Yesseinia I Anglero-Rodriguez, Florian A Lempp, Megha Subramanian, James McIninch, Mark K Schlegel, Dana Bohan, Emily Wong, Christopher R Brown, Donald J Foster, Adam B Castoreno, Tuyen Nguyen, Dara Cuffe, Martin Montiel-Ruiz, Hannah Kaiser, Anna Sahakyan, Roberto Spreafico, Svetlana Shulga Morskaya, Joseph D Barry, Daniel Berman, Ligang Zhang, Stephanie Lefebvre, Anne Kasper, Timothy Racie, Diann Weddle, Melissa Mobley, Kelly Wassarman, Anna Bisbe, Ivan Zlatev, Arlin Rogers, Lubomir Nechev, Joseph Dybowski, Saeho Chong, Jayaprakash Nair, Amy Simon, Kevin Sloan, Seungmin Hwang, Herbert W Virgin, Kevin Fitzgerald, Martin A Maier, Gregory Hinkle, Christy M Hebner, Akin Akinc, Vasant Jadhav
{"title":"High resistance barrier and prophylactic protection in preclinical models of SARS-CoV-2 with two siRNA combination","authors":"Yesseinia I Anglero-Rodriguez, Florian A Lempp, Megha Subramanian, James McIninch, Mark K Schlegel, Dana Bohan, Emily Wong, Christopher R Brown, Donald J Foster, Adam B Castoreno, Tuyen Nguyen, Dara Cuffe, Martin Montiel-Ruiz, Hannah Kaiser, Anna Sahakyan, Roberto Spreafico, Svetlana Shulga Morskaya, Joseph D Barry, Daniel Berman, Ligang Zhang, Stephanie Lefebvre, Anne Kasper, Timothy Racie, Diann Weddle, Melissa Mobley, Kelly Wassarman, Anna Bisbe, Ivan Zlatev, Arlin Rogers, Lubomir Nechev, Joseph Dybowski, Saeho Chong, Jayaprakash Nair, Amy Simon, Kevin Sloan, Seungmin Hwang, Herbert W Virgin, Kevin Fitzgerald, Martin A Maier, Gregory Hinkle, Christy M Hebner, Akin Akinc, Vasant Jadhav","doi":"10.1093/nar/gkae1195","DOIUrl":"https://doi.org/10.1093/nar/gkae1195","url":null,"abstract":"RNA interference is a natural antiviral mechanism that could be harnessed to combat SARS-CoV-2 infection by targeting and destroying the viral RNA. We identified potent lipophilic small interfering RNA (siRNA) conjugates targeting highly conserved regions of SARS-CoV-2 outside of the spike-encoding region capable of achieving ≥3-log viral reduction. Serial passaging studies demonstrated that a two-siRNA combination prevented development of resistance compared to a single siRNA approach. Viral resistance to single siRNA treatment occurred due to emergence of point mutations at critical positions required for siRNA-mediated target binding and cleavage, which led to a loss of siRNA efficacy. With a two-siRNA combination, emergence of mutations within the siRNA binding site was abolished. When delivered intranasally, two-siRNA combination protected Syrian hamsters from weight loss and lung pathology by viral infection upon prophylactic administration but not following onset of infection. Together, the data support potential utility of RNAi as a prophylactic approach with high resistance barrier to counteract SARS-CoV-2 emergent variants and complement vaccination. Most importantly, given that the siRNAs can be rapidly developed from a new pathogen sequence, this strategy has implications as a new type of preventive medicine that may protect against future coronavirus pandemics.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"12 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Suzanne W van der Veen, Jelmer J Dijkstra, Ellen C L Willemsen, René Houtman, Alexandra Milona, Nikolas Marchet, Maureen Spit, Danielle Hollman, Fried J T Zwartkruis, Michiel Vermeulen, Jose M Ramos Pittol, Saskia W C van Mil
{"title":"The farnesoid X receptor activates transcription independently of RXR at non-canonical response elements","authors":"Suzanne W van der Veen, Jelmer J Dijkstra, Ellen C L Willemsen, René Houtman, Alexandra Milona, Nikolas Marchet, Maureen Spit, Danielle Hollman, Fried J T Zwartkruis, Michiel Vermeulen, Jose M Ramos Pittol, Saskia W C van Mil","doi":"10.1093/nar/gkae1214","DOIUrl":"https://doi.org/10.1093/nar/gkae1214","url":null,"abstract":"The farnesoid X receptor (FXR) is a nuclear receptor (NR) known to obligately heterodimerize with the retinoid X receptor (RXR). FXR is expressed as four isoforms (α1–α4) that drive transcription from IR-1 (inverted repeat-1) response elements (REs). Recently, we found that FXR isoforms α2/α4 also activate transcription from non-canonical ER-2 (everted repeat-2) REs, mediating most metabolic effects of general FXR activation. Here, we explored molecular determinants of regulation by FXRα2 from ER-2 REs through quantitative interaction proteomics, site-directed mutagenesis and transcriptomics. We discovered FXRα2 binds to and activates ER-2 elements in vitro and in reporter assays independently of RXR. Genome-wide binding analysis in mouse liver revealed higher ER-2 motif enrichment in FXR sites lacking RXR. Abrogation of FXRα2:RXR heterodimerization abolished IR-1, but preserved ER-2 transactivation. Transcriptome-wide, RXR overexpression inhibited 25% of FXRα2 targets in HepG2. These genes were specifically activated by the heterodimerization-deficient mutant FXRα2L434R, enriched for ER-2 motifs at their promoters, and involved in lipid metabolism and ammonia detoxification. In conclusion, RXR acts as a molecular switch, inhibiting FXRα2 activation from ER-2 while enhancing it from canonical IR-1 REs. Our results showcase FXR as the first NR with isoform-specific RXR-independent REs, highlighting a new layer of regulation and complexity for RXR-heterodimerizing NRs.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"2 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vinoth Sundar Rajan, Sune Levin, Micah J McCauley, Mark C Williams, Ioulia Rouzina, L Marcus Wilhelmsson, Fredrik Westerlund
{"title":"Force-induced melting and S-DNA pathways for DNA overstretching exhibit distinct kinetics","authors":"Vinoth Sundar Rajan, Sune Levin, Micah J McCauley, Mark C Williams, Ioulia Rouzina, L Marcus Wilhelmsson, Fredrik Westerlund","doi":"10.1093/nar/gkae1183","DOIUrl":"https://doi.org/10.1093/nar/gkae1183","url":null,"abstract":"It is widely appreciated that double stranded DNA (dsDNA) is subjected to strong and dynamic mechanical forces in cells. Under increasing tension B-DNA, the most stable double-stranded (ds) form of DNA, undergoes cooperative elongation into a mixture of S-DNA and single stranded DNA (ssDNA). Despite significant effort, the structure, energetics, kinetics and the biological role of S-DNA remains obscure. We here stretch 60 base pair (bp) dsDNA oligonucleotides with a variable number of tricyclic cytosine, tC, modifications using optical tweezers. We observe multiple fast cooperative and reversible two-state transitions between B-DNA and S-DNA. Notably, tC modifications increase the transition force, while reducing the transition extension and free energy due to progressively increasing fraying of the dsDNA ends. We quantify the average number of bps undergoing the B-to-S transition, as well as the free energies and rates. This allows us to reconstruct the B-to-S free energy profiles in absence of force. We conclude that S-DNA is an entirely force-induced state, and that the B-to-S transition is much faster than internal dsDNA melting. We hypothesize that S-DNA may have a role as a transient intermediate in, for example, molecular motor-induced local dsDNA strand separation.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"1 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fei Ye, Xiao Chen, Yuan Li, Aili Ju, Yalan Sheng, Lili Duan, Jiachen Zhang, Zhe Zhang, Khaled A S Al-Rasheid, Naomi A Stover, Shan Gao
{"title":"Comprehensive genome annotation of the model ciliate Tetrahymena thermophila by in-depth epigenetic and transcriptomic profiling","authors":"Fei Ye, Xiao Chen, Yuan Li, Aili Ju, Yalan Sheng, Lili Duan, Jiachen Zhang, Zhe Zhang, Khaled A S Al-Rasheid, Naomi A Stover, Shan Gao","doi":"10.1093/nar/gkae1177","DOIUrl":"https://doi.org/10.1093/nar/gkae1177","url":null,"abstract":"The ciliate Tetrahymena thermophila is a well-established unicellular model eukaryote, contributing significantly to foundational biological discoveries. Despite its acknowledged importance, current studies on Tetrahymena biology face challenges due to gene annotation inaccuracy, particularly the notable absence of untranslated regions (UTRs). To comprehensively annotate the Tetrahymena macronuclear genome, we collected extensive transcriptomic data spanning various cell stages. To ascertain transcript orientation and transcription start/end sites, we incorporated data on epigenetic marks displaying enrichment towards the 5′ end of gene bodies, including H3 lysine 4 tri-methylation (H3K4me3), histone variant H2A.Z, nucleosome positioning and N6-methyldeoxyadenine (6mA). Cap-seq data was subsequently applied to validate the accuracy of identified transcription start sites. Additionally, we integrated Nanopore direct RNA sequencing (DRS), strand-specific RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) data. Using a newly developed bioinformatic pipeline, coupled with manual curation and experimental validation, our work yielded substantial improvements to the current gene models, including the addition of 2,481 new genes, updates to 23,936 existing genes, and the incorporation of 8,339 alternatively spliced isoforms. Furthermore, novel UTR information was annotated for 26,687 high-confidence genes. Intriguingly, 20% of protein-coding genes were identified to have natural antisense transcripts characterized by high diversity in alternative splicing, thus offering insights into understanding transcriptional regulation. Our work will enhance the utility of Tetrahymena as a robust genetic toolkit for advancing biological research, and provides a promising framework for genome annotation in other eukaryotes.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"38 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Venkatesh V Ranjan, Gage O Leighton, Chenbo Yan, Maria Arango, Janna Lustig, Rosario I Corona, Jun-Tao Guo, Yuri E Nesmelov, Zoltán Ivics, Irina V Nesmelova
{"title":"DNA binding and transposition activity of the Sleeping Beauty transposase: role of structural stability of the primary DNA-binding domain","authors":"Venkatesh V Ranjan, Gage O Leighton, Chenbo Yan, Maria Arango, Janna Lustig, Rosario I Corona, Jun-Tao Guo, Yuri E Nesmelov, Zoltán Ivics, Irina V Nesmelova","doi":"10.1093/nar/gkae1188","DOIUrl":"https://doi.org/10.1093/nar/gkae1188","url":null,"abstract":"DNA transposons have emerged as promising tools in both gene therapy and functional genomics. In particular, the Sleeping Beauty (SB) DNA transposon has advanced into clinical trials due to its ability to stably integrate DNA sequences of choice into eukaryotic genomes. The efficiency of the DNA transposon system depends on the interaction between the transposon DNA and the transposase enzyme that facilitates gene transfer. In this study, we assess the DNA-binding capabilities of variants of the SB transposase and demonstrate that the structural stability of the primary DNA-recognition subdomain, PAI, affects SB DNA-binding affinity and transposition activity. This fundamental understanding of the structure–function relationship of the SB transposase will assist the design of improved transposases for gene therapy applications.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"29 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anatolii Arseniev, Mikhail Panfilov, Georgii Pobegalov, Alina Potyseva, Polina Pavlinova, Maria Yakunina, Jookyung Lee, Sergei Borukhov, Konstantin Severinov, Mikhail Khodorkovskii
{"title":"Single-molecule studies reveal the off-pathway early paused state intermediates as a target of streptolydigin inhibition of RNA polymerase and its dramatic enhancement by Gre factors","authors":"Anatolii Arseniev, Mikhail Panfilov, Georgii Pobegalov, Alina Potyseva, Polina Pavlinova, Maria Yakunina, Jookyung Lee, Sergei Borukhov, Konstantin Severinov, Mikhail Khodorkovskii","doi":"10.1093/nar/gkae1135","DOIUrl":"https://doi.org/10.1093/nar/gkae1135","url":null,"abstract":"Antibiotic streptolydigin (Stl) inhibits bacterial transcription by blocking the trigger loop folding in the active center of RNA polymerase (RNAP), which is essential for catalysis. We use acoustic force spectroscopy to characterize the dynamics of transcription elongation in ternary elongation complexes (ECs) of RNAP in the presence of Stl at a single-molecule level. We found that Stl induces long-lived stochastic pauses while the instantaneous velocity of transcription between the pauses is unaffected. Stl enhances the short-lived pauses associated with an off-pathway early paused state intermediates of the RNAP nucleotide addition cycle. Unexpectedly, we found that transcript cleavage factors GreA and GreB, which were thought to be Stl competitors, do not alleviate the Stl-induced pausing; instead, they synergistically increase transcription inhibition by Stl. This is the first known instance of a transcriptional factor enhancing antibiotic activity. We propose a structural model of the EC-Gre-Stl complex that explains the observed Stl activities and provides insight into possible cooperative action of secondary channel factors and other antibiotics binding at the Stl pocket. These results offer a new strategy for high-throughput screening for prospective antibacterial agents.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"1 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Editor's Note 'Transcription factor binding sites in the pol geneintragenic regulatory region of HIV-1 are important for virus infectivity'.","authors":"","doi":"10.1093/nar/gkae1233","DOIUrl":"https://doi.org/10.1093/nar/gkae1233","url":null,"abstract":"","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kristin V Chesnutt, Gizem Yayli, Christine Toelzer, Mylène Damilot, Khan Cox, Gunjan Gautam, Imre Berger, László Tora, Michael G Poirier
{"title":"ATAC and SAGA histone acetyltransferase modules facilitate transcription factor binding to nucleosomes independent of their acetylation activity","authors":"Kristin V Chesnutt, Gizem Yayli, Christine Toelzer, Mylène Damilot, Khan Cox, Gunjan Gautam, Imre Berger, László Tora, Michael G Poirier","doi":"10.1093/nar/gkae1120","DOIUrl":"https://doi.org/10.1093/nar/gkae1120","url":null,"abstract":"Transcription initiation involves the coordination of multiple events, starting with activators binding specific DNA target sequences, which recruit transcription coactivators to open chromatin and enable binding of general transcription factors and RNA polymerase II to promoters. Two key human transcriptional coactivator complexes, ATAC (ADA-two-A-containing) and SAGA (Spt-Ada-Gcn5 acetyltransferase), containing histone acetyltransferase (HAT) activity, target genomic loci to increase promoter accessibility. To better understand the function of ATAC and SAGA HAT complexes, we used in vitro biochemical and biophysical assays to characterize human ATAC and SAGA HAT module interactions with nucleosomes and how a transcription factor (TF) coordinates these interactions. We found that ATAC and SAGA HAT modules bind nucleosomes with high affinity, independent of their HAT activity and the tested TF. ATAC and SAGA HAT modules directly interact with the VP16 activator domain and this domain enhances acetylation activity of both HAT modules. Surprisingly, ATAC and SAGA HAT modules increase TF binding to its DNA target site within the nucleosome by an order of magnitude independent of histone acetylation. Altogether, our results reveal synergistic coordination between HAT modules and a TF, where ATAC and SAGA HAT modules (i) acetylate histones to open chromatin and (ii) facilitate TF targeting within nucleosomes independently of their acetylation activity.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"14 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Downregulation of MLF1 safeguards cardiomyocytes against senescence-associated chromatin opening","authors":"Jian Lv, Qin Chen, Junmei Wang, Ningning Guo, Yu Fang, Qiuxiao Guo, Jiajie Li, Xiao Ma, Hongchao Zhan, Weihao Chen, Li Wang, Qingqing Yan, Jingjing Tong, Zhihua Wang","doi":"10.1093/nar/gkae1176","DOIUrl":"https://doi.org/10.1093/nar/gkae1176","url":null,"abstract":"Aging-associated cardiac hypertrophy (AACH) increases susceptibility to heart failure in the elderly. Chromatin remodeling contributes to the gene reprogramming in AACH; however, the intrinsic regulations remain elusive. We performed a transcriptome analysis for AACH in comparison with pressure-overload-induced pathological cardiac hypertrophy in mice and identified myeloid leukemia factor 1 (MLF1) as an aging-sensitive factor whose expression was reduced during aging but could be reversed by anti-aging administrations. In human AC16 cardiomyocytes, silencing MLF1 suppressed H2O2-induced cell senescence while the phenotype was exacerbated by MLF1 overexpression. RNA-seq analysis revealed that MLF1 functioned as a transcription activator, regulating genomic-clustered genes that mainly involved in inflammation and development. ATAC-seq analysis showed a prominent reduction in chromatin accessibility at the promoter regions of senescence effectors, like IL1B and p21, after MLF1 knockdown. Despite a potential interaction of MLF1 with the histone methyltransferase PRC2, its inhibition failed to reverse the impact of MLF1 knockdown. Instead, MLF1-mediated regulation was blunted by inhibiting the acetyltransferase EP300. CUT&Tag analysis showed that MLF1 bound to target promoters and recruited EP300 to promote H3K27ac deposition. Collectively, we identify MLF1 as a pro-aging epigenetic orchestrator that recruits EP300 to facilitate opening of the condensed chromatin encompassing senescence effectors.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"60 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marco T Radukic, Dinh To Le, Timo Krassuski, Philipp Borchert, David R F Leach, Kristian M Müller
{"title":"Degradation and stable maintenance of adeno-associated virus inverted terminal repeats in E. coli","authors":"Marco T Radukic, Dinh To Le, Timo Krassuski, Philipp Borchert, David R F Leach, Kristian M Müller","doi":"10.1093/nar/gkae1170","DOIUrl":"https://doi.org/10.1093/nar/gkae1170","url":null,"abstract":"Current plasmid propagation in E. coli compromises large inverted repeats, such as inverted terminal repeats (ITRs) of adeno-associated virus (AAV). Direct long-read sequencing analyses upon varying strains and culture conditions revealed ITR instability caused by a slipped misalignment mechanism, although other mechanism probably contribute. ITRs stabilized in absence of SbcC, which is part of the SbcCD nuclease complex, a human Mre11–Rad50 homolog, or at elevated growth temperatures (e.g. 42°C), with a combination being optimal. Resulting full ITR transgene plasmids improved rAAV yield and purity in HEK-293 productions. The findings advance plasmid biology, cloneable sequences and therapeutic AAV manufacturing.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"19 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
