Displaying publications 141 - 160 of 252 in total

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  1. Dose dependent elevation of plasma tocotrienol levels and its effect on arterial compliance, plasma total antioxidant status, and lipid profile in healthy humans supplemented with tocotrienol rich vitamin E
    Rasool AH, Yuen KH, Yusoff K, Wong AR, Rahman AR
    J Nutr Sci Vitaminol (Tokyo), 2006 Dec;52(6):473-8.
    PMID: 17330512
    Tocotrienols are a class of vitamin E reported to be potent antioxidants, besides having the ability to inhibit the HMG-CoA reductase enzyme. This study assessed the effects of 3 doses of tocotrienol-rich vitamin E (TRE) on plasma tocotrienol isomer concentration, arterial compliance, plasma total antioxidant status (TAS), aortic systolic blood pressure (ASBP), serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) in healthy males.

    METHODOLOGY: This randomised, blinded end-point, placebo-controlled clinical trial with a parallel design involved 36 healthy male subjects who took either an oral placebo or TRE at doses of 80, 160 or 320 mg daily for 2 mo. Baseline and end-of-treatment measurements of vitamin E concentration, arterial compliance [assessed by aortic femoral pulse wave velocity (PWV) and augmentation index (AI)], ASBP, plasma TAS, serum TC and LDL-C were taken.

    RESULTS: Baseline tocotrienol isomer concentrations were low and not detectable in some subjects. Upon supplementation, all TRE-treated groups showed significant difference from placebo for their change in alpha, gamma and delta tocotrienol concentrations from baseline to end of treatment. There was a linear dose and blood level relationship for all the isomers. There was no significant difference between groups for their change in PWV, AI, plasma TAS, ASBP, TC or LDL-C from baseline to end of treatment. Groups 160 mg (p = 0.024) and 320 mg (p = 0.049) showed significant reductions in their ASBP. Group 320 mg showed a significant 9.2% improvement in TAS.

    CONCLUSION: TRE at doses up to 320 mg daily were well tolerated. Treatment significantly increased alpha, delta, and gamma tocotrienol concentrations but did not significantly affect arterial compliance, plasma TAS, serum TC or LDL-C levels in normal subjects.

  2. DNA sequence analysis of a small cryptic plasmid from Lactococcus lactis subsp. lactis M14
    Raha AR, Hooi WY, Mariana NS, Radu S, Varma NR, Yusoff K
    Plasmid, 2006 Jul;56(1):53-61.
    PMID: 16675013
    A small plasmid designated pAR141 was isolated from Lactococcus lactis subsp. lactis M14 and its complete 1,594 base pair nucleotide sequence was determined. Analysis of the sequence indicated that this plasmid does not carry any industrially important determinants besides the elements involved in plasmid replication and control. The transcriptional repressor CopG and replication initiation protein RepB appeared as a single operon. A small countertranscribed RNA (ctRNA) coding region was found between the copG and repB genes. The double strand origin (dso) and single strand origin (sso) of rolling circle replicating (RCR) plasmids were also identified in pAR141, suggesting that this plasmid replicates by rolling circle (RC) mode. This observation was supported by S1 nuclease and Southern hybridization analyses.
  3. Goniothalamin induces apoptosis in vascular smooth muscle cells
    Chan KM, Rajab NF, Ishak MH, Ali AM, Yusoff K, Din LB, et al.
    Chem Biol Interact, 2006 Feb 1;159(2):129-40.
    PMID: 16297902
    Restenosis represents a major impediment to the success of coronary angioplasty. Abnormal proliferation of vascular smooth muscle cells (VSMCs) has been shown to be an important process in the pathogenesis of restenosis. A number of agents, particularly rapamycin and paclitaxel, have been shown to impact on this process. This study was carried out to determine the mechanisms of cytotoxicity of goniothalamin (GN) on VSMCs. Results from MTT cytotoxicity assay showed that the IC(50) for GN was 4.4 microg/ml (22 microM), which was lower compared to the clinically used rapamycin (IC(50) of 25 microg/ml [27.346 microM]). This was achieved primarily via apoptosis where up to 25.83 +/- 0.44% of apoptotic cells were detected after 72 h treatment with GN. In addition, GN demonstrated similar effects as rapamycin in inhibiting VSMCs proliferation using bromodeoxyuridine (BrdU) cell proliferation assay after 72 h treatment at IC(50) concentration (p > 0.05). In order to understand the mechanisms of GN, DNA damage detection using comet assay was determined at 2h post-treatment with GN. Our results showed that there was a concentration-dependent increase in DNA damage in VSMCs prior to cytotoxicity. Moreover, GN effects were comparable to rapamycin. In conclusion, our data show that GN initially induces DNA damage which subsequently leads to cytotoxicity primarily via apoptosis in VSMCs.
  4. Cytolytic effects and apoptosis induction of Newcastle disease virus strain AF2240 on anaplastic astrocytoma brain tumor cell line
    Ali R, Alabsi AM, Ali AM, Ideris A, Omar AR, Yusoff K, et al.
    Neurochem Res, 2011 Nov;36(11):2051-62.
    PMID: 21671106 DOI: 10.1007/s11064-011-0529-8
    Newcastle disease virus (NDV) is a member of genus Avulavirus within the family Paramyxoviridae. Interest of using NDV as an anticancer agent has arisen from its ability to kill tumor cells with limited toxicity to normal cells. In this investigation, the cytotolytic properties of NDV strain AF2240 were evaluated on brain tumor cell line, anaplastic astrocytoma (U-87MG), by using MTT assay. Cytological observations were studied using fluorescence microscopy and transmission electron microscopy to show the apoptogenic features of NDV on U-87MG. DNA laddering in agarose gel electrophoresis and terminal deoxyribonucleotide transferase-mediated dUTP-X nick end-labeling staining assay confirmed that the mode of cell death was by apoptosis. However, analysis of the cellular DNA content by flowcytometery showed that there was a loss of treated U-87MG cells in all cell cycle phases (G1, S and G2/M) accompanied with increasing in sub-G1 region (apoptosis peak). Early apoptosis was observed 6 h post-inoculation by annexin-V flow-cytometry method. It could be concluded that NDV strain AF2240 is a potent antitumor agent that induce apoptosis and its cytotoxicity increasing while increasing of time and virus titer.
  5. Partial protection against enterovirus 71 (EV71) infection in a mouse model immunized with recombinant Newcastle disease virus capsids displaying the EV71 VP1 fragment
    Ch'ng WC, Stanbridge EJ, Ong KC, Wong KT, Yusoff K, Shafee N
    J Med Virol, 2011 Oct;83(10):1783-91.
    PMID: 21837796 DOI: 10.1002/jmv.22198
    Enterovirus 71 (EV71) infection may cause severe neurological complications, particularly in young children. Despite the risks, there are still no commercially available EV71 vaccines. Hence, a candidate vaccine construct, containing recombinant Newcastle disease virus capsids that display an EV71 VP1 fragment (NPt-VP1(1-100) ) protein, was evaluated in a mouse model of EV71 infection. Previously, it was shown that this protein construct provoked a strong immune response in vaccinated adult rabbits. That study, however, did not address the issue of its effectiveness against EV71 infection in young animals. In the present study, EV71 viral challenge in vaccinated newborn mice resulted in more than 40% increase in survival rate. Significantly, half of the surviving mice fully recovered from their paralysis. Histological analysis of all of the surviving mice revealed a complete clearance of EV71 viral antigens from their brains and spinal cords. In hind limb muscles, the amounts of the antigens detected correlated with the degrees of tissue damage and paralysis. Findings from this study provide evidence that immunization with the NPt-VP1(1-100) immunogen in a newborn mouse model confers partial protection against EV71 infection, and also highlights the importance of NPt-VP1(1-100) as a possible candidate vaccine for protection against EV71 infections.
  6. Fulltext Lactococcus lactis M4, a potential host for the expression of heterologous proteins
    Noreen N, Hooi WY, Baradaran A, Rosfarizan M, Sieo CC, Rosli MI, et al.
    Microb Cell Fact, 2011;10:28.
    PMID: 21518457 DOI: 10.1186/1475-2859-10-28
    Many plasmid-harbouring strains of Lactococcus lactis have been isolated from milk and other sources. Plasmids of Lactococcus have been shown to harbour antibiotic resistance genes and those that express some important proteins. The generally regarded as safe (GRAS) status of L. lactis also makes it an attractive host for the production of proteins that are beneficial in numerous applications such as the production of biopharmaceutical and nutraceutical. In the present work, strains of L. lactis were isolated from cow's milk, plasmids were isolated and characterised and one of the strains was identified as a potential new lactococcal host for the expression of heterologous proteins.
  7. Fulltext The matrix (M) protein of Newcastle disease virus binds to human bax through its BH3 domain
    Molouki A, Hsu YT, Jahanshiri F, Abdullah S, Rosli R, Yusoff K
    Virol J, 2011;8:385.
    PMID: 21810274 DOI: 10.1186/1743-422X-8-385
    The underlying mechanisms by which Newcastle disease virus (NDV) kills cancer cells are still unclear. Recent discoveries have shown that many viruses contain Bcl-2 homology-like domains which enabled their interaction with Bcl-2 family members, and thereby accounting for their virulence and pathogenicity. Alignment of the protein sequences of Malaysian strain of NDV, known as AF2240, with those from members of the human Bcl-2 family showed many similar regions; most notably we found that its matrix (AF2240-M) protein, large (AF2240-L) protein and fusion (AF2240-F) protein all contain BH3-like regions. In addition, there are BH1-like domains in these proteins, where AF2240-F and Mcl-1 share 55% identity within this region. To further investigate our hypothesis that the presence of the BH3-like domains in these proteins may convey cytotoxicity, AF2240-M and AF2240-F genes were cloned into pFLAG and pEGFP.N2 vectors and transfected into HeLa cells. The expression of these constructs promoted cell death. As shown by flow cytometry, AF2240-M protein with deleted BH3-like region showed five-fold decrease in apoptosis. Moreover, the construct containing the N-terminal of AF2240-M showed nearly the same cell death rate as to that of the full-length protein, strongly suggesting that the BH3-like domain within this protein participates in promoting cell death. Moreover, AF2240-M transfection promoted Bax redistribution to mitochondria. Therefore, to determine whether there is any direct interaction between NDV viral proteins with some members of the Bcl-2 family, various constructs were co-transfected into HeLa cells. Co-immunoprecipitation trials showed that the AF2240-M indeed directly interacted with Bax protein via its BH3-domain, as the mutant proteins failed to interact with Bax. AF2240-F failed to interact with any of the tested proteins, although Bcl-XL slowed down the rate of cell death caused by this construct by nearly five-fold. In a parallel experiment, the level of expression of endogenous Bax and Bcl-2 after infection of HeLa cells with NDV was assessed by qRT-PCR, but no statistically significant change was observed. Consequently, the Bax/Bcl-2 ratio at the mRNA level did not alter. Overall, our study has shed additional light into the mechanisms by which NDV induces apoptosis.
  8. Purification of recombinant nucleocapsid protein of Newcastle disease virus from unclarified feedstock using expanded bed adsorption chromatography
    Tan YP, Ling TC, Tan WS, Yusoff K, Tey BT
    Protein Expr Purif, 2006 Mar;46(1):114-21.
    PMID: 16139513
    In the present work, a single-step purification of recombinant nucleocapsid protein (NP) of the Newcastle disease virus (NDV) directly from unclarified feedstock using an expanded bed adsorption chromatography (EBAC) was developed. Streamline 25 column (ID = 25 mm) was used as a contactor and Streamline chelating adsorbent immobilized with Ni2+ ion was used as affinity adsorbent. The dynamic binding capacity of Ni2+ -loaded Streamline chelating adsorbent for the NP protein in unclarified feedstock was found to be 2.94 mg ml(-1) adsorbent at a superficial velocity of 200 cm h(-1). The direct purification of NP protein from unclarified feedstock using expanded bed adsorption has resulted in a 31% adsorption and 9.6% recovery of NP protein. The purity of the NP protein recovered was about 70% and the volume of processing fluid was reduced by a factor of 10. The results of the present study show that the IMA-EBAC developed could be used to combine the clarification, concentration and initial purification steps into a single-step operation.
  9. Comparative evaluation of three purification methods for the nucleocapsid protein of Newcastle disease virus from Escherichia coli homogenates
    Tan YP, Ling TC, Yusoff K, Tan WS, Tey BT
    J Microbiol, 2005 Jun;43(3):295-300.
    PMID: 15995649
    In the present study, the performances of conventional purification methods, packed bed adsorption (PBA), and expanded bed adsorption (EBA) for the purification of the nucleocapsid protein (NP) of Newcastle disease virus (NDV) from Escherichia coli homogenates were evaluated. The conventional methods for the recovery of NP proteins involved multiple steps, such as centrifugation, precipitation, dialysis, and sucrose gradient ultracentrifugation. For the PBA, clarified feedstock was used for column loading, while in EBA, unclarified feedstock was used. Streamline chelating immobilized with Ni2+ ion was used as an affinity ligand for both PBA and EBA. The final protein yield obtained in conventional and PBA methods was 1.26% and 5.56%, respectively. It was demonstrated that EBA achieved the highest final protein yield of 9.6% with a purification factor of 7. Additionally, the total processing time of the EBA process has been shortened by 8 times compared to that of the conventional method.
  10. Isolation and molecular identification of Nipah virus from pigs
    AbuBakar S, Chang LY, Ali AR, Sharifah SH, Yusoff K, Zamrod Z
    Emerg Infect Dis, 2004 Dec;10(12):2228-30.
    PMID: 15663869
    Nipah viruses from pigs from a Malaysian 1998 outbreak were isolated and sequenced. At least two different Nipah virus strains, including a previously unreported strain, were identified. The findings highlight the possibility that the Malaysia outbreaks had two origins of Nipah virus infections.
  11. Discovery of a novel dual functional phenylpyrazole-styryl hybrid that induces apoptotic and autophagic cell death in bladder cancer cells
    Leong SW, Wang J, Okuda KS, Su Q, Zhang Y, Abas F, et al.
    Eur J Med Chem, 2023 Apr 20;254:115335.
    PMID: 37098306 DOI: 10.1016/j.ejmech.2023.115335
    Unpleasant side effects and resistance development remained the Achilles heel of chemotherapy. Since low tumor-selectivity and monotonous effect of chemotherapy are closely related to such bottleneck, targeting tumor-selective multi-functional anticancer agents may be an ideal strategy in the search of new safer drugs. Herein, we report the discovery of compound 21, a nitro-substituted 1,5-diphenyl-3-styryl-1H-pyrazole that possesses dual functional characteristics. The 2D- and 3D-culture-based studies revealed that 21 not only could induce ROS-independent apoptotic and EGFR/AKT/mTOR-mediated autophagic cell deaths in EJ28 cells simultaneously but also has the ability in inducing cell death at both proliferating and quiescent zones of EJ28 spheroids. The molecular modelling analysis showed that 21 possesses EGFR targeting capability as it forms stable interactions in the EGFR active site. Together with its good safety profile in the zebrafish-based model, the present study showed that 21 is promising and may lead to the discovery of tumor-selective multi-functional anti-cancer agents.
  12. Fulltext Immunomodulatory effects of Newcastle disease virus AF2240 strain on human peripheral blood mononuclear cells
    Lam HY, Yusoff K, Yeap SK, Subramani T, Abd-Aziz S, Omar AR, et al.
    Int J Med Sci, 2014;11(12):1240-7.
    PMID: 25317070 DOI: 10.7150/ijms.8170
    Immunotherapy has raised the attention of many scientists because it hold promise to be an attractive therapeutic strategy to treat a number of disorders. In this study, the immunomodulatory effects of low titers of Newcastle disease virus (NDV) AF2240 on human peripheral blood mononuclear cells (PBMC) were analyzed. We evaluated cytokine secretion and PBMC activation by cell proliferation assay, immunophenotyping and enzyme linked immunosorbent assay. The proliferation of the human PBMC was measured to be 28.5% and 36.5% upon treatment with 8 hemaglutinin unit (HAU) and 2 HAU of NDV respectively. Interestingly, the percentage of cells with activating markers CD16 and CD56 were increased significantly. Furthermore, the intracellular perforin and granzyme levels were also increased upon virus infection. Human PBMC treated with NDV titer 8 HAU was found to stimulate the highest level of cytokine production including interferon-γ, interleukin-2 and interleukin-12. The release of these proteins contributes to the antitumor effect of PBMC against MCF-7 breast cancer cells. Based on the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay, activated human PBMC showed high cytolytic efficiency towards human breast tumor cells. In summary, NDV was able to stimulate PBMC proliferation, cytokine secretion and cytolytic activity.
  13. Fulltext Cardiovascular disease risk factors and socioeconomic variables in a nation undergoing epidemiologic transition
    Rasiah R, Yusoff K, Mohammadreza A, Manikam R, Tumin M, Chandrasekaran SK, et al.
    BMC Public Health, 2013;13:886.
    PMID: 24066906 DOI: 10.1186/1471-2458-13-886
    Cardiovascular disease (CVD) related deaths is not only the prime cause of mortality in the world, it has also continued to increase in the low and middle income countries. Hence, this study examines the relationship between CVD risk factors and socioeconomic variables in Malaysia, which is a rapidly growing middle income nation undergoing epidemiologic transition.
  14. Oral vaccine of Lactococcus lactis harbouring pandemic H1N1 2009 haemagglutinin1 and nisP anchor fusion protein elevates anti-HA1 sIgA levels in mice
    Joan SS, Pui-Fong J, Song AA, Chang LY, Yusoff K, AbuBakar S, et al.
    Biotechnol Lett, 2016 May;38(5):793-9.
    PMID: 26758876 DOI: 10.1007/s10529-016-2034-2
    An oral lactococcal-based vaccine which haboured the haemagglutinin1 (HA1) antigen fused to nisP anchor protein for the purpose of surface displaying the HA1 antigen was developed against H1N1 virus.
  15. Fulltext The impact of physical activity on cumulative cardiovascular disease risk factors among Malaysian adults
    Rasiah R, Thangiah G, Yusoff K, Manikam R, Chandrasekaran SK, Mustafa R, et al.
    BMC Public Health, 2015;15:1242.
    PMID: 26673166 DOI: 10.1186/s12889-015-2577-5
    Numerous studies have shown the importance of physical activity in reducing the morbidity and mortality rates caused by cardiovascular disease (CVD). However, most of these studies emphasise little on the cumulative effect of CVD risk factors. Hence, this study investigates the association between physical exercise and cumulative CVD risk factors among adults in three different age groups.
  16. Fulltext Surface display of glycosylated Tyrosinase related protein-2 (TRP-2) tumour antigen on Lactococcus lactis
    Kalyanasundram J, Chia SL, Song AA, Raha AR, Young HA, Yusoff K
    BMC Biotechnol, 2015;15:113.
    PMID: 26715153 DOI: 10.1186/s12896-015-0231-z
    The exploitation of the surface display system of food and commensal lactic acid bacteria (LAB) for bacterial, viral, or protozoan antigen delivery has received strong interest recently. The Generally Regarded as Safe (GRAS) status of the Lactococcus lactis coupled with a non-recombinant strategy of in-trans surface display, provide a safe platform for therapeutic drug and vaccine development. However, production of therapeutic proteins fused with cell-wall anchoring motifs is predominantly limited to prokaryotic expression systems. This presents a major disadvantage in the surface display system particularly when glycosylation has been recently identified to significantly enhance epitope presentation. In this study, the glycosylated murine Tyrosinase related protein-2 (TRP-2) with the ability to anchor onto the L. lactis cell wall was produced in suspension adapted Chinese Hamster Ovary (CHO-S) cells by expressing TRP-2 fused with cell wall anchoring LysM motif (cA) at the C-terminus.
  17. Fulltext Physical Activity in Malaysia: Are We Doing Enough? Findings from the REDISCOVER Study
    Nik-Nasir NM, Md-Yasin M, Ariffin F, Mat-Nasir N, Miskan M, Abu-Bakar N, et al.
    Int J Environ Res Public Health, 2022 Dec 15;19(24).
    PMID: 36554769 DOI: 10.3390/ijerph192416888
    Physical activity (PA) in the form of structured or unstructured exercise is beneficial for health. This paper aims to study PA levels across four domains according to the International Physical Activity Questionnaire (IPAQ) and its associated factors. A total of 7479 Malaysian adult participants between 18 to 90 years old from the REDISCOVER study who completed the IPAQ were analyzed. PA was calculated as MET-min per week and were categorized according to insufficiently active, sufficiently active and very active. Multinomial regression was used to determine the association between sociodemographic, clinical factors and the level of PA. The mean age of the participants was 51.68 (±9.5 SD). The total reported physical activity in median (IQR) was 1584.0 (0-5637.3) MET-min per week. The highest total for PA was in the domestic domain which is 490 (0-2400) MET-min per week. Factors associated with sufficiently active or very active PA include Malay ethnicity, no formal education, elementary occupation, current smokers and high HDL. Whereas low income, male and normal BMI are less likely to participate in sufficiently active or very active PA. Intervention to encourage higher PA levels in all domains is important to achieve recommended PA targets.
  18. Fulltext Lactococcus lactis secreting phage lysins as a potential antimicrobial against multi-drug resistant Staphylococcus aureus
    Chandran C, Tham HY, Abdul Rahim R, Lim SHE, Yusoff K, Song AA
    PeerJ, 2022;10:e12648.
    PMID: 35251775 DOI: 10.7717/peerj.12648
    BACKGROUND: Staphylococcus aureus is an opportunistic Gram-positive bacterium that can form biofilm and become resistant to many types of antibiotics. The treatment of multi-drug resistant Staphylococcus aureus (MDRSA) infection is difficult since it possesses multiple antibiotic-resistant mechanisms. Endolysin and virion-associated peptidoglycan hydrolases (VAPGH) enzymes from bacteriophage have been identified as potential alternative antimicrobial agents. This study aimed to assess the ability of Lactococcus lactis NZ9000 secreting endolysin and VAPGH from S. aureus bacteriophage 88 to inhibit the growth of S. aureus PS 88, a MDRSA.

    METHOD: Endolysin and VAPGH genes were cloned and expressed in L. lactis NZ9000 after fusion with the SPK1 signal peptide for secretion. The recombinant proteins were expressed and purified, then analyzed for antimicrobial activity using plate assay and turbidity reduction assay. In addition, the spent media of the recombinant lactococcal culture was analyzed for its ability to inhibit the growth of the S. aureus PS 88.

    RESULTS: Extracellular recombinant endolysin (Endo88) and VAPGH (VAH88) was successfully expressed and secreted from L. lactis which was able to inhibit S. aureus PS 88, as shown by halozone formation on plate assays as well as inhibition of growth in the turbidity reduction assay. Moreover, it was observed that the spent media from L. lactis NZ9000 expressing Endo88 and VAH88 reduced the viability of PS 88 by up to 3.5-log reduction with Endo88 being more efficacious than VAH88. In addition, Endo88 was able to lyse all MRSA strains tested and Staphylococcus epidermidis but not the other bacteria while VAH88 could only lyse S. aureus PS 88.

    CONCLUSION: Recombinant L. lactisNZ9000 expressing phage 88 endolysin may be potentially developed into a new antimicrobial agent for the treatment of MDRSA infection.

  19. Development of a recombinant non-replicating Newcastle disease virus
    Cheow PS, Tan TK, Song AA, Yusoff K, Chia SL
    Avian Pathol, 2025 Feb;54(1):149-157.
    PMID: 39318350 DOI: 10.1080/03079457.2024.2403412
    Development of nr-NDV.Reverse transfection was applied for the recovery of nr-NDV.Propagation of nr-NDV was done by sub-passaging transfected BSR T7/5 cells.Safety profile was done to prove that the nr-NDV is non-replicating.
  20. Viral vectors: design and delivery for small RNA
    Koh WC, Yusoff K, Song AAL, Saad N, Chia SL
    J Med Microbiol, 2025 Feb;74(2).
    PMID: 39950625 DOI: 10.1099/jmm.0.001972
    RNA interference regulates gene expression by selectively silencing target genes through the introduction of small RNA molecules, such as microRNA, small interfering RNA and short hairpin RNA. These molecules offer significant therapeutic potential for diverse human ailments like cancer, viral infections and neurodegenerative disorders. Whilst non-viral vectors like nanoparticles have been extensively explored for delivering these RNAs, viral vectors, with superior specificity and delivery efficiency, remain less studied. This review examines current viral vectors for small RNA delivery, focusing on design strategies and characteristics. It compares the advantages and drawbacks of each vector, aiding readers in selecting the optimal one for small RNA delivery.
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