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Immunology/Inflammation

The immune and inflammation-related pathway including the Toll-like receptors pathway, the B cell receptor signaling pathway, the T cell receptor signaling pathway, etc.

Toll-like receptors (TLRs) play a central role in host cell recognition and responses to microbial pathogens. TLR4 initially recruits TIRAP and MyD88. MyD88 then recruits IRAKs, TRAF6, and the TAK1 complex, leading to early-stage activation of NF-κB and MAP kinases [1]. TLR4 is endocytosed and delivered to intracellular vesicles and forms a complex with TRAM and TRIF, which then recruits TRAF3 and the protein kinases TBK1 and IKKi. TBK1 and IKKi catalyze the phosphorylation of IRF3, leading to the expression of type I IFN [2].

BCR signaling is initiated through ligation of mIg under conditions that induce phosphorylation of the ITAMs in CD79, leading to the activation of Syk. Once Syk is activated, the BCR signal is transmitted via a series of proteins associated with the adaptor protein B-cell linker (Blnk, SLP-65). Blnk binds CD79a via non-ITAM tyrosines and is phosphorylated by Syk. Phospho-Blnk acts as a scaffold for the assembly of the other components, including Bruton’s tyrosine kinase (Btk), Vav 1, and phospholipase C-gamma 2 (PLCγ2) [3]. Following the assembly of the BCR-signalosome, GRB2 binds and activates the Ras-guanine exchange factor SOS, which in turn activates the small GTPase RAS. The original RAS signal is transmitted and amplified through the mitogen-activated protein kinase (MAPK) pathway, which including the serine/threonine-specific protein kinase RAF followed by MEK and extracellular signal related kinases ERK 1 and 2 [4]. After stimulation of BCR, CD19 is phosphorylated by Lyn. Phosphorylated CD19 activates PI3K by binding to the p85 subunit of PI3K and produce phosphatidylinositol-3,4,5-trisphosphate (PIP3) from PIP2, and PIP3 transmits signals downstream [5].

Central process of T cells responding to specific antigens is the binding of the T-cell receptor (TCR) to specific peptides bound to the major histocompatibility complex which expressed on antigen-presenting cells (APCs). Once TCR connected with its ligand, the ζ-chain–associated protein kinase 70 molecules (Zap-70) are recruited to the TCR-CD3 site and activated, resulting in an initiation of several signaling cascades. Once stimulation, Zap-70 forms complexes with several molecules including SLP-76; and a sequential protein kinase cascade is initiated, consisting of MAP kinase kinase kinase (MAP3K), MAP kinase kinase (MAPKK), and MAP kinase (MAPK) [6]. Two MAPK kinases, MKK4 and MKK7, have been reported to be the primary activators of JNK. MKK3, MKK4, and MKK6 are activators of P38 MAP kinase [7]. MAP kinase pathways are major pathways induced by TCR stimulation, and they play a key role in T-cell responses.

Phosphoinositide 3-kinase (PI3K) binds to the cytosolic domain of CD28, leading to conversion of PIP2 to PIP3, activation of PKB (Akt) and phosphoinositide-dependent kinase 1 (PDK1), and subsequent signaling transduction [8].

 

References

[1] Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors[J]. Nature immunology, 2010, 11(5): 373-384.

[2] Kawai T, Akira S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity[J]. Immunity, 2011, 34(5): 637-650.

[3] Packard T A, Cambier J C. B lymphocyte antigen receptor signaling: initiation, amplification, and regulation[J]. F1000Prime Rep, 2013, 5(40.10): 12703.

[4] Zhong Y, Byrd J C, Dubovsky J A. The B-cell receptor pathway: a critical component of healthy and malignant immune biology[C]//Seminars in hematology. WB Saunders, 2014, 51(3): 206-218.

[5] Baba Y, Matsumoto M, Kurosaki T. Calcium signaling in B cells: regulation of cytosolic Ca 2+ increase and its sensor molecules, STIM1 and STIM2[J]. Molecular immunology, 2014, 62(2): 339-343.

[6] Adachi K, Davis M M. T-cell receptor ligation induces distinct signaling pathways in naive vs. antigen-experienced T cells[J]. Proceedings of the National Academy of Sciences, 2011, 108(4): 1549-1554.

[7] Rincón M, Flavell R A, Davis R A. The Jnk and P38 MAP kinase signaling pathways in T cell–mediated immune responses[J]. Free Radical Biology and Medicine, 2000, 28(9): 1328-1337.

[8] Bashour K T, Gondarenko A, Chen H, et al. CD28 and CD3 have complementary roles in T-cell traction forces[J]. Proceedings of the National Academy of Sciences, 2014, 111(6): 2241-2246.

Targets for  Immunology/Inflammation

Products for  Immunology/Inflammation

  1. Cat.No. Product Name Information
  2. GC49887 7-(β-Hydroxyethyl)theophylline-d6 An internal standard for the quantification of 7-(β-hydroxyethyl)theophylline 7-(β-Hydroxyethyl)theophylline-d6  Chemical Structure
  3. GC45707 7-Azido-4-methylcoumarin A fluorescent H2S probe 7-Azido-4-methylcoumarin  Chemical Structure
  4. GC40978 7-epi Maresin 1 7-epi Maresin 1 is the inactive 7(S) epimer of Maresin 1, which contains a 7(R) hydroxyl group. 7-epi Maresin 1  Chemical Structure
  5. GC49312 7-Fluoro-2,1,3-benzoxadiazole-4-sulfonate (ammonium salt) 7-Fluoro-2,1,3-benzoxadiazole-4-sulfonate (ammonium salt) is a fluorescent label. 7-Fluoro-2,1,3-benzoxadiazole-4-sulfonate (ammonium salt)  Chemical Structure
  6. GC49051 7-hydroxy Methotrexate A metabolite of methotrexate 7-hydroxy Methotrexate  Chemical Structure
  7. GC42608 7-hydroxy Methotrexate (sodium salt)

    7-hydroxy Methotrexate (7-hydroxy MTX) is a phase I metabolite of MTX, which is converted by hepatic aldehyde oxidases.

    7-hydroxy Methotrexate (sodium salt)  Chemical Structure
  8. GC46241 7-keto Cholesterol-d7

    7-keto Cholesterol is a bioactive sterol and a major oxysterol component of oxidized LDL

    7-keto Cholesterol-d7  Chemical Structure
  9. GC48880 7-Methoxyflavone A flavone with diverse biological activities 7-Methoxyflavone  Chemical Structure
  10. GC13982 7-NINA non-selective NOS inhibitor 7-NINA  Chemical Structure
  11. GC12309 7-Nitroindazole nNOS inhibitor 7-Nitroindazole  Chemical Structure
  12. GC42616 7-oxo Staurosporine

    7-oxo Staurosporine is an antibiotic originally isolated from S.

    7-oxo Staurosporine  Chemical Structure
  13. GC52211 7-[1-(1H)-Tetrazolylacetamido]desacetoxycephalosporanic Acid A potential impurity in commercial preparations of cefazolin 7-[1-(1H)-Tetrazolylacetamido]desacetoxycephalosporanic Acid  Chemical Structure
  14. GC41136 8(S),15(S)-DiHETE 8(S),15(S)-DiHETE is formed when 15(S)-HETE is subjected to further oxidation by 15-LO. 8(S),15(S)-DiHETE  Chemical Structure
  15. GC42623 8-Bromoguanosine 8-Bromoguanosine is a brominated derivative of guanosine. 8-Bromoguanosine  Chemical Structure
  16. GC35199 8-Deoxygartanin 8-Deoxygartanin, a prenylated xanthones from G. 8-Deoxygartanin  Chemical Structure
  17. GC42627 8-Hydroxyguanine (hydrochloride) 8-Hydroxyguanine is produced by oxidative degradation of DNA by hydroxyl radical. 8-Hydroxyguanine (hydrochloride)  Chemical Structure
  18. GC18426 8-Nitroguanine 8-Nitroguanine is a nitrative guanine derivative formed by oxidative damage to the guanine base in DNA by reactive nitrogen species (RNS) during inflammation and in vitro by reaction of DNA with peroxynitrite and other RNS reagents. 8-Nitroguanine  Chemical Structure
  19. GN10212 8-O-Acetyl shanzhiside methyl ester 8-O-Acetyl shanzhiside methyl ester  Chemical Structure
  20. GC49275 8-Oxycoptisine 8-Oxycoptisine is a natural protoberberine alkaloid with anti-cancer activity. 8-Oxycoptisine  Chemical Structure
  21. GC46748 9(E),11(E)-12-nitro Conjugated Linoleic Acid A nitrated fatty acid 9(E),11(E)-12-nitro Conjugated Linoleic Acid  Chemical Structure
  22. GC46749 9(E),11(E)-9-nitro Conjugated Linoleic Acid A nitrated fatty acid 9(E),11(E)-9-nitro Conjugated Linoleic Acid  Chemical Structure
  23. GC42633 9(E)-Erythromycin A oxime (9E)-Erythromycin A oxime is a metabolite of the semisynthetic antibiotic roxithromycin . 9(E)-Erythromycin A oxime  Chemical Structure
  24. GC46753 9(S),12(S),13(S)-TriHOME An oxylipin 9(S),12(S),13(S)-TriHOME  Chemical Structure
  25. GC40324 9(S)-PAHSA 9-PAHSA is a newly identified endogenous lipid that belongs to a collection of branched fatty acid esters of hydroxy fatty acids (FAHFAs). 9(S)-PAHSA  Chemical Structure
  26. GC46757 9(Z),11(E)-Conjugated Linoleic Acid (sodium salt) An isomer of linoleic acid 9(Z),11(E)-Conjugated Linoleic Acid (sodium salt)  Chemical Structure
  27. GC42642 9,10-Anthracenediyl-bis(methylene)dimalonic Acid

    9,10-Anthracenediyl-bis(methylene)dimalonic acid (ABMDMA) is a reagent used to detect singlet oxygen generation.

    9,10-Anthracenediyl-bis(methylene)dimalonic Acid  Chemical Structure
  28. GC42644 9-Deazaguanine 9-Deazaguanine is an analog of guanine that acts as an inhibitor of purine nucleoside phosphorylase (PNP; Kd = 160 nM). 9-Deazaguanine  Chemical Structure
  29. GC42648 9-Methylstreptimidone 9-Methylstreptimidone is a microbial metabolite originally isolated from Streptomyces sp. 9-Methylstreptimidone  Chemical Structure
  30. GC42649 9-Nitrooleate Nitrated unsaturated fatty acids, such as 10- and 12-nitrolinoleate, cholesteryl nitrolinoleate, and nitrohydroxylinoleate, represent a new class of endogenous lipid-derived signalling molecules. 9-Nitrooleate  Chemical Structure
  31. GC42653 9-OxoOTrE 9-OxoOTrE is produced by the oxidation of 9-HpOTrE. 9-OxoOTrE  Chemical Structure
  32. GC40325 9-PAHSA Branched fatty acid esters of hydroxy fatty acids (FAHFAs) are newly identified endogenous lipids regulated by fasting and high-fat feeding and associated with insulin sensitivity. 9-PAHSA  Chemical Structure
  33. GC49237 93-O17O A cationic lipidoid 93-O17O  Chemical Structure
  34. GC49238 93-O17S A cationic lipidoid 93-O17S  Chemical Structure
  35. GC45960 9c(i472) 9c(i472) is a potent inhibitor of 15-LOX-1 (15-lipoxygenase-1) with an IC50 value of 0.19 μM. 9c(i472)  Chemical Structure
  36. GC45930 A 26771B A macrolide antibiotic A 26771B  Chemical Structure
  37. GC42660 A-39183A A-39183A is an active component of the A-39183 antibiotic complex produced by aerobic fermentation of Streptomyces NRRL 12049. A-39183A  Chemical Structure
  38. GC42661 A-54556B A-54556B is a natural acyldepsipeptide (ADEP) antibiotic isolated from the fermentation broth of S. A-54556B  Chemical Structure
  39. GC18936 A-83016F A-83016F is an aurodox antibiotic isolated from the actinomycete species A83016. A-83016F  Chemical Structure
  40. GC49309 A-943931 (hydrochloride hydrate) A histamine H4 receptor antagonist A-943931 (hydrochloride hydrate)  Chemical Structure
  41. GC35214 A-9758 A-9758 is a RORγ ligand and a potent, selective RORγt inverse agonist (IC50=5 nM), and exhibits robust potency against IL-17A release. A-9758  Chemical Structure
  42. GP10060 a-MSH, amide

    a-MSH (α-Melanocyte-Stimulating Hormone), amide engages the melanocortin-1 receptor and activates cyclic AMP (cAMP) signaling via a G-protein transporter, can synthesize melanin.

    a-MSH, amide  Chemical Structure
  43. GC19496 AAPH

    AAPH is a water-soluble azo compound

    AAPH  Chemical Structure
  44. GC42666 AAT-008 AAT-008 is an orally bioavailable and potent antagonist of the prostaglandin E2 (PGE2) receptor subtype 4 (EP4; IC50 = 16.3 nM in a human EP4 functional assay). AAT-008  Chemical Structure
  45. GC65293 AB-680 AB-680 is a highly potent, reversible and selective inhibitor of CD73 (an ecto-nucleotidase), with a Ki of 4.9 pM for hCD73, displays >10,000-fold selectivity over related ecto-nucleotidases CD39. Anti-tumor activity. AB-680  Chemical Structure
  46. GC42667 Abacavir Carboxylate Abacavir carboxylate is an inactive metabolite of the HIV-1 reverse transcriptase inhibitor abacavir. Abacavir Carboxylate  Chemical Structure
  47. GC46767 Abacavir-d4 An internal standard for the quantification of abacavir Abacavir-d4  Chemical Structure
  48. GC49766 Abafungin Abafungin, a antifungal agent, inhibitis the transmethylation at the C-24 position of the sterol side chain, catalyzed by the enzyme sterol-C-24-methyltransferase. Abafungin  Chemical Structure
  49. GC42668 ABC34 ABC34 is an inactive control probe for JJH260, the inhibitor of androgen-induced gene 1 (AIG1), an enzyme that hydrolyzes fatty acid esters of hydroxy fatty acids (FAHFAs). ABC34  Chemical Structure
  50. GC49745 ABT-263-d8 ABT-263-d8 is the deuterium labeled Navitoclax. Navitoclax (ABT-263) is a potent and orally active Bcl-2 family protein inhibitor that binds to multiple anti-apoptotic Bcl-2 family proteins, such as Bcl-xL, Bcl-2 and Bcl-w, with a Ki of less than 1 nM. ABT-263-d8  Chemical Structure
  51. GC42683 Abz-Ala-Pro-Glu-Glu-Ile-Met-Arg-Arg-Gln-EDDnp Abz-Ala-Pro-Glu-Glu-Ile-Met-Arg-Arg-Gln-EDDnp is a fluorescence-quenched peptide substrate for human neutrophil elastase (kcat/Km = 531 mM-1s-1). Abz-Ala-Pro-Glu-Glu-Ile-Met-Arg-Arg-Gln-EDDnp  Chemical Structure
  52. GC52499 Abz-Ala-Pro-Glu-Glu-Ile-Met-Arg-Arg-Gln-EDDnp (trifluoroacetate salt) A sensitive substrate for neutrophil elastase Abz-Ala-Pro-Glu-Glu-Ile-Met-Arg-Arg-Gln-EDDnp (trifluoroacetate salt)  Chemical Structure
  53. GC42684 Abz-Val-Ala-Asp-Nva-Arg-Asp-Arg-Gln-EDDnp (trifluoroacetate salt) Abz-Val-Ala-Asp-Nva-Arg-Asp-Arg-Gln-EDDnp is a fluorescence-quenched peptide substrate for human proteinase 3 (kcat/Km = 1,570 mM-1s-1). Abz-Val-Ala-Asp-Nva-Arg-Asp-Arg-Gln-EDDnp (trifluoroacetate salt)  Chemical Structure
  54. GC42685 Ac-ANW-AMC

    Ac-ANW-AMC is a fluorogenic substrate for the β5i/LMP7 subunit of the 20S immunoproteasome.

    Ac-ANW-AMC  Chemical Structure
  55. GC49704 Ac-FLTD-CMK (trifluoroacetate salt) An inhibitor of caspase-1, -4, -5, and -11 Ac-FLTD-CMK (trifluoroacetate salt)  Chemical Structure
  56. GA20621 Ac-muramic acid A component of bacterial cell walls. For a protected derivative of MurNAc see Q-1005. Ac-muramic acid  Chemical Structure
  57. GC52372 Ac-VDVAD-AFC (trifluoroacetate salt) A fluorogenic substrate for caspase-2 Ac-VDVAD-AFC (trifluoroacetate salt)  Chemical Structure
  58. GC15598 Ac2-26 inhibitor of leukocyte extravasation Ac2-26  Chemical Structure
  59. GC49263 Ac2-26 (human) (ammonium salt) An annexin A1-mimetic peptide Ac2-26 (human) (ammonium salt)  Chemical Structure
  60. GC35224 Ac2-26 TFA Ac2-26 TFA, an active N-terminal peptide of annexin A1 (AnxA1), attenuates ischemia-reperfusion-induced acute lung injury. Ac2-26 TFA  Chemical Structure
  61. GC42691 Aceclofenac ethyl ester A potential impurity found in commercial preparations of aceclofenac Aceclofenac ethyl ester  Chemical Structure
  62. GC42692 Aceclofenac methyl ester A potential impurity in commercial preparations of aceclofenac Aceclofenac methyl ester  Chemical Structure
  63. GC49911 Acetyl Hexapeptide-38 (trifluoroacetate salt) A hexapeptide Acetyl Hexapeptide-38 (trifluoroacetate salt)  Chemical Structure
  64. GC42700 Acetyl Pentapeptide-1 Acetyl pentapeptide-1 is a pentapeptide that decreases IL-8 secretion in human keratinocytes when used in combination with acetyl hexapeptide-36 and acetyl hexapeptide-38. Acetyl Pentapeptide-1  Chemical Structure
  65. GC18443 Acetyl-6-formylpterin Acetyl-6-formylpterin is an inhibitor of mucosal-associated invariant T (MAIT) cell activation. Acetyl-6-formylpterin  Chemical Structure
  66. GC11786 Acetylcysteine

    Acetylcysteine is the N-acetyl derivative of CYSTEINE.

    Acetylcysteine  Chemical Structure
  67. GC17416 ACHP IκB kinase inhibitor ACHP  Chemical Structure
  68. GN10536 Aconine Aconine  Chemical Structure
  69. GC49804 Acridine An azaarene Acridine  Chemical Structure
  70. GC40645 Actarit Actarit is an orally active immunomodulator that reduces symptoms in animal models and clinical trials of rheumatoid arthritis. Actarit  Chemical Structure
  71. GC41316 Actinopyrone A Actinopyrone A is a pyrone isolated from S. Actinopyrone A  Chemical Structure
  72. GC48842 Actiphenol A bacterial metabolite with antiviral activity Actiphenol  Chemical Structure
  73. GC46797 Acyclovir-d4 An internal standard for the quantification of acyclovir Acyclovir-d4  Chemical Structure
  74. GC46798 Adapalene-d3 An internal standard for the quantification of adapalene Adapalene-d3  Chemical Structure
  75. GC46805 Adefovir-d4 An internal standard for the quantification of adefovir Adefovir-d4  Chemical Structure
  76. GC31693 Adelmidrol Adelmidrol exerts important anti-inflammatory effects that are partly dependent on PPARγ. Adelmidrol  Chemical Structure
  77. GC49285 Adenosine 5’-methylenediphosphate (hydrate) An inhibitor of ecto-5’-nucleotidase Adenosine 5’-methylenediphosphate (hydrate)  Chemical Structure
  78. GC60040 ADH-503 ADH-503 ((Z)-Leukadherin-1 choline) is an orally active and allosteric CD11b agonist. ADH-503 leads to the repolarization of tumor-associated macrophages, reduction in the number of tumor-infiltrating immunosuppressive myeloid cells, and enhances dendritic cell responses. ADH-503  Chemical Structure
  79. GC42742 ADT-OH ADT-OH is a derivative of anethole dithiolethione (ADT) and synthetic hydrogen sulfide (H2S) donor. ADT-OH  Chemical Structure
  80. GC31649 ADU-S100 (ML RR-S2 CDA) ADU-S100 (ML RR-S2 CDA) (MIW815), an activator of stimulator of interferon genes (STING), leads to potent and systemic tumor regression and immunity. ADU-S100 (ML RR-S2 CDA)  Chemical Structure
  81. GC39161 ADU-S100 disodium salt ADU-S100 disodium salt (MIW815 disodium salt) is an activator of stimulator of interferon genes (STING). ADU-S100 disodium salt  Chemical Structure
  82. GC42743 AEM1 Cancer cell survival appears partly dependent on antioxidative enzymes, whose expression is regulated by the Keap1-Nrf2 pathway, to quench potentially toxic reactive oxygen species generated by their metastatic transformation. AEM1  Chemical Structure
  83. GC63485 Afimetoran Afimetoran is a toll-like receptor antagonist, which can be used in the research of inflammatory and autoimmune diseases. Afimetoran  Chemical Structure
  84. GC66396 Agatolimod Agatolimod (ODN 2006), a class B ODN (oligodeoxynucleotide), is a TLR9 agonist. Agatolimod is also an optimal CpG sequence for humans. Agatolimod stimulates very strong production of NO2 and IL-6 in HD11 cells. Agatolimod can be used for breast cancer research. Sequence: 5'-tcgtcgttttgtcgttttgtcgtt-3'. Agatolimod  Chemical Structure
  85. GC16831 Agmatine sulfate α2-adrenergic receptor ligand Agmatine sulfate  Chemical Structure
  86. GC35271 AHR antagonist 1 AHR antagonist 1 (AHR antagonist 1) is an aryl hydrocarbon receptor (AHR) antagonist. AHR antagonist 1  Chemical Structure
  87. GC39669 AHR antagonist 2 AHR antagonist 2 is a potent aryl hydrocarbon receptor (AHR) antagonist, extracted from patent WO2019101641A1, compound example 1, with IC50s of 0.885 and 2.03 nM for human and mouse AhR. AHR antagonist 2  Chemical Structure
  88. GC64275 AHR antagonist 5 AHR antagonist 5, a potent and orally active aryl hydrocarbon receptor (AHR) antagonist extracted from patent WO2018195397, example 39, has an IC50 of < 0.5 ?Μ. AHR antagonist 5 significantly inhibits tumor growth combined with checkpoint inhibitor anti-PD-1. AHR antagonist 5  Chemical Structure
  89. GC64208 AHR antagonist 5 free base AHR antagonist 5 free base is a selective and orally active aryl hydrocarbon receptor (AHR) inhibitor. AHR antagonist 5 free base effectively blocks AHR from translocating from the cytoplasm to the nucleus. AHR antagonist 5 free base is highly selective for AHR over other receptors, transporters, and kinases. AHR antagonist 5 free base  Chemical Structure
  90. GC16120 AI-3 Nrf2/Keap1 and Keap1/Cul3 interaction inhibitor AI-3  Chemical Structure
  91. GC46821 Ajoene A disulfide with diverse biological activities Ajoene  Chemical Structure
  92. GC45681 AKP-11 An S1P1 receptor agonist AKP-11  Chemical Structure
  93. GC42763 Alamethicin F50 Alamethicin F50 is a peptaibol isolated from Trichoderma. Alamethicin F50  Chemical Structure
  94. GC49773 Albendazole sulfone-d3 An internal standard for the quantification of albendazole sulfone Albendazole sulfone-d3  Chemical Structure
  95. GC48848 Albendazole-d7 An internal standard for the quantification of albendazole Albendazole-d7  Chemical Structure
  96. GC41080 Albofungin Albofungin is a xanthone isolated from A. Albofungin  Chemical Structure
  97. GC42764 Albuterol methyl ether Salbutamol (albuterol) is a selective β2-adrenergic partial agonist that is used as a bronchodilator. Albuterol methyl ether  Chemical Structure
  98. GC46826 Alclofenac An NSAID Alclofenac  Chemical Structure
  99. GC40638 Alclometasone Dipropionate Alclometasone dipropionate (ACM) is a corticosteroid. Alclometasone Dipropionate  Chemical Structure
  100. GN10298 Alibiflorin Alibiflorin  Chemical Structure
  101. GC42769 all-trans Retinoyl β-D-Glucuronide all-trans Retinoyl β-D-glucuronide is a metabolite of all-trans retinoic acid formed by the UDP-glucuronosyltransferase (UGT) system. all-trans Retinoyl β-D-Glucuronide  Chemical Structure

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