{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:53:18Z","timestamp":1789707198784,"version":"4.0.1"},"reference-count":54,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T00:00:00Z","timestamp":1656979200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["82170326"],"award-info":[{"award-number":["82170326"]}]},{"name":"National Natural Science Foundation of China","award":["81770328"],"award-info":[{"award-number":["81770328"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background: Previous studies have associated slowed ventricular conduction with the arrhythmogenesis mediated by the gap junction and sodium channel inhibitor heptanol in mouse hearts. However, they did not study the propagation patterns that might contribute to the arrhythmic substrate. This study used a multi-electrode array mapping technique to further investigate different conduction abnormalities in Langendorff-perfused mouse hearts exposed to 0.1 or 2 mM heptanol. Methods: Recordings were made from the left ventricular epicardium using multi-electrode arrays in spontaneously beating hearts during right ventricular 8 Hz pacing or S1S2 pacing. Results: In spontaneously beating hearts, heptanol at 0.1 and 2 mM significantly reduced the heart rate from 314 \u00b1 25 to 189 \u00b1 24 and 157 \u00b1 7 bpm, respectively (ANOVA, p &lt; 0.05 and p &lt; 0.001). During regular 8 Hz pacing, the mean LATs were increased by 0.1 and 2 mM heptanol from 7.1 \u00b1 2.2 ms to 19.9 \u00b1 5.0 ms (p &lt; 0.05) and 18.4 \u00b1 5.7 ms (p &lt; 0.05). The standard deviation of the mean LATs was increased from 2.5 \u00b1 0.8 ms to 10.3 \u00b1 4.0 ms and 8.0 \u00b1 2.5 ms (p &lt; 0.05), and the median of phase differences was increased from 1.7 \u00b1 1.1 ms to 13.9 \u00b1 7.8 ms and 12.1 \u00b1 5.0 ms by 0.1 and 2 mM heptanol (p &lt; 0.05). P5 took a value of 0.2 \u00b1 0.1 ms and was not significantly altered by heptanol at 0.1 or 2 mM (1.1 \u00b1 0.9 ms and 0.9 \u00b1 0.5 ms, p &gt; 0.05). P50 was increased from 7.3 \u00b1 2.7 ms to 24.0 \u00b1 12.0 ms by 0.1 mM heptanol and then to 22.5 \u00b1 7.5 ms by 2 mM heptanol (p &lt; 0.05). P95 was increased from 1.7 \u00b1 1.1 ms to 13.9 \u00b1 7.8 ms by 0.1 mM heptanol and to 12.1 \u00b1 5.0 ms by 2 mM heptanol (p &lt; 0.05). These changes led to increases in the absolute inhomogeneity in conduction (P5\u201395) from 7.1 \u00b1 2.6 ms to 31.4 \u00b1 11.3 ms, 2 mM: 21.6 \u00b1 7.2 ms, respectively (p &lt; 0.05). The inhomogeneity index (P5\u201395\/P50) was significantly reduced from 3.7 \u00b1 1.2 to 3.1 \u00b1 0.8 by 0.1 mM and then to 3.3 \u00b1 0.9 by 2 mM heptanol (p &lt; 0.05). Conclusion: Increased activation latencies, reduced CVs, and the increased inhomogeneity index of conduction were associated with both spontaneous and induced ventricular arrhythmias.<\/jats:p>","DOI":"10.3390\/life12070996","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T05:41:06Z","timestamp":1657086066000},"page":"996","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Heterogeneities in Ventricular Conduction Following Treatment with Heptanol: A Multi-Electrode Array Study in Langendorff-Perfused Mouse Hearts"],"prefix":"10.3390","volume":"12","author":[{"given":"Xiuming","family":"Dong","sequence":"first","affiliation":[{"name":"Henan SCOPE Research Institute of Electrophysiology Co., Ltd., Kaifeng 475000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5510-1253","authenticated-orcid":false,"given":"Gary","family":"Tse","sequence":"additional","affiliation":[{"name":"Cardiac Electrophysiology Unit, Cardiovascular Analytics Group, Hong Kong, China"},{"name":"Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China"},{"name":"Kent and Medway Medical School, Canterbury CT2 7FS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoliang","family":"Hao","sequence":"additional","affiliation":[{"name":"Henan SCOPE Research Institute of Electrophysiology Co., Ltd., Kaifeng 475000, China"},{"name":"Burdon Sanderson Cardiac Science Centre, BHF Centre of Research Excellence, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1125-0294","authenticated-orcid":false,"given":"Yimei","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"Research Center of Ion Channelopathy, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.ccep.2010.10.012","article-title":"Overview of Basic Mechanisms of Cardiac Arrhythmia","volume":"3","author":"Antzelevitch","year":"2011","journal-title":"Card. Electrophysiol. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"202","DOI":"10.15420\/aer.2020.04","article-title":"Anisotropic Cardiac Conduction","volume":"9","author":"Kotadia","year":"2020","journal-title":"Arrhythmia Electrophysiol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.cger.2012.08.005","article-title":"Mechanisms of arrhythmias and conduction disorders in older adults","volume":"28","author":"Mirza","year":"2012","journal-title":"Clin. Geriatr. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/ehf2.12068","article-title":"Ventricular conduction abnormalities as predictors of long-term survival in acute de novo and decompensated chronic heart failure","volume":"3","author":"Tolppanen","year":"2016","journal-title":"ESC Heart Fail."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2848759","DOI":"10.1155\/2016\/2848759","article-title":"Molecular and Electrophysiological Mechanisms Underlying Cardiac Arrhythmogenesis in Diabetes Mellitus","volume":"2016","author":"Tse","year":"2016","journal-title":"J. Diabetes Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.yjmcc.2020.12.008","article-title":"Mechanisms underlying age-associated manifestation of cardiac sodium channel gain-of-function","volume":"153","author":"Nowak","year":"2021","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2997","DOI":"10.1111\/jce.15262","article-title":"Right ventricular outflow tract electroanatomical abnormalities in asymptomatic and high-risk symptomatic patients with Brugada syndrome: Evidence for a new risk stratification tool?","volume":"32","author":"Letsas","year":"2021","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e005928","DOI":"10.1161\/CIRCEP.117.005928","article-title":"Right Ventricular Outflow Tract Electroanatomical Abnormalities Predict Ventricular Fibrillation Inducibility in Brugada Syndrome","volume":"11","author":"Letsas","year":"2018","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"8789617","DOI":"10.1155\/2016\/8789617","article-title":"Diabetes Increases Cryoinjury Size with Associated Effects on Cx43 Gap Junction Function and Phosphorylation in the Mouse Heart","volume":"2016","author":"Palatinus","year":"2016","journal-title":"J. Diabetes Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1007\/s00424-014-1675-z","article-title":"Sodium channels in the Cx43 gap junction perinexus may constitute a cardiac ephapse: An experimental and modeling study","volume":"467","author":"Veeraraghavan","year":"2015","journal-title":"Pflug. Arch."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.ijcard.2016.07.027","article-title":"Gap junction modifiers regulate electrical activities of the sinoatrial node and pulmonary vein: Therapeutic implications in atrial arrhythmogenesis","volume":"221","author":"Chang","year":"2016","journal-title":"Int. J. Cardiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.cardiores.2006.08.015","article-title":"Gap junction heterogeneity in reentrant ventricular tachycardia","volume":"72","author":"Veenstra","year":"2006","journal-title":"Cardiovasc. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1161\/01.RES.68.4.977","article-title":"Block of sodium current by heptanol in voltage-clamped canine cardiac Purkinje cells","volume":"68","author":"Nelson","year":"1991","journal-title":"Circ. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1111\/j.1540-8167.1996.tb00495.x","article-title":"Effect of coronary perfusion of heptanol on conduction and ventricular arrhythmias in infarcted canine myocardium","volume":"7","author":"Callans","year":"1996","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s12576-011-0187-2","article-title":"Ventricular arrhythmogenesis following slowed conduction in heptanol-treated, Langendorff-perfused mouse hearts","volume":"62","author":"Tse","year":"2012","journal-title":"J. Physiol. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4069","DOI":"10.3892\/mmr.2016.5738","article-title":"Gap junction inhibition by heptanol increases ventricular arrhythmogenicity by reducing conduction velocity without affecting repolarization properties or myocardial refractoriness in Langendorff-perfused mouse hearts","volume":"14","author":"Tse","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"85341","DOI":"10.18632\/oncotarget.19675","article-title":"Effects of pharmacological gap junction and sodium channel blockade on S1S2 restitution properties in Langendorff-perfused mouse hearts","volume":"8","author":"Tse","year":"2017","journal-title":"Oncotarget"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.crphys.2021.04.001","article-title":"Measures of repolarization variability predict ventricular arrhythmogenesis in heptanol-treated Langendorff-perfused mouse hearts","volume":"4","author":"Tse","year":"2021","journal-title":"Curr. Res. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.3389\/fphys.2018.01578","article-title":"Quantification of Beat-To-Beat Variability of Action Potential Durations in Langendorff-Perfused Mouse Hearts","volume":"9","author":"Tse","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/nnano.2012.265","article-title":"Multi-electrode array technologies for neuroscience and cardiology","volume":"8","author":"Spira","year":"2013","journal-title":"Nat. Nanotechnol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Issa, Z.F., Miller, J.M., and Zipes, D.P. (2012). Chapter 6\u2014Advanced Mapping and Navigation Modalities. Clinical Arrhythmology and Electrophysiology: A Companion to Braunwald\u2019s Heart Disease, W.B. Saunders. [2nd ed.].","DOI":"10.1016\/B978-1-4557-1274-8.00006-3"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1515\/jbcpp-2016-0110","article-title":"Isolated heart models for studying cardiac electrophysiology: A historical perspective and recent advances","volume":"28","author":"Yeo","year":"2017","journal-title":"J. Basic Clin. Physiol. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1515\/jbcpp-2016-0007","article-title":"Monophasic action potential recordings: Which is the recording electrode?","volume":"27","author":"Tse","year":"2016","journal-title":"J. Basic Clin. Physiol. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"H156","DOI":"10.1152\/ajpheart.00333.2012","article-title":"The continuing evolution of the Langendorff and ejecting murine heart: New advances in cardiac phenotyping","volume":"303","author":"Liao","year":"2012","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1016\/j.yjmcc.2011.02.018","article-title":"Retrograde heart perfusion: The Langendorff technique of isolated heart perfusion","volume":"50","author":"Bell","year":"2011","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_26","first-page":"H1254","article-title":"Quantification of spatial inhomogeneity in conduction and initiation of reentrant atrial arrhythmias","volume":"259","author":"Lammers","year":"1990","journal-title":"Am. J. Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e000340","DOI":"10.1161\/JAHA.113.000340","article-title":"Mkk4 is a negative regulator of the transforming growth factor beta 1 signaling associated with atrial remodeling and arrhythmogenesis with age","volume":"3","author":"Davies","year":"2014","journal-title":"J. Am. Heart Assoc."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1111\/apha.12324","article-title":"Arrhythmic substrate, slowed propagation and increased dispersion in conduction direction in the right ventricular outflow tract of murine Scn5a+\/\u2212 hearts","volume":"211","author":"Zhang","year":"2014","journal-title":"Acta Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/BF02505758","article-title":"Heptanol-induced decrease in cardiac gap junctional conductance is mediated by a decrease in the fluidity of membranous cholesterol-rich domains","volume":"136","author":"Bastiaanse","year":"1993","journal-title":"J. Membr. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"C1531","DOI":"10.1152\/ajpcell.1992.262.6.C1531","article-title":"Mechanism of heptanol-induced uncoupling of cardiac gap junctions: A perforated patch-clamp study","volume":"262","author":"Jongsma","year":"1992","journal-title":"Am. J. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3431","DOI":"10.1073\/pnas.85.10.3431","article-title":"Single-channel events and gating behavior of the cardiac gap junction channel","volume":"85","author":"Burt","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/BF00373136","article-title":"Electrical properties of gap junction channels in guinea-pig ventricular cell pairs revealed by exposure to heptanol","volume":"415","author":"Rudisuli","year":"1989","journal-title":"Pflug. Arch."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s004240000264","article-title":"The effect of heptanol on the electrical and contractile function of the isolated, perfused rabbit heart","volume":"440","author":"Keevil","year":"2000","journal-title":"Pflug. Arch."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4808","DOI":"10.1111\/bph.12554","article-title":"Investigation of connexin 43 uncoupling and prolongation of the cardiac QRS complex in preclinical and marketed drugs","volume":"171","author":"Burnham","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1111\/j.1472-8206.2011.00953.x","article-title":"QRS widening and QT prolongation under bupropion: A unique cardiac electrophysiological profile","volume":"26","author":"Caillier","year":"2012","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1113\/jphysiol.1983.sp014813","article-title":"The action of alcohols and other non-ionic surface active substances on the sodium current of the squid giant axon","volume":"341","author":"Haydon","year":"1983","journal-title":"J. Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"C273","DOI":"10.1152\/ajpcell.1989.256.2.C273","article-title":"Effects of general anesthetics on current flow across membranes in guinea pig myocytes","volume":"256","author":"Niggli","year":"1989","journal-title":"Am. J. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"C195","DOI":"10.1152\/ajpcell.1990.258.2.C195","article-title":"Structure-activity relations of the cardiac gap junction channel","volume":"258","author":"Spray","year":"1990","journal-title":"Am. J. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.cardiores.2004.01.019","article-title":"Pharmacology of gap junctions in the cardiovascular system","volume":"62","author":"Dhein","year":"2004","journal-title":"Cardiovasc. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1161\/01.RES.63.5.879","article-title":"Effects of cellular uncoupling on conduction in anisotropic canine ventricular myocardium","volume":"63","author":"Balke","year":"1988","journal-title":"Circ. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1161\/01.RES.60.5.780","article-title":"Effects of increasing intercellular resistance on transverse and longitudinal propagation in sheep epicardial muscle","volume":"60","author":"Delmar","year":"1987","journal-title":"Circ. Res."},{"key":"ref_42","first-page":"H179","article-title":"Electrical uncoupling and impulse propagation in isolated sheep Purkinje fibers","volume":"257","author":"Jalife","year":"1989","journal-title":"Am. J. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1161\/01.CIR.84.3.1307","article-title":"Differential effects of heptanol, potassium, and tetrodotoxin on reentrant ventricular tachycardia around a fixed obstacle in anisotropic myocardium","volume":"84","author":"Brugada","year":"1991","journal-title":"Circulation"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1161\/hc3801.095587","article-title":"Gap junction blockers decrease defibrillation thresholds without changes in ventricular refractoriness in isolated rabbit hearts","volume":"104","author":"Qi","year":"2001","journal-title":"Circulation"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"H10","DOI":"10.1152\/ajpheart.01074.2002","article-title":"Regional gap junction inhibition increases defibrillation thresholds","volume":"285","author":"Sims","year":"2003","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1067\/mtc.2002.124239","article-title":"Gap junction uncoupling protects the heart against ischemia","volume":"124","author":"Saltman","year":"2002","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1111\/j.0305-1870.2005.04246.x","article-title":"Delayed uncoupling contributes to the protective effect of heptanol against ischaemia in the rat isolated heart","volume":"32","author":"Chen","year":"2005","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"H1116","DOI":"10.1152\/ajpheart.00927.2001","article-title":"Increased vulnerability to inducible atrial fibrillation caused by partial cellular uncoupling with heptanol","volume":"283","author":"Ohara","year":"2002","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Tse, G., Tse, V., Yeo, J.M., and Sun, B. (2016). Atrial Anti-Arrhythmic Effects of Heptanol in Langendorff-Perfused Mouse Hearts. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0148858"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s00424-010-0906-1","article-title":"Delayed conduction and its implications in murine Scn5a(+\/\u2212) hearts: Independent and interacting effects of genotype, age, and sex","volume":"461","author":"Jeevaratnam","year":"2011","journal-title":"Pflug. Arch."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1016\/0002-9149(80)90475-0","article-title":"Natural and evoked atrial flutter due to circus movement in dogs. Role of abnormal atrial pathways, slow conduction, nonuniform refractory period distribution and premature beats","volume":"45","author":"Boineau","year":"1980","journal-title":"Am. J. Cardiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1161\/01.RES.39.2.168","article-title":"Circus movement in rabbit atrial muscle as a mechanism of tachycardia. II. The role of nonuniform recovery of excitability in the occurrence of unidirectional block, as studied with multiple microelectrodes","volume":"39","author":"Allessie","year":"1976","journal-title":"Circ. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1113\/expphysiol.2012.069369","article-title":"The mechanical uncoupler blebbistatin is associated with significant electrophysiological effects in the isolated rabbit heart","volume":"98","author":"Brack","year":"2013","journal-title":"Exp. Physiol."},{"key":"ref_54","first-page":"A16717","article-title":"Abstract 16717: Customizable High-density Microelectrode Arrays for Murine Cardiac Electrophysiology","volume":"134","author":"Vetter","year":"2016","journal-title":"Circulation"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/12\/7\/996\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:42:50Z","timestamp":1760139770000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/12\/7\/996"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,5]]},"references-count":54,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["life12070996"],"URL":"https:\/\/doi.org\/10.3390\/life12070996","relation":{"has-preprint":[{"id-type":"doi","id":"10.20944\/preprints202205.0153.v1","asserted-by":"object"}]},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,5]]}}}