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1.
Nat Nanotechnol ; 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33603239

RESUMO

Optical tweezers are widely used in materials assembly1, characterization2, biomechanical force sensing3,4 and the in vivo manipulation of cells5 and organs6. The trapping force has primarily been generated through the refractive index mismatch between a trapped object and its surrounding medium. This poses a fundamental challenge for the optical trapping of low-refractive-index nanoscale objects, including nanoparticles and intracellular organelles. Here, we report a technology that employs a resonance effect to enhance the permittivity and polarizability of nanocrystals, leading to enhanced optical trapping forces by orders of magnitude. This effectively bypasses the requirement of refractive index mismatch at the nanoscale. We show that under resonance conditions, highly doping lanthanide ions in NaYF4 nanocrystals makes the real part of the Clausius-Mossotti factor approach its asymptotic limit, thereby achieving a maximum optical trap stiffness of 0.086 pN µm-1 mW-1 for 23.3-nm-radius low-refractive-index (1.46) nanoparticles, that is, more than 30 times stronger than the reported value for gold nanoparticles of the same size. Our results suggest a new potential of lanthanide doping for the optical control of the refractive index of nanomaterials, developing the optical force tag for the intracellular manipulation of organelles and integrating optical tweezers with temperature sensing and laser cooling7 capabilities.

2.
Sci Adv ; 7(5)2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33571110

RESUMO

Na+/K+-ATPase (NKA) plays important roles in maintaining cellular homeostasis. Conversely, reduced NKA activity has been reported in aging and neurodegenerative diseases. However, little is known about the function of NKA in the pathogenesis of Parkinson's disease (PD). Here, we report that reduction of NKA activity in NKAα1+/- mice aggravates α-synuclein-induced pathology, including a reduction in tyrosine hydroxylase (TH) and deficits in behavioral tests for memory, learning, and motor function. To reverse this effect, we generated an NKA-stabilizing monoclonal antibody, DR5-12D, against the DR region (897DVEDSYGQQWTYEQR911) of the NKAα1 subunit. We demonstrate that DR5-12D can ameliorate α-synuclein-induced TH loss and behavioral deficits by accelerating α-synuclein degradation in neurons. The underlying mechanism for the beneficial effects of DR5-12D involves activation of NKAα1-dependent autophagy via increased AMPK/mTOR/ULK1 pathway signaling. Cumulatively, this work demonstrates that NKA activity is neuroprotective and that pharmacological activation of this pathway represents a new therapeutic strategy for PD.

3.
Biomaterials ; 270: 120680, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33588140

RESUMO

Pancreatic cancer (PC) is one kind of the most lethal malignancies worldwide, owing to its insidious symptoms, early metastases, and negative responses to current therapies. With an increasing understanding of pathology, the tumor microenvironment (TME) plays a significant role in ineffective treatment and poor prognosis of PC. Thus, a growing number of studies have focused on whether components of the TME could be effective targets for PC therapy. Biomaterials have been widely applied in cancer therapy, and numerous organic or inorganic biomaterials for TME regulation have been developed to inhibit the growth and metastasis of PC, as well as reverse therapeutic resistance. In this review, we discuss various biomaterials utilized to treat PC based on different components of the TME, including, but not limited to, extracellular matrix (ECM), abnormal tumor vascularization, and tumor-associated immune cells, as well as other unconventional therapeutic strategies. Besides, the perspectives on the underlying future of theranostic nanomedicines for PC therapy are also presented.

4.
Spectrochim Acta A Mol Biomol Spectrosc ; 252: 119518, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33561681

RESUMO

The first ultrafast fluorescence probe with response time in seconds (10 s) for fluoride ions (F-) has been proposed by conjugating dimethylthiophosphoryl group as a recognition unit with the near-infrared fluorophore of hemicyanine. The response mechanism is the F--induced cleavage of the dimethylthiophosphoryl group, along with the liberation of the fluorophore, which results in a distinctly enhanced fluorescence intensity at 730 nm (λex = 680 nm). The fluorescence enhancement of the probe is directly proportional to the F- concentration in the range of 10-300 µM with the detection limit of 4.28 µM. The probe has been successfully used to determine F- concentration in real water and toothpaste samples as well as image F- in living cells. The simplicity and quick response of this probe endow it with the ability of detecting F- rapidly in real samples.

6.
Carbohydr Polym ; 255: 117331, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33436174

RESUMO

Recently, integration of self-healing, color-tunable, sol-gel converted properties into hydrogel has attracted interest for preparing a reinforced multifunctional hydrogel. Herein, acidochromic regenerated cellulose (ARC) was incorporated into the polyvinyl alcohol/borax (PB) matrix for constructing a tough, self-healing, multicolor and sol-gel converted smart hydrogel (PB/ARC). The mechanical properties of PB/ARC hydrogel were improved after introducing ARC, which could bear a weight of 200 g and had high maximum tensile strength (6.8 times) and compressive strength (2.3 times). PB/ARC hydrogel automatically fused within 15 s after being cut and quickly recovered to the original state after being subjected to high shear strain, showing excellent self-healing ability. The color of hydrogel could be tuned between yellow and purple by altering pH values (5-12). In addition, PB/ARC hydrogel exhibited reversible sol-gel conversion in response to the change of acidity and alkalinity. This study offers a new and facile strategy for developing multifunctional smart hydrogel.

7.
Inflammation ; 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33411101

RESUMO

Endoplasmic reticulum stress is an important contributor to the cerebral ischemic injury. Sappanone A (SA), a kind of natural homoisoflavanone extracted from Caesalpinia sappan L, has been evidenced to exhibit anti-inflammatory and antioxidative properties. The present study aimed to investigate the potential neuroprotective effects of SA in cerebral ischemia-reperfusion injury. The potential neuroprotective effect of SA was tested in a rat model of middle cerebral artery occlusion (MCAO) allowing reperfusion and PC12 cell model of oxygen-glucose deprivation and reperfusion (OGD/R). Post-ischemic neuronal injury was evaluated by 2, 3, 5-triphenyltetrazolium chloride (TTC) and hematoxylin-eosin (H&E) staining. The levels of inflammatory factors and oxidative stress-related markers were detected using corresponding kits. Cell apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) or flow cytometry, and the expression of apoptosis-associated proteins was determined using western blot analysis. Subsequently, endoplasmic reticulum stress-related proteins were detected through western blot analysis, and CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP) was overexpressed to confirm the contribution of endoplasmic reticulum stress inhibition by SA to the neuroprotective effects post OGD/R. Results revealed that SA was effective in ameliorating cerebral infarction and pathological injuries post-reperfusion following MCAO, which is associated with reduced inflammation, oxidative stress, and cell apoptosis by SA in the brain. Consistently, these neuroprotective effects of SA post ischemia-reperfusion were also observed in a PC12 cell model of OGD/R. Importantly, endoplasmic reticulum stressors, including the CHOP, the 78 kDa glucose-regulated protein 78 (GRP78), and phosphorylated eukaryotic initiation factors 2α (EIF-2α), were significantly downregulated by SA, while CHOP overexpression attenuated the beneficial effects of SA on inflammation, oxidative stress, and apoptosis in OGD/R-induced PC12 cells. These results demonstrated that SA alleviates endoplasmic reticulum stress, ameliorating inflammation, oxidative stress, and apoptosis, and thereby serves as therapeutic potential for protection against cerebral ischemia-reperfusion injury in ischemic stroke.

8.
Pest Manag Sci ; 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33442936

RESUMO

BACKGROUND: Often, due to the occurrence of powdery mildew, cucumber leaf surfaces is changed into a more hydrophobic surface, which affects wetting and spreading of liquid pesticides, reducing their efficiency. The wetting and deposition behavior of liquid pesticides can be improved by adding surfactants to pesticides. Added surfactants affect the spray volume of the pesticide, which can lead to waste and a low utilization rate of the pesticide. It is important to further balance the relationship between deposition and wettability of pesticide liquid on the surfaces of healthy leaves and powdery mildew leaves of cucumber. RESULTS: This study evaluated the deposition and wettability of hexaconazole (Hexa) with surfactants on the surfaces of healthy leaves and powdery mildew leaves of cucumber. The deposition rates of Hexa with surfactants were lower than that of Hexa due to the loss of solution in conventional spray volume (750 L ha-1 ). The deposition rate of Hexa did not necessarily increase with increasing spray volume, and the deposition rate did not increase again after the spray volume increased to a certain level. Under the condition that the prevention and control effect were not reduced, we found that the volume of solution spray with added Silwet618 or AEO-5 should be adjusted to half of the normal volume, while the volume of solution spray with added 1227 or rosin-based quarternary ammonium should be adjusted to two-thirds of the normal volume to increase the deposition rate by approximately 30%. Regarding the wetting parameters, the results showed that the wettability of Hexa with Silwet618 was the best, but their combination was not ideal according to the composite index and deposition. By analyzing all the parameters, it was found that the spray volume reduction of Hexa with surfactant was approximately equal to the solution surface tension reduction, compared with the parameters of Hexa. CONCLUSION: The equilibrium relationship between deposition rate and wetting parameters was determined to provide guidance for the application of surfactants and to lower the dosage of pesticides to increase their efficiency and reduce their application.

9.
J Hazard Mater ; 403: 123690, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33264882

RESUMO

In this work, modified chitosan flocculants (MCS) was synthesized by using chitosan (CS), acrylamide, cationic monomers and hydrophobic monomers via low-pressure UV-initiated copolymerization. The flocculation performance of MCS was evaluated in emulsified oily wastewater treatment. The effect of cationic and hydrophobic structure on oil removal was studied, and the interactions between these functional groups and the components in oil were also analyzed. Results suggested that MCS flocculants exhibited excellent oil removal efficiency in a wide pH range (2.0‒10). The flocculation efficiency of 91 % was achieved at the dosages of 0.6 mL/L (6 mg/L). During pH of 2.0-10, the optimal cationic and hydrophobic monomer was DMC and VT, respectively. Silane groups were favorable for oil removal than the other hydrophobic structures. The cationic groups expanded the optimal pH range of MCS in flocculation, whereas hydrophobic groups considerably reduced the dosage of MCS. The experimental results showed that alkane, cyclic aromatic hydrocarbon compounds in oil can be easily removed by using MC4, whereas cycloalkanes compounds was effectively removed by MC6 and MC7 because of preferable demulsification capacity, and the hydrophobic interaction, interfacial adsorption and electrostatic attraction played the dominant in flocculation. Thus, the synthesized MCS is favorable for emulsified oily wastewater treatment.

10.
JCI Insight ; 6(3)2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33351789

RESUMO

Paucity of the glucose transporter-1 (Glut1) protein resulting from haploinsufficiency of the SLC2A1 gene arrests cerebral angiogenesis and disrupts brain function to cause Glut1 deficiency syndrome (Glut1 DS). Restoring Glut1 to Glut1 DS model mice prevents disease, but the precise cellular sites of action of the transporter, its temporal requirements, and the mechanisms linking scarcity of the protein to brain cell dysfunction remain poorly understood. Here, we show that Glut1 functions in a cell-autonomous manner in the cerebral microvasculature to affect endothelial tip cells and, thus, brain angiogenesis. Moreover, brain endothelial cell-specific Glut1 depletion not only triggers a severe neuroinflammatory response in the Glut1 DS brain, but also reduces levels of brain-derived neurotrophic factor (BDNF) and causes overt disease. Reduced BDNF correlated with fewer neurons in the Glut1 DS brain. Controlled depletion of the protein demonstrated that brain pathology and disease severity was greatest when Glut1 scarcity was induced neonatally, during brain angiogenesis. Reducing Glut1 at later stages had mild or little effect. Our results suggest that targeting brain endothelial cells during early development is important to ensure proper brain angiogenesis, prevent neuroinflammation, maintain BDNF levels, and preserve neuron numbers. This requirement will be essential for any disease-modifying therapeutic strategy for Glut1 DS.

11.
J Exp Med ; 218(2)2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33355624

RESUMO

Autophagy programs the metabolic and functional fitness of regulatory T (T reg) cells to establish immune tolerance, yet the mechanisms governing autophagy initiation in T reg cells remain unclear. Here, we show that the E3 ubiquitin ligase ZFP91 facilitates autophagy activation to sustain T reg cell metabolic programming and functional integrity. T reg cell-specific deletion of Zfp91 caused T reg cell dysfunction and exacerbated colonic inflammation and inflammation-driven colon carcinogenesis. TCR-triggered autophagy induction largely relied on T reg cell-derived ZFP91 to restrict hyperglycolysis, which is required for the maintenance of T reg cell homeostasis. Mechanistically, ZFP91 rapidly translocated from the nucleus to the cytoplasm in response to TCR stimulation and then mediated BECN1 ubiquitination to promote BECN1-PIK3C3 complex formation. Therefore, our results highlight a ZFP91-dependent mechanism promoting TCR-initiated autophagosome maturation to maintain T reg cell homeostasis and function.

12.
Mol Med Rep ; 23(2): 1, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33355376

RESUMO

The degeneration of intervertebral disc (IVD) tissue, initiated following the disappearance of notochordal cells (NCs), is characterized by the decreased number of nucleus pulposus (NP) cells (NPCs) and extracellular matrix. Transplanting proper cells into the IVD may sustain cell numbers, resulting in the synthesis of new matrix; this represents a minimally invasive regenerative therapy. However, the lack of cells with a correct phenotype severely hampers the development of regenerative therapy. The present study aimed to investigate whether porcine NC­rich NP tissue stimulates bone marrow­derived mesenchymal stem cell (BM­MSC) differentiation toward NC­like cells, which possess promising regenerative ability, for the treatment of disc degeneration diseases. BM­MSCs were successfully isolated from porcine femurs and tibiae, which expressed CD90 and CD105 markers and did not express CD45. Differentiation induction experiments revealed that the isolated cells had osteogenic and adipogenic differentiation potential. When co­cultured with NC­rich NP tissue, the BM­MSCs successfully differentiated into NC­like cells. Cell morphological analysis revealed that the cells exhibited an altered morphology, from a shuttle­like to a circular one, and the expression of NC marker genes, including brachyury, keratin­8, and keratin­18, was enhanced, and the cells exhibited the ability to generate aggrecan and collagen II. Taken together, the findings of the present study demonstrated that the primarily isolated and cultured BM­MSCs may be stimulated to differentiate into NC­like cells by porcine NC­rich NP explants, potentially providing an ideal cell source for regenerative therapies for disc degeneration diseases.

13.
J Exp Med ; 218(3)2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33151261

RESUMO

The liver maintains hematopoietic stem cells (HSCs) during development. However, it is not clear what cells are the components of the developing liver niche in vivo. Here, we genetically dissected the developing liver niche by systematically determining the cellular source of a key HSC niche factor, stem cell factor (SCF). Most HSCs were closely associated with sinusoidal vasculature. Using Scfgfp knockin mice, we found that Scf was primarily expressed by endothelial and perisinusoidal hepatic stellate cells. Conditional deletion of Scf from hepatocytes, hematopoietic cells, Ng2+ cells, or endothelial cells did not affect HSC number or function. Deletion of Scf from hepatic stellate cells depleted HSCs. Nearly all HSCs were lost when Scf was deleted from both endothelial and hepatic stellate cells. The expression of several niche factors was down-regulated in stellate cells around birth, when HSCs egress the developing liver. Thus, hepatic stellate and endothelial cells create perisinusoidal vascular HSC niche in the developing liver by producing SCF.

15.
J Cell Mol Med ; 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33215869

RESUMO

LLKL, a new traditional Chinese medicine formula containing Edgeworthia gardneri (Wall.) Meisn., Sibiraea angustata and Crocus sativus L. (saffron), was designed to ameliorate type 2 diabetes mellitus. Despite the therapeutic benefits of LLKL, its underlying mechanisms remain elusive. This study evaluated the LLKL anti-diabetic efficacy and its effect on gut microbiota to elucidate its mechanism of action in Zucker diabetic fatty rats. We found that administration of different LLKL concentrations (4.68, 2.34 and 1.17 g/kg/d) improved several diabetic parameters after a 6-week treatment. Moreover, LLKL modulated gut microbiota dysbiosis, increased the expression of occluding and maintained intestinal epithelial homeostasis, leading to a reduction in LPS, TNF-α and IL-6 levels. Hepatic transcriptomic analysis showed that the Toll-like receptor signalling pathway was markedly enriched by LLKL treatment. RT-qPCR results validated that LLKL treatment decreased the expressions of TLR4, MyD88 and CTSK. Furthermore, a gene set enrichment analysis indicated that LLKL enhanced the insulin signalling pathway and inhibited glycerolipid metabolism and fatty acid metabolism, which were verified by the liver biochemical analysis. These findings demonstrate that LLKL ameliorates hyperglycaemia, modulates the gut microbiota and regulates the gut-liver axis, which might contribute to its anti-diabetic effect.

16.
J Orthop Surg Res ; 15(1): 528, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176816

RESUMO

BACKGROUND: High tibial osteotomy (HTO) has a history of nearly 60 years and has been widely used in clinical practice. Biplanar open wedge high tibial osteotomy (BOWHTO), which evolved from HTO, is an important therapy for the knee osteoarthritis. In our previous research, we found that the decrease of hemoglobin levels after high tibial osteotomy ranges from between 17 to 41 g/L, but this is highly inconsistent with the intraoperative bleeding and postoperative drainage observed in clinical practice. The purpose of this study was to investigate the perioperative hidden blood loss (HBL) after biplanar open wedge high tibial osteotomy (BOWHTO), as well as to study the effect of the actual correction angle on blood loss. METHODS: A retrospective analysis was performed on 21 patients who underwent BOWHTO for osteoarthritis of the knee due to proximal tibia deformity. Gross equation was used to calculate the perioperative total blood loss (TBL) and HBL. The actual correction angle was measured by postoperative anteroposterior radiograph. The correlation between HBL and correction angle was determined through correlation analysis. RESULTS: The TBL was 823.5 ± 348.7 mL and the HBL was 601.6 ± 297.3 mL, total hemoglobin loss was 25.0 ± 10.7 g/L, and the mean HBL/patient's blood volume (H/P) was 13.19 ± 5.56% for 21 patients. The correlation coefficient of correction angle and H/P is statistically significant (|r| = 0.678, P = 0.001). CONCLUSIONS: The actual total blood loss after BOWHTO was significantly higher than the observed, and the HBL was objective existent after BOWHTO. The proportion of H/P is positively correlated with the correction angle.

17.
J Exp Bot ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33206180

RESUMO

The BES1/BZR1 transcription factors regulate the expression of brassinosteroid responsive genes and play pivotal roles in plant development. However, the function of BES1/BZR1 regulating kernel development remains unclear. In this study, maize ZmBES1/BZR1-5 is found to positively regulate kernel size. Candidate-gene association analysis showed that four and three SNPs related to ZmBES1/BZR1-5 were significantly associated with kernel width and 100-kernel weight in 513 diverse maize inbred lines, respectively. Overexpression of ZmBES1/BZR1-5 gene in Arabidopsis and rice both significantly increased seed size and weight, as well as smaller kernel produced in maize Mu transposon insertion and EMS mutants. The ZmBES1/BZR1-5 protein contains bHLH and BAM domains, shows no transcriptional activity as monomer but forms homodimer through BAM domain, and locates in nucleus. Chromatin immunoprecipitation sequencing (ChIP-seq), yeast one-hybrid (Y1H) and dual-luciferase assay demonstrate that ZmBES1/BZR1-5 protein binds to the promoter of AP2/EREBP genes (Zm00001d010676 and Zm00001d032077) and inhibits their transcription. cDNA library screening shows that ZmBES1/BZR1-5 interacts with casein kinase II subunit ß4 (ZmCKIIß4) and ferredoxin 2 (ZmFdx2) in vitro and vivo, respectively. Taken together, the study suggests that ZmBES1/BZR1-5 positively regulates kernel size and provides new insights into understanding the mechanism of kernel development in maize.

18.
BMC Plant Biol ; 20(1): 527, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33208102

RESUMO

BACKGROUND: The ratio of CO2 mesophyll conductance (gm) to Ribulose-1, 5-bisphosphate carboxylase/oxygenase (Rubisco) content has been suggested to positively affect photosynthetic nitrogen use efficiency (PNUE). The anatomical basis of gm has been quantified, but information on the relationship between cell-level anatomies and PNUE is less advanced. Here, hydroponic experiments were conducted in rice plants supplied with ammonium (NH4+) and nitrate (NO3-) under three N levels (low, 0.71 mM; intermediate, 2.86 mM; high, 7.14 mM) to investigate the gas exchange parameters, leaf anatomical structure and PNUE. RESULTS: The results showed a lower PNUE in plants supplied with high nitrogen and NH4+, which was positively correlated with the gm/Rubisco ratio. A one-dimensional within-leaf model revealed that the resistance to CO2 diffusion in the liquid phase (rliq) dominated the overall mesophyll resistance (rm), in which CO2 transfer resistance in the cell wall, cytoplasm and stroma were significantly affected by nitrogen supply. The chloroplast surface area exposed to intercellular space (Sc) per Rubisco rather than the gm/Sc ratio was positively correlated with PNUE and was thus considered a key component influencing PNUE. CONCLUSION: In conclusion, our study emphasized that Sc was the most important anatomical trait in coordinating gm and PNUE with contrasting N supply.

19.
Eur Radiol ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33210204

RESUMO

The original version of this article, published on 24 September 2020, unfortunately contained a mistake.

20.
Biol Psychiatry ; 2020 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-33032807

RESUMO

BACKGROUND: Neurogranin (Ng), encoded by the schizophrenia risk gene NRGN, is a calmodulin-binding protein enriched in the postsynaptic compartments, and its expression is reduced in the postmortem brains of patients with schizophrenia. Experience-dependent translation of Ng is critical for encoding contextual memory, and Ng regulates developmental plasticity in the primary visual cortex during the critical period. However, the overall impact of Ng on the neuronal signaling that regulates synaptic plasticity is unknown. METHODS: Altered Ng expression was achieved via virus-mediated gene manipulation in mice. The effect on long-term potentiation (LTP) was accessed using spike timing-dependent plasticity protocols. Quantitative phosphoproteomics analyses led to discoveries in significant phosphorylated targets. An identified candidate was examined with high-throughput planar patch clamp and was validated with pharmacological manipulation. RESULTS: Ng bidirectionally modulated LTP in the hippocampus. Decreasing Ng levels significantly affected the phosphorylation pattern of postsynaptic density proteins, including glutamate receptors, GTPases, kinases, RNA binding proteins, selective ion channels, and ionic transporters, some of which highlighted clusters of schizophrenia- and autism-related genes. Hypophosphorylation of NMDA receptor subunit Grin2A, one significant phosphorylated target, resulted in accelerated decay of NMDA receptor currents. Blocking protein phosphatase PP2B activity rescued the accelerated NMDA receptor current decay and the impairment of LTP mediated by Ng knockdown, implicating the requirement of synaptic PP2B activity for the deficits. CONCLUSIONS: Altered Ng levels affect the phosphorylation landscape of neuronal proteins. PP2B activity is required for mediating the deficit in synaptic plasticity caused by decreasing Ng levels, revealing a novel mechanistic link of a schizophrenia risk gene to cognitive deficits.

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