{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T10:35:53Z","timestamp":1771670153134,"version":"3.50.1"},"reference-count":61,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,1,24]],"date-time":"2019-01-24T00:00:00Z","timestamp":1548288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FAPESP and CNPq","award":["2016\/24577-3 and 310293\/2015-4"],"award-info":[{"award-number":["2016\/24577-3 and 310293\/2015-4"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Receptors of the transient receptor potential (TRP) channels superfamily are expressed in many tissues and have different physiological functions. However, there are few studies investigating the role of these channels in cardiorespiratory control in mammals. We assessed the role of central and peripheral TRPV1 receptors in the cardiorespiratory responses to hypoxia (10% O2) and hypercapnia (7% CO2) by measuring pulmonary ventilation (      V \u02d9  E     ), heart rate (HR), mean arterial pressure (MAP) and body temperature (Tb) of male Wistar rats before and after intraperitoneal (AMG9810 [2.85 \u00b5g\/kg, 1 mL\/kg]) or intracebroventricular (AMG9810 [2.85 \u00b5g\/kg, 1 \u00b5L] or AMG7905 [28.5 \u03bcg\/kg, 1 \u00b5L]) injections of TRPV1 antagonists. Central or peripheral injection of TRPV1 antagonists did not change cardiorespiratory parameters or Tb during room air and hypercapnic conditions. However, the hypoxic ventilatory response was exaggerated by both central and peripheral injection of AMG9810. In addition, the peripheral antagonist blunted the drop in Tb induced by hypoxia. Therefore, the current data provide evidence that TRPV1 channels exert an inhibitory modulation on the hypoxic drive to breathe and stimulate the Tb reduction during hypoxia.<\/jats:p>","DOI":"10.3390\/ph12010019","type":"journal-article","created":{"date-parts":[[2019,1,24]],"date-time":"2019-01-24T11:12:48Z","timestamp":1548328368000},"page":"19","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["TRPV1 Inhibits the Ventilatory Response to Hypoxia in Adult Rats, but Not the CO2-Drive to Breathe"],"prefix":"10.3390","volume":"12","author":[{"given":"Luis","family":"Patrone","sequence":"first","affiliation":[{"name":"Department of Animal Morphology and Physiology, Faculty of Agricultural and Veterinarian Sciences, UNESP at Jaboticabal, Rod. Prof. Paulo Donato Castellane s\/n, Jaboticabal SP 14870-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaime","family":"Duarte","sequence":"additional","affiliation":[{"name":"Department of Animal Morphology and Physiology, Faculty of Agricultural and Veterinarian Sciences, UNESP at Jaboticabal, Rod. Prof. Paulo Donato Castellane s\/n, Jaboticabal SP 14870-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K\u00eania","family":"B\u00edcego","sequence":"additional","affiliation":[{"name":"Department of Animal Morphology and Physiology, Faculty of Agricultural and Veterinarian Sciences, UNESP at Jaboticabal, Rod. Prof. Paulo Donato Castellane s\/n, Jaboticabal SP 14870-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandre","family":"Steiner","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-090, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrej","family":"Romanovsky","sequence":"additional","affiliation":[{"name":"Thermoregulation and Systemic Inflammation Laboratory (FeverLab), Trauma Research, St. Joseph\u2019s Hospital and Medical Center, Phoenix, AZ 85013, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4097-5286","authenticated-orcid":false,"given":"Luciane","family":"Gargaglioni","sequence":"additional","affiliation":[{"name":"Department of Animal Morphology and Physiology, Faculty of Agricultural and Veterinarian Sciences, UNESP at Jaboticabal, Rod. Prof. Paulo Donato Castellane s\/n, Jaboticabal SP 14870-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,1,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1113\/jphysiol.1930.sp002648","article-title":"Sinus caroticus and respiratory reflexes: I. Cerebral blood flow and respiration. Adrenaline apnoea","volume":"69","author":"Heymans","year":"1930","journal-title":"J. Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1113\/jphysiol.1982.sp014397","article-title":"Central chemosensitivity and the reaction theory","volume":"332","author":"Loeschcke","year":"1982","journal-title":"J. Physiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/S0034-5687(01)00297-3","article-title":"Central chemosensitivity of respiration: A brief overview","volume":"129","author":"Ballantyne","year":"2001","journal-title":"Respir. Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2791","DOI":"10.1152\/jn.00759.2010","article-title":"Involvement of TRP channels in the CO2 chemosensitivity of locus coeruleus neurons","volume":"105","author":"Cui","year":"2011","journal-title":"J. Neurophysiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1007\/978-3-319-18440-1_25","article-title":"Possible Role of TRP Channels in Rat Glomus Cells","volume":"860","author":"Kim","year":"2015","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"R37","DOI":"10.1152\/ajpregu.00668.2006","article-title":"Thermoregulation: Some concepts have changed. Functional architecture of the thermoregulatory system","volume":"292","author":"Romanovsky","year":"2007","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1080\/23328940.2015.1040604","article-title":"TRP ion channels in thermosensation, thermoregulation and metabolism","volume":"2","author":"Wang","year":"2015","journal-title":"Temperature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"H157","DOI":"10.1152\/ajpheart.00457.2014","article-title":"Role of TRP channels in the cardiovascular system","volume":"308","author":"Yue","year":"2015","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1002\/cne.10798","article-title":"Distribution of transient receptor potential channels in the rat carotid chemosensory pathway","volume":"464","author":"Buniel","year":"2003","journal-title":"J. Comp. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1124\/pr.109.001263","article-title":"The Transient Receptor Potential Vanilloid-1 Channel in Thermoregulation: A Thermosensor It Is Not","volume":"61","author":"Romanovsky","year":"2009","journal-title":"Pharmacol. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1111\/apha.12231","article-title":"Skin temperature: Its role in thermoregulation","volume":"210","author":"Romanovsky","year":"2014","journal-title":"Acta Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1124\/mol.116.104430","article-title":"Structure-Driven Pharmacology of Transient Receptor Potential Channel Vanilloid 1","volume":"90","author":"Sepulveda","year":"2016","journal-title":"Mol. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/0006-8993(91)90982-2","article-title":"Characterization of vanilloid receptors in the dorsal horn of pig spinal cord","volume":"547","author":"Szallasi","year":"1991","journal-title":"Brain Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.molbrainres.2004.12.003","article-title":"Expression and distribution of vanilloid receptor 1 (TRPV1) in the adult rat brain","volume":"135","author":"Kedei","year":"2005","journal-title":"Mol. Brain Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.tins.2008.12.006","article-title":"Hot flash: TRPV channels in the brain","volume":"32","author":"Kauer","year":"2009","journal-title":"Trends Neurosci."},{"key":"ref_16","first-page":"77","article-title":"TRPV1 in the central nervous system: Synaptic plasticity, function, and pharmacological implications","volume":"68","author":"Edwards","year":"2014","journal-title":"Prog. Drug Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.jss.2016.03.050","article-title":"TRPV1 and neuropeptide receptor immunoreactivity and expression in the rat lung and brainstem after lung ischemia-reperfusion injury","volume":"203","author":"Zhao","year":"2016","journal-title":"J. Surg. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.brainres.2018.09.005","article-title":"Transient receptor potential vanilloid 1-6 (Trpv1-6) gene expression in the mouse brain during estrous cycle","volume":"1701","author":"Kumar","year":"2018","journal-title":"Brain Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3655","DOI":"10.1073\/pnas.97.7.3655","article-title":"Distribution of mRNA for vanilloid receptor subtype 1 (VR1), and VR1-like immunoreactivity, in the central nervous system of the rat and human","volume":"97","author":"Mezey","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/s00424-016-1912-8","article-title":"Effects of a TRPV1 agonist capsaicin on respiratory rhythm generation in brainstem-spinal cord preparation from newborn rats","volume":"469","author":"Tani","year":"2017","journal-title":"Pflugers Arch."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"R134","DOI":"10.1152\/ajpregu.00049.2018","article-title":"Activation of TRPV1 in nucleus tractus solitarius reduces brown adipose tissue thermogenesis, arterial pressure, and heart rate","volume":"315","author":"Mohammed","year":"2018","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1152\/japplphysiol.01303.2010","article-title":"Anandamide modulates carotid sinus nerve afferent activity via TRPV1 receptors increasing responses to heat","volume":"112","author":"Roy","year":"2012","journal-title":"J. Appl. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.nbd.2018.08.004","article-title":"Vagal TRPV1 activation exacerbates thermal hyperpnea and increases susceptibility to experimental febrile seizures in immature rats","volume":"119","author":"Barrett","year":"2018","journal-title":"Neurobiol. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1097\/MNH.0b013e32835c8d4c","article-title":"Transient receptor potential vanilloid in blood pressure regulation","volume":"22","author":"Hollis","year":"2013","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1124\/jpet.109.160473","article-title":"Sensing of blood pressure increase by transient receptor potential vanilloid 1 receptors on baroreceptors","volume":"331","author":"Sun","year":"2009","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1124\/mol.105.015727","article-title":"Proton activation does not alter antagonist interaction with the capsaicin-binding pocket of TRPV1","volume":"68","author":"Gavva","year":"2005","journal-title":"Mol. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1124\/jpet.107.132233","article-title":"Antihyperalgesic effects of (R,E)-N-(2-hydroxy-2,3-dihydro-1H-inden-4-yl)-3-(2-(piperidin-1-yl)-4-(trifluoromethyl)phenyl)-acrylamide (AMG8562), a novel transient receptor potential vanilloid type 1 modulator that does not cause hyperthermia in rats","volume":"326","author":"Lehto","year":"2008","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Garami, A., Pakai, E., McDonald, H.A., Reilly, R.M., Gomtsyan, A., Corrigan, J.J., Pinter, E., Zhu, D.X.D., Lehto, S.G., and Gavva, N.R. (2018). TRPV1 antagonists that cause hypothermia, instead of hyperthermia, in rodents: Compounds\u2019 pharmacological profiles, in vivo targets, thermoeffectors recruited and implications for drug development. Acta Physiol., 223.","DOI":"10.1111\/apha.13038"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7459","DOI":"10.1523\/JNEUROSCI.1483-07.2007","article-title":"Nonthermal Activation of Transient Receptor Potential Vanilloid-1 Channels in Abdominal Viscera Tonically Inhibits Autonomic Cold-Defense Effectors","volume":"27","author":"Steiner","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.pain.2008.01.024","article-title":"Pharmacological blockade of the vanilloid receptor TRPV1 elicits marked hyperthermia in humans","volume":"136","author":"Gavva","year":"2008","journal-title":"Pain"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4285","DOI":"10.1096\/fj.15-272526","article-title":"The sympathetic nervous system is controlled by transient receptor potential vanilloid 1 in the regulation of body temperature","volume":"29","author":"Alawi","year":"2015","journal-title":"FASEB J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1038\/39807","article-title":"The capsaicin receptor: A heat-activated ion channel in the pain pathway","volume":"389","author":"Caterina","year":"1997","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8134","DOI":"10.1073\/pnas.100129497","article-title":"Acid potentiation of the capsaicin receptor determined by a key extracellular site","volume":"97","author":"Jordt","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1113\/jphysiol.2003.060350","article-title":"Depletion of substance P and glutamate by capsaicin blocks respiratory rhythm in neonatal rat in vitro","volume":"555","author":"Feldman","year":"2004","journal-title":"J. Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1523\/JNEUROSCI.5150-09.2010","article-title":"Contributions of different modes of TRPV1 activation to TRPV1 antagonist-induced hyperthermia","volume":"30","author":"Garami","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/S0896-6273(00)80564-4","article-title":"The cloned capsaicin receptor integrates multiple pain-producing stimuli","volume":"21","author":"Tominaga","year":"1998","journal-title":"Neuron"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.pupt.2006.11.010","article-title":"Acid-sensitive vagal sensory pathways and cough","volume":"20","author":"Kollarik","year":"2007","journal-title":"Pulm. Pharmacol. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"33868","DOI":"10.1074\/jbc.M702577200","article-title":"Potentiation of TRPC5 by protons","volume":"282","author":"Semtner","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.bbrc.2007.10.154","article-title":"Molecular determinant of sensing extracellular pH in classical transient receptor potential channel 5","volume":"365","author":"Kim","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1111\/j.1476-5381.1982.tb09326.x","article-title":"Influence of neonatally administered capsaicin on baroreceptor and chemoreceptor reflexes in the adult rat","volume":"77","author":"Bond","year":"1982","journal-title":"Br. J. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1152\/jappl.1991.70.3.1168","article-title":"Ventilatory responses to hypoxia and hypercapnia in awake rats pretreated with capsaicin","volume":"70","author":"Green","year":"1991","journal-title":"J. Appl. Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1152\/jappl.2000.89.5.1709","article-title":"Consequences of capsaicin treatment on pulmonary vagal reflexes and chemoreceptor activity in lambs","volume":"89","author":"Diaz","year":"2000","journal-title":"J. Appl. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1124\/jpet.107.125674","article-title":"Repeated Administration of Vanilloid Receptor TRPV1 Antagonists Attenuates Hyperthermia Elicited by TRPV1 Blockade","volume":"323","author":"Gavva","year":"2007","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/0306-4522(80)90054-8","article-title":"Restoration of reflex ventilatory response to hypoxia after removal of carotid bodies in the cat","volume":"5","author":"Smith","year":"1980","journal-title":"Neuroscience"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1097\/ALN.0000000000001812","article-title":"Transient Receptor Potential Vanilloid 1 Antagonists Prevent Anesthesia-induced Hypothermia and Decrease Postincisional Opioid Dose Requirements in Rodents","volume":"127","author":"Garami","year":"2017","journal-title":"Anesthesiology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/2045-8118-8-7","article-title":"Drug transport in brain via the cerebrospinal fluid","volume":"8","author":"Pardridge","year":"2011","journal-title":"Fluids Barriers CNS"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Davson, H. (1969). The Cerebrospinal Fluid. Handbook of Neurochemistry, Springer.","DOI":"10.1007\/978-1-4899-7321-4_3"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5259","DOI":"10.1113\/jphysiol.2009.175828","article-title":"Hypoxia reduces the hypothalamic thermogenic threshold and thermosensitivity","volume":"587","author":"Tattersall","year":"2009","journal-title":"J. Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1152\/jappl.1987.62.6.2477","article-title":"Hypoxia-induced changes in shivering and body temperature","volume":"62","author":"Gautier","year":"1987","journal-title":"J. Appl. Physiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1152\/jappl.2001.91.2.603","article-title":"Hypoxic metabolic response of the golden-mantled ground squirrel","volume":"91","author":"Barros","year":"2001","journal-title":"J. Appl. Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1242\/jeb.00057","article-title":"Transient peripheral warming accompanies the hypoxic metabolic response in the golden-mantled ground squirrel","volume":"206","author":"Tattersall","year":"2003","journal-title":"J. Exp. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.cbpa.2006.06.032","article-title":"Physiology of temperature regulation: Comparative aspects","volume":"147","author":"Bicego","year":"2007","journal-title":"Comp. Biochem. Physiol. A Mol. Integr. Physiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1146\/annurev.ph.53.030191.000443","article-title":"Interactions Between Hypoxia and Hypothermia","volume":"53","author":"Wood","year":"1991","journal-title":"Annu. Rev. Physiol."},{"key":"ref_54","first-page":"1249","article-title":"Oxygen as a modulator of body temperature","volume":"28","author":"Wood","year":"1995","journal-title":"Braz. J. Med. Biol. Res. Rev. Bras. Pesqui. Med. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1146\/annurev.physiol.64.081501.155856","article-title":"Hypoxia-Induced Anapyrexia: Implications and Putative Mediators","volume":"64","author":"Steiner","year":"2002","journal-title":"Annu. Rev. Physiol."},{"key":"ref_56","unstructured":"Paxinos, G., and Watson, C. (2007). The Rat Brain in Stereotaxic Coordinates, Elsevier."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1542\/peds.16.1.81","article-title":"A barometric method for measuring ventilation in newborn infants","volume":"16","author":"Drorbaugh","year":"1955","journal-title":"Pediatrics"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1007\/s00424-007-0338-8","article-title":"Locus coeruleus noradrenergic neurons and CO2 drive to breathing","volume":"455","author":"Biancardi","year":"2008","journal-title":"Pfl\u00fcgers Arch. Eur. J. Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.resp.2010.04.016","article-title":"Role of neurokinin-1 expressing neurons in the locus coeruleus on ventilatory and cardiovascular responses to hypercapnia","volume":"172","author":"Gargaglioni","year":"2010","journal-title":"Respir. Physiol. Neurobiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.resp.2013.09.001","article-title":"Cardiorespiratory effects of gap junction blockade in the locus coeruleus in unanesthetized adult rats","volume":"190","author":"Patrone","year":"2014","journal-title":"Respir. Physiol. Neurobiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3299","DOI":"10.1113\/JP275731","article-title":"Brainstem catecholaminergic neurones and breathing control during postnatal development in male and female rats","volume":"596","author":"Patrone","year":"2018","journal-title":"J. Physiol."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/12\/1\/19\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:28:30Z","timestamp":1760185710000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/12\/1\/19"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,24]]},"references-count":61,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,3]]}},"alternative-id":["ph12010019"],"URL":"https:\/\/doi.org\/10.3390\/ph12010019","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,24]]}}}