Frontiers in Cell and Developmental Biology最新文献

{"title":"Single-cell and bulk RNA-sequencing reveal PRRX2-driven cancer-associated fibroblast-mediated perineural invasion for predicting the immunotherapy outcome in colorectal cancer.","authors":"Mingxiao Chen, Yue Cai, Feng Han, Bo Li, Zhou Xu, Kaili Cui, Wenqi Bai, Feng Li","doi":"10.3389/fcell.2025.1620388","DOIUrl":"10.3389/fcell.2025.1620388","url":null,"abstract":"<p><strong>Background: </strong>Perineural invasion (PNI) is common in a variety of solid tumors and has been identified as an important pathway promoting tumor local invasion and distant metastasis. Its presence is usually associated with increased aggressiveness, malignant biology, and a worse patient prognosis. However, its specific role and regulatory mechanisms in colorectal cancer (CRC) remain unclear.</p><p><strong>Methods: </strong>In this study, we integrated 20 CRC single-cell transcriptome datasets, which contained 575,768 high-quality cells, and used the Scissor algorithm to map PNI phenotypes in TCGA bulk samples to the single-cell level. Nine cancer-associated fibroblast (CAF) subpopulations were identified and functionally annotated. We evaluated the clinical relevance of CAF subsets in TCGA and three independent cohorts (silu_2022, GSE39582, and GSE17536) using BayesPrism-based deconvolution. We analyzed transcriptional regulatory networks using pySCENIC and validated PRRX2 function by <i>in vitro</i> experiments. Immune infiltration characteristics were quantified using the ssGSEA score, and the association between the PRRX2 score and immune checkpoint inhibitor efficacy was analyzed in conjunction with two immunotherapy cohorts. In addition, we performed a drug sensitivity analysis based on the GDSC pharmacogenomics database to screen potential therapeutic agents.</p><p><strong>Results: </strong>In this study, we systematically revealed the characteristics of the perineural invasion-associated fibroblast subsets and their regulatory mechanisms. In PNI-positive tumors, the proportion of fibroblasts was significantly increased, with the enrichment of MMP2+ myofibroblastic cancer-associated fibroblasts (myCAFs), and facilitated perineural infiltration through extracellular matrix remodeling. Further analysis revealed that PRRX2 was a core regulator of MMP2+myCAFs, promoting perineural invasion through the activation of TGF-β signaling pathways. PRRX2 knockdown significantly inhibited fibroblast proliferation, clonogenic formation, and invasive migration capacity, and it reduced TGFB1 and NGF expressions. The clinical cohort validation demonstrated a significant correlation between the PRRX2-score and advanced tumor stage, along with vascular and lympho-vascular invasion (LVI). Furthermore, patients with high PRRX2 scores had a significantly worse prognosis. In addition, patients with high PRRX2 scores responded poorly to immune checkpoint inhibitors but may be sensitive to targeted agents or antibody-coupled drugs, which may serve as potential targets for combination therapy.</p><p><strong>Conclusion: </strong>This analysis established PRRX2-driven MMP2+myCAFs as pivotal mediators of CRC perineural invasion through TGF-β/ECM remodeling. The PRRX2 score serves as a biomarker for prognosis prediction and immunotherapy outcome.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1620388"},"PeriodicalIF":4.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12516196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291616","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":"Advances in mild photothermal hydrogel-based therapies for bone and soft tissue injuries.","authors":"Peng Na, Jing-Lun Jiang, Ren-Peng Lv, Fan Yang, Shi-Feng Li, Xian-Zhuo Chen","doi":"10.3389/fcell.2025.1696209","DOIUrl":"10.3389/fcell.2025.1696209","url":null,"abstract":"<p><p>Bone and soft tissue injuries resulting from trauma, metabolic disorders, and tumors pose a serious threat to public health, and their treatment faces numerous challenges, including infection, chronic inflammation, and impaired vascularization. Photothermal hydrogels, a new class of biomaterials, can sterilize tissues via photothermal therapy (PTT) and, through intelligent material design, exhibit multiple biological functions such as modulating the pathological microenvironment in bone and soft tissues. These properties have earned them a reputation as a \"star material\" in tissue engineering. However, excessive heating (above 50 °C) can cause irreversible thermal damage to tissues. Therefore, functional hydrogels that generate a mild photothermal effect (approximately 40 °C-45 °C) have recently become a research focus. This review provides a comprehensive overview of the types and fabrication strategies of photothermal agents used in mild photothermal hydrogels, systematically summarizes recent progress in their applications for bone and soft tissue injury repair, and delves into the underlying mechanisms by which they promote tissue regeneration. By summarizing current findings and outlining future perspectives on the use of mild photothermal hydrogels in modern regenerative medicine, we aim to advance the development of tissue engineering.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1696209"},"PeriodicalIF":4.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12511113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145279344","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":"Involvement of <i>ACSM</i> family genes in the reprogramming of lipid metabolism within tumors and their investigation as promising therapeutic targets.","authors":"Ke-Xin Fang, Zi-Qi Li, Jin-Liang Dong, Ze Yu","doi":"10.3389/fcell.2025.1663033","DOIUrl":"10.3389/fcell.2025.1663033","url":null,"abstract":"<p><p>Metabolic reprogramming of tumor cells is an important feature of oncogenesis and progression, with lipid metabolism playing a key role in this process. The enzymes encoded by the ACSM (Acyl-CoA Synthetase Medium-Chain Family) genes play a crucial role in fatty acid activation, affecting the energy supply and membrane synthesis of tumor cells. In recent years, research on the expression patterns of ACSM family genes in different tumor types and their regulatory mechanisms has gradually increased, revealing their close relationship with tumor development. However, current research on ACSM family genes still has some shortcomings, such as a lack of systematic large-scale clinical data support and an in-depth understanding of their regulatory networks. This work summarizes the role of ACSMs in tumor lipid metabolic reprogramming and explores their research progress as potential therapeutic targets, providing new ideas for future tumor treatment.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1663033"},"PeriodicalIF":4.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12511025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145279433","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":"A comparative transcriptomics analysis of mammalian and non-mammalian acute kidney injury (AKI) models.","authors":"Matthew R Hawkins, Diana Cervera, Tiffany M Tang, Rebecca A Wingert","doi":"10.3389/fcell.2025.1653967","DOIUrl":"10.3389/fcell.2025.1653967","url":null,"abstract":"<p><strong>Introduction: </strong>Acute kidney injury (AKI) is a complex clinical condition characterized by decline in renal function and widespread transcriptional dysregulation. While transcriptomic studies that compare human and other mammalian models of AKI have provided insight, much less is known about commonalities and contrasts between mammalian models and nontraditional and regenerative laboratory models. Understanding these molecular level responses to injury in both regenerative and non-regenerative models may reveal conserved and unique pathways in renal repair.</p><p><strong>Methods: </strong>To investigate transcriptional responses to AKI across species, we incorporated newly available RNA-seq data from zebrafish, axolotl, and spiny mouse models into an expanded cross-species comparative analysis. These were analyzed alongside existing and previously analyzed data from both human and mouse (Mus) models. Differential gene expression and gene-ontology (GO) enrichment analyses we utilized to identify conserved and regeneration-specific during injury and recovery phases.</p><p><strong>Results: </strong>Comparative transcriptomic analysis revealed distinct transcriptional programs in each species during AKI, including both shared and species-specific responses. Of note, zebrafish show differential expression of apolipoproteins, molecules of increasing interest to the greater field of nephrology. In the recovery setting, we show that animals with regenerative capacity have conserved and divergent transcriptional programs.</p><p><strong>Discussion: </strong>Our findings demonstrate that non-traditional animal models of AKI, such as zebrafish, axolotls, and spiny mice, provide valuable insights into the molecular basis of kidney regeneration. The identification of conserved and divergent injury responses suggests evolutionary conservation in core AKI mechanisms, while also pointing to regeneration-associated transcriptional programs that could inform future therapeutic strategies. This work underscores the importance of using non-traditional models as well as the value in comparative analysis with traditional models and clinical data.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1653967"},"PeriodicalIF":4.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12510925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145279371","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":"Modeling craniofacial spliceosomopathies: a pathway toward deciphering disease mechanisms.","authors":"Casey Griffin","doi":"10.3389/fcell.2025.1624043","DOIUrl":"10.3389/fcell.2025.1624043","url":null,"abstract":"<p><p>Craniofacial spliceosomopathies are syndromes resulting from mutations in components of the spliceosome, presenting with facial dysostosis in combination with other phenotypes. An outstanding question in the field is how mutations in the ubiquitously expressed spliceosome lead to such cell- and tissue-specific disorders. To understand the etiology of these diseases and decipher the underlying mechanisms, scientists have turned to modeling these disorders in the laboratory. <i>In vivo</i> modeling of these disorders includes the use of mice, zebrafish, and frogs, whereas <i>in vitro</i> modeling typically uses embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). The goal with these models is to recapitulate the human disorders in a manner that is conducive to scientific exploration. In this review, we briefly describe the major craniofacial spliceosomopathies and discuss recent advances using model systems that have helped understand the root cause of these conditions.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1624043"},"PeriodicalIF":4.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12510987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145279504","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":"Advances in tumor-associated macrophage-mediated chemotherapeutic resistance in glioma.","authors":"Xuebo Liu, Qi Yu","doi":"10.3389/fcell.2025.1676338","DOIUrl":"10.3389/fcell.2025.1676338","url":null,"abstract":"<p><p>Tumor-associated macrophages (TAMs) are a dominant immune component within the glioma microenvironment and are increasingly recognized as key contributors to therapeutic resistance, the major challenge in glioma management. Understanding their role is critical for developing novel therapies. This review synthesizes current knowledge on TAM-mediated chemoresistance in glioma. TAMs originate from bone marrow-derived monocytes and resident microglia, exhibiting significant heterogeneity and plasticity, particularly between pro-inflammatory (M1) and pro-tumorigenic (M2) phenotypes. M2-like TAMs drive resistance through multiple mechanisms: (1) Modulating drug metabolism/clearance (e.g., via CYP450 enzymes and P-glycoprotein); (2) Secreting protumor factors (TNF-α, ILs like IL-4/IL-6/IL-10, chemokines like CCL5/CCL22, growth factors like VEGF/EGF) that activate survival pathways, induce immunosuppression, promote angiogenesis, and enhance epithelial-mesenchymal transition (EMT); (3) Interacting with glioma stem cells (GSCs) to maintain stemness; (4) Facilitating microenvironmental adaptation (e.g., hypoxia/HIF-1α response); (5) Remodeling the extracellular matrix (ECM) via MMPs, increasing stiffness and impairing drug penetration. Targeting TAMs offers promising approaches to overcome resistance. Strategies include: (1) Reprogramming M2 to M1 phenotypes using agonists (TLR, STING, CD40) or inhibitors (STAT3/STAT6); (2) Metabolic modulation (targeting glycolysis, fatty acid oxidation, glutaminolysis); (3) Blocking recruitment axes (CCL2/CCR2, CSF-1/CSF-1R, CXCL12/CXCR4); (4) Depleting M2-TAMs (e.g., trabectedin, CAR-T cells, M2pep-drugs); (5) Enhancing phagocytosis (anti-SIRPα/CD47, anti-SIGLEC). TAMs are pivotal mediators of chemoresistance in glioma through diverse molecular and cellular mechanisms. Targeting TAM recruitment, polarization, function, or metabolism represents a promising therapeutic avenue. However, the complexity of the glioma microenvironment and blood-brain barrier necessitate combination strategies for clinical translation. Further research is needed to optimize specificity and overcome challenges like compensatory pathways and drug delivery.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1676338"},"PeriodicalIF":4.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12511076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145279323","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":"Editorial: Advances in dental pulp stem cell biology and applications.","authors":"Simona Delle Monache, Fanny Pulcini, Anne George","doi":"10.3389/fcell.2025.1695340","DOIUrl":"10.3389/fcell.2025.1695340","url":null,"abstract":"","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1695340"},"PeriodicalIF":4.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12511626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145279349","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 emerging roles of autophagy in the homeostasis of lysosome-related organelles.","authors":"Xinran Wang, Luan Zhang, Xueqin Cao, Yuting Zhao","doi":"10.3389/fcell.2025.1638905","DOIUrl":"10.3389/fcell.2025.1638905","url":null,"abstract":"","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1638905"},"PeriodicalIF":4.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12511120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145279440","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":"<i>GNA13</i> promotes brain metastasis of non-small cell lung cancer and EMT through the WNT/β catenin signaling pathway.","authors":"Jia-Qi Wu, Han-Peng Zou, Ruo-Yue Fan, Jing Cai, Ping Wei, Ming-Fang He, Jin Xiang","doi":"10.3389/fcell.2025.1652200","DOIUrl":"10.3389/fcell.2025.1652200","url":null,"abstract":"<p><strong>Background: </strong>Brain metastasis (BM) remains a major challenge in non-small cell lung cancer (NSCLC) treatment, with poorly understood mechanisms.</p><p><strong>Methods: </strong>A zebrafish xenograft model was established using the H1299 cell line to study NSCLC BM. RNA-Seq identified differentially expressed genes (DEGs) in metastasized to brain vs. non-metastasized cells. Clinical relevance of DEGs was validated using The Cancer Genome Atlas (TCGA) and Kaplan-Meier survival analysis. The anti-proliferation, migration, and invasion effects of <i>GNA13</i> were also detected using CCK8 assay, scratch wound healing assay, and transwell assay <i>in vitro</i>. The <i>in vivo</i> effects of <i>GNA13</i> in proliferation and migration were further examined in zebrafish embryos. Additionally, real-time quantitative PCR (RT-qPCR) and Western Blot were performed to validate and explore the underlying molecular mechanisms.</p><p><strong>Results: </strong>Through comprehensive RNA-Seq analysis of zebrafish xenograft model, we identified 177 DEGs significantly associated with NSCLC BM. KEGG and GO enrichment identified <i>GNA13</i> as a key mediator in NSCLC BM. Clinical correlation analysis confirmed that <i>GNA13</i> expression was associated with NSCLC BM and poor prognosis in lung cancer patients. Functional validation revealed that <i>GNA13</i> knockdown reduced H1299 cell viability, migration, and invasion, whereas overexpression in A549 cells increased viability migration, and invasion <i>in vitro</i>. These <i>in vitro</i> findings were further validated <i>in vivo</i>, where <i>GNA13</i> overexpression promoted tumor proliferation and metastatic potential. <i>GNA13</i> was shown to activate the Wnt/β-catenin signaling pathway and induce epithelial-mesenchymal transition (EMT), thereby enhancing the metastatic potential of lung cancer cells.</p><p><strong>Conclusion: </strong>This study identifies <i>GNA13</i> as a key gene of lung cancer BM. <i>GNA13</i> promotes EMT and enhances the proliferation and metastatic capacity of lung cancer cells by activating the Wnt/β-catenin signaling pathway. These findings suggest that <i>GNA13</i> may serve as a potential therapeutic target for preventing or treating BM in NSCLC.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1652200"},"PeriodicalIF":4.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12511054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145279352","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":"Machine learning based immune evasion signature for predicting the prognosis and immunotherapy benefit in stomach adenocarcinoma.","authors":"Wenwu Xue, Guanglin Zhang, Cui Yang, Tingting Tan, Weichun Zhang, Hongcai Chen","doi":"10.3389/fcell.2025.1656367","DOIUrl":"10.3389/fcell.2025.1656367","url":null,"abstract":"<p><strong>Background: </strong>Stomach adenocarcinoma (STAD) remains a major contributor to cancer-related mortality worldwide. Despite advances in immunotherapy, only a subset of STAD patients benefits from immune checkpoint inhibitors, largely due to tumor-intrinsic immune evasion mechanisms. Therefore, robust predictive biomarkers are urgently needed to guide prognosis assessment and therapeutic decision-making.</p><p><strong>Methods: </strong>An integrative machine learning framework incorporating 10 algorithms was applied to construct an immune evasion signature (IES) using 101 model combinations. The optimal model was selected based on concordance index (C-index) across validation datasets. The prognostic and immunological relevance of the IES was assessed via survival analyses, immune infiltration deconvolution, and multiple immunotherapy response metrics. Key genes were further validated using qPCR, immunohistochemistry, and <i>in vitro</i> functional assays.</p><p><strong>Results: </strong>A four-gene IES developed via the LASSO method demonstrated robust prognostic power across TCGA and multiple external cohorts. High IES score were associated with poor survival, reduced immune cell infiltration (e.g., CD8⁺ T cells, dendritic cells), elevated M2 macrophage abundance, and an immunosuppressive tumor microenvironment. Patients in the low IES score group exhibited favorable immunotherapy-associated features, including higher TMB, lower TIDE scores, and increased response rates in three independent immunotherapy datasets. Additionally, the IES stratified patients by sensitivity to chemotherapy and targeted therapies. KLF16, one of the signature genes, was upregulated in STAD and promoted cancer cell proliferation <i>in vitro</i>.</p><p><strong>Conclusion: </strong>We established a novel IES with strong potential to predict prognosis and immunotherapy response in STAD. This IES may serve as a valuable tool for risk stratification and individualized treatment planning in clinical practice.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1656367"},"PeriodicalIF":4.6,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12507746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145279485","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}