Imperial College London

Dr Hailin Zhao

Faculty of MedicineDepartment of Surgery & Cancer

Research Associate
 
 
 
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Contact

 

hailin.zhao06

 
 
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Location

 

Chelsea and Westminster HospitalChelsea and Westminster Campus

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Summary

 

Publications

Publication Type
Year
to

110 results found

Liao Z, Ou X, Zhou C, Ma D, Zhao H, Huang Het al., 2022, Xenon attenuated neonatal lipopolysaccharide exposure induced neuronal necroptosis and subsequently improved cognition in juvenile rats, Frontiers in Pharmacology, Vol: 13

Background: Neonatal sepsis is known to cause neurodevelopment impairment and has been reported to increase risks for neurological/psychiatric disorders. In this study, we investigated the effect of xenon, a well-known potent neuroprotective gas, on neonatal sepsis-induced neurodevelopment impairment in rats together with underlying mechanism by focusing on receptor-interacting protein kinase (RIP) mediated neuronal necroptosis. Methods: 3-day-old Sprague–Dawley rat pups were exposed to either 70% xenon or N2 balanced with O2 for 6 h, during which lipopolysaccharide (LPS) was injected intraperitoneally for 3 times (500 μg/kg for the 1st and 250 μg/kg for the second and third dose; n = 6–10/group). In another cohort of 3-day-old rat pups, intracerebroventricular injection of necrostatin-1 (4μg in 4μl saline, a RIP-1-targeted inhibitor of necroptosis) was performed 20 min after the third dose of LPS. The learning ability and memory were assessed 25 days after LPS injection. Then, their hippocampus was collected for neuronal necroptosis with RIP and MIKL assessments using western blot and in situ immunostaining. Systemic and neuro-inflammation was also assessed. Results: LPS insult resulted in elevation of pro-inflammatory cytokine TNF-? and IL-6, caused neuronal necroptosis and damaged synaptic integrity at the brain developing stage, which finally led to the long-term cognitive impairment. Xenon inhibited necroptosis associated mediator RIP-1, RIP-3, and MLKL activation, protected neurons and attenuated cognitive dysfunction induced by LPS. Like xenon, the similar pattern changes induced by a RIP-1 inhibitor Necrostatin-1 were also found. Conclusion: This study indicates that necroptosis is involved in neonatal sepsis-induced neurofunctional impairments and xenon may be a novel therapeutic strategy to prevent/treat cognitive impairment in neonatal septic patients.

Journal article

Wong R, Zhang Y, Zhao H, Ma Det al., 2022, Circular RNAs in organ injury: recent development, JOURNAL OF TRANSLATIONAL MEDICINE, Vol: 20

Journal article

Iwasaki M, Zhao H, Hu C, Saito J, Wu L, Sherwin A, Ishikawa M, Sakamoto A, Buggy D, Ma Det al., 2022, The differential cancer growth associated with anaesthetics in a cancer xenograft model of mice: mechanisms and implications of postoperative cancer recurrence, CELL BIOLOGY AND TOXICOLOGY, ISSN: 0742-2091

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Huang H, Liu P, Ma D, Zhang H, Xu H, Zhou J, Zhao H, Zhao T, Li Cet al., 2022, Triiodothyronine attenuates neurocognitive dysfunction induced by sevoflurane in the developing brain of neonatal rats, JOURNAL OF AFFECTIVE DISORDERS, Vol: 297, Pages: 455-462, ISSN: 0165-0327

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Ma D, 2022, Methionine restriction prevents lipopolysaccharide-inducedacute lung injury via modulating CSE/H2S pathway, Nutrients, Vol: 14, Pages: 1-15, ISSN: 2072-6643

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) result in high mortality, whereas effective treatments are limited. Methionine restriction (MR) has been reported to offer various benefits against multiple pathological processes of organ injuries. However, it remains unknown whether MR has any potential therapeutic value for ALI/ARDS. The current study was set to investigate the therapeutic potential of MR on lipopolysaccharide (LPS)-induced ALI and its underlying mechanisms. We found that MR attenuated LPS-induced pulmonary edema, hemorrhage, atelectasis, and alveolar epithelial cell injuries in mice. MR upregulated cystathionine-gamma-lyase (CSE) expression and enhanced the production of hydrogen sulfide (H2S). MR also inhibited the activation of Toll-like receptors 4 (TLR4)/NF-κB/NOD-like receptor protein 3 (NLRP3), then reduced IL-1β, IL-6, and TNF-α release and immune cell infiltration. Moreover, the protective effects of MR on LPS-induced ALI were abrogated by inhibiting CSE, whereas exogenous H2S treatment alone mimicked the protective effects of MR in Cse−/− mice after LPS administration. In conclusion, our findings showed that MR attenuated LPS-induced lung injury through CSE and H2S modulation. This work suggests that developing MR towards clinical use for ALI/ARDS patients may be a valuable strategy.

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Liu L, Sun Q, Davis F, Mao J, Zhao H, Ma Det al., 2022, Epithelial-mesenchymal transition in organ fibrosis development: current understanding and treatment strategies, BURNS & TRAUMA, Vol: 10, ISSN: 2321-3868

Journal article

Chen Q, Qin Z, Sun Y, Liu X, Soo AP, Chang E, Sun Q, Yi B, Wang D-X, Zhao H, Ma D, Gu Jet al., 2022, Dexmedetomidine Activates Akt, STAT6 and IRF4 Modulating Cytoprotection and Macrophage Anti-Inflammatory Phenotype Against Acute Lung Injury in vivo and in vitro, JOURNAL OF INFLAMMATION RESEARCH, Vol: 15, Pages: 2707-2720

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Chen L, Alam A, Pac-Soo A, Chen Q, Shang Y, Zhao H, Yao S, Ma Det al., 2021, Pretreatment with valproic acid alleviates pulmonary fibrosis through epithelial-mesenchymal transition inhibition in vitro and in vivo., Lab Invest, Vol: 101, Pages: 1166-1175

Epithelial-mesenchymal transition (EMT) plays a crucial role in the development of pulmonary fibrosis. This study aims to investigate the effects of valproic acid (VPA) on EMT in vitro and in vivo. In vitro, EMT was induced by the administration of transforming growth factor-β1 (TGF-β1) in a human alveolar epithelial cell line (A549). The dose effects of VPA (0.1-3 mM) on EMT were subsequently evaluated at different timepoints. VPA (1 mM) was applied prior to the administration of TGF-β1 and the expression of E-cadherin, vimentin, p-Smad2/3 and p-Akt was assessed. In addition, the effects of a TGF-β type I receptor inhibitor (A8301) and PI3K-Akt inhibitor (LY294002) on EMT were evaluated. In vivo, the effects of VPA on bleomycin-induced lung fibrosis were evaluated by assessing variables such as survival rate, body weight and histopathological changes, whilst the expression of E-cadherin and vimentin in lung tissue was also evaluated. A8301 and LY294002 were used to ascertain the cellular signaling pathways involved in this model. The administration of VPA prior to TGF-β1 in A549 cells prevented EMT in both a time- and concentration-dependent manner. Pretreatment with VPA downregulated the expression of both p-Smad2/3 and p-Akt. A8301 administration increased the expression of E-cadherin and reduced the expression of vimentin. LY294002 inhibited Akt phosphorylation induced by TGF-β1 but failed to prevent EMT. Pretreatment with VPA both increased the survival rate and prevented the loss of body weight in mice with pulmonary fibrosis. Interestingly, both VPA and A8301 prevented EMT and facilitated an improvement in lung structure. Overall, pretreatment with VPA attenuated the development of pulmonary fibrosis by inhibiting EMT in mice, which was associated with Smad2/3 deactivation but without Akt cellular signal involvement. This study investigated the effect of valproic acid (VPA) on epithelial-mesenchymal transition (EMT). In vitro, VP

Journal article

Chen L, Alam A, Pac-Soo A, Chen Q, Shang Y, Zhao H, Yao S, Ma Det al., 2021, Pretreatment with valproic acid alleviates pulmonary fibrosis through epithelial-mesenchymal transition inhibition in vitro and in vivo, LABORATORY INVESTIGATION, Vol: 101, Pages: 1166-1175, ISSN: 0023-6837

Journal article

Ishikawa M, Iwasaki M, Zhao H, Saito J, Hu C, Sun Q, Sakamoto A, Ma Det al., 2021, Inhalational Anesthetics Inhibit Neuroglioma Cell Proliferation and Migration via miR-138,-210 and-335, INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol: 22

Journal article

Ishikawa M, Iwasaki M, Zhao H, Saito J, Hu C, Sun Q, Sakamoto A, Ma Det al., 2021, Sevoflurane and Desflurane Exposure Enhanced Cell Proliferation and Migration in Ovarian Cancer Cells via miR-210 and miR-138 Downregulation, INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol: 22

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Zhao H, Davies R, Ma D, 2021, Potential therapeutic value of dexmedetomidine in COVID-19 patients admitted to ICU., Br J Anaesth, Vol: 126, Pages: e33-e35

Journal article

Iwasaki M, Saito J, Zhao H, Sakamoto A, Hirota K, Ma Det al., 2020, Inflammation Triggered by SARS-CoV-2 and ACE2 Augment Drives Multiple Organ Failure of Severe COVID-19: Molecular Mechanisms and Implications, INFLAMMATION, Vol: 44, Pages: 13-34, ISSN: 0360-3997

Journal article

Zhen C, Zhao H, Wu L, Alam A, Eguchi S, Weng H, Ma Det al., 2020, The Role of Neutrophil NETosis in Organ Injury: Novel Inflammatory Cell Death Mechanisms, INFLAMMATION, Vol: 43, Pages: 2021-2032, ISSN: 0360-3997

Journal article

Yang S-R, Hua K-F, Chu LJ, Hwu Y-K, Yang S-M, Wu C-Y, Lin T-J, Weng J-C, Zhao H, Hsu W-H, Liu F-C, Liaw W-J, Ma D, Ka S-M, Chen Aet al., 2020, Xenon blunts NF-kappa B/NLRP3 inflammasome activation and improves acute onset of accelerated and severe lupus nephritis in mice, KIDNEY INTERNATIONAL, Vol: 98, Pages: 378-390, ISSN: 0085-2538

Journal article

Zhang W, Sheng B, Chen S, Zhao H, Wu L, Sun Y, Cui J, Zhu X, Ma Det al., 2020, Sevoflurane Enhances Proliferation, Metastatic Potential of Cervical Cancer Cells via the Histone Deacetylase 6 Modulation In Vitro, ANESTHESIOLOGY, Vol: 132, Pages: 1469-1481, ISSN: 0003-3022

Journal article

Hu C, Huang Y, Wu L, Zhao H, Pac Soo C, Lian Q, Ma Det al., 2020, Apoptosis and necroptosis occur in the different brain regions of hippocampus in a rat model of hypoxia asphyxia, INTERNATIONAL JOURNAL OF NEUROSCIENCE, Vol: 131, Pages: 843-853, ISSN: 0020-7454

Journal article

Hu C, Liu Z, Zhao H, Wu L, Lian Q, Ma D, Li JVet al., 2020, A biochemical comparison of the lung, colonic, brain, renal, and ovarian cancer cell lines using 1H-NMR spectroscopy, Bioscience Reports, Vol: 40, ISSN: 0144-8463

Cancer cell lines are very often used for cancer research. However, continuous genetic instability-induced heterogeneity of cell lines can hinder the reproducibility of cancer research. Molecular profiling approaches including transcriptomics, chromatin modification profiling and proteomics are used to evaluate the phenotypic characteristics of cell lines. However, these do not reflect the metabolic function at the molecular level. Metabolic phenotyping is a powerful tool to profile the biochemical composition of cell lines. In this study, 1H-NMR spectroscopy-based metabolic phenotyping was used to detect metabolic differences among 5 cancer cell lines, namely, lung (A549), colonic (Caco2), brain (H4), renal (RCC), and ovarian (SKOV3) cancer cells. The concentrations of choline, creatine, lactate, alanine, fumarate and succinate varied remarkably among different cell types.The significantly higher intracellular concentrations of glutathione, myo-inositol, and phosphocholine were found in the SKOV3 cell line relative to other cell lines. Glutamate is higher in both SKOV3 and RCC cells compared to other cell lines. For cell culture media analysis, isopropanol was found to be the highest in RCC media, followed by A549 and SKOV3 media, while acetone was the highest in A549, followed by RCC and SKOV3. These results demonstrated that 1H-NMR-based metabolic phenotyping approach allows us to characterize specific metabolic signatures of cancer cell lines and provides phenotypical information of cellular metabolism.

Journal article

Zhao H, Chen Q, Huang H, Suen KC, Alam A, Cui J, Ciechanowicz S, Ning J, Lu K, Takata M, Gu J, Ma Det al., 2019, Osteopontin mediates necroptosis in lung injury after transplantation of ischaemic renal allografts in rats, BRITISH JOURNAL OF ANAESTHESIA, Vol: 123, Pages: 519-530, ISSN: 0007-0912

Journal article

Duan J, Yang Z, Huang J, Zhu Y, Zhao H, Unwith S, Gao X, Lu K, Ning Jet al., 2019, Inhibition of tyrosine kinases protects against lipopolysaccharide-induced acute lung injury by preventing nuclear export of Nrf2, JOURNAL OF CELLULAR BIOCHEMISTRY, Vol: 120, Pages: 12331-12339, ISSN: 0730-2312

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Wu L, Zhao H, Weng H, Ma Det al., 2019, Lasting effects of general anesthetics on the brain in the young and elderly: "mixed picture" of neurotoxicity, neuroprotection and cognitive impairment, JOURNAL OF ANESTHESIA, Vol: 33, Pages: 321-335, ISSN: 0913-8668

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Chen L, Zhao H, Alam A, Mi E, Eguchi S, Yao S, Ma Det al., 2019, Postoperative remote lung injury and its impact on surgical outcome, BMC ANESTHESIOLOGY, Vol: 19, ISSN: 1471-2253

Journal article

Sun Y-B, Zhao H, Mu D-L, Zhang W, Cui J, Wu L, Alam A, Wang D-X, Ma Det al., 2019, Dexmedetomidine inhibits astrocyte pyroptosis and subsequently protects the brain in in vitro and in vivo models of sepsis, Cell Death and Disease, Vol: 10, ISSN: 2041-4889

Sepsis is life-threatening and often leads to acute brain damage. Dexmedetomidine, an α2-adrenoceptor agonist, has been reported to possess neuroprotective effects against various brain injury but underlying mechanisms remain elusive. In this study, in vitro and in vivo models of sepsis were used to explore the effects of dexmedetomidine on the inflammasome activity and its associated glia pyroptosis and neuronal death. In vitro, inflammasome activation and pyroptosis were found in astrocytes following lipopolysaccharide (LPS) exposure. Dexmedetomidine significantly alleviated astrocyte pyroptosis and inhibited histone release induced by LPS. In vivo, LPS treatment in rats promoted caspase-1 immunoreactivity in astrocytes and caused an increase in the release of pro-inflammatory cytokines of IL-1β and IL-18, resulting in neuronal injury, which was attenuated by dexmedetomidine; this neuroprotective effect was abolished by α2-adrenoceptor antagonist atipamezole. Dexmedetomidine significantly reduced the high mortality rate caused by LPS challenge. Our data demonstrated that dexmedetomidine may protect glia cells via reducing pyroptosis and subsequently protect neurons, all of which may preserve brain function and ultimately improve the outcome in sepsis.

Journal article

Li T, Chen L, Zhao H, Wu L, Masters J, Han C, Hirota K, Ma Det al., 2019, Both Bupivacaine and Levobupivacaine inhibit colon cancer cell growth but not melanoma cells in vitro, Journal of Anesthesia, Vol: 33, Pages: 17-25, ISSN: 0913-8668

BackgroundRetrospective studies indicate that the use of regional anaesthesia causes a reduction in cancer recurrence after oncological surgery, which could be due to anaesthetic’s negating effect on immunosuppression related to the surgical stress response. Local anaesthetics may also exert direct suppressive effects on malignant cells, an area where further investigation is urgently needed.MethodsHuman colon cancer cells and human melanoma cells were cultured and then treated with 1 mM bupivacaine or levobupivacaine for up to 24 or 48 h. Their migratory ability was measured by scratch assay, proliferation determined with Ki67 immunofluorescence staining, and apoptosis accessed with annexin V and PI staining on flow cytometry. The effects of bupivacaine and levobupivacaine on cellular signaling and molecular response, specifically, on endoplasmic reticulum stress (ERS), were studied with immunostaining and western blot.ResultsIn colon cancer cells, treatment with bupivacaine and levobupivacaine significantly inhibited cell migration (**p < 0.01, ***p < 0.001; n = 4) and proliferation (**p < 0.01; n = 4), while increasing the expression of CHOP (***p < 0.001; n = 4) and decreased the expression of Grp78 (*p < 0.05; n = 4). These effects were not mirrored by melanoma cells, such that no significant increase in apoptosis was seen in either melanoma cell lines following treatment.ConclusionThese in vitro data suggested that both bupivacaine and levobupivacaine suppress colorectal adenocarcinoma cell proliferation and migration, which are concurrent with increased endoplasmic reticulum stress. Conversely, melanoma cells are more resilient to these two commonly used local anaesthetics. Further in vivo studies or clinical trials are needed.

Journal article

Singh M, Nabavi E, Zhou Y, Gallina ME, Zhao H, Ruenraroengsak P, Porter AE, Ma D, Cass AEG, Hanna GB, Elson DSet al., 2019, Laparoscopic fluorescence image-guided photothermal therapy enhances cancer diagnosis and treatment, Nanotheranostics, Vol: 3, Pages: 89-102, ISSN: 2206-7418

Endoscopy is the gold standard investigation in the diagnosis of gastrointestinal cancers and the management of early and pre-malignant lesions either by resection or ablation. Recently gold nanoparticles have shown promise in cancer diagnosis and therapeutics (theranostics). The combination of multifunctional gold nanoparticles with near infrared fluorescence endoscopy for accurate mapping of early or pre-malignant lesions can potentially enhance diagnostic efficiency while precisely directing endoscopic near infrared photothermal therapy for established cancers. The integration of endoscopy with near infrared fluorescence imaging and photothermal therapy was aided by the accumulation of our multifunctionalized PEG-GNR-Cy5.5-anti-EGFR-antibody gold nanorods within gastrointestinal tumor xenografts in BALB/c mice. Control mice (with tumors) received either gold nanorods or photothermal therapy, while study mice received both treatment modalities. Local (tumor-centric) and systemic effects were examined for 30 days. Clear endoscopic near infrared fluorescence signals were observed emanating specifically from tumor sites and these corresponded precisely to the tumor margins. Endoscopic fluorescence-guided near infrared photothermal therapy successfully induced tumor ablations in all 20 mice studied, with complete histological clearance and minimal collateral damage. Multi-source analysis from histology, electron microscopy, mass spectrometry, blood, clinical evaluation, psychosocial and weight monitoring demonstrated the inherent safety of this technology. The combination of this innovative nanotechnology with gold standard clinical practice will be of value in enhancing the early optical detection of gastrointestinal cancers and a useful adjunct for its therapy.

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Ning J, Zhao H, Chen B, Mi EZ, Yang Z, Qing W, Lam KWJ, Yi B, Chen Q, Gu J, Ichim T, Bogin V, Lu K, Ma Det al., 2019, Argon Mitigates Impaired Wound Healing Process and Enhances Wound Healing In Vitro and In Vivo, THERANOSTICS, Vol: 9, Pages: 477-490, ISSN: 1838-7640

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Wang C, Datoo T, Zhao H, Wu L, Date A, Jiang C, Sanders RD, Wang G, Bevan C, Ma Det al., 2018, Midazolam and Dexmedetomidine Affect Neuroglioma and Lung Carcinoma Cell Biology In Vitro and In Vivo, ANESTHESIOLOGY, Vol: 129, Pages: 1000-1014, ISSN: 0003-3022

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Ma J, Chen Q, Li J, Zhao H, Mi E, Chen Y, Yi B, Ning J, Ma D, Lu K, Gu Jet al., 2018, Dexmedetomidine-Mediated Prevention of Renal Ischemia-Reperfusion Injury Depends in Part on Cholinergic Anti-Inflammatory Mechanisms., Anesth Analg

BACKGROUND: Organ ischemia-reperfusion injury often induces local and systemic inflammatory responses, which in turn worsen organ injury. These inflammatory responses can be regulated by the central nervous system, particularly by the vagal nerve and nicotinic acetylcholine receptors, which are the key components of cholinergic anti-inflammatory pathway. Activation of the cholinergic anti-inflammatory pathway can suppress excessive inflammatory responses and be a potential strategy for prevention of ischemia-reperfusion injury of organs including the kidney. METHODS: Vagal nerve activity, plasma acetylcholine, catecholamine and inflammatory mediators, renal tissue injury, and cell death were measured in mice with bilateral renal ischemia/reperfusion with or without treatment with dexmedetomidine (Dex), an α2-adrenergic receptor agonist. RESULTS: Dex significantly increased the discharge frequency of the cervical vagal nerve by up to 142 Hz (mean) (P < .001), and preserved kidney gross morphology and structure and attenuated cell apoptosis after ischemia-reperfusion. Furthermore, Dex also significantly increased acetylcholine release to 135.8 pmol/L (median) when compared to that (84.7 pmol/L) in the sham group (P < .001) and reduced the levels of several inflammatory mediators induced by renal ischemia/reperfusion. All the effects were abolished by vagotomy, splenectomy, or combinative administration of atipamezole, an α2-adrenergic receptor antagonist. CONCLUSIONS: Our findings suggest that Dex provides renoprotection, at least in part, through anti-inflammatory effects of the parasympathetic nervous system activation in addition to its direct actions on α2-adrenergic receptors.

Journal article

Zhao H, Ma D, Huang H, Alam A, Chen Q, Suen KC, Cui J, Sun Q, Ologunde R, Zhang W, Lian Qet al., 2018, VEGF mitigates histone induced pyroptosis in the remote liver injury associated with renal allograft ischemia-reperfusion injury in rats, American Journal of Transplantation, Vol: 18, Pages: 1890-1903, ISSN: 1600-6135

Clinical evidence indicated a possible link between renal injury and remote liver injury. Herein, we investigated whether extracellular histone mediates remote hepatic damage following renal graft ischemia-reperfusion injury, whilst vascular endothelial growth factor (VEGF) is protective against remote hepatic injury. In vitro, hepatocyte HepG2 cultures were treated with histone. In vivo, the Brown-Norway renal graft was stored in 4°C preserving solution for 24 hours and then transplanted into Lewis rat recipient; blood samples and livers from recipients were harvested 24 hours after surgery. Prolonged cold ischemia in renal grafts enhanced liver injury 24 hours after engraftment. Caspase-1, ASC, NLRP3 and AIM2 expression in hepatocyte, CD68+ infiltrating macrophages, tissue and serum IL-1β and IL-18 were greatly elevated, indicating that pyroptosis occurred in the liver and resulted in acute liver functional impairment. Blocking caspase-1 pathway decreased the number of necrotic hepatocytes. VEGF treatment suppressed the hepatocyte pyroptosis and liver function was partially restored. Our data suggested that renal allograft ischemia-reperfusion injury is likely associated with acute liver damage due to hepatocyte pyroptosis induced by histone and such injury may be protected by VEGF administration. VEGF, therefore, may serve as a new strategy against other remote organ injuries related to renal transplant.

Journal article

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