 1 (PICK1)-dependent degradation of PKCα protein in RBCs contributes to RBCs functional loss. Mechanistically, NR2B forms a complex with PKCα and PICK1 to promote the degradation of PKCα in a phosphorylation- and proteasome-dependent manner. Similar deficits in PKCα expression and response sensitivity were observed in acute ocular hypertension and optic never crush models. In conclusion, we find that three separate experimental models of neurodegeneration, often used to specifically target RGCs, disrupt RBCs function prior to the loss of RGCs. Our findings provide useful information for developing new diagnostic tools and treatments for retinal ganglion cells degeneration disease.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31773414

RESUMO

The outbreak of acute hepatopancreatic necrosis disease (AHPND) has caused great economic losses to the shrimp culture sector. However, the use of antibiotics to fight this disease has resulted in negative impacts on human health and the environment. Thus, the use of natural alternatives to antibiotics may be a better solution. In this study, four Bacillus species obtained from the guts of shrimps (Fenneropenaeus penicillatus and Penaeus monodon) showed antimicrobial activity against the AHPND-causing Vibrio parahaemolyticus strain 3HP using the cross-streaking and agar spot methods. Two of the Bacillus isolates, B2 and BT, also showed good probiotic properties, exhibiting tolerance to bile, good adhesion to shrimp mucus, non-hemolytic, susceptibility to antibiotics and being safe towards hosts. Moreover, a seaweed-probiotic blend (a combination of Bacillus B2 and 20 mg/ml of the red seaweed Gracilaria sp.) exhibited synergistic in vitro inhibition against V. parahaemolyticus strain 3HP, with an observed inhibition zone of 5.0 mm. The broth co-culture experiment results further indicated that the seaweed-probiotic blend inhibited V. parahaemolyticus through competitive exclusion. The in vivo challenge trials also confirmed that this seaweed-probiotic blend significantly reduced the mortality of shrimps post-challenge with the AHPND-causing V. parahaemolyticus strain 3HP (p < 0.05) compared to the negative control (mortality rate = 13.88% vs 72.19%). Thus, this seaweed-probiotic blend may serve as an alternative to antibiotics in controlling the outbreak of AHPND.

16.
ACS Omega ; 4(19): 18334-18341, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31720535

RESUMO

Here, we report our trials to regulate the luminescence performance of the macrocyclic samarium(III) complex and prepare four excellent luminescent Sm(III) complex-doped poly(methylmethacrylate) (PMMA) composites. Four 23-membered [1 + 1] Schiff-base macrocyclic mononuclear Sm(III) complexes, Sm-2 a -Sm-2 d , originating from dialdehydes with different pendant arms and 1,2-bis(2-aminoethoxy)ethane, have been constructed by the template method. Crystal structures reveal that every Sm(III) ion with the coordination geometry of a distorted bicapped square antiprism is capsulated by the macrocyclic cavity environment forming the "lasso-type" protection. Relative photophysical properties of macrocyclic Sm(III) complexes are carefully investigated in solid-state, methanol solution, and doped PMMA film, and all these show characteristic emissions of the Sm(III) ion associated with satisfactory lifetimes and quantum yields in all media, which could be comparable to reported outstanding examples. Especially, the luminescence performance for this type of Sm(III) complex could be regulated in the solid state by the use of different functional groups in the pendant arm while it is not achieved in solution and the doped PMMA composite. High emitting and air-stable plastic materials could be obtained when these Sm(III) complexes are doped in PMMA with 0.1 wt % mixing ratio, and the corresponding maximum lifetime and quantum yield are 61.2 µs and 0.63% in the case of complex Sm-2 a , respectively. We believe that these highly luminescent "lasso-type" Sm(III) complexes and doped PMMA composites are valuable references in the design of luminescent lanthanide(III) hybrid materials.

17.
Neuropsychiatr Dis Treat ; 15: 2487-2502, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695385

RESUMO

Objective: There is increasing neuroimaging evidence that type 2 diabetes patients with retinal microvascular complications show abnormal brain functional and structural architecture and are at an increased risk of cognitive decline and dementia. However, changes in the topological properties of the functional brain connectome in diabetic retinopathy (DR) patients remain unknown. The aim of this study was to explore the topological organization of the brain connectome in DR patients using graph theory approaches. Methods: Thirty-five DR patients (18 males and 17 females) and 38 healthy controls (HCs) (18 males and 20 females), matched for age, sex, and education, underwent resting-state magnetic resonance imaging scans. Graph theory analysis was performed to investigate the topological properties of brain functional connectome at both global and nodal levels. Results: Both DR and HC groups showed high-efficiency small-world network in their brain functional networks. Notably, the DR group showed reduction in the clustering coefficient (P=0.0572) and local efficiency (P=0.0151). Furthermore, the DR group showed reduced nodal centralities in the default-mode network (DMN) and increased nodal centralities in the visual network (VN) (P<0.01, Bonferroni-corrected). The DR group also showed abnormal functional connections among the VN, DMN, salience network (SN), and sensorimotor network (SMN). Altered network metrics and nodal centralities were significantly correlated with visual acuity and fasting blood glucose level in DR patients. Conclusion: DR patients showed abnormal topological organization of the human brain connectome. Specifically, the DR group showed reduction in the clustering coefficient and local efficiency, relative to HC group. Abnormal nodal centralities and functional disconnections were mainly located in the DMN, VN, SN, and SMN in DR patients. Furthermore, the disrupted topological attributes showed correlations with clinical variables. These findings offer important insight into the neural mechanism of visual loss and cognitive deficits in DR patients.

18.
Exp Eye Res ; 189: 107826, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31586450

RESUMO

PURPOSE: To investigate the potential protective effect of novel G protein coupled estrogen receptor (GPER1) against the neurotoxicity induced by NMDA in the mouse retina. METHODS: We induce retinal ganglion cells (RGCs) toxic injury through intravitreal injection of NMDA or acute ocular hypertension (AOH) induced by anterior chamber infusion with saline. Endogenous ligand 17-ß-estradiol (E2), GPER1 agonist (G-1), and E2 with GPER1 antagonist (G-15) or classic estrogen receptor α and ß (ERα and ERß) antagonist tamoxifen (TAM) were subcutaneous administered before NMDA to identify the possible involved receptors. Immunofluorescence staining was performed to explore the survival of RGCs and Müller cell gliosis. TUNEL staining was used to evaluate the RGC apoptosis. The involved molecular pathway was detected via antibody array expression profiling. RESULTS: Activation of estrogen receptor by E2 or G-1 could significantly rescue the RGCs injury in NMDA administration. The protective effect was carried exclusively by GPER1 activation. E2 application can still mimicked the protective function when estrogen receptor α and ß (ERα and ERß) blocked by tamoxifen (TAM), while the effects was blocked by GPER1 antagonist G-15. Moreover, the TUNEL positive RGCs and GFAP expression level were both attenuated in G-1 application and the effects could be reversed by G-15. In addition, application of the PI3K/Akt antagonist LY294002 counteracted the effect of G-1. And a number of apoptosis regulatory factors decreased dramatically in the G-1 group, including Bad, Caspase 3, Caspase 7, Smad2, P-53 and TAK1. Also, similar protective effect of G-1 was spotted in acute ocular hypertension (AOH) model. CONCLUSION: Estrogen played a protective role via a novel estrogen receptor, GPER1, instead of classical receptors ERα or ERß. Activation of GPER1 attenuated RGCs apoptosis and Müller cells gliosis, indicating GPER1 as a potential treatment target in RGCs degeneration diseases.


Assuntos
Regulação da Expressão Gênica , RNA/genética , Receptores Estrogênicos/genética , Receptores Acoplados a Proteínas-G/genética , Degeneração Retiniana/genética , Células Ganglionares da Retina/metabolismo , Tamoxifeno/farmacologia , Animais , Apoptose , Western Blotting , Modelos Animais de Doenças , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , N-Metilaspartato/toxicidade , RNA/metabolismo , Receptores Estrogênicos/biossíntese , Receptores Estrogênicos/efeitos dos fármacos , Receptores Acoplados a Proteínas-G/biossíntese , Receptores Acoplados a Proteínas-G/efeitos dos fármacos , Degeneração Retiniana/tratamento farmacológico , Degeneração Retiniana/metabolismo , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/patologia , Moduladores Seletivos de Receptor Estrogênico/farmacologia
20.
Curr Alzheimer Res ; 16(7): 659-674, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31580243

RESUMO

Alzheimer's disease is the world's most common dementing illness. It is pathologically characterized by ß-amyloid accumulation, extracellular senile plaques and intracellular neurofibrillary tangles formation, and neuronal necrosis and apoptosis. Neuroinflammation has been widely recognized as a crucial process that participates in AD pathogenesis. In this review, we briefly summarized the involvement of microglia in the neuroinflammatory process of Alzheimer's disease. Its roles in the AD onset and progression are also discussed. Numerous molecules, including interleukins, tumor necrosis factor alpha, chemokines, inflammasomes, participate in the complex process of AD-related neuroinflammation and they are selectively discussed in this review. In the end of this paper from an inflammation- related perspective, we discussed some potential therapeutic choices.

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