| MeSH term | MeSH ID | Detail |
|---|---|---|
| Leukemia, Hairy Cell | D007943 | 5 associated lipids |
| Abetalipoproteinemia | D000012 | 7 associated lipids |
| Xanthomatosis | D014973 | 17 associated lipids |
| Carcinoma, Hepatocellular | D006528 | 140 associated lipids |
Total
4
lanosterol
lanosterol is a lipid of Sterol Lipids (ST) class. Lanosterol is associated with abnormalities such as Infection, Atherosclerosis, Myocardial Infarction, Chagas Disease and Fatty Liver. The involved functions are known as Signal, Cytokinesis, physiological aspects, Stereochemistry and ergosterol biosynthetic process. Lanosterol often locates in Body tissue, Membrane, Plasma membrane, Tissue membrane and Cytoskeletal Filaments. The associated genes with lanosterol are Retinoic Acid Response Element, P4HTM gene, CYP51A1 gene, HM13 gene and SC4MOL gene. The related lipids are pneumocysterol, Sterols, lanosteryl acetate, ebericol and cycloartenol. The related experimental models are Knock-out.
Cross Reference
Introduction
To understand associated biological information of lanosterol, we collected biological information of abnormalities, associated pathways, cellular/molecular locations, biological functions, related genes/proteins, lipids and common seen animal/experimental models with organized paragraphs from literatures.
What diseases are associated with lanosterol?
lanosterol is suspected in Atherosclerosis, Chagas Disease, vaginalis, hypercholesterolemia, Obesity, Infection and other diseases in descending order of the highest number of associated sentences.
Related references are mostly published in these journals:
| Disease | Cross reference | Weighted score | Related literature |
|---|
Loading... please refresh the page if content is not showing up.
Possible diseases from mapped MeSH terms on references
We collected disease MeSH terms mapped to the references associated with lanosterol
PubChem Associated disorders and diseases
What pathways are associated with lanosterol
Lipid pathways are not clear in current pathway databases. We organized associated pathways with lanosterol through full-text articles, including metabolic pathways or pathways of biological mechanisms.
Related references are published most in these journals:
| Pathway name | Related literatures |
|---|
Loading... please refresh the page if content is not showing up.
PubChem Biomolecular Interactions and Pathways
Link to PubChem Biomolecular Interactions and PathwaysWhat cellular locations are associated with lanosterol?
Visualization in cellular structure
Associated locations are in red color. Not associated locations are in black.
Related references are published most in these journals:
| Location | Cross reference | Weighted score | Related literatures |
|---|
Loading... please refresh the page if content is not showing up.
What functions are associated with lanosterol?
Related references are published most in these journals:
| Function | Cross reference | Weighted score | Related literatures |
|---|
What lipids are associated with lanosterol?
Related references are published most in these journals:
| Lipid concept | Cross reference | Weighted score | Related literatures |
|---|
Loading... please refresh the page if content is not showing up.
What genes are associated with lanosterol?
Related references are published most in these journals:
| Gene | Cross reference | Weighted score | Related literatures |
|---|
What common seen animal models are associated with lanosterol?
Knock-out
Knock-out are used in the study 'Dual biosynthetic pathways to phytosterol via cycloartenol and lanosterol in Arabidopsis.' (Ohyama K et al., 2009), Knock-out are used in the study 'Expression, purification, and characterization of Aspergillus fumigatus sterol 14-alpha demethylase (CYP51) isoenzymes A and B.' (Warrilow AG et al., 2010) and Knock-out are used in the study 'Potential biological functions of cytochrome P450 reductase-dependent enzymes in small intestine: novel link to expression of major histocompatibility complex class II genes.' (D'Agostino J et al., 2012).
Related references are published most in these journals:
| Model | Cross reference | Weighted score | Related literatures |
|---|
Loading... please refresh the page if content is not showing up.
NCBI Entrez Crosslinks
All references with lanosterol
Download all related citations| Authors | Title | Published | Journal | PubMed Link |
|---|---|---|---|---|
| Dutra RC et al. | The antinociceptive effects of the tetracyclic triterpene euphol in inflammatory and neuropathic pain models: The potential role of PKCε. | 2015 | Neuroscience | pmid:26143011 |
| Singh GB et al. | Hypotensive activity of 8,24-euphadien-3 beta-ol (euphol). | 1989 | Planta Med. | pmid:2616667 |
| Li G et al. | Endophytic Diaporthe sp. LG23 Produces a Potent Antibacterial Tetracyclic Triterpenoid. | 2015 | J. Nat. Prod. | pmid:26186257 |
| Hejtmancik JF | Ophthalmology: Cataracts dissolved. | 2015 | Nature | pmid:26200338 |
| Zhao L et al. | Lanosterol reverses protein aggregation in cataracts. | 2015 | Nature | pmid:26200341 |
| Mosa RA et al. | In vivo antihyperglycemic activity of a lanosteryl triterpene from Protorhus longifolia. | 2015 | Molecules | pmid:26205060 |
| Zhao XR et al. | Inhibitory Effects of Highly Oxygenated Lanostane Derivatives from the Fungus Ganoderma lucidum on P-Glycoprotein and α-Glucosidase. | 2015 | J. Nat. Prod. | pmid:26222905 |
| Ruan W et al. | Distinct Responses of Cytotoxic Ganoderma lucidum Triterpenoids in Human Carcinoma Cells. | 2015 | Phytother Res | pmid:26292672 |
| Hu ZX et al. | Kadcoccinones A-F, New Biogenetically Related Lanostane-Type Triterpenoids with Diverse Skeletons from Kadsura coccinea. | 2015 | Org. Lett. | pmid:26348535 |
| Gundersen BB | Clearing cataracts without surgery. | 2015 | Lab Anim (NY) | pmid:26398599 |
| Chen CL et al. | Euphol from Euphorbia tirucalli Negatively Modulates TGF-β Responsiveness via TGF-β Receptor Segregation inside Membrane Rafts. | 2015 | PLoS ONE | pmid:26448474 |
| Lee S et al. | Lanosterol influences cytoplasmic maturation of pig oocytes in vitro and improves preimplantation development of cloned embryos. | 2016 | Theriogenology | pmid:26494176 |
| Kuo YH et al. | Antidiabetic and Antihyperlipidemic Properties of a Triterpenoid Compound, Dehydroeburicoic Acid, from Antrodia camphorata in Vitro and in Streptozotocin-Induced Mice. | 2015 | J. Agric. Food Chem. | pmid:26503742 |
| Quinlan RA | DRUG DISCOVERY. A new dawn for cataracts. | 2015 | Science | pmid:26542559 |
| Chang TY et al. | Isolation and partial characterization of a cholesterol-requiring mutant of Chinese hamster ovary cells. | 1977 | Proc. Natl. Acad. Sci. U.S.A. | pmid:265577 |
| Wang J et al. | Protective Effect of Eburicoic Acid of the Chicken of the Woods Mushroom, Laetiporus sulphureus (Higher Basidiomycetes), Against Gastric Ulcers in Mice. | 2015 | Int J Med Mushrooms | pmid:26559696 |
| Stäubert C et al. | Increased lanosterol turnover: a metabolic burden for daunorubicin-resistant leukemia cells. | 2016 | Med. Oncol. | pmid:26698156 |
| Qiu J et al. | Neuroprotective and antioxidant lanostanoid triterpenes from the fruiting bodies of Ganoderma atrum. | 2016 | Fitoterapia | pmid:26709153 |
| Isaka M et al. | Antitubercular Lanostane Triterpenes from Cultures of the Basidiomycete Ganoderma sp. BCC 16642. | 2016 | J. Nat. Prod. | pmid:26716912 |
| Shanmugam PM et al. | Effect of lanosterol on human cataract nucleus. | 2015 | Indian J Ophthalmol | pmid:26862091 |
| Aoyama Y et al. | The 3-hydroxy group of lanosterol is essential for orienting the substrate site of cytochrome P-450(14DM) (lanosterol 14 alpha- demethylase). | 1989 | Biochim. Biophys. Acta | pmid:2688742 |
| Amen YM et al. | Lucidumol C, a new cytotoxic lanostanoid triterpene from Ganoderma lingzhi against human cancer cells. | 2016 | J Nat Med | pmid:26899240 |
| Pfaller M et al. | Effects of cilofungin (LY121019) on carbohydrate and sterol composition of Candida albicans. | 1989 | Eur. J. Clin. Microbiol. Infect. Dis. | pmid:2695329 |
| Popják G et al. | Inhibition of cholesterol synthesis and cell growth by 24(R,S),25-iminolanosterol and triparanol in cultured rat hepatoma cells. | 1989 | J. Biol. Chem. | pmid:2703486 |
| Novack GD | Eyes on New Product Development. | 2016 | J Ocul Pharmacol Ther | pmid:27058691 |
| Azrolan NI and Coleman PS | A discoordinate increase in the cellular amount of 3-hydroxy-3-methylglutaryl-CoA reductase results in the loss of rate-limiting control over cholesterogenesis in a tumour cell-free system. | 1989 | Biochem. J. | pmid:2705993 |
| Yeagle PL et al. | Differential effects of cholesterol and lanosterol on artificial membranes. | 1977 | Proc. Natl. Acad. Sci. U.S.A. | pmid:270726 |
| Li HJ et al. | Enhancement of ganoderic acid production by constitutively expressing Vitreoscilla hemoglobin gene in Ganoderma lucidum. | 2016 | J. Biotechnol. | pmid:27080449 |
| Sakamoto S et al. | Detection of Ganoderic Acid A in Ganoderma lingzhi by an Indirect Competitive Enzyme-Linked Immunosorbent Assay. | 2016 | Planta Med. | pmid:27093250 |
| Warrilow AG et al. | The Investigational Drug VT-1129 Is a Highly Potent Inhibitor of Cryptococcus Species CYP51 but Only Weakly Inhibits the Human Enzyme. | 2016 | Antimicrob. Agents Chemother. | pmid:27161631 |
| Aoyama Y and Yoshida Y | Interaction of lanosterol to cytochrome P-450 purified from yeast microscomes: evidence for contribution of cytochrome P-450 to lanosterol metabolism. | 1978 | Biochem. Biophys. Res. Commun. | pmid:27189 |
| Han J et al. | Officimalonic acids A-H, lanostane triterpenes from the fruiting bodies of Fomes officinalis. | 2016 | Phytochemistry | pmid:27216472 |
| Kwon J et al. | Lanostane Triterpenes Isolated from Antrodia heteromorpha and Their Inhibitory Effects on RANKL-Induced Osteoclastogenesis. | 2016 | J. Nat. Prod. | pmid:27266877 |
| Kuo YH et al. | Dehydroeburicoic Acid from Antrodia camphorata Prevents the Diabetic and Dyslipidemic State via Modulation of Glucose Transporter 4, Peroxisome Proliferator-Activated Receptor α Expression and AMP-Activated Protein Kinase Phosphorylation in High-Fat-Fed Mice. | 2016 | Int J Mol Sci | pmid:27271603 |
| Hargrove TY et al. | Human sterol 14α-demethylase as a target for anticancer chemotherapy: towards structure-aided drug design. | 2016 | J. Lipid Res. | pmid:27313059 |
| Katja DG et al. | Cytototoxic constituents from the bark of Chisocheton cumingianus (Meliaceae). | 2017 | J Asian Nat Prod Res | pmid:27329305 |
| AÄimoviÄ J et al. | Cytochrome P450 metabolism of the post-lanosterol intermediates explains enigmas of cholesterol synthesis. | 2016 | Sci Rep | pmid:27334049 |
| Venkatesh R et al. | Comment to: Effect of lanosterol on human nuclei. | 2016 | Indian J Ophthalmol | pmid:27488164 |
| Nes WD et al. | Metabolism of 24(R,S),25-epiminolanosterol to 25-aminolanosterol and lanosterol by Gibberella fujikuroi. | 1989 | Arch. Biochem. Biophys. | pmid:2751307 |
| OuYang Q et al. | Transcriptional profiling analysis of Penicillium digitatum, the causal agent of citrus green mold, unravels an inhibited ergosterol biosynthesis pathway in response to citral. | 2016 | BMC Genomics | pmid:27514516 |
| Sonoda Y et al. | Metabolism of 24,25-dihydrolanosterol analogs by partially purified cytochrome P-450(14DM) from rat liver microsomes. | 1989 | Chem. Pharm. Bull. | pmid:2752483 |
| Sakamoto S et al. | Immunochromatographic strip assay for detection of bioactive Ganoderma triterpenoid, ganoderic acid A in Ganoderma lingzhi. | 2016 | Fitoterapia | pmid:27575328 |
| Gill BS et al. | Evaluating anti-oxidant potential of ganoderic acid A in STAT 3 pathway in prostate cancer. | 2016 | Mol. Biol. Rep. | pmid:27640015 |
| Skinner C and Miraldi Utz V | Pharmacological approaches to restoring lens transparency: Real world applications. | Ophthalmic Genet. | pmid:27648776 | |
| Hu ZX et al. | Rearranged 6/6/5/6-Fused Triterpenoid Acids from the Stems of Kadsura coccinea. | 2016 | J. Nat. Prod. | pmid:27704807 |
| Zhang G et al. | Ethylene promotes mycelial growth and ganoderic acid biosynthesis in Ganoderma lucidum. | 2017 | Biotechnol. Lett. | pmid:27771819 |
| Wang XL et al. | Improved Production and Antitumor Properties of Triterpene Acids from Submerged Culture of Ganoderma lingzhi. | 2016 | Molecules | pmid:27775633 |
| Hongthong S et al. | Cytotoxic lanostanes from fruits of Garcinia wallichii Choisy (Guttiferae). | 2016 | Bioorg. Med. Chem. Lett. | pmid:27793565 |
| Kim JW et al. | Effects of Ganodermanondiol, a New Melanogenesis Inhibitor from the Medicinal Mushroom Ganoderma lucidum. | 2016 | Int J Mol Sci | pmid:27801787 |
| Lai KH et al. | Cytotoxic Lanostanoids from Poria cocos. | 2016 | J. Nat. Prod. | pmid:27808511 |
| Zhang DH et al. | Overexpression of the homologous lanosterol synthase gene in ganoderic acid biosynthesis in Ganoderma lingzhi. | 2017 | Phytochemistry | pmid:27894599 |
| Iglesias J and Gibbons GF | Oxidative metabolism of cholesterol precursors: sensitivity to ketoconazole, an inhibitor of cytochrome P-450. | 1989 Mar-May | Steroids | pmid:2799848 |
| Nes WD et al. | Concerning the role of 24,25-dihydrolanosterol and lanostanol in sterol biosynthesis by cultured cells. | 1989 Mar-May | Steroids | pmid:2799854 |
| Maitra US et al. | Biosynthetic preparation of labeled 4,4-dimethylzymosterol. | 1989 Mar-May | Steroids | pmid:2799859 |
| Suarez-Medellin J et al. | In Silico Analysis of Lanostanoids Characterized in Ganoderma Mushrooms (Agaricomycetes) as Potential Ligands of the Vitamin D Receptor. | 2016 | Int J Med Mushrooms | pmid:28008815 |
| Dai J et al. | Elimination of quiescent slow-cycling cells via reducing quiescence depth by natural compounds purified from Ganoderma lucidum. | 2017 | Oncotarget | pmid:28099150 |
| Wang CN et al. | The aggregation of human platelet induced by ganodermic acid S. | 1989 | Biochim. Biophys. Acta | pmid:2819092 |
| Tallman KA et al. | Probes for protein adduction in cholesterol biosynthesis disorders: Alkynyl lanosterol as a viable sterol precursor. | 2017 | Redox Biol | pmid:28258022 |
| Schrack S et al. | Oxysterols in cosmetics-Determination by planar solid phase extraction and gas chromatography-mass spectrometry. | 2016 | J Chromatogr A | pmid:28314390 |
| Cao FR et al. | Plasma and brain pharmacokinetics of ganoderic acid A in rats determined by a developed UFLC-MS/MS method. | 2017 | J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. | pmid:28346885 |
| Isaka M et al. | Antitubercular Activity of Mycelium-Associated Ganoderma Lanostanoids. | 2017 | J. Nat. Prod. | pmid:28504879 |
| Wang J et al. | Eburicoic acid from Laetiporus sulphureus (Bull.:Fr.) Murrill attenuates inflammatory responses through inhibiting LPS-induced activation of PI3K/Akt/mTOR/NF-κB pathways in RAW264.7 cells. | 2017 | Naunyn Schmiedebergs Arch. Pharmacol. | pmid:28577049 |
| Araldi E et al. | Lanosterol Modulates TLR4-Mediated Innate Immune Responses in Macrophages. | 2017 | Cell Rep | pmid:28658622 |
| Wang X et al. | Ganoderic acid A inhibits proliferation and invasion, and promotes apoptosis in human hepatocellular carcinoma cells. | 2017 | Mol Med Rep | pmid:28731159 |
| Huang SZ et al. | Lanostane-type triterpenoids from the fruiting body of Ganoderma calidophilum. | 2017 | Phytochemistry | pmid:28800421 |
| Park JW et al. | Nitric oxide stimulates cellular degradation of human CYP51A1, the highly conserved lanosterol 14α-demethylase. | 2017 | Biochem. J. | pmid:28830911 |
| Wang XL et al. | Efficient Accumulation and In Vitro Antitumor Activities of Triterpene Acids from Submerged Batch--Cultured Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes). | 2017 | Int J Med Mushrooms | pmid:28845771 |
| Lv L et al. | Quantitation of lanosterol in the vitreous humor of rabbits after ocular administration of lanosterol/thermogel formulation by ultra high performance liquid chromatography-tandem mass spectrometry with the electrospray ionization mode. | 2017 | J Chromatogr A | pmid:28888677 |
| Sidjui LS et al. | Bioactive Seco-Lanostane-Type Triterpenoids from the Roots of Leplaea mayombensis. | 2017 | J. Nat. Prod. | pmid:28945373 |
| Yusakul G et al. | Bacterial Expression of a Single-Chain Variable Fragment (scFv) Antibody against Ganoderic Acid A: A Cost-Effective Approach for Quantitative Analysis Using the scFv-Based Enzyme-Linked Immunosorbent Assay. | 2017 | Biol. Pharm. Bull. | pmid:28966249 |
| Kidane ME et al. | Sterol methyltransferase a target for anti-amoeba therapy: towards transition state analog and suicide substrate drug design. | 2017 | J. Lipid Res. | pmid:29042405 |
| Lin CH et al. | Eburicoic Acid, a Triterpenoid Compound from Antrodia camphorata, Displays Antidiabetic and Antihyperlipidemic Effects in Palmitate-Treated C2C12 Myotubes and in High-Fat Diet-Fed Mice. | 2017 | Int J Mol Sci | pmid:29099085 |
| Lu DL et al. | Reproducibility of serum oxysterols and lanosterol among postmenopausal women: Results from EPIC-Heidelberg. | 2018 | Clin. Biochem. | pmid:29108727 |
| Aoyama Y et al. | Role of the 8-double bond of lanosterol in the enzyme-substrate interaction of cytochrome P-450(14DM) (lanosterol 14 alpha-demethylase). | 1989 | Biochim. Biophys. Acta | pmid:2917143 |
| Emmons GT et al. | 24,25-epoxysterols. Differentiation of 24R and 24S epimers by 13C nuclear magnetic resonance spectroscopy. | 1989 | J. Lipid Res. | pmid:2918248 |
| Vidal-Limon AM et al. | Molecular Dynamics and Virtual Screening Analysis of Lanosterol Derivatives from Ganoderma Medicinal Mushrooms (Agaricomycetes) as Selective Ligands of Human Androgen Receptor. | 2017 | Int J Med Mushrooms | pmid:29199581 |
| Gao Y et al. | In Vitro and In Vivo Activity of Fomitopsis Pinicola (Sw. Ex Fr.) Karst Chloroform (Fpkc) Extract Against S180 Tumor Cells. | 2017 | Cell. Physiol. Biochem. | pmid:29241162 |
| Freitas HF et al. | Cloning, expression, purification and spectrophotometric analysis of lanosterol 14-alpha demethylase from Leishmania braziliensis (LbCYP51). | 2018 | Mol. Biol. Rep. | pmid:29363024 |
| Chen XQ et al. | Lanostane triterpenes from the mushroom Ganoderma resinaceum and their inhibitory activities against α-glucosidase. | 2018 | Phytochemistry | pmid:29490285 |
| Teng Y et al. | Hebecarposides A-K, antiproliferative lanostane-type triterpene glycosides from the leaves of Lyonia ovalifolia var. hebecarpa. | 2018 | Phytochemistry | pmid:29660562 |
| Zhu J et al. | Ganoderic Acid A improves high fat diet-induced obesity, lipid accumulation and insulin sensitivity through regulating SREBP pathway. | 2018 | Chem. Biol. Interact. | pmid:29852127 |
| Rippon JW | A new era in antimycotic agents. | 1986 | Arch Dermatol | pmid:3006601 |
| Barrett-Bee K et al. | Biochemical studies with a novel antifungal agent, ICI 195,739. | 1988 | Ann. N. Y. Acad. Sci. | pmid:3063170 |
| Aoyama Y et al. | Isolation and characterization of an altered cytochrome P-450 from a yeast mutant defective in lanosterol 14 alpha-demethylation. | 1987 | J. Biol. Chem. | pmid:3115990 |
| Raederstorff D and Rohmer M | Polyterpenoids as cholesterol and tetrahymanol surrogates in the ciliate Tetrahymena pyriformis. | 1988 | Biochim. Biophys. Acta | pmid:3130105 |
| Lange Y and Muraski MF | Topographic heterogeneity in cholesterol biosynthesis. | 1988 | J. Biol. Chem. | pmid:3132462 |
| Malvoisin E et al. | Relationship between membrane sterol composition and responsiveness to 12-O-tetradecanoylphorbol 13-acetate in HL-60 human promyelocytic leukaemia cell lines. | 1988 | Biochem. J. | pmid:3162674 |
| Pinkerton FD et al. | Inhibitors of sterol synthesis. 14 alpha-ethyl-5 alpha-cholest-7-ene-3 beta,15 alpha-diol induces changes in the sterol composition and the morphology of CHO-K1 cells. | 1988 | Biochem. Biophys. Res. Commun. | pmid:3196343 |
| Cooper AB et al. | Synthesis and antifungal properties of 14-aminomethyl-substituted lanosterol derivatives. | 1988 | Ann. N. Y. Acad. Sci. | pmid:3214062 |
| Sekigawa Y et al. | Metabolism of 32-hydroxylated 24,25-dihydrolanosterols by partially purified cytochrome P-450(14)DM from rat liver microsomes. | 1988 | Chem. Pharm. Bull. | pmid:3240513 |
| Parish EJ et al. | A facile synthesis of lanost-8-en-3 beta-ol-24-one (24-ketolanosterol). An inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. | 1988 | Chem. Phys. Lipids | pmid:3242953 |
| Field RB and Holmlund CE | Isolation of 2,3;22,23-dioxidosqualene and 24,25-oxidolanosterol from yeast. | 1977 | Arch. Biochem. Biophys. | pmid:327938 |
| Gevers Leuven JA et al. | The effect of cyclandelate on cholesterol metabolism in patients with familial hypercholesterolaemia. | 1987 | Drugs | pmid:3304952 |
| M'Baya B and Karst F | In vitro assay of squalene epoxidase of Saccharomyces cerevisiae. | 1987 | Biochem. Biophys. Res. Commun. | pmid:3307781 |
| Bard M et al. | Characterization of a cytochrome P450 deficient mutant of Candida albicans. | 1987 | Biochem. Biophys. Res. Commun. | pmid:3307785 |
| Aoyama Y et al. | 7-Oxo-24,25-dihydrolanosterol: a novel lanosterol 14 alpha-demethylase (P-45014DM) inhibitor which blocks electron transfer to the oxyferro intermediate. | 1987 | Biochim. Biophys. Acta | pmid:3318933 |
| Trocha PJ et al. | Yeast mutants blocked in removing the methyl group of lanosterol at C-14. Separation of sterols by high-pressure liquid chromatography. | 1977 | Biochemistry | pmid:334248 |
| Marco de la Calle C et al. | A relationship between the activities of hepatic lanosterol 14 alpha-demethylase and 3-hydroxy-3-methylglutaryl-CoA reductase. | 1988 | Biochem. J. | pmid:3355520 |
| Aguilera JA et al. | Regulation of hepatic cholesterogenesis by polar steroids accumulated after cholesterol feeding. | 1988 | Biosci. Rep. | pmid:3408811 |
| Shafiee A et al. | Oxidative demethylation of lanosterol in cholesterol biosynthesis: accumulation of sterol intermediates. | 1986 | J. Lipid Res. | pmid:3514778 |