STEM CELLS最新文献

{"title":"The impact of donor and recipient age on post-transplantation clonality in murine hematopoiesis.","authors":"Lars Thielecke, Kalpana Nattamai, Aishlin Hassan, Ingmar Glauche, Hartmut Geiger, Kerstin Cornils","doi":"10.1093/stmcls/sxaf059","DOIUrl":"10.1093/stmcls/sxaf059","url":null,"abstract":"<p><strong>Introduction: </strong>The sustained production of blood and immune cells is driven by a pool of hematopoietic stem cells (HSCs) and their offspring. Due to the intrinsic heterogeneity of HSCs, the composition of emergent clones changes over time, leading to a reduced clonality in aging mice and humans. Theoretical analyses suggest that clonal conversion rates and clonal complexity depend not only on HSC heterogeneity, but also on additional stress conditions. These insights are particularly relevant in the context of stem cell transplantations, which still remain the only curative option for many hematologic diseases, increasingly considered viable for elderly individuals. However, age-related clonal changes post-transplantation are not well understood.</p><p><strong>Methods: </strong>To address this, we conducted a barcode-based assessment of clonality to investigate post-transplantation changes in both homo- and hetero-chronic settings, combined with low- and high-intensity pre-conditioned recipients.</p><p><strong>Results: </strong>A robust and polyclonal engraftment was observed across all groups, but with distinct differences in barcode diversity. In particular, transplanted aged HSCs showed no changes in clonality, regardless of recipient age or pre-conditioning. Young HSCs transplanted into severely pre-conditioned old hosts as well as under reduced pre-conditioning, allowed for full lymphoid reconstitution, but showed substantial differences in clonality. Also, myeloid lineage bias, a hallmark of aged HSCs, was confirmed at a clonal level across all experimental groups. Overall, we found that aged HSCs generally maintain clonal diversity similar to young HSCs, but notable differences emerge under hetero-chronic conditions and varying pre-conditioning regimens.</p><p><strong>Conclusion: </strong>These findings challenge current paradigms and underscore the complex interactions between aging and transplantation conditions.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12622992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human obesity decreases the anti-inflammatory functionality of adipose tissue-derived mesenchymal stem/stomal cells by upregulating IL-1β expression.","authors":"Li Xing, Xiangyang Zhu, Nattawat Klomjit, Bo Lu, Mina Al Saeedi, Amir Lerman, Alfonso Eirin, Lilach O Lerman","doi":"10.1093/stmcls/sxaf058","DOIUrl":"10.1093/stmcls/sxaf058","url":null,"abstract":"<p><strong>Importance: </strong>Mesenchymal stromal cells (MSCs) possess therapeutic properties that mediate repair. Obesity impairs MSC functionality and therapeutic efficacy, possibly by eliciting dynamic modifications of epigenetic markers, like 5-hydroxymethylcytosine (5hmC).</p><p><strong>Objective: </strong>We hypothesized that human obesity alters the 5hmC landscape and anti-inflammatory capacity of adipose tissue-derived MSCs to activate the prominent inflammatory signaling mediator Interleukin (IL)-1β.</p><p><strong>Design, setting, participants, intervention: </strong>Adipose tissue samples were collected from obese and lean individuals (body mass index ≥30 or <30 kg/m2, respectively, n = 11 each) during weight-loss or kidney donation surgery.</p><p><strong>Main outcomes and measures: </strong>MSCs were harvested and analyzed for 5hmC profiles (MeDIP-seq) and mRNA expression (RNA-seq) (n = 5 each). Subsequently, MSCs or a vehicle were injected into mice, (n = 6 each) and two-weeks later, kidneys were evaluated using in-vivo magnetic resonance imaging and ex vivo studies. The role of IL-1β was then studied in-vitro in MSC-induced immunomodulation using siRNA in macrophages.</p><p><strong>Results: </strong>Compared to MSC from lean patients, obese-MSC genes showed 2087 differential 5hmC modifications and 175 differential mRNA expression. Among them, 14 genes with overlapping alterations were involved in regulation of cytokine production, prominently IL-1β. Injecting obese MSCs elevated renal expression of IL-1β and M1 macrophage count but lowered kidney perfusion. Silencing IL-1β in obese-MSCs in vitro reduced M1 phenotype switching in co-incubated macrophages.</p><p><strong>Conclusions and relevance: </strong>Obesity induces epigenetic and gene expression changes in MSCs, particularly in IL-1β, associated with impaired anti-inflammatory functionality of MSCs. Targeting IL-1β could be a useful therapeutic approach to modulate the decline in MSC functionality resulting from obesity.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular signature and regulatory network of human umbilical cord mesenchymal stromal cells as a niche for hematopoietic stem cells and progenitors.","authors":"Pornprapa Srimorkun, Kittisak Suanpan, Korakot Atjanasuppat, Piamsiri Sawaisorn, Werapath Somchit, Teerapong Siriboonpiputtana, Oytip Nathalang, Suradej Hongeng, Sawang Petvises, Usanarat Anurathapan","doi":"10.1093/stmcls/sxaf057","DOIUrl":"10.1093/stmcls/sxaf057","url":null,"abstract":"<p><p>The fate of hematopoietic stem cells (HSCs) is determined by a complex regulatory network supporting self-renewal and quiescence within a niche. Umbilical cord mesenchymal stromal cells (UC-MSCs) are classified as an alternative niche for the expansion of hematopoietic stem and progenitor cells (HSPCs). The molecular mechanisms by which UC-MSCs regulate hematopoiesis are still not fully understood. In this study, the cocultures of UC-MSCs and umbilical cord blood CD34+ (UCB-CD34+) cells were established. Immunophenotype, cell proliferation, and hematopoietic function of UCB-CD34+ cells were evaluated on days 0 to 7. UC-MSCs promoted UCB-CD34+ cell proliferation but were less effective at preserving their stemness. Notably, UC-MSCs promoted the myeloid lineage commitment, significantly observed on day 3. Integrative transcriptomic analysis highlighted the molecular signature and regulatory networks of UC-MSCs. The long non-coding RNA (lncRNA)-RNA binding protein (RBP) interaction network and lncRNA cis- and trans-regulatory networks were evident. The significant 3-gene modules and a set of 10-hub genes were identified in the protein-protein interaction (PPI) network, including RPS16, CD74, RPL35, COX7C, RPL38, RPS28, RPS27, RPS10, TARDBP, and TOMM7. These findings exemplify the niche activity of UC-MSCs in regulating cell differentiation, genomic stability maintenance, and modulation of the hematopoietic supportive niche. The transcriptional landscape, together with the identified regulatory networks, gene modules, and key hub genes provide new insights into the molecular mechanisms of UC-MSCs and establish a basis for refining ex vivo culture systems for therapeutic HSC expansion.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuronal branching in stem cell models of mitochondrial and neurological diseases.","authors":"Selene Lickfett, Carmen Menacho, Sidney Cambridge, Alessandro Prigione","doi":"10.1093/stmcls/sxaf050","DOIUrl":"10.1093/stmcls/sxaf050","url":null,"abstract":"<p><p>Neuronal branching, the extension and arborization of neurites, is critical for establishing and maintaining functional neural circuits. Emerging evidence suggests that mitochondria play an important role in regulating this process. In this review, we explore how the use of human induced pluripotent stem cell (iPSC)-derived neuronal models in two dimensions (2D) and three dimensions (3D) could help uncover possible mechanisms linking mitochondrial function and dysfunction to neuronal branching capacity. We highlight examples of iPSC-based models of mitochondrial and neurological diseases where aberrant neurite growth has been observed and discuss the potential therapeutic implications. Additionally, we review current methodologies for assessing neurite outgrowth in 2D and 3D neuronal models, addressing their strengths and limitations. Insights gained from these models emphasize the significance of mitochondrial health in neuronal branching and demonstrate the potential of iPSC-derived neurons and brain organoids for studying disrupted neuronal morphology. Harnessing these human stem cell models to devise phenotypic drug discovery platforms can eventually pave the way for innovative therapeutic interventions, particularly in the context of disorders with poorly understood genetic mechanisms and limited therapeutic options.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12552108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PNO1 served as a potential biomarker to promote the stemness and progression of breast cancer via the NF-κB signaling pathway.","authors":"Xiaorui Wang, Ping Yue, Dongming Liu, Xinrui Wen, Xiehua Zhang, Bo Sun, Yi Luo, Liwei Chen, Weidong Li, Hong Liu, Yuchao He, Zhongsheng Tong, Hua Guo","doi":"10.1093/stmcls/sxaf060","DOIUrl":"10.1093/stmcls/sxaf060","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is a highly heterogeneous disease with diverse phenotypes. At present, increasing evidence supports the role of ribosomal biogenesis in human diseases and tumorigenesis. PNO1, as a ribosome assembly factor, plays a key role in the biological synthesis of ribosomes and ribosomal protein mutations associated with human diseases and tumor development. This study explored PNO1's role as a prognostic biomarker for breast cancer.</p><p><strong>Methods: </strong>Clinical samples and online datasets were used to determine PNO1 expression in breast cancers with different molecular phenotypes and clinicopathological subtypes. CCK-8 assays, colony formation assays, wound healing, and transwell assays were performed to investigate tumor cell proliferation, migration, and invasion. Western blot, flow cytometry, and sphere-formation assays were used to assess the effect of PNO1 on breast cancer stemness. RNA-sequencing analysis was also performed to elucidate the underlying mechanism.</p><p><strong>Results: </strong>Results showed that the expression level of PNO1 was upregulated in breast cancer samples. In addition, high PNO1 expression was positively correlated with poor survival in breast cancer patients with different molecular types. Moreover, PNO1 was associated with breast cancer heterogeneity by promoting its stem-like properties both in vitro and in vivo through the NF-κB signaling pathway, which can be suppressed by JSH-23.</p><p><strong>Conclusions: </strong>Our study found that PNO1 expression was positively correlated with poor survival in different molecular subtypes of breast cancer and that PNO1 promoted stem-like properties of breast cancer by activating NF-κB activity. Collectively, PNO1 is a potential prognostic biomarker that plays an important role in breast cancer progression.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145090868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of peroxisome function promotes oxidative stress-induced hematopoiesis.","authors":"Emma A Schindhelm, Amada Blake, Megan M Constans, Kai Braaten, Aly L Thorn, Willa Durose, Maggie Lorentson, Ashish O Gupta, Paul J Orchard, Nancy Braverman, Gerald V Raymond, Troy C Lund","doi":"10.1093/stmcls/sxaf054","DOIUrl":"10.1093/stmcls/sxaf054","url":null,"abstract":"<p><p>The role of peroxisomes in hematopoiesis remains poorly understood. The PEX1-Gly844Asp knock-in mouse lacks peroxisome formation and is peroxisome deficient. We observed that peroxisome-deficient animals had up to 50% greater numbers of peripheral lymphocytes, neutrophils, and platelets which contained 2-fold greater reactive oxygen species (ROS, P = .0002). The marrow contained 2-fold greater numbers of cells and colony forming unit (P = .0009 and <.0001, respectively). We found expansion (up to 3-fold) in the hematopoietic stem and progenitor cell (HSPC) compartment compared to that of wild-type (WT) animals demonstrated by: in vivo enumeration of Lin-SCA1+c-KIT+ (LSK) (P < .0001). Importantly through competitive bone marrow transplant experiments (primary and secondary), we show that peroxisome-deficient cells outcompete WT. We further demonstrate that peroxisome-deficient HSPC harbor very high levels of intrinsic ROS which are attenuated after repopulation. Isolation of mesenchymal stem cells (MSC) isolated from peroxisome-deficient mice also showed elevated levels of ROS. Finally, we found elevated levels of stem cell factor (SCF) in the plasma of peroxisome-deficient mice, and peroxisome-deficient MSC expressed 2-fold more SCF compared to WT. Chemical induction of ROS also increased SCF expression by MSC. Lin-SCA1+c-KIT+ expanded 10-fold greater in the absence of SCF on peroxisome-deficient MSC than that on WT MSC. In conclusion, the increase in HSPC numbers is, in part, driven by response to ROS in the microenvironment leading to increased SCF. These data add new insight into the role of peroxisomes in the bone marrow niche.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Giant panda umbilical cord mesenchymal stem cell-derived exosomes promote dermal fibroblast proliferation and wound healing.","authors":"Yuliang Liu, Hongyan Li, Yuan Li, Donghui Wang, Jiasong Chen, Zhixiang Yuan, Rongrui Zhang, Mingyue Zhang, Zhigang Cai, Rong Hou, Junhui An","doi":"10.1093/stmcls/sxaf051","DOIUrl":"10.1093/stmcls/sxaf051","url":null,"abstract":"<p><strong>Background: </strong>UC‑MSC‑Exos (umbilical cord mesenchymal stem cell‑derived exosomes) offer a potential therapy for captive giant pandas. This study aimed to clarify their proteomic and miRNA profiles and functions to understand therapeutic mechanisms and optimize their application.</p><p><strong>Methods: </strong>UC‑MSC‑Exos were isolated from giant panda UC‑MSC culture supernatant by ultracentrifugation. Proteomic and miRNA profiles were identified by mass spectrometry and high‑throughput small RNA sequencing, respectively. Dual‑luciferase gene reporter assays were used to evaluate the impact of miR‑21‑5p on DF proliferation.</p><p><strong>Results: </strong>Giant panda UC‑MSC‑Exos are rich in proteins and miRNAs. They significantly boosted DF proliferation and migration, mediated by growth factors like PDGF, TGF‑β1, b‑FGF, and miR‑21‑5p. We found that miR‑21‑5p contributes to fibroblast proliferation by targeting the programmed cell death 4 (PDCD4) and reversion inducing cysteine rich protein with Kazal motifs (RECK) genes, attenuating the expression of α‑smooth muscle actin (α‑SMA) induced by TGF‑β1, and impeding the differentiation of fibroblasts into myoblasts.</p><p><strong>Conclusions: </strong>This study comprehensively reveals the functional properties of giant panda UC‑MSC‑Exos as well as their therapeutic potential in wound healing, providing insights for improving tissue regeneration and health in giant pandas.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Modulating the mesenchymal stromal cell microenvironment alters exosome RNA content and ligament healing capacity.","authors":"","doi":"10.1093/stmcls/sxaf052","DOIUrl":"10.1093/stmcls/sxaf052","url":null,"abstract":"","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":"43 11","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12539864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human cortical neurons rapidly generated by embryonic stem cell programming integrate into the stroke-injured rat cortex.","authors":"Raquel Martinez-Curiel, Mazin Hajy, Oleg Tsupykov, Linda Jansson, Natalia Avaliani, Juliane Tampé, Emanuela Monni, Galyna Skibo, Olle Lindvall, Sara Palma-Tortosa, Zaal Kokaia","doi":"10.1093/stmcls/sxaf049","DOIUrl":"10.1093/stmcls/sxaf049","url":null,"abstract":"<p><p>Stem cell sources capable of producing appropriate cells for replacement will be necessary for functional repair of the injured brain. Here, we have determined whether transcription factor programming of human embryonic stem (hES) cells can be used to generate layer-specific cortical neurons capable of integrating into the stroke-injured rat cortex. Human embryonic stem cells were programmed via overexpression of neurogenin 2 (NGN2). After 7 days, hES-induced neurons (hES-iNs) were characterized in vitro using immunocytochemistry, RT-qPCR, and whole-cell patch-clamp. Cortical ischemic stroke was induced in rats via distal middle cerebral artery occlusion. Forty-eight hours later, hES-iNs were transplanted into the somatosensory cortex adjacent to the ischemic lesion. Three months thereafter, brains were analyzed for expression of neuronal markers, axonal myelination, and synapse formation using immunohistochemistry and immunoelectron microscopy (iEM). Overexpression of NGN2 in hES cells for 7 days generated excitatory neurons, expressing cortical markers at different stages of maturation. After transplantation, the hES-iNs expressed markers of both immature and mature neurons and of upper and deep cortical layers. The hES-iNs sent widespread projections to both hemispheres, and iEM revealed that they were myelinated by host oligodendrocytes and had formed efferent synaptic connections with host cortical neurons. The hES cells programmed via NGN2 overexpression gave rise to subtypes of cortical neurons, capable of integrating structurally into the injured brain, more rapidly than neurons produced by previous protocols. Functional characterization of the grafted hES-iNs and their impact on the balance between brain excitation and inhibition are now highly warranted. This new stem cell source should be considered when, in the future, the most suitable candidate will be selected for clinical translation.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12532315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144615603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linking mitochondria, fatty acids, and hematopoietic stem cell expansion during infection: implications for aging and metabolic diseases.","authors":"Katherine Hampton, Alyssa Polski-Delve, Charlotte Hellmich, Stuart A Rushworth","doi":"10.1093/stmcls/sxaf053","DOIUrl":"10.1093/stmcls/sxaf053","url":null,"abstract":"<p><p>In steady state, hematopoietic stem cells (HSCs) reside quiescently in their hypoxic niche with minimal mitochondrial activity, maintaining characteristically low levels of reactive oxygen species (ROS) and instead favoring glycolysis to meet their low energy requirements. However, stress, such as acute infection, triggers a state of emergency hematopoiesis during which HSCs expand more rapidly to produce up to 10-fold more downstream differentiated immune cells. To cope with this demand, HSCs increase their energy production by switching from low ATP-yielding glycolysis to high ATP-yielding mitochondrial oxidative phosphorylation. It is this metabolic switch that enables rapid HSC expansion and differentiation into downstream progeny to increase the immune cell pool and effectively clear the infection. This metabolic switch relies on the sufficient availability of healthy mitochondria as well as fuel in the form of free fatty acids to drive the necessary production of cellular components. This concise review aims to focus on how HSCs increase their mitochondrial content and fuel ATP production via fatty acid oxidation and the impact of HSC dysfunction during aging and other metabolic diseases.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12532312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}