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1.
Cereb Cortex ; 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32080708

RESUMO

The corpus callosum is the commissural bridge of white-matter bundles important for the human brain functions. Previous studies have analyzed the structural links between cortical gray-matter networks and subregions of corpus callosum. While meaningful white-matter functional networks (WM-FNs) were recently reported, how these networks functionally link with distinct subregions of corpus callosum remained unknown. The current study used resting-state functional magnetic resonance imaging of the Human Connectome Project test-retest data to identify 10 cerebral WM-FNs in 119 healthy subjects and then parcellated the corpus callosum into distinct subregions based on the functional connectivity between each callosal voxel and above networks. Our results demonstrated the reproducible identification of WM-FNs and their links with known gray-matter functional networks across two runs. Furthermore, we identified reliably parcellated subregions of the corpus callosum, which might be involved in primary and higher order functional systems by functionally connecting with WM-FNs. The current study extended our knowledge about the white-matter functional signals to the intrinsic functional organization of human corpus callosum, which could help researchers understand the neural substrates underlying normal interhemispheric functional connectivity as well as dysfunctions in various mental disorders.

2.
Appl Microbiol Biotechnol ; 104(4): 1609-1619, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31900556

RESUMO

The emergence of antibiotic-resistant beta-hemolytic Streptococcus agalactiae strains poses increasing threat to human beings globally. As an attempt to create a novel lysin with improved activity against S. agalactiae, a chimeric lysin, ClyV, was constructed by fusing the enzymatically active domain (EAD) from PlyGBS lysin (GBS180) and the cell wall binding domain (CBD) from PlyV12 lysin (V12CBD). Plate lysis assay combined with lytic kinetic analysis demonstrated that ClyV has improved activity than its parental enzymatic domain GBS180 against multiple streptococci. Biochemical characterization showed that ClyV is active from pH 7 to 10, with the optimum pH of 9, and is stable under NaCl concentration of < 500 mM. In a S. agalactiae infection model, a single intraperitoneally administration of 0.1 mg/mouse of ClyV protected 100% mice, while it was observed that ~ 29% survive in group that received a single dose of 0.1 mg/mouse of GBS180. Moreover, a high dose of 0.8 mg/mouse ClyV did not show any adverse effects to the health or survival rate of the mice. Considering the robust bactericidal activity and good safety profile of ClyV, it represents a potential candidate for the treatment of S. agalactiae infections.

3.
Stem Cell Res ; 42: 101690, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31901832

RESUMO

The human induced pluripotent stem cell line NCCDFWi001-A was derived from peripheral blood mononuclear cells (PBMC) of a 26-year-old female Marfan syndrome patient carrying two compound heterozygous variants FBN1c.2613A > C, (p.Leu871Phe) and c.684_736 + 4del. The established patient-derived iPSC showed expression of pluripotent stem cell markers and had the ability to differentiate into all of the three germ layers and possessed a normal karyotype.

4.
Orphanet J Rare Dis ; 15(1): 6, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31915033

RESUMO

BACKGROUND: Loeys-Dietz syndrome (LDS) is a rare connective tissue disorder for which 6 genes in the TGF-ß pathway have been identified as causative. With the widespread use of genetic testing, the range of known clinical and genetic profiles has broadened, but these features have not been fully elucidated thus far. METHODS AND RESULTS: Using gene panel sequencing or whole exome sequencing, we identified 54 unique rare variants in LDS genes in 57 patients with thoracic aneurysms/dissections, including 27 pathogenic mutations (P + LP) and 27 variants of unknown significance (VUSLP + VUS). Genotype-phenotype correlation analysis revealed that carriers with P/LP/ VUSLP variants in TGFBR1/TGFBR2/SMAD3 genes had significantly more severe cardiovascular features (cardiovascular death/dissection) than carriers with VUSs in these 3 genes at an early age and had less favorable event-free survival. Additionally, carriers with VUS in combination with other risk factors, such as hypertension, might be prone to developing an aortic dissection, as indicated by the fact that 5/8 (62.5%) patients with VUSs in our cohort developed aortic dissections in the presence of hypertension, compared with 25.0% (3/12) in the absence of hypertension (p = 0.047). CONCLUSIONS: To date, this was the largest cohort of LDS patients ever reported in China, and the present study expanded the known mutation and phenotypic spectra of LDS, which might help refine our knowledge of LDS.

5.
Neuropsychologia ; 138: 107343, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-31952981

RESUMO

Developmental dyslexia is known to involve dysfunctions in multiple brain regions; however, a clear understanding of the brain networks behind this disorder is still lacking. The present study examined the functional network connectivity in Chinese dyslexic children with resting-state electroencephalography (EEG) recordings. EEG data were recorded from 27 dyslexic children and 40 age-matched controls, and a minimum spanning tree (MST) analysis was performed to examine the network connectivity in the delta, theta, alpha, and beta frequency bands. The results show that, compared to age-matched controls, Chinese dyslexic children had global network deficiencies in the beta band, and the network topology was more path-like. Moderate correlations are observed between MST degree metric and rapid automatized naming and morphological awareness tests. These observations, together with the findings in alphabetic languages, show that brain network deficiency is a common neural underpinning of dyslexia across writing systems.

6.
Pharmacol Res ; 153: 104657, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31982488

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and constitutes a major risk factor for progression to cirrhosis, liver failure and hepatocellular carcinoma (HCC). The occurrence of NAFLD is closely associated with abnormal lipid metabolism and implies a high risk of type 2 diabetes and cardiovascular disease. Therefore, specific and effective drugs for the prevention and treatment of NAFLD are necessary. Hypericin (HP) is one of the main active ingredients of Hypericum perforatum L., and we previously revealed its protective role in islet ß-cells and its effects against type 2 diabetes. In this study, we aimed to explore the preventive and therapeutic effects of HP against NAFLD and the underlying mechanisms in vitro and in vivo. Here, we demonstrated that HP improved cell viability by reducing apoptosis and attenuated lipid accumulation in hepatocytes both in vitro and in vivovia attenuating oxidative stress, inhibiting lipogenesis and enhancing lipid oxidization. Thus, HP exhibited significant preventive and therapeutic effects against HFHS-induced NAFLD and dyslipidemia in mice. Furthermore, we demonstrated that HP directly bound to PKACα and activated PKA/AMPK signaling to elicit its effects against NAFLD, suggesting that PKACα is one of the drug targets of HP. In addition, the enhancing effect of HP on lipolysis in adipocytes through the activation of PKACα was also elucidated. Together, the conclusions indicated that HP, of which one of the targets is PKACα, has the potential to be used as a preventive or therapeutic drug against NAFLD or abnormal lipid metabolism in the future.

7.
Cells ; 9(1)2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31940841

RESUMO

Activation of hepatic macrophages represents the critical driving force to promote cholestatic liver injury. Exosomes, as important small extracellular vesicles released by almost all types of cells, contribute to intercellular communication. We previously reported that cholangiocyte-derived exosomal long noncoding RNA (lncRNA) H19 plays a vital role in disrupting bile acid homeostasis in hepatocytes and promoting the activation of hepatic stellate cells (HSCs). Exosomal H19 derived from cholangiocytes was rapidly taken up by Kupffer cells. However, the mechanistic links between exosomal lncRNA H19 and macrophage-driven inflammation in cholestasis remain unclear. Here, we reported that the hepatic H19 level was closely correlated with macrophage activation and hepatic fibrosis in both Mdr2-/- and bile duct ligation (BDL) cholestatic mouse models, as well as in human primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) patients. Exosomal H19 significantly induced the expression and secretion of chemokine (C-C motif) ligand 2 (CCL-2) and interleukin 6 (IL-6) in Kupffer cells. H19-enriched exosomes enhanced the activation M1 polarization of Kupffer cells and promoted the recruitment and differentiation of bone marrow-derived macrophages, which were inhibited by a CCL-2 pharmacological inhibitor. In conclusion, Cholangiocyte-derived exosomal H19 played a critical role in macrophage activation, differentiation, and chemotaxis through CCL-2/CCR-2 signaling pathways, which represent a therapeutic target for cholestatic liver diseases.

8.
Antimicrob Agents Chemother ; 64(2)2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31767724

RESUMO

Streptococcus pneumoniae is a leading human pathogen uniquely characterized by choline moieties on the bacterial surface. Our previous work reported a pneumococcus-specific chimeric lysin, ClyJ, which combines the CHAP (cysteine, histidine-dependent amidohydrolase/peptidase) enzymatically active domain (EAD) from the PlyC lysin and the cell wall binding domain (CBD) from the phage SPSL1 lysin, which imparts choline binding specificity. Here, we demonstrate that the lytic activity of ClyJ can be further improved by editing the linker sequence adjoining the EAD and CBD. Keeping the net charge of the linker constant, we constructed three ClyJ variants containing different lengths of linker sequence. Circular dichroism showed that linker editing has only minor effects on the folding of the EAD and CBD. However, thermodynamic examination combined with biochemical analysis demonstrated that one variant, ClyJ-3, with the shortest linker, displayed improved thermal stability and bactericidal activity, as well as reduced cytotoxicity. In a pneumococcal mouse infection model, ClyJ-3 showed significant protective efficacy compared to that of the ClyJ parental lysin or the Cpl-1 lysin, with 100% survival at a single ClyJ-3 intraperitoneal dose of 100 µg/mouse. Moreover, a ClyJ-3 dose of 2 µg/mouse had the same efficacy as a ClyJ dose of 40 µg/mouse, suggesting a 20-fold improvement in vivo Taking these results together, the present study not only describes a promising pneumococcal lysin with improved potency, i.e., ClyJ-3, but also implies for the first time that the linker sequence plays an important role in determining the activity of a chimeric lysin, providing insight for future lysin engineering studies.

9.
J Colloid Interface Sci ; 563: 218-228, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31874309

RESUMO

Designing highly efficient, recyclable and environmentally friendly adsorbent for the removal of heavy metal ions from wastewater plays a key role in sewage treatment system. In this study, a magnetic Fe3O4@MnO2 core-shell nanoflower attached to Aspergillus niger carbon microtube was developed as a perfect adsorbent for the removal of Pb2+ from water solution. Benefiting from the synergistic effect of high adsorption capacity of metal oxides, magnetism of Fe3O4 and large size of Aspergillus niger carbon, the synthesized adsorbent achieves an extremely high adsorption capacity of 934 mg/g and a faster adsorption speed of 5 min, which is a splendid performance among reported adsorbent of Pb2+ from water solution. Supported by FTIR spectra, a large amount of carbon dioxide and hydroxyl groups were proved to exist on the surface of the Fe3O4@MnO2/CT, where the functional groups with negative charges play a key role in facilitating the interface adsorption process. Moreover, the amorphous magnetically adsorbent with a size of about 300 nm have a specific surface area of 151 m2/g and the high saturation magnetization of the adsorbent is highly beneficial to the re-recovery of the adsorbent. After five cycles of testing, the adsorbent can still guarantee a maximum saturated adsorption capacity of more than 86%. The lead element is adsorbed on the surface of the adsorbent in the form of basic lead carbonate, which suggests that the basic adsorption mechanism is chemical adsorption.

10.
Nanoscale Res Lett ; 14(1): 371, 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31820137

RESUMO

The near-infrared (NIR) photoelectric properties of multilayer Bi2O2Se nanofilms were systematically studied in this paper. Multilayer Bi2O2Se nanofilms demonstrate a sensitive photo response to NIR, including a high photoresponsivity (~ 101 A/W), a quick response time (~ 30 ms), a high external quantum efficiency (~ 20,300%), and a high detection rate (1.9 × 1010 Jones). These results show that the device based on multilayer Bi2O2Se nanofilms might have great potentials for future applications in ultrafast, highly sensitive NIR optoelectronic devices.

11.
J Control Release ; 317: 195-215, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31794799

RESUMO

In recent years, nanomedicines have emerged as a promising method for central nervous system drug delivery, enabling the drugs to overcome the blood-brain barrier and accumulate preferentially in the brain. Despite the current success of brain-targeted nanomedicines, limitations still exist in terms of the targeting specificity. Based on the molecular mechanism, the exact cell populations and subcellular organelles where the injury occurs and the drugs take effect have been increasingly accepted as a more specific target for the next generation of nanomedicines. Dual and multi-targeted nanoparticles integrate different targeting functionalities and have provided a paradigm for precisely delivering the drug to the pathological site inside the brain. The targeting process often involves the sequential or synchronized navigation of the targeting moieties, which allows highly controlled drug delivery compared to conventional targeting strategies. Herein, we focus on the up-to-date design of pathological site-specific nanoparticles for brain drug delivery, highlighting the dual and multi-targeting strategies that were employed and their impact on improving targeting specificity and therapeutic effects. Furthermore, the background discussion of the basic properties of a brain-targeted nanoparticle and the common lesion features classified by neurological pathology are systematically summarized.

12.
Adv Mater ; 31(52): e1904601, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31721329

RESUMO

The use of a ternary active layer offers a promising approach to enhance the power conversion efficiency (PCE) of polymer solar cells (PSCs) via simply incorporating a third component. Here, a ternary PSC with improved efficiency and stability facilitated by a new small molecule IBC-F is demonstrated. Even though the PBDB-T:IBC-F-based device gives an extremely low PCE of only 0.21%, a remarkable PCE of 15.06% can be realized in the ternary device based on PBDB-T:IE4F-S:IBC-F with 20% IBC-F, which is ≈10% greater than that (PCE = 13.70%) of the control binary device based on PBDB-T:IE4F-S. The improvement in the device performance of the ternary PSC is mainly attributed to the enhancement of fill factor, which is due to the improved charge dissociation and extraction, suppressed bimolecular and trap-assisted recombination, longer charge-carrier lifetime, and enhanced intermolecular interactions for preferential face-on orientation. Additionally, the ternary device with 20% IBC-F shows better thermal and photoinduced stability over the control binary device. This work provides a new angle to develop the third components for building ternary PSCs with enhanced photovoltaic performance and stability for practical applications.

13.
Nanoscale ; 11(46): 22440-22445, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31746893

RESUMO

High-throughput growth of large size transition metal dichalcogenide (TMD) single crystals is an important challenge for their applications in the next generation electronic and optoelectronic integration devices. Here we report the high-throughput growth of submillimeter monolayer TMD single crystals by two-stage space confined chemical vapor deposition, where the nucleation density of TMD crystals is significantly decreased for the growth of large size monolayer crystals by the space confinement effect. Moreover, high-throughput growth of submillimeter TMD crystals is also achieved by stacking the substrates along the perpendicular direction to the flow of the reaction gases. The mobilities of the TMD materials produced in this way are up to 1.2, 17.0 and 25.0 cm2 (V s)-1 for monolayer WS2, WSe2 and MoS2 single crystals, respectively. The results demonstrate that two-stage space confined growth is a highly promising method for high-throughput fabrication of high-quality submillimeter monolayer TMD single crystals, which will pave a new pathway to large-scale production of TMD-based electronic and optoelectronic devices.

14.
Clin Gerontol ; : 1-10, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31603051

RESUMO

Objectives: Older adults are disproportionately vulnerable to frauds of many kinds, and fear of aging has been conjectured to be a primary factor in older adults' vulnerability to fraud; however, no study has examined how and when fear of aging is associated with older adults' vulnerability to fraud. Methods: In this cross-sectional study, a sample of 251 Chinese older adults (M = 68.1, SD = 6.43) completed measures regarding fear of aging, intolerance of uncertainty, self-control, and vulnerability to fraud. Results: The results revealed that intolerance of uncertainty partially mediated the association between fear of aging and vulnerability to fraud. This indirect effect of fear of aging on vulnerability to fraud was only significant for older adults with lower levels of self-control. Conclusions: The association between fear of aging and older adults' vulnerability to fraud through intolerance of uncertainty varies as a function of self-control. Clinical implications: Clinicians may focus on reducing the fear of aging, decreasing intolerance of uncertainty, and enhancing self-control as promising pathways to develop effective interventions and outreach strategies aimed at protecting older adults from fraud.

15.
ACS Appl Mater Interfaces ; 11(43): 40339-40346, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31603307

RESUMO

Constructing random copolymers has been regarded as an easy and effective approach to design polymer donors for state-of-the-art polymer solar cells (PSCs). In this work, we develop a naphtho[2,3-c]thiophene-4,9-dione-based copolymer PBN-Cl as a donor material for PSCs, and a moderate power conversion efficiency (PCE) of 11.21% is achieved with a relatively low fill factor (FF) of 0.615. We then incorporate a similar acceptor unit benzo[1,2-c:4,5-c']dithiophene-4,8-dione (BDD) into the polymeric backbone of PBN-Cl to tune its photovoltaic performance, and a significantly higher PCE of 14.05% is achieved from the random polymer PBN-Cl-B80 containing 80% BDD unit. The enhanced PCE of the PBN-Cl-B80-based device mainly relies on the higher FF value, resulting from the improved charge mobility properties, reduced bimolecular and trap-assisted recombination, and more appropriate phase separation. The results demonstrate a feasible strategy to tune the photovoltaic performance of polymer donors by constructing a random polymer with a compatible component.

16.
Small ; 15(43): e1904482, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31512402

RESUMO

Bi2 O2 Se is emerging as a photosensitive functional material for optoelectronics, and its photodetection mechanism is mostly considered to be a photoconductive regime in previous reports. Here, the bolometric effect is discovered in Bi2 O2 Se photodetectors. The coexistence of photoconductive effect and bolometric effect is generally observed in multiwavelength photoresponse measurements and then confirmed with microscale local heating experiments. The unique photoresponse of Bi2 O2 Se photodetectors may arise from a change of hot electrons during temperature rises instead of photoexcited holes and electrons. Direct proof of the bolometric effect is achieved by real-time temperature tracking of Bi2 O2 Se photodetectors under time evolution after light excitation. Moreover, the Bi2 O2 Se bolometer shows a high temperature coefficient of resistance (-1.6% K-1 ), high bolometric coefficient (-31 nA K-1 ), and high bolometric responsivity (>320 A W-1 ). These findings offer a new approach to develop bolometric photodetectors based on Bi2 O2 Se layered materials.

17.
Sensors (Basel) ; 19(19)2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31547194

RESUMO

Raman spectroscopy visualization is a challenging task due to the interference of complex background noise and the number of selected measurement points. In this paper, a super-resolution image reconstruction algorithm for Raman spectroscopy is studied to convert raw Raman data into pseudo-color super-resolution imaging. Firstly, the Raman spectrum data of a single measurement point is measured multiple times to calculate the mean value to remove the random background noise, and innovatively introduce the Retinex algorithm and the median filtering algorithm which improve the signal-to-noise ratio. The novel method of using deep neural network performs a super-resolution reconstruction operation on the gray image. An adaptive guided filter that automatically adjusts the filter radius and penalty factor is proposed to highlight the contour of the cell, and the super-resolution reconstruction of the pseudo-color image of the Raman spectrum is realized. The average signal-to-noise ratio of the reconstructed pseudo-color image sub-band reaches 14.29 db, and the average value of information entropy reaches 4.30 db. The results show that the Raman-based cell pseudo-color image super-resolution reconstruction algorithm is an effective tool to effectively remove noise and high-resolution visualization. The contrast experiments show that the pseudo-color image Kullback-Leiber (KL) entropy of the color image obtained by the method is small, the boundary is obvious, and the noise is small, which provide technical support for the development of sophisticated single-cell imaging Raman spectroscopy instruments.

18.
Biotechnol Biofuels ; 12: 200, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31452681

RESUMO

Background: Filamentous fungi secret hydrolytic enzymes like cellulase and hemicellulase outside the cells, serving as important scavengers of plant biomass in nature and workhorses in the enzyme industry. Unlike the extensive study on the mechanism of cellulase production in fungi, research on spatiotemporal distribution and secretion of cellulase in fungi is lacking, retarding the deeper understanding of the molecular mechanism behind the fungal cellulase production. Result: Recombinant Trichoderma reesei strains RBGL, RCBH, and RCMC were successfully constructed from T. reesei RUT-C30, expressing red fluorescent protein DsRed-tagged versions of ß-glucosidase (BGL), cellobiohydrolase (CBH), and endoglucanase (CMC), respectively. With the assistance of these strains, we found that all three cellulase components BGL, CBH, and CMC diffused throughout the whole fungal mycelium with major accumulation at the hyphal apexes. These enzymes located in ER, Golgi, vacuoles and cell membrane/wall, but not septum, and secreted abundantly into the culture medium. Moreover, the major secretion of CBH and CMC started more early than that of BGL. Brefeldin A (BFA) completely blocked cellulase expression and secretion in T. reesei. Conclusion: Based on recombinant T. reesei RBGL, RCBH, and RCMC expressing DsRed-fused versions of BGL, CBH, and CMC, respectively, the distribution and secretion of cellulase production in T. reesei were first visualized directly in a dynamic way, preliminarily mapping the location and secretion of T. reesei cellulase and providing evidence for revealing the secretion pathways of cellulase in T. reesei. The obtained results suggest that cellulase excretion majorly occurs via the conventional ER-Golgi secretory pathway, and might be assisted through unconventional protein secretion pathways.

19.
Sci Rep ; 9(1): 10048, 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31296887

RESUMO

We present a two-dimensional (2D) parity-time-symmetric (PT-symmetry) phononic crystals (PCs) with balanced gain and loss medium. Using the super cell method of rectangular lattice, we exhibit the thresholdless spontaneous PT-symmetry breaking in the band structure. The numerical results show that the asymmetric scattering properties obviously occur in a non-Hermitian system. At two specific incident frequencies, unidirectional reflectionless and perfect transmission behaviors exist individually in opposite directions, which are accompanied by a phase transition of π. Based on the generalized Snell's law, combining such a PT-symmetric medium, we design a novel metamaterial crystal for PT-symmetric acoustic flat focusing. Its focus frequency can also be modulated by the gain/loss parameter. The novel flat focusing based on the PT-symmetry that we propose opens a new door for high-dimensional applications of non-Hermitian metamaterials in acoustic wave manipulation.

20.
Nanoscale ; 11(28): 13469-13476, 2019 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-31287485

RESUMO

The realization of p-n homojunctions, which can be achieved via spatially controlled carrier-type modulation, remains a challenge for two-dimensional transition metal dichalcogenides. Here, we report an effective method to tune intrinsic n-type few-layer MoSe2 to p-type through controlling precisely the ultraviolet-ozone treatment time, which can be attributed to the surface charge transfer from the underlying MoSe2 to MoOx (x < 3). The resulting hole mobility and concentration are ∼20.1 cm2 V-1 s-1 and ∼1.9 × 1012 cm-2, respectively, and the on-off ratio is ∼105, which are comparable to the values of pristine n-type MoSe2. Moreover, the lateral p-n homojunction prepared by partially treating MoSe2 displays a high rectification ratio of 2.4 × 104, an ideality factor of 1.1, and a high photoresponsivity of 0.23 A W-1 to the 633 nm laser at Vd = 0 V and Vg = 0 V due to the built-in potential in the p-n homojunction area. Our findings ensure the MoSe2 p-n diode as a promising candidate for future low-power operating photodevices.

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