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1.
Dalton Trans ; 48(48): 17925-17935, 2019 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-31793567

RESUMO

Three novel copper(ii) complexes, Cu(L1)2 (1), Cu(L2)2·2DMF (2), and Cu(L3)2·2DMF (3), were synthesized using three aroylhydrazone ligands, (E)-2-hydroxy-N'-(1-(pyrazin-2-yl)ethylidene)benzohydrazide (HL1), (E)-3-hydroxy-N'-(1-(pyrazin-2-yl)ethylidene)benzohydrazide (HL2) and (E)-4-hydroxy-N'-(1-(pyrazin-2-yl)ethylidene)benzohydrazide (HL3). The complexes were characterized by elemental analysis, infrared (IR), and Ultraviolet-visible light (UV-vis) spectroscopy. The X-ray crystal structures of the complexes all possess a distorted octahedral coordination geometry. Both an absorption spectral titration and a competitive binding assay (ethidium bromide, 4',6-diamidino-2-phenylindole (DAPI), and methyl green) revealed that complexes 2 and 3 bind readily to calf thymus DNA (ctDNA) through intercalative and minor groove binding modes. Complexes 2 and 3 also exhibited oxidative cleavage of supercoiled plasmid DNA (pUC19) in the presence of ascorbic acid as an activator. Cytotoxicity studies showed that complexes 2 and 3 possessed high cytotoxicities toward the HeLa human cervical cancer cell line, but weak toxicities toward the L929 normal mouse fibroblast cell line. We therefore have reason to believe that complexes 2 and 3 both show potential as promising anticancer candidate drugs.

2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(6): 1876-1880, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-31839053

RESUMO

OBJECTIVE: To investigate the expression level of T lymphocyte subsets in elderly patients with newly diagnosed multiple myeloma (NDMM), and to evaluated the prognostic value of T lymphocytic abnormalities in elderly NDMM patients. METHODS: Pretreated peripheral blood of 39 newly diagnosed elder patients with MM was tested by multi-parameter flow cytometry (MFC) to quantitatively detect T lymphocyte subsets, including CD4+T cell, CD8+T cell, and CD4/CD8 ratio. The prognostic values T-lymphocyte subset were evaluated in newly diagnosed elderly patients with MM. RESULTS: The median follow-up time was 21.5 (range, 3.0-66.0) months. Absolute counts of CD4+T cell and CD4/CD8 ratio positively correlated with prognosis. In the multivariate COX analysis, lower CD4/CD8 ratio and CD4+T cell counts were identified to be independent adverse prognostic factors for OS. CONCLUSION: Lower CD4/CD8 ratio and CD4+T cell counts at initial diagnosis are independent unfavorable prognostic factors for elderly patients with MM, and T lymphocyte subsets are crucial indicators for MM patients' prognosis.

3.
Biomed Res Int ; 2019: 5768285, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31886229

RESUMO

We investigated the effects of a human umbilical cord mesenchymal stem cell-conditioned medium (MSC-CM)/chitosan/collagen/ß-glycerophosphate (ß-GP) thermosensitive hydrogel (MSC-CM/hydrogel) on mice with third-degree burns. MSC-CM was collected and mixed with chitosan, collagen, and ß-GP to generate the thermosensitive MSC-CM/hydrogel, which was stored in the liquid phase at 4°C. The wounds of established third-degree burned mice were then externally covered with the MSC-CM/hydrogel, which formed a gel when placed on the wounds at physiological temperature. Injured mice in three additional groups were treated with unconditioned MSC medium (UM), MSC-CM, or UM/chitosan/collagen/ß-GP thermosensitive hydrogels. Skin wound samples were obtained 4, 14, and 28 days after burning for further analysis by hematoxylin and eosin and Ki-67 staining. Wound healing rates and times, in addition to immunohistochemical results, were then compared and analyzed among the four groups. Application of the MSC-CM/hydrogel shortened healing time, limited the area of inflammation, enhanced reepithelialization, promoted the formation of high-quality, well-vascularized granulation tissue, and attenuated the formation of fibrotic and hypertrophic scar tissue. In summary, MSC-CM/hydrogel effectively promotes wound healing in third-degree burned mice.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31840859

RESUMO

The present study aimed to investigate the effects of protein restriction and subsequent realimentation on caecal barrier function, caecal microbial composition and metabolites in weaned piglets. Thirty-six 28-day-old weaned piglets were randomly assigned to a control group and a treatment group. The piglets were fed diets containing 18.83% (normal) or 13.05% (low) of crude protein from the 1st to 14th day, after which all piglets were fed diets containing 18.83% of crude protein from the 15th to 28th day. The results showed that protein restriction increased caecal bacterial diversity and richness as well as the abundance of Ruminococcus 2, Faecalibacterium and Lachnospiraceae_uncultured, but reduced the abundance and the gene copies of Lactobacillus in the treatment group compared with the control group on day 14. Protein restriction also decreased the concentrations of isovaleric acid and total branched-chain fatty acids. During the succedent protein realimentation stage, the abundance of Ruminococcaceae UCG-014 and the concentrations of lactic acid, acetic acid, butyric acid and total short-chain fatty acids were increased in the treatment group on day 28. Furthermore, the ammonia concentration was reduced, while the gene mRNA levels of caecal barrier function were increased in the treatment group both on days 14 and 28. In conclusion, dietary protein restriction and realimentation could change caecal microbial composition and metabolites, and eventually influence caecal barrier function. The present study may provide a new insight into protein restriction and realimentation in weaned piglets.

6.
Sci Rep ; 9(1): 19766, 2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31875029

RESUMO

Currently, little is known regarding the value of quantitative parameters derived from the intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) with integrated slice-specific shimming (iShim) sequence in detecting old myocardial infarction and myocardial fibrosis. This study was to investigate the value of IVIM-MRI with iShim sequence in diagnosing old myocardial infarction and fibrosis. Thirty-five patients with both old myocardial infarction and myocardial fibrosis and 12 healthy volunteers were prospectively enrolled to undergo cardiac diffusion-weighted imaging (DWI) using seven b-values (0, 20, 60, 80, 120, 200 and 600 s/mm2). The iShim sequence was used for IVIM data acquisition, and the diffusion parameters, D, D* and f values for IVIM, and conventional apparent diffusion coefficient (ADC) were evaluated on the anterior, posterior and lateral walls of the ventricular septum using the short axis of the heart. Significant differences were found in the D, D* and f values between healthy subjects and patients with old myocardial infarction and myocardial fibrosis (P = 0.000), with the median value of the D and f significantly smaller in the myocardial infarction and fibrosis than in the normal control but the median value of D* significantly greater in the myocardial infarction and fibrosis than in the normal control. In the receiver operating curve analysis, the areas under the curve were 0.939, 0.988 and 0.959 for the D, D* and f values, respectively. The sensitivities and specificities were 84.6% and 94.4% for D, 88.9% and 84.6% for D* and 100% and 93.1% for the f values, respectively. In conclusion, the IVIM-derived parameters (D, D* and f) obtained using the iShim DWI technique showed high capacity in diagnosing old myocardial infarction and myocardial fibrosis by providing diffusion and perfusion information, which may have great importance in future clinical practice.

7.
Front Neurol ; 10: 1099, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31681158

RESUMO

The Willis covered stent (WCS) may prolapse into the aneurysmal sac due to device migration or foreshortening. We present a useful salvage strategy that can reorient a prolapsed WCS into a more suitable alignment. An intra-procedural prolapse of a WCS into a large cavernous aneurysm occurred in a 70-year-old female patient. A pipeline embolization device (PED) was used to retrieve the WCS and successfully accomplish flow diversion. Maintaining proximal access and ensuring that the microwire is securely held within the central axis of the herniated stent are critical until the entire parent vessel can be reconstructed. This salvage technique may help to regain proximal access and reposition the flow diversion constructs following WCS prolapse.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31774489

RESUMO

There are reports that depression induced by frontal lobe injury (FLI) has a devastating effect on human mental health. We previously reported that fasciculation and elongation protein zeta-1 (FEZ1) was essential for astrocytic protection of dopamine neurons. Studies of glutamate-glutamine cycle in mental illness have been reported, whereas not from the perspective of astrocytes. This study was designed to investigate the roles of astrocytic FEZ1 and glutamate-glutamine cycle after FLI. A model of FLI was established by inserting a blade into the right frontal lobe of rats. Behavioral tests were used to observe the behavioral changes of FLI rats. Neuropathologic examinations, including immunohistochemistry, were conducted. Behavioral tests showed that FLI decreased exploratory activity. Western blot analysis revealed that the expression of astroglial proteins overall decreased in the initial injury stage, as well as FEZ1. Immunohistochemistry showed a shift of FEZ1 localization from neurons in sham-lesioned rats to astrocytes in FLI rats, and showed the expression profile of glutamate transporter 1 and glutamine synthetase (GS) was consistent with Western blot observation. Our results indicate that astrocytic FEZ1 and glutamate-glutamine cycle dysfunction may be involved in the pathogenesis of depression after FLI.

9.
Leukemia ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31776466

RESUMO

Recurrent oncogenic mutations of MyD88 have been identified in a variety of lymphoid malignancies. Gain-of-function mutations of MyD88 constitutively activate downstream NF-κB signaling pathways, resulting in increased cellular proliferation and survival. However, whether MyD88 activity can be aberrantly regulated in MyD88-wild-type lymphoid malignancies remains poorly understood. SPOP is an adaptor protein of CUL3-based E3 ubiquitin ligase complex and frequently mutated genes in prostate and endometrial cancers. In this study, we reveal that SPOP binds to and induces the nondegradative ubiquitination of MyD88 by recognizing an atypical SPOP-binding motif in MyD88. This modification blocks Myddosome assembly and downstream NF-κB activation. SPOP is mutated in a subset of lymphoid malignancies, including diffuse large B-cell lymphoma (DLBCL). Lymphoid malignancies-associated SPOP mutants exhibited impaired binding to MyD88 and suppression of NF-κB activation. The DLBCL-associated, SPOP-binding defective mutants of MyD88 escaped from SPOP-mediated ubiquitination, and their effect on NF-κB activation is stronger than that of wild-type MyD88. Moreover, SPOP suppresses DLBCL cell growth in vitro and tumor xenograft in vivo by inhibiting the MyD88/NF-κB signaling. Therefore, SPOP acts as a tumor suppressor in DLBCL. Mutations in the SPOP-MyD88 binding interface may disrupt the SPOP-MyD88 regulatory axis and promote aberrant MyD88/NF-κB activation and cell growth in DLCBL.

10.
J Inorg Biochem ; 203: 110919, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31783217

RESUMO

In this work, three aroylhydrazone ligands ((E)-2-hydroxy-N'-(1-(pyrazin-2-yl)ethylidene)benzohydrazide, HL1; (E)-3-hydroxy-N'-(1-(pyrazin-2-yl)ethylidene)benzohydrazide, HL2; and (E)-4-hydroxy-N'-(1-(pyrazin-2-yl)ethylidene)benzohydrazide, HL3) and their complexes with nickel (Ni(L1)2, NiL1; Ni(L2)2∙2DMF, NiL2; Ni(L3)2∙2DMF, NiL3) were prepared. The single crystal X-ray structures analysis of three compounds showed that they were neutral. The ligand adopts tridentate chelating mode. The nickel ion is six-coordinate with two O atoms and four N atoms from two ligands, and forms an octahedral arrangement. The investigation of DNA binding ability by ultraviolet and fluorescence titrations showed that NiL2 and NiL3 exhibit moderate binding affinity toward calf Thymus DNA. Spectroscopy, molecular docking, and molecular dynamics simulation indicated that NiL2 and NiL3 bind at the minor groove of DNA through intercalation.

11.
Mol Cancer ; 18(1): 170, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31771591

RESUMO

BACKGROUND: The gene encoding the E3 ubiquitin ligase substrate-binding adaptor SPOP is frequently mutated in primary prostate cancer, but how SPOP mutations contribute to prostate cancer pathogenesis remains poorly understood. Stress granules (SG) assembly is an evolutionarily conserved strategy for survival of cells under stress, and often upregulated in human cancers. We investigated the role of SPOP mutations in aberrant activation of the SG in prostate cancer and explored the relevanve of the mechanism in therapy resistance. METHODS: We identified SG nucleating protein Caprin1 as a SPOP interactor by using the yeast two hybrid methods. A series of functional analyses in cell lines, patient samples, and xenograft models were performed to investigate the biological significance and clinical relevance of SPOP regulation of SG signaling in prostate cancer. RESULTS: The cytoplasmic form of wild-type (WT) SPOP recognizes and triggers ubiquitin-dependent degradation of Caprin1. Caprin1 abundance is elevated in SPOP-mutant expressing prostate cancer cell lines and patient specimens. SPOP WT suppresses SG assembly, while the prostate cancer-associated mutants enhance SG assembly in a Caprin1-dependent manner. Knockout of SPOP or expression of prostate cancer-associated SPOP mutants conferred resistance to death caused by SG inducers (e.g. docetaxel, sodium arsenite and H2O2) in prostate cancer cells. CONCLUSIONS: SG assembly is aberrantly elevated in SPOP-mutated prostate cancer. SPOP mutations cause resistance to cellular stress induced by chemtherapeutic drug such as docetaxel in prostate cancer.

12.
Opt Express ; 27(21): 29547-29557, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31684214

RESUMO

Flexible electronics, as a futuristic technology, is presenting tremendous impact in areas of wearable displaying, energy saving, and adaptive camouflage. In this work, we constructed a simple triple-layered electrochemical device with high flexibility using the electroplated nickel (Ni) grid electrode and the multifunctional hydrogel. The Ni grid electrode with low resistance (0.5 Ω/sq), high optical transparency (84.8%) and good mechanical flexibility, is beneficial for efficient electron injection, while the transparent lithium chloride hydrogel functions simultaneously for ion storage, ion transportation and counter-conducting. The thin polymer poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT: PSS) film is utilized as the electrochromic (EC) material and it also distributes the electrons evenly for uniform coloration. The triple-layered EC architecture not only simplifies the manufacturing procedures but also improves the device performance in terms of optical contrast and mechanical robustness. The device shows fast response for coloration and bleaching with an absolute transmittance contrast of 40% and a contrast retention over 72% after 2500 bending cycles. The ability of the flexible electrochromic device for conformable attaching was also investigated without obvious performance degradation. The electroplated Ni grid electrode and the multifunctional hydrogel are advantageous in constructing flexible electrochromic devices in terms of the response time, the working stability and the bending capability, paving a way for next-generation flexible electronics.

13.
J Biomater Sci Polym Ed ; : 1-18, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31724490

RESUMO

Biological modifications of the silk fibroin (silk) material have broad applications in textiles, biomedical materials and other industrial materials. It is economical to incorporate nanoparticles to the biosynthesis of silk fibroin by adding them to silkworm larval diets. This strategy may result in the rapid stable production of modified silk. Glucose-coated silver nanoparticles (AgNPs) were used to improve the AgNPs' biocompatibility, and the AgNPs were efficiently incorporated into silk by feeding. Larvae fed with AgNPs produced silk with significantly improved antibacterial properties and altered silk secondary structures. Both positive and negative effects on the growth and synthesis of silk proteins were observed after different AgNPs doses. Larvae feeding with low concentration of 0.02% and medium 0.20% AgNPs have greater transfer efficiencies of AgNPs to silk compared with feeding high concentration of 2.00% AgNPs. In addition, the elongation and tensile strength of the produced silk fibers were also significantly increased, with greater mammalian cell compatibility. The appropriate AgNPs concentration in the diet of silkworms can promote the synthesis of silk proteins, enhance their mechanical properties, improve their antibacterial property and inhibit the presence of Gram-negative bacteria.

14.
Int J Biol Sci ; 15(10): 2170-2181, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31592097

RESUMO

Hyperproteinemia is a severe metabolic disease characterized by abnormally elevated plasma protein concentrations (PPC). However, there is currently no reliable animal model for PPC, and the pathological mechanism of hyperproteinemia thus remains unclear. In this study, we evaluated the effects of hyperproteinemia on reproductive development in an invertebrate silkworm model with a controllable PPC and no primary disease effects. High PPC inhibited the synthesis of vitellogenin and 30K protein essential for female ovarian development in the fat body of metabolic tissues, and inhibited their transport through the hemolymph to the ovary. High PPC also induced programmed cell death in testis and ovary cells, slowed the development of germ cells, and significantly reduced the reproductive coefficient. Furthermore, the intensities and mechanisms of high-PPC-induced reproductive toxicity differed between sexes in this silkworm model.

15.
J Chem Phys ; 151(12): 124906, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31575207

RESUMO

Fast deformation of entangled melts is known to cause chain stretching due to affinelike straining of the entanglement network. Since the chain deformation may also result in perturbations of covalent bond angles and bond length, there are always possible enthalpic effects. In this study, we first subject polystyrene and PMMA of different molecular weights to either uniaxial melt extension or planar extension and subsequently impose rapid thermal quenching to preserve the chain deformation. Then, such pre-melt-deformed samples are annealed at various temperatures below the glass transition temperature Tg. During annealing, these samples can undergo appreciable contraction on a time scale much shorter than the alpha relaxation time. Significant retractive stress is observed when such contracting samples are held fixed during the annealing. The stress level can be nearly as high as the Cauchy stress produced during melt stretching. These observations not only allowed us to investigate glassy chain dynamics as well as the molecular nature of mechanical stress but may also suggest that pre-melt-stretched polymers can cause segmental mobilization in the glassy state. The available evidence indicates that the retractive stress is enthalpic in origin, associated with the conformational distortion at the bond level produced by melt stretching.

16.
Org Lett ; 21(22): 9198-9202, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31647672

RESUMO

This communication highlights the use of chiral sulfinamides as nitrogen nucleophiles in intermolecular aza-Michael reactions. When chiral sulfinamides are coupled to a chloroethyl group, the corresponding novel annulating reagents can be used to streamline the stereoselective synthesis of complex pyrrolidine-containing molecules. As a result, it has enabled a medicinal chemistry campaign for the synthesis of biologically active RORγt inverse agonists.

17.
J Med Chem ; 62(21): 9931-9946, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31638797

RESUMO

RORγt is an important nuclear receptor that regulates the production of several pro-inflammatory cytokines such as IL-17 and IL-22. As a result, RORγt has been identified as a potential target for the treatment of various immunological disorders such as psoriasis, psoriatic arthritis, and inflammatory bowel diseases. Structure and computer-assisted drug design led to the identification of a novel series of tricyclic RORγt inverse agonists with significantly improved in vitro activity in the reporter (Gal4) and human whole blood assays compared to our previous chemotype. Through careful structure activity relationship, several potent and selective RORγt inverse agonists have been identified. Pharmacokinetic studies allowed the identification of the lead molecule 32 with a low peak-to-trough ratio. This molecule showed excellent activity in an IL-2/IL-23-induced mouse pharmacodynamic study and demonstrated biologic-like efficacy in an IL-23-induced preclinical model of psoriasis.

18.
J Basic Microbiol ; 59(11): 1154-1162, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31553498

RESUMO

Nitric oxide (NO) reductase (NorCB) of Pseudomonas aeruginosa is an essential enzyme that metabolizes NO and alleviates anaerobic NO toxicity during denitrification processes under anaerobic conditions. However, the molecular functions of norCB in the presence of oxygen are poorly understood. This study utilized norCB knockout from P. aeruginosa ATCC 9027 to analyze the resulting phenotypic changes of ΔnorCB in comparison to the wild-type parental strain (WT) and the complementary strain (ΔnorCB-com). The results demonstrated an increase in planktonic growth and biofilm formation by ΔnorCB compared to WT and ΔnorCB-com in the presence of isothiazolones under aerobic conditions. Deletion of norCB led to increased swimming ability and decreased pyocyanin production. Inactivation of norCB also led to an increase of cellular H2 O2 concentration due to decreased activity of its catalases. In addition, the deletion of norCB also influenced the relative expressions of several other genes, including norD, nirS, hmgA, and hpd. These findings provide preliminary evidence that norCB in P. aeruginosa plays an essential role in bacterial life process under aerobic conditions and improves the application of denitrification in the next step.

19.
Sci Rep ; 9(1): 12673, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481699

RESUMO

MADS-box transcription factors possess many functions in plant reproduction and development. However, few MADS-box genes related to secondary metabolites regulation have been identified. In Hevea brasiliensis, natural rubber is a representative cis-polyisoprenoids in secondary metabolism which occurs in the rubber laticifer cells, the molecular regulation basis of natural rubber biosynthesis is not clear. Here, a total of 24 MADS-box genes including 4 type I MADS-box genes and 20 type II MADS-box genes were identified in the transcriptome of rubber tree latex. The phylogenetic analysis was performed to clarify the evolutionary relationships of all the 24 rubber tree MADS-box proteins with MADS-box transcription factors from Arabidopsis thaliana and Oryza sativa. Four type I MADS-box genes were subdivided into Mα (3 genes) and Mß (1 gene). Twenty type II MADS-box genes were subclassified into MIKC* (8 genes) and MIKCc (12 genes). Eight MADS-box genes (HblMADS3, 5, 6, 7, 9, 13, 23, 24) were predominant expression in laticifers. ABA up-regulated the expression of HblMADS9, and the expression of HblMADS3, HblMADS5, HblMADS24 were up-regulated by MeJA. The function of HblMADS24 was elucidated. HblMADS24 bound HbFPS1 promoter in yeast and HblMADS24 activated HbFPS1 promoter in tobacco plants. Moreover, we proposed that HblMADS24 is a transcription activator of HbFPS1 which taking part in natural rubber biosynthesis.

20.
J Ind Microbiol Biotechnol ; 46(12): 1757-1768, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31512096

RESUMO

Through our previous study, we found an up-regulation in the expression of nitrite reductase (nirS) in the isothiazolone-resistant strain of Pseudomonas aeruginosa. However, the definitive molecular role of nirS in ascribing the resistance remained elusive. In the present study, the nirS gene was deleted from the chromosome of P. aeruginosa ATCC 9027 and the resulting phenotypic changes of ΔnirS were studied alongside the wild-type (WT) strain under aerobic conditions. The results demonstrated a decline in the formations of biofilms but not planktonic growth by ΔnirS as compared to WT, especially in the presence of benzisothiazolinone (BIT). Meanwhile, the deletion of nirS impaired swimming motility of P. aeruginosa under the stress of BIT. To assess the influence of nirS on the transcriptome of P. aeruginosa, RNA-seq experiments comparing the ΔnirS with WT were also performed. A total of 694 genes were found to be differentially expressed in ΔnirS, of which 192 were up-regulated, while 502 were down-regulated. In addition, these differently expressed genes were noted to significantly enrich the carbon metabolism along with glyoxylate and dicarboxylate metabolisms. Meanwhile, results from RT-PCR suggested the contribution of mexEF-oprN to the development of BIT resistance by ΔnirS. Further, c-di-GMP was less in ΔnirS than in WT, as revealed by HPLC. Taken together, our results confirm that nirS of P. aeruginosa ATCC 9027 plays a role in BIT resistance along with biofilm formation and further affects several metabolic patterns under aerobic conditions.

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