Asha Bhardwaj, Leena Sapra, Divya Madan, Vineet Ahuja, Hanuman Prasad Sharma, Thirumurthy Velpandian, Pradyumna K Mishra, Rupesh K Srivastava
{"title":"Gut-resident Tregs (GTregs) play a pivotal role in maintaining bone health under post-menopausal osteoporotic conditions.","authors":"Asha Bhardwaj, Leena Sapra, Divya Madan, Vineet Ahuja, Hanuman Prasad Sharma, Thirumurthy Velpandian, Pradyumna K Mishra, Rupesh K Srivastava","doi":"10.1093/jleuko/qiaf008","DOIUrl":"https://doi.org/10.1093/jleuko/qiaf008","url":null,"abstract":"<p><p>Osteoporosis is a skeletal condition characterized by the deterioration of bone tissue. The immune system plays a crucial role in maintaining bone homeostasis and combating the development of osteoporosis. Immunoporosis is the term used to describe the recent convergence of research on the immune system's role in osteoporosis. The gut harbors the largest component of the immune system and there is growing evidence that intestinal immunity plays a vital role in regulating bone health. Gut-resident regulatory T cells (GTregs) are essential in inhibiting immune responses and preventing various inflammatory manifestations. Our findings show that GTregs are pivotal in the pathophysiology of post-menopausal osteoporosis (PMO). We investigated the potential of GTregs in regulating the development of bone cells in vitro. We observed that GTregs significantly enhance osteoblastogenesis with concomitant inhibition of osteoclastogenesis in a cell-ratio-dependent manner. We further report that the deficiency of short-chain fatty acids (SCFAs) in osteoporotic conditions substantially disrupts the composition of GTregs, leading to a loss of peripherally derived Tregs (pTregs) and an expansion of thymus-derived Tregs (tTregs). Moreover, the administration of probiotics Lactobacillus rhamnosus (UBLR-58) and Bifidobacterium longum (UBBL-64) modulated the GTregs compartment in an SCFA-dependent manner to mitigate inflammatory bone loss in PMO. Notably, SCFAs-primed GTregs were found to be significantly more effective in inhibiting osteoclastogenesis compared to unprimed GTregs. Altogether our results, for the first time, highlight the crucial role of GTregs in the pathophysiology of PMO, with potential clinical implications.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carola Ledderose, Eleftheria-Angeliki Valsami, Mark Elevado, Ava Stevenson, Reem Abutabikh, Julian Curatolo, Wolfgang G Junger
{"title":"Adenosine accumulation in the blood of newborn mice weakens antimicrobial host defenses.","authors":"Carola Ledderose, Eleftheria-Angeliki Valsami, Mark Elevado, Ava Stevenson, Reem Abutabikh, Julian Curatolo, Wolfgang G Junger","doi":"10.1093/jleuko/qiaf003","DOIUrl":"https://doi.org/10.1093/jleuko/qiaf003","url":null,"abstract":"<p><p>Pediatric intensive care patients are particularly susceptible to severe bacterial infections because of ineffective neutrophil responses. The reasons why neutrophils of newborns are less responsive than those of adults are not clear. Because adenosine triphosphate (ATP) and adenosine (ADO) tightly regulate neutrophils, we studied whether the ATP and ADO levels in the blood of newborn mice could impair the function of their neutrophils. We observed significant changes in plasma ATP and ADO levels throughout the lifespan of mice. ADO levels in newborns were significantly higher than in older mice, while ATP levels were significantly lower. These changes were particularly striking in newborn and juvenile mice with ATP and ADO levels of about 80 and 600 nM in newborns versus 130 and 190 nM in juveniles, respectively. The ratios of the ATP versus ADO levels of newborns were (with 0.2) significantly lower than those of juveniles (1.4) and adults (0.5). These low ATP/ADO ratios correlated with significantly weakened neutrophil activation responses following in vitro stimulation with a formyl peptide receptor agonist and a markedly higher morbidity and mortality rate of newborns following bacterial infection. We found that enhanced AMP hydrolysis via CD73, a lack of ADO breakdown by adenosine deaminase, and reduced ADO uptake by nucleoside transporters are responsible for the low ATP/ADO ratios in blood of newborn mice. We conclude that the extracellular ADO accumulation in newborn mice impairs inflammatory responses and reduces the ability of neutrophils to mount effective antimicrobial defenses against bacterial infections.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Protocols for circulating neutrophil depletion in neonatal C57Bl/6 mice.","authors":"Devashis Mukherjee, Sriram Satyavolu, Sarah Cioffi, Asha Thomas, Yuexin Li, Lalitha Nayak","doi":"10.1093/jleuko/qiaf005","DOIUrl":"https://doi.org/10.1093/jleuko/qiaf005","url":null,"abstract":"<p><p>Murine neonatal neutrophil depletion strategies have problems achieving deep neutrophil clearance and accurate residual neutrophil fraction detection. An isotype switch method can achieve profound neutrophil clearance using a combination of anti-Ly6G and anti-rat κ Ig light chain antibodies in adult C57Bl/6 mice, proven by extra- and intracellular Ly6G detection by flow cytometry. We adapted this technique to neonatal mice, testing four neutrophil depletion strategies in the peripheral circulation, bone marrow, and spleen. Four protocols were tested: P3 Ly6G and P1-3 Ly6G (anti-Ly6G on postnatal days (P) 3 and 1-3 respectively), and P3 Dual and P1-3 Dual (anti-Ly6G and anti-rat κ Ig light chain on P3 and P1-3 respectively). Intracellular and extracellular Ly6G presence was detected using flow cytometry. Isotype control antibodies were used as controls. P1-3 Dual protocol achieved significantly better neutrophil depletion than the P1-3 Ly6G or P3 Ly6G protocols (97% vs. 74% and 97% vs. 50%, respectively) in the peripheral circulation. The P3 Dual protocol alone was enough to achieve significantly better neutrophil clearance (93%) than any of the Ly6G alone protocols. The Ly6G alone protocols led to near-total elimination of extracellular Ly6G. However, there was a significant presence of intracellular Ly6G in the CD45+ cell population, evading detection by extracellular Ly6G antibody-based detection methods. P3 protocols perform better than P1-3 protocols for bone marrow and splenic neutrophil clearance. Thus, the P3 Dual protocol might be the most effective and ethical protocol to induce profound neutrophil depletion in neonatal mice, an alternative to daily anti-Ly6G injections.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Thymic Eosinophils: What Are You Doing Here?","authors":"Dominique M Gatti, Lisa A Reynolds","doi":"10.1093/jleuko/qiaf001","DOIUrl":"https://doi.org/10.1093/jleuko/qiaf001","url":null,"abstract":"<p><p>The thymus is a primary lymphoid organ where major types of T lymphocytes undergo essential developmental processes. Eosinophils are among the cell types present in microenvironments within the thymus, and perhaps surprisingly, the role of thymic eosinophils, especially during homeostatic conditions, remains unclear. Major physiological events impact thymic organization and function throughout life: including age-related involution, pregnancy, and exposure to chemotherapy or radiation. In this Review, we summarize literature that has explored factors that regulate the accumulation, phenotype, and location of thymic eosinophils during homeostatic development and during conditions where homeostasis is perturbed. Further, we discuss the current theories as to the function of thymic eosinophils, and we consider how the heterogeneity of thymic eosinophil populations may reflect a temporal, spatial, and situational multi-functionality of thymic eosinophils.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Miyuki Sakuma, Adam Viens, Alex Hopke, Daniel John Floyd, Musie Ghebremichael, Michael K Mansour, Daniel Irimia
{"title":"Neutrophil Extracellular Traps Capture the human pathogen, Candida albicans, in blood and Delay Hyphal Transformation.","authors":"Miyuki Sakuma, Adam Viens, Alex Hopke, Daniel John Floyd, Musie Ghebremichael, Michael K Mansour, Daniel Irimia","doi":"10.1093/jleuko/qiaf002","DOIUrl":"https://doi.org/10.1093/jleuko/qiaf002","url":null,"abstract":"<p><p>In tissues, neutrophils neutralize Candida albicans through phagocytosis and delay C. albicans hyphae growth by deploying neutrophil extracellular traps (NETs). However, in the bloodstream, the dynamic interactions between NETs and C. albicans are far less understood. Here, we employ a microfluidic assay and measure a significant increase in intact NETs in blood within 3 hours after adding C. albicans yeast or hyphae. We show that C. albicans yeast can be captured efficiently on NETs, thereby delaying the transition to hyphal growth. We measure higher amounts of intact NETs in blood samples from invasive candidiasis patients compared to healthy participants, both with and without stimulation. These findings suggest that both C. albicans yeast and hyphae in the bloodstream stimulate NET release, potentially aiding in their removal from the blood.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kirsten Pfeffer, Thai H Ho, Yvette Ruiz, Douglas F Lake
{"title":"A method for screening functional anti-Treg antibodies using a Treg-like cell line.","authors":"Kirsten Pfeffer, Thai H Ho, Yvette Ruiz, Douglas F Lake","doi":"10.1093/jleuko/qiae257","DOIUrl":"https://doi.org/10.1093/jleuko/qiae257","url":null,"abstract":"<p><p>Regulatory T cells can suppress activated T cell proliferation by direct cell-contact, although the exact mechanism is poorly understood. Identification of a Treg-specific cell surface molecule that mediates suppression would offer a unique target for cancer immunotherapy to inhibit Treg immunosuppressive function or deplete Tregs in the tumor microenvironment. In this study, we explored a method of whole cell immunization using a Treg-like cell line (MoT cells) to generate and screen monoclonal antibodies that bound cell surface proteins in their native conformations and functionally reversed Treg-mediated suppression. From the 105 hybridomas that bound to the MoT cell surface, a functional screen utilizing conventional Treg suppression assays revealed 32 candidate antibodies that exhibited functional activity (reversed or enhanced suppressive activity). As an example, we characterized one anti-MoT mAb, 12E7, that exhibited strong binding to MoT cells and conventional Treg cell surfaces. This candidate antibody was subsequently found to bind to a potential suppressive target, CD44, and demonstrated the ability to partially reverse MoT and conventional human Treg-mediated suppression.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
He Ren, Jiacheng He, Jie Dong, Guoqian Jiang, Jianlei Hao, Liang Han
{"title":"Specific BCG-related gene expression levels correlate with immune cell infiltration and prognosis in melanoma.","authors":"He Ren, Jiacheng He, Jie Dong, Guoqian Jiang, Jianlei Hao, Liang Han","doi":"10.1093/jleuko/qiae064","DOIUrl":"10.1093/jleuko/qiae064","url":null,"abstract":"<p><p>Melanoma, caused by malignant melanocytes, is known for its invasiveness and poor prognosis. Therapies are often ineffective due to their heterogeneity and resistance. Bacillus Calmette-Guérin (BCG), primarily a tuberculosis vaccine, shows potential in treating melanoma by activating immune responses. In this study, data from The Cancer Genome Atlas and the National Center for Biotechnology Information Gene Expression Omnibus database were utilized to determine pivotal DEGs such as DSC2, CXCR1, BOK, and CSTB, which are significantly upregulated in BCG-treated blood samples and are strongly associated with the prognosis of melanoma. We employ tools like edgeR and ggplot2 for functional and pathway analysis and develop a prognostic model using LASSO Cox regression analysis to predict patient survival. A notable finding is the correlation between BCG-related genes and immune cell infiltration in melanoma, highlighting the potential of these genes as both biomarkers and therapeutic targets. Additionally, the study examines genetic alterations in these genes and their impact on the disease. This study highlights the necessity of further exploring BCG-related genes for insights into melanoma pathogenesis and treatment enhancement, suggesting that BCG's role in immune activation could offer novel therapeutic avenues in cancer treatment.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140119803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qinglin Hu, Bing Yue, Jing Liu, Yuxia Gao, Xin Huang, Yi Hu
{"title":"Pan-cancer bioinformatics indicates zinc finger protein 207 is a promising prognostic biomarker and immunotherapeutic target.","authors":"Qinglin Hu, Bing Yue, Jing Liu, Yuxia Gao, Xin Huang, Yi Hu","doi":"10.1093/jleuko/qiae147","DOIUrl":"10.1093/jleuko/qiae147","url":null,"abstract":"<p><p>In the era of personalized cancer treatment, understanding the complexities of tumor biology and immune modulation is paramount. This comprehensive analysis delves into the multifaceted role of zinc finger protein 207 (ZNF207) in pan-cancer, shedding light on its involvement in tumorigenesis, immune evasion, and therapeutic implications. Through integrated genomic and clinical data analysis, we reveal consistent upregulation of ZNF207 across diverse cancer types, highlighting its potential as a prognostic marker and therapeutic target, particularly for liver cancers. Notably, ZNF207 demonstrates intricate associations with clinical-pathological features, immune subtypes, and molecular pathways, indicating its pervasive influence in cancer biology. Furthermore, our study uncovers ZNF207's involvement in immune escape mechanisms, suggesting its potential as a modulator of immune responses within the tumor microenvironment. These findings underscore the significance of ZNF207 in shaping cancer progression and immune landscape, presenting promising avenues for targeted therapy and immunomodulation. Recognizing ZNF207's multifaceted contributions to cancer progression and immune evasion suggests its central role in understanding tumor immunology, beyond mere therapeutic targeting. Nevertheless, further mechanistic studies are imperative to elucidate ZNF207's precise molecular mechanisms and therapeutic implications in cancer treatment. This study primarily utilized various bioinformatics tools such as TIMER 2.0, cProSite, UALCAN, SangerBox, GEPIA2, TISIDB, and TIDE to analyze the expression of ZNF207 in multiple cancer samples from the TCGA database.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141544926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Foxo1 drives the TGFβ1-dependent dichotomy of Th17 cell fates.","authors":"Mengjuan Zhang, Yude Guan, Meijuan Han, Fandi Kong, Aoyu Xu, Xiaohan Jin, Xiao Hu, Fang Dong, Nianchao Zhang, Xiuping Peng, Dantong Liu, Yongyan Chen, Ruxin Zhao, Xiulei Zhu, Yanan Zhang, Congcong Lu, Wen Hou, Lei Liu, Dan Li, Zhihui Zhang, Xiaomin Zhang, Song Zhang","doi":"10.1093/jleuko/qiae004","DOIUrl":"10.1093/jleuko/qiae004","url":null,"abstract":"<p><p>T-helper 17 cells play a dual role in immunological responses, serving as essential components in tissue homeostasis and host defense against microbial pathogens while also contributing to proinflammatory conditions and autoimmunity. While transforming growth factor β1 is pivotal for the differentiation of nonpathogenic T-helper 17 cells, the role of transforming growth factor β3 and activin in steering T-helper 17 cells toward a pathogenic phenotype has been acknowledged. However, the molecular mechanisms governing this dichotomy remain elusive. In this study, we demonstrate that the transcription factor Foxo1 is upregulated in a transforming growth factor β1 dose-dependent manner, serving as a critical regulator that specifically modulates the fate of pathogenic T-helper 17 cells. Analyses in both patients with uveitis and an experimental autoimmune uveitis mouse model reveal a strong correlation between disease severity and diminished Foxo1 expression levels. Ectopic expression of Foxo1 selectively attenuates T-helper 17A production under pathogenic T-helper 17-inducing conditions. Moreover, enhanced Foxo1 expression, triggered by transforming growth factor β1 signaling, is implicated in fatty acid metabolism pathways that favor nonpathogenic T-helper 17 differentiation. Our drug screening identifies several US Food and Drug Administration-approved compounds can upregulate Foxo1. Collectively, our findings offer evidence that Foxo1 serves as a molecular switch to specifically control pathogenic vs nonpathogenic T-helper 17 differentiation in a transforming growth factor β1-dependent manner. Targeting Foxo1 could be a promising therapeutic strategy for autoimmune diseases.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139403209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lingbiao Wang, Hao Cheng, Xiaoxia Wang, Fangming Zhu, Na Tian, Zhan Xu, Hanlin Yin, Minrui Liang, Xue Yang, Xinnan Liu, Hongying Shan, Rong Fu, Boran Cao, Dan Li, Lianbo Xiao, Liangjing Lu, Sheng-Ming Dai, Qingwen Wang, Ling Lv, Hejian Zou, Bin Li
{"title":"Deubiquitination of aryl hydrocarbon receptor by USP21 negatively regulates T helper 17 cell differentiation.","authors":"Lingbiao Wang, Hao Cheng, Xiaoxia Wang, Fangming Zhu, Na Tian, Zhan Xu, Hanlin Yin, Minrui Liang, Xue Yang, Xinnan Liu, Hongying Shan, Rong Fu, Boran Cao, Dan Li, Lianbo Xiao, Liangjing Lu, Sheng-Ming Dai, Qingwen Wang, Ling Lv, Hejian Zou, Bin Li","doi":"10.1093/jleuko/qiae148","DOIUrl":"10.1093/jleuko/qiae148","url":null,"abstract":"<p><p>Aryl hydrocarbon receptor (AhR) is a key transcription factor that modulates the differentiation of T helper 17 (Th17) cells. How AhR is regulated at the post-translational level in Th17 cells remains largely unclear. Here, we identify USP21 as a newly defined deubiquitinase of AhR. We demonstrate that USP21 interacts with and stabilizes AhR by removing the K48-linked polyubiquitin chains from AhR. Interestingly, USP21 inhibits the transcriptional activity of AhR in a deubiquitinating-dependent manner. USP21 deubiquitinates AhR at the K432 residue, and the maintenance of ubiquitination on this site is required for the intact transcriptional activity of AhR. Moreover, the deficiency of USP21 promotes the differentiation of Th17 cells both in vitro and in vivo. Consistently, adoptive transfer of USP21-deficient naïve CD4+ T cells elicits more severe colitis in Rag1-/- recipients. Therefore, our study reveals a novel mechanism in which USP21 deubiquitinates AhR and negatively regulates the differentiation of Th17 cells.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}