Mangyu Choe , Alex E. Ekvik , Gretchen Stalnaker , Hijai R. Shin , Denis V. Titov
{"title":"Genetically encoded tool for manipulation of ΔΨm identifies its role as the driver of ISR induced by ATP synthase dysfunction","authors":"Mangyu Choe , Alex E. Ekvik , Gretchen Stalnaker , Hijai R. Shin , Denis V. Titov","doi":"10.1016/j.chembiol.2025.03.007","DOIUrl":"10.1016/j.chembiol.2025.03.007","url":null,"abstract":"<div><div>Mitochondrial membrane potential (ΔΨm) is one of the key parameters controlling cellular bioenergetics. Investigation of the role of ΔΨm in live cells is complicated by a lack of tools for its direct manipulation without off-target effects. Here, we adopted the uncoupling protein UCP1 from brown adipocytes as a genetically encoded tool for direct manipulation of ΔΨm. We validated the ability of exogenously expressed UCP1 to induce uncoupled respiration and lower ΔΨm in mammalian cells. UCP1 expression lowered ΔΨm to the same extent as chemical uncouplers but did not inhibit cell proliferation, suggesting that it manipulates ΔΨm without the off-target effects of chemical uncouplers. Using UCP1, we revealed that elevated ΔΨm is the driver of the integrated stress response induced by ATP synthase inhibition in mammalian cells.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 4","pages":"Pages 620-630.e6"},"PeriodicalIF":6.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143838211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Engineering electrogenetic interfaces for mammalian cell control","authors":"Maysam Mansouri , Martin Fussenegger","doi":"10.1016/j.chembiol.2025.01.003","DOIUrl":"10.1016/j.chembiol.2025.01.003","url":null,"abstract":"<div><div>Human body cells and our daily electronic devices both communicate information within their distinct worlds by regulating the flow of electrons across specified membranes. While electronic devices depend on the flow of electrons generated by conductive materials to communicate within a digital network, biological systems use ion gradients, created in analog biochemical reactions, to trigger biological data transmission throughout multicellular systems. Electrogenetics is an emerging concept in synthetic biology in which electrons generated by digital electronic devices program customized electron-responsive biological units within living cells. In this paper, we outline endeavors to design direct electrogenetic interfaces to control cell behaviors in therapeutically engineered mammalian cells. We also discuss prospects for the world of electrogenetics, focusing on how to engineer the next generation of therapeutic cells controlled by electronic devices and the internet of the body.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 4","pages":"Pages 521-528"},"PeriodicalIF":6.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143050284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mohammed A. Toure , Keisuke Motoyama , Yichen Xiang , Julie Urgiles , Florian Kabinger , Ann-Sophie Koglin , Ramya S. Iyer , Kaitlyn Gagnon , Amruth Kumar , Samuel Ojeda , Drew A. Harrison , Matthew G. Rees , Jennifer A. Roth , Christopher J. Ott , Richard Schiavoni , Charles A. Whittaker , Stuart S. Levine , Forest M. White , Eliezer Calo , Andre Richters , Angela N. Koehler
{"title":"Targeted degradation of CDK9 potently disrupts the MYC-regulated network","authors":"Mohammed A. Toure , Keisuke Motoyama , Yichen Xiang , Julie Urgiles , Florian Kabinger , Ann-Sophie Koglin , Ramya S. Iyer , Kaitlyn Gagnon , Amruth Kumar , Samuel Ojeda , Drew A. Harrison , Matthew G. Rees , Jennifer A. Roth , Christopher J. Ott , Richard Schiavoni , Charles A. Whittaker , Stuart S. Levine , Forest M. White , Eliezer Calo , Andre Richters , Angela N. Koehler","doi":"10.1016/j.chembiol.2025.03.001","DOIUrl":"10.1016/j.chembiol.2025.03.001","url":null,"abstract":"<div><div>CDK9 coordinates signaling events that regulate transcription and is implicated in oncogenic pathways, making it an actionable target for drug development. While numerous CDK9 inhibitors have been developed, success in the clinic has been limited. Targeted degradation offers a promising alternative. A comprehensive evaluation of degradation versus inhibition is needed to assess when degradation might offer superior therapeutic outcomes. We report a selective and potent CDK9 degrader with rapid kinetics, comparing its downstream effects to those of a conventional inhibitor. We validated that CDK9 inhibition triggers a compensatory feedback mechanism that dampens its anticipated effect on MYC expression and found that this was absent when degraded. Importantly, degradation is more effective at disrupting MYC transcriptional regulation and subsequently destabilizing nucleolar homeostasis, likely by abrogation of both enzymatic and scaffolding functions of CDK9. These findings suggest that CDK9 degradation offers a more robust strategy to overcome limitations associated with its inhibition.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 4","pages":"Pages 542-555.e10"},"PeriodicalIF":6.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Felix Deschner , Dietrich Mostert , Jan-Martin Daniel , Alexander Voltz , Dana Carina Schneider , Navid Khangholi , Jürgen Bartel , Laís Pessanha de Carvalho , Madita Brauer , Tatiana E. Gorelik , Christian Kleeberg , Timo Risch , F.P. Jake Haeckl , Laura Herraiz Benítez , Anastasia Andreas , Andreas Martin Kany , Gwenaëlle Jézéquel , Walter Hofer , Mathias Müsken , Jana Held , Jennifer Herrmann
{"title":"Natural products chlorotonils exert a complex antibacterial mechanism and address multiple targets","authors":"Felix Deschner , Dietrich Mostert , Jan-Martin Daniel , Alexander Voltz , Dana Carina Schneider , Navid Khangholi , Jürgen Bartel , Laís Pessanha de Carvalho , Madita Brauer , Tatiana E. Gorelik , Christian Kleeberg , Timo Risch , F.P. Jake Haeckl , Laura Herraiz Benítez , Anastasia Andreas , Andreas Martin Kany , Gwenaëlle Jézéquel , Walter Hofer , Mathias Müsken , Jana Held , Jennifer Herrmann","doi":"10.1016/j.chembiol.2025.03.005","DOIUrl":"10.1016/j.chembiol.2025.03.005","url":null,"abstract":"<div><div>Antimicrobial resistance is a threat to human health rendering current first-line antibiotics ineffective. New agents overcoming resistance mechanisms are urgently needed to guarantee successful treatment of human disease in the future. Chlorotonils, a natural product class with yet unknown mode of action, were shown to have broad-spectrum activity against multi-resistant Gram-positive bacteria and the malaria parasite <em>Plasmodium falciparum,</em> with promising activity and safety in murine infection models. Here, we report that chlorotonils can target the cell membrane, cell wall, and protein biosynthesis. They can be characterized by a rapid onset of action via interference with ion homeostasis leading to membrane depolarization, however, without inducing severe barrier failure or cellular lysis. Further characterization confirmed binding of chlorotonils to bacterial membrane lipids eventually leading to uncontrolled potassium transport. Additionally, we identified functional inhibition of the peptidoglycan biosynthesis protein YbjG and methionine aminopeptidase MetAP as secondary targets of chlorotonils.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 4","pages":"Pages 586-602.e15"},"PeriodicalIF":6.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143798015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hélène Guillorit , Sébastien Relier , Benjamin Zagiel , Audrey Di Giorgio , Chris Planque , Bastien Felipe , Hélène Hérault , Lucile Bansard , Céline Bouclier , Béatrice Chabi , François Casas , Ornella Clara , Béatrice Bonafos , Xavier Mialhe , Chantal Cazevieille , Szimonetta Hideg , Armelle Choquet , Amandine Bastide , Julie Pannequin , Maria Duca , Alexandre David
{"title":"Streptomycin targets tumor-initiating cells by disrupting oxidative phosphorylation","authors":"Hélène Guillorit , Sébastien Relier , Benjamin Zagiel , Audrey Di Giorgio , Chris Planque , Bastien Felipe , Hélène Hérault , Lucile Bansard , Céline Bouclier , Béatrice Chabi , François Casas , Ornella Clara , Béatrice Bonafos , Xavier Mialhe , Chantal Cazevieille , Szimonetta Hideg , Armelle Choquet , Amandine Bastide , Julie Pannequin , Maria Duca , Alexandre David","doi":"10.1016/j.chembiol.2025.03.008","DOIUrl":"10.1016/j.chembiol.2025.03.008","url":null,"abstract":"<div><div>Tumor initiating cells (TICs) are the roots of current shortcomings in advanced and metastatic cancer treatment. Endowed with self-renewal and multi-lineage differentiation capacity, TICs can disseminate and seed metastasis in distant organ. Our work identified streptomycin (SM), a potent bactericidal antibiotic, as a molecule capable of specifically targeting non-adherent TIC from colon and breast cancer cell lines. SM induces iron-dependent, reactive oxygen species (ROS)-mediated cell death, which is mechanistically distinct from RSL3-induced ferroptosis. SM-induced cell death is associated with profound alterations in mitochondrial morphology. This effect results from COX1 inhibition, which disrupts the regulation of the cytochrome <em>c</em> oxidase complex and triggers mitochondrial ROS production. SM’s aldehyde group is essential, as its reduction into dihydrostreptomycin (DSM) abolishes its activity. These findings reveal a mechanism of action for streptomycin, shedding light on TIC metabolism and resistance, with potential implications for advanced cancer treatment.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 4","pages":"Pages 570-585.e7"},"PeriodicalIF":6.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143806305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nicholas Kwiatkowski , Tong Liang , Zhe Sha , Philip N. Collier , Annan Yang , Murugappan Sathappa , Atanu Paul , Lijing Su , Xiaozhang Zheng , Robert Aversa , Kunhua Li , Revonda Mehovic , Christina Kolodzy , Susanne B. Breitkopf , Dapeng Chen , Charles L. Howarth , Karen Yuan , Hakryul Jo , Joseph D. Growney , Matthew Weiss , Juliet Williams
{"title":"CDK2 heterobifunctional degraders co-degrade CDK2 and cyclin E resulting in efficacy in CCNE1-amplified and overexpressed cancers","authors":"Nicholas Kwiatkowski , Tong Liang , Zhe Sha , Philip N. Collier , Annan Yang , Murugappan Sathappa , Atanu Paul , Lijing Su , Xiaozhang Zheng , Robert Aversa , Kunhua Li , Revonda Mehovic , Christina Kolodzy , Susanne B. Breitkopf , Dapeng Chen , Charles L. Howarth , Karen Yuan , Hakryul Jo , Joseph D. Growney , Matthew Weiss , Juliet Williams","doi":"10.1016/j.chembiol.2025.03.006","DOIUrl":"10.1016/j.chembiol.2025.03.006","url":null,"abstract":"<div><div><em>CCNE1</em> amplification drives aberrant CDK2-cyclin E1 activity in cancer. Despite activity of CDK2 inhibitors, their therapeutic margins are limited by poor CDK selectivity. We developed a degrader with high selectivity for CDK2 over CDK1 that also unexpectedly led to cyclin E1 degradation and potent and complete suppression of RB phosphorylation at concentrations with low CDK2 occupancy and negligible CDK1 degradation. Co-depletion of CDK2 and cyclin E1 also resensitized palbociclib-adapted breast cancer cells to cell cycle blockade. Overall, the improved potency and selectivity of the degrader for CDK2 over small-molecule inhibitors drives antiproliferative activity with greater specificity for <em>CCNE1</em><sup><em>amp</em></sup> cancer cells and RB dependency. Using an orally administered degrader, we demonstrate deep and sustained RB pathway suppression, which is needed to induce stasis in <em>CCNE1</em><sup><em>amp</em></sup> tumors. These results highlight the potential of this modality to target CDK2 potently and selectivity in this biomarker-defined patient population with high unmet need.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 4","pages":"Pages 556-569.e24"},"PeriodicalIF":6.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143838210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ruili Cao , Daniel T.D. Jones , Li Pan , Annie Yang , Shumei Wang , Sathish K.R. Padi , Shaun Rawson , Jon C. Aster , Stephen C. Blacklow
{"title":"Molecular mechanism of PP2A/B55α phosphatase inhibition by IER5","authors":"Ruili Cao , Daniel T.D. Jones , Li Pan , Annie Yang , Shumei Wang , Sathish K.R. Padi , Shaun Rawson , Jon C. Aster , Stephen C. Blacklow","doi":"10.1016/j.chembiol.2025.03.004","DOIUrl":"10.1016/j.chembiol.2025.03.004","url":null,"abstract":"<div><div>PP2A serine/threonine phosphatases are heterotrimeric complexes that execute many essential physiologic functions. These activities are modulated by additional regulatory proteins, such as ARPP19, FAM122A, and IER5. Here, we report the cryoelectron microscopy (cryo-EM) structure of a complex of PP2A/B55α with the N-terminal structured region of IER5 (IER5-N50), which occludes a surface on B55α used for substrate recruitment, and show that IER5-N50 inhibits PP2A/B55α catalyzed dephosphorylation of pTau in biochemical assays. Mutations of full-length IER5 that disrupt its PP2A/B55α interface interfere with co-immunoprecipitation of PP2A/B55α. IER5 antagonism of B55α in keratinocytes is required for expression of <em>KRT1</em>, a differentiation marker. Mini-IER5 composed of IER5-N50 and a nuclear localization sequence restores this activity in IER5 knockout cells. Using structural bioinformatics, we identify homology of IER5-N50 with SERTA (SEI-1, RBT-1, and TARA) domain containing proteins. These studies define the molecular basis of PP2A/B55α nuclear inhibition by IER5 and suggest a roadmap for selective pharmacologic modulation of PP2A/B55α complexes.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 4","pages":"Pages 631-642.e7"},"PeriodicalIF":6.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143806304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Natalia Horbach , Małgorzata Kalinka , Natalia Ćwilichowska-Puślecka , Abdulla Al Mamun , Agata Mikołajczyk-Martinez , Boris Turk , Scott J. Snipas , Paulina Kasperkiewicz , Katarzyna M. Groborz , Marcin Poręba
{"title":"Visualization of calpain-1 activation during cell death and its role in GSDMD cleavage using chemical probes","authors":"Natalia Horbach , Małgorzata Kalinka , Natalia Ćwilichowska-Puślecka , Abdulla Al Mamun , Agata Mikołajczyk-Martinez , Boris Turk , Scott J. Snipas , Paulina Kasperkiewicz , Katarzyna M. Groborz , Marcin Poręba","doi":"10.1016/j.chembiol.2025.03.002","DOIUrl":"10.1016/j.chembiol.2025.03.002","url":null,"abstract":"<div><div>Calpain-1, a calcium-dependent cysteine protease, plays a vital role in cellular processes such as cell death, cytoskeletal remodeling, signal transduction, and cell cycle progression. While its role in apoptosis, including substrate cleavage for orderly disassembly, is well established, its involvement in pyroptosis remains less understood. This study focused on developing chemical tools to detect calpain-1 activity. Using the hybrid combinatorial substrate library (HyCoSuL) approach with unnatural amino acids, we designed fluorescent substrates, inhibitors, and fluorescent activity-based probe (ABP) specific to calpain-1, enabling its visualization in living cells. We further investigated calpain-1’s expression alongside cell death proteins in immune cells using mass cytometry and observed strong colocalization with gasdermin D (GSDMD). Additionally, we demonstrated that calpain-1 can hydrolyze GSDMD <em>in vitro</em>. Through fluorescence-based substrate assays and mass spectrometry, we identified putative cleavage sites within the GSDMD sequence that may promote pyroptosis. These findings underscore calpain-1’s multifaceted role in cell death pathways, extending beyond apoptosis.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 4","pages":"Pages 603-619.e7"},"PeriodicalIF":6.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Silas T. Miller , Christian B. Macdonald , Srivatsan Raman
{"title":"Understanding, inhibiting, and engineering membrane transporters with high-throughput mutational screens","authors":"Silas T. Miller , Christian B. Macdonald , Srivatsan Raman","doi":"10.1016/j.chembiol.2025.03.003","DOIUrl":"10.1016/j.chembiol.2025.03.003","url":null,"abstract":"<div><div>Promiscuous membrane transporters play vital roles across domains of life, mediating the uptake and efflux of structurally and chemically diverse substrates. Although many transporter structures have been solved, the fundamental rules of polyspecific transport remain inscrutable. In recent years, high-throughput genetic screens have solidified as powerful tools for comprehensive, unbiased measurements of variant function and hypothesis generation, but have had infrequent application and limited impact in the transporter field. In this primer, we describe the principles of high-throughput screening methods available for studying polyspecific transporters and comment on the necessity and potential of high-throughput methods for deciphering these transporters in particular. We present several screening approaches which could provide a fundamental understanding of the molecular basis of function and promiscuity in transporters. We further posit how this knowledge can be leveraged to design inhibitors that combat multidrug resistance and engineer transporters as needed tools for synthetic biology and biotechnology applications.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 4","pages":"Pages 529-541"},"PeriodicalIF":6.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yizhen Jin , Sadhan Jana , Mikail E. Abbasov , Hening Lin
{"title":"Antibiotic target discovery by integrated phenotypic and activity-based profiling of electrophilic fragments","authors":"Yizhen Jin , Sadhan Jana , Mikail E. Abbasov , Hening Lin","doi":"10.1016/j.chembiol.2025.02.001","DOIUrl":"10.1016/j.chembiol.2025.02.001","url":null,"abstract":"<div><div>The emergence of antibiotic resistance necessitates the discovery of novel bacterial targets and antimicrobial agents. Here, we present a bacterial target discovery framework that integrates phenotypic screening of cysteine-reactive fragments with competitive activity-based protein profiling to map and functionally characterize the targets of screening hits. Using this approach, we identify β-ketoacyl-acyl carrier protein synthase III (FabH) and MiaA tRNA prenyltransferase as primary targets of a hit fragment, 10-F05, that confer bacterial stress resistance and virulence in <em>Shigella flexneri</em>. Mechanistic investigations elucidate that covalent C112 modification in FabH, an enzyme involved in bacterial fatty acid synthesis, results in its inactivation and consequent growth inhibition. We further demonstrate that irreversible C273 modification at the MiaA RNA-protein interaction interface abrogates substrate tRNA binding, attenuating resistance and virulence through decreased translational accuracy. Our findings underscore the efficacy of integrating phenotypic and activity-based profiling of electrophilic fragments to accelerate the identification and pharmacologic validation of new therapeutic targets.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 3","pages":"Pages 434-448.e9"},"PeriodicalIF":6.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143507382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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