Bioorganic Chemistry最新文献

{"title":"Corrigendum to \"Discovery of neuroprotective agents: Potent, brain penetrating, lipoic acid derivatives for the potential treatment of ischemic stroke by regulating oxidative stress and inflammation - A preliminary study\" [Bioorg. Chem. 147 (2024) 107339].","authors":"Chenchen Zhu, Yun Wang, Yi Li, Tingfang Wang, Fei Ye, Wei Su, Ting Chen, Chuan Zhang, Liyan Xiong","doi":"10.1016/j.bioorg.2024.107927","DOIUrl":"https://doi.org/10.1016/j.bioorg.2024.107927","url":null,"abstract":"","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":" ","pages":"107927"},"PeriodicalIF":4.5,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro and in vivo studies of a decanuclear Ni(II) complex as a potential anti-breast cancer agent.","authors":"Haitao Zhu, Houcong Li, Yuxin Ji, Min Hou, Qingling Yang, Lili Liang, Wenge Li","doi":"10.1016/j.bioorg.2024.107949","DOIUrl":"https://doi.org/10.1016/j.bioorg.2024.107949","url":null,"abstract":"<p><p>A non-platinum-metal decanuclear complex [Ni₁₀L₄(CH₃COO)₈ (C₂H₅OH)₈]·8(C₂H₅OH) (Ni₁₀ complex) has been developed with a tri-dentate 2,3-dihydroxybenzaldehyde-2-aminophenol Schiff base ligand (H₃L). Single crystal X-ray analysis reveals that the Ni₁₀ complex displays a sandwich loaf-shaped decanuclear structure and its anticancer activity was evaluated. The cell cytotoxicity results indicating that the Ni₁₀ complex is most effective to human breast cancer cells MDA-MB-231 and its mechanism were further investigated. Flow cytometry analysis showed that the Ni₁₀ complex triggered cell cycle arrest and induced apoptosis of MDA-MB-231 cells. Western blot analysis of the changes of intracellular protein expression showed that Ni₁₀ triggers MDA-MB-231 apoptosis through mitochondrial mediated apoptosis signaling pathways. In vivo experiments showed that the Ni₁₀ complex significantly suppressed breast tumor growth with low toxicity against major organs in a nude mice model. The good treatment effect, low toxicity and pharmacological mechanisms of the decanuclear Ni^II complex may provide a clue for the research and development of non-platinum multinuclear based chemotherapeutic drugs.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"107949"},"PeriodicalIF":4.5,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering substrate promiscuity and specificity of indolethylamine N-methyltransferase family enzymes from amphibian toads.","authors":"An-An Zhang, Chengyu Zhou, Guo-Qiang Lin, Qing-Li He, Qunfei Zhao","doi":"10.1016/j.bioorg.2024.107950","DOIUrl":"https://doi.org/10.1016/j.bioorg.2024.107950","url":null,"abstract":"<p><p>N-methylation is a crucial post-modification process in natural product biosynthesis and also contributes to the metabolism of various physiological substances, such as neurotransmitter, hormone, and trace elements. In this study, we identified seven indolethylamine N-methyltransferase (INMT) family enzymes from the amphibian toad Bufo gargarizan with distinct catalytic properties. Among these enzymes, BNMT 1, BNMT 5, BNMT 6 and BNMT 7 exhibited notable promiscuity, demonstrating the ability to methylate multiple derivatives of indolethylamine, phenylethylamine, phenylethanolamine, and nicotinamide. Conversely, BNMT 3 and BNMT 4 exhibited more specific substrate preferences, targeting particular phenylethylamine, phenylethanolamine, and nicotinamide-type substrates. Additionally, one enzyme, BNMT 11, exhibiting high specificity towards phenylethanolamines. By employing molecular docking and mutating key amino acids, we provided a rational explanation for the promiscuity and specificity mechanisms exhibited by these enzymes. This research offers valuable insights into the catalytic mechanisms of INMT family enzymes in B. gargarizans, as well as other organisms. Moreover, the identification of these broadly substrate-specific enzymes holds promise for leveraging synthetic biology in the production of a wide variety of naturally occurring N-methylated compounds.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"107950"},"PeriodicalIF":4.5,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenylboronic acid-functionalized copper nanoclusters with sensitivity and selectivity for the ratiometric detection of luteolin.","authors":"Xingyu Hou, He Zuo, Na Sun, Yongqiang Wang, Rui Jia, Yuguang Lv, Lixin Ding","doi":"10.1016/j.bioorg.2024.107946","DOIUrl":"https://doi.org/10.1016/j.bioorg.2024.107946","url":null,"abstract":"<p><p>A desirable ratiometric fluorescent probe was designed by using 3-carboxyphenylboronic acid functionalized polyethyleneimine ethoxylated modified copper nanoclusters (CPBA@PEI-CuNCs) for detecting luteolin (LTL, cis-diols structure) with sensitivity and selectivity. Characterization techniques were carried out with the TEM, PSD, FT-IR, XPS and XRD, confirming its successful formation with a quantum yield of 40.49 %. As the optimal excitation wavelength at 386 nm, the fluorescence intensity was detected by fluorophotometer. Meanwhile, the nanoprobe has two emission wavelengths 396 and 473 nm. According to the fluorescence quenching intensity ratio (F₄₇₃/F₃₉₆), the LOD reached as low as 1.22 nM within the range from 0.11 to 600 μM. The CPBA@PEI-CuNCs exhibited pH-controlled, covalent, and reversible binding properties. Using PEI capped by CuNCs, cytotoxicity is reduced for potential treatment purposes. Additionally, the developed probe was used for LTL detection, HepG2 cell imaging and pH-responsive drug delivery in real samples with carrot leaves, peanut shells, and perilla leaves samples. CPBA@PEI-CuNCs demonstrated repeatability and reproducibility, making it a cost-effective and practical tool for fluorescence analysis in detection.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"107946"},"PeriodicalIF":4.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eco-conscious synthesis of novel 1,2,4-triazolo[1,5-a]pyrimidine derivatives as potent Anti-microbial agent and comparative study of cell viability and cytotoxicity in HEK-293 cell line utilizingIndian gooseberry (Phyllanthus emblica) fruit extract.","authors":"Bhaktiben R Bhatt, Kamalkishor Pandey, Tarosh Patel, Anupama Modi, Chandani Halpani, Vaibhav D Bhatt, Bharat C Dixit","doi":"10.1016/j.bioorg.2024.107936","DOIUrl":"https://doi.org/10.1016/j.bioorg.2024.107936","url":null,"abstract":"<p><p>Antimicrobial resistance (AMR) is a pressing global health challenge that necessitates the search for novel antimicrobial agents and synthetic methodologies. This study investigates the synthesis and antimicrobial efficacy of 25 novel 1,2,4-triazolo[1,5-a]pyrimidine derivatives, catalyzed by Amla (Phyllanthus emblica) fruit juice, which is rich in organic acids and polyphenolic compounds, thus serving as an environmentally sustainable catalyst, in adherence to green chemistry principles. The synthesis is achieved through a one-pot, solvent-free process that yields high quantities of the desired compounds in significantly less time compared to traditional methods. Comprehensive antimicrobial evaluation was conducted against a range of clinically relevant microorganisms, including Chromobacterium violaceum, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Candida albicans, Cryptococcus neoformans and Aspergillus niger. Concurrently, cytotoxic assays were performed on HEK-293 cells, to assess safety profiles, revealing that compounds B-1, B-6, B-7, B-14 and B-15 exhibited potent antimicrobial activity while maintaining low cytotoxicity and high cell viability. These findings underscore the therapeutic potential of the synthesized compounds in combatting infectious diseases and addressing the challenges posed by AMR, highlighting the critical importance of dose optimization in therapeutic applications. This study combats contagious diseases, mitigates AMR challenges and contributes significantly to the field of antimicrobial drug discovery, emphasizing the need for sustainable synthetic strategies that align with future pharmaceutical endeavors. Our research not only advances the understanding of these novel compounds but also supports ongoing efforts to develop safe and effective therapies against resistant pathogens.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"107936"},"PeriodicalIF":4.5,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Copper(II) aromatic heterocyclic complexes of Gatifloxacin with multi-targeting capabilities for antibacterial therapy and combating antibiotic resistance.","authors":"Xiao-Yin Wu, Qi-Yan Liu, Shan Jiang, Zheng-Yin Pan, Jia-Hao Dong, Bai-Hua Chen, Jin-Hao Li, Ya-Shu Liu, Yingju Liu, Liang He","doi":"10.1016/j.bioorg.2024.107938","DOIUrl":"https://doi.org/10.1016/j.bioorg.2024.107938","url":null,"abstract":"<p><p>In recent years, the pace of novel antibiotic development has been relatively slow, intensifying the urgency of the antibiotic resistance issue. Consequently, scientists have turned their attention to enhancing antibiotic activity by coordinating antibiotics with metal elements. This study designs and synthesizes three novel antibacterial copper complexes based on Gatifloxacin. These complexes exhibit potent antibacterial activity, notably Cu-1, with a minimum inhibitory concentration (MIC) of only 0.063 μg/mL against Staphylococcus aureus (S.aureus), demonstrating potent bacteriostatic capabilities. Further investigations unveil the antibacterial mechanisms of complex Cu-1, revealing its ability not only to suppress the activities of DNA gyrase and topoisomerases IV, but also to effectively inhibit biofilm formation and disrupt the integrity of cell membrane. This multi-targeting action contributes to mitigating the risk of bacterial resistance emergence. Additionally, synergy between Cu-1 and conventional antibiotics is confirmed through checkerboard assays, offering novel strategies for antibacterial therapy. In vivo experiments using a murine model of S.aureus infection demonstrate the significant antibacterial efficacy of Cu-1, providing robust support for its potential in treating S.aureus infections. This study demonstrates that the coordination complexes formed by copper, Gatifloxacin and suitable aromatic heterocyclic ligands exhibit multi-targeting characteristics against bacteria, offering a new direction for combating antibiotic resistance in antibacterial therapy.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"107938"},"PeriodicalIF":4.5,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel 5-Fluorouracil analogues versus perfluorophenyl ureas as potent anti-breast cancer agents: Design, robust synthesis, in vitro, molecular docking, pharmacokinetics ADMET analysis and dynamic simulations.","authors":"Farid M Sroor, Ahmed F El-Sayed, Khaled Mahmoud","doi":"10.1016/j.bioorg.2024.107944","DOIUrl":"https://doi.org/10.1016/j.bioorg.2024.107944","url":null,"abstract":"<p><p>To investigate the therapeutic potential of 5-Fluorouracil-based analogues, a straightforward synthetic technique was employed to synthesize a novel series of 5-arylurea uracil derivatives (AUFU01-03) and aryl-urea derivatives bearing perfluorophenyl (AUPF01-03). Reliable tools such as infrared (IR), Nuclear Magnetic Resonance (NMR) spectra, and elemental analyses were utilized to confirm the chemical structures and purity of these compounds. In comparison to healthy noncancerous control skin fibroblast cells (BJ-1), we examined the antiproliferative efficacy of compounds (AUFU01-03) and (AUPF01-03) against specific human malignant cell lines of the breast (MCF-7), and colon (HCT-116). Based on the MTT experiment results, compounds AUFU03 and AUPF01-03 possessed highly cytotoxic effects. Among these, cytotoxicity was demonstrated by compounds AUPF01-03 with IC₅₀ values (AUPF01, IC₅₀ = 167 ± 0.57 µM, AUPF02, IC₅₀ = 23.4 ± 0.68 µM and AUPF03, IC₅₀ = 28.8 ± 1.13 µM, respectively, on MCF-7), relative to 5-Fluorouracil as reference drug (IC₅₀ = 160.7 ± 0.22 µM). Compound AUPF01 showed safety on BJ-1 cells up to a concentration of 100 µM (% cytotoxicity = 3.9 ± 0.42 %), so AUPF01 was selected for further studies. At the gene, the expression levels of BCL-2 gene were decreased significantly in MCF-7 + 5-FU and reached the lowest level in MCF-7 + AUPF01. In contrast, the expression levels of pro-apoptotic genes (p53 and BAX) were increased in MCF-7 + 5-FU, and reached a significantly higher level in MCF-7 + AUPF01. Apoptosis/necrosis assays demonstrated that AUPF01 induced S and G2/M phase cell cycle arrest in MCF-7 cells. Moreover, the efficacy of these compounds against anti-cancer protein receptors was assessed using molecular docking. The results indicated that compound AUPF01 exhibited high binding energies, effectively interacting with the active sites of crucial proteins such as EGFR, CDK2, ERalfa, BAX1, BCL2, and P53. These interactions involved a diverse range of chemical bonding types, suggesting the potential of these substances to inhibit enzyme activities. Moreover, computational ADMET analyses of these compounds demonstrated compliance with Lipinski's criteria, indicating favorable physicochemical properties. Additionally, molecular dynamics (MD) simulations revealed stable complexes of AUPF01 with EGFR, CDK2, ERalfa, BAX1, BCL2, and P53, as evidenced by (RMSD) values, RMSF values, and (SASA) values for the respective complexes.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"107944"},"PeriodicalIF":4.5,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive utilization of in silico approach and in vitro experiment to unveil the molecular mechanisms of mono (2-ethylhexyl) phthalate-induced lung adenocarcinoma.","authors":"Wenwen Wang, Junying Li, Xingwang Qie","doi":"10.1016/j.bioorg.2024.107947","DOIUrl":"https://doi.org/10.1016/j.bioorg.2024.107947","url":null,"abstract":"<p><p>Mono (2-ethylhexyl) phthalate (MEHP), the main bioactive metabolite of commonly used plasticizer Di (2-ethylhexyl) phthalate, has received increasing attention due to its carcinogenic toxicity. This study aims to systematically explore the molecular mechanisms underlying MEHP-induced lung adenocarcinoma (LUAD). Firstly, network toxicology was employed to construct the interaction network of MEHP-targeted LUAD-related proteins and identify core proteins. Subsequently, functional analyses were used to determine the key pathways of these proteins enriched. Next, expression and survival analyses of multiple public datasets were conducted to emphasize the importance of core genes, and an optimized prognostic model was constructed based on independent prognostic genes to explore the relationship of gene risk with immune infiltration and immunotherapy. Ultimately, molecular docking and dynamics simulation were used to predict the binding modes and affinities of MEHP with core proteins, and surface plasmon resonance experiments were utilized to further validate their direct interactions. The findings demonstrated that MEHP targets 167 LUAD-related proteins, including 28 core target proteins. These proteins form the critical networks that regulate cancer and immune-associated pathways to induce the occurrence and development of LUAD, and further coordinate patient prognosis and treatment by altering the immune microenvironment. Most importantly, their direct interactions (especially PTGS2) lay the structural foundation of MEHP regulating core proteins, greatly supporting its LUAD toxicity. In conclusion, this study introduces a novel approach for evaluating the safety of plasticizers and elucidates the molecular mechanisms behind MEHP-induced LUAD, thus offering new and effective targets and strategies for cancer prevention and treatment.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"107947"},"PeriodicalIF":4.5,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Steroid and bioactive molecule conjugates: Improving therapeutic approaches in disease management.","authors":"Anna Kawka, Hanna Koenig, Tomasz Pospieszny","doi":"10.1016/j.bioorg.2024.107933","DOIUrl":"https://doi.org/10.1016/j.bioorg.2024.107933","url":null,"abstract":"<p><p>Conjugates of steroids and other natural bioactive molecules (such as amino acids or carbohydrates) have proven promising compounds with diverse biological effects. This literature review summarises the importance of steroid conjugates in a broad spectrum of therapeutic applications. Steroid conjugates exhibit improved pharmacokinetic properties, improved target specificity, and reduced side effects compared to the parent compounds. This increases their clinical usefulness. Their versatility extends to drug delivery systems, enabling precise modulation of drug release kinetics and bioavailability. Moreover, steroid conjugates are vital in treating inflammatory and neurodegenerative diseases, hormonal disorders, cancer therapy, and combating microbial infections. The review presents the current state of research on steroid conjugates, highlighting the crucial role of steroid conjugates in modern medicine and their potential to revolutionise therapeutic paradigms and improve patient outcomes. Steroid compounds are excellent for developing agents with better bioavailability and are used as drug carriers or hydrogelators.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"107933"},"PeriodicalIF":4.5,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure-Based identification of a potent KDM7A inhibitor exerts anticancer activity through transcriptionally reducing MKRN1 in taxol- resistant and -sensitive triple-negative breast cancer cells.","authors":"Jin-Jin Shi, Yan-Jun Liu, Zhi-Guo Liu, Ru-Yi Chen, Ran Wang, Jing Yu, Chang-Yun Li, Guan-Jun Yang, Jiong Chen","doi":"10.1016/j.bioorg.2024.107945","DOIUrl":"https://doi.org/10.1016/j.bioorg.2024.107945","url":null,"abstract":"<p><p>KDM7A, a histone demethylase implicated in cancer proliferation, metastasis, and drug resistance, represents a crucial therapeutic target. Utilizing \"mcule.com\" for virtual screening of 100,000 compounds from the ZINC database, we identified 12 compounds with high affinity for KDM7A, with compound 4 emerging as the leading candidate for effectively inhibiting KDM7A's demethylase activity. Analysis of the GTRD database, the Breast Cancer Gene Expression Miner website, and recent studies highlighted MKRN1, a gene associated with cell proliferation and drug resistance, as a key intersecting factor. Compared to 2,4-pyridine dicarboxylic acid, compound 4 significantly reduced breast cancer stem cells and induced G1 phase cell cycle arrest. Mechanistically, compound 4 inhibited KDM7A's binding to H3K27me3, decreased MKRN1 transcription, and increased the levels of cell cycle regulators p16, p21, and p27, while reducing stem cell markers ALDH1A1, CD44, and CD133. These findings suggest that compound 4 could serve as a promising lead for selective KDM7A-targeting drugs. Additionally, this study is the first to demonstrate MKRN1 as a downstream gene of KDM7A, showing significant inhibitory effects in both taxol-resistant and drug-sensitive triple-negative breast cancer (TNBC) cells. This research offers new insights into the anticancer mechanisms of KDM7A inhibitors and underscores KDM7A's potential as a therapeutic target against TNBC.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"107945"},"PeriodicalIF":4.5,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}