Generic placeholder image

Current Nanoscience

Editor-in-Chief

ISSN (Print): 1573-4137
ISSN (Online): 1875-6786

Review Article

Antimicrobial Applications of Nanoliposome Encapsulated Silver Nanoparticles: A Potential Strategy to Overcome Bacterial Resistance

Author(s): M.R. Mozafari*, Sarabanou Torkaman, Fatemeh Mahsa Karamouzian, Babak Rasti* and Bikash Baral

Volume 17, Issue 1, 2021

Published on: 12 July, 2020

Page: [26 - 40] Pages: 15

DOI: 10.2174/1573413716999200712184148

Price: $65

Abstract

Bacterial infections result in hundreds of million cases of severe illness annually worldwide. Rapidly increasing drug resistance of pathogens further aggravates this threat to human health and warrants the search for effective broad-spectrum antibacterial agents. Silver metal has a long history of application in human medicine and healthcare. In ancient times, silver was employed as a disinfectant for water purification and storage while it is still being used as an antimicrobial ingredient in some nanotechnology-based products. Encapsulation of antimicrobial substances such as silver nanoparticles in nanoliposomes could provide protection and targeting for the encapsulated or entrapped material. Nanoliposomes are biocompatible and biodegradable drug delivery systems with the ability to encapsulate both lipid-soluble and water-soluble compounds, as well as metal ions. Furthermore, nanoliposomes have been shown to be able to deliver encapsulated agents to target bacteria in vitro as well as in vivo. In this review, we present the use of nanoliposome-encapsulated silver nanoparticles as an efficient system for antibacterial applications.

Keywords: Antibacterial, antimicrobial resistance, biocide, encapsulation, nanoliposome, nanosilver, theranostics.

Graphical Abstract

[1]
Silverman, J.A.; Deitcher, S.R. Marqibo® (vincristine sulfate liposome injection) improves the pharmacokinetics and pharmacodynamics of vincristine. Cancer Chemother. Pharmacol., 2013, 71(3), 555-564.
[http://dx.doi.org/10.1007/s00280-012-2042-4] [PMID: 23212117]
[2]
Ereshefsky, L.; Mascarenas, C.A. Comparison of the effects of different routes of antipsychotic administration on pharmacokinetics and pharmacodynamics. J. Clin. Psychiatry, 2003, 64(Suppl. 16), 18-23.
[PMID: 14680415]
[3]
Rani, V. Nanomedicine and its applications. J. Chem. Pharm. Res., 2015, 7(7), 216-227.
[4]
Mozafari, M.R., Ed.; Nanocarrier Technologies: Frontiers of Nanotherapy; Springer: Dordrecht, The Netherlands, 2006.
[http://dx.doi.org/10.1007/978-1-4020-5041-1]
[5]
Singh, M.; Singh, S.; Prasad, S.; Gambhir, I.S. Nanotechnology in medicine and antibacterial effect of silver nanoparticles. Dig. J. Nanomater. Biostruct., 2008, 3(3), 115-122.
[6]
Jamil, B.; Bokhari, H.; Imran, M. Mechanism of action: how nano-antimicrobials act? Curr. Drug Targets, 2017, 18(3), 363-373.
[http://dx.doi.org/10.2174/1389450116666151019101826] [PMID: 26477460]
[7]
Danaei, M.; Dehghankhold, M.; Ataei, S.; Hasanzadeh Davarani, F.; Javanmard, R.; Dokhani, A.; Khorasani, S.; Mozafari, M.R. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics, 2018, 10(2), 57.
[http://dx.doi.org/10.3390/pharmaceutics10020057] [PMID: 29783687]
[8]
Mozafari, M.R. Liposomes: an overview of manufacturing techniques. Cell. Mol. Biol. Lett., 2005, 10(4), 711-719.
[PMID: 16341279]
[9]
Mozafari, M.R. Nanoliposomes: preparation and analysis. Methods Mol. Biol., 2010, 605, 29-50.
[http://dx.doi.org/10.1007/978-1-60327-360-2_2] [PMID: 20072871]
[10]
Ottenbrite, R.M.; Kim, S.W., Eds.; Polymeric Drugs and Drug Delivery Systems; CRC Press, 2019.
[http://dx.doi.org/10.1201/9780429136405]
[11]
Mozafari, M.R.; Javanmard, R.; Raji, M. Tocosome: Novel drug delivery system containing phospholipids and tocopheryl phosphates. Int. J. Pharm., 2017, 528(1-2), 381-382.
[http://dx.doi.org/10.1016/j.ijpharm.2017.06.037] [PMID: 28619450]
[12]
Wang, L.; Hu, C.; Shao, L. The antimicrobial activity of nanoparticles: present situation and prospects for the future. Int. J. Nanomedicine, 2017, 12, 1227-1249.
[http://dx.doi.org/10.2147/IJN.S121956] [PMID: 28243086]
[13]
Heidarpour, F.; Ghani, W.A.; Ahmadun, F.R.; Sobri, S.; Zargar, M.; Mozafari, M.R. Nanosilver coated polypropylene water filter: I. Manufacture by electron beam gun using a modified Balzers 760 machine. Dig. J. Nanomater. Biostruct., 2010, 5(3), 787-796.
[14]
Heidarpour, F.; Ghani, W.W.A.K.; Bin Ahmadun, F.R.; Mozafari, M.R. Nano silver-coated polypropylene water filter: II. Evaluation of antimicrobial efficiency. Dig. J. Nanomater. Biostruct., 2010, 5(3), 797-804.
[15]
Heidarpour, F.; Ghani, W.W.A.K.; Fakhru’l-Razi, A.; Sobri, S.; Heydarpour, V.; Zargar, M.; Mozafari, M.R. Complete removal of pathogenic bacteria from drinking water using nano silver-coated cylindrical polypropylene filters. Clean Technol. Environ. Policy, 2011, 13(3), 499-507.
[http://dx.doi.org/10.1007/s10098-010-0332-2]
[16]
Fernando, S.S.; Gunasekara, T.D.; Holton, J. Antimicrobial nanoparticles: applications and mechanisms of action. SLJID, 2018, 8(1), 1-11.
[http://dx.doi.org/10.4038/sljid.v8i1.8167]
[17]
Mahmoudi, E.; Ng, L.Y.; Ang, W.L.; Chung, Y.T.; Rohani, R.; Mohammad, A.W. Enhancing morphology and separation performance of polyamide 6,6 membranes by minimal incorporation of silver decorated graphene oxide nanoparticles. Sci. Rep., 2019, 9(1), 1216.
[http://dx.doi.org/10.1038/s41598-018-38060-x] [PMID: 30718690]
[18]
Bernardo, M.P.; Moreira, F.K.; Mattoso, L.H.; Raja, S. Innovations in Antimicrobial Engineered Nanomaterials. Advanced Nanostructured Materials for Environmental Remediation; Naushad, M.; Rajendran, S; Gracia, F., Ed.; Springer: Cham, 2019, pp. 253-277.
[http://dx.doi.org/10.1007/978-3-030-04477-0_10]
[19]
Seil, J.T.; Webster, T.J. Antimicrobial applications of nanotechnology: methods and literature. Int. J. Nanomedicine, 2012, 7, 2767-2781.
[PMID: 22745541]
[20]
Sirelkhatim, A.; Mahmud, S.; Seeni, A.; Kaus, N.H.M.; Ann, L.C.; Bakhori, S.K.M.; Hasan, H.; Mohamad, D. Review on zinc oxide nanoparticles: Antibacterial activity and toxicity mechanism. Nano-Micro Lett., 2015, 7(3), 219-242.
[http://dx.doi.org/10.1007/s40820-015-0040-x] [PMID: 30464967]
[21]
Nissen, S.; Furkert, F.H. Antimicrobial efficacy of a silver layer on hydrogel lenses. Ophthalmologe, 2000, 97(9), 640-643.
[http://dx.doi.org/10.1007/s003470070054] [PMID: 11147340]
[22]
Feng, Q.L.; Wu, J.; Chen, G.Q.; Cui, F.Z.; Kim, T.N.; Kim, J.O. A mechanistic study of the antibacterial effect of silver ions on Escherichia coli and Staphylococcus aureus. J. Biomed. Mater. Res., 2000, 52(4), 662-668.
[http://dx.doi.org/10.1002/1097-4636(20001215)52:4<662:AID-JBM10>3.0.CO;2-3] [PMID: 11033548]
[23]
Peiris, M.K.; Gunasekara, C.P.; Jayaweera, P.M.; Arachchi, N.D.; Fernando, N. Biosynthesized silver nanoparticles: are they effective antimicrobials? Mem. Inst. Oswaldo Cruz, 2017, 112(8), 537-543.
[http://dx.doi.org/10.1590/0074-02760170023] [PMID: 28767978]
[24]
Marambio-Jones, C.; Hoek, E.M. A review of the antibacterial effects of silver nanomaterials and potential implications for human health and the environment. J. Nanopart. Res., 2010, 12(5), 1531-1551.
[http://dx.doi.org/10.1007/s11051-010-9900-y]
[25]
Chen, X.; Schluesener, H.J. Nanosilver: a nanoproduct in medical application. Toxicol. Lett., 2008, 176(1), 1-12.
[http://dx.doi.org/10.1016/j.toxlet.2007.10.004] [PMID: 18022772]
[26]
Jain, P.; Pradeep, T. Potential of silver nanoparticle-coated polyurethane foam as an antibacterial water filter. Biotechnol. Bioeng., 2005, 90(1), 59-63.
[http://dx.doi.org/10.1002/bit.20368] [PMID: 15723325]
[27]
Chen, C.Y.; Chiang, C.L. Preparation of cotton fibers with antibacterial silver nanoparticles. Mater. Lett., 2008, 62(21-22), 3607-3609.
[http://dx.doi.org/10.1016/j.matlet.2008.04.008]
[28]
Li, Q.; Mahendra, S.; Lyon, D.Y.; Brunet, L.; Liga, M.V.; Li, D.; Alvarez, P.J.J. Antimicrobial nanomaterials for water disinfection and microbial control: potential applications and implications. Water Res., 2008, 42(18), 4591-4602.
[http://dx.doi.org/10.1016/j.watres.2008.08.015] [PMID: 18804836]
[29]
El-Sayed, M.A. Some interesting properties of metals confined in time and nanometer space of different shapes. Acc. Chem. Res., 2001, 34(4), 257-264.
[http://dx.doi.org/10.1021/ar960016n] [PMID: 11308299]
[30]
Amendola, V.; Meneghetti, M. Laser ablation synthesis in solution and size manipulation of noble metal nanoparticles. Phys. Chem. Chem. Phys., 2009, 11(20), 3805-3821.
[http://dx.doi.org/10.1039/b900654k] [PMID: 19440607]
[31]
Iravani, S.; Korbekandi, H.; Mirmohammadi, S.V.; Zolfaghari, B. Synthesis of silver nanoparticles: chemical, physical and biological methods. Res. Pharm. Sci., 2014, 9(6), 385-406.
[PMID: 26339255]
[32]
Zhang, X.F.; Liu, Z.G.; Shen, W.; Gurunathan, S. Silver nanoparticles: Synthesis, characterization, properties, applications, and therapeutic approaches. Int. J. Mol. Sci., 2016, 17(9), 1534.
[http://dx.doi.org/10.3390/ijms17091534] [PMID: 27649147]
[33]
Rais, A.; Anam, M. Green synthesis (using plant extracts) of Ag and Au nanoparticles. Glob. J. Nanomed., 2017, 2(3)555589
[34]
Klaus-Joerger, T.; Joerger, R.; Olsson, E.; Granqvist, C. Bacteria as workers in the living factory: metal-accumulating bacteria and their potential for materials science. Trends Biotechnol., 2001, 19(1), 15-20.
[http://dx.doi.org/10.1016/S0167-7799(00)01514-6] [PMID: 11146098]
[35]
Arokiyaraj, S.; Vincent, S.; Saravanan, M.; Lee, Y.; Oh, Y.K.; Kim, K.H. Green synthesis of silver nanoparticles using Rheum palmatum root extract and their antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. Artif. Cells Nanomed. Biotechnol., 2017, 45(2), 372-379.
[http://dx.doi.org/10.3109/21691401.2016.1160403] [PMID: 27023851]
[36]
Patra, S.; Mukherjee, S.; Barui, A.K.; Ganguly, A.; Sreedhar, B.; Patra, C.R. Green synthesis, characterization of gold and silver nanoparticles and their potential application for cancer therapeutics. Mater. Sci. Eng. C, 2015, 53, 298-309.
[http://dx.doi.org/10.1016/j.msec.2015.04.048] [PMID: 26042718]
[37]
Garmasheva, I.; Kovalenko, N.; Voychuk, S.; Ostapchuk, A.; Livins’ka, O.; Oleschenko, L. Lactobacillus species mediated synthesis of silver nanoparticles and their antibacterial activity against opportunistic pathogens in vitro. Bioimpacts, 2016, 6(4), 219-223.
[http://dx.doi.org/10.15171/bi.2016.29] [PMID: 28265538]
[38]
Minaeian, S.; Shahverdi, A.R.; Nohi, A.S. Extracellular biosynthesis of silver nanoparticles by some bacteria. JSIAU, 2008, 17(66), 1-4.
[39]
Peiris, M.M.K.; Fernando, S.S.N.; Jayaweera, P.M.; Arachchi, N.D.H.; Guansekara, T.D.C.P. Comparison of antimicrobial properties of silver nanoparticles synthesized from selected bacteria. Indian J. Microbiol., 2018, 58(3), 301-311.
[http://dx.doi.org/10.1007/s12088-018-0723-3] [PMID: 30013274]
[40]
Das, C.A.; Kumar, V.G.; Dhas, T.S.; Karthick, V.; Govindaraju, K.; Joselin, J.M.; Baalamurugan, J. Antibacterial activity of silver nanoparticles (biosynthesis): A short review on recent advances. Biocatal. Agric. Biotechnol., 2020, 27101593
[41]
Kalpana, D.; Lee, Y.S. Synthesis and characterization of bactericidal silver nanoparticles using cultural filtrate of simulated microgravity grown Klebsiella pneumoniae. Enzyme Microb. Technol., 2013, 52(3), 151-156.
[http://dx.doi.org/10.1016/j.enzmictec.2012.12.006] [PMID: 23410925]
[42]
Loo, Y.Y.; Chieng, B.W.; Nishibuchi, M.; Radu, S. Synthesis of silver nanoparticles by using tea leaf extract from Camellia sinensis. Int. J. Nanomedicine, 2012, 7, 4263-4267.
[PMID: 22904632]
[43]
Khorrami, S.; Zarrabi, A.; Khaleghi, M.; Danaei, M.; Mozafari, M.R. Selective cytotoxicity of green synthesized silver nanoparticles against the MCF-7 tumor cell line and their enhanced antioxidant and antimicrobial properties. Int. J. Nanomedicine, 2018, 13, 8013-8024.
[http://dx.doi.org/10.2147/IJN.S189295] [PMID: 30568442]
[44]
Mozafari, M.R.; Mortazavi, S.M. Nanoliposomes: From Fundamentals to Recent Developments; Trafford Publishing Ltd: Oxford, UK, 2005.
[45]
Khorasani, S.; Danaei, M.; Mozafari, M.R. Nanoliposome technology for the food and nutraceutical industries. Trends Food Sci. Technol., 2018, 79, 106-115.
[http://dx.doi.org/10.1016/j.tifs.2018.07.009]
[46]
Mozafari, M.R.; Flanagan, J.; Matia-Merino, L.; Awati, A.; Omri, A.; Suntres, Z.E.; Singh, H. Recent trends in the lipid-based nanoencapsulation of antioxidants and their role in foods. J. Sci. Food Agric., 2006, 86(13), 2038-2045.
[http://dx.doi.org/10.1002/jsfa.2576]
[47]
Mugabe, C.; Halwani, M.; Azghani, A.O.; Lafrenie, R.M.; Omri, A. Mechanism of enhanced activity of liposome-entrapped aminoglycosides against resistant strains of Pseudomonas aeruginosa. Antimicrob. Agents Chemother., 2006, 50(6), 2016-2022.
[http://dx.doi.org/10.1128/AAC.01547-05] [PMID: 16723560]
[48]
Ferreyra Maillard, A.P.V.; Dalmasso, P.R.; López de Mishima, B.A.; Hollmann, A. Interaction of green silver nanoparticles with model membranes: possible role in the antibacterial activity. Colloids Surf. B Biointerfaces, 2018, 171, 320-326.
[http://dx.doi.org/10.1016/j.colsurfb.2018.07.044] [PMID: 30055472]
[49]
Colas, J.C.; Shi, W.; Rao, V.S.; Omri, A.; Mozafari, M.R.; Singh, H. Microscopical investigations of nisin-loaded nanoliposomes prepared by Mozafari method and their bacterial targeting. Micron, 2007, 38(8), 841-847.
[http://dx.doi.org/10.1016/j.micron.2007.06.013] [PMID: 17689087]
[50]
Hong, M.S.; Lim, S.J.; Oh, Y.K.; Kim, C.K. pH-sensitive, serum-stable and long-circulating liposomes as a new drug delivery system. J. Pharm. Pharmacol., 2002, 54(1), 51-58.
[http://dx.doi.org/10.1211/0022357021771913] [PMID: 11829129]
[51]
Chu, C.J.; Dijkstra, J.; Lai, M.Z.; Hong, K.; Szoka, F.C. Efficiency of cytoplasmic delivery by pH-sensitive liposomes to cells in culture. Pharm. Res., 1990, 7(8), 824-834.
[http://dx.doi.org/10.1023/A:1015908831507] [PMID: 2172955]
[52]
Gerasimov, O.V.; Boomer, J.A.; Qualls, M.M.; Thompson, D.H. Cytosolic drug delivery using pH- and light-sensitive liposomes. Adv. Drug Deliv. Rev., 1999, 38(3), 317-338.
[http://dx.doi.org/10.1016/S0169-409X(99)00035-6] [PMID: 10837763]
[53]
Roux, E.; Passirani, C.; Scheffold, S.; Benoit, J.P.; Leroux, J.C. Serum-stable and long-circulating, PEGylated, pH-sensitive liposomes. J. Control. Release, 2004, 94(2-3), 447-451.
[http://dx.doi.org/10.1016/j.jconrel.2003.10.024] [PMID: 14976960]
[54]
Lai, M.Z.; Düzgüneş, N.; Szoka, F.C. Effects of replacement of the hydroxyl group of cholesterol and tocopherol on the thermotropic behavior of phospholipid membranes. Biochemistry, 1985, 24(7), 1646-1653.
[http://dx.doi.org/10.1021/bi00328a012] [PMID: 3839132]
[55]
Webb, M.S.; Wheeler, J.J.; Bally, M.B.; Mayer, L.D. The cationic lipid stearylamine reduces the permeability of the cationic drugs verapamil and prochlorperazine to lipid bilayers: implications for drug delivery. Biochim. Biophys. Acta, 1995, 1238(2), 147-155.
[http://dx.doi.org/10.1016/0005-2736(95)00121-I] [PMID: 7548129]
[56]
Johnsson, M.; Edwards, K. Phase behavior and aggregate structure in mixtures of dioleoylphosphatidylethanolamine and poly(ethylene glycol)-lipids. Biophys. J., 2001, 80(1), 313-323.
[http://dx.doi.org/10.1016/S0006-3495(01)76016-X] [PMID: 11159404]
[57]
Lutwyche, P.; Cordeiro, C.; Wiseman, D.J.; St-Louis, M.; Uh, M.; Hope, M.J.; Webb, M.S.; Finlay, B.B. Intracellular delivery and antibacterial activity of gentamicin encapsulated in pH-sensitive liposomes. Antimicrob. Agents Chemother., 1998, 42(10), 2511-2520.
[http://dx.doi.org/10.1128/AAC.42.10.2511] [PMID: 9756749]
[58]
Cordeiro, C.; Wiseman, D.J.; Lutwyche, P.; Uh, M.; Evans, J.C.; Finlay, B.B.; Webb, M.S. Antibacterial efficacy of gentamicin encapsulated in pH-sensitive liposomes against an in vivo Salmonella enterica serovar typhimurium intracellular infection model. Antimicrob. Agents Chemother., 2000, 44(3), 533-539.
[http://dx.doi.org/10.1128/AAC.44.3.533-539.2000] [PMID: 10681314]
[59]
Momekova, D.; Rangelov, S.; Lambov, N. Long-circulating, pH-sensitive liposomes. Methods Mol. Biol., 2010, 605, 527-544.
[http://dx.doi.org/10.1007/978-1-60327-360-2_35] [PMID: 20072904]
[60]
Yan, X.; Scherphof, G.L.; Kamps, J.A. Liposome opsonization. J. Liposome Res., 2005, 15(1-2), 109-139.
[http://dx.doi.org/10.1081/LPR-64971] [PMID: 16194930]
[61]
Metselaar, J.M. Liposomal targeting of glucocorticoids: a novel treatment approach for inflammatory disorders., PhD Thesis, Utrecht University, Utrecht, Netherlands. 2003.
[62]
Deodhar, S.; Dash, A.K. Long circulating liposomes: challenges and opportunities. Ther. Deliv., 2018, 9(12), 857-872.
[http://dx.doi.org/10.4155/tde-2018-0035] [PMID: 30444455]
[63]
Milani, D.; Athiyah, U.; Hariyadi, D.M.; Pathak, Y.V. Surface Modification of Nanoparticles for Targeted Drug Delivery; Pathak, Y., Ed.; Springer: Cham, 2019, pp. 207-220.
[http://dx.doi.org/10.1007/978-3-030-06115-9_11]
[64]
Sesarman, A.; Tefas, L.; Sylvester, B.; Licarete, E.; Rauca, V.; Luput, L.; Patras, L.; Banciu, M.; Porfire, A. Anti-angiogenic and anti-inflammatory effects of long-circulating liposomes co-encapsulating curcumin and doxorubicin on C26 murine colon cancer cells. Pharmacol. Rep., 2018, 70(2), 331-339.
[http://dx.doi.org/10.1016/j.pharep.2017.10.004] [PMID: 29477042]
[65]
Yang, S. Preparation, in vitro characterization and pharmacokinetic study of coenzyme Q10 long-circulating liposomes. Drug Res. (Stuttg.), 2018, 68(5), 270-279.
[http://dx.doi.org/10.1055/s-0043-121876] [PMID: 29190857]
[66]
Pi, J.; Liu, Z.; Shu, L.; Li, L.; Wang, Y.; Li, N.; Li, J. Tissue distribution study of salvianolic acid B long-circulating liposomes in mice by UPLC-MS/MS determination. Pak. J. Pharm. Sci., 2015, 28(1), 213-220.
[PMID: 25553697]
[67]
Deodhar, S. Development and in-vitro evaluation of long circulating liposomes for targeted delivery of gemcitabine and irinotecan in pancreatic ductal adenocarcinoma Doctoral dissertation, Creighton University,, 2018.
[68]
Silva, J.O.; Fernandes, R.S.; Lopes, S.C.; Cardoso, V.N.; Leite, E.A.; Cassali, G.D.; Marzola, M.C.; Rubello, D.; Oliveira, M.C.; de Barros, A.L.B. pH-sensitive, long-circulating liposomes as an alternative tool to deliver doxorubicin into tumors: a feasibility animal study. Mol. Imaging Biol., 2016, 18(6), 898-904.
[http://dx.doi.org/10.1007/s11307-016-0964-7] [PMID: 27172938]
[69]
Tefas, L.R.; Sylvester, B.; Tomuta, I.; Sesarman, A.; Licarete, E.; Banciu, M.; Porfire, A. Development of antiproliferative long-circulating liposomes co-encapsulating doxorubicin and curcumin, through the use of a quality-by-design approach. Drug Des. Devel. Ther., 2017, 11, 1605-1621.
[http://dx.doi.org/10.2147/DDDT.S129008] [PMID: 28579758]
[70]
Khan, A.U.; Khan, M.; Cho, M.H.; Khan, M.M. Selected nanotechnologies and nanostructures for drug delivery, nanomedicine and cure. Bioprocess Biosyst. Eng., 2020, 19, 1-9.
[http://dx.doi.org/10.1007/s00449-020-02330-8] [PMID: 32193755]
[71]
Bakker-Woudenberg, I.A.; Schiffelers, R.M.; Storm, G.; Becker, M.J.; Guo, L. Long-circulating sterically stabilized liposomes in the treatment of infections. Methods Enzymol., 2005, 391, 228-260.
[http://dx.doi.org/10.1016/S0076-6879(05)91014-8] [PMID: 15721385]
[72]
Momekova, D.; Momekov, G.; Ivanova, J.; Pantcheva, I.; Drakalska, E.; Stoyanov, N.; Guenova, M.; Michova, A.; Balashev, K.; Arpadjan, S.; Mitewa, M.; Rangelov, S.; Lambov, N. Sterically stabilized liposomes as a platform for salinomycin metal coordination compounds: physicochemical characterization and in vitro evaluation. J. Drug Deliv. Sci. Technol., 2013, 23(3), 215-223.
[http://dx.doi.org/10.1016/S1773-2247(13)50033-5]
[73]
Podaru, G. Exploring controlled drug release from magneto liposomes (Doctoral dissertation, Kansas State University),, 2017.
[74]
Zangabad, P.S.; Mirkiani, S.; Shahsavari, S.; Masoudi, B.; Masroor, M.; Hamed, H.; Jafari, Z.; Taghipour, Y.D.; Hashemi, H.; Karimi, M.; Hamblin, M.R. Stimulus-responsive liposomes as smart nanoplatforms for drug delivery applications. Nanotechnol. Rev., 2018, 7(1), 95-122.
[http://dx.doi.org/10.1515/ntrev-2017-0154] [PMID: 29404233]
[75]
Nobuto, H.; Sugita, T.; Kubo, T.; Shimose, S.; Yasunaga, Y.; Murakami, T.; Ochi, M. Evaluation of systemic chemotherapy with magnetic liposomal doxorubicin and a dipole external electromagnet. Int. J. Cancer, 2004, 109(4), 627-635.
[http://dx.doi.org/10.1002/ijc.20035] [PMID: 14991586]
[76]
Guo, Y.; Zhang, Y.; Ma, J.; Li, Q.; Li, Y.; Zhou, X.; Zhao, D.; Song, H.; Chen, Q.; Zhu, X. Light/magnetic hyperthermia triggered drug released from multi-functional thermo-sensitive magnetoliposomes for precise cancer synergetic theranostics. J. Control. Release, 2018, 272, 145-158.
[http://dx.doi.org/10.1016/j.jconrel.2017.04.028] [PMID: 28442407]
[77]
Chechetka, S.A.; Yuba, E.; Kono, K.; Yudasaka, M.; Bianco, A.; Miyako, E. Magnetically and near-infrared light-powered supramolecular nanotransporters for the remote control of enzymatic reactions. Angew. Chem. Int. Ed. Engl., 2016, 55(22), 6476-6481.
[http://dx.doi.org/10.1002/anie.201602453] [PMID: 27079747]
[78]
Leighton, T.G. What is ultrasound? Prog. Biophys. Mol. Biol., 2007, 93(1-3), 3-83.
[http://dx.doi.org/10.1016/j.pbiomolbio.2006.07.026] [PMID: 17045633]
[79]
Schroeder, A.; Kost, J.; Barenholz, Y. Ultrasound, liposomes, and drug delivery: principles for using ultrasound to control the release of drugs from liposomes. Chem. Phys. Lipids, 2009, 162(1-2), 1-16.
[http://dx.doi.org/10.1016/j.chemphyslip.2009.08.003] [PMID: 19703435]
[80]
Javadi, M.; Pitt, W.G.; Belnap, D.M.; Tsosie, N.H.; Hartley, J.M. Encapsulating nanoemulsions inside eLiposomes for ultrasonic drug delivery. Langmuir, 2012, 28(41), 14720-14729.
[http://dx.doi.org/10.1021/la303464v] [PMID: 22989347]
[81]
Mason, T.J. Chemistry with Ultrasound; London; New York: Published for the Society of Chemical Industry by Elsevier Applied Science: New York, NY, USA , 1990.
[82]
Rychak, J.J.; Klibanov, A.L. Nucleic acid delivery with microbubbles and ultrasound. Adv. Drug Deliv. Rev., 2014, 72, 82-93.
[http://dx.doi.org/10.1016/j.addr.2014.01.009] [PMID: 24486388]
[83]
Silva, C.O.; Pinho, J.O.; Lopes, J.M.; Almeida, A.J.; Gaspar, M.M.; Reis, C. Current trends in cancer nanotheranostics: Metallic, polymeric, and lipid-based systems. Pharmaceutics, 2019, 11(1), 22.
[http://dx.doi.org/10.3390/pharmaceutics11010022] [PMID: 30625999]
[84]
Sirsi, S.R.; Borden, M.A. State-of-the-art materials for ultrasound-triggered drug delivery. Adv. Drug Deliv. Rev., 2014, 72, 3-14.
[http://dx.doi.org/10.1016/j.addr.2013.12.010] [PMID: 24389162]
[85]
Husseini, G.A.; Pitt, W.G. Micelles and nanoparticles for ultrasonic drug and gene delivery. Adv. Drug Deliv. Rev., 2008, 60(10), 1137-1152.
[http://dx.doi.org/10.1016/j.addr.2008.03.008] [PMID: 18486269]
[86]
Pitt, W.G.; Husseini, G.A.; Staples, B.J. Ultrasonic drug delivery--a general review. Expert Opin. Drug Deliv., 2004, 1(1), 37-56.
[http://dx.doi.org/10.1517/17425247.1.1.37] [PMID: 16296719]
[87]
Husseini, G.A.; Myrup, G.D.; Pitt, W.G.; Christensen, D.A.; Rapoport, N.Y. Factors affecting acoustically triggered release of drugs from polymeric micelles. J. Control. Release, 2000, 69(1), 43-52.
[http://dx.doi.org/10.1016/S0168-3659(00)00278-9] [PMID: 11018545]
[88]
Ahmed, S.E.; Martins, A.M.; Husseini, G.A. The use of ultrasound to release chemotherapeutic drugs from micelles and liposomes. J. Drug Target., 2015, 23(1), 16-42.
[http://dx.doi.org/10.3109/1061186X.2014.954119] [PMID: 25203857]
[89]
Lin, H.Y.; Thomas, J.L. Factors affecting responsivity of unilamellar liposomes to 20 kHz ultrasound. Langmuir, 2004, 20(15), 6100-6106.
[http://dx.doi.org/10.1021/la049866z] [PMID: 15248690]
[90]
Schroeder, A.; Avnir, Y.; Weisman, S.; Najajreh, Y.; Gabizon, A.; Talmon, Y.; Kost, J.; Barenholz, Y. Controlling liposomal drug release with low frequency ultrasound: mechanism and feasibility. Langmuir, 2007, 23(7), 4019-4025.
[http://dx.doi.org/10.1021/la0631668] [PMID: 17319706]
[91]
Rediske, A.M.; Roeder, B.L.; Brown, M.K.; Nelson, J.L.; Robison, R.L.; Draper, D.O.; Schaalje, G.B.; Robison, R.A.; Pitt, W.G. Ultrasonic enhancement of antibiotic action on Escherichia coli biofilms: an in vivo model. Antimicrob. Agents Chemother., 1999, 43(5), 1211-1214.
[http://dx.doi.org/10.1128/AAC.43.5.1211] [PMID: 10223938]
[92]
Rediske, A.M.; Roeder, B.L.; Nelson, J.L.; Robison, R.L.; Schaalje, G.B.; Robison, R.A.; Pitt, W.G. Pulsed ultrasound enhances the killing of Escherichia coli biofilms by aminoglycoside antibiotics in vivo. Antimicrob. Agents Chemother., 2000, 44(3), 771-772.
[http://dx.doi.org/10.1128/AAC.44.3.771-772.2000] [PMID: 10681355]
[93]
Carmen, J.C.; Roeder, B.L.; Nelson, J.L.; Beckstead, B.L.; Runyan, C.M.; Robison, R.A.; Pitt, W.G. The treatment of implanted biofilms with low-frequency ultrasound and gentamicin. Am. J. Infect. Control, 2004, 33, 78-82.
[http://dx.doi.org/10.1016/j.ajic.2004.08.002] [PMID: 15761406]
[94]
Carmen, J.C.; Roeder, B.L.; Nelson, J.L.; Beckstead, B.L.; Runyan, C.M.; Schaalje, G.B.; Robison, R.A.; Pitt, W.G. Ultrasonically enhanced vancomycin activity against Staphylococcus epidermidis biofilms in vivo. J. Biomater. Appl., 2004, 18(4), 237-245.
[http://dx.doi.org/10.1177/0885328204040540] [PMID: 15070512]
[95]
Qian, Z.; Stoodley, P.; Pitt, W.G. Effect of low-intensity ultrasound upon biofilm structure from confocal scanning laser microscopy observation. Biomaterials, 1996, 17(20), 1975-1980.
[http://dx.doi.org/10.1016/0142-9612(96)00022-1] [PMID: 8894091]
[96]
Qian, Z.; Sagers, R.D.; Pitt, W.G. The role of insonation intensity in acoustic-enhanced antibiotic treatment of bacterial biofilms. Colloids Surf. B Biointerfaces, 1997, 9(5), 239-245.
[http://dx.doi.org/10.1016/S0927-7765(97)00029-5]
[97]
Qian, Z.; Sagers, R.D.; Pitt, W.G. Investigation of the mechanism of the bioacoustic effect. J. Biomed. Mater. Res., 1999, 44(2), 198-205.
[http://dx.doi.org/10.1002/(SICI)1097-4636(199902)44:2<198:AID-JBM10>3.0.CO;2-P] [PMID: 10397921]
[98]
Rediske, A.M.; Hymas, W.C.; Wilkinson, R.; Pitt, W.G. Ultrasonic enhancement of antibiotic action on several species of bacteria. J. Gen. Appl. Microbiol., 1998, 44(4), 283-288.
[http://dx.doi.org/10.2323/jgam.44.283] [PMID: 12501423]
[99]
Rediske, A.M.; Rapoport, N.; Pitt, W.G. Reducing bacterial resistance to antibiotics with ultrasound. Lett. Appl. Microbiol., 1999, 28(1), 81-84.
[http://dx.doi.org/10.1046/j.1365-2672.1999.00461.x] [PMID: 10030038]
[100]
Qian, Z.; Sagers, R.D.; Pitt, W.G. The effect of ultrasonic frequency upon enhanced killing of P. aeruginosa biofilms. Ann. Biomed. Eng., 1997, 25(1), 69-76.
[http://dx.doi.org/10.1007/BF02738539] [PMID: 9124740]
[101]
Johnson, L.L.; Peterson, R.V.; Pitt, W.G. Treatment of bacterial biofilms on polymeric biomaterials using antibiotics and ultrasound. J. Biomater. Sci. Polym. Ed., 1998, 9(11), 1177-1185.
[http://dx.doi.org/10.1163/156856298X00712] [PMID: 9860179]
[102]
Yang, M.; Xie, S.; Adhikari, V.P.; Dong, Y.; Du, Y.; Li, D. The synergistic fungicidal effect of low-frequency and low-intensity ultrasound with amphotericin B-loaded nanoparticles on C. albicans in vitro. Int. J. Pharm., 2018, 542(1-2), 232-241.
[http://dx.doi.org/10.1016/j.ijpharm.2018.03.033] [PMID: 29559330]
[103]
Wust, P.; Hildebrandt, B.; Sreenivasa, G.; Rau, B.; Gellermann, J.; Riess, H.; Felix, R.; Schlag, P.M. Hyperthermia in combined treatment of cancer. Lancet Oncol., 2002, 3(8), 487-497.
[http://dx.doi.org/10.1016/S1470-2045(02)00818-5] [PMID: 12147435]
[104]
Dicheva, B.M.; Koning, G.A. Targeted thermosensitive liposomes: an attractive novel approach for increased drug delivery to solid tumors. Expert Opin. Drug Deliv., 2014, 11(1), 83-100.
[http://dx.doi.org/10.1517/17425247.2014.866650] [PMID: 24320104]
[105]
Yatvin, M.B.; Weinstein, J.N.; Dennis, W.H.; Blumenthal, R. Design of liposomes for enhanced local release of drugs by hyperthermia. Science, 1978, 202(4374), 1290-1293.
[http://dx.doi.org/10.1126/science.364652] [PMID: 364652]
[106]
Landon, C.D.; Park, J.Y.; Needham, D.; Dewhirst, M.W. Nanoscale drug delivery and hyperthermia: the materials design and preclinical and clinical testing of low temperature-sensitive liposomes used in combination with mild hyperthermia in the treatment of local cancer. Open Nanomed. J., 2011, 3, 38-64.
[http://dx.doi.org/10.2174/1875933501103010038] [PMID: 23807899]
[107]
Needham, D.; Anyarambhatla, G.; Kong, G.; Dewhirst, M.W. A new temperature-sensitive liposome for use with mild hyperthermia: characterization and testing in a human tumor xenograft model. Cancer Res., 2000, 60(5), 1197-1201.
[PMID: 10728674]
[108]
Needham, D. Temperature-Sensitive Liposomal Formulation U.S. Patent no. 6200598B1 2001.
[109]
Hayashi, H.; Kono, K.; Takagishi, T. Temperature-dependent associating property of liposomes modified with a thermosensitive polymer. Bioconjug. Chem., 1998, 9(3), 382-389.
[http://dx.doi.org/10.1021/bc9701454] [PMID: 9576813]
[110]
Kono, K.; Yoshino, K.; Takagishi, T. Effect of poly(ethylene glycol) grafts on temperature-sensitivity of thermosensitive polymer-modified liposomes. J. Control. Release, 2002, 80(1-3), 321-332.
[http://dx.doi.org/10.1016/S0168-3659(02)00018-4] [PMID: 11943408]
[111]
Kneidl, B.; Peller, M.; Winter, G.; Lindner, L.H.; Hossann, M. Thermosensitive liposomal drug delivery systems: state of the art review. Int. J. Nanomedicine, 2014, 9, 4387-4398.
[PMID: 25258529]
[112]
Gaber, M.H.; Hong, K.; Huang, S.K.; Papahadjopoulos, D. Thermosensitive sterically stabilized liposomes: formulation and in vitro studies on mechanism of doxorubicin release by bovine serum and human plasma. Pharm. Res., 1995, 12(10), 1407-1416.
[http://dx.doi.org/10.1023/A:1016206631006] [PMID: 8584472]
[113]
Gaber, M.H.; Wu, N.Z.; Hong, K.; Huang, S.K.; Dewhirst, M.W.; Papahadjopoulos, D. Thermosensitive liposomes: extravasation and release of contents in tumor microvascular networks. Int. J. Radiat. Oncol. Biol. Phys., 1996, 36(5), 1177-1187.
[http://dx.doi.org/10.1016/S0360-3016(96)00389-6] [PMID: 8985041]
[114]
Gaber, M.H. Modulation of doxorubicin resistance in multidrug-resistance cells by targeted liposomes combined with hyperthermia. J. Biochem. Mol. Biol. Biophys., 2002, 6(5), 309-314.
[http://dx.doi.org/10.1080/10258140290033066] [PMID: 12385965]
[115]
Zhang, W.; Yu, W.; Ding, X.; Yin, C.; Yan, J.; Yang, E.; Guo, F.; Sun, D.; Wang, W. Self-assembled thermal gold nanorod-loaded thermosensitive liposome-encapsulated ganoderic acid for antibacterial and cancer photochemotherapy. Artif. Cells Nanomed. Biotechnol., 2019, 47(1), 406-419.
[http://dx.doi.org/10.1080/21691401.2018.1559177] [PMID: 30724609]
[116]
Choi, K.Y.; Liu, G.; Lee, S.; Chen, X. Theranostic nanoplatforms for simultaneous cancer imaging and therapy: current approaches and future perspectives. Nanoscale, 2012, 4(2), 330-342.
[http://dx.doi.org/10.1039/C1NR11277E] [PMID: 22134683]
[117]
Muthu, M.S.; Feng, S.S. Theranostic liposomes for cancer diagnosis and treatment: current development and pre-clinical success. Expert Opin. Drug Deliv., 2013, 10(2), 151-155.
[http://dx.doi.org/10.1517/17425247.2013.729576] [PMID: 23061654]
[118]
Seleci, M.; Ag Seleci, D.; Scheper, T.; Stahl, F. Theranostic liposome-nanoparticle hybrids for drug delivery and bioimaging. Int. J. Mol. Sci., 2017, 18(7), 1415.
[http://dx.doi.org/10.3390/ijms18071415] [PMID: 28671589]
[119]
Al-Jamal, W.T.; Kostarelos, K. Liposomes: from a clinically established drug delivery system to a nanoparticle platform for theranostic nanomedicine. Acc. Chem. Res., 2011, 44(10), 1094-1104.
[http://dx.doi.org/10.1021/ar200105p] [PMID: 21812415]
[120]
Yang, C.; Ding, N.; Xu, Y.; Qu, X.; Zhang, J.; Zhao, C.; Hong, L.; Lu, Y.; Xiang, G. Folate receptor-targeted quantum dot liposomes as fluorescence probes. J. Drug Target., 2009, 17(7), 502-511.
[http://dx.doi.org/10.1080/10611860903013248] [PMID: 19489689]
[121]
Wen, C.J.; Zhang, L.W.; Al-Suwayeh, S.A.; Yen, T.C.; Fang, J.Y. Theranostic liposomes loaded with quantum dots and apomorphine for brain targeting and bioimaging. Int. J. Nanomedicine, 2012, 7, 1599-1611.
[PMID: 22619515]
[122]
Grange, C.; Geninatti-Crich, S.; Esposito, G.; Alberti, D.; Tei, L.; Bussolati, B.; Aime, S.; Camussi, G. Combined delivery and magnetic resonance imaging of neural cell adhesion molecule-targeted doxorubicin-containing liposomes in experimentally induced Kaposi’s sarcoma. Cancer Res., 2010, 70(6), 2180-2190.
[http://dx.doi.org/10.1158/0008-5472.CAN-09-2821] [PMID: 20215497]
[123]
Feng, L.; Cheng, L.; Dong, Z.; Tao, D.; Barnhart, T.E.; Cai, W.; Chen, M.; Liu, Z. Theranostic liposomes with hypoxia-activated prodrug to effectively destruct hypoxic tumors post-photodynamic therapy. ACS Nano, 2017, 11(1), 927-937.
[http://dx.doi.org/10.1021/acsnano.6b07525] [PMID: 28027442]
[124]
Lasic, D.D. Mechanisms of liposome formation. J. Liposome Res., 1995, 5(3), 431-441.
[http://dx.doi.org/10.3109/08982109509010233]
[125]
Mohammadabadi, M.R.; Mozafari, M.R. Enhanced efficacy and bioavailability of thymoquinone using nanoliposomal dosage form. J. Drug Deliv. Sci. Technol., 2018, 47, 445-453.
[http://dx.doi.org/10.1016/j.jddst.2018.08.019]
[126]
Lasic, D.D. Novel applications of liposomes. Trends Biotechnol., 1998, 16(7), 307-321.
[http://dx.doi.org/10.1016/S0167-7799(98)01220-7] [PMID: 9675915]
[127]
Schott, H.; Schwendener, R. Incorporation of lipophilic antitumor and antiviral drugs into the lipid bilayer of small unilamellar liposomes.Liposome Technology; Gregory, G., Ed.; CRC Press, 2016, pp. 75-86.
[128]
Amoabediny, G.; Ochi, M.M.; Rezayat, S.M.; Akbarzadeh, A.; Ebrahimi, B. Targeted nano-liposome co-entrapping anti-cancer drugs US9855216B2, 2018.
[129]
Akbarzadeh, A.; Rezaei-Sadabady, R.; Davaran, S.; Joo, S.W.; Zarghami, N.; Hanifehpour, Y.; Samiei, M.; Kouhi, M.; Nejati-Koshki, K. Liposome: classification, preparation, and applications. Nanoscale Res. Lett., 2013, 8(1), 102.
[http://dx.doi.org/10.1186/1556-276X-8-102] [PMID: 23432972]
[130]
Zarrabi, A.; Alipoor Amro Abadi, M.; Khorasani, S.; Mohammadabadi, M.R.; Jamshidi, A.; Torkaman, S.; Taghavi, E.; Mozafari, M.R.; Rasti, B. Nanoliposomes and tocosomes as multifunctional nanocarriers for the encapsulation of nutraceutical and dietary molecules. Molecules, 2020, 25(3), 638.
[http://dx.doi.org/10.3390/molecules25030638] [PMID: 32024189]
[131]
Mozafari, M.R.; Danaei, M.; Javanmard, R.; Raji, M.; Maherani, B. Nanoscale lipidic carrier systems: importance of preparation method and solvents. Glob. J. Nanomed., 2017, 2(4)555593
[132]
Wagner, A.; Vorauer-Uhl, K. Liposome technology for industrial purposes. J. Drug Deliv., 2011, 2011591325
[http://dx.doi.org/10.1155/2011/591325] [PMID: 21490754]
[133]
Low, W.L.; Martin, C.; Hill, D.J.; Kenward, M.A. Antimicrobial efficacy of liposome-encapsulated silver ions and tea tree oil against Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans. Lett. Appl. Microbiol., 2013, 57(1), 33-39.
[http://dx.doi.org/10.1111/lam.12082] [PMID: 23581401]
[134]
Eid, K.A.; Azzazy, H.M. Sustained broad-spectrum antibacterial effects of nanoliposomes loaded with silver nanoparticles. Nanomedicine (Lond.), 2014, 9(9), 1301-1310.
[http://dx.doi.org/10.2217/nnm.13.89] [PMID: 24024570]
[135]
Azzazy, H.M.E.S.; Abduo, S.M.S.; Eid, K.A.M.; Guirgis, B.S.S. Direct detection of disease biomarkers in clinical specimens using cationic nanoparticle-based assays versatile and green methods for synthesis of anisotropic silver nanostructures US20150017258A1, 2015.
[136]
Chanda, D. Liposomal Uptake of Silver and Gold Nanoparticles. Master's Thesis. Louisiana State University and Agricultural and Mechanical College,, 2013.
[137]
Mozafari, M.R.; Reed, C.J.; Rostron, C.; Kocum, C.; Piskin, E. Construction of stable anionic liposome-plasmid particles using the heating method: a preliminary investigation. Cell. Mol. Biol. Lett., 2002, 7(3), 923-927.
[PMID: 12378277]
[138]
Lee, J.H.; Shin, Y.; Lee, W.; Whang, K.; Kim, D.; Lee, L.P.; Choi, J.W.; Kang, T. General and programmable synthesis of hybrid liposome/metal nanoparticles. Sci. Adv., 2016, 2(12)e1601838
[http://dx.doi.org/10.1126/sciadv.1601838] [PMID: 28028544]
[139]
Taggar, A.S.; Alnajim, J.; Anantha, M.; Thomas, A.; Webb, M.; Ramsay, E.; Bally, M.B. Copper-topotecan complexation mediates drug accumulation into liposomes. J. Control. Release, 2006, 114(1), 78-88.
[http://dx.doi.org/10.1016/j.jconrel.2006.05.019] [PMID: 16842880]
[140]
Petersen, A.L.; Binderup, T.; Rasmussen, P.; Henriksen, J.R.; Elema, D.R.; Kjær, A.; Andresen, T.L. 64Cu loaded liposomes as positron emission tomography imaging agents. Biomaterials, 2011, 32(9), 2334-2341.
[http://dx.doi.org/10.1016/j.biomaterials.2010.11.059] [PMID: 21216003]
[141]
Bilgin, M.D.; Elçin, A.E.; Elçin, Y.M. Topical use of liposomal copper palmitate formulation blocks porphyrin-induced photosensitivity in rats. J. Photochem. Photobiol. B, 2005, 80(2), 107-114.
[http://dx.doi.org/10.1016/j.jphotobiol.2005.03.009] [PMID: 15893469]
[142]
Zhang, L.C.; Chen, L.Y.; Wang, L. Surface modification of titanium and titanium alloys: technologies, developments and future interests. Adv. Eng. Mater., 2019, 20191901258
[143]
Ding, Z.; Fan, Q.; Wang, L. A review on friction stir processing of titanium alloy: characterization, method, microstructure, properties. Metall. Mater. Trans., B, Process Metall. Mater. Proc. Sci., 2019, 50(5), 2134-2162.
[http://dx.doi.org/10.1007/s11663-019-01634-9]
[144]
Chihara, Y.; Fujimoto, K.; Kondo, H.; Moriwaka, Y.; Sasahira, T.; Hirao, Y.; Kuniyasu, H. Anti-tumor effects of liposome-encapsulated titanium dioxide in nude mice. Pathobiology, 2007, 74(6), 353-358.
[http://dx.doi.org/10.1159/000110029] [PMID: 18087200]
[145]
Hadaruga, D.I.; Hadaruga, N.G.; Lazau, C.; Craciun, C.; Grozescu, I. Liposomes containing titanium dioxide nanoparticles. J. Agroaliment. Processes Technol., 2010, 16(1), 62-66.

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy
Request history8.2.27PHP Version798msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[20:14:31] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
  • warninglog[20:14:32] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • warninglog[20:14:32] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[20:14:32] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • Booting (256ms)time
  • Application (542ms)time
  • 1 x Application (67.95%)
    542ms
    1 x Booting (32.05%)
    256ms
    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
    36 statements were executed, 4 of which were duplicates, 32 unique. Show only duplicated388ms
    • 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 ('316600437','',1,1740773671,1740773671) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1740773671
      3.32msalphaeurekaselec_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 ('316600437','/article/108107',1,1740773671,1740773671)
      260μsalphaeurekaselec_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 >= 316600437 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316600437) 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 >= 316600437 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316600437) 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 >= 316600437 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316600437) 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 >= 316600437 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316600437) 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 >= 316600437 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316600437) 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 >= 316600437 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316600437) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 316600437 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316600437) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 316600437 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316600437) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 316600437 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316600437) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 316600437 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316600437) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 316600437 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316600437) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 316600437 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316600437) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 316600437 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316600437) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 316600437 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316600437) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 316600437 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316600437) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 316600437 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316600437) limit 1
      38.25msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 316600437
      • 1: 316600437
      • 2: 316600437
      • 3: 316600437
      • 4: 316600437
      • 5: 316600437
      • 6: 316600437
      • 7: 316600437
      • 8: 316600437
      • 9: 316600437
      • 10: 316600437
      • 11: 316600437
      • 12: 316600437
      • 13: 316600437
      • 14: 316600437
      • 15: 316600437
      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=108107
      3.49msalphaeurekaselec_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` = 27 limit 1
      1.62msalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 27
      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=27) and sj.journal_id!=27 group by `j`.`nid`) as `aggregate_table`
      770μsalphaeurekaselec_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=27) and sj.journal_id!=27 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      2.6msalphaeurekaselec_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=27) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      12.28msalphaeurekaselec_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=27) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      1.87msalphaeurekaselec_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` = '108107'
      15.13msalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 108107
      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` = '108107'
      28.98msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 108107
      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` = '108107' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      9.97msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 108107
      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
      6.41msalphaeurekaselec_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
      800μsalphaeurekaselec_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 = 27 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      67.76msalphaeurekaselec_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 = 27 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      19.33msalphaeurekaselec_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 = 27 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      10.91msalphaeurekaselec_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` = 108107 limit 1
      300μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 108107
      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 = 108107 and content_type = 'article' order by status desc limit 1
      13.95msalphaeurekaselec_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` = 183687 limit 1
      590μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 183687
      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
      360μsalphaeurekaselec_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` = 'CNANO' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      470μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CNANO
      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 = '108107' 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) )
      570μsalphaeurekaselec_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 = '10505' 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) )
      470μsalphaeurekaselec_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 = '2981' 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) )
      540μsalphaeurekaselec_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 <= 316600437 and j.to_ip >=316600437 )) and ((j.from_date <= 1740773671 and j.to_date >= 1740773671 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2981) 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 <= 316600437 and j.to_ip >=316600437 )) and ((j.from_date <= 1740773671 and j.to_date >= 1740773671 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2981) 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 <= 316600437 and j.to_ip >=316600437 )) and ((j.from_date <= 1740773671 and j.to_date >= 1740773671 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2981)
      94.88msalphaeurekaselec_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 <= 316600437 and j.to_ip >=316600437 )) and ((j.from_date <= 1740773672 and j.to_date >= 1740773672 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 10505) 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 <= 316600437 and j.to_ip >=316600437 )) and ((j.from_date <= 1740773672 and j.to_date >= 1740773672 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 10505) 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 <= 316600437 and j.to_ip >=316600437 )) and ((j.from_date <= 1740773672 and j.to_date >= 1740773672 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 10505)
      9.06msalphaeurekaselec_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 <= 316600437 and j.to_ip >=316600437 )) and ((j.from_date <= 1740773672 and j.to_date >= 1740773672 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 108107) 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 <= 316600437 and j.to_ip >=316600437 )) and ((j.from_date <= 1740773672 and j.to_date >= 1740773672 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 108107) 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 <= 316600437 and j.to_ip >=316600437 )) and ((j.from_date <= 1740773672 and j.to_date >= 1740773672 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 108107)
      940μsalphaeurekaselec_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` < '26' and is_uploaded = 1 and issue_id = 10505 order by cast(first_page as SIGNED) desc limit 1
      810μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 26
      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` > '40' and is_uploaded = 1 and issue_id = 10505 order by cast(first_page as SIGNED) asc limit 1
      710μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 40
      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` = 'en'
      1.62msalphaeurekaselec_live_10_06_2022ArticleController.php#2497
      Bindings
      • 0: en
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2497
      • 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` = 1
      18.36msalphaeurekaselec_live_10_06_2022MultiLanguage.php#23
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/MultiLanguage.php:23
      • 14. app/Http/Controllers/ArticleController.php:2498
      • 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 `id` from `multilanguage_article` where `article_id` = 108107 limit 1
      3.96msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 108107
      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` = 27 and `b`.`banner_from_date` <= 1740773672 and `b`.`banner_to_date` >= 1740773672 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      10.37msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 27
      • 3: 1740773672
      • 4: 1740773672
      • 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` = 27 and `b`.`banner_from_date` <= 1740773672 and `b`.`banner_to_date` >= 1740773672 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.64msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 27
      • 3: 1740773672
      • 4: 1740773672
      • 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='814baf4dfbb8e26c4f613cef42ae69c7'
      5.05msalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:291
      • 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\MultiLanguage
    1MultiLanguage.php#?
        _token
        ugzSSxGyqprnx665oVD8LFp94BTuXmRJDjts618t
        uc_cart_id
        814baf4dfbb8e26c4f613cef42ae69c7
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/108107" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/108107
        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:9 [ "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6InBuRG0xdkNwWkUra0hPTnI5RUVrK0E9PSIsInZhbHVlIjoiSnFHVmMwS1lKWnJuS2lmaUJYa3pwd2F4ejV2OEQ1Tk1LRVpDRHNSY3JDcz0iLCJtYWMiOiJiZjgxMzUxMTVkN2UyNmI0OGJkYzQ5MzgyMTkzYmVkZTFmYTFiNDZjNGRlMzI3YTdlZDYzYTQ2YmEzMTcyZTVlIiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6InBuRG0xdkNwWkUra0hPTnI5RUVrK0E9PSIsInZhbHVlIjoiSnFHVmMwS1lKWnJuS2lmaUJYa3pwd2F4ejV2OEQ1Tk1LRVpDRHNSY3JDcz0iLCJtYWMiOiJiZjgxMzUxMTVkN2Uy" ] "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
        0 of 0
        array:1 [ "wayfindertarget" => null ]
        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 => "Fri, 28 Feb 2025 20:14:32 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6ImhBY1FHWWxiOWJnQ2VjdnhJQWJLWFE9PSIsInZhbHVlIjoiR0xxVVZ2V3ozRlhDLzdVYnpENllUd1V6dzJUMCtzRDMwcDFHdzNxZ1RZQXpBZ3pLTUF5RTNUYlVkdTlKeURwcm5YY1l3ZWFGY280TmlZeHpZVElOMG1nUWtYd1dqMHlacnVZRUNmQmdHelhUbTBUZnhGZlk4b1AvV013cTB1eUwiLCJtYWMiOiIzODE2ODY2OTgwZDJkNzBjOGJkMzE1ZmY0MmViZWI0NWE3YTExMTY4OTJiZDU5YzMxYmEwNDFmY2JkZmE2ZTI3IiwidGFnIjoiIn0%3D; expires=Mon, 03 Mar 2025 08:14:32 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6ImhBY1FHWWxiOWJnQ2VjdnhJQWJLWFE9PSIsInZhbHVlIjoiR0xxVVZ2V3ozRlhDLzdVYnpENllUd1V6dzJUMCtzRDMwcDFHdzNxZ1RZQXpBZ3pLTUF5RTNUYlVkdTlKeURwcm5YY1l3Z" 1 => "alphaeurekaselectnet_session=eyJpdiI6IkYyeXFVd2wveUJKbDltSmE2ZE11R2c9PSIsInZhbHVlIjoiQlVrTmRZOTB1b3EvTWFDb0ErQUVMYUhydUlFSDlUVzRkaVVCNWp2MmhMMVV4NUczcDg2RmVvRWJuVnpPc2k5cU1zMVUydHhRdElNRW4wTWhZT0w4MHhpbjdmelpsdGZEK0dDNnZkTkxMS3hZM0I0SmJhd3BoUHlQY1l0MmtYcEMiLCJtYWMiOiI0ZDJkZTQ3NjVjZTlmYmIwYWY1MDI0Y2QwNGY5ZDllMjUxZDA1ZWJiMWI1YmYxNGQ4NzUxNDdlNzcyYjYyYTEyIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6IkYyeXFVd2wveUJKbDltSmE2ZE11R2c9PSIsInZhbHVlIjoiQlVrTmRZOTB1b3EvTWFDb0ErQUVMYUhydUlFSDlUVzRkaVVCNWp2MmhMMVV4NUczcDg2RmVvRWJ" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6ImhBY1FHWWxiOWJnQ2VjdnhJQWJLWFE9PSIsInZhbHVlIjoiR0xxVVZ2V3ozRlhDLzdVYnpENllUd1V6dzJUMCtzRDMwcDFHdzNxZ1RZQXpBZ3pLTUF5RTNUYlVkdTlKeURwcm5YY1l3ZWFGY280TmlZeHpZVElOMG1nUWtYd1dqMHlacnVZRUNmQmdHelhUbTBUZnhGZlk4b1AvV013cTB1eUwiLCJtYWMiOiIzODE2ODY2OTgwZDJkNzBjOGJkMzE1ZmY0MmViZWI0NWE3YTExMTY4OTJiZDU5YzMxYmEwNDFmY2JkZmE2ZTI3IiwidGFnIjoiIn0%3D; expires=Mon, 03-Mar-2025 08:14:32 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6ImhBY1FHWWxiOWJnQ2VjdnhJQWJLWFE9PSIsInZhbHVlIjoiR0xxVVZ2V3ozRlhDLzdVYnpENllUd1V6dzJUMCtzRDMwcDFHdzNxZ1RZQXpBZ3pLTUF5RTNUYlVkdTlKeURwcm5YY1l3Z" 1 => "alphaeurekaselectnet_session=eyJpdiI6IkYyeXFVd2wveUJKbDltSmE2ZE11R2c9PSIsInZhbHVlIjoiQlVrTmRZOTB1b3EvTWFDb0ErQUVMYUhydUlFSDlUVzRkaVVCNWp2MmhMMVV4NUczcDg2RmVvRWJuVnpPc2k5cU1zMVUydHhRdElNRW4wTWhZT0w4MHhpbjdmelpsdGZEK0dDNnZkTkxMS3hZM0I0SmJhd3BoUHlQY1l0MmtYcEMiLCJtYWMiOiI0ZDJkZTQ3NjVjZTlmYmIwYWY1MDI0Y2QwNGY5ZDllMjUxZDA1ZWJiMWI1YmYxNGQ4NzUxNDdlNzcyYjYyYTEyIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6IkYyeXFVd2wveUJKbDltSmE2ZE11R2c9PSIsInZhbHVlIjoiQlVrTmRZOTB1b3EvTWFDb0ErQUVMYUhydUlFSDlUVzRkaVVCNWp2MmhMMVV4NUczcDg2RmVvRWJ" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "ugzSSxGyqprnx665oVD8LFp94BTuXmRJDjts618t" "uc_cart_id" => "814baf4dfbb8e26c4f613cef42ae69c7" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/article/108107" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-28 20:14:32GET/article/108107414361