Inflammation and regeneration最新文献

{"title":"Designer cell therapy for tissue regeneration.","authors":"Noyuri Zama, Satoshi Toda","doi":"10.1186/s41232-024-00327-4","DOIUrl":"10.1186/s41232-024-00327-4","url":null,"abstract":"<p><p>Cancer cell therapy, particularly chimeric antigen receptor (CAR) T-cell therapy for blood cancers, has emerged as a powerful new modality for cancer treatment. Therapeutic cells differ significantly from conventional drugs, such as small molecules and biologics, as they possess cellular information processing abilities to recognize and respond to abnormalities in the body. This capability enables the targeted delivery of therapeutic factors to specific locations and times. Various types of designer cells have been developed and tested to overcome the shortcomings of CAR T cells and expand their functions in the treatment of solid tumors. In particular, synthetic receptor technologies are a key to designing therapeutic cells that specifically improve tumor microenvironment. Such technologies demonstrate great potential for medical applications to regenerate damaged tissues as well that are difficult to cure with conventional drugs. In this review, we introduce recent developments in next-generation therapeutic cells for cancer treatment and discuss the application of designer therapeutic cells for tissue regeneration.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":"44 1","pages":"15"},"PeriodicalIF":0.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10941617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140141319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of inflammatory diseases via the control of mRNA decay.","authors":"Masanori Yoshinaga, Osamu Takeuchi","doi":"10.1186/s41232-024-00326-5","DOIUrl":"10.1186/s41232-024-00326-5","url":null,"abstract":"<p><p>Inflammation orchestrates a finely balanced process crucial for microorganism elimination and tissue injury protection. A multitude of immune and non-immune cells, alongside various proinflammatory cytokines and chemokines, collectively regulate this response. Central to this regulation is post-transcriptional control, governing gene expression at the mRNA level. RNA-binding proteins such as tristetraprolin, Roquin, and the Regnase family, along with RNA modifications, intricately dictate the mRNA decay of pivotal mediators and regulators in the inflammatory response. Dysregulated activity of these factors has been implicated in numerous human inflammatory diseases, underscoring the significance of post-transcriptional regulation. The increasing focus on targeting these mechanisms presents a promising therapeutic strategy for inflammatory and autoimmune diseases. This review offers an extensive overview of post-transcriptional regulation mechanisms during inflammatory responses, delving into recent advancements, their implications in human diseases, and the strides made in therapeutic exploitation.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":"44 1","pages":"14"},"PeriodicalIF":0.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10941436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140141320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronological transitions of hepatocyte growth factor treatment effects in spinal cord injury tissue.","authors":"Yuji Okano, Yoshitaka Kase, Yu Suematsu, Masaya Nakamura, Hideyuki Okano","doi":"10.1186/s41232-024-00322-9","DOIUrl":"10.1186/s41232-024-00322-9","url":null,"abstract":"<p><p>Inflammatory responses are known to suppress neural regeneration in patients receiving stem cell-based regenerative therapy for spinal cord injury (SCI). Consequently, pathways involved in neurogenesis and immunomodulation, such as the hepatocyte growth factor (HGF)/MET signaling cascade, have garnered significant attention. Notably, various studies, including our own, have highlighted the enhanced recovery of locomotor functions achieved in SCI animal models by combining HGF pretreatment and human induced stem cell-derived neural stem/progenitor cell (hiPSC-NS/PC) transplantation. However, these studies implicitly hypothesized that the functionality of HGF in SCI would be time consistent and did not elucidate its dynamics. In the present article, we investigated the time-course of the effect of HGF on SCI, aiming to uncover a more precise mechanism for HGF administration, which is indispensable for developing crystallizing protocols for combination therapy. To this end, we performed a detailed investigation of the temporal variation of HGF using the RNA-seq data we obtained in our most recent study. Leveraging the time-series design of the data, which we did not fully exploit previously, we identified three components in the effects of HGF that operate at different times: early effects, continuous effects, and delayed effects. Our findings suggested a concept where the three components together contribute to the acceleration of neurogenesis and immunomodulation, which reinforce the legitimacy of empirically fine-tuned protocols for HGF administration and advocate the novel possibility that the time-inconsistent effects of HGF progressively augment the efficacy of combined therapy.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":"44 1","pages":"10"},"PeriodicalIF":0.0,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10935783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140112532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene editing technology to improve antitumor T-cell functions in adoptive immunotherapy.","authors":"Yusuke Ito, Satoshi Inoue, Yuki Kagoya","doi":"10.1186/s41232-024-00324-7","DOIUrl":"10.1186/s41232-024-00324-7","url":null,"abstract":"<p><p>Adoptive immunotherapy, in which tumor-reactive T cells are prepared in vitro for adoptive transfer to the patient, can induce an objective clinical response in specific types of cancer. In particular, chimeric antigen receptor (CAR)-redirected T-cell therapy has shown robust responses in hematologic malignancies. However, its efficacy against most of the other tumors is still insufficient, which remains an unmet medical need. Accumulating evidence suggests that modifying specific genes can enhance antitumor T-cell properties. Epigenetic factors have been particularly implicated in the remodeling of T-cell functions, including changes to dysfunctional states such as terminal differentiation and exhaustion. Genetic ablation of key epigenetic molecules prevents the dysfunctional reprogramming of T cells and preserves their functional properties.Clustered, regularly interspaced, short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas)-based gene editing is a valuable tool to enable efficient and specific gene editing in cultured T cells. A number of studies have already identified promising targets to improve the therapeutic efficacy of CAR-T cells using genome-wide or focused CRISPR screening. In this review, we will present recent representative findings on molecular insights into T-cell dysfunction and how genetic modification contributes to overcoming it. We will also discuss several technical advances to achieve efficient gene modification using the CRISPR and other novel platforms.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":"44 1","pages":"13"},"PeriodicalIF":0.0,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10926667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140103062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The gateway reflex regulates tissue-specific autoimmune diseases.","authors":"Yuki Tanaka, Izuru Ohki, Kaoru Murakami, Satoshi Ozawa, Yaze Wang, Masaaki Murakami","doi":"10.1186/s41232-024-00325-6","DOIUrl":"10.1186/s41232-024-00325-6","url":null,"abstract":"<p><p>The dynamic interaction and movement of substances and cells between the central nervous system (CNS) and peripheral organs are meticulously controlled by a specialized vascular structure, the blood-brain barrier (BBB). Experimental and clinical research has shown that disruptions in the BBB are characteristic of various neuroinflammatory disorders, including multiple sclerosis. We have been elucidating a mechanism termed the \"gateway reflex\" that details the entry of immune cells, notably autoreactive T cells, into the CNS at the onset of such diseases. This process is initiated through local neural responses to a range of environmental stimuli, such as gravity, electricity, pain, stress, light, and joint inflammation. These stimuli specifically activate neural pathways to open gateways at targeted blood vessels for blood immune cell entry. The gateway reflex is pivotal in managing tissue-specific inflammatory diseases, and its improper activation is linked to disease progression. In this review, we present a comprehensive examination of the gateway reflex mechanism.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":"44 1","pages":"12"},"PeriodicalIF":0.0,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10919025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140051362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic network of the gut microbiota in inflammatory bowel disease.","authors":"Kohei Sugihara, Nobuhiko Kamada","doi":"10.1186/s41232-024-00321-w","DOIUrl":"10.1186/s41232-024-00321-w","url":null,"abstract":"<p><p>Gut dysbiosis is closely linked to the pathogenesis of inflammatory bowel disease (IBD). Emerging studies highlight the relationship between host metabolism and the modulation of gut microbiota composition through regulating the luminal microenvironment. In IBD, various disease-associated factors contribute to the significant perturbation of host metabolism. Such disturbance catalyzes the selective proliferation of specific microbial populations, particularly pathobionts such as adherent invasive Escherichia coli and oral-derived bacteria. Pathobionts employ various strategies to adapt better to the disease-associated luminal environments. In addition to the host-microbe interaction, recent studies demonstrate that the metabolic network between commensal symbionts and pathobionts facilitates the expansion of pathobionts in the inflamed gut. Understanding the metabolic network among the host, commensal symbionts, and pathobionts provides new insights into the pathogenesis of IBD and novel avenues for treating IBD.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":"44 1","pages":"11"},"PeriodicalIF":0.0,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10913301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140041202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of Staphylococcus aureus quorum sensing in cutaneous and systemic infections.","authors":"Yuriko Yamazaki, Tomoka Ito, Masakazu Tamai, Seitaro Nakagawa, Yuumi Nakamura","doi":"10.1186/s41232-024-00323-8","DOIUrl":"10.1186/s41232-024-00323-8","url":null,"abstract":"<p><strong>Background: </strong>Staphylococcus aureus is a leading cause of human bacterial infections worldwide. It is the most common causative agent of skin and soft tissue infections, and can also cause various other infections, including pneumonia, osteomyelitis, as well as life-threatening infections, such as sepsis and infective endocarditis. The pathogen can also asymptomatically colonize human skin, nasal cavity, and the intestine. S. aureus colonizes approximately 20-30% of human nostrils, being an opportunistic pathogen for subsequent infection. Its strong ability to silently spread via human contact makes it difficult to eradicate S. aureus. A major concern with S. aureus is its capacity to develop antibiotic resistance and adapt to diverse environmental conditions. The variability in the accessory gene regulator (Agr) region of the genome contributes to a spectrum of phenotypes within the bacterial population, enhancing the likelihood of survival in different environments. Agr functions as a central quorum sensing (QS) system in S. aureus, allowing bacteria to adjust gene expression in response to population density. Depending on Agr expression, S. aureus secretes various toxins, contributing to virulence in infectious diseases. Paradoxically, expressing Agr may be disadvantageous in certain situations, such as in hospitals, causing S. aureus to generate Agr mutants responsible for infections in healthcare settings.</p><p><strong>Main body: </strong>This review aims to demonstrate the molecular mechanisms governing the diverse phenotypes of S. aureus, ranging from a harmless colonizer to an organism capable of infecting various human organs. Emphasis will be placed on QS and its role in orchestrating S. aureus behavior across different contexts.</p><p><strong>Short conclusion: </strong>The pathophysiology of S. aureus infection is substantially influenced by phenotypic changes resulting from factors beyond Agr. Future studies are expected to give the comprehensive understanding of S. aureus overall profile in various settings.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":"44 1","pages":"9"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10905890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutual interaction of neurons and astrocytes derived from iPSCs with APP V717L mutation developed the astrocytic phenotypes of Alzheimer's disease.","authors":"Sopak Supakul, Rei Murakami, Chisato Oyama, Tomoko Shindo, Yuki Hatakeyama, Maika Itsuno, Hiroko Bannai, Shinsuke Shibata, Sumihiro Maeda, Hideyuki Okano","doi":"10.1186/s41232-023-00310-5","DOIUrl":"10.1186/s41232-023-00310-5","url":null,"abstract":"<p><strong>Background: </strong>The development of induced pluripotent stem cells (iPSCs) technology has enabled human cellular disease modeling for inaccessible cell types, such as neural cells in the brain. However, many of the iPSC-derived disease models established to date typically involve only a single cell type. These monoculture models are inadequate for accurately simulating the brain environment, where multiple cell types interact. The limited cell type diversity in monoculture models hinders the accurate recapitulation of disease phenotypes resulting from interactions between different cell types. Therefore, our goal was to create cell models that include multiple interacting cell types to better recapitulate disease phenotypes.</p><p><strong>Methods: </strong>To establish a co-culture model of neurons and astrocytes, we individually induced neurons and astrocytes from the same iPSCs using our novel differentiation methods, and then co-cultured them. We evaluated the effects of co-culture on neurons and astrocytes using immunocytochemistry, immuno-electron microscopy, and Ca²⁺ imaging. We also developed a co-culture model using iPSCs from a patient with familial Alzheimer's disease (AD) patient (APP ^V717L mutation) to investigate whether this model would manifest disease phenotypes not seen in the monoculture models.</p><p><strong>Results: </strong>The co-culture of the neurons and astrocytes increased the branching of astrocyte processes, the number of GFAP-positive cells, neuronal activities, the number of synapses, and the density of presynaptic vesicles. In addition, immuno-electron microscopy confirmed the formation of a tripartite synaptic structure in the co-culture model, and inhibition of glutamate transporters increased neuronal activity. Compared to the co-culture model of the control iPSCs, the co-culture model of familial AD developed astrogliosis-like phenotype, which was not observed in the monoculture model of astrocytes.</p><p><strong>Conclusions: </strong>Co-culture of iPSC-derived neurons and astrocytes enhanced the morphological changes mimicking the in vivo condition of both cell types. The formation of the functional tripartite synaptic structures in the co-culture model suggested the mutual interaction between the cells. Furthermore, the co-culture model with the APP ^V717L mutation expressed in neurons exhibited an astrocytic phenotype reminiscent of AD brain pathology. These results suggest that our co-culture model is a valuable tool for disease modeling of neurodegenerative diseases.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":"44 1","pages":"8"},"PeriodicalIF":0.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10900748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139992173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid and high-purity differentiation of human medium spiny neurons reveals LMNB1 hypofunction and subtype necessity in modeling Huntington's disease.","authors":"Junjiao Wu, Jie Ren, Hongfei Cui, Yali Xie, Yu Tang","doi":"10.1186/s41232-024-00320-x","DOIUrl":"10.1186/s41232-024-00320-x","url":null,"abstract":"<p><strong>Background: </strong>Different neural subtypes are selectively lost in diverse neurodegenerative diseases. Huntington's disease (HD) is an inherited neurodegenerative disease characterized by motor abnormalities that primarily affect the striatum. The Huntingtin (HTT) mutation involves an expanded CAG repeat, leading to insoluble polyQ, which renders GABA⁺ medium spiny neurons (MSN) more venerable to cell death. Human pluripotent stem cells (hPSCs) technology allows for the construction of disease-specific models, providing valuable cellular models for studying pathogenesis, drug screening, and high-throughput analysis.</p><p><strong>Methods: </strong>In this study, we established a method that allows for rapid and efficient generation of MSNs (> 90%) within 21 days from hPSC-derived neural progenitor cells, by introducing a specific combination of transcription factors.</p><p><strong>Results: </strong>We efficiently induced several neural subtypes, in parallel, based on the same cell source, and revealed that, compared to other neural subtypes, MSNs exhibited higher polyQ aggregation propensity and overexpression toxicity, more severe dysfunction in BDNF/TrkB signaling, greater susceptibility to BDNF withdrawal, and more severe disturbances in nucleocytoplasmic transport (NCT). We further found that the nuclear lamina protein LMNB1 was greatly reduced in HD neurons and mislocalized to the cytoplasm and axons. Knockdown of HTT or treatment with KPT335, an orally selective inhibitor of nuclear export (SINE), effectively attenuated the pathological phenotypes and alleviated neuronal death caused by BDNF withdrawal.</p><p><strong>Conclusions: </strong>This study thus establishes an effective method for obtaining MSNs and underscores the necessity of using high-purity MSNs to study HD pathogenesis, especially the MSN-selective vulnerability.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":"44 1","pages":"7"},"PeriodicalIF":0.0,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10870681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel artificial nerve transplantation of human iPSC-derived neurite bundles enhanced nerve regeneration after peripheral nerve injury.","authors":"Takayuki Nishijima, Kentaro Okuyama, Shinsuke Shibata, Hiroo Kimura, Munehisa Shinozaki, Takehito Ouchi, Yo Mabuchi, Tatsukuni Ohno, Junpei Nakayama, Manabu Hayatsu, Keiko Uchiyama, Tomoko Shindo, Eri Niiyama, Sayaka Toita, Jiro Kawada, Takuji Iwamoto, Masaya Nakamura, Hideyuki Okano, Narihito Nagoshi","doi":"10.1186/s41232-024-00319-4","DOIUrl":"10.1186/s41232-024-00319-4","url":null,"abstract":"<p><strong>Background: </strong>Severe peripheral nerve damage always requires surgical treatment. Autologous nerve transplantation is a standard treatment, but it is not sufficient due to length limitations and extended surgical time. Even with the available artificial nerves, there is still large room for improvement in their therapeutic effects. Novel treatments for peripheral nerve injury are greatly expected.</p><p><strong>Methods: </strong>Using a specialized microfluidic device, we generated artificial neurite bundles from human iPSC-derived motor and sensory nerve organoids. We developed a new technology to isolate cell-free neurite bundles from spheroids. Transplantation therapy was carried out for large nerve defects in rat sciatic nerve with novel artificial nerve conduit filled with lineally assembled sets of human neurite bundles. Quantitative comparisons were performed over time to search for the artificial nerve with the therapeutic effect, evaluating the recovery of motor and sensory functions and histological regeneration. In addition, a multidimensional unbiased gene expression profiling was carried out by using next-generation sequencing.</p><p><strong>Result: </strong>After transplantation, the neurite bundle-derived artificial nerves exerted significant therapeutic effects, both functionally and histologically. Remarkably, therapeutic efficacy was achieved without immunosuppression, even in xenotransplantation. Transplanted neurite bundles fully dissolved after several weeks, with no tumor formation or cell proliferation, confirming their biosafety. Posttransplant gene expression analysis highlighted the immune system's role in recovery.</p><p><strong>Conclusion: </strong>The combination of newly developed microfluidic devices and iPSC technology enables the preparation of artificial nerves from organoid-derived neurite bundles in advance for future treatment of peripheral nerve injury patients. A promising, safe, and effective peripheral nerve treatment is now ready for clinical application.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":"44 1","pages":"6"},"PeriodicalIF":0.0,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10863150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139725452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}