{"title":"Navigation of Nanos germ cell specification factor to germ granules -posttranscriptional regulation hubs - across species.","authors":"Bellary Lakshmi, Matisa Alla, Jadwiga Jaruzelska","doi":"10.1093/biolre/ioaf105","DOIUrl":"https://doi.org/10.1093/biolre/ioaf105","url":null,"abstract":"<p><p>NANOS, initially identified in D. melanogaster (fruit fly) as a morphogen essential for body patterning and germ cell development, is a highly conserved RNA-binding protein critical for germ cell formation across species. NANOS dysfunction leads to infertility from flies to humans. While D. melanogaster has a single Nanos gene, paralogs (Nanos1-3) exist in species like C. elegans (roundworm), Danio rerio (zebrafish), X. laevis (clawed frog), and mammals, each with distinct reproductive roles. Nanos mRNA is one of the most conserved components of germ granules, characteristic cytoplasmic ribonucleoprotein condensates found in the cytoplasm of animal germ cells. The germ granules are essential for the posttranscriptional temporal regulation of germ cell specification, development, maintenance, and integrity across species. Their origin, cytoplasmic sub-localizations, structure and shape differ depending on the sex and developmental stage. This review examines the biological significance and dynamics of Nanos within germ granules across various model organisms. A central question is whether NANOS gene mutations linked to infertility drive the remodelling of germ cell granules. This question also extends to other conserved germ granule components discussed in this review. Addressing these issues will enhance our understanding of the molecular mechanisms underlying human infertility.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sorafenib inhibits ovarian inflammation and fibrosis in polycystic ovary syndrome by targeting the PDGFA/PDGFRα/NF-κB pathway in granulosa cells†.","authors":"Xitong Liu, Yuhui Wang, Yang Wang, Yixuan Bai, Ahui Kang, Qingqing Cai, Haiou Liu, Mengyu Zhang, Congjian Xu, Feifei Zhang","doi":"10.1093/biolre/ioaf082","DOIUrl":"https://doi.org/10.1093/biolre/ioaf082","url":null,"abstract":"<p><p>The etiology of polycystic ovary syndrome (PCOS) remains unknown. However, emerging evidence is increasingly suggesting that ovarian inflammation and fibrosis are among the primary causes of pathological changes. Sorafenib is a multiple kinases inhibitor that targets receptor tyrosine kinases including vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR). Sorafenib was found to inhibit the activation of nuclear factor kappa B (NF-κB). However, the effects of sorafenib on PCOS ovarian inflammation and fibrosis remained unknown. Our findings demonstrated that sorafenib effectively inhibited the PDGFA/PDGFRα axis, which subsequently led to the suppression of NF-κB activation. This inhibition further resulted in a decrease in chemokine expression, thereby impeding the recruitment and polarization of macrophages. Consequently, this process resulted in the down-regulation of collagen deposition. These results provide a new perspective and direction for the clinical treatment of PCOS.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shirin Fatima, Sayantan Sur, Jyoti Tiwari, Sangeeta Rani, Shalie Malik
{"title":"Endogenous regulation of behavior and reproductive physiology in a resident passerine songbird†.","authors":"Shirin Fatima, Sayantan Sur, Jyoti Tiwari, Sangeeta Rani, Shalie Malik","doi":"10.1093/biolre/ioaf073","DOIUrl":"https://doi.org/10.1093/biolre/ioaf073","url":null,"abstract":"<p><p>Seasonal timing of reproductive events requires the interaction of the circannual clock and environmental cues. Many avian species exhibit robust circannual rhythms in controlled environments. However, the molecular changes preceding changes in physiology and behavior are poorly understood. The spotted munia (Lonchura punctulata) is an ideal experimental animal to investigate this question as it shows a strong annual cyclicity under prolonged captive conditions. In the current experiment, birds (18 males + 18 females) were maintained under equinox photoperiod (12L:12D, L = light, ~1.86 W/m2; D = dark, <0.00014 W/m2) with constant temperature (22 ± 2°C) and humidity (58 ± 2%) for ~10 months. Based on gonadal status, we identified pre-breeding, breeding, and onset of regression phases and measured body weight, histological changes, active and sleep behavior, and hypothalamic gene expressions. Body fattening, gonadal recrudescence, and organ-specific lipid accumulation were observed during the breeding phase. Increased allopreening behavior coupled with reduced sleep suggested increased social interaction and nighttime vigilance during the reproductive period. The elevated hypothalamic Gonadotropin-Releasing Hormone expression, plasma testosterone, and corticosterone levels during the pre-breeding phase prepared the birds for upcoming reproductive processes. Overall, our data provide evidence of endogenous molecular changes under constant environmental conditions that might inform conserved mechanisms across species.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Krzysztof Damaziak, Agata Marzec, Wojciech Wójcik, Beata Horecka, Mateusz Osiadacz, Julia Riedel, Paweł Pstrokoński, Sebastian Mielnicki
{"title":"Elongated shape and unusual eggshell microstructure enable first confirmed hatching of avian twins.","authors":"Krzysztof Damaziak, Agata Marzec, Wojciech Wójcik, Beata Horecka, Mateusz Osiadacz, Julia Riedel, Paweł Pstrokoński, Sebastian Mielnicki","doi":"10.1093/biolre/ioaf100","DOIUrl":"https://doi.org/10.1093/biolre/ioaf100","url":null,"abstract":"<p><p>The aim of the study was to elucidate the causes that led to the hatching of goose twins for the first time. Analyses included the reconstruction of the egg's dimensions based on preserved fragments of shell and characterization of its microstructure. Sequencing of the genome of the twins was performed. Based on the results, the dimensions of the egg were recreated, while the structure and porosity of the shell were also characterized. Our findings indicate that the main factors that allowed the twins to survive to the end of incubation were, first, the highly elongated shape of the egg, which \"forced\" the embryos to adopt a parallel position in line with the long axis of the egg, and, second, the shell's altered porosity indices. The pores in the twins' post-hatching shell had a smaller surface area, but there were significantly more of them than in the control shells. As a result, for the twins' egg, the total pore area of the shell and the ratio of total pore area to shell thickness was low. These changes, contributed to changes in the dynamics of water diffusion from the egg, adapting it to the needs of the two embryos. Analyses, including whole-genome sequencing, indicate that most of the SNP variants, and insertions and deletions in both twins' cases were located within introns and in the intergenic parts of the genome. A comparison of the type and frequency of SNP and InDel variations showed that the twins are characterized by high level of genetic similarity.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jaspreet K Rishi, Christian Montes, Justin W Walley, Aileen F Keating
{"title":"Ovarian SUMO-2/3 targets and their differential response to genotoxic stress induced by 7,12-dimethylbenz(a)anthracene exposure in lean and obese female mice.","authors":"Jaspreet K Rishi, Christian Montes, Justin W Walley, Aileen F Keating","doi":"10.1093/biolre/ioaf101","DOIUrl":"https://doi.org/10.1093/biolre/ioaf101","url":null,"abstract":"<p><p>SUMOylation is a post-translational modification critical for oocyte development and chromatin-associated processes. Environmental exposures and obesity can cause follicle depletion and exposure to 7,12-dimethylbenz(a)anthracene (DMBA) altered ovarian SUMO protein abundance in lean and obese mice. Thus, the hypothesis that exposure to DMBA may alter ovarian protein SUMOylation as a mode of ovotoxicity dampened by obesity was tested. Lean and obese mice (KK.Cg-a/a and KK.Cg-Ay/J) were exposed to either corn oil or DMBA (1 mg/kg) intraperitoneally for 7d (n = 4/treatment) and ovaries were flash-frozen on the second day of diestrus. Protein was isolated followed by immunoprecipitation using a SUMO-2/3 antibody and precipitated proteins were identified via liquid chromatography-tandem mass spectrometry. A total of 114 SUMO-2/3 ovarian protein targets were identified. Obesity basally altered (P ≤ 0.05) the abundance of 55 SUMOylated proteins with an additional 11 proteins tending (P ≤ 0.1) to be altered. In lean mice, DMBA altered (P < 0.05) the level of SUMOylation profile of 18 proteins with an additional three proteins tending (P ≤ 0.1) to be changed by DMBA exposure. In obese mice, DMBA exposure altered (P < 0.05) the abundance of 29 SUMOylated proteins and seven proteins had a tendency towards being different (P ≤ 0.1). DMBA exposure of lean compared to obese mice affected (P < 0.05) SUMOylation of 43 proteins, and four additional proteins tended (P ≤ 0.1) to differ. These findings suggest that protein SUMOylation is a mode of ovotoxicity which is influenced by physiological status.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiyang Zhang, Wenlong Zhao, Samantha Cheron, Mary B Zelinski, Qiang Zhang, Shuo Xiao
{"title":"Vitrification preserves oocyte transcriptome in a 3D in vitro follicle development and oocyte maturation system.","authors":"Jiyang Zhang, Wenlong Zhao, Samantha Cheron, Mary B Zelinski, Qiang Zhang, Shuo Xiao","doi":"10.1093/biolre/ioaf097","DOIUrl":"https://doi.org/10.1093/biolre/ioaf097","url":null,"abstract":"<p><p>Vitrification is increasingly used to cryopreserve gametes and embryos in assisted reproductive technology (ART). Our prior research demonstrates that vitrification preserves the viability and functionality of follicles. However, its impact on oocyte remains unknown. The current study investigates whether vitrification maintains the oocyte transcriptome during in vitro follicle development and oocyte maturation. Immature mouse preantral follicles were vitrified, then warmed and cultured in vitro for 8 days to grow to the preovulatory stage, followed with induction of ovulation and oocyte maturation on day 9, with fresh follicles as the control. Oocytes at germinal vesicle (GV) stage from grown preovulatory follicles on day 8 and oocytes at metaphase II (MII) post-ovulation on day 9 were collected for single-oocyte Smart-Seq2 RNA sequencing. Principal component analysis separated GV and MII oocytes into two distinct clusters, but oocytes from fresh and vitrified follicles largely overlapped. Differentially expressed genes (DEG) analysis revealed that oocytes from fresh and vitrified follicles, at either GV or MII stage, had comparable expression of maternal effect genes and other genes related to oocyte meiotic and developmental competence. There was a significant transcriptomic change in oocytes during GV-to-MII transition. Gene ontology and KEGG analysis identified DEGs between GV and MII oocytes related to cell cycle, RNA processing, mitochondrion, and ribosome. In summary, our study demonstrates that vitrification preserves oocyte transcriptome during in vitro follicle development and oocyte maturation, supporting its potential for fertility preservation. Moreover, key DEGs identified during GV-to-MII transition indicate their potential functions in oocyte meiotic and developmental competence.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Paulina Lipinska, Katrien Smits, Ann Van Soom, Krishna Chaitanya Pavani, Ewelina Warzych
{"title":"Follicular fluid extracellular vesicles support energy metabolism of bovine oocytes, improving blastocyst development and quality†.","authors":"Paulina Lipinska, Katrien Smits, Ann Van Soom, Krishna Chaitanya Pavani, Ewelina Warzych","doi":"10.1093/biolre/ioaf096","DOIUrl":"https://doi.org/10.1093/biolre/ioaf096","url":null,"abstract":"<p><p>Extracellular vesicles (EVs), from follicular fluid seem to play a significant role in communication within ovarian follicles in several species. The present study aimed to examine the supporting effect of follicular fluid derived small EVs (FF-sEVs) during in vitro maturation (IVM) of bovine cumulus-oocyte complexes (COCs) under conditions of disturbed energy metabolism. Bovine COCs were matured in vitro with inhibitors targeting lipid metabolism (etomoxir) or glucose metabolism (iodoacetate combined with dehydroepiandrosterone), in the presence or absence of FF-sEVs. Following maturation, oocytes and cumulus cells were analyzed by real-time qPCR and stained to visualize lipid droplets. The uptake of FF-sEVs was visualised by fluorescent labelling. In vitro fertilization and embryo culture were followed by mass spectrometry analysis of hatched blastocysts. We demonstrate for the first time that FF-sEVs are transported from the medium into the oocytes, via the cumulus cells and through transzonal projections (TZPs) into the perivitelline space and ooplasm. Cumulus cells under metabolic stress conditions exhibit an increased FF-sEVs uptake from the maturation medium. FF-sEVs supplementation during metabolic stress conditions enhances the MII rate in oocytes and positively affects subsequent embryo development and quality revealed by altered metabolic activity. Lipid droplet parameters and gene expression in cumulus cells and oocytes are affected by FF-sEVs supplementation, which is more pronounced in cumulus cells. Our findings show that FF-sEVs supplementation during IVM under metabolic stress conditions significantly affects COCs, with a positive effect on further blastocyst quality. We provide novel insights into the role of FF-sEVs in oocyte maturation and blastocyst development.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Paula R Brown, Martin A Estermann, Artiom Gruzdev, Gregory J Scott, Thomas B Hagler, Manas K Ray, Humphrey Hung-Chang Yao
{"title":"Generation of a Nr2f2-driven inducible Cre mouse to target interstitial cells in the reproductive system.","authors":"Paula R Brown, Martin A Estermann, Artiom Gruzdev, Gregory J Scott, Thomas B Hagler, Manas K Ray, Humphrey Hung-Chang Yao","doi":"10.1093/biolre/ioaf094","DOIUrl":"https://doi.org/10.1093/biolre/ioaf094","url":null,"abstract":"<p><p>The orphan nuclear receptor Nr2f2, also known as COUP-TFII, play important roles in the development and function of multiple organs, including the reproductive system. NR2F2 is expressed in the interstitial cells of both embryonic and adult testes, ovaries, and reproductive tracts. Taking advantage of such unique expression pattern, we have developed a tamoxifen inducible Cre model, Nr2f2-iCreERT2, which specifically and efficiently targets interstitial cells in both male and female reproductive organs across embryonic and adult stages. This model offers a powerful tool for gene knockout studies specifically in the interstitial compartment, without affecting the supporting or germ cells. Additionally, it enables interstitial cell lineage tracing, facilitating the assessment of the interstitial's contribution to non-interstitial cell types during development and differentiation.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gang Yang, Muhammad Rizwan, Ke Cheng, Yanqing Huang, Chunfang Wang
{"title":"Vitamin D3 Regulates Sperm Mitochondrial Function Essential for Zebrafish Reproductive Ability: Insights into Non-Classical Roles.","authors":"Gang Yang, Muhammad Rizwan, Ke Cheng, Yanqing Huang, Chunfang Wang","doi":"10.1093/biolre/ioaf092","DOIUrl":"https://doi.org/10.1093/biolre/ioaf092","url":null,"abstract":"<p><p>Vitamin D (VD) has attracted increasing research interest in recent years, mainly after several \"non-classical\" targets were identified, including the reproductive organs. Cytochrome P450 family member 27b1 (Cyp27b1) is the key enzyme for the conversion of VD3 to the active form 1,25(OH)2D3, which catalyzes the hydroxylation of 25(OH)D3 at the 1α position. Cyp27b1 are expressed in oocytes and testicular Sertoli cells, suggesting that VD plays an important role in the regulation of reproductive physiology. This study was aimed to investigate the influence of VD3 on male zebrafish reproduction by administering different levels of VD3 (0, 1400, and 11,200 IU/kg) and creating cyp27b1 knockout zebrafish models. The findings revealed that the dietary level of VD3 and the knockout of the cyp27b1 gene did not affect zebrafish germ cell development or spermatogenesis. However, VD3 deficiency impaired E2 and T synthesis, reduced sperm motility, resulted in mitochondrial dysfunction, blocked mitochondrial biogenesis, and reduced ATP content. Additionally, the study found that VD3 deficiency in male zebrafish did not impact the normal growth and development of offspring embryos. In summary, this research demonstrated the role of VD3 in regulating sperm motility by modulating mitochondrial function and biogenesis to regulate ATP synthesis. This study reveals a novel role of VD3 in reproductive processes and provides a new insight for understanding the role of VD3 in animal and human reproductive health.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yu-Chin Lien, Mengyuan Kan, Rita Leite, James P Garifallou, Blanca E Himes, Virginia D Winn, Samuel Parry, Jerome F Strauss, Rebecca A Simmons
{"title":"Race and Sex Differences in Placental Lipid Metabolism are Associated with Spontaneous Early Preterm Birth.","authors":"Yu-Chin Lien, Mengyuan Kan, Rita Leite, James P Garifallou, Blanca E Himes, Virginia D Winn, Samuel Parry, Jerome F Strauss, Rebecca A Simmons","doi":"10.1093/biolre/ioaf085","DOIUrl":"https://doi.org/10.1093/biolre/ioaf085","url":null,"abstract":"<p><p>Placental dysfunction is implicated in the pathogenesis of spontaneous preterm birth (SPTB). We investigated race (self-identified maternal race) and fetal sex differences in the placental metabolome and transcriptome associated with early SPTB (< 32 weeks). Long-chain polyunsaturated fatty acids, acylcarnitines, acylglycerols, plasmalogens, and lysophospholipids were remarkably different between SPTB and Term placentas. These alterations were much more profound in Black than White SPTB placentas. Mode of delivery and BMI had no effect on these differences. The lipid metabolic pathways disrupted in early SPTB placentas also exhibited fetal sex differences, particularly between Black male and Black female placentas. Expression of genes involved in multiple lipid metabolism regulating pathways (e.g. PI3K/AKT signaling and phospholipase activity), especially eicosanoid synthesis and secretion, were significantly altered in early SPTB placentas. The race- and sex-specific changes in lipid metabolites and gene expression were consistent with inflammation in SPTB placentas, which was further supported by dysregulation of various inflammation and immune response pathways. These findings reveal race and fetal sex differences in lipid metabolism and inflammation in SPTB placentas and suggest greater dysfunction and inflammation in Black compared to White SPTB placentas, which may explain mechanisms underlying early SPTB and the risk of SPTB in different populations.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}