Review Article

脂肪酸结合蛋白4 (FABP4)在肾病中的作用

卷 27, 期 22, 2020

页: [3657 - 3664] 页: 8

弟呕挨: 10.2174/0929867325666181008154622

价格: $65

摘要

越来越多的证据表明,肥胖和代谢综合征是肾脏疾病发生发展的独立危险因素。除了炎症、脂肪毒性和血流动力学因素外,脂肪因子被认为在肾脏疾病和代谢紊乱之间的关系中发挥重要作用。脂肪酸结合蛋白4 (fatty acid binding protein 4, FABP4)是关键的脂肪因子之一,主要在脂肪细胞和巨噬细胞中表达,最近被证实与肾功能不全和肾损伤有关。临床和实验研究均提出循环FABP4作为肾脏损伤的一种新的预测因子,它也可能是终末期肾脏疾病(ESRD)患者心血管事件的预测因子。在小鼠和人肾脏的肾小球细胞和上皮管细胞中也检测到FABP4,这些细胞中FABP4的表达参与了肾脏疾病的发病机制。此外,实验研究表明抑制FABP4对肾脏损伤具有保护作用。在这里,我们综述了有关FABP4在病理生理学方面作用,以及它作为肾脏疾病的预测因子和治疗靶点潜在功能的最新研究进展。

关键词: 脂肪酸结合蛋白4,肾脏疾病,脂肪因子,靶向药物,预测因子,终末期肾脏疾病。

[1]
Eckardt, K.U.; Coresh, J.; Devuyst, O.; Johnson, R.J.; Köttgen, A.; Levey, A.S.; Levin, A. Evolving importance of kidney disease: from subspecialty to global health burden. Lancet, 2013, 382(9887), 158-169.
[http://dx.doi.org/10.1016/S0140-6736(13)60439-0] [PMID: 23727165]
[2]
Jha, V.; Garcia-Garcia, G.; Iseki, K.; Li, Z.; Naicker, S.; Plattner, B.; Saran, R.; Wang, A.Y.; Yang, C.W. Chronic kidney disease: global dimension and perspectives. Lancet, 2013, 382(9888), 260-272.
[http://dx.doi.org/10.1016/S0140-6736(13)60687-X] [PMID: 23727169]
[3]
Lozano, R.; Naghavi, M.; Foreman, K.; Lim, S.; Shibuya, K.; Aboyans, V.; Abraham, J.; Adair, T.; Aggarwal, R.; Ahn, S.Y.; Alvarado, M.; Anderson, H.R.; Anderson, L.M.; Andrews, K.G.; Atkinson, C.; Baddour, L.M.; Barker-Collo, S.; Bartels, D.H.; Bell, M.L.; Benjamin, E.J.; Bennett, D.; Bhalla, K.; Bikbov, B.; Bin Abdulhak, A.; Birbeck, G.; Blyth, F.; Bolliger, I.; Boufous, S.; Bucello, C.; Burch, M.; Burney, P.; Carapetis, J.; Chen, H.; Chou, D.; Chugh, S.S.; Coffeng, L.E.; Colan, S.D.; Colquhoun, S.; Colson, K.E.; Condon, J.; Connor, M.D.; Cooper, L.T.; Corriere, M.; Cortinovis, M.; de Vaccaro, K.C.; Couser, W.; Cowie, B.C.; Criqui, M.H.; Cross, M.; Dabhadkar, K.C.; Dahodwala, N.; De Leo, D.; Degenhardt, L.; Delossantos, A.; Denenberg, J.; Des Jarlais, D.C.; Dharmaratne, S.D.; Dorsey, E.R.; Driscoll, T.; Duber, H.; Ebel, B.; Erwin, P.J.; Espindola, P.; Ezzati, M.; Feigin, V.; Flaxman, A.D.; Forouzanfar, M.H.; Fowkes, F.G.; Franklin, R.; Fransen, M.; Freeman, M.K.; Gabriel, S.E.; Gakidou, E.; Gaspari, F.; Gillum, R.F.; Gonzalez-Medina, D.; Halasa, Y.A.; Haring, D.; Harrison, J.E.; Havmoeller, R.; Hay, R.J.; Hoen, B.; Hotez, P.J.; Hoy, D.; Jacobsen, K.H.; James, S.L.; Jasrasaria, R.; Jayaraman, S.; Johns, N.; Karthikeyan, G.; Kassebaum, N.; Keren, A.; Khoo, J.P.; Knowlton, L.M.; Kobusingye, O.; Koranteng, A.; Krishnamurthi, R.; Lipnick, M.; Lipshultz, S.E.; Ohno, S.L.; Mabweijano, J.; MacIntyre, M.F.; Mallinger, L.; March, L.; Marks, G.B.; Marks, R.; Matsumori, A.; Matzopoulos, R.; Mayosi, B.M.; McAnulty, J.H.; McDermott, M.M.; McGrath, J.; Mensah, G.A.; Merriman, T.R.; Michaud, C.; Miller, M.; Miller, T.R.; Mock, C.; Mocumbi, A.O.; Mokdad, A.A.; Moran, A.; Mulholland, K.; Nair, M.N.; Naldi, L.; Narayan, K.M.; Nasseri, K.; Norman, P.; O’Donnell, M.; Omer, S.B.; Ortblad, K.; Osborne, R.; Ozgediz, D.; Pahari, B.; Pandian, J.D.; Rivero, A.P.; Padilla, R.P.; Perez-Ruiz, F.; Perico, N.; Phillips, D.; Pierce, K.; Pope, C.A., III; Porrini, E.; Pourmalek, F.; Raju, M.; Ranganathan, D.; Rehm, J.T.; Rein, D.B.; Remuzzi, G.; Rivara, F.P.; Roberts, T.; De León, F.R.; Rosenfeld, L.C.; Rushton, L.; Sacco, R.L.; Salomon, J.A.; Sampson, U.; Sanman, E.; Schwebel, D.C.; Segui-Gomez, M.; Shepard, D.S.; Singh, D.; Singleton, J.; Sliwa, K.; Smith, E.; Steer, A.; Taylor, J.A.; Thomas, B.; Tleyjeh, I.M.; Towbin, J.A.; Truelsen, T.; Undurraga, E.A.; Venketasubramanian, N.; Vijayakumar, L.; Vos, T.; Wagner, G.R.; Wang, M.; Wang, W.; Watt, K.; Weinstock, M.A.; Weintraub, R.; Wilkinson, J.D.; Woolf, A.D.; Wulf, S.; Yeh, P.H.; Yip, P.; Zabetian, A.; Zheng, Z.J.; Lopez, A.D.; Murray, C.J.; AlMazroa, M.A.; Memish, Z.A. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet, 2012, 380(9859), 2095-2128.
[http://dx.doi.org/10.1016/S0140-6736(12)61728-0] [PMID: 23245604]
[4]
Wahba, I.M.; Mak, R.H. Obesity and obesity-initiated metabolic syndrome: mechanistic links to chronic kidney disease. Clin. J. Am. Soc. Nephrol., 2007, 2(3), 550-562.
[http://dx.doi.org/10.2215/CJN.04071206] [PMID: 17699463]
[5]
Gameiro, J.; Gonçalves, M.; Pereira, M.; Rodrigues, N.; Godinho, I.; Neves, M.; Gouveia, J.; Silva, Z.C.E.; Jorge, S.; Lopes, J.A. Obesity, acute kidney injury and mortality in patients with sepsis: a cohort analysis. Ren. Fail., 2018, 40(1), 120-126.
[http://dx.doi.org/10.1080/0886022X.2018.1430588] [PMID: 29388454]
[6]
Briffa, J.F.; McAinch, A.J.; Poronnik, P.; Hryciw, D.H. Adipokines as a link between obesity and chronic kidney disease. Am. J. Physiol. Renal Physiol., 2013, 305(12), F1629-F1636.
[http://dx.doi.org/10.1152/ajprenal.00263.2013] [PMID: 24107418]
[7]
Yao, F.; Li, Z.; Ehara, T.; Yang, L.; Wang, D.; Feng, L.; Zhang, Y.; Wang, K.; Shi, Y.; Duan, H.; Zhang, L. Fatty Acid-Binding Protein 4 mediates apoptosis via endoplasmic reticulum stress in mesangial cells of diabetic nephropathy. Mol. Cell. Endocrinol., 2015, 411, 232-242.
[http://dx.doi.org/10.1016/j.mce.2015.05.003] [PMID: 25958041]
[8]
Shi, M.; Huang, R.; Guo, F.; Li, L.; Feng, Y.; Wei, Z.; Zhou, L.; Ma, L.; Fu, P. Pharmacological inhibition of fatty acid-binding protein 4 (fabp4) protects against renal ischemia-reperfusion injury. RSC Advances, 2018, 8, 15207-15214.
[http://dx.doi.org/10.1039/C8RA00122G]
[9]
Huang, R.; Shi, M.; Guo, F.; Feng, Y.; Feng, Y.; Liu, J.; Li, L.; Liang, Y.; Xiang, J.; Lei, S.; Ma, L.; Fu, P. Pharmacological inhibition of fatty acid-binding protein 4 (fabp4) protects against rhabdomyolysis-induced acute kidney injury. Front. Pharmacol., 2018, 9, 917.
[http://dx.doi.org/10.3389/fphar.2018.00917] [PMID: 30135658]
[10]
Furuhashi, M.; Tuncman, G.; Görgün, C.Z.; Makowski, L.; Atsumi, G.; Vaillancourt, E.; Kono, K.; Babaev, V.R.; Fazio, S.; Linton, M.F.; Sulsky, R.; Robl, J.A.; Parker, R.A.; Hotamisligil, G.S. Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2. Nature, 2007, 447(7147), 959-965.
[http://dx.doi.org/10.1038/nature05844] [PMID: 17554340]
[11]
Furuhashi, M.; Hotamisligil, G.S. Fatty acid-binding proteins: role in metabolic diseases and potential as drug targets. Nat. Rev. Drug Discov., 2008, 7(6), 489-503.
[http://dx.doi.org/10.1038/nrd2589] [PMID: 18511927]
[12]
Spiegelman, B.M.; Frank, M.; Green, H. Molecular cloning of mRNA from 3T3 adipocytes. Regulation of mRNA content for glycerophosphate dehydrogenase and other differentiation-dependent proteins during adipocyte development. J. Biol. Chem., 1983, 258(16), 10083-10089.
[PMID: 6411703]
[13]
Hunt, C.R.; Ro, J.H.; Dobson, D.E.; Min, H.Y.; Spiegelman, B.M. Adipocyte P2 gene: developmental expression and homology of 5′-flanking sequences among fat cell-specific genes. Proc. Natl. Acad. Sci. USA, 1986, 83(11), 3786-3790.
[http://dx.doi.org/10.1073/pnas.83.11.3786] [PMID: 3520554]
[14]
Hertzel, A.V.; Bernlohr, D.A. The mammalian fatty acid-binding protein multigene family: molecular and genetic insights into function. Trends Endocrinol. Metab., 2000, 11(5), 175-180.
[http://dx.doi.org/10.1016/S1043-2760(00)00257-5] [PMID: 10856918]
[15]
Melki, S.A.; Abumrad, N.A. Expression of the adipocyte fatty acid-binding protein in streptozotocin-diabetes: effects of insulin deficiency and supplementation. J. Lipid Res., 1993, 34(9), 1527-1534.
[PMID: 7693843]
[16]
Distel, R.J.; Robinson, G.S.; Spiegelman, B.M. Fatty acid regulation of gene expression. Transcriptional and post-transcriptional mechanisms. J. Biol. Chem., 1992, 267(9), 5937-5941.
[PMID: 1372897]
[17]
Makowski, L.; Boord, J.B.; Maeda, K.; Babaev, V.R.; Uysal, K.T.; Morgan, M.A.; Parker, R.A.; Suttles, J.; Fazio, S.; Hotamisligil, G.S.; Linton, M.F. Lack of macrophage fatty-acid-binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis. Nat. Med., 2001, 7(6), 699-705.
[http://dx.doi.org/10.1038/89076] [PMID: 11385507]
[18]
Furuhashi, M.; Saitoh, S.; Shimamoto, K.; Miura, T. Fatty acid-binding protein 4 (fabp4): Pathophysiological insights and potent clinical biomarker of metabolic and cardiovascular diseases. Clin. Med. Insights Cardiol., 2015, 8(Suppl. 3), 23-33.
[http://dx.doi.org/10.4137/CMC.S17067] [PMID: 25674026]
[19]
Pelton, P.D.; Zhou, L.; Demarest, K.T.; Burris, T.P. PPARgamma activation induces the expression of the adipocyte fatty acid binding protein gene in human monocytes. Biochem. Biophys. Res. Commun., 1999, 261(2), 456-458.
[http://dx.doi.org/10.1006/bbrc.1999.1071] [PMID: 10425206]
[20]
Fu, Y.; Luo, N.; Lopes-Virella, M.F. Oxidized LDL induces the expression of ALBP/aP2 mRNA and protein in human THP-1 macrophages. J. Lipid Res., 2000, 41(12), 2017-2023.
[PMID: 11108735]
[21]
Fu, Y.; Luo, N.; Lopes-Virella, M.F.; Garvey, W.T. The adipocyte lipid binding protein (ALBP/aP2) gene facilitates foam cell formation in human THP-1 macrophages. Atherosclerosis, 2002, 165(2), 259-269.
[http://dx.doi.org/10.1016/S0021-9150(02)00305-2] [PMID: 12417276]
[22]
Kazemi, M.R.; McDonald, C.M.; Shigenaga, J.K.; Grunfeld, C.; Feingold, K.R. Adipocyte fatty acid-binding protein expression and lipid accumulation are increased during activation of murine macrophages by toll-like receptor agonists. Arterioscler. Thromb. Vasc. Biol., 2005, 25(6), 1220-1224.
[http://dx.doi.org/10.1161/01.ATV.0000159163.52632.1b] [PMID: 15705927]
[23]
Wang, X.Q.; Yang, K.; He, Y.S.; Lu, L.; Shen, W.F. Receptor mediated elevation in FABP4 levels by advanced glycation end products induces cholesterol and triacylglycerol accumulation in THP-1 macrophages. Lipids, 2011, 46(6), 479-486.
[http://dx.doi.org/10.1007/s11745-011-3542-4] [PMID: 21336983]
[24]
Makowski, L.; Brittingham, K.C.; Reynolds, J.M.; Suttles, J.; Hotamisligil, G.S. The fatty acid-binding protein, aP2, coordinates macrophage cholesterol trafficking and inflammatory activity. Macrophage expression of aP2 impacts peroxisome proliferator-activated receptor gamma and IkappaB kinase activities. J. Biol. Chem., 2005, 280(13), 12888-12895.
[http://dx.doi.org/10.1074/jbc.M413788200] [PMID: 15684432]
[25]
Diakov, T.T.; Kane, P.M. Regulation of vacuolar proton-translocating ATPase activity and assembly by extracellular pH. J. Biol. Chem., 2010, 285(31), 23771-23778.
[http://dx.doi.org/10.1074/jbc.M110.110122] [PMID: 20511227]
[26]
Shum, B.O.; Mackay, C.R.; Gorgun, C.Z.; Frost, M.J.; Kumar, R.K.; Hotamisligil, G.S.; Rolph, M.S. The adipocyte fatty acid-binding protein aP2 is required in allergic airway inflammation. J. Clin. Invest., 2006, 116(8), 2183-2192.
[http://dx.doi.org/10.1172/JCI24767] [PMID: 16841093]
[27]
Elmasri, H.; Karaaslan, C.; Teper, Y.; Ghelfi, E.; Weng, M.; Ince, T.A.; Kozakewich, H.; Bischoff, J.; Cataltepe, S. Fatty acid binding protein 4 is a target of VEGF and a regulator of cell proliferation in endothelial cells. FASEB J., 2009, 23(11), 3865-3873.
[http://dx.doi.org/10.1096/fj.09-134882] [PMID: 19625659]
[28]
Rodríguez-Calvo, R.; Girona, J.; Alegret, J.M.; Bosquet, A.; Ibarretxe, D.; Masana, L. Role of the fatty acid-binding protein 4 in heart failure and cardiovascular disease. J. Endocrinol., 2017, 233(3), R173-R184.
[http://dx.doi.org/10.1530/JOE-17-0031] [PMID: 28420707]
[29]
Gray, S.; Kim, J.K. New insights into insulin resistance in the diabetic heart. Trends Endocrinol. Metab., 2011, 22(10), 394-403.
[http://dx.doi.org/10.1016/j.tem.2011.05.001] [PMID: 21680199]
[30]
Xu, A.; Wang, Y.; Xu, J.Y.; Stejskal, D.; Tam, S.; Zhang, J.; Wat, N.M.; Wong, W.K.; Lam, K.S. Adipocyte fatty acid-binding protein is a plasma biomarker closely associated with obesity and metabolic syndrome. Clin. Chem., 2006, 52(3), 405-413.
[http://dx.doi.org/10.1373/clinchem.2005.062463] [PMID: 16423904]
[31]
Kralisch, S.; Fasshauer, M. Adipocyte fatty acid binding protein: a novel adipokine involved in the pathogenesis of metabolic and vascular disease? Diabetologia, 2013, 56(1), 10-21.
[http://dx.doi.org/10.1007/s00125-012-2737-4] [PMID: 23052058]
[32]
Cabré, A.; Lázaro, I.; Girona, J.; Manzanares, J.M.; Marimón, F.; Plana, N.; Heras, M.; Masana, L. Plasma fatty acid-binding protein 4 increases with renal dysfunction in type 2 diabetic patients without microalbuminuria. Clin. Chem., 2008, 54(1), 181-187.
[http://dx.doi.org/10.1373/clinchem.2007.094672] [PMID: 18024526]
[33]
Sommer, G.; Ziegelmeier, M.; Bachmann, A.; Kralisch, S.; Lossner, U.; Kratzsch, J.; Blüher, M.; Stumvoll, M.; Fasshauer, M. Serum levels of adipocyte fatty acid-binding protein (AFABP) are increased in chronic haemodialysis (CD). Clin. Endocrinol. (Oxf.), 2008, 69(6), 901-905.
[http://dx.doi.org/10.1111/j.1365-2265.2008.03277.x] [PMID: 18419784]
[34]
Ebert, T.; Hopf, L.M.; Wurst, U.; Bachmann, A.; Kralisch, S.; Lössner, U.; Platz, M.; Kratzsch, J.; Stolzenburg, J.U.; Dietel, A.; Grisk, O.; Beige, J.; Anders, M.; Bast, I.; Klöting, N.; Blüher, M.; Stumvoll, M.; Fasshauer, M. Circulating adipocyte fatty acid binding protein is increased in chronic and acute renal dysfunction. Nutr. Metab. Cardiovasc. Dis., 2014, 24(9), 1027-1034.
[http://dx.doi.org/10.1016/j.numecd.2014.03.006] [PMID: 24813306]
[35]
Iwamoto, M.; Miyoshi, T.; Doi, M.; Takeda, K.; Kajiya, M.; Nosaka, K.; Nakayama, R.; Hirohata, S.; Usui, S.; Kusachi, S.; Sakane, K.; Nakamura, K.; Ito, H. Elevated serum adipocyte fatty acid-binding protein concentrations are independently associated with renal dysfunction in patients with stable angina pectoris. Cardiovasc. Diabetol., 2012, 11, 26.
[http://dx.doi.org/10.1186/1475-2840-11-26] [PMID: 22433902]
[36]
Toruner, F.; Altinova, A.E.; Akturk, M.; Kaya, M.; Arslan, E.; Bukan, N.; Kan, E.; Yetkin, I.; Arslan, M. The relationship between adipocyte fatty acid binding protein-4, retinol binding protein-4 levels and early diabetic nephropathy in patients with type 2 diabetes. Diabetes Res. Clin. Pract., 2011, 91(2), 203-207.
[http://dx.doi.org/10.1016/j.diabres.2010.11.011] [PMID: 21176857]
[37]
Yeung, D.C.; Xu, A.; Tso, A.W.; Chow, W.S.; Wat, N.M.; Fong, C.H.; Tam, S.; Sham, P.C.; Lam, K.S. Circulating levels of adipocyte and epidermal fatty acid-binding proteins in relation to nephropathy staging and macrovascular complications in type 2 diabetic patients. Diabetes Care, 2009, 32(1), 132-134.
[http://dx.doi.org/10.2337/dc08-1333] [PMID: 18931100]
[38]
Okazaki, Y.; Furuhashi, M.; Tanaka, M.; Mita, T.; Fuseya, T.; Ishimura, S.; Watanabe, Y.; Hoshina, K.; Akasaka, H.; Ohnishi, H.; Yoshida, H.; Saitoh, S.; Shimamoto, K.; Miura, T. Urinary excretion of fatty acid-binding protein 4 is associated with albuminuria and renal dysfunction. PLoS One, 2014, 9(12)e115429
[http://dx.doi.org/10.1371/journal.pone.0115429] [PMID: 25506691]
[39]
Yeung, D.C.; Xu, A.; Cheung, C.W.; Wat, N.M.; Yau, M.H.; Fong, C.H.; Chau, M.T.; Lam, K.S. Serum adipocyte fatty acid-binding protein levels were independently associated with carotid atherosclerosis. Arterioscler. Thromb. Vasc. Biol., 2007, 27(8), 1796-1802.
[http://dx.doi.org/10.1161/ATVBAHA.107.146274] [PMID: 17510463]
[40]
Xu, A.; Tso, A.W.; Cheung, B.M.; Wang, Y.; Wat, N.M.; Fong, C.H.; Yeung, D.C.; Janus, E.D.; Sham, P.C.; Lam, K.S. Circulating adipocyte-fatty acid binding protein levels predict the development of the metabolic syndrome: a 5-year prospective study. Circulation, 2007, 115(12), 1537-1543.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.106.647503] [PMID: 17389279]
[41]
Tso, A.W.; Xu, A.; Sham, P.C.; Wat, N.M.; Wang, Y.; Fong, C.H.; Cheung, B.M.; Janus, E.D.; Lam, K.S. Serum adipocyte fatty acid binding protein as a new biomarker predicting the development of type 2 diabetes: a 10-year prospective study in a Chinese cohort. Diabetes Care, 2007, 30(10), 2667-2672.
[http://dx.doi.org/10.2337/dc07-0413] [PMID: 17620449]
[42]
El Nahas, M. Cardio-Kidney-Damage: a unifying concept. Kidney Int., 2010, 78(1), 14-18.
[http://dx.doi.org/10.1038/ki.2010.123] [PMID: 20445499]
[43]
Furuhashi, M.; Ishimura, S.; Ota, H.; Hayashi, M.; Nishitani, T.; Tanaka, M.; Yoshida, H.; Shimamoto, K.; Hotamisligil, G.S.; Miura, T. Serum fatty acid-binding protein 4 is a predictor of cardiovascular events in end-stage renal disease. PLoS One, 2011, 6(11)e27356
[http://dx.doi.org/10.1371/journal.pone.0027356] [PMID: 22102888]
[44]
Chen, Y.C.; Hsu, B.G.; Lee, C.J.; Ho, C.C.; Ho, G.J.; Lee, M.C. Serum adipocyte fatty acid-binding protein level is associated with arterial stiffness quantified with cardio-ankle vascular index in kidney transplant patients. Clin. Exp. Nephrol., 2018, 22(1), 188-195.
[http://dx.doi.org/10.1007/s10157-017-1438-1] [PMID: 28660445]
[45]
Tanaka, M.; Furuhashi, M.; Okazaki, Y.; Mita, T.; Fuseya, T.; Ohno, K.; Ishimura, S.; Yoshida, H.; Miura, T. Ectopic expression of fatty acid-binding protein 4 in the glomerulus is associated with proteinuria and renal dysfunction. Nephron Clin. Pract., 2014, 128(3-4), 345-351.
[http://dx.doi.org/10.1159/000368412] [PMID: 25592475]
[46]
Matthys, E.; Patel, Y.; Kreisberg, J.; Stewart, J.H.; Venkatachalam, M. Lipid alterations induced by renal ischemia: pathogenic factor in membrane damage. Kidney Int., 1984, 26(2), 153-161.
[http://dx.doi.org/10.1038/ki.1984.149] [PMID: 6503134]
[47]
Zimmerman, A.W.; Veerkamp, J.H. Fatty-acid-binding proteins do not protect against induced cytotoxicity in a kidney cell model. Biochem. J., 2001, 360(Pt 1), 159-165.
[http://dx.doi.org/10.1042/bj3600159] [PMID: 11696003]
[48]
Soccio, R.E.; Chen, E.R.; Rajapurkar, S.R.; Safabakhsh, P.; Marinis, J.M.; Dispirito, J.R.; Emmett, M.J.; Briggs, E.R.; Fang, B.; Everett, L.J.; Lim, H.W.; Won, K.J.; Steger, D.J.; Wu, Y.; Civelek, M.; Voight, B.F.; Lazar, M.A. Genetic variation determines ppargamma function and anti-diabetic drug response in vivo. Cell, 2015, 162(1), 33-44.
[http://dx.doi.org/10.1016/j.cell.2015.06.025] [PMID: 26140591]
[49]
Buckingham, R.E.; Al-Barazanji, K.A.; Toseland, C.D.; Slaughter, M.; Connor, S.C.; West, A.; Bond, B.; Turner, N.C.; Clapham, J.C. Peroxisome proliferator-activated receptor-gamma agonist, rosiglitazone, protects against nephropathy and pancreatic islet abnormalities in Zucker fatty rats. Diabetes, 1998, 47(8), 1326-1334.
[http://dx.doi.org/10.2337/diabetes.47.8.1326] [PMID: 9703335]
[50]
Yoshimoto, T.; Naruse, M.; Nishikawa, M.; Naruse, K.; Tanabe, A.; Seki, T.; Imaki, T.; Demura, R.; Aikawa, E.; Demura, H. Antihypertensive and vasculo- and renoprotective effects of pioglitazone in genetically obese diabetic rats. Am. J. Physiol., 1997, 272(6 Pt 1), E989-E996.
[http://dx.doi.org/10.1152/ajpendo.1997.272.6.E989] [PMID: 9227442]
[51]
Guan, Y.; Zhang, Y.; Schneider, A.; Davis, L.; Breyer, R.M.; Breyer, M.D. Peroxisome proliferator-activated receptor-gamma activity is associated with renal microvasculature. Am. J. Physiol. Renal Physiol., 2001, 281(6), F1036-F1046.
[http://dx.doi.org/10.1152/ajprenal.0025.2001] [PMID: 11704554]
[52]
Adida, A.; Spener, F. Adipocyte-type fatty acid-binding protein as inter-compartmental shuttle for peroxisome proliferator activated receptor gamma agonists in cultured cell. Biochim. Biophys. Acta, 2006, 1761(2), 172-181.
[http://dx.doi.org/10.1016/j.bbalip.2006.02.006] [PMID: 16574478]
[53]
Ayers, S.D.; Nedrow, K.L.; Gillilan, R.E.; Noy, N. Continuous nucleocytoplasmic shuttling underlies transcriptional activation of PPARgamma by FABP4. Biochemistry, 2007, 46(23), 6744-6752.
[http://dx.doi.org/10.1021/bi700047a] [PMID: 17516629]
[54]
Gillilan, R.E.; Ayers, S.D.; Noy, N. Structural basis for activation of fatty acid-binding protein 4. J. Mol. Biol., 2007, 372(5), 1246-1260.
[http://dx.doi.org/10.1016/j.jmb.2007.07.040] [PMID: 17761196]
[55]
Floresta, G.; Pistarà, V.; Amata, E.; Dichiara, M.; Marrazzo, A.; Prezzavento, O.; Rescifina, A. Adipocyte fatty acid binding protein 4 (FABP4) inhibitors. A comprehensive systematic review. Eur. J. Med. Chem., 2017, 138, 854-873.
[http://dx.doi.org/10.1016/j.ejmech.2017.07.022] [PMID: 28738306]
[56]
Hornigold, N.; Johnson, T.S.; Huang, L.; Haylor, J.L.; Griffin, M.; Mooney, A. Inhibition of collagen I accumulation reduces glomerulosclerosis by a Hic-5-dependent mechanism in experimental diabetic nephropathy. Lab. Invest., 2013, 93(5), 553-565.
[http://dx.doi.org/10.1038/labinvest.2013.42] [PMID: 23508044]
[57]
Xu, H.; Hertzel, A.V.; Steen, K.A.; Wang, Q.; Suttles, J.; Bernlohr, D.A. Uncoupling lipid metabolism from inflammation through fatty acid binding protein-dependent expression of UCP2. Mol. Cell. Biol., 2015, 35(6), 1055-1065.
[http://dx.doi.org/10.1128/MCB.01122-14] [PMID: 25582199]
[58]
Zarjou, A.; Agarwal, A. Sepsis and acute kidney injury. J. Am. Soc. Nephrol., 2011, 22(6), 999-1006.
[http://dx.doi.org/10.1681/ASN.2010050484] [PMID: 21566052]
[59]
Akchurin, O.M.; Kaskel, F. Update on inflammation in chronic kidney disease. Blood Purif., 2015, 39(1-3), 84-92.
[http://dx.doi.org/10.1159/000368940] [PMID: 25662331]

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Request history8.2.27PHP Version1.5sRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[17:27:41] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
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  • Application (1.3s)time
  • 1 x Application (86.8%)
    1.30s
    1 x Booting (13.2%)
    198ms
    14 templates were rendered
    • articlearticle.blade.php#?blade
    • includes.article_top_bannerarticle_top_banner.blade.php#?blade
    • includes.article_referencearticle_reference.blade.php#?blade
    • export_citation_formexport_citation_form.blade.php#?blade
    • includes.article_bottom_bannerarticle_bottom_banner.blade.php#?blade
    • includes.inc_related_journalsinc_related_journals.blade.php#?blade
    • includes.inc_related_ebooksinc_related_ebooks.blade.php#?blade
    • includes.journal_rightmenujournal_rightmenu.blade.php#?blade
    • includes.journal_right_bannerjournal_right_banner.blade.php#?blade
    • layouts.appapp.blade.php#?blade
    • layouts._login_access_login_access.blade.php#?blade
    • layouts._header_header.blade.php#?blade
    • layouts._main_menu_main_menu.blade.php#?blade
    • layouts._footer_menu_footer_menu.blade.php#?blade
    uri
    GET article/{article_id}/{param?}
    middleware
    web, check_user_access
    controller
    App\Http\Controllers\ArticleController@GetArticleDetails
    namespace
    App\Http\Controllers
    where
    as
    article
    file
    app/Http/Controllers/ArticleController.php:1974-2510
    40 statements were executed, 4 of which were duplicates, 36 unique. Show only duplicated1.19s
    • Connection Establishedalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 9. middleware::check_user_access:24
      • 10. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 11. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address (ip_address,visitor_agent,visitor_count, created_on,updated_on) VALUES ('316609994','',1,1740677261,1740677261) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1740677261
      19.5msalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 11. middleware::check_user_access:24
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address_detail (ip_address,visitor_url,visitor_count, created_on,updated_on) VALUES ('316609994','/article/93518/cn',1,1740677261,1740677261)
      250μsalphaeurekaselec_live_10_06_2022UserAccessCheck.php#27
      Backtrace
      • 11. middleware::check_user_access:27
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_trail WHERE to_ip >= 316609994 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316609994) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_corporate WHERE to_ip >= 316609994 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316609994) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_token WHERE to_ip >= 316609994 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316609994) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_trail WHERE to_ip >= 316609994 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316609994) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_corporate WHERE to_ip >= 316609994 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316609994) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_token WHERE to_ip >= 316609994 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316609994) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 316609994 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316609994) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 316609994 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316609994) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 316609994 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316609994) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 316609994 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316609994) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 316609994 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316609994) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 316609994 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316609994) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 316609994 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316609994) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 316609994 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316609994) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 316609994 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316609994) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 316609994 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316609994) limit 1
      95.31msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 316609994
      • 1: 316609994
      • 2: 316609994
      • 3: 316609994
      • 4: 316609994
      • 5: 316609994
      • 6: 316609994
      • 7: 316609994
      • 8: 316609994
      • 9: 316609994
      • 10: 316609994
      • 11: 316609994
      • 12: 316609994
      • 13: 316609994
      • 14: 316609994
      • 15: 316609994
      Backtrace
      • 14. app/Models/UserAccess/UserAccess.php:784
      • 15. middleware::check_user_access:114
      • 16. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 18. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
    • SELECT at.type_name, p.copyright, p.publisher_location,m.month,y.year, a.publish_on, a.nid article_nid,a.article_id, a.pmid, a.issue_id, a.title, a.abstract,a.podcast,a.altmetric_score,a.altmetric_url,a.kudos_url, a.page_count, a.first_page, a.elocator, a.last_page, i.publication_date, a.file_name, a.file_path, a.doi, a.is_epub,a.epub_type, a.volume_id, a.is_uploaded, a.editor_choice, a.is_epub, j.image_file_name, a.article_no, a.art_type AS article_type, a.supplementary_filename,a.html_filename,a.prc_filename,a.epub_filename, a.graph_abs_lg_filename, a.graph_abs_sm_filename, a.oa_image_lg_filename, a.oa_image_sm_filename, j.journal_banner,a.animated_abstract,a.erratum_in,a.erratum_for, (CASE WHEN a.issue_id =0 THEN j.epub_price ELSE j.price END) AS sell_price, j.epub_price, j.nid AS jour_nid, j.title AS journal_title, j.issn, j.eissn,j.journal_id, j.subtitle AS jour_subtitle, v.volume_id,v.volume_name AS volume, v.year_id, i.title AS issue, i.month_id ,i.type issue_type, j.subtitle,j.formerly_title, ac.subtitle AS epub_title,a.crossmark_enabled,a.text_mining_urls,a.license_urls,a.created, a.receivedate, a.revisedate, a.acceptdate,js.js_title FROM article a LEFT JOIN article_section ac ON a.is_epub = ac.art_sec_id LEFT JOIN journal_section js ON a.js_id = js.js_id LEFT JOIN article_type at ON a.art_type = at.art_type_id LEFT JOIN issue i ON a.issue_id = i.issue_id LEFT JOIN month m ON m.id = i.month_id LEFT JOIN volume v ON v.volume_id = a.volume_id INNER JOIN year y ON y.id = v.year_id INNER JOIN journal j ON j.journal_id = a.journal_id INNER JOIN publisher p ON p.publisher_id = j.publisher_id WHERE a.article_id=93518
      67.65msalphaeurekaselec_live_10_06_2022Article.php#408
      Backtrace
      • 11. app/Models/Article.php:408
      • 12. app/Http/Controllers/ArticleController.php:2515
      • 13. app/Http/Controllers/ArticleController.php:2035
      • 14. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 15. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `journal` where `journal_id` = 25 limit 1
      1.33msalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 25
      Backtrace
      • 14. app/Models/Journal.php:64
      • 15. app/Http/Controllers/ArticleController.php:2516
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=25) and sj.journal_id!=25 group by `j`.`nid`) as `aggregate_table`
      1.99msalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 16. app/Models/Subject.php:200
      • 17. app/Http/Controllers/ArticleController.php:2517
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=25) and sj.journal_id!=25 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      1.99msalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 14. app/Models/Subject.php:200
      • 15. app/Http/Controllers/ArticleController.php:2517
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=25) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      208msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 16. app/Models/Subject.php:220
      • 17. app/Http/Controllers/ArticleController.php:2518
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=25) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      43.55msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 14. app/Models/Subject.php:220
      • 15. app/Http/Controllers/ArticleController.php:2518
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `keywords` where `article_id` = '93518'
      7.87msalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 93518
      Backtrace
      • 13. app/Models/Keywords.php:43
      • 14. app/Http/Controllers/ArticleController.php:2519
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `article_citation` where `article_id` = '93518'
      18.71msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 93518
      Backtrace
      • 13. app/Models/Article.php:1570
      • 14. app/Http/Controllers/ArticleController.php:2520
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select CONCAT_WS(' ',au.first_name, ' ', ifnull(au.initials,''), ' ', au.last_name) as authors, CONCAT(au.last_name, IFNULL(CONCAT(' ', au.initials), ''), ' ', au.first_name) AS authorsRIS, CONCAT_WS(' ',au.last_name, ' ', ifnull(au.initials,''), ' ', au.first_name) as authorsCiteAs, CONCAT_WS(' ',au.first_name, IFNULL(CONCAT(' ', au.initials), ''), IFNULL(CONCAT(' ', au.last_name), '')) as authorsmodal , `au`.*, `af`.`ror_id`, `af`.`institution`, `af`.`department`, `af`.`country`, `af`.`city`, `af`.`address`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.institution,','),''), ifnull(concat(af.department,','),''), ifnull(concat(af.address,','),''), ifnull(concat(af.city,','),''), ifnull(concat(af.country,','),''), ifnull(concat(af.postal_code,','),''), ifnull(concat(af.phone,','),''), ifnull(concat(af.fax,','),''))) SEPARATOR '|')) as `author_affiliation`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.web_view,','),''))) SEPARATOR '|')) as `web_view` from `author` as `au` left join `author_affiliation` as `af` on `au`.`author_id` = `af`.`author_id` where `au`.`article_id` = '93518' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      4.33msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 93518
      Backtrace
      • 13. app/Models/Author.php:86
      • 14. app/Http/Controllers/ArticleController.php:2533
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      370μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2535
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `subtitle` from `journal` where `continues_publication_journal` = 1
      760μsalphaeurekaselec_live_10_06_2022Article.php#1960
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/Article.php:1960
      • 14. app/Http/Controllers/ArticleController.php:2062
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • Select j.subtitle, v.volume_id as volume_id,v.year_id,y.year as year,v.volume_name, v.total_no_of_issues, i.issue_id as issue_id,i.title as issue, i.publication_date as issue_pub_date from journal j join volume v on j.journal_id = v.journal_id join issue i on v.volume_id = i.volume_id join article a on a.issue_id = i.issue_id join year y on v.year_id = y.id where j.journal_id = 25 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      358msalphaeurekaselec_live_10_06_2022Issue.php#298
      Backtrace
      • 11. app/Models/Issue.php:298
      • 12. app/Http/Controllers/ArticleController.php:2068
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 1 and a.journal_id = 25 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      126msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2070
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 4 and a.journal_id = 25 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      132msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2071
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select pdf, html, epub, prc from `article_metrics` where `article_id` = 93518 limit 1
      460μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 93518
      Backtrace
      • 14. app/Models/Article.php:744
      • 15. app/Http/Controllers/ArticleController.php:2091
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from content_by_diseases where content_id = 93518 and content_type = 'article' order by status desc limit 1
      350μsalphaeurekaselec_live_10_06_2022Article.php#751
      Backtrace
      • 11. app/Models/Article.php:751
      • 12. app/Http/Controllers/ArticleController.php:2094
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `node_meta` where `nid` = 166053 limit 1
      280μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 166053
      Backtrace
      • 14. app/Models/Meta.php:30
      • 15. app/Http/Controllers/ArticleController.php:2101
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      310μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2108
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `tbl_ht_submission` as `h` where `h`.`subtitle` = 'CMC' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      480μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CMC
      Backtrace
      • 13. app/Models/Article.php:2025
      • 14. app/Http/Controllers/ArticleController.php:2112
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '93518' and content_type = 'a' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      510μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2186
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '9928' and content_type = 'i' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      430μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2207
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '2698' and content_type = 'v' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      410μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2231
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316609994 and j.to_ip >=316609994 )) and ((j.from_date <= 1740677262 and j.to_date >= 1740677262 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2698) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316609994 and j.to_ip >=316609994 )) and ((j.from_date <= 1740677262 and j.to_date >= 1740677262 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2698) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316609994 and j.to_ip >=316609994 )) and ((j.from_date <= 1740677262 and j.to_date >= 1740677262 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2698)
      51.87msalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2272
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316609994 and j.to_ip >=316609994 )) and ((j.from_date <= 1740677262 and j.to_date >= 1740677262 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9928) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316609994 and j.to_ip >=316609994 )) and ((j.from_date <= 1740677262 and j.to_date >= 1740677262 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9928) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316609994 and j.to_ip >=316609994 )) and ((j.from_date <= 1740677262 and j.to_date >= 1740677262 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9928)
      960μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2297
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316609994 and j.to_ip >=316609994 )) and ((j.from_date <= 1740677262 and j.to_date >= 1740677262 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 93518) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316609994 and j.to_ip >=316609994 )) and ((j.from_date <= 1740677262 and j.to_date >= 1740677262 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 93518) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316609994 and j.to_ip >=316609994 )) and ((j.from_date <= 1740677262 and j.to_date >= 1740677262 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 93518)
      1msalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2329
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `first_page` < '3657' and is_uploaded = 1 and issue_id = 9928 order by cast(first_page as SIGNED) desc limit 1
      740μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 3657
      Backtrace
      • 14. app/Models/Article.php:1819
      • 15. app/Http/Controllers/ArticleController.php:2470
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `last_page` > '3664' and is_uploaded = 1 and issue_id = 9928 order by cast(first_page as SIGNED) asc limit 1
      660μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 3664
      Backtrace
      • 14. app/Models/Article.php:1831
      • 15. app/Http/Controllers/ArticleController.php:2472
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `language_id` from `multilanguage` where `short_code` = 'cn'
      240μsalphaeurekaselec_live_10_06_2022ArticleController.php#2486
      Bindings
      • 0: cn
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2486
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `source_lang_label`, `target_lang_label` from `multilanguage_labels` where `target_lang_id` = 2
      300μsalphaeurekaselec_live_10_06_2022MultiLanguage.php#23
      Bindings
      • 0: 2
      Backtrace
      • 13. app/Models/MultiLanguage.php:23
      • 14. app/Http/Controllers/ArticleController.php:2487
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `multilanguage_article` where (`language_id` = 2 and `article_id` = 93518)
      9.49msalphaeurekaselec_live_10_06_2022ArticleController.php#2488
      Bindings
      • 0: 2
      • 1: 93518
      Backtrace
      • 15. app/Http/Controllers/ArticleController.php:2488
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `keyword` from `multilanguage_keywords` where (`language_id` = 2 and `article_id` = 93518)
      4.65msalphaeurekaselec_live_10_06_2022ArticleController.php#2489
      Bindings
      • 0: 2
      • 1: 93518
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2489
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select CONCAT_WS(' ',au.first_name, ' ', ifnull(au.initials,''), ' ', au.last_name) as authors, CONCAT_WS(' ',au.last_name, ', ', ifnull(au.initials,''), ' ', au.first_name) as authorsRIS, CONCAT_WS(' ',au.last_name, ' ', ifnull(au.initials,''), ' ', au.first_name) as authorsCiteAs , `au`.*, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.institution,','),''), ifnull(concat(af.department,','),''), ifnull(concat(af.address,','),''), ifnull(concat(af.city,','),''), ifnull(concat(af.country,','),''), ifnull(concat(af.postal_code,','),''), ifnull(concat(af.phone,','),''), ifnull(concat(af.fax,','),''))) SEPARATOR '|')) as `author_affiliation`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.web_view,','),''))) SEPARATOR '|')) as `web_view` from `multilanguage_authors` as `au` left join `multilanguage_author_affiliation` as `af` on `au`.`id` = `af`.`author_id` where `au`.`article_id` = 93518 group by `au`.`id` order by `au`.`article_id` asc, `au`.`sequence` asc
      6.57msalphaeurekaselec_live_10_06_2022MultiLangAuthor.php#30
      Bindings
      • 0: 93518
      Backtrace
      • 13. app/Models/MultiLangAuthor.php:30
      • 14. app/Http/Controllers/ArticleController.php:2493
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `multilanguage_journal`.`title` from `multilanguage_journal` where `multilanguage_journal`.`journal_id` = 25 and `language_id` = 2
      12.91msalphaeurekaselec_live_10_06_2022ArticleController.php#2495
      Bindings
      • 0: 25
      • 1: 2
      Backtrace
      • 13. app/Http/Controllers/ArticleController.php:2495
      • 14. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 15. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `id` from `multilanguage_article` where `article_id` = 93518 limit 1
      2.87msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 93518
      Backtrace
      • 16. app/Http/Controllers/ArticleController.php:2506
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 25 and `b`.`banner_from_date` <= 1740677262 and `b`.`banner_to_date` >= 1740677262 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.58msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 25
      • 3: 1740677262
      • 4: 1740677262
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 25 and `b`.`banner_from_date` <= 1740677262 and `b`.`banner_to_date` >= 1740677262 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.56msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 25
      • 3: 1740677262
      • 4: 1740677262
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='4e1ad8e213779461249f311044015709'
      300μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\MultiLangArticle
    2MultiLangArticle.php#?
    App\Models\MultiLanguage
    1MultiLanguage.php#?
        _token
        UxEHjZQs9pWFJzpPMZ2sMYq8cm9Y2iroovLamtRZ
        uc_cart_id
        4e1ad8e213779461249f311044015709
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/93518/cn" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/93518/cn
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:8 [ "accept-encoding" => array:1 [ 0 => "gzip, deflate" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] "connection" => array:1 [ 0 => "keep-alive" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] ]
        request_cookies
        []
        
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Thu, 27 Feb 2025 17:27:42 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IlN6ZS95MHpqL2pVZ3U3STZFc1psQ2c9PSIsInZhbHVlIjoiVG9BUHh0OTBvaXd2K0NiNUFQTlkraWNzZjNFQ1dseS9lcWc4b1ZWdU5aenRBd2txcVNLcW1YWWxrWG9kb0ttSVRuQmVoc2hGeUFDSnZBSmNCdmZ1cDRxMmV5YUlHMnZyNTViRVpLdTFBdVhESXUxWEFwRHIwUGlnS25tZWppa2giLCJtYWMiOiI3NWNhYzhlODExNGMxODM5OWU2NjNhYzg2Y2VhNWRjYTg0NmY3MWRiNTM4YTg0ODNiZTE5NmNkOGE4NzY0ZGViIiwidGFnIjoiIn0%3D; expires=Sun, 02 Mar 2025 05:27:42 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IlN6ZS95MHpqL2pVZ3U3STZFc1psQ2c9PSIsInZhbHVlIjoiVG9BUHh0OTBvaXd2K0NiNUFQTlkraWNzZjNFQ1dseS9lcWc4b1ZWdU5aenRBd2txcVNLcW1YWWxrWG9kb0ttSVRuQmVoc" 1 => "alphaeurekaselectnet_session=eyJpdiI6IkltVzNqT0o5dW96RUZ3alJoZHNiekE9PSIsInZhbHVlIjoiQU84VzJPTGJCVHFiT09USWVoTitzQ1hHeWMrRml6N1ZXUitqMHlEL2EzVGFPMVBvSGZ2STlOMnB5OEFuTTgvR3RHcEJlUTFISStFSDBMYjlRdzFKOVk4ZUdiWVpza1FZZWU5aUFYZ0dza0pBdUh0NkxMSWZNaW5aVmZ2MGhGWm8iLCJtYWMiOiIxMDhjODJiOTMyNzUxYzkxY2ZiNGI1YjU4ZjNmMmQwNDkzZWYyZTVhMWRjZmZkYjgzOWZjYzZkZDJiYzNjM2E4IiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6IkltVzNqT0o5dW96RUZ3alJoZHNiekE9PSIsInZhbHVlIjoiQU84VzJPTGJCVHFiT09USWVoTitzQ1hHeWMrRml6N1ZXUitqMHlEL2EzVGFPMVBvSGZ2STlOMnB" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IlN6ZS95MHpqL2pVZ3U3STZFc1psQ2c9PSIsInZhbHVlIjoiVG9BUHh0OTBvaXd2K0NiNUFQTlkraWNzZjNFQ1dseS9lcWc4b1ZWdU5aenRBd2txcVNLcW1YWWxrWG9kb0ttSVRuQmVoc2hGeUFDSnZBSmNCdmZ1cDRxMmV5YUlHMnZyNTViRVpLdTFBdVhESXUxWEFwRHIwUGlnS25tZWppa2giLCJtYWMiOiI3NWNhYzhlODExNGMxODM5OWU2NjNhYzg2Y2VhNWRjYTg0NmY3MWRiNTM4YTg0ODNiZTE5NmNkOGE4NzY0ZGViIiwidGFnIjoiIn0%3D; expires=Sun, 02-Mar-2025 05:27:42 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IlN6ZS95MHpqL2pVZ3U3STZFc1psQ2c9PSIsInZhbHVlIjoiVG9BUHh0OTBvaXd2K0NiNUFQTlkraWNzZjNFQ1dseS9lcWc4b1ZWdU5aenRBd2txcVNLcW1YWWxrWG9kb0ttSVRuQmVoc" 1 => "alphaeurekaselectnet_session=eyJpdiI6IkltVzNqT0o5dW96RUZ3alJoZHNiekE9PSIsInZhbHVlIjoiQU84VzJPTGJCVHFiT09USWVoTitzQ1hHeWMrRml6N1ZXUitqMHlEL2EzVGFPMVBvSGZ2STlOMnB5OEFuTTgvR3RHcEJlUTFISStFSDBMYjlRdzFKOVk4ZUdiWVpza1FZZWU5aUFYZ0dza0pBdUh0NkxMSWZNaW5aVmZ2MGhGWm8iLCJtYWMiOiIxMDhjODJiOTMyNzUxYzkxY2ZiNGI1YjU4ZjNmMmQwNDkzZWYyZTVhMWRjZmZkYjgzOWZjYzZkZDJiYzNjM2E4IiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6IkltVzNqT0o5dW96RUZ3alJoZHNiekE9PSIsInZhbHVlIjoiQU84VzJPTGJCVHFiT09USWVoTitzQ1hHeWMrRml6N1ZXUitqMHlEL2EzVGFPMVBvSGZ2STlOMnB" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "UxEHjZQs9pWFJzpPMZ2sMYq8cm9Y2iroovLamtRZ" "uc_cart_id" => "4e1ad8e213779461249f311044015709" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/article/93518/cn" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-27 17:27:42GET/article/93518/cn314403