ACS Chemical Biology最新文献

{"title":"Comprehensive and Facile Strategy for Enhanced Visualization of Sialylated RNA via Dual Bioorthogonal Labeling","authors":"Jingwen Ge,&nbsp;Jixuan Han,&nbsp;Xiaocui Fang,&nbsp;Chen Wang* and Yanlian Yang*,&nbsp;","doi":"10.1021/acschembio.5c00133","DOIUrl":"10.1021/acschembio.5c00133","url":null,"abstract":"<p >Metabolic oligosaccharide engineering advancements in 2021 facilitated the discovery of glycoRNA, a glycan-modified RNA found on cell membranes, exhibiting sialic acid-terminated glycosylation across various cell types and mammals. However, the current imaging process is complex, cumbersome, and restricted to the recognition of specific sequences only. To overcome this limitation, we developed an enhanced visualization strategy for sialylated RNA, employing a dual bioorthogonal approach that integrates metabolic labeling of sialic acid (Sia) and RNA with orthogonal reactions. This method facilitates the recognition of total sialylated RNA through the use of tunable Sia and RNA probes, which can be regulated to initiate proximity-induced hybridization chain reaction amplification, effectively enhancing the fluorescence signal without the requirement for supplementary proteases. Our strategy offers high versatility, simplifies visualization steps, and broadens the recognition scope. It has been successfully employed in comparative analyses of RNA glycosylation states across breast, lung, and leukemic cell lines, demonstrating its potential as a robust tool for exploring the roles of sialylated RNA in biological processes and disease progression.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"20 8","pages":"1884–1891"},"PeriodicalIF":3.8,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758718","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":"The Role of MegaMolecule Antibody Structure in Internalization and Signaling","authors":"Daniel J. Sykora,&nbsp;Sraeyes Sridhar,&nbsp;Justin A. Modica,&nbsp;Ragini Yeeravalli,&nbsp;Rahul K. Salaria,&nbsp;Zhaoyi Gu,&nbsp;Maciej S. Lesniak and Milan Mrksich*,&nbsp;","doi":"10.1021/acschembio.5c00421","DOIUrl":"10.1021/acschembio.5c00421","url":null,"abstract":"<p >This manuscript describes the synthesis of 26 megamolecule-based antibody scaffolds that target the receptor tyrosine kinase HER2 (ERBB2). The scaffolds include mono-, bi-, and trivalent structures that present high- or low-affinity Fab or nanobody domains. Cell binding, internalization, and cytotoxicity were compared with those of the parent monoclonal antibody trastuzumab. Increasing scaffold valency from two to three domains only modestly increased binding efficiency and did not increase the internalization rate. Further, inhibition of cell proliferation was not impacted by scaffold valency. Targeting multiple epitopes on HER2 with a biparatopic scaffold significantly increased the internalization rate (approximately 3-fold) over trastuzumab but could either promote or inhibit cell proliferation. This work is significant both for demonstrating how the megamolecule approach can generate large numbers of diverse and structurally defined antibody mimics and revealing the critical influence of structural characteristics of the molecules are to their biological activities.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"20 8","pages":"2014–2027"},"PeriodicalIF":3.8,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740612","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":"Select Azo Compounds Post-translationally Modulate HTRA1 Abundance and Activity Potentially through Interactions at the Trimer Interface","authors":"John D. Hulleman*,&nbsp;Seungje Jeon,&nbsp;Sofia Bali,&nbsp;Sophia M. DiCesare,&nbsp;Ali Abbas,&nbsp;Steffi Daniel,&nbsp;Antonio J. Ortega,&nbsp;Gracen E. Collier,&nbsp;Julian Yang,&nbsp;Archishman Bhattacharyaa,&nbsp;Melissa K. McCoy,&nbsp;Lukasz A. Joachimiak and Bruce A. Posner,&nbsp;","doi":"10.1021/acschembio.4c00818","DOIUrl":"10.1021/acschembio.4c00818","url":null,"abstract":"<p >High-temperature requirement protein A1 (HTRA1) is a secreted serine protease with diverse substrates, including extracellular matrix proteins, proteins involved in amyloid deposition, and growth factors. Accordingly, HTRA1 has been implicated in a variety of neurodegenerative diseases including a leading cause of blindness in the elderly, age-related macular degeneration (AMD). In fact, genomewide association studies have identified that the 10q26 locus that contains <i>HTRA1</i> confers the strongest genetic risk factor for AMD. A recent study has suggested that AMD-associated risk alleles located in the <i>HTRA1</i> gene correlate with a significant age-related defect in HTRA1 synthesis in the retinal pigmented epithelium (RPE) within the eye, possibly accounting for AMD susceptibility. Thus, we sought to identify small molecule enhancers of HTRA1 transcription and/or protein abundance using an unbiased high-throughput screening approach. To accomplish this goal, we used CRISPR/Sp.Cas9 engineering to introduce an 11-amino-acid luminescent peptide tag (HiBiT) onto the C-terminus of HTRA1 in immortalized ARPE-19 cells. Editing was very efficient (∼88%), verified by genomic DNA analysis, short interfering RNA (siRNA), and HiBiT blotting. A total of 1920 compounds from two libraries were screened. An azo compound with reported antiamyloidogenic and cardioprotective activity, Chicago Sky Blue 6B (CSB), was identified as an enhancer of endogenous HTRA1 secretion (2.0 ± 0.3 fold) and intracellular levels (1.7 ± 0.2 fold). These results were counter-screened using HiBiT complement factor H (CFH) edited ARPE-19 cells, verified using HiBiT blotting, and were not due to <i>HTRA1</i> transcriptional changes. Importantly, serine hydrolase activity-based protein profiling (SH-ABPP) demonstrated that CSB does not affect HTRA1’s specific activity. However, interestingly, in follow-up studies, Congo Red, another azo compound structurally similar to CSB, also substantially increased intracellular HTRA1 levels (up to 3.6 ± 0.3 fold) but was found to significantly impair HTRA1 enzymatic reactivity (0.45 ± 0.07 fold). Computational modeling of potential azo dye interaction with HTRA1 suggests that CSB and Congo Red can bind to the noncatalytic face of the trimer interface but with different orientation tolerances and interaction energies. These studies identify select azo dyes as HTRA1 chemical probes that may serve as starting points for future HTRA1-centered small molecule therapeutics.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"20 8","pages":"1849–1862"},"PeriodicalIF":3.8,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740611","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":"Optimizing PDIA1 Inhibition as a Strategy to Inhibit NLRP3 Inflammasome Activation and Activity","authors":"Chavin Buasakdi,&nbsp;Caroline R. Stanton,&nbsp;Prerona Bora,&nbsp;Priyadarshini Chatterjee,&nbsp;Michael J. Bollong* and R. Luke Wiseman*,&nbsp;","doi":"10.1021/acschembio.5c00221","DOIUrl":"10.1021/acschembio.5c00221","url":null,"abstract":"<p >The NLRP3 inflammasome is a protein complex that promotes pro-inflammatory signaling as part of the innate immune response. Hyperactivation of the NLRP3 inflammasome has been implicated in many inflammatory and neurodegenerative diseases, leading to significant effort in developing strategies to limit its activation to intervene in these disorders. We previously showed that pharmacologic inhibition of endoplasmic reticulum (ER)-localized protein disulfide isomerase PDIA1 suppresses NLRP3 activation and activity, identifying PDIA1 as a potential therapeutic target to mitigate hyperactive NLRP3 activity. Herein, we screen PDIA1 inhibitors to identify highly potent compounds, including P1 and PACMA31, that pharmacologically target PDIA1 and block NLRP3 inflammasome assembly and activity. While sustained treatment with these PDIA1 inhibitors reduces THP1 viability, we show that acute treatment with these compounds is sufficient to both fully modify PDIA1 and inhibit NLRP3 inflammasome activity independent of any overt cellular toxicity. These results establish a treatment paradigm that can be exploited to develop highly selective PDIA1 inhibitors to mitigate hyperactive NLRP3 inflammasome activity implicated in etiologically diverse diseases.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"20 8","pages":"1892–1901"},"PeriodicalIF":3.8,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725839","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":"Cytosolic Delivery of Anionic Cyclic Dinucleotide STING Agonists with Locally Supercharged Viral Capsids","authors":"Paul Huang,&nbsp;Paige E. Pistono,&nbsp;Hannah S. Martin,&nbsp;Jennifer L. Fetzer and Matthew B. Francis*,&nbsp;","doi":"10.1021/acschembio.5c00125","DOIUrl":"10.1021/acschembio.5c00125","url":null,"abstract":"<p >Cyclic dinucleotide (CDN) STING agonists represent a powerful new immunotherapy treatment modality and are a class of nucleotide-based therapies with broad clinical potential. However, they face practical challenges in administration, largely due to their poor pharmacological properties. We report the development of a drug delivery platform for CDNs and other anionic small-molecule drugs using bacteriophage MS2 viral capsids with engineered cationic residues. Relative to viral capsids lacking locally supercharged regions, these assemblies exhibit substantial increases in mammalian cell uptake while avoiding cell toxicity and hemolysis. A synthetic strategy was developed to attach CDN drugs covalently to the interior capsid surfaces through reductively cleavable disulfide linkers, which allowed for traceless drug release upon cell entry and exposure to reductive cytosolic environments. MS2-mediated CDN delivery into immune cell populations resulted in an approximately 100-fold increase in delivery efficiency compared with free drugs and showed enhanced STING activation as well as downstream cytokine release.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"20 8","pages":"1875–1883"},"PeriodicalIF":3.8,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725837","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":"Dual Isotopologue Profiling of Bacterial Pathogens and their Host Cells: Metabolic Adaptation of Human Macrophages and Fallopian Tube Cells to Intracellular Chlamydia trachomatis","authors":"Sandra Radziej,&nbsp;Adriana Moldovan,&nbsp;Mark Klöpfer,&nbsp;Werner Goebel,&nbsp;Thomas Rudel and Wolfgang Eisenreich*,&nbsp;","doi":"10.1021/acschembio.5c00268","DOIUrl":"10.1021/acschembio.5c00268","url":null,"abstract":"<p ><i>Chlamydia trachomatis</i> is a Gram-negative bacterium that utilizes multiple host-derived substrates to ensure its intracellular survival. In this study, human fallopian tube (HFT) cells, and human macrophages polarized toward a pro-inflammatory (M1-like) or anti-inflammatory (M2-like) state were infected with <i>C. trachomatis</i> and cocultivated in the presence of [U-¹³C₆]glucose. Samples were analyzed <i>in toto</i> by dual isotopologue profiling with a focus on specific bacterial and host-specific metabolites. Immunofluorescence and ultrastructural analysis, as well as detection of the bacteria-specific metabolites (i.e., the branched-chain iso-C15:0 and anteiso-C15:0 fatty acids, and the cell wall component meso-diaminopimelic acid), confirmed that HFT cells and M2-like, but not M1-like macrophages, allow replication of <i>C. trachomatis</i>. The ¹³C-labeling patterns in these metabolites reflected their known biosynthetic pathways, but also upstream carbon fluxes via the uptake of host amino acids and glucose phosphate into the intracellular bacteria. Differential analysis of infected vs noninfected host cells showed that, in HFT cells and M2-like macrophages, the chlamydial infection upregulated glucose uptake into the host cells, glucose conversion into pyruvate and lactate via host glycolysis, and release of lactate into the medium. The rates of these processes were higher in HFT cells than in M2-like macrophages. We here establish dual isotopologue profiling as a suitable method to analyze the dynamics of host-intracellular pathogen interactions.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"20 8","pages":"1902–1915"},"PeriodicalIF":3.8,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acschembio.5c00268","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Controlling Electron Flow in Carbofluorescein Voltage Indicators","authors":"Jack T. McCann,&nbsp;Katharine M. Henn,&nbsp;Susanna K. Yaeger-Weiss,&nbsp;Minyi He and Evan W. Miller*,&nbsp;","doi":"10.1021/acschembio.5c00356","DOIUrl":"10.1021/acschembio.5c00356","url":null,"abstract":"<p >Interrogating biochemistry and biophysics with fluorescent reporters that respond to environmental cues is a powerful way to study dynamic processes in living systems in a noninvasive manner. Voltage-sensitive fluorophores (VF dyes) that utilize a photoinduced electron transfer-based mechanism to detect membrane potential (<i>V</i>_m) are a powerful method for noninvasive monitoring of bioelectrical signaling. We recently showed that VF dyes can “run in reverse” (ReverseVF) by introducing an electron withdrawing group to flip the direction of electron flow in the system. This first generation of ReverseVFs possessed both a low voltage sensitivity and signal-to-noise ratio (SNR), prompting further exploration of the system to develop a more sensitive <i>V</i>_m probe. In this work, we develop the second generation of ReverseVFs, addressing several hypotheses about the physical organic processes that drive the voltage sensitivity of VF probes. Here, we highlight the novel 4-NO₂ carbofluorescein VF: it displays a turn-on response to membrane hyperpolarization, with a nearly 4-fold increase in voltage sensitivity and 10-fold increase in SNR compared to previous generations. The high brightness and sensitivity of 4-NO₂ carbofluorescein VF enables both two-color voltage imaging in cells and action potential detection with cellular resolution across multiple neurons.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"20 8","pages":"1999–2005"},"PeriodicalIF":3.8,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725836","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":"Segmental Isotope Labeling of the Prion Protein: Identification of a Key Residue for Copper-Mediated Interdomain Structure","authors":"Francesca A. Pavlovici,&nbsp;Kevin Singewald,&nbsp;Samuel Kaplan,&nbsp;Eefei Chen and Glenn L. Millhauser*,&nbsp;","doi":"10.1021/acschembio.5c00336","DOIUrl":"10.1021/acschembio.5c00336","url":null,"abstract":"<p >The cellular prion protein is composed of two domains: a disordered N-terminal toxic effector domain and a three-helix C-terminal regulatory domain. Copper is thought to form a bridge between these two domains, inhibiting the protein’s inherent neurotoxicity. However, the molecular details of how copper interacts with the C-terminal regulatory surface are unclear. To assess the potential role of conserved C-terminal His residues in copper coordination, we applied sortase-mediated ligation to create an expressed murine prion protein with segmental ¹⁵N-labeling of the N-terminal domain. Pulsed EPR methods applied to a 1:1 protein:copper complex revealed both ¹⁴N and ¹⁵N couplings, consistent with simultaneous coordination of the two proteins’ domains to the copper center. Mutagenesis studies localized C-terminal copper coordination to His176, present on the second α-helix. The cumulative EPR results reveal a copper coordination environment composed of three His residues from the protein’s N-terminal domain, along with His176. The feasibility of these findings was tested with AlphaFold 3 simulations. These results further refine the molecular details of the prion protein’s autoregulation, emphasizing the critical role of its copper cofactor. Moreover, this interdisciplinary work demonstrates how sortase-mediated ligation combined with pulsed EPR sensitive to distinct nuclear spin systems provides a new strategy for assessing metal ion binding to proteins.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"20 8","pages":"1980–1989"},"PeriodicalIF":3.8,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697079","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":"Origin of the Different Binding Affinities of (9R)- and (9S)-Hexahydrocannabinol (HHC) for the CB1 and CB2 Cannabinoid Receptors","authors":"Pan-Pan Chen,&nbsp;Meng Duan,&nbsp;Qingyang Zhou,&nbsp;Fang Liu,&nbsp;Yi Tang*,&nbsp;Neil K. Garg* and K. N. Houk*,&nbsp;","doi":"10.1021/acschembio.5c00399","DOIUrl":"10.1021/acschembio.5c00399","url":null,"abstract":"<p >Hexahydrocannabinols (HHCs) are emerging cannabinoids that have become available for recreational use and were recently classified as Schedule II under an international treaty. Although often advertised for having desirable effects, recent studies have shown that commercial products typically contain variable amounts of two epimers, (9<i>R</i>)-HHC and (9<i>S</i>)-HHC. In turn, these epimers have been shown to have different binding affinities to the CB₁ and CB₂ receptors. We report a computational study that interrogates the origins of these differing affinities. Molecular docking and molecular dynamics simulations were employed to investigate the binding of (9<i>R</i>)-HHC and (9<i>S</i>)-HHC to cannabinoid receptors CB₁ and CB₂. Computational results show key binding interactions and highlight important conformational effects. For both receptors, the (9<i>R</i>)-HHC isomer exists primarily in a chair conformation, placing the C9 methyl substituent in a favorable equatorial position in the active sites. However, (9<i>S</i>)-HHC exists in equilibrium between the chair and twist-boat conformations within the receptor’s active site, ultimately leading to less favorable binding in the CB₁ and CB₂ active sites, making (9<i>S</i>)-HHC a less favorable ligand compared to (9<i>R</i>)-HHC. These studies explain the relative binding of HHCs and are expected to enable the investigation of other cannabinoids that display improved or selective receptor binding.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"20 8","pages":"2006–2013"},"PeriodicalIF":3.8,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697078","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":"Harnessing Nanobodies for Precision Targeting of Proteoforms: Opportunities and Challenges in Therapeutics and Diagnostics","authors":"Elise M. Van Fossen,&nbsp;Oscar Rodriguez,&nbsp;Madelyn Berger,&nbsp;Rowan Wooldridge,&nbsp;Leo Gorham,&nbsp;Abdullah Shouaib,&nbsp;Amy C. Sims,&nbsp;John T. Melchior* and Samantha M. Powell*,&nbsp;","doi":"10.1021/acschembio.5c00329","DOIUrl":"10.1021/acschembio.5c00329","url":null,"abstract":"<p >Proteoforms are biologically distinct yet structurally similar proteins that play key roles in driving disease progression but are rarely accounted for in the development of therapeutics and diagnostics. Nanobodies (Nbs) have emerged as a therapeutic and diagnostic “silver bullet” as they possess unique structural and functional attributes that offer advantages over traditional antibodies. One of the most profound advantages of Nbs is the heightened sensitivity and ability to distinguish subtle changes in the conformation of a given protein. Thus, Nbs have significant potential as therapeutic and diagnostic agents that can identify and distinguish specific pathological proteoforms that underlie a given disease. However, there remain significant challenges in obtaining sufficient quantities and purities of specific proteoform antigens that are required for engineering proteoform-specific Nbs. Recent advancements in chemical biology tools for precision proteoform synthesis have made this task feasible for the first time. In this perspective, we discuss the advantages and challenges associated with developing proteoform-specific Nbs and how success in this endeavor will significantly advance the fields of therapeutics and diagnostics.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"20 8","pages":"1817–1827"},"PeriodicalIF":3.8,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acschembio.5c00329","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}