Journal of Leukocyte Biology最新文献

{"title":"High CD163+CD206+ macrophage infiltration in the bone marrow microenvironment of newly diagnosed multiple myeloma patients.","authors":"Dong-Hai Han, Ya-Ru Li, Hui-Ping Li, Xiao-Qin Pian, Jin-Hong Gao, Ya-Peng Zhang, Bin-Tao Huang, Da Gao, Hong-Yan Zhao","doi":"10.1093/jleuko/qiag076","DOIUrl":"10.1093/jleuko/qiag076","url":null,"abstract":"<p><p>Multiple myeloma (MM) is a neoplastic disease caused by abnormal clonal plasma cells in the bone marrow (BM). Macrophages (MФs) are essential components of BM microenvironment and crucial mediators of plasma cells. Therefore, investigating alterations in the specific MФ subsets within the MM BM microenvironment is of significant importance for elucidating the underlying mechanisms of MM. Here, using flow cytometry, we characterized the dynamics of BM MФ subsets in newly diagnosed multiple myeloma (NDMM) patients and complete remission multiple myeloma (CRMM) patients. We found that NDMM patients exhibited increased infiltration of CD163+CD206+ MФs and elevated levels of interleukin (IL)-6 and IL-10 in the BM compared with CRMM patients and healthy control subjects. BM intermediate monocytes and nonclassical monocytes were increased in NDMM patients compared with those in CRMM patients and healthy control subjects. Furthermore, we observed upregulated CCR2 and CSF-R expression on the BM CD163+CD206+ MФs. Notably, the BM CD163+CD206+CCR2+ MФs were positively correlated with the increased level of IL-6, while CD163+CD206+CSF-R+ MФs were positively correlated with the level of IL-10. Additionally, clinical correlation analysis revealed that an increased proportion of CD163+CD206+CCR2+ MФs was negatively correlated with hemoglobin levels and positively correlated with β2-microglobulin and lactate dehydrogenase. Moreover, a higher proportion of CD163+CD206+CCR2+ MФs was detected in the BM of MM patients with poor prognosis. Altogether, our findings suggest that higher proportion of BM CD163+CD206+ MФs is involved in pathogenesis of MM, and that CCR2 may be potential therapeutic targets for improving antitumor therapy in MM.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148308148","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":"Sombrero vesicles: from overlooked structures to primary mediators of eosinophil secretion.","authors":"Rossana C N Melo, Peter F Weller","doi":"10.1093/jleuko/qiag072","DOIUrl":"10.1093/jleuko/qiag072","url":null,"abstract":"<p><p>Eosinophils, cells of the innate immune system, have a unique architecture, which includes morphologically complex secretory granules and a prominent, activation-responsive vesiculotubular system. In human eosinophils, this system is collectively termed eosinophil sombrero vesicles (EoSVs) because of its peculiar morphology feasibly identifiable by transmission electron microscopy. Considered as \"microgranules\" or \"small granules\" in the past, EoSVs are currently defined as active components of the eosinophil secretory pathway, sprouting from specific granules and trafficking granule-derived products in the eosinophil cytoplasm. Eosinophil secretory proteins associated with EoSVs include cationic proteins, cytokines, cytokine receptors, membrane fusion complexes, and tetraspanins. Beyond the intracellular landscape, emerging evidence has revealed a more complex functional repertoire for EoSVs. This review offers an overview of EoSVs as key participants in the mechanisms of eosinophil secretion during immune responses, incorporating the recent understanding of these transport carriers as extracellular vesicles, potentially implicated in the traffic of eosinophil products in the extracellular medium and intercellular communication.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148175781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The anti-CD33 antibody drug conjugate gemtuzumab ozogamicin depletes and functionally resets CD33+ myeloid-derived suppressor cells in patients with metastatic cancer: a phase 2 single-arm, open-label trial.","authors":"Carmela De Santo, Aimee Jackson, Francis Mussai, Saly Al-Taei, Neeraj Lal, Thomas Starkey, Livingstone Fultang, Nicola McJannett, Victoria Kunene, Lucinda Billingham, Anna Lawson, Su Lee, Joseph Rogers, Gary Middleton","doi":"10.1093/jleuko/qiag083","DOIUrl":"10.1093/jleuko/qiag083","url":null,"abstract":"<p><p>We previously demonstrated that the anti-CD33 antibody drug conjugate gemtuzumab ozogamicin (GO) binds CD33-expressing monocytic myeloid-derived suppressor cells (M-MDSCs), is internalized, and decreases those cells' viability. Treatment of MDSCs with GO restores T-cell proliferation in co-culture, overcomes M-MDSC suppression of CAR-T cell proliferation, and enhances target-cell killing. Gemtuzumab Ozogamicin Therapy in Hemophagocytic Lymphohistiocytosis or Macrophage Activation Syndrome (GOTHAM) is a phase 2 single-arm clinical trial for which patients were eligible if they had a diagnosis of solid cancer with radiological or clinical evidence of disease progression, or primary or secondary hemophagocytic lymphohistiocytosis, or macrophage activation syndrome disease relapsing or refractory to treatment at enrollment. An initial regimen of 3 mg/m2 GO on days 1, 8, and 15 was tested, adjusted to 21-d intervals: days 1, 22, and 43. The primary outcome was the impact of GO therapy on peripheral CD33+ myeloid cells. Using 2 schedules of GO, we could not convincingly demonstrate safe feasibility in patients with solid cancer, because of neutropenia. However, GO reproducibly and significantly reduced circulating MDSCs. Importantly, there is consistent preliminary evidence that, upon rebound, the monocyte population of CD33+ cells is replaced with nonsuppressive monocytes. These data support the phase 1b dose-escalation testing of GO up to 2 mg/m2 in combination with immune checkpoint blockade and other immunotherapies in patients with solid cancer to find a dose that depletes and repolarizes MDSCs without causing undue neutropenia, paving the way to use GO as an immune potentiator in this patient population. Trial registration: ISRCTN 89158144.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13346843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148277565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A TNFR2 biparatopic antagonist reverses immune suppression through a crosslinking-resistant and ADCC-independent mechanism.","authors":"Shusu Liu, Zhichao Eric Ai, Jinli Xie, Kai Yu, Fei Chen, Zhongzhou Zheng, Yijie Gao, Zhipeng Yan","doi":"10.1093/jleuko/qiag086","DOIUrl":"10.1093/jleuko/qiag086","url":null,"abstract":"<p><p>Tumor necrosis factor receptor 2 (TNFR2) is a promising immunotherapeutic target due to its high upregulation on immunosuppressive populations, like regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). The clinical efficacy of conventional bivalent TNFR2 antagonists, such as BI1808, is fundamentally constrained by a heavy reliance on Fc-mediated effector functions and a significant risk of \"agonistic conversion\" upon crosslinking within the tumor microenvironment. To overcome these liabilities, we engineered \"Duo1,\" a novel biparatopic antagonist that enables simultaneous, monovalent engagement of 2 distinct TNFR2 epitopes. Biophysical analysis confirmed Duo1 forms stable 1:1 complexes with TNFR2 with high-affinity (KD = 0.165 nM), structurally locking the target to prevent the receptor oligomerization required for agonistic signaling. Crucially, while conventional bivalent frameworks convert into potent agonists upon crosslinking, Duo1 maintains absolute, durable antagonism regardless of FcγR engagement. Functionally, Duo1 potently suppressed Treg differentiation and reversed Treg-mediated immunosuppression in vitro without impairing CD8 + effector T cell or CD4 + conventional T cell function. In a TNFR2-humanized MC38 syngeneic model, Duo1 mediated significant, dose-dependent tumor growth inhibition comparable to benchmark BI1808. Notably, this antitumor efficacy was fully preserved in an effector-silent (PGLALA) variant, confirming that its therapeutic mechanism operates through pure antagonistic signaling blockade, independent of Fc-mediated effector functions. Furthermore, treatment with Duo1 significantly remodeled the tumor microenvironment, markedly reducing immunosuppressive populations and increasing the intratumoral CD8+/Treg ratio. By uncoupling antitumor activity from both the risks of crosslinking induced agonistic conversion and a dependence on immune cell mediated effector function, Duo1 represents a highly superior next-generation immunotherapeutic paradigm for TNFR2-rich, immunosuppressive malignancies.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148317519","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":"Differences in the cell wall architecture drive strain-specific IgA induction by Limosilactobacillus reuteri.","authors":"Ran Lu, Brianna K Swartwout, Jee-Hwan Oh, Sahitya Ranjan Biswas, Jan-Peter van Pijkeren, Xin M Luo","doi":"10.1093/jleuko/qiag088","DOIUrl":"10.1093/jleuko/qiag088","url":null,"abstract":"<p><p>Limosilactobacillus reuteri (formerly Lactobacillus reuteri) is a well-studied commensal bacterium known for various health benefits. Our recent findings reveal that the human-derived strain L. reuteri CF48-3A enhances endogenous neonatal immunoglobulin A (IgA) production in mice. In a comparative analysis between the human isolates CF48-3A and PTA-6475, we observed that only CF48-3A induces splenocyte IgA production in vitro, highlighting strain-specific functional diversity within L. reuteri. Further study revealed that the 2 strains modulate B cell IgA production through distinct mechanisms, largely due to differences in surface proteins and activation of Toll-like receptor 2 (TLR2). While CF48-3A promotes IgA+ plasmablast differentiation and proliferation, PTA-6475 fails to promote antibody-secreting cell (ASC) populations and does not induce IgA. This latter phenotype was traced to differences in the cell surface architecture. A derivative of PTA-6475 in which 8 genes encoding cell surface proteins were inactivated (L. reuteri VPL4366) gained the function to promote plasmablast differentiation and IgA induction. Additionally, IgA induction by CF48-3A and L. reuteri VPL4366 appears to occur, at least partially, via TLR2 signaling, and is not associated with B lymphocyte stimulator (BLyS) or TGF-β signaling. These in vitro findings emphasize that the strain-specific cell wall architecture plausibly impacts L. reuteri on IgA induction and suggests unique mechanisms by which L. reuteri strains influence B cell differentiation.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148317532","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":"Autofluorescence enables detection and quantification of EETosis in human leukocyte cultures.","authors":"Masashi Akiyama, Koichi Kokame","doi":"10.1093/jleuko/qiag096","DOIUrl":"10.1093/jleuko/qiag096","url":null,"abstract":"<p><p>Eosinophils are leukocytes involved in defense against multicellular parasites and other pathogens. Like neutrophils, eosinophils can undergo a cytolytic form of cell death known as eosinophil extracellular trap cell death (EETosis), during which they release DNA and cytoplasmic granules to form eosinophil extracellular traps (EETs). Here, we demonstrate that eosinophil granules released during EETosis exhibit distinct autofluorescence in both purified human eosinophil cultures and mixed leukocyte cultures. This autofluorescence allowed detection of EETosis in mixed leukocyte cultures without additional staining or eosinophil isolation. We further show that 2 vanilloid compounds, previously identified as inhibitors of NETosis, suppress phorbol 12-myristate 13-acetate-induced EETosis. By measuring the autofluorescence intensity of released eosinophil granules, we successfully quantified the inhibitory effects of these compounds on EETosis. Our autofluorescence-based assay enables rapid and convenient detection of EETosis and provides a useful tool for in vitro studies of eosinophil biology.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148375982","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":"Cold atmospheric plasma as an immunomodulator: suppression of T-cell hyperactivation and graft-vs-host disease via redox regulation.","authors":"Thoh Maikho, Raghavendra S Patwardhan, Binita Kislay Kumar, Deepak Sharma, Santosh K Sandur","doi":"10.1093/jleuko/qiag066","DOIUrl":"10.1093/jleuko/qiag066","url":null,"abstract":"<p><p>Cold atmospheric plasma (CAP) has garnered substantial attention in biomedical science, owing to its wide therapeutic applications in wound healing, disinfection, dentistry, cancer care, and inflammation. The anti-inflammatory effects of CAP have been studied, but, to our knowledge, there are no reports investigating its effect on T cell hyperactivation-associated pathologies. This study examines CAP's impact on antigen-driven and homeostatic T cell proliferation and its potential to prevent acute graft-vs-host disease (GvHD). CAP treatment significantly attenuated GvHD-associated mortality and morbidity in mice. CAP inhibited stimulation-induced T cell activation, surface marker expression, cytokine secretion, and proliferation, without inducing cell death, indicating noncytotoxic immunomodulation. CAP modulated cellular redox, and pretreatment with N-acetylcysteine- or PEGylated catalase-abrogated CAP-mediated suppression of mitogen-induced T cell responses. Moreover, CAP-mediated inhibition of stimulation-induced T cell responses was associated with suppression of the immune-regulatory, redox-sensitive transcription factors NF-κB and Nrf2. These findings underscore immunotherapeutic potential of CAP in treatment of disorders linked to T cell hyperactivation.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148376027","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":"Metabolic and epigenetic regulation of microglia memory in neurological disorders.","authors":"Xiaoya Wang, Yunpeng Jia, Xinyi Yan, Youwei Wang","doi":"10.1093/jleuko/qiag085","DOIUrl":"https://doi.org/10.1093/jleuko/qiag085","url":null,"abstract":"<p><p>As tissue-resident innate immune cells of the central nervous system, microglia are capable of acquiring innate immune memory-a persistent state of functional reprogramming triggered by prior stimuli. This memory typically manifests as 3 distinct phenotypes: trained immunity, immune tolerance, and immune exhaustion. In this review, we synthesize current knowledge on the metabolic and epigenetic mechanisms that govern these 3 forms of microglial innate immune memory. We further summarize and discuss how each phenotype is induced in microglia and its respective pathophysiological roles in neurological disorders. Owing to their slow turnover and unique tissue-resident characteristics, microglia sustain long-lasting memory states that can profoundly influence the trajectory of neuroinflammation and neurodegeneration. Finally, we highlight the bidirectional effects of microglial immune memory on disease progression, discuss emerging therapeutic strategies aimed at modulating these memory states, and outline key translational challenges that remain to be addressed.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":"118 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148411630","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":"BET inhibition curbs macrophage inflammation, lipid accumulation, and atherogenesis by disrupting the YAP/TAZ-BRD4 axis.","authors":"Praveen Krishna Veerasubramanian, Vijaykumar S Meli, Hamza Atcha, Wenqi Wang, Timothy L Downing, Wendy F Liu","doi":"10.1093/jleuko/qiag017","DOIUrl":"10.1093/jleuko/qiag017","url":null,"abstract":"<p><p>Macrophage dysfunction is hallmark of atherosclerotic disease, characterized by inflammation and uptake of oxidized low-density lipoproteins. We investigate the role of the epigenetic reader bromodomain-containing protein 4 (BRD4) in orchestrating macrophage responses through interactions with the mechanosensitive transcriptional coactivators YAP/TAZ. Suppression of BRD4 via bromodomain and extra-terminal motif (BET) protein inhibitors (BETi) unveils a remarkable capacity to mitigate YAP/TAZ-driven inflammation. Knockdown of YAP, TAZ, or BRD4 in macrophages shows a significant convergence of inflammatory genes under the regulatory purview of these transcriptional regulators. In addition, persistent activation of YAP and TAZ initiates a partial inflammatory phenotype in macrophages, which is effectively ameliorated with BETi. Notably, CD36 and low-density lipoprotein receptor-1 (LOX1), pivotal receptors involved in uptake of oxidized low-density lipoprotein, emerge as direct YAP/TAZ targets. We employed a BD2-specific BETi, ABBV-744, in an AAV-PCSK9-induced atherosclerosis model to test the therapeutic potential of BET inhibition. Although reduction in cholesterol levels is modest, BETi substantially curtails plaque formation, diminishing macrophage infiltration, and suppressing the upregulation of YAP/TAZ and oxidized low-density lipoprotein uptake receptors associated with atherogenesis. Intriguingly, even in conditions marked by heightened YAP/TAZ expression induced by myeloid cell-targeted YAP/TAZ overexpression, BETi effectively dampens inflammation, mitigates foam cell formation, and disease progression. Our work underscores the considerable promise of targeting the YAP/TAZ-BRD4 axis as a therapeutic strategy for averting atherosclerosis, thereby disrupting the relentless cycle of inflammation, mechanosensory responses, and oxLDL uptake characteristic of atherosclerosis progression.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13412306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147773776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rotavirus-specific intestinal resident memory T cells induced by oral vaccination in early-life mice may contribute to protective immunity.","authors":"Catherine Montenegro, Martín Alonso Rondón, Siyuan Ding, Federico Perdomo-Celis, Manuel A Franco","doi":"10.1093/jleuko/qiag080","DOIUrl":"10.1093/jleuko/qiag080","url":null,"abstract":"<p><p>Resident memory T cells (Trm) are key mediators of protective immunity at barrier sites, yet their development during early life remains poorly defined. Here, we show that early-life oral vaccination with a heterologous rhesus rotavirus (RV) induces short-lived intestinal Trm that are negative by intravascular staining and express a CD44+CD69+CD103+/-P2X7R+ phenotype. Blocking lymphocyte homing with an anti-α4β7 antibody during vaccination did not alter the magnitude of RV-specific intestinal T cells or affect protection following murine RV challenge. In contrast, reduction of RV-specific intraepithelial lymphocytes by nicotinamide adenine dinucleotide treatment, or genetic deletion of the aryl hydrocarbon receptor repressor (Ahrr-/- mice)-which also exhibit decreased intraepithelial CD8+ T cells after infection-resulted in increased viral antigen shedding upon challenge. These results suggest that intestinal Trm cells induced by early-life vaccination may contribute to protection against RV infection.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148239431","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}