bioRxiv : the preprint server for biology最新文献

{"title":"Histopathological Evaluation of Pulmonary Arterial Remodeling in COVID-19.","authors":"Sergiy G Gychka, Sofiia I Nikolaienko, Nataliia V Shults, Volodymyr M Vasylyk, Bohdan O Pasichnyk, Iryna V Kagan, Yulia V Dibrova, Muin Tuffaha, Yuichiro J Suzuki","doi":"10.1101/2024.12.12.628253","DOIUrl":"10.1101/2024.12.12.628253","url":null,"abstract":"<p><p>A positive-sense single-stranded RNA virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), caused the coronavirus disease 2019 (COVID-19) pandemic that devastated the world. While this is a respiratory virus, one feature of the SARS-CoV-2 infection was recognized to cause pathogenesis of other organs. Because the membrane fusion protein of SARS-CoV-2, the spike protein, binds to its major host cell receptor angiotensin-converting enzyme 2 (ACE2) that regulates a critical mediator of cardiovascular diseases, angiotensin II, COVID-19 is largely associated with vascular pathologies. In fact, we have previous reported that postmortem lung tissues collected from patients who died of COVID-19 exhibited thickened pulmonary vascular walls and reduced vascular lumen. The present study extended these findings by further characterizing the pulmonary vasculature of COVID-19 patients using larger sample sizes and providing mechanistic information through histological observations. The examination of 56 autopsy lung samples showed thickened vascular walls of small pulmonary arteries after 14 days of disease compared to H1N1 influenza patients who died before COVID- 19 pandemic started. Pulmonary vascular remodeling in COVID-19 patients was associated with hypertrophy of the smooth muscle layer, perivascular fibrosis, edema and lymphostasis, inflammatory infiltration, perivascular hemosiderosis and neoangiogenesis. We found a correlation between the duration of hospital stay and the thickness of the muscular layer of pulmonary arterial walls. These results further confirm that COVID-19 affects the pulmonary vasculature and warrants an evaluation of patients that survived COVID-19 for possible future development of pulmonary arterial hypertension.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11661234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142879365","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":"Angiotensin peptides enhance SARS-CoV-2 spike protein binding to its host cell receptors.","authors":"Katelin X Oliveira, Yuichiro J Suzuki","doi":"10.1101/2024.12.12.628247","DOIUrl":"10.1101/2024.12.12.628247","url":null,"abstract":"<p><p>Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus that caused the Coronavirus Disease 2019 (COVID-19) pandemic, has a spike glycoprotein that is involved in recognizing and fusing to host cell receptors, such as angiotensin-converting enzyme 2 (ACE2), neuropilin-1 (NRP1), and AXL tyrosine-protein kinase. Since the major spike protein receptor is ACE2, an enzyme that regulates angiotensin II (1-8), this study tested the hypothesis that angiotensin II (1-8) influences the binding of the spike protein to its receptors. While angiotensin II (1-8) did not influence spike-ACE2 binding, we found that it significantly enhances spike-AXL binding. Our experiments showed that longer lengths of angiotensin, such as angiotensin I (1-10), did not significantly affect spike-AXL binding. In contrast, shorter lengths of angiotensin peptides, in particular, angiotensin IV (3-8), strongly increased spike-AXL binding. Angiotensin IV (3-8) also enhanced spike protein binding to ACE2 and NRP1. The discovery of the enhancing effects of angiotensin peptides on spike-host cell receptor binding may suggest that these peptides could be pharmacological targets to treat COVID-19 and post-acute sequelae of SARS-CoV-2 (PASC), which is also known as long COVID.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11661167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142879198","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":"Monitoring in vivo transcription with synthetic serum markers.","authors":"Sho Watanabe, Sangsin Lee, Manwal Harb, Shirin Nouraein, Emma Raisley, Honghao Li, Nicolas Buitrago, Beatrice Pforr, Jerzy O Szablowski","doi":"10.1101/2024.12.10.627810","DOIUrl":"10.1101/2024.12.10.627810","url":null,"abstract":"<p><p>Understanding transcription profiles of living tissues is critical for biology and medicine. However, measurement of the transcript levels is typically done in homogenized tissues post-mortem. Here, we present a new platform that enables non-invasive monitoring of specific mRNA levels <i>in vivo</i> , without tissue destruction. We achieved this by combining two cutting-edge tools - synthetic serum markers, called Released Markers of Activity ( <b>RMAs</b> ), and RNA-based sensors of transcription. We call this platform IN-vivo Tracking of ACtive Transcription, or <b>INTACT</b> . In INTACT, when the target mRNA is expressed, the RNA sensor detects it and triggers the production and release of RMA reporters into the blood. Once in blood, the RMAs can be easily measured through a simple blood draw. Our data shows that INTACT can measure transcription of transgenes, as well as endogenous transcripts, such as <i>c-Fos</i> or <i>Arc</i> , both <i>in vivo</i> in the brain and in tissue culture. INTACT enables simple measurement of transcript level histories in genetically-targetable cell populations of living animals.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11661152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142879230","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":"CRISPR-Edited DPSCs, Constitutively Expressing BDNF Enhance Dentin Regeneration in Injured Teeth.","authors":"Ji Hyun Kim, Muhammad Irfan, Sreelekshmi Sreekumar, Stephanie Kim, Atsawasuwan Phimon, Seung Chung","doi":"10.1101/2024.12.11.627879","DOIUrl":"10.1101/2024.12.11.627879","url":null,"abstract":"<p><p>Dental caries is one of the most common health issues worldwide arising from the complex interactions of bacteria. In response to harmful stimuli, desirable outcome for the tooth is the formation of tertiary dentin, a protective reparative process that generates new hard tissue. This reparative dentinogenesis is associated with significant inflammation, which triggers the recruitment and differentiation of dental pulp stem cells (DPSCs). Previously, we have shown that brain-derived neurotrophic factor (BDNF) and its receptor TrkB, key mediators of neural functions, are activated during the DPSC-mediated dentin regeneration process. In this study, we further define the role of inflammation in this process and apply stem cell engineering to enhance dentin regeneration in injured teeth. Our data show that TrkB expression and activation in DPSCs rapidly increase during odontogenic differentiation, further amplified by inflammatory inducers and mediators such as TNFα, LTA, and LPS. An in vivo dentin formation assessment was conducted using a mouse pulp-capping/caries model, where CRISPR-engineered DPSCs overexpressing BDNF were transplanted into inflamed pulp tissue. This transplantation significantly enhanced dentin regeneration in injured teeth. To further explore potential downstream pathways, we conducted transcriptomic profiling of TNFα-treated DPSCs, both with and without TrkB antagonist CTX-B. The results revealed significant changes in gene expression related to immune response, cytokine signaling, and extracellular matrix interactions. Taken together, our study advances our understanding of the role of BDNF in dental tissue engineering using DPSCs and identifies potential therapeutic avenues for improving dental tissue repair and regeneration strategies.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11661210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142879496","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":"The kinesin KIF3AC recycles endocytosed integrin to polarize adhesion formation towards the leading edge.","authors":"Johnny A Z Rockenbach, Guilherme P F Nader, Susumu Antoku, Gregg G Gundersen","doi":"10.1101/2024.12.09.627580","DOIUrl":"10.1101/2024.12.09.627580","url":null,"abstract":"<p><p>The recycling of integrin endocytosed during focal adhesion (FA) disassembly is critical for cell migration and contributes to the polarized formation of new FAs toward the leading edge. How this occurs is unclear. Here, we sought to identify the kinesin motor protein(s) that is involved in recycling endocytosed integrin back to the plasma membrane. We show that the kinesin-2 heterodimer, KIF3AC and the Rab11 adaptor protein RCP are required for FA reformation after the disassembly of FAs in mouse and human fibroblasts. In the absence of KIF3AC, integrin does not return to the cell surface after FA disassembly and is found in the Rab11 endocytic recycling compartment. Biochemical pulldowns revealed that KIF3C associated with β1 integrin in an RCP dependent fashion, but only after FA disassembly. KIF3AC knockdown inhibited cell migration, trafficking of RCP toward the leading edge, and polarized formation of FAs at the leading edge. These results show that KIF3AC promotes cell migration by recycling integrin so that it generates new FAs in a polarized fashion.</p><p><strong>Summary: </strong>The study reveals that the heterodimeric kinesin-2 motor KIF3AC and its adaptor RCP are crucial for polarized formation of focal adhesions at the front of migrating fibroblasts. KIF3AC and RCP associate with intracellularly recycling integrin to promote its return to the cell surface after its endocytosis from disassembled focal adhesions.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11661233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142879562","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":"Molecular Crowding Suppresses Mechanical Stress-Driven DNA Strand Separation.","authors":"Parth Rakesh Desai, John F Marko","doi":"10.1101/2024.12.11.628023","DOIUrl":"10.1101/2024.12.11.628023","url":null,"abstract":"<p><p>Molecular crowding influences DNA mechanics and DNA - protein interactions and is ubiquitous in living cells. Quantifying the effects of molecular crowding on DNA supercoiling is essential to relating <i>in-vitro</i> experiments to <i>in-vivo</i> DNA supercoiling. We use single molecule magnetic tweezers to study DNA supercoiling in the presence of dehydrating or crowding co-solutes. To study DNA supercoiling, we apply a stretching force of 0.8 pN to the DNA and then rotate one end of the DNA to induce supercoiling. In a 200 mM NaCl buffer without co-solutes, negatively supercoiled DNA absorbs some of the tortional stress by forming locally melted DNA regions. The base-pairs in these locally melted regions are believed to adopt a configuration where nucleotide base pairing is disrupted. We find that the presence of dehydrating co-solutes like glycerol and ethylene glycol results in further destabilization of base-pairs in negatively supercoiled DNA. The presence of polyethylene glycol, commonly used as crowding agents, suppresses local strand separation and results in plectoneme formation even when DNA is negatively supercoiled. The results presented in this letter suggest many further directions for studies of DNA supercoiling and supercoiled DNA - protein interactions in molecular conditions that approximate <i>in-vivo</i> molecular composition.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11661227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142879078","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":"Analysis of natural structures and chemical mapping data reveals local stability compensation in RNA.","authors":"Robert L Cornwell-Arquitt, Riley Nigh, Michael T Hathaway, Joseph D Yesselman, David A Hendrix","doi":"10.1101/2024.12.11.627843","DOIUrl":"10.1101/2024.12.11.627843","url":null,"abstract":"<p><p>RNA molecules adopt complex structures that perform essential biological functions across all forms of life, making them promising candidates for therapeutic applications. However, our ability to design new RNA structures remains limited by an incomplete understanding of their folding principles. While global metrics such as the minimum free energy are widely used, they are at odds with naturally occurring structures and incompatible with established design rules. Here, we introduce local stability compensation (LSC), a principle that RNA folding is governed by the local balance between destabilizing loops and their stabilizing adjacent stems, challenging the focus on global energetic optimization. Analysis of over 100,000 RNA structures revealed that LSC signatures are particularly pronounced in bulges and their adjacent stems, with distinct patterns across different RNA families that align with their biological functions. To validate LSC experimentally, we systematically analyzed thousands of RNA variants using DMS chemical mapping. Our results demonstrate that stem reactivity correlates strongly with LSC (R² = 0.458 for hairpin loops) and that structural perturbations affect folding primarily within ~6 nucleotides from the loop. These findings establish LSC as a fundamental principle that could enhance the rational design of functional RNAs.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11661157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142879195","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 Xenografts of Triple-Negative Breast Cancer Enable Deconvolution and Prediction of Chemotherapy Responses.","authors":"Jonathan T Lei, Lacey E Dobrolecki, Chen Huang, Ramakrishnan R Srinivasan, Suhas V Vasaikar, Alaina N Lewis, Christina Sallas, Na Zhao, Jin Cao, John D Landua, Chang In Moon, Yuxing Liao, Susan G Hilsenbeck, C Kent Osborne, Mothaffar F Rimawi, Matthew J Ellis, Varduhi Petrosyan, Bo Wen, Kai Li, Alexander B Saltzman, Antrix Jain, Anna Malovannaya, Gerburg M Wulf, Elisabetta Marangoni, Shunqiang Li, Daniel C Kraushaar, Tao Wang, Senthil Damodaran, Xiaofeng Zheng, Funda Meric-Bernstam, Gloria V Echeverria, Meenakshi Anurag, Xi Chen, Bryan E Welm, Alana L Welm, Bing Zhang, Michael T Lewis","doi":"10.1101/2024.12.09.627518","DOIUrl":"10.1101/2024.12.09.627518","url":null,"abstract":"<p><p>Combination chemotherapy remains essential for clinical management of triple-negative breast cancer (TNBC). Consequently, responses to individual agents cannot be easily delineated at the single patient level, even though some patients might not require all drugs in the combination. Herein, we conduct multi-omic analyses of orthotopic TNBC patient-derived xenografts (PDXs) treated with single agent carboplatin, docetaxel, or the combination. Combination responses were usually no better than the best single agent, with enhanced response in only ~13% of PDX, and apparent antagonism in a comparable percentage. Single-omic comparisons showed largely non-overlapping results between genes associated with single agent and combination treatments that could be validated in independent patient cohorts. Multi-omic analyses of PDXs identified agent-specific biomarkers/biomarker combinations, nominating high Cytokeratin-5 (KRT5) as a general marker of responsiveness. Notably, integrating proteomic with transcriptomic data improved predictive modeling of pathologic complete response to combination chemotherapy. PDXs refractory to all treatments were enriched for signatures of dysregulated mitochondrial function. Targeting this process indirectly in a PDX with HDAC inhibition plus chemotherapy <i>in vivo</i> overcomes chemoresistance. These results suggest possible resistance mechanisms and therapeutic strategies in TNBC to overcome chemoresistance, and potentially allow optimization of chemotherapeutic regimens.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11661147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142879449","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":"Machine Learning Models for Segmentation and Classification of Cyanobacterial Cells.","authors":"Clair A Huffine, Zachary L Maas, Anton Avramov, Chris Brininger, Jeffrey C Cameron, Jian Wei Tay","doi":"10.1101/2024.12.11.628068","DOIUrl":"10.1101/2024.12.11.628068","url":null,"abstract":"<p><p>Timelapse microscopy has recently been employed to study the metabolism and physiology of cyanobacteria at the single-cell level. However, the identification of individual cells in brightfield images remains a significant challenge. Traditional intensity-based segmentation algorithms perform poorly when identifying individual cells in dense colonies due to a lack of contrast between neighboring cells. Here, we describe a newly developed software package called Cypose which uses machine learning (ML) models to solve two specific tasks: segmentation of individual cyanobacterial cells, and classification of cellular phenotypes. The segmentation models are based on the Cellpose framework, while classification is performed using a convolutional neural network named Cyclass. To our knowledge, these are the first developed ML-based models for cyanobacteria segmentation and classification. When compared to other methods, our segmentation models showed improved performance and were able to segment cells with varied morphological phenotypes, as well as differentiate between live and lysed cells. We also found that our models were robust to imaging artifacts, such as dust and cell debris. Additionally, the classification model was able to identify different cellular phenotypes using only images as input. Together, these models improve cell segmentation accuracy and enable high-throughput analysis of dense cyanobacterial colonies and filamentous cyanobacteria.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11661284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142879479","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":"Molecular mechanisms of GSK3β-driven modulation of ABLIM1 and titin interactions in cardiac muscle.","authors":"Bin Sun, Alec Loftus, Brandon Beh Goh Beh, Aalaythia Hepburn, Peter Kekenes-Huskey","doi":"10.1101/2024.12.07.627363","DOIUrl":"https://doi.org/10.1101/2024.12.07.627363","url":null,"abstract":"<p><p>The heart adapts to cardiac demand through a variety of mechanisms. Some of these adaptations include chemical modifications of myofilament proteins responsible for cell contraction. Interestingly, many of these chemical modifications, such as phosphorylation, are found in unstructured, or intrinsically disordered, regions of proteins. For these myofilament assoiciated proteins with intrinsic disorder (MAPIDs), it has been difficult to determine how their disordered regions influence the function of the intact protein or the myofilament as a whole. Given that cardiac dysfunction can be accompanied by dramatic shifts in post-translational modifications (PTMs) of myofilament proteins, assessment of these impacts in intrinsically disordered regions is important. We hypothesized that regulation of the actin-binding myofilament protein LIM protein 1, ABLIM1, through its IDRs occurs because PTMs, namely phosphorylation, alter their conformation ensembles. The change in conformations thereby toggles their availability for binding protein partners. To evaluate this hypothesis, we used molecular dynamics to simulate ABLIM1 and thereby determine its conformation ensemble before and after phosphorylation. In accordance with published phosphorylation data in GSK3β knockout models, our results indicate that local changes in the physicochemical properties of ABLIM1's IDRs via phosphorylation can influence its global ensemble properties, with the potential to impact its interaction with myofilament targets like titin. These findings provide important molecular-level insights into a mechanism of regulating cardiomyocyte contraction.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11661090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142879228","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}