SLAS Discovery最新文献

{"title":"Characterization and comparison of hypoxia inducing factors on tumor growth and metastasis between two- and three-dimensional cancer models","authors":"Leo Li-Ying Chan ,&nbsp;Sarah L. Kessel ,&nbsp;Bo Lin ,&nbsp;Anna Juncker-Jensen ,&nbsp;Paul Weingarten","doi":"10.1016/j.slasd.2023.10.007","DOIUrl":"10.1016/j.slasd.2023.10.007","url":null,"abstract":"<div><p>The monocarboxylic acid transporter 4 (Mct-4), a downstream biomarker of hypoxia inducing factor (HIF)-1α, is involved in the cellular response to hypoxia, as indicated by the hypoxic response element in its promoter region. Using a tumorsphere assay as an in vitro 3-dimensional (3D) model generated using 384-well ultra-low attachment (ULA) plates for cell proliferation analysis using a plate-based image cytometer, we identify a hypoxic response in the tumorsphere model that is distinct from that of cells grown under 2-dimensional (2D) normoxic conditions and demonstrate a key role for Mct-4 in enabling 3D growth. The tumorsphere model yields evidence of an essential role for Mct-4 in multiple cell lines, which were genetically modified to underexpress and overexpress Mct-4, evidence not apparent in a standard 2D model of growth in the same cell lines. In addition, we identify the effects of overexpressing Mct-4 in cancer cell migration using a transwell chamber assay. We also show that the response to hypoxia may be circumvented by transfection with a CMV promoter driven Mct-4, which confers constitutive 3D growth, wherein tumorsphere growth inhibition by small molecule HIF-1α inhibitors is mitigated. Finally, we demonstrate quantifiable gene/protein expression differences between 2D and 3D cancer models based on the normoxic and hypoxic conditions. Therefore, the tumorsphere 3D model generated using 384-well ULA plates in combination with high-throughput image cytometer is demonstrated to provide a convenient, robust, and reproducible tool and method for the elucidation of mechanisms of action underlying tumor growth and migration in the hypoxic tumor microenvironment.</p></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"29 1","pages":"Pages 59-65"},"PeriodicalIF":3.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2472555223000771/pdfft?md5=177dab2f5907cc4b2a8d24f9e03b04af&pid=1-s2.0-S2472555223000771-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136127865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Micro/nano topological modification of TiO2 nanotubes activates Thy-1 signaling to control osteogenic differentiation of stem cells","authors":"Li Jinsheng ,&nbsp;Deng Qing ,&nbsp;Chen Junhao ,&nbsp;Si Qiqi ,&nbsp;Chen Jieru ,&nbsp;Yang Liwen ,&nbsp;Guo Zhiyun ,&nbsp;Guo Tailin ,&nbsp;Weng Jie","doi":"10.1016/j.slasd.2023.12.011","DOIUrl":"10.1016/j.slasd.2023.12.011","url":null,"abstract":"<div><p>Micro/nano topological modification is critical for improving the in vivo behaviors of bone implants, regulating multiple cellular functions. Titania (TiO₂) nanotubes show the capacity of promoting osteoblast-related cell differentiation and induce effective osseointegration, serving as a model material for studying the effects of micro/nano-topological modifications on cells. However, the intracellular signaling pathways by which TiO₂ nanotubes regulate the osteogenic differentiation of stem cells are not fully defined. Thy-1 (CD90), a cell surface glycoprotein anchored by glycosylphosphatidylinositol, has been considered a key molecule in osteoblast differentiation in recent years. Nevertheless, whether the micro/nano topology of the implant surface leads to changes in Thy-1 is unknown, as well as whether these changes promote osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Here, TiO₂ nanotubes of various diameters were prepared by adjusting the anodizing voltage. qPCR and immunoblot were carried out to assess the mechanism by which TiO₂ nanotubes regulate Thy-1. The results revealed Ti plates harboring TiO₂ nanotubes ∼100-nm diameter (TNT-100) markedly upregulated Thy-1. Subsequently, upregulated Thy-1 promoted the activation of Fyn/RhoA/MLC Ⅱ/F-actin axis, which enhanced the nuclear translocation of YAP. After Thy-1 knockdown by siRNA, the Fyn/RhoA/MLC Ⅱ/F-actin axis was significantly inhibited and TiO₂ nanotubes showed decreased effects on osteogenic differentiation. Therefore, Thy-1 upregulation might be a major mechanism by which micro/nano-topological modification of TiO₂ nanotubes promotes osteogenic differentiation in BMSCs. This study provides novel insights into the molecular mechanism of TiO₂ nanotubes, which may help design improved bone implants for clinical application.</p></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"29 3","pages":"Article 100139"},"PeriodicalIF":3.1,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2472555223001120/pdfft?md5=a5a06a6783815479240aae3965bb25a0&pid=1-s2.0-S2472555223001120-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139063244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FLECS technology for high-throughput screening of hypercontractile cellular phenotypes in fibrosis: A function-first approach to anti-fibrotic drug discovery","authors":"Yao Wang ,&nbsp;Enrico Cortes ,&nbsp;Ricky Huang ,&nbsp;Jeremy Wan ,&nbsp;Junyi Zhao ,&nbsp;Boris Hinz ,&nbsp;Robert Damoiseaux ,&nbsp;Ivan Pushkarsky","doi":"10.1016/j.slasd.2023.12.010","DOIUrl":"10.1016/j.slasd.2023.12.010","url":null,"abstract":"<div><p>The pivotal role of myofibroblast contractility in the pathophysiology of fibrosis is widely recognized, yet HTS approaches are not available to quantify this critically important function in drug discovery. We developed, validated, and scaled-up a HTS platform that quantifies contractile function of primary human lung myofibroblasts upon treatment with pro-fibrotic TGF-β1. With the fully automated assay we screened a library of 40,000 novel small molecules in under 80 h of total assay run-time. We identified 42 hit compounds that inhibited the TGF-β1-induced contractile phenotype of myofibroblasts, and enriched for 19 that specifically target myofibroblasts but not phenotypically related smooth muscle cells. Selected hits were validated in an <em>ex vivo</em> lung tissue models for their inhibitory effects on fibrotic gene upregulation by TGF-β1. Our results demonstrate that integrating a functional contraction test into the drug screening process is key to identify compounds with targeted and diverse activity as potential anti-fibrotic agents.</p></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"29 3","pages":"Article 100138"},"PeriodicalIF":3.1,"publicationDate":"2023-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2472555223001090/pdfft?md5=26cf5443295c04ca2fa385e66bc86a32&pid=1-s2.0-S2472555223001090-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139063246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design of experiments for the automated development of a multicellular cardiac model for high-throughput screening","authors":"Kavita Raniga ,&nbsp;William Stebbeds ,&nbsp;Arun Shivalingam ,&nbsp;Michelle Pemberton ,&nbsp;Chris Denning","doi":"10.1016/j.slasd.2023.10.006","DOIUrl":"10.1016/j.slasd.2023.10.006","url":null,"abstract":"<div><p>Cardiovascular toxicity remains a major cause of drug attrition in early drug development, clinical trials, and post-market surveillance. <em>In vitro</em> assessment of cardiovascular liabilities often relies on single cell type-based model systems coupled with functional assays, like calcium flux and multielectrode arrays. Although these models offer high-throughput capabilities and demonstrate good predictivity for functional cardiotoxicities, they fail to consider the vital contribution of non-myocyte cells, thus limiting the potential for integrated risk assessment. Complex 3D hPSC-derived multicellular cardiac model systems have been growing in popularity; however, many of these models are limited to low-throughput with lengthy development timelines and high costs, which hampers their suitability to drug discovery.</p><p>To optimize the development of an <em>in vitro</em> multicellular model system containing human-induced pluripotent stem-cell derived cardiomyocytes, endothelial cells and cardiac fibroblasts, we employed the Synthace platform, which enables scientists to express complex experimental intent in a simple format (e.g. Design of Experiments) and to translate this to automation protocols using no-code. Utilizing this approach, we systematically screened the impact of multiple cell culture parameters, including the co-culture of three cell types, on cardiac contractility, with minimal hands-on time. Our platform accelerates the assay development process, providing users with an efficient means to explore and optimize the experimental space for the development of multicellular models. This is particularly valuable in scenarios involving variable biological responses and limited understanding of underling mechanisms. Moreover, users can make better use of resources, streamline their workflows, and drive data-driven decision-making throughout the assay development journey.</p></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"28 8","pages":"Pages 410-417"},"PeriodicalIF":3.1,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S247255522300076X/pdfft?md5=929999b07186c9c55f421bdaa5efed64&pid=1-s2.0-S247255522300076X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136128285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanobodies: A Game-Changer in Cell-Mediated Immunotherapy for Cancer","authors":"Mujahed I. Mustafa ,&nbsp;Ahmed Mohammed","doi":"10.1016/j.slasd.2023.08.008","DOIUrl":"10.1016/j.slasd.2023.08.008","url":null,"abstract":"<div><p>Nanobodies are small, single-domain antibodies that have emerged as a promising tool in cancer immunotherapy. These molecules can target specific antigens on cancer cells and trigger an immune response against them. In this mini-review article, we highlight the potential of nanobodies in cell-mediated immunotherapy for cancer treatment. We discuss the advantages of nanobodies over conventional antibodies, their ability to penetrate solid tumors, and their potential to enhance the efficacy of other immunotherapeutic agents. We also provide an overview of recent preclinical and clinical studies that have demonstrated the effectiveness of nanobody-based immunotherapy in various types of cancer.</p></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"28 8","pages":"Pages 358-364"},"PeriodicalIF":3.1,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2472555223000655/pdfft?md5=df3195ebf43d028972b7a863fedf2b6b&pid=1-s2.0-S2472555223000655-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10522994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of assays to support identification and characterization of modulators of DExH-box helicase DHX9","authors":"Deepali Gotur,&nbsp;April Case,&nbsp;Julie Liu,&nbsp;E. Allen Sickmier ,&nbsp;Nicholas Holt,&nbsp;Kevin E. Knockenhauer,&nbsp;Shihua Yao,&nbsp;Young-Tae Lee,&nbsp;Robert A. Copeland,&nbsp;Shane M. Buker,&nbsp;P. Ann Boriack-Sjodin","doi":"10.1016/j.slasd.2023.08.006","DOIUrl":"10.1016/j.slasd.2023.08.006","url":null,"abstract":"<div><p>DHX9 is a DExH-box RNA helicase that utilizes hydrolysis of all four nucleotide triphosphates (NTPs) to power cycles of 3′ to 5′ directional movement to resolve and/or unwind double stranded RNA, DNA, and RNA/DNA hybrids, R-loops, triplex-DNA and G-quadraplexes. DHX9 activity is important for both viral amplification and maintaining genomic stability in cancer cells; therefore, it is a therapeutic target of interest for drug discovery efforts. Biochemical assays measuring ATP hydrolysis and oligonucleotide unwinding for DHX9 have been developed and characterized, and these assays can support high-throughput compound screening efforts under balanced conditions. Assay development efforts revealed DHX9 can use double stranded RNA with 18-mer poly(U) 3′ overhangs and as well as significantly shorter overhangs at the 5′ or 3′ end as substrates. The enzymatic assays are augmented by a robust SPR assay for compound validation. A mechanism-derived inhibitor, GTPγS, was characterized as part of the validation of these assays and a crystal structure of GDP bound to cat DHX9 has been solved. In addition to enabling drug discovery efforts for DHX9, these assays may be extrapolated to other RNA helicases providing a valuable toolkit for this important target class.</p></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"28 8","pages":"Pages 376-384"},"PeriodicalIF":3.1,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2472555223000631/pdfft?md5=19d6634fca9b39208f94d49e0353b6d9&pid=1-s2.0-S2472555223000631-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10118703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of tau-tubulin kinase 1 inhibitors by microfluidics-based mobility shift assay from a kinase inhibitor library","authors":"Jinlei Wang ,&nbsp;Ying Lin ,&nbsp;Xiaoyu Xu ,&nbsp;Yonghui Wang ,&nbsp;Qiong Xie","doi":"10.1016/j.slasd.2023.06.003","DOIUrl":"10.1016/j.slasd.2023.06.003","url":null,"abstract":"<div><p>Tau tubulin kinase 1 (TTBK1) is a serine/threonine/tyrosine kinase that phosphorylates multiple residues in tau protein. Hyperphosphorylated tau is the main cause of tauopathy, such as Alzheimer's disease (AD). Therefore, preventing tau phosphorylation by inhibiting TTBK1 has been proposed as a therapeutic strategy for AD. However, few substrates of TTBK1 are reported for a biochemical assay and few inhibitors targeting TTBK1 have been reported so far. In this study, we identified a fluorescein amidite (FAM)-labeled peptide 15 from a small peptide library as the optimal peptide substrate for human TTBK1 (hTTBK1). We then developed and validated a microfluidics-based mobility shift assay (MMSA) with peptide 15. We further confirmed that peptide 15 could also be used in the ADP-Glo kinase assay. The established MMSA was applied for screening of a 427-compound kinase inhibitor library, yielding five compounds with IC₅₀s of several micro molars against hTTBK1. Among them, three compounds, AZD5363, A-674,563 and GSK690693 inhibited hTTBK1 in an ATP competitive manner and molecular docking simulations revealed that they enter the ATP pocket and form one or two hydrogen bonds to the hinge region with hTTBK1. Another hit compound, piceatannol, showed non-ATP competitive inhibitory effect on hTTBK1 and may serve as a starting point to develop highly selective hTTBK1 inhibitors. Altogether, this study provided a new <em>in vitro</em> platform for the development of novel hTTBK1 inhibitors that might have potential applications in AD prevention.</p></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"28 8","pages":"Pages 385-393"},"PeriodicalIF":3.1,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2472555223000497/pdfft?md5=8fe6e5c960b9b98dccf62d6d9abccb47&pid=1-s2.0-S2472555223000497-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9822806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role Of Vaccines Against COVID-19 Pandemic","authors":"Professor Dr. Batool Mutar Mahdi ,&nbsp;Dr. Mustafa Almukhtar","doi":"10.1016/j.slasd.2023.07.002","DOIUrl":"10.1016/j.slasd.2023.07.002","url":null,"abstract":"<div><p>Coronaviruses (CoV) are one of the largest families of viruses that infect human beings causing mild common cold or severe diseases like <span>Middle East Respiratory Syndrome (MERS-CoV)</span><svg><path></path></svg>, and Severe Acute Respiratory Syndrome (SARS-CoV). A new strain emerged known as novel coronavirus (nCoV) causing fatal respiratory failure disease. This virus was characterized by rapid spread from asymptomatic and symptomatic patients to healthy people. Thus, vaccine should be considered as one of the important protective measures to control the spread of this virus. One of the challenges to this vaccine is the high mutation rate of this virus and appearance of new strains. Therefore, vaccine should stimulate the immune system in order to overcome the emergence of new strain of this virus.</p></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"28 8","pages":"Pages 355-357"},"PeriodicalIF":3.1,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2472555223000515/pdfft?md5=3af6b7c219d2d83d0879facfc5306584&pid=1-s2.0-S2472555223000515-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9874135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Graph neural networks for the identification of novel inhibitors of a small RNA","authors":"Christopher L. Haga,&nbsp;Xue D. Yang,&nbsp;Ibrahim S. Gheit,&nbsp;Donald G. Phinney","doi":"10.1016/j.slasd.2023.10.002","DOIUrl":"10.1016/j.slasd.2023.10.002","url":null,"abstract":"<div><p>MicroRNAs (miRNAs) play a crucial role in post-transcriptional gene regulation and have been implicated in various diseases, including cancers and lung disease. In recent years, Graph Neural Networks (GNNs) have emerged as powerful tools for analyzing graph-structured data, making them well-suited for the analysis of molecular structures. In this work, we explore the application of GNNs in ligand-based drug screening for small molecules targeting miR-21. By representing a known dataset of small molecules targeting miR-21 as graphs, GNNs can learn complex relationships between their structures and activities, enabling the prediction of potential miRNA-targeting small molecules by capturing the structural features and similarity between known miRNA-targeting compounds. The use of GNNs in miRNA-targeting drug screening holds promise for the discovery of novel therapeutic agents and provides a computational framework for efficient screening of large chemical libraries.</p></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"28 8","pages":"Pages 402-409"},"PeriodicalIF":3.1,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2472555223000710/pdfft?md5=cf43d9172dd2449988ff99574d605ae3&pid=1-s2.0-S2472555223000710-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41241999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HTS discovery of PARP1-HPF1 complex inhibitors in cancer","authors":"Timothy Kellett ,&nbsp;Rida Noor ,&nbsp;Qiong Zhou ,&nbsp;Hector Esquer ,&nbsp;Rita Sala ,&nbsp;Petra Stojanovic ,&nbsp;Johannes Rudolph ,&nbsp;Karolin Luger ,&nbsp;Daniel V. LaBarbera","doi":"10.1016/j.slasd.2023.10.003","DOIUrl":"10.1016/j.slasd.2023.10.003","url":null,"abstract":"<div><p>PARP1/2 inhibitors (PARPi) are effective clinically used drugs for the treatment of cancers with BRCA deficiencies. PARPi have had limited success and applicability beyond BRCA deficient cancers, and their effect is diminished by resistance mechanisms. The recent discovery of Histone PARylation Factor (HPF1) and the role it plays in the PARylation reaction by forming a shared active site with PARP1 raises the possibility that novel inhibitors that target the PARP1–HPF1 complex can be identified. Herein we describe a simple and cost-effective high-throughput screening (HTS) method aimed at discovering inhibitors of the PARP1–HPF1 complex. Upon HTS validation, we first applied this method to screen a small PARP-focused library of compounds and then scale up our approach using robotic automation to conduct a pilot screen of 10,000 compounds and validating &gt;100 hits. This work demonstrates for the first time the capacity to discover potent inhibitors of the PARP1-HPF1 complex, which may have utility as probes to better understand the DNA damage response and as therapeutics for cancer.</p></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"28 8","pages":"Pages 394-401"},"PeriodicalIF":3.1,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2472555223000692/pdfft?md5=fe301035b3580ce7c1e6668e001bf023&pid=1-s2.0-S2472555223000692-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41242000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}