PLoS Biology最新文献

{"title":"Cyclic tri-adenylate controls a CARF-TM effector in type II Panoptes anti-phage systems.","authors":"Sabine Grüschow, Peter Wotherspoon, Emma Hilton-Balfe, Shirley Graham, Malcolm F White","doi":"10.1371/journal.pbio.3003934","DOIUrl":"10.1371/journal.pbio.3003934","url":null,"abstract":"<p><p>Cyclic nucleotide second messengers are used in all domains of life to amplify viral infection signals and activate cellular defences. In prokaryotes, CBASS (cyclic nucleotide-based antiphage signalling system) and type III CRISPR-Cas systems generate a range of cyclic nucleotides which bind and allosterically activate effector proteins to mount an anti-viral response. Viruses have evolved counter measures to antagonise these signalling pathways in the form of cyclic nucleotide sponges and phosphodiesterases that sequester or degrade these molecules to subvert immunity. Recently, the Panoptes system was shown to function as a guard against these viral tactics. The type I Panoptes polymerase, mCpol, generates cyclic dinucleotides as decoy molecules that, when sequestered by phage proteins, results in the activation of the membrane-permeabilising effector 2TMβ to halt the phage infection cycle. Here, we investigate the type II Panoptes system, demonstrating that it generates cyclic tri-adenylate (cA3) to maintain a CRISPR-associated Rossmann fold-transmembrane (CARF-TM) effector in an inactive, dimeric state. When cA3 is sequestered or degraded, the CARF protein undergoes conformational changes. In vivo, the absence of cA3 results in membrane disruption and growth arrest. Type II Panoptes provides defence against phages that express the cA3-degrading enzyme Acb1; phage escapers introduce mutations into the acb1 gene to avoid triggering the Panoptes system. These findings expand our understanding of the guard systems that constitute a fascinating component of the bacterial immune system.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 9","pages":"e3003934"},"PeriodicalIF":7.2,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13577387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148978440","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}

{"title":"R1-32-like public antibodies acquire tolerance to SARS-CoV-2 antigenic drift through somatic hypermutation.","authors":"Chuanying Niu, Xiaohan Huang, Qihong Yan, Banghui Liu, Xijie Gao, Yidong Song, Jingjing Wang, Longyu Wang, Zimu Li, Huiran Zheng, Ping He, Xiaodong Huang, Hang Yuan, Binqian Zou, Yuedong Yang, Fandi Wu, Yicheng Yao, Gul Habib, Xinwen Chen, Ling Chen, Jun He, Jianhua Yao, Jincun Zhao, Xiaoli Xiong","doi":"10.1371/journal.pbio.3003996","DOIUrl":"10.1371/journal.pbio.3003996","url":null,"abstract":"<p><p>R1-32-like public antibodies, characterized by shared IGHV1-69/IGLV1-40 usage, are elicited in more than 50% of individuals with COVID-19 and have been implicated in driving recurrent mutations at L452SARS2 and F490SARS2 within their convergent epitope in the SARS-CoV-2 spike receptor-binding domain. These mutations effectively mediate escape from non-affinity-matured R1-32-like antibodies with germline-like sequences. Here, we characterize four affinity-matured human R1-32-like antibodies, C092, C807, BD56-104, and BD56-597, that tolerate L452SARS2 and F490SARS2 mutations. We show that this tolerance arises from residues introduced by somatic hypermutation at convergent positions across multiple CDR loops and surrounding regions, thereby creating additional contacts that reinforce epitope binding. An unusual N354SARS2 glycosylation site, which emerged in BA.2.86 and became fixed in its descendants, is linked to escape from affinity-matured R1-32-like antibodies, implying ongoing selection by this public antibody class. Using an AI model trained on extensive neutralization data, we further identified ZL525, an ultrapotent human R1-32-like antibody with pan-SARS-CoV-2 variant activity, including against the highly evasive KP.3 variant carrying the N354SARS2 glycosylation, and broad sarbecovirus cross-reactivity extending to SARS-CoV-1. Together, these findings show how affinity maturation enables public antibodies to adapt to viral antigenic drift, reveal how public antibody responses contribute to shaping SARS-CoV-2 antigenic evolution, and demonstrate the potential of AI-empowered strategies for discovering broadly neutralizing antibodies.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 9","pages":"e3003996"},"PeriodicalIF":7.2,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13667928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148978446","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}

{"title":"How the mosquito's carbon dioxide sense gets an internal boost.","authors":"Chih-Ying Su","doi":"10.1371/journal.pbio.3003958","DOIUrl":"10.1371/journal.pbio.3003958","url":null,"abstract":"<p><p>Mosquitoes use CO2 as a critical cue to sense if humans are nearby. A new study in PLOS Biology reveals that CO2-sensing neurons in mosquitoes can amplify each other's signals, creating a neural echo chamber that may explain the remarkable sensitivity of mosquitoes to human presence.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 9","pages":"e3003958"},"PeriodicalIF":7.2,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13567756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148946079","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}

{"title":"Recurrent synapses between CO2-sensitive olfactory sensory neurons enable robust CO2 detection in Aedes aegypti mosquitoes.","authors":"Jialu Bao, Wesley Alford, Avinash Khandelwal, Laurel Walsh, George Lantz, Santiago Poncio, Laia Serratosa Capdevila, Yervand Azatian, Brian DePasquale, David G C Hildebrand, Meg A Younger, Wei-Chung Allen Lee","doi":"10.1371/journal.pbio.3003959","DOIUrl":"10.1371/journal.pbio.3003959","url":null,"abstract":"<p><p>The mosquito Aedes aegypti's human host-seeking behavior depends on the integration of multiple sensory cues. One of these cues, carbon dioxide (CO2), gates odorant and heat pathways and activates host-seeking behavior. The neuronal circuits underlying processing of CO2 information remain unclear. We used automated serial-section transmission electron microscopy (EM) to image and reconstruct the circuitry of the glomeruli that are innervated by the Ae. aegypti maxillary palp, including the glomerulus that responds to CO2. Notably, CO2-sensitive olfactory sensory neurons (OSNs) make high levels of recurrent synaptic connections with one another, while making a low density of feedforward synapses. At some of these contacts between CO2 OSNs, we observe ribbon-like presynaptic structures, which may further enhance recurrent signaling. We compared both feedforward and recurrent connectivity with all olfactory glomeruli in Drosophila melanogaster, and we found more recurrent connections between the Ae. aegypti CO2-responsive OSNs than in any D. melanogaster glomeruli. We developed a computational circuit model that demonstrates recurrent synapses are necessary for robust CO2 detection under normal physiological conditions. Together, elevated levels of recurrent connectivity and ribbon-like structures may amplify sensory information detected by CO2-sensitive OSNs to support mosquito activation and sensitization by CO2, even in the presence of high levels of other odorants in the environment. We propose that this circuit organization supports the salience of CO2 as a mosquito host cue.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 9","pages":"e3003959"},"PeriodicalIF":7.2,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13561330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931779","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}

{"title":"Brain structural and functional connectivity converge prenatally but diverge after birth.","authors":"Ruoke Zhao, Mingyang Li, Yuqi Zhang, Ruike Chen, Chenglin Ning, Zhiyong Zhao, Zhihan Yan, Meihao Wang, Dan Wu","doi":"10.1371/journal.pbio.3003927","DOIUrl":"10.1371/journal.pbio.3003927","url":null,"abstract":"<p><p>Brain anatomical architecture supports its functional activity and complex cognitive processes. However, how the structure-function (SF) relationship establishes and develops during early life, as well as its underlying mechanisms, remain largely unclear. To address these questions, we leveraged multimodal MRI data from two large-scale public databases, the developing Human Connectome Project (dHCP) and the Baby Connectome Project (BCP), to characterize the spatiotemporal dynamics of SF coupling from the perinatal period to toddlerhood. Our results revealed that SF coupling at birth exhibited a spatial variation along the sensorimotor-association cortical axis. During the perinatal period (26-44 postmenstrual weeks), SF coupling strengthened drastically and followed three distinct developmental trajectories across the cortex, with sensorimotor and visual areas showing the fastest growth and the earliest plateau. After birth, SF coupling shifted toward a weakening pattern across the cortex during infancy and toddlerhood (1-28 months). These developmental changes of SF coupling were more strongly associated with the maturation of functional connectivity, which first converged toward the local structural architecture prenatally and then diverged postnatally through the expansion of global inter-modular pathways. Furthermore, SF coupling at birth, the developmental transition point, exhibited a significant association with individual differences in cognition and language outcomes at 18 months of age. Collectively, these findings offer valuable insights into the organizational principles underlying structural and functional network development during early life as well as the complex evolving relationship between them.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 9","pages":"e3003927"},"PeriodicalIF":7.2,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13557396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148921468","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}

{"title":"Seaweed carbon removal cannot keep up with climate-driven loss.","authors":"Karen Filbee-Dexter, Albert Pessarrodona, Kira A Krumhansl, Thomas Wernberg","doi":"10.1371/journal.pbio.3003949","DOIUrl":"10.1371/journal.pbio.3003949","url":null,"abstract":"<p><p>The prevailing narrative of seaweed carbon as a possible climate change mitigation solution overlooks the central challenge that climate change itself is adversely impacting seaweed forests worldwide, potentially shifting these ecosystems from carbon sinks to carbon sources. In this Essay, we show that climate-induced seaweed forest loss is eroding their carbon sink capacity three to four orders of magnitude (1,000-10,000×) faster than it can currently be restored or recovered through active interventions. We consider that this stark disparity calls for a fundamental shift in seaweed carbon research away from a focus on future sequestration gains and toward explicitly assessing the risk of carbon emissions from climate-driven ecosystem loss.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 9","pages":"e3003949"},"PeriodicalIF":7.2,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13552959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148913812","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}

{"title":"Growth-rate coordination across the width of a leaf preserves its flatness.","authors":"Kate Harline, Brendan Lane, Maura J Zimmermann, Antoine Fruleux, Gabriella Mosca, Sören Strauss, Nik Tavakolian, James W Satterlee, Chun-Biu Li, Abhyudai Singh, Arezki Boudaoud, Richard S Smith, Adrienne H K Roeder","doi":"10.1371/journal.pbio.3003993","DOIUrl":"10.1371/journal.pbio.3003993","url":null,"abstract":"<p><p>The growth and division of cells in plant leaves is highly dynamic in time and space, even though cells cannot move relative to their neighbors. Thus, organ shape must emerge from carefully coordinated growth, especially in leaves that remain relatively flat as they grow. Here we explored the phenotype of the jagged and wavy (jaw-D) mutant in Arabidopsis thaliana, in which the leaves do not remain flat. It has previously been shown that the jaw-D mutant phenotype is caused by the overexpression of miR319, which represses TCP transcription factors, thus delaying maturation of the leaf. We analyzed cell dynamics in wild type and jaw-D by performing time-lapse live imaging of developing leaves. We found that the progression of maturation from the tip of the leaf downward was delayed in jaw-D relative to wild type based on several markers of maturation, in agreement with the role of TCP transcription factors in promoting maturation. We further found that these changes in maturation were accompanied by differences in the coordination of growth across the leaf, particularly across the mediolateral axis, causing growth conflicts that prevent the leaf from remaining flat. Modeling revealed that curvature develops when growth is uneven across the leaf in the direction perpendicular to the direction of growth. Although leaf flatness is often framed as a problem that requires the local synchronization of growth on the abaxial versus adaxial sides (bottom versus top) of the leaf, our results based on the jaw-D phenotype suggest that wild-type plants also need to coordinate growth more globally across the leaf blade to maintain flatness.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 9","pages":"e3003993"},"PeriodicalIF":7.2,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13585336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148913884","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}

{"title":"Discovery Stack Pilot demonstrates the feasibility and outcomes of a scientist-designed peer-review model that separates quality and impact.","authors":"Maureen A McGargill, Beiyun C Liu, Michael S Kuhns, Daniel Mucida, Isabella Rauch, Lauren B Rodda, Meghan A Koch, Hugo Gonzalez Velozo, Ken Cadwell, Tanya S Freedman, Tiffany C Scharschmidt, Richard Sever, Jose Ordovas-Montanes, Sara Suliman, Andrew Oberst, Brooke Runnette, Matthew F Krummel","doi":"10.1371/journal.pbio.3003986","DOIUrl":"10.1371/journal.pbio.3003986","url":null,"abstract":"<p><p>Peer review serves as the cornerstone of scientific quality control. Yet, the current journal-centric system is hindered by long timelines, high publication costs, inconsistent review quality, systemic biases, and editorial gatekeeping. Notably, the system relies on misaligned measures of impact that are tethered to journal branding and conflate scientific rigor (Quality) with perceived significance (Impact). Here, we report findings from the Discovery Stack Pilot Study, which tested a scientist-designed, journal-independent peer review model. The Discovery Stack model integrates in-line reviewer comments to promote constructive feedback and separately evaluates scientific Quality and Impact using defined criteria. To examine feasibility and effectiveness, manuscripts were reviewed in parallel with traditional journal review. A total of 162 reviews were completed, and survey data from 86 participants were analyzed. The results showed that reviewers effectively evaluated Quality and Impact as separate dimensions, with Quality scores being more consistent across reviewers than Impact scores. Participants strongly supported the core elements of the Discovery Stack model and expressed enthusiasm for its broader adoption to enhance transparency, efficiency, and value in peer review. Future studies will explore integrating this model into a digital platform for reviewing and curating scientific discoveries to improve the production and dissemination of high-quality research.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 9","pages":"e3003986"},"PeriodicalIF":7.2,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13614658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148913820","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}

{"title":"The distribution of fitness effects of nonsynonymous mutations varies phylogenetically across animals.","authors":"Meixi Lin, Sneha Chakraborty, Carlos Eduardo G Amorim, Sergio F Nigenda-Morales, Annabel C Beichman, Paulina G Nuñez-Valencia, Jonathan C Mah, Jacqueline A Robinson, Christopher C Kyriazis, Christian D Huber, Andrew E Webb, Sarah D Kocher, Frederick I Archer, Andrés Moreno-Estrada, Robert K Wayne, Kirk E Lohmueller","doi":"10.1371/journal.pbio.3003976","DOIUrl":"10.1371/journal.pbio.3003976","url":null,"abstract":"<p><p>The distribution of fitness effects (DFE) describes the selection coefficients of newly arising mutations and fundamentally influences population genetic processes. However, the extent and mechanisms of differences in the DFE for non-synonymous mutations have not been systematically investigated across species with divergent phylogenetic histories and ecologies. Here, we inferred the DFE in natural populations of 11 animal (sub)species, including humans, mice, fin whales, vaquitas, wolves, collared flycatchers, pied flycatchers, halictid bees, Drosophila, and mosquitoes. We found that mammals have a higher proportion of strongly deleterious mutations (defined as s≤-0.01; 22% to 47% in mammals; 0.0% to 5.4% in insects and birds) and a lower proportion of weakly deleterious mutations than insects and birds. Further, the DFE co-varies with phylogeny, such that the mean mutation effects are more similar in closely related species (Pagel's λ = 0.84, P = 0.01). Next, we investigated whether various summary statistics of the DFE were related to variation in life-history traits across these organisms. We found some support for genome size, body mass, and long-term effective population size being correlated with the DFE. Overall, our findings are consistent with predictions derived independently from the Fisher's Geometric Model (FGM), which defines organismal complexity as the number of phenotypes under selection. FGM predicts that mutations are more deleterious in complex organisms, while strongly deleterious mutations occur more frequently in smaller populations. Our study demonstrates strong phylogenetic signal in the evolution of a fundamental population genetics parameter, and proposes that, through mechanisms of epistasis, long-term population size and organismal complexity could be underlying variation in the DFE across animals.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 9","pages":"e3003976"},"PeriodicalIF":7.2,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13592725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148913806","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}

{"title":"Hyperglycemic stress aggravates diabetic retinopathy and nephropathy by promoting cilium disassembly via a deacetylation- and methylation-mediated regulatory mechanism.","authors":"Jie Ran, Changfeng Wei, Yang Yang, Yufei Zhang, Guizhi Guo, Nan Ma, Long Yin, Hongjun Fan, Jingrui Li, Heng Guo, Renshuai Zhang, Runa Wang, Dengwen Li, Min Liu","doi":"10.1371/journal.pbio.3003975","DOIUrl":"10.1371/journal.pbio.3003975","url":null,"abstract":"<p><p>Primary cilia are essential microtubule-based sensory organelles, and their dysfunction has been increasingly linked to metabolic stress. However, the underlying molecular mechanisms remain poorly understood. Herein, we reveal that ciliary defects in retinal photoreceptors and renal tubules exacerbate tissue damage during the progression of diabetic complications. Under hyperglycemic stress, protein arginine methyltransferase 1 (PRMT1) and histone deacetylase 6 (HDAC6) are significantly upregulated in both retinal and renal tissues. Genetic ablation of either enzyme effectively preserves ciliary architecture and restores organ function in diabetic mice. Mechanistically, PRMT1 localizes to the basal body, where it interacts with and methylates HDAC6 at arginine 16, consequently enhancing HDAC6 stability. In turn, HDAC6 mediates the deacetylation of PRMT1 at lysine 128, which elevates PRMT1 protein levels. This mutual modification crosstalk establishes a pathological positive feedback loop that stabilizes a pro-disassembly complex at the basal body, thereby potentiating ciliary impairment and expediting the progression of diabetic complications. Pharmacological inhibition of the PRMT1-HDAC6 loop significantly attenuates the pathological features of both diabetic retinopathy and nephropathy. Collectively, our findings uncover a reciprocal regulatory mechanism mediated by deacetylation and arginine methylation that drives cilium disassembly under hyperglycemic stress, providing promising therapeutic targets for the treatment of metabolic ciliopathies.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 9","pages":"e3003975"},"PeriodicalIF":7.2,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13541193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148888381","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}