Pub Date : 2025-01-01Epub Date: 2024-12-17DOI: 10.1016/j.slasd.2024.100206
Prasiddha Guragain, Sunil Singh, Hossein Tavana
Three-dimensional (3D) tumor models provide physiologically relevant tumor environments and have become a major tool in cancer research and drug discovery. This article presents a protocol for creating a 3D organotypic tumor model by embedding a cancer cell spheroid within a collagen matrix containing dispersed fibroblasts. This model offers significant advantages over the conventional monolayer cell culture, monoculture spheroids of cancer cells, and intermixed co-culture of cancer and stromal cells by mimicking the spatial organization and mechanical properties of a solid tumor. Compatible with robotic automation, our protocol significantly enhances reproducibility and scalability of creating a tumor model to study tumor-stromal interactions and test therapeutic compounds
{"title":"Protocol to develop A 3D tumor model for drug testing applications","authors":"Prasiddha Guragain, Sunil Singh, Hossein Tavana","doi":"10.1016/j.slasd.2024.100206","DOIUrl":"10.1016/j.slasd.2024.100206","url":null,"abstract":"<div><div>Three-dimensional (3D) tumor models provide physiologically relevant tumor environments and have become a major tool in cancer research and drug discovery. This article presents a protocol for creating a 3D organotypic tumor model by embedding a cancer cell spheroid within a collagen matrix containing dispersed fibroblasts. This model offers significant advantages over the conventional monolayer cell culture, monoculture spheroids of cancer cells, and intermixed co-culture of cancer and stromal cells by mimicking the spatial organization and mechanical properties of a solid tumor. Compatible with robotic automation, our protocol significantly enhances reproducibility and scalability of creating a tumor model to study tumor-stromal interactions and test therapeutic compounds</div></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"30 ","pages":"Article 100206"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866355","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}
Pub Date : 2025-01-01Epub Date: 2024-12-17DOI: 10.1016/j.slasd.2024.100205
Cui Lin , Yijie Wang , Tao Peng , Pengpeng Liu , Yuanyuan Liang , Wencheng Kang , Xiaoping Yu , Yang Song , Xuping Shentu
Neuron-specific enolase (NSE) is currently the most reliable biomarker for small cell lung cancer (SCLC), which is important for disease monitoring, clinical evaluation and diagnosis. However, traditional methods suffer from various disadvantages, including instability, complexity, time-consuming operations, and the necessity for standards. In this study, we developed a calibration-free concentration analysis (CFCA) method based on surface plasmon resonance (SPR) technology, to accurately quantify the active concentration of NSE without relying on any standards. Based on the principle of CFCA, the active concentration of NSE can be calculated by observing binding rate variations at two flow rates under partial mass transport limitation and combining it with the known diffusion coefficient of the NSE. Using the method of CFCA, the active concentration of NSE was determined was only 0.48 mg/mL with an intra-day repeatability of 4.75%. The method has the advantages of simplicity, rapidity, realistic analysis and ease of implementation of high-throughput automated detection. Therefore, the method is expected to become the main measurement method for protein active concentration, which will be beneficial for the development of active protein standards.
{"title":"Absolute quantification of Neuron-specific enolase based on surface plasmon resonance","authors":"Cui Lin , Yijie Wang , Tao Peng , Pengpeng Liu , Yuanyuan Liang , Wencheng Kang , Xiaoping Yu , Yang Song , Xuping Shentu","doi":"10.1016/j.slasd.2024.100205","DOIUrl":"10.1016/j.slasd.2024.100205","url":null,"abstract":"<div><div>Neuron-specific enolase (NSE) is currently the most reliable biomarker for small cell lung cancer (SCLC), which is important for disease monitoring, clinical evaluation and diagnosis. However, traditional methods suffer from various disadvantages, including instability, complexity, time-consuming operations, and the necessity for standards. In this study, we developed a calibration-free concentration analysis (CFCA) method based on surface plasmon resonance (SPR) technology, to accurately quantify the active concentration of NSE without relying on any standards. Based on the principle of CFCA, the active concentration of NSE can be calculated by observing binding rate variations at two flow rates under partial mass transport limitation and combining it with the known diffusion coefficient of the NSE. Using the method of CFCA, the active concentration of NSE was determined was only 0.48 mg/mL with an intra-day repeatability of 4.75%. The method has the advantages of simplicity, rapidity, realistic analysis and ease of implementation of high-throughput automated detection. Therefore, the method is expected to become the main measurement method for protein active concentration, which will be beneficial for the development of active protein standards.</div></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"30 ","pages":"Article 100205"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866347","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}
Pub Date : 2025-01-01Epub Date: 2024-12-13DOI: 10.1016/j.slasd.2024.100203
Tien T.T. Truong , Toan V. Phan , Yamin Oo , Oranart Matangkasombut , João N. Ferreira
{"title":"A novel platform for oral epithelia sheet biofabrication via magnetic 3D bioprinting","authors":"Tien T.T. Truong , Toan V. Phan , Yamin Oo , Oranart Matangkasombut , João N. Ferreira","doi":"10.1016/j.slasd.2024.100203","DOIUrl":"10.1016/j.slasd.2024.100203","url":null,"abstract":"","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"30 ","pages":"Article 100203"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831069","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":"The history, landscape, and outlook of human cell line authentication and security","authors":"Elijah Harbut , Yiorgos Makris , Alexander Pertsemlidis , Leonidas Bleris","doi":"10.1016/j.slasd.2024.100194","DOIUrl":"10.1016/j.slasd.2024.100194","url":null,"abstract":"","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"29 8","pages":"Article 100194"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634405","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}
Pub Date : 2024-12-01Epub Date: 2024-11-08DOI: 10.1016/j.slasd.2024.100193
Antje Pommereau , Francesca Sassone , Alessandro Poli , Marcella De Silvestris , Lia Scarabottolo , Yasmin Zuschlag , Thomas Licher , Felix Bärenz
GLUT9/SLC2A9 is a urate transporter and takes a fundamental role in the maintenance of normal serum urate levels. GLUT9 is the sole transporter of reabsorbed urate from renal epithelial cells to blood, thus making it an ideal pharmacological target for the development of urate-lowering drugs. None of the three currently available assays for studying GLUT9 pharmacological inhibition can support a high throughput drug discovery screening campaign. In this manuscript we present two novel assay technologies which can be used in a drug discovery screening cascade for GLUT9: a GLUT9 membrane potential assay for primary screening; and a solid-supported membrane (SSM)-based supported electrophysiological assay for secondary screening.
{"title":"The development of a novel high-throughput membrane potential assay and a solid-supported membrane (SSM)-based electrophysiological assay to study the pharmacological inhibition of GLUT9/SLC2A9 isoforms in a drug discovery program","authors":"Antje Pommereau , Francesca Sassone , Alessandro Poli , Marcella De Silvestris , Lia Scarabottolo , Yasmin Zuschlag , Thomas Licher , Felix Bärenz","doi":"10.1016/j.slasd.2024.100193","DOIUrl":"10.1016/j.slasd.2024.100193","url":null,"abstract":"<div><div>GLUT9/SLC2A9 is a urate transporter and takes a fundamental role in the maintenance of normal serum urate levels. GLUT9 is the sole transporter of reabsorbed urate from renal epithelial cells to blood, thus making it an ideal pharmacological target for the development of urate-lowering drugs. None of the three currently available assays for studying GLUT9 pharmacological inhibition can support a high throughput drug discovery screening campaign. In this manuscript we present two novel assay technologies which can be used in a drug discovery screening cascade for GLUT9: a GLUT9 membrane potential assay for primary screening; and a solid-supported membrane (SSM)-based supported electrophysiological assay for secondary screening.</div></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"29 8","pages":"Article 100193"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634404","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}
Pub Date : 2024-12-01Epub Date: 2024-10-28DOI: 10.1016/j.slasd.2024.100190
Chayanit Chaweewannakorn , Khin The Nu Aye , Joao N. Ferreira
Over the past decade, there has been a rapid development in the use of magnetic three dimensional (3D) based cell culture systems. Concerning the skeletal muscle, 3D culture systems can provide biological insights for translational clinical research in the fields of muscle physiology and metabolism. These systems can enhance the cell culture environment by improving spatially-oriented cellular assemblies and morphological features closely mimicking the in vivo tissues/organs, since they promote strong interactions between cells and the extracellular matrix (ECM). However, the time-consuming and complex nature of 3D traditional culture techniques pose a challenge to the widespread adoption of 3D systems. Herein, a bench protocol is presented for creating an innovative, promptly assembled and user-friendly culture platform for the magnetic 3D bioprinting of skeletal muscle spheroids. Our protocol findings revealed consistent morphological outcomes and the functional development of skeletal muscle tissue, as evidenced by the expression of muscle-specific contractile proteins and myotubes and the responsiveness to stimulation with cholinergic neurotransmitters. This proof-of-concept protocol confirmed the future potential for further validation and application of spheroid-based assays in human skeletal muscle research.
{"title":"Magnetic 3D bioprinting of skeletal muscle spheroid for a spheroid-based screening assay","authors":"Chayanit Chaweewannakorn , Khin The Nu Aye , Joao N. Ferreira","doi":"10.1016/j.slasd.2024.100190","DOIUrl":"10.1016/j.slasd.2024.100190","url":null,"abstract":"<div><div>Over the past decade, there has been a rapid development in the use of magnetic three dimensional (3D) based cell culture systems. Concerning the skeletal muscle, 3D culture systems can provide biological insights for translational clinical research in the fields of muscle physiology and metabolism. These systems can enhance the cell culture environment by improving spatially-oriented cellular assemblies and morphological features closely mimicking the in vivo tissues/organs, since they promote strong interactions between cells and the extracellular matrix (ECM). However, the time-consuming and complex nature of 3D traditional culture techniques pose a challenge to the widespread adoption of 3D systems. Herein, a bench protocol is presented for creating an innovative, promptly assembled and user-friendly culture platform for the magnetic 3D bioprinting of skeletal muscle spheroids. Our protocol findings revealed consistent morphological outcomes and the functional development of skeletal muscle tissue, as evidenced by the expression of muscle-specific contractile proteins and myotubes and the responsiveness to stimulation with cholinergic neurotransmitters. This proof-of-concept protocol confirmed the future potential for further validation and application of spheroid-based assays in human skeletal muscle research.</div></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"29 8","pages":"Article 100190"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570581","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}
Pub Date : 2024-12-01Epub Date: 2024-11-05DOI: 10.1016/j.slasd.2024.100191
Blaž Andlovic , Alexander Wolf , Malgorzata Hiltmann , Bert M. Klebl , Jan Eickhoff , Christian Ottmann
The Hippo pathway plays an important role in organ size control and tissue homeostasis. Dysregulation is involved in many pathologies, including cancer, which has attracted interest in targeting the Hippo pathway. Since the upstream components are bona fide tumor suppressors, it is feasible to target oncogenic downstream targets such as TAZ, a key downstream effector in the Hippo pathway. Its activity is regulated by phosphorylation on multiple sites, with Ser89 playing a critical role in regulation of TAZ activity. Phosphorylation of TAZ at Ser89 promotes binding to 14–3–3 scaffolding proteins, preventing nuclear translocation and abolishing target gene transcription. Here we describe the development of a cell-based assay suitable for high-throughput screening, based on a split NanoLuc luciferase, for monitoring interactions between 14 3–3 and TAZ in living cells. We have validated the assay by screening of a kinase-biased library. The assay can be quickly adapted for higher throughput and thus offers a valuable tool to study new signal inputs involved in regulation of TAZ activity as well as for identification of molecules that modulate the Hippo pathway.
{"title":"Development of a live cell assay for real-time monitoring the interactions between the Hippo pathway components 14-3-3 and TAZ","authors":"Blaž Andlovic , Alexander Wolf , Malgorzata Hiltmann , Bert M. Klebl , Jan Eickhoff , Christian Ottmann","doi":"10.1016/j.slasd.2024.100191","DOIUrl":"10.1016/j.slasd.2024.100191","url":null,"abstract":"<div><div>The Hippo pathway plays an important role in organ size control and tissue homeostasis. Dysregulation is involved in many pathologies, including cancer, which has attracted interest in targeting the Hippo pathway. Since the upstream components are <em>bona fide</em> tumor suppressors, it is feasible to target oncogenic downstream targets such as TAZ, a key downstream effector in the Hippo pathway. Its activity is regulated by phosphorylation on multiple sites, with Ser89 playing a critical role in regulation of TAZ activity. Phosphorylation of TAZ at Ser89 promotes binding to 14–3–3 scaffolding proteins, preventing nuclear translocation and abolishing target gene transcription. Here we describe the development of a cell-based assay suitable for high-throughput screening, based on a split NanoLuc luciferase, for monitoring interactions between 14 3–3 and TAZ in living cells. We have validated the assay by screening of a kinase-biased library. The assay can be quickly adapted for higher throughput and thus offers a valuable tool to study new signal inputs involved in regulation of TAZ activity as well as for identification of molecules that modulate the Hippo pathway.</div></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"29 8","pages":"Article 100191"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607587","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}
Pub Date : 2024-12-01Epub Date: 2024-10-19DOI: 10.1016/j.slasd.2024.100188
Rama Balakrishnan , Ellen L. Berg , Christopher C. Butler , Alex M. Clark , Sheryl P. Denker , Isabella Feierberg , Jason Harris , Timothy P. Ikeda , Samantha Jeschonek , Vladimir A. Makarov , Christopher Southan , Dana Vanderwall , Peter Winstanley
We present a standardized metadata template for assays used in pharmaceutical drug discovery research, according to the FAIR principles. We also describe the use of an automated tool for annotating assays from a variety of sources, including PubChem, commercial assay providers, and the peer-reviewed literature, to this metadata template. Adoption of a standardized metadata template will allow drug discovery scientists to better understand and compare the increasing amounts of assay data becoming available, and will facilitate the use of artificial intelligence tools and other computational methods for analysis and prediction. Since bioassays drive advances in biomedical research, improvements in assay metadata can improve productivity in discovery of new therapeutics, platform technologies, and assay methods.
{"title":"Bioassay protocol metadata annotation: Proposed standards adoption","authors":"Rama Balakrishnan , Ellen L. Berg , Christopher C. Butler , Alex M. Clark , Sheryl P. Denker , Isabella Feierberg , Jason Harris , Timothy P. Ikeda , Samantha Jeschonek , Vladimir A. Makarov , Christopher Southan , Dana Vanderwall , Peter Winstanley","doi":"10.1016/j.slasd.2024.100188","DOIUrl":"10.1016/j.slasd.2024.100188","url":null,"abstract":"<div><div>We present a standardized metadata template for assays used in pharmaceutical drug discovery research, according to the FAIR principles. We also describe the use of an automated tool for annotating assays from a variety of sources, including PubChem, commercial assay providers, and the peer-reviewed literature, to this metadata template. Adoption of a standardized metadata template will allow drug discovery scientists to better understand and compare the increasing amounts of assay data becoming available, and will facilitate the use of artificial intelligence tools and other computational methods for analysis and prediction. Since bioassays drive advances in biomedical research, improvements in assay metadata can improve productivity in discovery of new therapeutics, platform technologies, and assay methods.</div></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"29 8","pages":"Article 100188"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482706","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}
Pub Date : 2024-12-01Epub Date: 2024-11-04DOI: 10.1016/j.slasd.2024.100189
Ryan Chan , Christian Shema Mugisha , Vorada Chuenchob , Stephanie A. Moquin , Ujjini H. Manjunatha , Nadine Jarrousse , Vineet D. Menachery , Xuping Xie , Erika L. Flannery , Richard T. Eastman
Over the past 25 years, the global community has faced challenges posed by three distinct outbreaks of coronaviruses including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The identification of a novel alphacoronavirus canine CoV (CCoV-HuPn2018) in human patients in Malaysia underscores the potential for crossover infections to humans. The threat of the ever-evolving nature of viral infections as well as the lingering health and socioeconomic effects of the recent SARS-CoV-2 pandemic emphasize the urgent need for advanced antiviral drug screening tools that can be quickly implemented to strengthen preparedness and preventive measures against future outbreaks. Here, we present the development and validation of a novel RNA-fluorescence in situ hybridization (FISH) imaging assay as a 384-well, high-throughput rapid response platform for antiviral drug discovery. RNA-FISH is a powerful tool to visualize specific mRNA in cultured cells using a high-content imaging platform. The flexibility of RNA-FISH probe sets allows for the rapid design of viral genome-specific probes, enabling in vitro assay development to test for inhibition of viral replication by either biologic or small molecule inhibitors. Screening of 170 antiviral compounds in concentration-response demonstrates a strong correlation between the RNA-FISH assay and an immunofluorescence assay (IFA) for both human coronaviruses HCoV-OC43 and HCoV-229E. Additionally, we successfully applied this methodology in the context of CCoV strain 1–71, proving rapid development and deployment, opening new avenues for the evaluation of antiviral drugs to potential future emerging threats.
{"title":"Rapid-response RNA-fluorescence in situ hybridization (FISH) assay platform for coronavirus antiviral high-throughput screening","authors":"Ryan Chan , Christian Shema Mugisha , Vorada Chuenchob , Stephanie A. Moquin , Ujjini H. Manjunatha , Nadine Jarrousse , Vineet D. Menachery , Xuping Xie , Erika L. Flannery , Richard T. Eastman","doi":"10.1016/j.slasd.2024.100189","DOIUrl":"10.1016/j.slasd.2024.100189","url":null,"abstract":"<div><div>Over the past 25 years, the global community has faced challenges posed by three distinct outbreaks of coronaviruses including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The identification of a novel alphacoronavirus canine CoV (CCoV-HuPn2018) in human patients in Malaysia underscores the potential for crossover infections to humans. The threat of the ever-evolving nature of viral infections as well as the lingering health and socioeconomic effects of the recent SARS-CoV-2 pandemic emphasize the urgent need for advanced antiviral drug screening tools that can be quickly implemented to strengthen preparedness and preventive measures against future outbreaks. Here, we present the development and validation of a novel RNA-fluorescence <em>in situ</em> hybridization (FISH) imaging assay as a 384-well, high-throughput rapid response platform for antiviral drug discovery. RNA-FISH is a powerful tool to visualize specific mRNA in cultured cells using a high-content imaging platform. The flexibility of RNA-FISH probe sets allows for the rapid design of viral genome-specific probes, enabling <em>in vitro</em> assay development to test for inhibition of viral replication by either biologic or small molecule inhibitors. Screening of 170 antiviral compounds in concentration-response demonstrates a strong correlation between the RNA-FISH assay and an immunofluorescence assay (IFA) for both human coronaviruses HCoV-OC43 and HCoV-229E. Additionally, we successfully applied this methodology in the context of CCoV strain 1–71, proving rapid development and deployment, opening new avenues for the evaluation of antiviral drugs to potential future emerging threats.</div></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"29 8","pages":"Article 100189"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142578690","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}
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