ChemBioChem最新文献

{"title":"Comparative Evaluation of Two Fluorescent Covalent Probes for Nucleophilic Amino Acid Sensing","authors":"Jacopo Venditti,&nbsp;Marco Paolino,&nbsp;Germano Giuliani,&nbsp;Gabriele Manenti,&nbsp;Alessandro Donati,&nbsp;Claudia Bonechi,&nbsp;Beatrice De Bonis,&nbsp;Giusy Tassone,&nbsp;Samuele Maramai,&nbsp;Chiara Botta,&nbsp;Lluís Blancafort,&nbsp;Andrea Cappelli","doi":"10.1002/cbic.70547","DOIUrl":"https://doi.org/10.1002/cbic.70547","url":null,"abstract":"<p>New covalent probes <b>2</b> and <b>3</b> were designed by linking the 9,9-dimethyl-2-phenyl-9<i>H</i>-fluorene fluorophore to two electrophilic groups showing potentially different reactivities toward nucleophilic amino acid residues. The reactivities of probes <b>2</b> and <b>3</b> were characterized using dimethyl sulfoxide as the solvent in place of buffered aqueous solutions owing to the high lipophilicity of the probes that could produce aggregation phenomena. The two covalent probes revealed different reactivity profiles. In fact, the Morita–Baylis–Hillman adduct (MBHA) derivative <b>2</b> showed a relatively low selectivity in reacting with <i>N</i>α-acetyl-<i>L</i>-lysine methyl ester, <i>N</i>α-acetyl-<i>L</i>-histidine methyl ester, and <i>N</i>-acetyl-<i>L</i>-cysteine methyl ester, whereas the acrylanilide derivative <b>3</b> showed a peculiar chemo-selectivity toward <i>N</i>-acetyl-<i>L</i>-cysteine methyl ester. Photophysical characterization studies revealed that MBHA derivative <b>2</b> behaved as a fluorogenic probe displaying a certain sensitivity to the amino acid covalently linked. On the other hand, acrylanilide derivative <b>3</b> was found to increase its emission features after reacting with <i>N</i>-acetyl-<i>L</i>-cysteine methyl. Owing to its promising features, the capability of MBHA probe <b>2</b> of labeling proteins was finally tested with recombinant human serum albumin (HSA) by employing different techniques such as NMR spectroscopy, circular dichroism spectroscopy, SDS-PAGE, and computational docking simulations to obtain information about the interaction of probe <b>2</b> with HSA.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 19","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149072516","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":"Realization of a Manufacturing-Scale Synthesis of Niraparib Using an Evolved Transaminase","authors":"Rhiannon E. H. Jones,&nbsp;Sandy Chang,&nbsp;Neal Desai,&nbsp;Ashley Hughes,&nbsp;Lydia Jordan,&nbsp;Justin M. Kaplan,&nbsp;Jonathan Latham,&nbsp;Zhi Liu,&nbsp;Calvin Manning,&nbsp;Joel Melby,&nbsp;Catherine Roerden,&nbsp;Qiaogong Su,&nbsp;Robert Whitten,&nbsp;Katherine Honicker","doi":"10.1002/cbic.70508","DOIUrl":"10.1002/cbic.70508","url":null,"abstract":"<p>The scale-up of biocatalytic processes for pharmaceutical manufacture still presents key challenges. Here, we describe the development of a transaminase used in the manufacturing-scale synthesis of niraparib, a small molecule poly(ADP-ribose) polymerase (PARP) inhibitor. Realization of a commercial process began with the engineering of an improved enzyme variant over nine rounds of directed evolution. In tandem, process development was carried out, intensifying the substrate concentration and applying key insights on transaminase performance. The optimized process and enzyme were demonstrated over multiple batches at plant scale, and analysis of the CO₂ footprint per kilogram showed that the optimized process using the evolved enzyme had an 80% reduction in emission impact compared to pre-evolution, highlighting the valuable improvements made through this multidisciplinary effort.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 18","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149068937","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":"A 4′-Thioribouridine Modification Mimics 2′-O-Methoxyethyl in ASO-Like 20-Mers Targeting PTEN Knockdown","authors":"Joanna E. Parkes,&nbsp;Caecilie M. M. Benckendorff,&nbsp;Anna L. Malinowska,&nbsp;Jacob Roberts,&nbsp;Harley L. Huynh,&nbsp;Sritama Bose,&nbsp;Loïc M. Cochard,&nbsp;Aisling Ní Cheallaigh,&nbsp;Sarah L. Lovelock,&nbsp;Peter L. Oliver,&nbsp;Gavin J. Miller","doi":"10.1002/cbic.70533","DOIUrl":"10.1002/cbic.70533","url":null,"abstract":"<p>Gapmer antisense oligonucleotides (ASOs) represent a clinically validated therapeutic platform, with a 2′-<i>O</i>-methoxyethyl modification commonplace within the flanking regions. An alternative sugar modification, incorporation of 4′-thioribose, has demonstrated enhanced nuclease resistance in siRNAs and aptamers, but incorporation of this motif into gapmer architectures remains underexplored. Herein, we report the synthesis of a 4′-thiouridine phosphoramidite building block and its incorporation into gapmer ASOs targeting <i>PTEN</i>. Evaluation of sequences containing 4′-thiouridine in the flanking regions (compared with 2′-<i>O</i>-methoxyethyl) and varying phosphorothioate linkage composition demonstrates that the modified gapmers maintain equivalent knockdown efficacy under transfection and gymnotic delivery. These findings indicate 4′-thioribose as an alternative sugar modification for wider exploration within gapmer ASOs.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 18","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13616438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149068997","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 Highly Cytotoxic Antisense Oligonucleotides Targeting Essential Genes in Human Ovarian and Lung Cancer Cells","authors":"Zain Hussein,&nbsp;Elena V. Misnik,&nbsp;Meera Alaji,&nbsp;Christina Patra,&nbsp;Rami Mhanna,&nbsp;Abadeer Habib,&nbsp;Ahmed A. Eldeeb,&nbsp;Dmitry M. Kolpashchikov","doi":"10.1002/cbic.70544","DOIUrl":"10.1002/cbic.70544","url":null,"abstract":"<p>Therapeutic nucleic acid (TNA)-based gene silencing strategies, such as antisense oligonucleotides (ASOs), have been explored for cancer treatment. However, no ASO-based anticancer drugs are currently available, largely because of limited therapeutic efficacy. Conventional ASO-based cancer therapies typically target oncogenes or cancer-associated genes because constitutively active ASOs may also damage normal tissues. We hypothesized that this limitation can be overcome by conditionally activating ASOs only in response to cancer-specific biomarkers. In this paradigm, therapeutic efficacy is determined by the potential of the released ASO rather than by the cancer specificity of its target, allowing any gene essential for cell survival to serve as a target. Our aim was to identify the most cytotoxic ASO sequences for cancer cells. We designed 37 ASOs targeting 13 candidate genes and evaluated them in human ovarian adenocarcinoma (SKOV3) and lung adenocarcinoma (A549) cell lines. An ASO targeting <i>DARS1</i> exhibited the strongest activity, inducing apoptotic cell death in both cell types. Additional ASOs targeting <i>DYNC1I2</i> and <i>EIF2S3</i> were identified as effective candidates in SKOV3 and A549 cells, respectively. Importantly, the selected ASOs exhibited low toxicity toward the tested noncancerous cell line. These findings identify <i>DARS1</i>, <i>DYNC1I2</i>, and <i>EIF2S3</i> as promising targets for marker-dependent ASO-based cancer therapy.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 18","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149068934","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":"Nanorulers for Super-Resolution Microscopy","authors":"Gerti Beliu,&nbsp;Alan M. Szalai,&nbsp;Guillermo Acuna,&nbsp;Alexey Chizhik,&nbsp;José Ignacio Gallea,&nbsp;Jörg Enderlein","doi":"10.1002/cbic.70529","DOIUrl":"10.1002/cbic.70529","url":null,"abstract":"<p>Super-resolution fluorescence microscopy has advanced into a regime where molecular-scale organization can be resolved with nanometer precision. In this context, the accurate interpretation of imaging data increasingly depends on well-defined calibration standards. Nanorulers have emerged as essential tools to validate resolution, quantify labeling performance, and benchmark analytical methods. Current approaches include DNA-based, protein-based, and virus-based nanorulers, each offering distinct advantages in terms of programmability, structural definition, and biological relevance. This minireview provides an overview of these complementary strategies, with a particular focus on recent developments in protein-based nanorulers enabled by advances in protein engineering and site-specific labeling. Together, these approaches contribute to establishing reliable calibration frameworks for quantitative molecular bioimaging.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 18","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13616436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149068977","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":"Cobamide Scavenging and Import via a Multiprotein Extracellular Relay in Bacteroides thetaiotaomicron","authors":"Alexander Drake,&nbsp;Romila Mascarenhas","doi":"10.1002/cbic.70539","DOIUrl":"10.1002/cbic.70539","url":null,"abstract":"<p>Cobamides, the structurally diverse family of cobalt-containing cofactors, are required by most bacteria yet synthesized by a subset of prokaryotes, making cobamide acquisition a major determinant of microbial fitness. <i>Bacteroides</i> <i>thetaiotaomicron</i>, an abundant commensal of the human gut, is auxotrophic for cobamides and relies on environmental scavenging to support its metabolism. To meet this demand in a competitive and diverse cobamide environment of the gut, <i>B</i><i>.</i> <i>thetaiotaomicron</i> employs a B₁₂-uptake (Btu) system that extends far beyond the well-studied <i>Escherichia</i> <i>coli</i> Btu system. Rather than relying on a single outer membrane (OM) transporter, <i>B</i><i>.</i> <i>thetaiotaomicron</i> deploys a multiprotein extracellular relay in which surface-exposed BtuJ lipoproteins capture cobamides extracellularly and transfer them to BtuH and BtuG lipoproteins at the OM. BtuG forms a stable complex with the TonB-dependent transporter BtuB, coupling cobamide capture to periplasmic translocation, and the inner membrane BtuFCD complex completes cytoplasmic delivery. BtuJ-enriched OM vesicles further extend cobamide capture into the extracellular environment, and cobamide-dependent riboswitches couple Btu protein expression to the availability and chemical identity of intracellular cobamides. We review the structural and mechanistic evidence for each stage of this relay, propose a model for cobamide import, and identify outstanding questions that will illuminate cobamide scavenging across gut bacteria.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 18","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13616437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069008","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":"Synthesis and In Vivo Incorporation of 4-Difluoromethyl-L-Phenylalanine Into Proteins","authors":"Daniel S. Honeycutt,&nbsp;Jason M. Mrosla,&nbsp;Sarah A. Sexton,&nbsp;Giovanni E. Cavalli,&nbsp;Emmerson G. Bartels,&nbsp;Brian Pallares,&nbsp;William K. McCarthy,&nbsp;Ruojun Wu,&nbsp;Fang Wang,&nbsp;Jacob M. Goldberg","doi":"10.1002/cbic.70541","DOIUrl":"10.1002/cbic.70541","url":null,"abstract":"<p>The difluoromethyl group exhibits unique chemical and nuclear magnetic resonance (NMR) spectroscopic properties. Here, the synthesis and characterization of 4-difluoromethyl-L-phenylalanine is reported. Methods have been developed to incorporate this versatile unnatural amino acid into full-length green fluorescent protein and carbonic anhydrase, using an orthogonal transfer RNA (tRNA)/synthetase pair with standard genetic code expansion techniques. Taking advantage of the characteristic ¹⁹F NMR behavior of the difluoromethyl group, the potential application of the difluoromethyl group as a probe in protein NMR studies was explored.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 18","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13599698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023326","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":"Photoreactive Pantetheinyl Mimics Reveal Design Limitations for Crypto-Acyl Carrier Proteins","authors":"Anna-Kay R. West,&nbsp;Tawakalitu A. Afolabi-Balogun,&nbsp;Christian C. Martin,&nbsp;Lizbeth Cambron,&nbsp;Mujeeb A. Wakeel,&nbsp;Joshua A. Baccile,&nbsp;Constance B. Bailey","doi":"10.1002/cbic.202500952","DOIUrl":"10.1002/cbic.202500952","url":null,"abstract":"<p>Polyketide synthases (PKS), fatty acid synthases (FAS), and non-ribosomal peptide synthetases (NRPS) span a variety of protein architectures and catalytic modalities. Common to all these biosynthetic modalities is the centrality of a phosphopantetheinylated carrier protein, which shuttles substrate either inter- or intramolecularly between discrete domains that catalyze enzymatic transformations within the assembly line, resulting in these biosynthetic classes being termed “thiotemplated.” In all thiotemplated biosynthetic assembly lines, transient protein–protein interactions mediated by the carrier protein are essential for chain extension and catalysis. In recent years, synthetic analogs of phosphopantetheine (Ppant), known as “crypto-ACPs,” have become powerful tools for probing certain protein–protein interactions in thiotemplated systems. These crypto-ACP probes are usually created through a chemoenzymatic process. Most existing crypto-ACP probes are designed around mechanism-based approaches, which are aimed at capturing specific protein interactions within these pathways. To develop a more versatile probe capable of capturing a broader range of transient protein–protein interactions, we designed and synthesized a series of diazirine-based phosphopantetheinylated mimics suitable for photocrosslinking using a commonly employed beta-alanine linkage for synthetic tractability. We then evaluated the efficiency of loading <i>Escherichia coli</i> AcpP with these diazirine probes as well as crosslinking with <i>Escherichia coli</i> FabD. Examination of both loading and crosslinking revealed that deviations from the structure of the natural substrate (4′-phosphopantetheine) of the phosphopantetheinyl (Ppant) arm of the carrier protein resulted in inefficient loading, leading to poor or no crosslinking. These results highlight the limitations of synthetic and structural modularity in <i>crypto</i>-ACP design and will assist future strategies for interrogating protein–protein interactions of this nature.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 18","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13599679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023283","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":"Artificial Intelligence and Virtual Screening to Identify Small Molecules Inhibiting Transglutaminase 2 for Investigation and Treatment of Breast Cancer","authors":"Carlo M. Bergamini,&nbsp;Niel M. Henriksen,&nbsp;Brianna Ryan,&nbsp;Taylor A. Prince,&nbsp;Anna Terrazzan,&nbsp;Pietro Ancona,&nbsp;Cristina Zuccato,&nbsp;Gianluca Aguiari,&nbsp;Valentina Rosta,&nbsp;Jeffrey W. Keillor,&nbsp;Alessandro Trentini,&nbsp;Nicoletta Bianchi","doi":"10.1002/cbic.70542","DOIUrl":"10.1002/cbic.70542","url":null,"abstract":"<p>Artificial intelligence-assisted virtual screening enables identification of chemically diverse bioactive small molecules. We targeted transglutaminase 2 (TG2), a multifunctional protein associated with mesenchymal-like features in breast cancer. Approximately 10 million compounds were screened against the catalytic site of open TG2 using the AtomNet structure-based deep-learning model. The top 30,000 candidates underwent physicochemical and structural filtering, diversity clustering, and manual selection, yielding 84 compounds for experimental evaluation. Fourteen induced apoptosis in MCF-7, eight retained activity in MDA-MB-436, and three in MDA-MB-231 cells, also reducing transamidase activity in cellular lysates. Chemical-space and fingerprint analyses placed <b>C10</b>, <b>C12,</b> and <b>G11</b> outside the principal clusters of known active TG2 inhibitors, identifying structurally differentiated, nonpeptidic scaffolds. Docking into open and intermediate TG2 conformations consistently ranked <b>G11</b> as the most favorable candidate, with predicted binding near the catalytic core. In a 5-(biotinamido)pentylamine (5-BAP-based assay, <b>G11</b> inhibited purified recombinant human TG2 with an IC₅₀ of 7.64 ± 2.87 μM, while an independent dimethyl casein–dansyl cadaverine assay confirmed concentration-dependent inhibition and yielded an estimated <i>K_i</i> of 44 ± 11 μM, assuming competitive inhibition with respect to the substrate. Finally, <b>G11</b> did not significantly affect the viability of HEK293 cells, which express negligible or very low levels of TG2.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 18","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.70542","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023339","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":"Site-Specific Features Guiding Effective Reversible Photocontrol of Tryptophan Synthase With the Unnatural Amino Acid AzoF","authors":"Caroline Hiefinger,&nbsp;Sabine Laberer,&nbsp;Lukas Drexler,&nbsp;Cristina Duran,&nbsp;Michael Bartl,&nbsp;Sílvia Osuna,&nbsp;Andrea Hupfeld","doi":"10.1002/cbic.70546","DOIUrl":"10.1002/cbic.70546","url":null,"abstract":"<p>This study delivers initial guidelines for the selection of effective incorporation positions for the azobenzene-based unnatural amino acid AzoF to facilitate the successful engineering of light-sensitive enzymes, dubbed photoxenases. Although photoxenases gain interest for the photocontrol of enzymatic activity across various fields their design has so far remained challenging. To ease particularly the selection of AzoF incorporation sites, we have systematically evaluated a total of 85 positions that differ in their biochemical and biophysical features in the bi-enzyme model system tryptophan synthase. Medium-throughput production of AzoF-containing variants, activity-based screening and evaluation of photocontrol, and subsequent validation of the screening results allowed us to identify three site-specific features that promote photocontrol with a success rate of up to 83% when combined. These features include positions in domains with catalytically important conformational transitions, positions determined via molecular dynamics based shortest path map analysis, and positions that originally contain a hydrophilic side chain. Ultimately, our results underscore the complexity of predicting suitable incorporation sites but simultaneously provide a fundamental framework for the improved rational design of future photoxenases with AzoF.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 18","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13599677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023355","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}