bioRxiv : the preprint server for biology最新文献

{"title":"The Rodent Electronic Nicotine Delivery System: Apparatus for Voluntary Nose-Only E-Cigarette Aerosol Inhalation.","authors":"Amy L Odum, Mariah E Willis-Moore, Kiernan T Callister, Jeremy M Haynes, Charles C J Frye, Lucy N Scribner, David N Legaspi, Daniel Santos Da Silva, Aaron L Olsen, Tadd T Truscott, Preston T Alden, Rick A Bevins, Adam M Leventhal, Stephen T Lee, Brenna Gomer, Abby D Benninghoff","doi":"10.1101/2024.12.21.629932","DOIUrl":"10.1101/2024.12.21.629932","url":null,"abstract":"<p><p>Tobacco use is the leading cause of death globally and in the U.S. After decades of decline, driven by decreases in combusted tobacco use, nicotine product use has increased due to Electronic Nicotine Delivery Systems, also known as e-cigarettes or vapes. Preclinical models of nicotine self-administration can serve as important lodestars in the search for effective intervention and prevention tactics. Current variants of the task have substantial limitations, however. Therefore, we created the Rodent Electronic Nicotine Delivery System, a novel low-cost non-proprietary nose-only preclinical model of nicotine aerosol self-administration. We confirmed that RENDS sequesters nicotine aerosol in the nose port by measuring fine particulate matter (PM < 2.5 microns) generated by e-cigarettes. We also showed that rats robustly self-administer flavored nicotine aerosol, resulting in high blood levels of cotinine (the major nicotine metabolite) and spontaneous somatic withdrawal symptoms. Thus, we provide strong validation of the operation and function of the RENDS, opening the door to an open-source preclinical aerosol model of nicotine self-administration that is relatively low cost. Four existing operant chambers can be retrofitted with the RENDS for less than $325/chamber. All RENDS diagrams and plans for custom designed components are on Open Science Framework ( https://osf.io/x2pqf/?view_only=775b55435b8e428f98e6da384ef7889d ).</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11702806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142962615","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":"Identification of novel plasma proteomic biomarkers of Dupuytren Disease.","authors":"Blake Hummer, Paola Sebastiani, Anastasia Leshchyk, Anastasia Gurinovich, Cecilie Bager, Morten Karsdal, Signe Nielsen, Charles Eaton","doi":"10.1101/2024.12.13.628406","DOIUrl":"https://doi.org/10.1101/2024.12.13.628406","url":null,"abstract":"<p><p>Dupuytren Disease (DD) is a chronic progressive disease that can cause disabling hand deformities. The most common treatments have high rates of complications and early recurrence. Dupuytren lacks a staging biomarker profile to develop preventive therapeutics to improve long-term outcomes. This multi-omic study aimed to create a DD blood proteomic biomarker profile by comparing DD plasma to a healthy control group. We measured circulating collagen metabolism peptides and found normal Collagen I synthesis but impaired Collagen I degradation in DD. We measured 6995 serum protein aptamers and identified 68 proteins with statistically significant differences from the control group. We developed two Diagnostic Proteomic Risk Scores (DPRS) based on hypothesis-free and hypothesis-based analyses. In independent data, our hypothesis-free and the hypothesis-based DPRS distinguished Dupuytren from control subjects with 76.5% and 70.6% accuracy, respectively. Our hypothesis- based DPRS also distinguished DD subjects with different disease progression rates based on subject age at the time of their first corrective procedure (p=0.0018). This pilot study is the first to provide evidence that Collagen I accumulation in DD is due to impaired degradation rather than increased collagen synthesis. It also describes novel DPRS that have potential use as diagnostic and staging biomarker panels for Dupuytren disease.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11702579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434899","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":"Genomic Resources for the Scuttle Fly Megaselia abdita: A Model Organism for Comparative Developmental Studies in Flies.","authors":"Ayse Tenger-Trolander, Ezra Amiri, Valentino Gantz, Chun Wai Kwan, Sheri A Sanders, Urs Schmidt-Ott","doi":"10.1101/2025.01.13.631075","DOIUrl":"10.1101/2025.01.13.631075","url":null,"abstract":"<p><p>The order Diptera (true flies) holds promise as a model taxon in evolutionary developmental biology due to the inclusion of the model organism, Drosophila melanogaster, and the ability to cost-effectively rear many species in laboratories. One of them, the scuttle fly Megaselia abdita (Phoridae) has been used in the field of evolutionary developmental biology for 30 years and is an excellent phylogenetic intermediate between fruit flies and mosquitoes but remains underdeveloped in genomic resources. Here, we present a de novo chromosome-level assembly and annotation of M. abdita and transcriptomes of 9 embryonic and 4 postembryonic stages. We also compare 9 stage-matched embryonic transcriptomes between M. abdita and D. melanogaster. Our analysis of these resources reveals extensive chromosomal synteny with D. melanogaster, 28 orphan genes with embryo-specific expression including a novel F-box LRR gene in M. abdita, and conserved and diverged features of gene expression dynamics between M. abdita and D. melanogaster. Collectively, our results provide a new reference for studying the diversification of developmental processes in flies.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049578","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":"Alanine Scanning to Define Membrane Protein-Lipid Interaction Sites Using Native Mass Spectrometry.","authors":"Hiruni S Jayasekera, Farhana Afrin Mohona, Madison J De Jesus, Katherine M Miller, Michael T Marty","doi":"10.1101/2024.10.24.620105","DOIUrl":"10.1101/2024.10.24.620105","url":null,"abstract":"<p><p>Lipids surrounding membrane proteins interact with different sites on the protein at varying specificities, ranging from highly specific to weak interactions. These interactions can modulate the structure, function, and stability of membrane proteins. Thus, to better understand membrane protein structure and function, it is important to identify the locations of lipid binding and the relative specificities of lipid binding at these sites. In our previous native mass spectrometry (MS) study, we developed a single and double mutant analysis approach to profile the contribution of specific residues toward lipid binding. Here, we extend this method by screening a broad range of mutants of AqpZ to identify specific lipid binding sites and by measuring binding of different lipid types to measure the selectivity of different lipids at selected binding sites. We complemented these native MS studies with molecular dynamics (MD) simulations to visualize lipid interactions at selected sites. We discovered that AqpZ is selective towards cardiolipins (CL) but only at specific sites. Specifically, CL orients with its headgroup facing the cytoplasmic side, and its acyl chains interact with a hydrophobic pocket located at the monomeric interface within the lipid bilayer. Overall, this integrative approach provides unique insights into lipid binding sites and the selectivity of various lipids towards AqpZ, enabling us to map the AqpZ protein structure based on the lipid affinity.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11527333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560024","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":"Cell-type specific profiling of human entorhinal cortex at the onset of Alzheimer's disease neuropathology.","authors":"Patricia Rodriguez-Rodriguez, Wei Wang, Christina Tsagkogianni, Irena Feng, Ana Morello-Megias, Kaahini Jain, Vilma Alanko, Han-Ali Kahvecioglu, Elyas Mohammadi, Xiaofei Li, Marc Flajolet, Anna Sandebring-Matton, Silvia Maioli, Noemi Vidal, Ana Milosevic, Jean-Pierre Roussarie","doi":"10.1101/2024.12.31.630881","DOIUrl":"10.1101/2024.12.31.630881","url":null,"abstract":"<p><p>Neurons located in layer II of the entorhinal cortex (ECII) are the primary site of pathological tau accumulation and neurodegeneration at preclinical stages of Alzheimer's disease (AD). Exploring the alterations that underlie the early degeneration of these cells is essential to develop therapies that curb the disease before symptom onset. Here we performed cell-type specific profiling of human EC at the onset of AD neuropathology. We identify an early response to amyloid pathology by microglia and oligodendrocytes. Importantly, we provide the first insight into neuronal alterations that coincide with incipient tau pathology: the signaling pathway for Reelin, recently shown to be a major AD resilience gene is dysregulated in ECII neurons, while the secreted synaptic organizer molecules NPTX2 and CBLN4, emerging AD biomarkers, are downregulated in surrounding neurons. By uncovering the complex multicellular landscape of EC at these early AD stages, this study paves the way for detailed characterization of the mechanisms governing NFT formation and opens long-needed novel therapeutic avenues.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11722323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974390","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":"Multilayer regulation underlies the functional precision and evolvability of the olfactory system.","authors":"Jérôme Mermet, Steeve Cruchet, Asfa Sabrin Borbora, Daehan Lee, Phing Chian Chai, Andre Jang, Karen Menuz, Richard Benton","doi":"10.1101/2025.01.16.632932","DOIUrl":"10.1101/2025.01.16.632932","url":null,"abstract":"<p><p>Sensory neurons must be reproducibly specified to permit accurate neural representation of external signals but also able to change during evolution. We studied this paradox in the <i>Drosophila</i> olfactory system by establishing a single-cell transcriptomic atlas of all developing antennal sensory lineages, including latent neural populations that normally undergo programmed cell death (PCD). This atlas reveals that transcriptional control is robust, but imperfect, in defining selective sensory receptor expression. A second layer of precision is afforded by the intersection of expression of functionally-interacting receptor subunits. A third layer is defined by stereotyped PCD patterning, which masks promiscuous receptor expression in neurons fated to die and removes \"empty\" neurons lacking receptors. Like receptor choice, PCD is under lineage-specific transcriptional control; promiscuity in this regulation leads to previously-unappreciated heterogeneity in neuronal numbers. Thus functional precision in the mature olfactory system belies developmental noise that might facilitate the evolution of sensory pathways.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049550","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":"Disease-associated Kv1.3 variants are energy compromised with impaired nascent chain folding.","authors":"Aaron Sykes, Lannawill Caruth, Shefali Setia Verma, Toshinori Hoshi, Carol Deutsch","doi":"10.1101/2025.01.17.631970","DOIUrl":"10.1101/2025.01.17.631970","url":null,"abstract":"<p><p>Human Kv1.3, encoded by <i>KCNA3</i> , is expressed in neuronal and immune cells. Its impaired expression or function produces chronic inflammatory disease and autoimmune disorders, the severity of which correlates with Kv1.3 protein expression. The intersubunit recognition domain, T1, at the cytosolic N-terminus of Kv1.3, acquires secondary, tertiary, and quaternary structures during early biogenesis while the nascent protein is attached to the ribosome and/or the ER membrane. In this study, we ask whether native <i>KCNA3</i> gene variants in T1 are associated with human disease and whether they manifest early-stage folding defects, energetic instabilities, and conformational distortion of subunits. We use three approaches: first, the unbiased \"genome-first\" approach to determine phenotype associations of specific <i>KCNA3</i> rare variants. Second, we use biochemical assays to assess early-stage tertiary and quaternary folding and membrane association of these variants during early biogenesis. Third, we use all-atom molecular dynamics simulations of the T1 tetramer to assess structural macroscopic and energetic stability differences between wildtype (WT) Kv1.3 and a single-point variant, R114G. Measured folding probabilities and membrane associations are dramatically reduced in several of the native variants compared to WT. Simulations strikingly show that the R114G variant produces more energetically unstable and dynamic T1 domains, concomitant with tertiary unwinding and impaired formation of symmetrical tetramers. Our findings identify molecular mechanisms by which rare variants influence channel assembly, potentially contributing to diverse clinical phenotypes underlying human disease.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049488","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":"Proliferative arrest induces neuronal differentiation and innate immune responses in normal and Creutzfeldt-Jakob Disease agent (CJ) infected rat septal neurons.","authors":"Nathan Pagano, Gerard Aguilar Perez, Rolando Garcia-Milian, Laura Manuelidis","doi":"10.1101/2024.07.26.605349","DOIUrl":"10.1101/2024.07.26.605349","url":null,"abstract":"<p><p>Rat post-mitotic septal neurons, engineered to proliferate and arrest under physiological conditions can be maintained for weeks without cytotoxic effects. Nine independent cDNA libraries were made to follow arrest-induced neural differentiation and innate immune responses in normal uninfected and CJ agent infected septal neurons for weeks. CJ infection created a non-productive latent (CJ-) and a productive (CJ+) high infectivity model (10 logs/gm). Arrest of normal uninfected cells upregulated a plethora of anti-proliferative transcripts and known neuronal differentiation transcripts (e.g., Agtr2, Neuregulin-1, GDF6, SFRP4 and Prnp). Notably, many activated IFN innate immune genes were simultaneously upregulated (e.g., OAS1, RTP4, ISG20, GTB4, CD80, cytokines, chemokines and complement) along with clusterin (CLU) that binds misfolded proteins. Arrest of latently infected CJ-cells induced even more profound global transcript differences. CJ+ cells markedly downregulated the anti-proliferative controls seen in arrested normal cells. CJ+ infection also suppressed neuronal differentiation transcripts, including Prnp which is essential for CJ agent infection. Additionally, IFN and cytokine/chemokine pathways were also strongly enhanced. Analysis of the 342 CJ+ unique transcripts revealed additional innate immune and anti-viral-linked transcripts, e.g., Il17, ISG15, and RSAD2 (viperin). These data show: 1) innate immune transcripts are produced by normal neurons during differentiation; 2) CJ infection enhances and expands anti-viral responses; 3) non-productive latent infection can epigenetically imprint many proliferative pathways to thwart complete arrest. Consequently, human blood and intestinal myeloid peripheral cells that are latently infected (silent) for many years may be stimulated in vitro to produce CJ+ linked diagnostic transcripts.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11312452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918582","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":"Development of avian influenza A(H5) virus datasets for Nextclade enables rapid and accurate clade assignment.","authors":"Jordan T Ort, Sonja A Zolnoski, Tommy T-Y Lam, Richard Neher, Louise H Moncla","doi":"10.1101/2025.01.07.631789","DOIUrl":"10.1101/2025.01.07.631789","url":null,"abstract":"<p><p>The ongoing panzootic of highly pathogenic avian influenza (HPAI) A(H5) viruses is the largest in history, with unprecedented transmission to multiple mammalian species. Avian influenza A viruses of the H5 subtype circulate globally among birds and are classified into distinct clades based on their hemagglutinin (HA) genetic sequences. Thus, the ability to accurately and rapidly assign clades to newly sequenced isolates is key to surveillance and outbreak response. Co-circulation of endemic, low pathogenic avian influenza (LPAI) A(H5) lineages in North American and European wild birds necessitates the ability to rapidly and accurately distinguish between infections arising from these lineages and epizootic HPAI A(H5) viruses. However, currently available clade assignment tools are limited and often require command line expertise, hindering their utility for public health surveillance labs. To address this gap, we have developed datasets to enable A(H5) clade assignments with Nextclade, a drag-and-drop tool originally developed for SARS-CoV-2 genetic clade classification. Using annotated reference datasets for all historical A(H5) clades, clade 2.3.2.1 descendants, and clade 2.3.4.4 descendants provided by the Food and Agriculture Organization/World Health Organization/World Organisation for Animal Health (FAO/WHO/WOAH) H5 Working Group, we identified clade-defining mutations for every established clade to enable tree-based clade assignment. We then created three Nextclade datasets which can be used to assign clades to A(H5) HA sequences and call mutations relative to reference strains through a drag-and-drop interface. Nextclade assignments were benchmarked with 19,834 unique sequences not in the reference set using a pre-released version of LABEL, a well-validated and widely used command line software. Prospective assignment of new sequences with Nextclade and LABEL produced very well-matched assignments (match rates of 97.8% and 99.1% for the 2.3.2.1 and 2.3.4.4 datasets, respectively). The all-clades dataset also performed well (94.8% match rate) and correctly distinguished between all HPAI and LPAI strains. This tool additionally allows for the identification of polybasic cleavage site sequences and potential N-linked glycosylation sites. These datasets therefore provide an alternative, rapid method to accurately assign clades to new A(H5) HA sequences, with the benefit of an easy-to-use browser interface.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019717","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":"I/σI vs {Rmerg, Rmeas, Rpim, CC1/2} for Crystal Diffraction Data Quality Evaluation.","authors":"Zhengqing Fu, Brian V Geisbrecht, Samuel Bouyain, Fred Dyda, John J Chrzas, Palani Kandavelu, Darcie J Miller, Bi-Cheng Wang","doi":"10.1101/2024.12.10.627855","DOIUrl":"10.1101/2024.12.10.627855","url":null,"abstract":"<p><p>X-ray crystal diffraction has provided atomic-level structural information on biological macromolecules. Data quality determines the reliability of structural models. In most cases, multiple data sets are available from different crystals and/or collected with different experimental settings. Reliable metrics are critical to rank and select the data set with the highest quality. Many measures have been created or modified for data quality evaluation. However, some are duplicate in functionality, and some are likely misused due to misunderstanding, which causes confusion or problems, especially at synchrotron beamlines where experiments proceed quickly. In this work, these measures are studied through both theoretical analysis and experimental data with various characteristics, which demonstrated that: 1). {Rmerg, Rmeas, Rpim, CC1/2} all measure the equivalence of reflections, and the low-shell values of these metrics can be used as reliable indicators for correctness (or trueness) of Laue symmetry; 2). High-shell I/σI is a reliable and better indicator to select resolution cutoff while the overall value measures the overall strength of the data.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11661158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142879327","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}