Cellular and Molecular Life Sciences最新文献

{"title":"FGF receptor kinase inhibitors exhibit broad antiviral activity by targeting Src family kinases.","authors":"Debora Stefanova, Dominik Olszewski, Mirco Glitscher, Michael Bauer, Luca Ferrarese, Daria Wüst, Eberhard Hildt, Urs F Greber, Sabine Werner","doi":"10.1007/s00018-024-05502-x","DOIUrl":"10.1007/s00018-024-05502-x","url":null,"abstract":"<p><p>The development of antiviral strategies is a key task of biomedical research, but broad-spectrum virus inhibitors are scarce. Here we show that fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitors reduce infection of several cell types with DNA and RNA viruses by blocking early stages of infection, but not viral cell association. Unexpectedly, their antiviral activity was largely independent of FGFR kinase inhibition. RNA profiling showed upregulation of interferon response genes by FGFR inhibitors, but their expression did not correlate with the antiviral activity in infected cells. Using bioinformatics analysis of kinome data, targeted kinase assays, siRNA-mediated knock-down and pharmacological inhibition experiments, we show that blockade of Src family kinases, in particular Lyn, is mainly responsible for the antiviral activity of FGFR inhibitors. These results identify FGFR inhibitors as broad-spectrum antiviral agents and suggest the poorly studied Lyn kinase as a promising target for the treatment of viral infections.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"81 1","pages":"471"},"PeriodicalIF":6.2,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11612106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766626","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":"Knockout of onecut2 inhibits proliferation and promotes apoptosis of tumor cells through SKP2-mediated p53 acetylation in hepatocellular carcinoma.","authors":"Cunjie Li, Yuxin Xiao, Jieling Zhou, Shifeng Liu, Ligang Zhang, Xinran Song, Xinhua Guo, Qifang Song, Jianfu Zhao, Ning Deng","doi":"10.1007/s00018-024-05518-3","DOIUrl":"10.1007/s00018-024-05518-3","url":null,"abstract":"<p><p>Onecut2 (OC2) plays a vital regulatory role in tumor growth, metastasis and angiogenesis. In this study, we report the regulatory role and specific molecular mechanism of OC2 in the apoptosis of hepatocellular carcinoma (HCC) cells. We found that OC2 knockout via the CRISPR/CAS9 system not only significantly inhibited the proliferation and angiogenesis of HCC cells but also significantly promoted apoptosis. The apoptosis rate of the OC2 knockout HCC cell line reached 30.514%. In a mouse model, the proliferation inhibition rate of tumor cells reached 98.8%. To explore the mechanism of apoptosis, ChIP-Seq and dual-luciferase reporter assays were carried out. The results showed that OC2 could directly bind to the promotor of SKP2 and regulate its expression. Moreover, downregulating the expression of OC2 and SKP2 could release p300, promote the acetylation of p53, increase the expression of p21 and p27, and promote the apoptosis of HCC cells. Moreover, the overexpression of OC2 or SKP2 in the knockout HCC cell line clearly inhibited the acetylation level of p53 and reduced cell apoptosis. This study revealed that OC2 could regulate the apoptosis of HCC cells through the SKP2/p53/p21 axis, which may provide some therapeutic targets for HCC in the clinic.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"81 1","pages":"469"},"PeriodicalIF":6.2,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11604872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750094","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":"Downregulated KLF4, induced by m6A modification, aggravates intestinal barrier dysfunction in inflammatory bowel disease.","authors":"Xingchao Zhu, Jiayu Wang, Huan Zhang, Hongqin Yue, Jinghan Zhu, Juntao Li, Kun Wang, Kanger Shen, Kexi Yang, Xia Leng, Qinhua Xi, Tongguo Shi","doi":"10.1007/s00018-024-05514-7","DOIUrl":"10.1007/s00018-024-05514-7","url":null,"abstract":"<p><strong>Background: </strong>Krüppel-like factor 4 (KLF4), a transcription factor, is involved in various biological processes. However, the role of KLF4 in regulating the intestinal epithelial barrier (IEB) in inflammatory bowel disease (IBD) and its mechanism have not been extensively studied.</p><p><strong>Methods: </strong>KLF4 expression in IBD patients and colitis mice was analyzed using Gene Expression Omnibus(GEO) database, immunohistochemistry (IHC) and Western blot. The roles of KLF4 in IEB and colitis symptoms were verified in dextran sulfate sodium (DSS)-induced and 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis model mice using an adenovirus carrying KLF4 shRNA (shKLF4-Adv). Furthermore, the influence of KLF4 on trans-epithelium electrical resistance (TEER), paracellular permeability, apical junction complex (AJC) protein expression and apoptosis was assessed in vitro and in vivo. MeRIP and RIP assays were used to verify the effects of m6A modification on KLF4 expression.</p><p><strong>Results: </strong>KLF4 expression was significantly decreased in IBD patients and was negatively associated with inflammatory features. KLF4 deletion aggravated colitis symptoms and IEB injuries by reducing AJC protein expression and increasing apoptosis in mice with colitis. Furthermore, KLF4 transcriptionally regulated the expression of AJC proteins and inhibited apoptosis by reducing cellular ROS levels and proinflammatory cytokine expression. Moreover, we observed that METTL3/ALKBH5/YTHDF2-mediated m6A modification led to a decrease in KLF4 expression in Caco-2 cells. In addition, APTO-253, an inducer of KLF4, exhibited a synergistic effect with mesalazine on IEB function.</p><p><strong>Conclusions: </strong>Our study demonstrated that KLF4 is a crucial regulator of IEB, suggesting that targeting KLF4 may be a promising therapeutic alternative for IBD.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"81 1","pages":"470"},"PeriodicalIF":6.2,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11607297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750092","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":"CLIP170 enhancing FOSL1 expression via attenuating ubiquitin-mediated degradation of β-catenin drives renal cell carcinoma progression.","authors":"Yuanbin Huang, Zhihao Wen, Shuyao Tao, Zhenlong Yu, Xiaogang Wang, Xiancheng Li, Lu Gao","doi":"10.1007/s00018-024-05504-9","DOIUrl":"10.1007/s00018-024-05504-9","url":null,"abstract":"<p><p>Protein interactions are fundamental for all cellular metabolic activities. Cytoplasmic linker protein 170 (CLIP170) plays diverse roles in cellular processes and the development of malignant tumors. Renal cell carcinoma (RCC) poses a significant challenge in oncology owing to its invasive nature, metastatic potential, high recurrence rates, and poor prognosis. However, the specific mechanisms and roles of CLIP170 underlying its involvement in RCC progression remain unclear. The findings of this study revealed a significant upregulation of CLIP170 in RCC tumor tissues. Elevated CLIP170 expression correlated positively with advanced clinical and pathological stages and was associated with poor overall survival in RCC patients. Functional assays in vitro demonstrated that elevated CLIP170 levels enhanced RCC cell proliferation, migration and invasion. Mechanistically, 4D-label free proteomics library identified that CLIP170 increased the level of FOSL1 in the Wnt signaling pathway. Immunoprecipitation and molecular docking were performed to unveil that CLIP170 formed a complex with β-catenin, inhibiting β-catenin degradation via the ubiquitin-proteasome pathway. Elevated β-catenin levels within RCC cells played a central role in promoting the transcriptional expression of FOSL1, thereby facilitating RCC cell proliferation and epithelial-mesenchymal transition (EMT) progression. In vivo investigations corroborated these findings, illustrating that CLIP170 regulated β-catenin and FOSL1 expression, driving tumor growth in RCC. This study highlights the crucial role of CLIP170 in promoting FOSL1 expression by preventing β-catenin ubiquitination and degradation, thus promoting RCC tumor progression. It suggests the CLIP170/β-catenin/FOSL1 axis as a potential therapeutic target for RCC treatment.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"81 1","pages":"467"},"PeriodicalIF":6.2,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11604886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738576","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":"Stereoselective block of the hERG potassium channel by the Class Ia antiarrhythmic drug disopyramide.","authors":"Yihong Zhang, Aziza El Harchi, Andrew F James, Shigetoshi Oiki, Christopher E Dempsey, Jules C Hancox","doi":"10.1007/s00018-024-05498-4","DOIUrl":"10.1007/s00018-024-05498-4","url":null,"abstract":"<p><p>Potassium channels encoded by human Ether-à-go-go-Related Gene (hERG) are inhibited by diverse cardiac and non-cardiac drugs. Disopyramide is a chiral Class Ia antiarrhythmic that inhibits hERG at clinical concentrations. This study evaluated effects of disopyramide enantiomers on hERG current (I_hERG) from hERG expressing HEK 293 cells at 37 °C. S(+) and R(-) disopyramide inhibited wild-type (WT) I_hERG with IC₅₀ values of 3.9 µM and 12.9 µM respectively. The attenuated-inactivation mutant N588K had little effect on the action of S(+) disopyramide but the IC₅₀ for the R(-) enantiomer was ~ 15-fold that for S(+) disopyramide. The enhanced inactivation mutant N588E only slightly increased the potency of R(-) disopyramide. S6 mutation Y652A reduced S(+) disopyramide potency more than that of R(-) disopyramide (respective IC₅₀ values ~ 49-fold and 11-fold their WT controls). The F656A mutation also exerted a stronger effect on S(+) than R(-) disopyramide, albeit with less IC₅₀ elevation. A WT-Y652A tandem dimer exhibited a sensitivity to the enantiomers that was intermediate between that of WT and Y652A, suggesting Y652 groups on adjacent subunits contribute to the binding. Moving the Y (normally at site 652) one residue in the N- terminal (up) direction in N588K hERG markedly increased the blocking potency of R(-) disopyramide. Molecular dynamics simulations using a hERG pore model produced different binding modes for S(+) and R(-) disopyramide consistent with the experimental observations. In conclusion, S(+) disopyramide interacts more strongly with S6 aromatic binding residues on hERG than does R(-) disopyramide, whilst optimal binding of the latter is more reliant on intact inactivation.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"81 1","pages":"466"},"PeriodicalIF":6.2,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11604869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738578","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":"GLP-1 and GIP agonism has no direct actions in human hepatocytes or hepatic stellate cells.","authors":"Natália da Silva Lima, Alba Cabaleiro, Eva Novoa, Cristina Riobello, Patrick J Knerr, Yantao He, Eva M Esquinas-Román, Ismael González-García, Vincent Prevot, Markus Schwaninger, Carlos Dieguez, Miguel López, Timo D Müller, Marta Varela-Rey, Jonathan D Douros, Ruben Nogueiras","doi":"10.1007/s00018-024-05507-6","DOIUrl":"10.1007/s00018-024-05507-6","url":null,"abstract":"<p><p>The use of incretin agonists for managing metabolic dysfunction-associated steatohepatitis (MASH) is currently experiencing considerable interest. However, whether these compounds have a direct action on MASH is still under debate. This study aims to investigate whether GLP-1R/GIPR agonists act directly in hepatocytes and hepatic stellate cells (HSCs). For this, human hepatocyte and HSCs lines, as well as primary human hepatocytes and HSCs treated with Liraglutide, Acyl-GIP or the GLP-1/GIP dual agonist (MAR709) were used. We show that the concentrations of each compound, which were effective in insulin release, did not induce discernible alterations in either hepatocytes or HSCs. In hepatocytes displaying elevated fatty acid content after the treatment with oleic acid and palmitic acid, none of the three compounds reduced lipid concentration. Similarly, in HSCs activated with transforming growth factor-β (TGFb), Liraglutide, Acyl-GIP and MAR709 failed to ameliorate the elevated expression of fibrotic markers. The three compounds were also ineffective in phosphorylating CREB, which mediates insulinotropic actions, in both hepatocytes and HSCs. These findings indicate that incretin agonists have no direct actions in human hepatocytes or hepatic stellate cells, suggesting that their beneficial effects in patients with MASH are likely mediated indirectly, potentially through improvements in body weight, insulin resistance and glycemic control.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"81 1","pages":"468"},"PeriodicalIF":6.2,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11604888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738577","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":"Correction: IER3IP1-mutations cause microcephaly by selective inhibition of ER-Golgi transport.","authors":"Mihaela Anitei, Francesca Bruno, Christina Valkova, Therese Dau, Emilio Cirri, Iván Mestres, Federico Calegari, Christoph Kaether","doi":"10.1007/s00018-024-05508-5","DOIUrl":"10.1007/s00018-024-05508-5","url":null,"abstract":"","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"81 1","pages":"465"},"PeriodicalIF":6.2,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142726251","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":"β'-COP mediated loading of PPARγ into trophoblast-derived extracellular vesicles.","authors":"Xiaofang Luo, Hao Wang, Biyang Yin, Biao Huang, Jinfeng Cao, Hongbo Qi","doi":"10.1007/s00018-024-05494-8","DOIUrl":"10.1007/s00018-024-05494-8","url":null,"abstract":"<p><p>Fetal growth restriction (FGR) is characterized by impaired fetal growth and dysregulated lipid metabolism. Extracellular vesicles (EVs) have been proved playing a crucial role in transporting biomolecules from the mother to the fetus. However, the mechanisms underlying cargo sorting and loading into trophoblastic EVs remain elusive. This study focuses on examining how the essential fatty acid regulator, peroxisome proliferator-activated receptor gamma (PPARγ), is sorted and loaded into EVs originating from trophoblasts. We conducted proteomic analysis on placenta-derived EVs from normal and FGR pregnancies. Interactions between PPARγ and coat protein complex I (COPI) subunit were evaluated using co-immunoprecipitation and bioinformatics simulation. Molecular dynamics simulations were conducted to identify critical binding sites between β'-coat protein complex I (β'-COP), a subunit of COPI, and PPARγ. lentivirus-mediated knockout and overexpression techniques were employed to elucidate the role of β'-COP in PPARγ loading into EVs. Our findings demonstrate that PPARγ protein levels are significantly decreased in EVs from FGR placentas. β'-COP subunit directly interacts with PPARγ in trophoblasts, mediating its sorting into early endosomes and multivesicular bodies for EVs incorporation. Knockout of β'-COP impaired PPARγ loading into EVs. Molecular dynamics simulations identified critical binding sites for the interaction between β'-COP and PPARγ. Mutation of these sites significantly weakened the β'-COP-PPARγ interaction and reduced PPARγ levels in trophoblastic EVs. In conclusion, β'-COP mediates sorting and loading of PPARγ into trophoblastic EVs. This study provides insights into regulating EVs cargo loading and potential strategies for targeted cargo delivery from the maternal to the fetal circulation.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"81 1","pages":"464"},"PeriodicalIF":6.2,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142726264","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":"Regulation of formin INF2 and its alteration in INF2-linked inherited disorders.","authors":"Leticia Labat-de-Hoz, M Ángeles Jiménez, Isabel Correas, Miguel A Alonso","doi":"10.1007/s00018-024-05499-3","DOIUrl":"10.1007/s00018-024-05499-3","url":null,"abstract":"<p><p>Formins are proteins that catalyze the formation of linear filaments made of actin. INF2, a formin, is crucial for correct vesicular transport, microtubule stability and mitochondrial division. Its activity is regulated by a complex of cyclase-associated protein and lysine-acetylated G-actin (KAc-actin), which helps INF2 adopt an inactive conformation through the association of its N-terminal diaphanous inhibitory domain (DID) with its C-terminal diaphanous autoinhibitory domain. INF2 activation can occur through calmodulin binding, KAc-actin deacetylation, G-actin binding, or association with the Cdc42 GTPase. Mutations in the INF2 DID are linked to focal segmental glomerulosclerosis (FSGS), affecting podocytes, and Charcot-Marie-Tooth disease, which affects Schwann cells and leads to axonal loss. At least 80 pathogenic DID variants of INF2 have been identified, with potential for many more. These mutations disrupt INF2 regulation, leading to excessive actin polymerization. This in turn causes altered intracellular trafficking, abnormal mitochondrial dynamics, and profound transcriptional reprogramming via the MRTF/SRF complex, resulting in mitotic abnormalities and p53-mediated cell death. This sequence of events could be responsible for progressive podocyte loss during glomerular degeneration in FSGS patients. Pharmacological targeting of INF2 or actin polymerization could offer the therapeutic potential to halt the progression of FSGS and improve outcomes for patients with INF2-linked disease.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"81 1","pages":"463"},"PeriodicalIF":6.2,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715447","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":"IQGAP1 promotes early B cell development, is essential for the development of marginal zone (MZ) B cells, and is critical for both T-dependent and T-independent antibody responses.","authors":"Ravi K Lella, Subramaniam Malarkannan","doi":"10.1007/s00018-024-05509-4","DOIUrl":"10.1007/s00018-024-05509-4","url":null,"abstract":"<p><p>IQGAP1 is a multi-functional scaffold protein. However, its role in B cell development and function is unknown. Here, we show IQGAP1 as an essential scaffold that regulates early B cell development and function. Iqgap1^-/- mice contained significantly increased numbers of B220⁺ B, B220⁺IgM^- pro/pre-B, and B220^LowIgM⁺ immature-B cells in the bone marrow. In the spleens of the Iqgap1^-/- mice, newly formed and follicular B cell numbers were increased, while the marginal zone B cell numbers were significantly reduced. Lack of IQGAP1 reduced T-dependent and T-independent humoral responses. Mechanistically, the lack of IQGAP1 considerably decreased the phosphorylation of Mek1/2, Erk1/2, and Jnk1/2. B cells from Iqgap1^-/- mice failed to suppress IL-7R-mediated activation of Stat5a/b, an essential step for cell-cycle exit and initiate light-chain recombination, reducing RS rearrangement frequency. Our study provides the first evidence that IQGAP1-based signalosome is necessary for the development and functions of B cells.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"81 1","pages":"462"},"PeriodicalIF":6.2,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709344","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}