bioRxiv : the preprint server for biology最新文献

{"title":"Comparative proteomic analysis of skin wound healing responses to biomaterial treatments identifies key pathways which govern differential regenerative outcomes.","authors":"Alejandra Suarez-Arnedo, Eleanor L P Caston, Yining Liu, Hongxia Baia, David Muddiman, Tatiana Segura","doi":"10.1101/2025.05.19.654672","DOIUrl":"https://doi.org/10.1101/2025.05.19.654672","url":null,"abstract":"<p><p>The wound healing cascade is characterized by the steady progression of distinct stages. Though biomaterials are used clinically to enhance wound closure rate and quality of healed tissue, their mechanisms of action are less understood. Here we use proteomic analysis to characterize changes in the wound healing response across three biomaterial treatments: a clinically used collagen hydrogel, and two synthetic biomaterials that are characterized by an increased regenerative response either through decreased fibrosis or through an activation of adaptive immunity. We identified close to 5,000 proteins shared across the biomaterial treatment groups, sampled at timepoints representing the inflammation, proliferation, and resolution phases of wound healing. The collagen hydrogel maintains an enrichment of immune-related pathways throughout the healing process. The fibrosis-suppressing material enriches gene ontology (GO) terms related to increased epidermis development pathways, collagen synthesis, and collagen fibril organization. In contrast, the adaptive immunity-activating biomaterial shows an early enrichment of GO terms related to broad immunity and inflammation. Later, this same material promotes keratinization, muscle and lipid oxidation GO pathways. Taken together, this work determines the key temporal pathways (immunity, keratinization, muscle system process, and ECM organization) mediated by three biomaterials, which result in varying healed tissue structure.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12139933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interaction of yeast V-ATPase with TLDc protein Rtc5p.","authors":"Md Murad Khan, Roshanak Ebrahimi, Rebecca A Oot, Stephan Wilkens","doi":"10.1101/2025.05.24.655954","DOIUrl":"https://doi.org/10.1101/2025.05.24.655954","url":null,"abstract":"<p><p>The eukaryotic vacuolar H ⁺ -ATPase (V-ATPase) is regulated by reversible disassembly into autoinhibited V ₁ -ATPase and V _o proton channel subcomplexes, a mode of regulation conserved from yeast to humans. While signals that govern V-ATPase assembly have been studied in the cellular context, the molecular mechanisms of the process at the level of the enzyme remain poorly understood. We recently discovered that Oxr1p, one of the two TLDc domain proteins in yeast, is essential for rapid V-ATPase <i>disassembly in vivo</i> . How the second TLDc protein, Rtc5p, functions in reversible disassembly, however, is less clear. Here we find that Rtc5p promotes assembly of functional holo V-ATPase from purified V ₁ and V _o subcomplexes <i>in vitro</i> . CryoEM structures show that Rtc5p's TLDc domain binds the C-terminal domain of the V ₁ -B subunit, with Rtc5p's C-terminal a-helix inserting into the catalytic hexamer, thereby opening a second catalytic site distal to its binding site. Unlike Oxr1p, however, which when deleted produces a distinct phenotype, Rtc5p does not appear to be essential for glucose driven enzyme (re)assembly, hinting at the presence of multiple assembly pathways <i>in vivo</i> .</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12139955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient-Derived Three-Dimensional Lung Tumor Models to Evaluate Response to Immunotherapy.","authors":"Kayla F Goliwas, Kenneth P Hough, Sruti Sivan, Sierra L Single, Sameer S Deshmukh, Joel L Berry, Maya Khalil, Benjamin Wei, Yanis Boumber, Mohammad Athar, Aakash Desai, Selvarangan Ponnazhagan, James M Donahue, Jessy S Deshane","doi":"10.1101/2025.05.19.654890","DOIUrl":"https://doi.org/10.1101/2025.05.19.654890","url":null,"abstract":"<p><p>Novel preclinical models that better mimic the <i>in vivo</i> tumor microenvironment are needed for advanced understanding of tumor biology and resistance/response to therapy. Herein, we report development of a novel <i>ex vivo</i> patient-derived three-dimensional lung tumor model (3D-LTM), that maintains features of human extracellular matrix, cell-cell interactions, and tissue architecture to evaluate a rapid response to immune checkpoint inhibitors (ICI). Within this model system, we recapitulated the heterogeneity of response to immunotherapy observed in non-small cell lung cancer (NSCLC) patients and defined signatures associated with response for predicting early response of ICI in patients. Spatial transcriptomics of the 3D-LTMs identified positive correlation of CD8 ⁺ T cell populations, CD4 ⁺ memory T cells, mast cells, NK cells, endothelial cells and non-classical monocytes with response status, whereas macrophages negatively correlated with response status. Pathway analysis of gene expression showed that chemokine signaling related pathways were activated in responder 3D-LTM tissues, whereas suppression of antigen presentation-related pathways and activation of T _reg differentiation-related pathways was associated with 3D-LTMs that were not considered responders. This model system has utility for rapid testing of novel immune directed therapy outcomes and for developing biomarkers of ICI response in NSCLC.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12139938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phosphorylation enables allosteric control of a viral condensate.","authors":"Julia Acker, Xinyu Wang, Daniel Desirò, Tanushree Agarwal, Alice Colyer, Cyril Haller, Rob Scrutton, Lee Sherry, Kadi L Saar, Rosie Murray, Ksenia Fominykh, Sai Hou Chong, Jeremy D Schmit, Antonio N Calabrese, Tuomas P J Knowles, Alexander Borodavka","doi":"10.1101/2025.05.24.655949","DOIUrl":"https://doi.org/10.1101/2025.05.24.655949","url":null,"abstract":"<p><p>In many viruses, intrinsically disordered proteins (IDPs) drive the formation of replicative organelles essential for viral production. In species A rotaviruses, the disordered protein NSP5 forms condensates in cells via liquid-liquid phase separation (LLPS). Yet the sequence diversity of NSP5 raises the question of whether condensate formation is conserved across all strains and if distinct variants employ alternative mechanisms for nucleating phase separation. Using a machine learning approach, we demonstrate that NSP5 variants differ significantly in their propensity to phase-separate. We engineered a variant incorporating amino acid signatures from strains with low LLPS tendency, which failed to phase separate in vitro yet supported the formation of replicative condensates in recombinant viruses in cells. Low-tendency LLPS strains require phosphorylation of NSP5 to nucleate phase separation, whereas high-tendency strains do not, suggesting distinct nucleation mechanisms. Furthermore, hydrogen-deuterium exchange mass spectrometry revealed a phosphorylation-driven allosteric switch between binding sites on the high-propensity variant. These findings establish that phosphorylation plays a context-dependent role in the formation of replicative organelles across diverse rotaviruses.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12139845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Tandem Repeat Atlas for the Genome of Inbred Mouse Strains: A Genetic Variation Resource.","authors":"Wenlong Ren, Weida Liu, Zhuoqing Fang, Egor Dolzhenko, Ben Weisburd, Zhuanfen Cheng, Gary Peltz","doi":"10.1101/2025.05.23.655792","DOIUrl":"https://doi.org/10.1101/2025.05.23.655792","url":null,"abstract":"<p><p>Tandem repeats (TRs) are a significant source of genetic variation in the human population; and TR alleles are responsible for over 60 human genetic diseases and for inter-individual differences in many biomedical traits. Therefore, we utilized long-read sequencing and state of the art computational programs to produce a database with 2,528,854 TRs covering 39 inbred mouse strains. As in humans, murine TRs are abundant and were primarily located in intergenic regions. However, there were important species differences: murine TRs did not have the extensive number of repeat expansions like those associated with human repeat expansion diseases and they were not associated with transposable elements. We demonstrate by analysis of two biomedical phenotypes, which were identified over 40 years ago, that this TR database can enhance our ability to characterize the genetic basis for trait differences among the inbred strains.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12139781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel PFAS in Alligator Blood Discovered with Non-Targeted Ion Mobility Spectrometry-Mass Spectrometry.","authors":"Anna K Boatman, Gregory P Kudzin, Kylie D Rock, Matthew P Guillette, Frank Robb, Scott M Belcher, Erin S Baker","doi":"10.1101/2025.03.20.644452","DOIUrl":"10.1101/2025.03.20.644452","url":null,"abstract":"<p><p>Per- and polyfluoroalkyl substances (PFAS) are a large and growing class of chemicals gaining global attention due to their persistence, mobility, and toxicity. Given the diverse chemical properties of PFAS and their varying distributions in water and tissue, monitoring of different matrices is critical to determine their presence and accumulation. Here, we used a platform combining liquid chromatography, ion mobility spectrometry, and high-resolution mass spectrometry for non-targeted analysis to detect and identify PFAS in alligator plasma from North Carolina (5 years, 2018-2022) and Florida (2021 only). Structures for 12 PFAS were elucidated, including 2 novel structures, and an additional 34 known PFAS were detected. Three of these compounds were previously unreported in environmental media. More PFAS were detected in North Carolina alligators and no novel PFAS were detected in Florida gators. Quantitative analysis of 21 of the known PFAS revealed that plasma concentrations did not change over the 5-year study.</p><p><strong>Highlights: </strong>46 PFAS were detected in blood plasma from North Carolina and Florida alligators using LC-IMS-HRMSStructures for 12 previously unreported PFAS were elucidated, including 2 novel structuresCape Fear River alligators had the most types and highest concentrations of PFAS.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A screen of chromatin-targeting compounds identifies TAF1 as a novel regulator of HIV latency.","authors":"Samuel D Burgos, Airlie M Ward, Manickam Ashokkumar, Kimberly P Enders, Lindsey I James, David M Margolis, Edward P Browne","doi":"10.1101/2025.05.24.655900","DOIUrl":"https://doi.org/10.1101/2025.05.24.655900","url":null,"abstract":"<p><p>Antiretroviral therapy (ART) suppresses HIV replication but fails to eliminate the virus due to the persistence of a transcriptionally silent reservoir, which remains the primary barrier to a cure. HIV latency is maintained through chromatin-mediated repression, making epigenetic regulators attractive therapeutic targets. To identify new modulators of latency, we screened a focused library of 84 chromatin-targeting small molecules. This screen identified BAY-299, a bromodomain inhibitor selective for TAF1 and BRD1, as a latency-modulating compound. BAY-299 reactivated HIV expression and enhanced the efficacy of established latency-reversing agents (LRAs), including vorinostat, prostratin, and iBET-151, in cell line models. CRISPR/Cas9-mediated knockout experiments demonstrated that TAF1, but not BRD1, is essential for maintaining HIV latency and that TAF1 depletion selectively increases HIV transcription with minimal effects on host gene expression. Dual knockout of TAF1 and Tat revealed that the reactivation effect is partially Tat dependent. CUT&RUN analysis further showed that TAF1 depletion increases RNA Polymerase II occupancy across the HIV gene body, suggesting enhanced transcriptional elongation. These findings identify TAF1 as a novel regulator of HIV latency and demonstrate the utility of targeted chemical screening to uncover therapeutic vulnerabilities within the latent reservoir.</p><p><strong>Importance: </strong>HIV remains incurable due to the persistence of a transcriptionally silent reservoir in infected cells that is not eliminated by antiretroviral therapy. This transcriptionally silent state, known as latency, is controlled by host cell factors that regulate access to the viral genome. In this study, we identified the host protein TAF1 as a key regulator that maintains HIV in a latent state. Using both genetic and chemical approaches, we demonstrated that reducing TAF1 levels selectively increases HIV gene expression without broadly disrupting host gene transcription. These findings highlight a previously unrecognized mechanism of HIV latency control and identify TAF1 as a potential therapeutic target. Understanding how host chromatin regulators contribute to latency is essential for developing strategies that aim to eliminate the persistent HIV reservoir.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12139756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pleiotropic mutational effects on function and stability constrain the antigenic evolution of influenza hemagglutinin.","authors":"Timothy C Yu, Caroline Kikawa, Bernadeta Dadonaite, Andrea N Loes, Janet A Englund, Jesse D Bloom","doi":"10.1101/2025.05.24.655919","DOIUrl":"https://doi.org/10.1101/2025.05.24.655919","url":null,"abstract":"<p><p>The evolution of human influenza virus hemagglutinin (HA) involves simultaneous selection to acquire antigenic mutations that escape population immunity while preserving protein function and stability. Epistasis shapes this evolution, as an antigenic mutation that is deleterious in one genetic background may become tolerated in another. However, the extent to which epistasis can alleviate pleiotropic conflicts between immune escape and protein function/stability is unclear. Here, we measure how all amino acid mutations in the HA of a recent human H3N2 influenza strain affect its cell entry function, acid stability, and neutralization by human serum antibodies. We find that epistasis has enabled emergence of antigenic mutations that were detrimental to HA's cell entry function in earlier strains. However, epistasis appears insufficient to overcome the pleiotropic costs of antigenic mutations that impair HA's stability, explaining why some mutations that strongly escape human antibodies never fix in nature. Our results refine our understanding of the mutational constraints that shape influenza evolution: epistasis can enable antigenic change, but pleiotropic effects can restrict its trajectory.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12139742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"sandwrm: an R package for estimating Wright's neighborhood size and species-level genetic diversity.","authors":"Zachary B Hancock, Gideon S Bradburd","doi":"10.1101/2025.05.19.654925","DOIUrl":"https://doi.org/10.1101/2025.05.19.654925","url":null,"abstract":"<p><p>In most natural populations, individuals in close proximity are more related on average than those at greater distances; this pattern gives rise to geographic population genetic structure. Despite extensive theoretical work on spatial population genetics, few empirical methods exist to estimate the components of theoretical models of genetic relatedness in continuous space. One classic model of relatedness in continuous space is the Wright-Malécot model, which predicts that the probability of identity-by-descent decays as a function of geographic distances. The shape of this decay curve is dictated by the dynamics of local dispersal and mating, as well as population density. This model can be reformulated to describe the probability of identity-by-state, in which case it decays to an asymptote, the value of which is determined by the historical demography of the population. Collectively, these features can be modeled in a likelihood-based framework to estimate neighborhood size and long-term diversity from pairwise genetic and geographic distance. In this article, we introduce the R package sandwrm Spatial Analysis of Neighborhood size and Diversity using WRight-Malécot), which takes a Bayesian approach to estimate key parameters of populations that are both dispersal-limited and distributed continuously across a landscape.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12139757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selectivity filter mutation in Na _V 1.5 promotes ventricular tachycardia.","authors":"Zoja Selimi, Mikhail Tarasov, Xiaolei Meng, Patrícia Dias, Bianca Moise, Rengasayee Veeraraghavan, Przemysław B Radwański","doi":"10.1101/2025.05.19.654350","DOIUrl":"https://doi.org/10.1101/2025.05.19.654350","url":null,"abstract":"<p><p>Loss-of-Function (LoF) mutations in the <i>SCN5A</i> gene, which encodes for the predominant cardiac Na _V isoform, Na _V 1.5 result in either deficiency in the channel expression or function. Impaired Na _V 1.5 expression and function underlie reduced peak Na ⁺ current (I _Na ) and result in ventricular conduction velocity slowing, predisposing the heart to conduction block and ventricular arrhythmias clinically associated with Brugada syndrome (BrS). Recently, a missense mutation in Na _V 1.5 selectivity filter (DEKA motif), K1419E (DE <b>E</b> A) has been identified in patients with BrS. Despite early characterization of mutations in selectivity filter of other Na _V isoforms, little is known about the impact of DE <b>E</b> A on Na _V 1.5 function as well as on cardiac electrophysiology. Therefore, we generated a mouse heterozygous for Na _V 1.5 DE <b>E</b> A to characterize the mutation and investigate the outcome of this functionally deficient Na _V 1.5 variant on cardiac electrophysiology and arrhythmias. Heterologous expression system and isolated cardiomyocytes revealed lower current density and unchanged Na _V 1.5 expression in DE <b>E</b> A vs. wild type (DEKA). On the organ level, optical mapping revealed conduction velocity slowing in DE <b>E</b> A hearts, which was accentuated by flecainide resulting <i>in vivo</i> ventricular arrhythmias. Overall, to our knowledge, we provide the first mechanistic insight into the proarrhythmic consequences of a functionally deficient BrS mutation in Na _V 1.5.</p><p><strong>Condensed abstract: </strong>Na _V 1.5 mutations have been associated with life-threatening arrhythmias. Recently, a selectivity filter mutation (K1419E-Na _V 1.5, DEKA→DE <b>E</b> A), has been linked to Brugada Syndrome (BrS). While DEKA mutations in other Na _V isoforms affected channel conductance, the impact of DE <b>E</b> A on Na _V 1.5 and arrhythmogenesis is unknown. Therefore, we generated mice heterozygous for Na _V 1.5-DE <b>E</b> A. Cardiomyocytes isolated from DE <b>E</b> A hearts exhibited substantial reduction in sodium current, ventricular conduction slowing and susceptibility to ventricular arrhythmias in vivo that were unmasked by flecainide. Together, DE <b>E</b> A murine model is the first to recapitulate a functional deficiency in Na _V 1.5, and thus offers insight into the proarrhythmic mechanism of BrS.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12139751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}