SLAS Discovery最新文献

{"title":"New homocysteine consumption assay for high-throughput screening of human cystathionine-β-synthase","authors":"Dalibor Nakládal ,&nbsp;Rick Oerlemans ,&nbsp;Miroslava Molitorisová ,&nbsp;Nikola Chomaničová ,&nbsp;Gabriel Zorkócy ,&nbsp;Christina Yoseif ,&nbsp;Adrianus Cornelis van der Graaf ,&nbsp;Stanislav Stuchlík ,&nbsp;Guido Krenning ,&nbsp;Matthew R. Groves ,&nbsp;André Heeres ,&nbsp;Zdenko Levarski ,&nbsp;Ján Kyselovič ,&nbsp;Rob H. Henning ,&nbsp;Leo E. Deelman","doi":"10.1016/j.slasd.2025.100234","DOIUrl":"10.1016/j.slasd.2025.100234","url":null,"abstract":"<div><div>Hyperhomocysteinemia is a risk factor for cardiovascular disease, neurological disorders, and bone abnormalities. The key enzyme in homocysteine metabolism, cystathionine-β-synthase (CBS) is recognized as a target for new homocysteine-lowering therapies including enzyme replacement and gene therapy. Currently, there are no pharmacotherapies available that enhance CBS activity through its allosteric mechanism. The only known allosteric activator of CBS is S-adenosyl-<span>L</span>-methionine (SAM), which is available as a food supplement, but its effectiveness is limited by low membrane permeability and universal involvement in methylation reactions as a substrate. The discovery of CBS activators in high-throughput screening is challenging due to a lack of dedicated assays. Available HTS-compatible activity assays for CBS rely on measuring the product hydrogen sulfide or methanethiol where the signal increases with increased CBS activity. In the case of fluorescence-based assays, it is challenging to discern activators from autofluorescent compounds.</div><div>In this study, we introduce a homocysteine consumption assay for isolated human CBS (HconCBS) based on the absorbance of Ellman's reagent. This assay leverages a decrease in signal upon CBS activation, with performance parameters exceeding the requirements for high-throughput screening. In a commercial library of 3010 compounds, the HconCBS assay identified 10 hit compounds as more active than SAM, whereas a fluorescence-based assay using 7-azido-4-methylcoumarin (AzMC) identified 141 hits. HconCBS identified 101 compounds with autoabsorbance which did not include hit compounds, while the fluorescence-based assay identified 383 autofluorescent compounds which included all hit compounds. While 4 out of 10 HconCBS hits were confirmed when purchased from a new source, the compounds affected homocysteine rather than CBS. Nevertheless, HconCBS consistently detected the CBS activator seleno-adenosyl-<span>L</span>-methionine (SeAM) added to 4 library plates and re-discovered the same library hits in 3 out of 4 re-screened plates.</div><div>Taken together, HconCBS was designed to enable the discovery of allosteric CBS activators with greater reliability than fluorescence-based methods. Despite identifying some compounds that acted on homocysteine rather than CBS, the assay consistently identified the CBS activators SAM and SeAM and demonstrated reproducibility across two screening rounds. These findings establish HconCBS as a valuable tool for identifying potential therapeutic candidates for hyperhomocysteinemia, addressing a key gap in the development of CBS-targeted pharmacotherapies.</div></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"32 ","pages":"Article 100234"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SLAS special issue editorial 2025: Outcomes from antiviral drug discovery for pathogens of pandemic concern","authors":"Timothy P. Spicer,&nbsp;Louis D. Scampavia","doi":"10.1016/j.slasd.2025.100231","DOIUrl":"10.1016/j.slasd.2025.100231","url":null,"abstract":"","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"32 ","pages":"Article 100231"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a cell-based target engagement assay for pyruvate dehydrogenase kinase","authors":"Mya D. Gough ,&nbsp;Matthew B. Robers ,&nbsp;Cesear R. Corona ,&nbsp;Ranjit K. Mehta ,&nbsp;Mukesh K. Nyati ,&nbsp;Peter L. Toogood","doi":"10.1016/j.slasd.2025.100227","DOIUrl":"10.1016/j.slasd.2025.100227","url":null,"abstract":"<div><div>Pyruvate dehydrogenase kinases (PDHKs) are non-canonical serine/threonine kinases that regulate the pyruvate dehydrogenase complex. Given their central role in metabolism, dysregulation of PDHKs has been linked with a broad variety of pathological conditions, such as cardiovascular disease, diabetes, lactic acidosis, and cancer. While there are many small molecule PDHK inhibitors, including several that have advanced into clinical development, no PDHK inhibitor has been approved for therapeutic use for any indication. Currently the field lacks well-characterized tool compounds that can probe PDHK biology and differentiate between PDHK isoforms. Moreover, disconnects between biochemical and cell-based assays have complicated efforts to understand the biological effect of inhibiting PDHK catalytic activity. To better understand how PDHK inhibitors function in cells, we have developed a cell-based assay using NanoBRET Target Engagement technology. Here, we describe the use of NanoBRET to evaluate binding at the PDHK ATP and lipoamide sites. Using these assays, we have profiled previously described PDHK inhibitors and demonstrated the ability of NanoBRET to distinguish between PDHK inhibitors with different mechanisms of action and to elucidate isoform selectivity.</div></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"32 ","pages":"Article 100227"},"PeriodicalIF":2.7,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694675","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":"Enhancing throughput and robustness of the fibroblast to myofibroblast transition assay","authors":"Elisabeth Bäck ,&nbsp;Jessica Bjärkby ,&nbsp;Leire Escudero-Ibarz ,&nbsp;Stefan Tångefjord ,&nbsp;Johan Jirholt ,&nbsp;Mei Ding","doi":"10.1016/j.slasd.2025.100226","DOIUrl":"10.1016/j.slasd.2025.100226","url":null,"abstract":"<div><div>Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive age-related lung disease with an average survival of 3–5 years post-diagnosis if left untreated. It is characterized by lung fibrosis, inflammation, and destruction of lung architecture, leading to worsening respiratory symptoms and physiological impairment, ultimately culminating in progressive respiratory failure. The development of novel therapeutics for the treatment of IPF represents a significant unmet medical need. Fibroblast to myofibroblast transition (FMT) in response to fibrogenic mediators such as transforming growth factor beta 1 (TGF-β1) has been identified as a key cellular phenotype driving the formation of myofibroblasts and lung fibrosis in IPF. Establishing a robust and high-throughput in vitro human FMT assay is crucial for uncovering new disease targets and for efficiently screening compounds for the advancement of novel therapeutics aimed at targeting myofibroblast activity. However, creating a robust FMT assay suitable for high-throughput drug screening has proven challenging due to the requisite level of automation.</div><div>In this study, we focus on evaluating different automation approaches for liquid exchange and compound dosing in the human FMT assay. A semi-automated assay, capable of screening a large number of compounds that inhibit TGF-β1-induced FMT in both Normal Human Lung Fibroblasts (NHLF) and IPF-patient derived Disease Human Lung Fibroblasts (IPF-DHLF), has been successfully developed and optimized. We demonstrate that the optimized FMT assay using liquid handling automation exhibits great assay reproducibility, shows good assay translation using human lung fibroblasts from normal healthy versus IPF-patients, and demonstrates acceptable human primary donor variability. This allows for the standardization of comparisons of compound anti-fibrotic potency across IPF projects.</div></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"32 ","pages":"Article 100226"},"PeriodicalIF":2.7,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639935","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":"A secretome screen in primary human lung fibroblasts identifies FGF9 as a novel regulator of cellular senescence","authors":"Jenna Bradley ,&nbsp;Patrick O'Shea ,&nbsp;Catherine Wrench ,&nbsp;Johann Mattsson ,&nbsp;Roxane Paulin ,&nbsp;Catherine Overed-Sayer ,&nbsp;Laura Rosenberg ,&nbsp;Henric Olsson ,&nbsp;Davide Gianni","doi":"10.1016/j.slasd.2025.100223","DOIUrl":"10.1016/j.slasd.2025.100223","url":null,"abstract":"<div><div>Senescent cells contribute to the pathogenesis of idiopathic pulmonary fibrosis (IPF), a disease with significant unmet need and therefore, there is an interest in discovering new drug targets that regulate this process. We design and perform a phenotypic screen with a secreted protein library in primary human lung fibroblasts to identify modulators of cell senescence. We identify FGF9 as a suppressor of several senescence phenotypes reducing stimulated p21 expression, enlarged morphology, DNA damage and SASP secretion, which is consistent with both DNA-damage and ROS induced senescence. We also show that FGF9 reduces fibroblast activation in both healthy and IPF fibroblasts shown by a reduction in pro-fibrotic markers such as α-smooth muscle actin and COL1A1 mRNA. Our findings identify FGF9 as a suppressor of both senescence and fibrotic features in lung fibroblasts and therefore could be targeted as a new therapeutic strategy for respiratory diseases such as IPF.</div></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"32 ","pages":"Article 100223"},"PeriodicalIF":2.7,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538194","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":"Corelet™ platform: Precision high throughput screening for targeted drug discovery of biomolecular condensates","authors":"Aislinn Mayfield ,&nbsp;Xin Zhang,&nbsp;Ivan Efremov,&nbsp;Michael G Kauffman,&nbsp;John F Reilly,&nbsp;Bahareh Eftekharzadeh","doi":"10.1016/j.slasd.2025.100224","DOIUrl":"10.1016/j.slasd.2025.100224","url":null,"abstract":"<div><div>Biomolecular condensates (BMCs) are crucial for cellular organization and function, and their dysregulation is linked to neurological, oncologic and inflammatory diseases. This highlights the need for advanced investigative tools leading to targeted BMC therapeutics. To address this need, Nereid Therapeutics uses Corelet™ technology and an automated high-throughput screening (HTS) platform to precisely quantify phase separation events and identify BMC modulators for previously undruggable targets. Hundreds of thousands of small molecules have been screened utilizing Corelet technology, yielding small molecule BMC-modulating compounds which serve as the basis for the development of targeted therapies for diseases with high unmet need.</div></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"32 ","pages":"Article 100224"},"PeriodicalIF":2.7,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538195","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":"Combinatorial screen of targeted agents with the PI3K inhibitors inavolisib, alpelisib, duvelisib, and copanlisib in multi-cell type tumor spheroids","authors":"Thomas S. Dexheimer ,&nbsp;Zahra Davoudi ,&nbsp;Nathan P. Coussens ,&nbsp;Thomas Silvers ,&nbsp;Joel Morris ,&nbsp;Naoko Takebe ,&nbsp;Rabih Said ,&nbsp;Jeffrey A. Moscow ,&nbsp;James H. Doroshow ,&nbsp;Beverly A. Teicher","doi":"10.1016/j.slasd.2025.100222","DOIUrl":"10.1016/j.slasd.2025.100222","url":null,"abstract":"<div><div>Dysregulation of the phosphatidylinositol 3-kinase (PI3K) pathway is a key contributor to cancer, making PI3K inhibitors a promising approach for targeted therapy. The selectivity of available inhibitors varies across different PI3K isoforms. Alpelisib and inavolisib are selective for the α-isoform, while duvelisib targets the δ- and γ-isoforms, and copanlisib is a pan-PI3K inhibitor, active against all isoforms. This study investigated the activity of these four PI3K inhibitors in combination with other targeted agents using multi-cell type tumor spheroids composed of 60% malignant cells, 25% endothelial cells, and 15% mesenchymal stem cells. Twenty-nine tumor spheroid models were evaluated, including twenty-six patient-derived cancer cell lines from the NCI Patient-Derived Models Repository and three established cell lines from the NCI-60 human tumor cell line panel. Additive and/or synergistic effects were observed with alpelisib or inavolisib or copanlisib in combination with a RAS/MEK/ERK pathway inhibitor, either selumetinib (MEK), ravoxertinib (ERK 1/2), or tovorafenib (DAY101, RAF). Combinations of each of these three PI3K inhibitors with the KRAS mutation specific inhibitors MTRX1133 (KRAS G12D) or sotorasib (KRAS G12C) had selective activity in cell lines harboring the corresponding target. Lastly, combination effects were observed from vertical inhibition of the PI3K/AKT/mTOR pathway with a PI3K inhibitor in combination with either the mTORC1/2 inhibitor sapanisertib or an AKT inhibitor, ipatasertib or afuresertib.</div></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"32 ","pages":"Article 100222"},"PeriodicalIF":2.7,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506646","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":"A novel high-throughput screening platform to identify inhibitors of DNAJB1-PRKACA-driven transcriptional activity in fibrolamellar carcinoma","authors":"Nihal Bharath ,&nbsp;Emma DiPietro ,&nbsp;Olivia Durfee ,&nbsp;Ina Kycia ,&nbsp;Jennifer Splaine ,&nbsp;Praveen Sethupathy ,&nbsp;Michael S. Rogers ,&nbsp;Khashayar Vakili","doi":"10.1016/j.slasd.2025.100221","DOIUrl":"10.1016/j.slasd.2025.100221","url":null,"abstract":"<div><div>Fibrolamellar carcinoma (FLC) is a primary liver cancer with a poor prognosis, primarily due to the lack of effective chemotherapeutic options. The <em>DNAJB1-PRKACA</em> (DP) gene fusion is recognized as the key oncogenic driver in FLC. This fusion arises from a ∼400 kb heterozygous deletion on chromosome 19, which fuses exon 1 of <em>DNAJB1</em> with exons 2–10 of <em>PRKACA</em>, the gene encoding the catalytic subunit of protein kinase A (PKA). While targeting DP is considered a promising therapeutic approach, attempts to inhibit the kinase function of the DP fusion protein have been largely unsuccessful due to off-target effects on wild-type PKA.</div><div>In response to this challenge, we developed a high-throughput screening (HTS) assay to identify inhibitors of DP's downstream signaling pathways involved in transcriptional regulation. Our previous research identified <em>LINC00473</em> as a transcriptional marker for DP protein expression, and <em>LINC00473</em> is known to be upregulated in FLC tumors. Additionally, evidence suggests that <em>LINC00473</em> promotes FLC tumor growth.</div><div>Based on the relationship between DP and <em>LINC00473</em> expression, we engineered the HEK-DP-Luc reporter cell line by modifying HEK293 cells to express DP at the endogenous locus and to express the NanoLuc luciferase gene under the control of the <em>LINC00473</em> promoter and enhancer. We have optimized the HEK-DP-Luc cells for HTS, and here we present our pipeline for primary screening and counter-screening to identify compounds that inhibit DP's downstream transcriptional activity. This HTS platform provides a novel approach for therapeutic drug discovery in FLC.</div></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"32 ","pages":"Article 100221"},"PeriodicalIF":2.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416366","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":"Comparative evaluation of cell-based assay technologies for scoring drug-induced condensation of SARS-CoV-2 nucleocapsid protein","authors":"Rui Tong Quek ,&nbsp;Cyna R. Shirazinejad ,&nbsp;Christina L. Young ,&nbsp;Kierra S. Hardy ,&nbsp;Samuel Lim ,&nbsp;Phillip J. Elms ,&nbsp;David T. McSwiggen ,&nbsp;Timothy J. Mitchison ,&nbsp;Pamela A. Silver","doi":"10.1016/j.slasd.2025.100220","DOIUrl":"10.1016/j.slasd.2025.100220","url":null,"abstract":"<div><div>Protein-nucleic acid phase separation has been implicated in many diseases such as viral infections, neurodegeneration, and cancer. There is great interest in identifying condensate modulators (CMODs), which are small molecules that alter the dynamics and functions of phase-separated condensates, as a potential therapeutic modality. Most CMODs were identified in cellular high-content screens (HCS) where micron-scale condensates were characterized by fluorescence microscopy. These approaches lack information on protein dynamics, are limited by microscope resolution, and are insensitive to subtle condensation phenotypes missed by overfit analysis pipelines. Here, we evaluate two alternative cell-based assays: high-throughput single molecule tracking (htSMT) and proximity-based condensate biosensors using NanoBIT (split luciferase) and NanoBRET (bioluminescence resonance energy transfer) technologies. We applied these methods to evaluate condensation of the SARS-CoV-2 nucleocapsid (N) protein under GSK3 inhibitor treatment, which we had previously identified in our HCS campaign to induce condensation with well-defined structure-activity relationships (SAR). Using htSMT, we observed robust changes in N protein diffusion as early as 3 h post GSK3 inhibition. Proximity-based N biosensors also reliably reported on condensation, enabling the rapid assaying of large compound libraries with a readout independent of imaging. Both htSMT and proximity-based biosensors performed well in a screening format and provided information on CMOD activity that was complementary to HCS. We expect that this expanded toolkit for interrogating phase-separated proteins will accelerate the identification of CMODs for important therapeutic targets.</div></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"31 ","pages":"Article 100220"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082458","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":"NF-kB oscillation profiles decode response to anti-EGFR monoclonal antibodies","authors":"Donatella Romaniello ,&nbsp;Lorenzo Dall'Olio ,&nbsp;Martina Mazzeschi ,&nbsp;Anna Francia ,&nbsp;Federica Pagano ,&nbsp;Valerio Gelfo ,&nbsp;Gabriele D'Uva ,&nbsp;Enrico Giampieri ,&nbsp;Mattia Lauriola","doi":"10.1016/j.slasd.2025.100219","DOIUrl":"10.1016/j.slasd.2025.100219","url":null,"abstract":"<div><div>A direct connection between an inflammatory environment and cancer has been extensively proven over the years. We previously reported that the presence of interleukin 1 (IL-1) is responsible for the lack of response to monoclonal antibody targeting epidermal growth factor receptor (EGFR) in colorectal cancer (CRC).</div><div>Considering the driver role of NF-kB in controlling the expression of IL-1, herein, we investigate the dynamics of the oscillatory profile of the NF-kB response to monoclonal antibody, on the background of an inflammatory environment. NF-kB is a typical transcription factor that displays intrinsic oscillatory behavior, whose biological relevance in term for example of decoding response to monoclonal antibodies, remains unclear.</div><div>Using live cell luciferase techniques, we recorded NF-kB activity over time in response to cetuximab (CTX) alone or in combination with IL-1 cytokines. Our results revealed an additive effect of these two agents on NF-kB activation, which was specific to CTX responsive cells. In contrast, CTX resistant cells did not display a significant change in the NF-kB profile under the IL-1 plus CTX combination. These results suggest an immediate interactive crosstalk between IL-1 and EGFR in the activation of NF-kB signaling pathway, which may lay the basis for the development of drug tolerant persister cells (DTP), leading to CTX resistance.</div></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"31 ","pages":"Article 100219"},"PeriodicalIF":2.7,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076444","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}