PLoS Genetics最新文献

{"title":"A conserved protein tyrosine phosphatase, PTPN-22, functions in diverse developmental processes in C. elegans.","authors":"Shaonil Binti, Adison G Linder, Philip T Edeen, David S Fay","doi":"10.1371/journal.pgen.1011219","DOIUrl":"10.1371/journal.pgen.1011219","url":null,"abstract":"<p><p>Protein tyrosine phosphatases non-receptor type (PTPNs) have been studied extensively in the context of the adaptive immune system; however, their roles beyond immunoregulation are less well explored. Here we identify novel functions for the conserved C. elegans phosphatase PTPN-22, establishing its role in nematode molting, cell adhesion, and cytoskeletal regulation. Through a non-biased genetic screen, we found that loss of PTPN-22 phosphatase activity suppressed molting defects caused by loss-of-function mutations in the conserved NIMA-related kinases NEKL-2 (human NEK8/NEK9) and NEKL-3 (human NEK6/NEK7), which act at the interface of membrane trafficking and actin regulation. To better understand the functions of PTPN-22, we carried out proximity labeling studies to identify candidate interactors of PTPN-22 during development. Through this approach we identified the CDC42 guanine-nucleotide exchange factor DNBP-1 (human DNMBP) as an in vivo partner of PTPN-22. Consistent with this interaction, loss of DNBP-1 also suppressed nekl-associated molting defects. Genetic analysis, co-localization studies, and proximity labeling revealed roles for PTPN-22 in several epidermal adhesion complexes, including C. elegans hemidesmosomes, suggesting that PTPN-22 plays a broad role in maintaining the structural integrity of tissues. Localization and proximity labeling also implicated PTPN-22 in functions connected to nucleocytoplasmic transport and mRNA regulation, particularly within the germline, as nearly one-third of proteins identified by PTPN-22 proximity labeling are known P granule components. Collectively, these studies highlight the utility of combined genetic and proteomic approaches for identifying novel gene functions.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"20 8","pages":"e1011219"},"PeriodicalIF":4.0,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent secondary contact, genome-wide admixture, and asymmetric introgression of neo-sex chromosomes between two Pacific island bird species.","authors":"Elsie H Shogren, Jason M Sardell, Christina A Muirhead, Emiliano Martí, Elizabeth A Cooper, Robert G Moyle, Daven C Presgraves, J Albert C Uy","doi":"10.1371/journal.pgen.1011360","DOIUrl":"10.1371/journal.pgen.1011360","url":null,"abstract":"<p><p>Secondary contact between closely related taxa represents a \"moment of truth\" for speciation-an opportunity to test the efficacy of reproductive isolation that evolved in allopatry and to identify the genetic, behavioral, and/or ecological barriers that separate species in sympatry. Sex chromosomes are known to rapidly accumulate differences between species, an effect that may be exacerbated for neo-sex chromosomes that are transitioning from autosomal to sex-specific inheritance. Here we report that, in the Solomon Islands, two closely related bird species in the honeyeater family-Myzomela cardinalis and Myzomela tristrami-carry neo-sex chromosomes and have come into recent secondary contact after ~1.1 my of geographic isolation. Hybrids of the two species were first observed in sympatry ~100 years ago. To determine the genetic consequences of hybridization, we use population genomic analyses of individuals sampled in allopatry and in sympatry to characterize gene flow in the contact zone. Using genome-wide estimates of diversity, differentiation, and divergence, we find that the degree and direction of introgression varies dramatically across the genome. For sympatric birds, autosomal introgression is bidirectional, with phenotypic hybrids and phenotypic parentals of both species showing admixed ancestry. In other regions of the genome, however, the story is different. While introgression on the Z/neo-Z-linked sequence is limited, introgression of W/neo-W regions and mitochondrial sequence (mtDNA) is highly asymmetric, moving only from the invading M. cardinalis to the resident M. tristrami. The recent hybridization between these species has thus enabled gene flow in some genomic regions but the interaction of admixture, asymmetric mate choice, and/or natural selection has led to the variation in the amount and direction of gene flow at sex-linked regions of the genome.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"20 8","pages":"e1011360"},"PeriodicalIF":4.0,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An autoregulatory poison exon in Smndc1 is conserved across kingdoms and influences organism growth.","authors":"Andrea E Belleville, James D Thomas, Jackson Tonnies, Austin M Gabel, Andrea Borrero Rossi, Priti Singh, Christine Queitsch, Robert K Bradley","doi":"10.1371/journal.pgen.1011363","DOIUrl":"10.1371/journal.pgen.1011363","url":null,"abstract":"<p><p>Many of the most highly conserved elements in the human genome are \"poison exons,\" alternatively spliced exons that contain premature termination codons and permit post-transcriptional regulation of mRNA abundance through induction of nonsense-mediated mRNA decay (NMD). Poison exons are widely assumed to be highly conserved due to their presumed importance for organismal fitness, but this functional importance has never been tested in the context of a whole organism. Here, we report that a poison exon in Smndc1 is conserved across mammals and plants and plays a molecular autoregulatory function in both kingdoms. We generated mouse and A. thaliana models lacking this poison exon to find its loss leads to deregulation of SMNDC1 protein levels, pervasive alterations in mRNA processing, and organismal size restriction. Together, these models demonstrate the importance of poison exons for both molecular and organismal phenotypes that likely explain their extraordinary conservation.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"20 8","pages":"e1011363"},"PeriodicalIF":4.0,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11357089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141992529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Finemap-MiXeR: A variational Bayesian approach for genetic finemapping.","authors":"Bayram Cevdet Akdeniz, Oleksandr Frei, Alexey Shadrin, Dmitry Vetrov, Dmitry Kropotov, Eivind Hovig, Ole A Andreassen, Anders M Dale","doi":"10.1371/journal.pgen.1011372","DOIUrl":"10.1371/journal.pgen.1011372","url":null,"abstract":"<p><p>Genome-wide association studies (GWAS) implicate broad genomic loci containing clusters of highly correlated genetic variants. Finemapping techniques can select and prioritize variants within each GWAS locus which are more likely to have a functional influence on the trait. Here, we present a novel method, Finemap-MiXeR, for finemapping causal variants from GWAS summary statistics, controlling for correlation among variants due to linkage disequilibrium. Our method is based on a variational Bayesian approach and direct optimization of the Evidence Lower Bound (ELBO) of the likelihood function derived from the MiXeR model. After obtaining the analytical expression for ELBO's gradient, we apply Adaptive Moment Estimation (ADAM) algorithm for optimization, allowing us to obtain the posterior causal probability of each variant. Using these posterior causal probabilities, we validated Finemap-MiXeR across a wide range of scenarios using both synthetic data, and real data on height from the UK Biobank. Comparison of Finemap-MiXeR with two existing methods, FINEMAP and SuSiE RSS, demonstrated similar or improved accuracy. Furthermore, our method is computationally efficient in several aspects. For example, unlike many other methods in the literature, its computational complexity does not increase with the number of true causal variants in a locus and it does not require any matrix inversion operation. The mathematical framework of Finemap-MiXeR is flexible and may also be applied to other problems including cross-trait and cross-ancestry finemapping.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"20 8","pages":"e1011372"},"PeriodicalIF":4.0,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11349196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141989309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"XOL-1 regulates developmental timing by modulating the H3K9 landscape in C. elegans early embryos.","authors":"Eshna Jash, Anati Alyaa Azhar, Hector Mendoza, Zoey M Tan, Halle Nicole Escher, Dalia S Kaufman, Györgyi Csankovszki","doi":"10.1371/journal.pgen.1011238","DOIUrl":"10.1371/journal.pgen.1011238","url":null,"abstract":"<p><p>Sex determination in the nematode C. elegans is controlled by the master regulator XOL-1 during embryogenesis. Expression of xol-1 is dependent on the ratio of X chromosomes and autosomes, which differs between XX hermaphrodites and XO males. In males, xol-1 is highly expressed and in hermaphrodites, xol-1 is expressed at very low levels. XOL-1 activity is known to be critical for the proper development of C. elegans males, but its low expression was considered to be of minimal importance in the development of hermaphrodite embryos. Our study reveals that XOL-1 plays an important role as a regulator of developmental timing during hermaphrodite embryogenesis. Using a combination of imaging and bioinformatics techniques, we found that hermaphrodite embryos have an accelerated rate of cell division, as well as a more developmentally advanced transcriptional program when xol-1 is lost. Further analyses reveal that XOL-1 is responsible for regulating the timing of initiation of dosage compensation on the X chromosomes, and the appropriate expression of sex-biased transcriptional programs in hermaphrodites. We found that xol-1 mutant embryos overexpress the H3K9 methyltransferase MET-2 and have an altered H3K9me landscape. Some of these effects of the loss of xol-1 gene were reversed by the loss of met-2. These findings demonstrate that XOL-1 plays an important role as a developmental regulator in embryos of both sexes, and that MET-2 acts as a downstream effector of XOL-1 activity in hermaphrodites.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"20 8","pages":"e1011238"},"PeriodicalIF":4.0,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11349215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141989310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive analysis of the functional impact of single nucleotide variants of human CHEK2.","authors":"Claire E McCarthy-Leo, George S Brush, Roger Pique-Regi, Francesca Luca, Michael A Tainsky, Russell L Finley","doi":"10.1371/journal.pgen.1011375","DOIUrl":"10.1371/journal.pgen.1011375","url":null,"abstract":"<p><p>Loss of function mutations in the checkpoint kinase gene CHEK2 are associated with increased risk of breast and other cancers. Most of the 3,188 unique amino acid changes that can result from non-synonymous single nucleotide variants (SNVs) of CHEK2, however, have not been tested for their impact on the function of the CHEK2-enocded protein (CHK2). One successful approach to testing the function of variants has been to test for their ability to complement mutations in the yeast ortholog of CHEK2, RAD53. This approach has been used to provide functional information on over 100 CHEK2 SNVs and the results align with functional assays in human cells and known pathogenicity. Here we tested all but two of the 4,887 possible SNVs in the CHEK2 open reading frame for their ability to complement RAD53 mutants using a high throughput technique of deep mutational scanning (DMS). Among the non-synonymous changes, 770 were damaging to protein function while 2,417 were tolerated. The results correlate well with previous structure and function data and provide a first or additional functional assay for all the variants of uncertain significance identified in clinical databases. Combined, this approach can be used to help predict the pathogenicity of CHEK2 variants of uncertain significance that are found in susceptibility screening and could be applied to other cancer risk genes.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"20 8","pages":"e1011375"},"PeriodicalIF":4.0,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11349238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141989308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Candida albicans' inorganic phosphate transport and evolutionary adaptation to phosphate scarcity.","authors":"Maikel Acosta-Zaldívar, Wanjun Qi, Abhishek Mishra, Udita Roy, William R King, Yuping Li, Jana Patton-Vogt, Matthew Z Anderson, Julia R Köhler","doi":"10.1371/journal.pgen.1011156","DOIUrl":"10.1371/journal.pgen.1011156","url":null,"abstract":"<p><p>Phosphorus is essential in all cells' structural, metabolic and regulatory functions. For fungal cells that import inorganic phosphate (Pi) up a steep concentration gradient, surface Pi transporters are critical capacitators of growth. Fungi must deploy Pi transporters that enable optimal Pi uptake in pH and Pi concentration ranges prevalent in their environments. Single, triple and quadruple mutants were used to characterize the four Pi transporters we identified for the human fungal pathogen Candida albicans, which must adapt to alkaline conditions during invasion of the host bloodstream and deep organs. A high-affinity Pi transporter, Pho84, was most efficient across the widest pH range while another, Pho89, showed high-affinity characteristics only within one pH unit of neutral. Two low-affinity Pi transporters, Pho87 and Fgr2, were active only in acidic conditions. Only Pho84 among the Pi transporters was clearly required in previously identified Pi-related functions including Target of Rapamycin Complex 1 signaling, oxidative stress resistance and hyphal growth. We used in vitro evolution and whole genome sequencing as an unbiased forward genetic approach to probe adaptation to prolonged Pi scarcity of two quadruple mutant lineages lacking all 4 Pi transporters. Lineage-specific genomic changes corresponded to divergent success of the two lineages in fitness recovery during Pi limitation. Initial, large-scale genomic alterations like aneuploidies and loss of heterozygosity eventually resolved, as populations gained small-scale mutations. Severity of some phenotypes linked to Pi starvation, like cell wall stress hypersensitivity, decreased in parallel to evolving populations' fitness recovery in Pi scarcity, while severity of others like membrane stress responses diverged from Pi scarcity fitness. Among preliminary candidate genes for contributors to fitness recovery, those with links to TORC1 were overrepresented. Since Pi homeostasis differs substantially between fungi and humans, adaptive processes to Pi deprivation may harbor small-molecule targets that impact fungal growth, stress resistance and virulence.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"20 8","pages":"e1011156"},"PeriodicalIF":4.0,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11343460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141977010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing portability of trans-ancestral polygenic risk scores through tissue-specific functional genomic data integration.","authors":"Bradley Crone, Alan P Boyle","doi":"10.1371/journal.pgen.1011356","DOIUrl":"10.1371/journal.pgen.1011356","url":null,"abstract":"<p><p>Portability of trans-ancestral polygenic risk scores is often confounded by differences in linkage disequilibrium and genetic architecture between ancestries. Recent literature has shown that prioritizing GWAS SNPs with functional genomic evidence over strong association signals can improve model portability. We leveraged three RegulomeDB-derived functional regulatory annotations-SURF, TURF, and TLand-to construct polygenic risk models across a set of quantitative and binary traits highlighting functional mutations tagged by trait-associated tissue annotations. Tissue-specific prioritization by TURF and TLand provide a significant improvement in model accuracy over standard polygenic risk score (PRS) models across all traits. We developed the Trans-ancestral Iterative Tissue Refinement (TITR) algorithm to construct PRS models that prioritize functional mutations across multiple trait-implicated tissues. TITR-constructed PRS models show increased predictive accuracy over single tissue prioritization. This indicates our TITR approach captures a more comprehensive view of regulatory systems across implicated tissues that contribute to variance in trait expression.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"20 8","pages":"e1011356"},"PeriodicalIF":4.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 kpc-1 3'UTR facilitates dendritic transport and translation efficiency of mRNAs for dendrite arborization of a mechanosensory neuron important for male courtship.","authors":"Mushaine Shih, Yan Zou, Tarsis Ferreira, Nobuko Suzuki, Eunseo Kim, Chiou-Fen Chuang, Chieh Chang","doi":"10.1371/journal.pgen.1011362","DOIUrl":"10.1371/journal.pgen.1011362","url":null,"abstract":"<p><p>A recently reported Schizophrenia-associated genetic variant in the 3'UTR of the human furin gene, a homolog of C. elegans kpc-1, highlights an important role of the furin 3'UTR in neuronal development. We isolate three kpc-1 mutants that display abnormal dendrite arborization in PVD neurons and defective male mating behaviors. We show that the kpc-1 3'UTR participates in dendrite branching and self-avoidance. The kpc-1 3'UTR facilitates mRNA localization to branching points and contact points between sibling dendrites and promotes translation efficiency. A predicted secondary structural motif in the kpc-1 3'UTR is required for dendrite self-avoidance. Animals with over-expression of DMA-1, a PVD dendrite receptor, exhibit similar dendrite branching and self-avoidance defects that are suppressed with kpc-1 over-expression. Our results support a model in which KPC-1 proteins are synthesized at branching points and contact points to locally down-regulate DMA-1 receptors to promote dendrite branching and self-avoidance of a mechanosensory neuron important for male courtship.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"20 8","pages":"e1011362"},"PeriodicalIF":4.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of rice GENERAL REGULATORY FACTOR14h (GF14h) on low-temperature seed germination and its application to breeding.","authors":"Yusaku Sugimura, Kaori Oikawa, Yu Sugihara, Hiroe Utsushi, Eiko Kanzaki, Kazue Ito, Yumiko Ogasawara, Tomoaki Fujioka, Hiroki Takagi, Motoki Shimizu, Hiroyuki Shimono, Ryohei Terauchi, Akira Abe","doi":"10.1371/journal.pgen.1011369","DOIUrl":"10.1371/journal.pgen.1011369","url":null,"abstract":"<p><p>Direct seeding is employed to circumvent the labor-intensive process of rice (Oryza sativa) transplantation, but this approach requires varieties with vigorous low-temperature germination (LTG) when sown in cold climates. To investigate the genetic basis of LTG, we identified the quantitative trait locus (QTL) qLTG11 from rice variety Arroz da Terra, which shows rapid seed germination at lower temperatures, using QTL-seq. We delineated the candidate region to a 52-kb interval containing GENERAL REGULATORY FACTOR14h (GF14h) gene, which is expressed during seed germination. The Arroz da Terra GF14h allele encodes functional GF14h, whereas Japanese rice variety Hitomebore harbors a 4-bp deletion in the coding region. Knocking out functional GF14h in a near-isogenic line (NIL) carrying the Arroz da Terra allele decreased LTG, whereas overexpressing functional GF14h in Hitomebore increased LTG, indicating that GF14h is the causal gene behind qLTG11. Analysis of numerous Japanese rice accessions revealed that the functional GF14h allele was lost from popular varieties during modern breeding. We generated a NIL in the Hitomebore background carrying a 172-kb genomic fragment from Arroz da Terra including GF14h. The NIL showed superior LTG compared to Hitomebore, with otherwise comparable agronomic traits. The functional GF14h allele from Arroz da Terra represents a valuable resource for direct seeding in cold regions.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"20 8","pages":"e1011369"},"PeriodicalIF":4.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11343456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}