{"title":"Pathophysiological functions of semaphorins in the sympathetic nervous system.","authors":"Yumiko Mizuno, Yoshimitsu Nakanishi, Atsushi Kumanogoh","doi":"10.1186/s41232-023-00281-7","DOIUrl":"https://doi.org/10.1186/s41232-023-00281-7","url":null,"abstract":"<p><p>Upon exposure to external stressors, the body senses them and activates the sympathetic nervous system (SNS) to maintain the homeostasis, which is known as the \"fight-or-flight\" response. Recent studies have revealed that the SNS also plays pivotal roles in regulating immune responses, such as hematopoiesis, leukocyte mobilization, and inflammation. Indeed, overactivation of the SNS causes many inflammatory diseases, including cardiovascular diseases, metabolic disorders, and autoimmune diseases. However, the molecular basis essential for SNS-mediated immune regulation is not completely understood. In this review, we focus on axon guidance cues, semaphorins, which play multifaceted roles in neural and immune systems. We summarize the functions of semaphorins in the crosstalk between the SNS and the immune system, exploring its pathophysiological roles.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2023-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10249228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9608602","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}
Junichi Kushioka, Simon Kwoon-Ho Chow, Masakazu Toya, Masanori Tsubosaka, Huaishuang Shen, Qi Gao, Xueping Li, Ning Zhang, Stuart B Goodman
{"title":"Bone regeneration in inflammation with aging and cell-based immunomodulatory therapy.","authors":"Junichi Kushioka, Simon Kwoon-Ho Chow, Masakazu Toya, Masanori Tsubosaka, Huaishuang Shen, Qi Gao, Xueping Li, Ning Zhang, Stuart B Goodman","doi":"10.1186/s41232-023-00279-1","DOIUrl":"https://doi.org/10.1186/s41232-023-00279-1","url":null,"abstract":"<p><p>Aging of the global population increases the incidence of osteoporosis and associated fragility fractures, significantly impacting patient quality of life and healthcare costs. The acute inflammatory reaction is essential to initiate healing after injury. However, aging is associated with \"inflammaging\", referring to the presence of systemic low-level chronic inflammation. Chronic inflammation impairs the initiation of bone regeneration in elderly patients. This review examines current knowledge of the bone regeneration process and potential immunomodulatory therapies to facilitate bone healing in inflammaging.Aged macrophages show increased sensitivity and responsiveness to inflammatory signals. While M1 macrophages are activated during the acute inflammatory response, proper resolution of the inflammatory phase involves repolarizing pro-inflammatory M1 macrophages to an anti-inflammatory M2 phenotype associated with tissue regeneration. In aging, persistent chronic inflammation resulting from the failure of M1 to M2 repolarization leads to increased osteoclast activation and decreased osteoblast formation, thus increasing bone resorption and decreasing bone formation during healing.Inflammaging can impair the ability of stem cells to support bone regeneration and contributes to the decline in bone mass and strength that occurs with aging. Therefore, modulating inflammaging is a promising approach for improving bone health in the aging population. Mesenchymal stem cells (MSCs) possess immunomodulatory properties that may benefit bone regeneration in inflammation. Preconditioning MSCs with pro-inflammatory cytokines affects MSCs' secretory profile and osteogenic ability. MSCs cultured under hypoxic conditions show increased proliferation rates and secretion of growth factors. Resolution of inflammation via local delivery of anti-inflammatory cytokines is also a potential therapy for bone regeneration in inflammaging. Scaffolds containing anti-inflammatory cytokines, unaltered MSCs, and genetically modified MSCs can also have therapeutic potential. MSC exosomes can increase the migration of MSCs to the fracture site and enhance osteogenic differentiation and angiogenesis.In conclusion, inflammaging can impair the proper initiation of bone regeneration in the elderly. Modulating inflammaging is a promising approach for improving compromised bone healing in the aging population.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2023-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10210469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9531297","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 Ragulator complex: delving its multifunctional impact on metabolism and beyond.","authors":"Kohei Tsujimoto, Hyota Takamatsu, Atsushi Kumanogoh","doi":"10.1186/s41232-023-00278-2","DOIUrl":"10.1186/s41232-023-00278-2","url":null,"abstract":"<p><p>Our understanding of lysosomes has undergone a significant transformation in recent years, from the view that they are static organelles primarily responsible for the disposal and recycling of cellular waste to their recognition as highly dynamic structures. Current research posits that lysosomes function as a signaling hub that integrates both extracellular and intracellular stimuli, thereby regulating cellular homeostasis. The dysregulation of lysosomal function has been linked to a wide range of diseases. Of note, lysosomes contribute to the activation of mammalian target of rapamycin complex 1 (mTORC1), a key regulator of cellular metabolism. The Ragulator complex, a protein complex anchored on the lysosomal membrane, was initially shown to tether the mTORC1 complex to lysosomes. Recent research has substantially expanded our understanding of the roles of the Ragulator complex in lysosomes, including roles in the regulation of metabolism, inflammation, cell death, cell migration, and the maintenance of homeostasis, via interactions with various proteins. This review summarizes our current knowledge on the diverse functions of the Ragulator complex, highlighting important protein interactions.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10175929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9812656","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":"Regeneration of invariant natural killer T (iNKT) cells: application of iPSC technology for iNKT cell-targeted tumor immunotherapy.","authors":"Takahiro Aoki, Shinichiro Motohashi, Haruhiko Koseki","doi":"10.1186/s41232-023-00275-5","DOIUrl":"https://doi.org/10.1186/s41232-023-00275-5","url":null,"abstract":"<p><p>Invariant natural killer T (iNKT) cells are a subset of innate-like T cells restricted by a major histocompatibility complex (MHC) class I-like molecule, CD1d. iNKT cells express an invariant T cell receptor (TCR) encoded by Vα14 Jα18 in mice and Vα24 Jα18 in humans and are activated by recognizing glycolipid antigens, such as α-galactosylceramide (αGalCer), presented by CD1d. iNKT cells exhibit anti-tumor activity via their NK-like cytotoxicity and adjuvant activity. Although iNKT cell-targeted immunotherapy is a conceptually promising approach, we still found a technical hurdle for its clinical implementation which is mainly due to the low frequency of iNKT cells, particularly in humans. To compensate for this, we proposed to generate adequate numbers of clinically competent NKT cells from induced pluripotent stem cells (iPSCs) for cancer immunotherapy. Toward this goal, we first obtained the proof of concept (POC) for this approach in mice. We developed a technology to differentiate iPSCs into iNKT cells (iPSC-iNKT cells) and found iPSC-iNKT cells efficiently rejected a syngeneic experimental thymoma by inducing antigen-specific CD8 T cells. After achieving the POC in mice, we developed human iPSC-iNKT cells, which had a high correlation in their gene expression profiles with parental iNKT cells. Human iPSC-iNKT cells also exhibited anti-tumor activity and adjuvant activity for human NK cells in vivo. Based on this supporting evidence for the anti-tumor activity of human iPSC-iNKT cells, we began to generate good manufacturing practice (GMP)-grade iPSC-iNKT cells. As of now, the first-in-human clinical trial of iPSC-iNKT cell therapy is ongoing as a single-agent, dose-escalation study for patients with advanced head and neck cancer. Demonstration of the safety of iPSC-iNKT cell therapy may allow us to improve the strategy by further reinforcing the therapeutic activity of iPSC-iNKT, cells either by gene-editing or combinatorial use with other immune cell products such as dendritic cells. Sixteen years after the establishment of the iPSC technology, we are reaching the first checkpoint to evaluate the clinical efficacy of iPSC-derived immune cells.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2023-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10176773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9459732","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":"Neuroinflammation in Alzheimer's disease: microglial signature and their relevance to disease.","authors":"Akira Sobue, Okiru Komine, Koji Yamanaka","doi":"10.1186/s41232-023-00277-3","DOIUrl":"https://doi.org/10.1186/s41232-023-00277-3","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the most common form of dementia, pathologically characterized by senile plaques and neurofibrillary tangles (NFTs), resulting in neurodegeneration. Neuroinflammation, defined as the activation of glial cells such as microglia and astrocytes, is observed surrounding senile plaques and affected neurons in AD. Recently conducted genome-wide association studies (GWAS) indicate that a large section of identified AD risk genes are involved in immune responses and are enriched in microglia. Microglia are innate immune cells in the central nervous system (CNS), which are involved in immune surveillance and maintenance of homeostasis in the CNS. Recently, a novel subpopulation of activated microglia named as disease-associated microglia (DAM), also known as activated response microglia (ARM) or microglial neurodegenerative phenotype (MGnD), was identified in AD model mice. These microglia closely associate with β-amyloid (Aβ) plaques and exhibit characteristic gene expression profiles accompanied with reduced expressions of homeostatic microglial genes. However, it remains unclear whether decreased homeostatic microglia functions or increased DAM/ARM/MGnD functions correlate with the degree of neuronal loss in AD. To translate the results of rodent studies to human AD, precuneus, the brain region vulnerable to β-amyloid accumulation in preclinical AD, is of high interest, as it can provide novel insights into the mechanisms of microglia response to Aβ in early AD. In this study, we performed comparative analyses of gene expression profiles of microglia among three representative neurodegenerative mouse models and the human precunei with early AD pathology. We proceeded to evaluate the identified genes as potential therapeutic targets for AD. We believe that our findings will provide important resources to better understand the role of glial dysfunction in AD.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2023-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10170691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9505630","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}
Nicole Labusek, Yanis Mouloud, Christian Köster, Eva Diesterbeck, Tobias Tertel, Constanze Wiek, Helmut Hanenberg, Peter A Horn, Ursula Felderhoff-Müser, Ivo Bendix, Bernd Giebel, Josephine Herz
{"title":"Extracellular vesicles from immortalized mesenchymal stromal cells protect against neonatal hypoxic-ischemic brain injury.","authors":"Nicole Labusek, Yanis Mouloud, Christian Köster, Eva Diesterbeck, Tobias Tertel, Constanze Wiek, Helmut Hanenberg, Peter A Horn, Ursula Felderhoff-Müser, Ivo Bendix, Bernd Giebel, Josephine Herz","doi":"10.1186/s41232-023-00274-6","DOIUrl":"https://doi.org/10.1186/s41232-023-00274-6","url":null,"abstract":"<p><strong>Background: </strong>Human mesenchymal stromal cell (MSC)-derived extracellular vesicles (EV) revealed neuroprotective potentials in various brain injury models, including neonatal encephalopathy caused by hypoxia-ischemia (HI). However, for clinical translation of an MSC-EV therapy, scaled manufacturing strategies are required, which is challenging with primary MSCs due to inter- and intra-donor heterogeneities. Therefore, we established a clonally expanded and immortalized human MSC line (ciMSC) and compared the neuroprotective potential of their EVs with EVs from primary MSCs in a murine model of HI-induced brain injury. In vivo activities of ciMSC-EVs were comprehensively characterized according to their proposed multimodal mechanisms of action.</p><p><strong>Methods: </strong>Nine-day-old C57BL/6 mice were exposed to HI followed by repetitive intranasal delivery of primary MSC-EVs or ciMSC-EVs 1, 3, and 5 days after HI. Sham-operated animals served as healthy controls. To compare neuroprotective effects of both EV preparations, total and regional brain atrophy was assessed by cresyl-violet-staining 7 days after HI. Immunohistochemistry, western blot, and real-time PCR were performed to investigate neuroinflammatory and regenerative processes. The amount of peripheral inflammatory mediators was evaluated by multiplex analyses in serum samples.</p><p><strong>Results: </strong>Intranasal delivery of ciMSC-EVs and primary MSC-EVs comparably protected neonatal mice from HI-induced brain tissue atrophy. Mechanistically, ciMSC-EV application reduced microglia activation and astrogliosis, endothelial activation, and leukocyte infiltration. These effects were associated with a downregulation of the pro-inflammatory cytokine IL-1 beta and an elevated expression of the anti-inflammatory cytokines IL-4 and TGF-beta in the brain, while concentrations of cytokines in the peripheral blood were not affected. ciMSC-EV-mediated anti-inflammatory effects in the brain were accompanied by an increased neural progenitor and endothelial cell proliferation, oligodendrocyte maturation, and neurotrophic growth factor expression.</p><p><strong>Conclusion: </strong>Our data demonstrate that ciMSC-EVs conserve neuroprotective effects of primary MSC-EVs via inhibition of neuroinflammation and promotion of neuroregeneration. Since ciMSCs can overcome challenges associated with MSC heterogeneity, they appear as an ideal cell source for the scaled manufacturing of EV-based therapeutics to treat neonatal and possibly also adult brain injury.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2023-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10108458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9678980","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 human induced pluripotent stem cell model from a patient with hereditary cerebral small vessel disease carrying a heterozygous R302Q mutation in HTRA1.","authors":"Emi Qian, Masahiro Uemura, Hiroya Kobayashi, Shiho Nakamura, Fumiko Ozawa, Sho Yoshimatsu, Mitsuru Ishikawa, Osamu Onodera, Satoru Morimoto, Hideyuki Okano","doi":"10.1186/s41232-023-00273-7","DOIUrl":"https://doi.org/10.1186/s41232-023-00273-7","url":null,"abstract":"<p><p>Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is an inherited cerebral small vessel disease (CSVD) caused by biallelic mutations in the high-temperature requirement serine peptidase A1 (HTRA1) gene. Even heterozygous mutations in HTRA1 are recently revealed to cause cardinal clinical features of CSVD. Here, we report the first establishment of a human induced pluripotent stem cell (hiPSC) line from a patient with heterozygous HTRA1-related CSVD. Peripheral blood mononuclear cells (PBMCs) were reprogrammed by the transfection of episomal vectors encoding human OCT3/4 (POU5F1), SOX2, KLF4, L-MYC, LIN28, and a murine dominant-negative mutant of p53 (mp53DD). The established iPSCs had normal morphology as human pluripotent stem cells and normal karyotype (46XX). Moreover, we found that the HTRA1 missense mutation (c.905G>A, p.R302Q) was heterozygous. These iPSCs expressed pluripotency-related markers and had the potential to differentiate into all three germ layers in vitro. HTRA1 and the supposed disease-associated gene NOG were differentially expressed in the patient iPSCs at mRNA levels compared to those of control lines. The iPSC line would facilitate in vitro research for understanding the cellular pathomechanisms caused by the HTRA1 mutation including its dominant-negative effect.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2023-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10069112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9253166","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":"Molecular hydrogen promotes wound healing by inducing early epidermal stem cell proliferation and extracellular matrix deposition.","authors":"Pengxiang Zhao, Zheng Dang, Mengyu Liu, Dazhi Guo, Ruiliu Luo, Mingzi Zhang, Fei Xie, Xujuan Zhang, Youbin Wang, Shuyi Pan, Xuemei Ma","doi":"10.1186/s41232-023-00271-9","DOIUrl":"https://doi.org/10.1186/s41232-023-00271-9","url":null,"abstract":"<p><strong>Background: </strong>Despite progress in developing wound care strategies, there is currently no treatment that promotes the self-tissue repair capabilities. H<sub>2</sub> has been shown to effectively protect cells and tissues from oxidative and inflammatory damage. While comprehensive effects and how H<sub>2</sub> functions in wound healing remains unknown, especially for the link between H<sub>2</sub> and extracellular matrix (ECM) deposition and epidermal stem cells (EpSCs) activation.</p><p><strong>Methods: </strong>Here, we established a cutaneous aseptic wound model and applied a high concentration of H<sub>2</sub> (66% H<sub>2</sub>) in a treatment chamber. Molecular mechanisms and the effects of healing were evaluated by gene functional enrichment analysis, digital spatial profiler analysis, blood perfusion/oxygen detection assay, in vitro tube formation assay, enzyme-linked immunosorbent assay, immunofluorescent staining, non-targeted metabonomic analysis, flow cytometry, transmission electron microscope, and live-cell imaging.</p><p><strong>Results: </strong>We revealed that a high concentration of H<sub>2</sub> (66% H<sub>2</sub>) greatly increased the healing rate (3 times higher than the control group) on day 11 post-wounding. The effect was not dependent on O<sub>2</sub> or anti-reactive oxygen species functions. Histological and cellular experiments proved the fast re-epithelialization in the H<sub>2</sub> group. ECM components early (3 days post-wounding) deposition were found in the H<sub>2</sub> group of the proximal wound, especially for the dermal col-I, epidermal col-III, and dermis-epidermis-junction col-XVII. H<sub>2</sub> accelerated early autologous EpSCs proliferation (1-2 days in advance) and then differentiation into myoepithelial cells. These epidermal myoepithelial cells could further contribute to ECM deposition. Other beneficial outcomes include sustained moist healing, greater vascularization, less T-helper-1 and T-helper-17 cell-related systemic inflammation, and better tissue remodelling.</p><p><strong>Conclusion: </strong>We have discovered a novel pattern of wound healing induced by molecular hydrogen treatment. This is the first time to reveal the direct link between H<sub>2</sub> and ECM deposition and EpSCs activation. These H<sub>2</sub>-induced multiple advantages in healing may be related to the enhancement of cell viability in various cells and the maintenance of mitochondrial functions at a basic level in the biological processes of life.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2023-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10044764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9572174","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":"Group 2 innate lymphoid cells and their surrounding environment.","authors":"Maiko Naito, Atsushi Kumanogoh","doi":"10.1186/s41232-023-00272-8","DOIUrl":"https://doi.org/10.1186/s41232-023-00272-8","url":null,"abstract":"<p><p>Since the discovery of group 2 innate lymphoid cells (ILC2s) in 2010, subsequent studies have revealed their developmental pathways, mechanisms of activation and regulation, and immunological roles in tissue homeostasis and tissue-specific diseases in various organs. Although ILC2s are known to express tissue-specific features depending on where they reside, how the surrounding environment affects the functions of ILC2s remains to be fully elucidated. Recent histologic analyses revealed that ILC2s resides in specific perivascular regions in peripheral tissues with their function being controlled by the surrounding cells via cytokines, lipid mediators, neurotransmitters, and cell-cell interactions through surface molecules. This review summarizes the interactions between ILC2s and surrounding cells, including epithelial cells, neurons, immune cells, and mesenchymal cells, with the objective of promoting the development of novel diagnostic and therapeutic methods for ILC2-related diseases.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2023-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10026507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9214613","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}