Molecular Diversity最新文献

{"title":"In silico prediction of drug-induced cardiotoxicity with ensemble machine learning and structural pattern recognition.","authors":"Siwen Li, Haojie Xu, Fengxi Liu, Rong Ni, Yinping Shi, Xiao Li","doi":"10.1007/s11030-025-11266-8","DOIUrl":"https://doi.org/10.1007/s11030-025-11266-8","url":null,"abstract":"<p><p>Drug-induced cardiotoxicity poses a significant risk to human health, and reliable predictive models are needed for safety assessment. In this study, a range of machine and deep learning models were developed for five cardiotoxicity end points, including heart failure (HF), arrhythmia (ARR), heart block (HB), hypertension (HP), and heart attack (HA). A total of 110 predictive models were constructed for each cardiotoxicity endpoint using various algorithms and molecular descriptors, and consensus models were developed based on the best-performing individual classifiers. The consensus models consistently outperformed individual models in cross-validation and external validation. Further molecular property analysis revealed that cardiotoxic compounds tend to exhibit higher molecular weight, increased lipophilicity (logP), lower hydrogen bonding capacity (HBD and HBA), and reduced topological polar surface area (TPSA). Additionally, key structural alerts (SAs), including secondary amines, benzene derivatives, sulfonamide/sulfonylurea groups, and heterocyclic structures, were identified. These SAs may mediate cardiotoxicity through ion channel inhibition, oxidative stress induction, and calcium homeostasis disruption. This study provides an integrated machine learning and deep learning computational framework for drug cardiotoxicity assessment and provides an exploration of the structural characteristics of cardiotoxic compounds, which is helpful for the discovery of safer drugs and chemical risk assessment.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of FLF-15 as a novel selective inhibitor of ADAM17 to prevent hepatocellular carcinoma metastasis.","authors":"Qing Li, Dao-Ping Wang, Ting Zhong, Ai-Ling Ling-Hu, Jia-Lin Chen, Fang Luo, Feng Zhang, Ming-Zhi Su, Ying Yang, Yan-Hua Fan","doi":"10.1007/s11030-025-11275-7","DOIUrl":"https://doi.org/10.1007/s11030-025-11275-7","url":null,"abstract":"<p><p>The poor prognosis of hepatocellular carcinoma (HCC) is mainly due to its high metastatic properties. Hence, metastasis inhibition might provide a reliable strategy for HCC treatment. As its pivotal role in the tumor cell proliferation, survival and metastasis, a disintegrin and metalloproteinase 17 (ADAM17) has become an attractive target for cancer therapy. Nevertheless, the role of ADAM17 in HCC metastasis and its underlying mechanisms remain enigmatic. In the present study, we discovered a novel ADAM17 inhibitor FLF-15, with an IC₅₀ value of 10.43 nM. Further mechanistic studies showed that FLF-15 inhibits HCC migration and invasion in vitro and in vivo mainly by reducing interleukin-6 receptor (IL-6R) shedding, which inhibits IL-6 trans-signaling, while also leading to a reduction in IL-6 levels and downregulation of IL-6 classic-signaling. Furthermore, we revealed an overlapping but distinct biological effects of IL-6 classic and trans-signaling in HCC. Specifically, JAK2/STAT3 and ERK1/2 signaling can be stimulated by both IL-6 classic and trans-signaling pathway. However, AKT appears to be only activated by IL-6 trans-signaling pathway, suggesting its essential role for FLF-15 induced metastasis suppression in HCC. Taken together, our study identified FLF-15 as a novel ADAM17 inhibitor and elucidated its underlying mechanism of HCC metastasis suppression. These findings indicated FLF-15 might be a promising candidate for the development of HCC therapeutic agents.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative transcriptomic and structural analysis identifies PTGS2 as a key target in ischemic stroke associated with neuroinflammation.","authors":"Saleh I Alaqel, Abida Khan, Mashael N Alanazi, Naira Nayeem, Hayet Ben Khaled, Mohd Imran","doi":"10.1007/s11030-025-11244-0","DOIUrl":"https://doi.org/10.1007/s11030-025-11244-0","url":null,"abstract":"<p><p>Ischemic stroke is a leading cause of mortality and long-term disability worldwide, primarily driven by neuroinflammatory damage. Prostaglandin-endoperoxide synthase 2 (PTGS2), which encodes the cyclooxygenase-2 (COX-2) enzyme, plays a central role in mediating inflammatory pathways, making it a key therapeutic target in ischemic stroke. This study presents a comprehensive analysis aimed at identifying potential PTGS2 inhibitors for mitigating neuroinflammatory damage in ischemic stroke. Gene expression profiling of the GSE16561 dataset, comprising control and stroke patient samples, revealed 329 differentially expressed genes (DEGs), including PTGS2 and ZFHX3, central to neuroinflammatory and vascular remodeling pathways. Modular co-expression analysis identified distinct gene clusters associated with oxidative stress, apoptosis, and blood-brain barrier dysfunction, providing insights into molecular mechanisms underlying stroke pathology. To complement gene-level analysis, molecular clustering and feature correlation studies were performed on a dataset of compounds using PubChem and substructure descriptors. Hierarchical clustering revealed four molecular clusters, with Cluster 2 compounds (CHEMBL44468 and CHEMBL462709) showing unique features like sulfur-containing and bridged-ring systems. These descriptors were validated as contributors to molecular differentiation through t-SNE visualization and heatmap analysis. Molecular docking, dynamics, and MM-GBSA studies further highlighted the strong binding affinities of these compounds to the PTGS2 active site, supporting their potential to modulate inflammatory pathways implicated in stroke. This integrative approach, combining gene expression analysis, molecular clustering, and docking studies, underscores the potential of Cluster 2 compounds as promising candidates. This study provides a framework for advancing ischemic stroke therapeutics and targeted anti-inflammatory drug development by bridging transcriptomic insights with structural studies.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in pyrazolo[3,4-b]pyridine chemistry: synthesis techniques and biological activity.","authors":"Anhar Abdel-Aziem, Sawsan A Fouad","doi":"10.1007/s11030-025-11231-5","DOIUrl":"https://doi.org/10.1007/s11030-025-11231-5","url":null,"abstract":"<p><p>In recent years, attention has been drawn to pyrazolo[3,4-b] pyridine and its derivatives due to their substantial pharmacological activities such as antidepressant, anticancer, antiviral, antifungal, antioxidant, anticoagulant, anti-Alzheimer, and antimicrobial. Besides their medicinal uses, they act as herbicides, fungicides, and are also used as agrochemicals, inhibitors for a wide range of kinases, and fibroblast growth factor receptors. Additionally, pyrazolo[3,4-b] pyridines are used in developing organic materials for different applications such as chemosensors and corrosion inhibitors for mild steel. This review aims to provide an in-depth overview of the latest advancements regarding synthetic routes, reactions, and biological importance of pyrazolo [3,4-b] pyridine during 2019-2025 which will be a useful resource for interested researchers engaged in this area. The synthetic methodologies focus on metal-catalyst, nanocatalyst, microwave-assisted synthesis, multicomponent reactions, and other green chemistry approaches. Emphasizing the significance of these scaffolds in drug discovery and medicinal chemistry, new developments and future directions in the design of innovative pyrazolo[3,4-b]pyridine-based therapies are also covered.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and bioactivity of tetrahydrothiopyran derivatives as potential acaricides against Psoroptes cuniculi.","authors":"Dongdong Chen, Yan Wang, Yujun Wu, Xinying Sun, Yaxuan Wang, Qi Li, Wennuo Zhou, Wen Wu, Jie Long","doi":"10.1007/s11030-025-11256-w","DOIUrl":"https://doi.org/10.1007/s11030-025-11256-w","url":null,"abstract":"<p><p>Thirty-two tetrahydrothiopyran derivatives were synthesized, and their acaricidal activities against Psoroptes cuniculi were evaluated in vitro. The results showed that eight compounds exhibited higher acaricidal activity than ivermectin when evaluated by mass concentration, while six compounds showed superior activity when assessed by molar concentration. Compound b10 showed the lowest LC₅₀ value [62.3 µg/mL (0.12 mM)] and LT₅₀ value (2.2 h at 4.5 mM), far lower than ivermectin [LC₅₀ = 223.3 µg/mL (0.26 mM), LT₅₀ = 8.7 h]. Structure-activity relationship (SAR) analysis showed that the presence of the sulfone structure is crucial for activity, while the types and positions of substituents on the benzene rings are two main factors affecting the activity. Molecular docking results demonstrated that compounds a10, b9, b10 and b11 exhibited good affinity with the AChE protein, along with potential binding modes, suggesting AChE as a promising acaricidal drug target. Overall, these results suggest that tetrahydrothiopyran derivatives, particularly their sulfone derivatives have great potential for the development of novel acaricides.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure-based screening of small-molecule interleukin-23 inhibitors inspired by monoclonal antibody interactions.","authors":"Khac-Minh Thai, Thi-Thanh-Thao Vu, Quang-Minh Mai, Minh-Tri Le","doi":"10.1007/s11030-025-11257-9","DOIUrl":"https://doi.org/10.1007/s11030-025-11257-9","url":null,"abstract":"<p><p>Interleukin-23 (IL-23) is a key driver of chronic inflammatory diseases, yet current therapies rely on costly monoclonal antibodies. This study aims to identify small-molecule IL-23 inhibitors using an in silico approach that mimics antibody interactions. The structure of IL-23 and the monoclonal antibody Risankizumab was reconstructed using homology modeling and deep learning. Key binding sites were characterized and used to generate 3D pharmacophore models, which guided virtual screening of compounds from DrugBank and ZINC12 databases. Top candidates were evaluated via ADMET filtering, molecular docking, molecular dynamics simulations and MM/GBSA binding free energy calculations. ZINC20572287 (r3-7) demonstrated stable binding within the IL-23p19 pocket and maintained strong hydrogen bonding over a 600 ns simulation. In contrast, no potent IL-12p40 inhibitors were identified. These findings suggest r3-7 as a promising scaffold for developing cost-effective IL-23-targeted therapeutics.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pangenome-based network analysis of Acinetobacter baumannii reveals the landscape of conserved therapeutic targets.","authors":"Thejaswi Bhat, Manish Kumar, Krishna Kumar Ballamoole, Vijaya Kumar Deekshit, Pavan Gollapalli","doi":"10.1007/s11030-025-11252-0","DOIUrl":"https://doi.org/10.1007/s11030-025-11252-0","url":null,"abstract":"<p><p>The increasing prevalence of Acinetobacter baumannii infections and its severity demand the acute necessity for innovative therapeutic targets against it. This study employs comprehensive pangenome analysis to investigate 124 A. baumannii multidrug-resistant strains, to determine the most promising therapeutic targets derived from its core genome. Nucleotide diversity analysis of core and variable gene clusters identified key polymorphisms, suggesting significant evolutionary adaptation. Our findings revealed significant presence/absence variation (PAV) in resistance genes across strains, with 97 antimicrobial drug resistance genes identified. Two gene clusters, cluster-288 and cluster-566, harbored resistance-related genes encoding for beta-lactamase and multidrug efflux pump, respectively, were identified from the core genome that plays a pivotal role in conferring multidrug resistance. The functional enrichment analysis of these gene clusters highlighted key proteins, such as penicillin-binding proteins and outer membrane efflux proteins, as potential targets for drug design. Furthermore, we analyzed the physicochemical properties, virulence potential, active site prediction, and predicted conserved motifs. Structural predictions via 3D modeling and molecular dynamics simulations revealed high stability of key proteins, with RMSD values of 0.52 nm for outer membrane channel subunit AdeK and 0.85 nm for beta-lactamase, suggesting these proteins' potential as novel drug targets and their structural integrity under physiological conditions. Principal component analysis (PCA) highlighted distinct motion patterns within these proteins, providing insights into their functional dynamics. This research contributes to ongoing efforts to combat antibiotic resistance through innovative approaches in drug design and therapeutic interventions.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pyrazole in drug development: a medicinal-chemistry based analysis of USFDA-approved drugs in last decade.","authors":"Nisha Bansal, Elagandhula Sathish, M Arockia Babu, Ganesh Bushi, Abhay M Gaidhane, Thakur Gurjeet Singh, Damini Singh, Glowi Alasiri, Mohammad Fareed, Bhupinder Kumar","doi":"10.1007/s11030-025-11260-0","DOIUrl":"https://doi.org/10.1007/s11030-025-11260-0","url":null,"abstract":"<p><p>Among the diversity of existing heterocycles, nitrogen-containing heterocycles, i.e., azaheterocycles, are the most popular entity in drug discovery. In the present review, we have focused on the structural diversity of pyrazole in drug discovery and the critical analysis of approved drugs bearing this versatile pharmacophore in the past decade (2014-2023). The investigation of the USFDA-approved drug-bearing pyrazole scaffold revealed that a total of 20 drugs were approved during the period of analysis. The bifurcation of approved drugs led us to conclude that nine drugs (45%) were to treat cancer, followed by four drugs for rare genetic diseases, three for treating infection, two for neurological conditions, and one for rheumatoid arthritis and glaucoma, respectively. The investigation also revealed that the majority of drugs (65%) were indicated to be used in rare forms of cancer and diseases. Besides this, the review also highlighted that 53% of approved drugs were launched in tablet form, and 80% of these drugs were intended to be given by oral route. The drug metabolism analysis revealed that 25% of approved drugs undergo Phase 1 metabolism via CYP3A4, followed by the combined involvement of CYP3A4 and CYP2C9 for 10% of approved drugs. The drugs are chiefly excreted via the fecal route (12) and the urine (7). The structural diversity revealed that the majority of pyrazole drugs comprised a pyridine ring (7) in conjugation. At the same time, fluorine was the key halogen substituent, and amine was the major non-halogenated substituent in the approved drugs. The review is, therefore, a congregated effort to not only compile and update the USFDA-approved drugs containing pyrazole but also explore their in-depth medicinal chemistry-based analysis to enrich the medicinal chemist and allied sciences researchers for their comprehensive read.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug repurposing for renin inhibition: identifying panobinostat for hypertension management.","authors":"Nisha Bansal, Mohammad Khalid Parvez, M Arockia Babu, Mohammed S Al-Dosari, Thakur Gurjeet Singh, Nemat Ali, Umesh Yadav, Ganesh Bushi, Abhay M Gaidhane","doi":"10.1007/s11030-025-11253-z","DOIUrl":"https://doi.org/10.1007/s11030-025-11253-z","url":null,"abstract":"<p><p>Renin, an aspartyl protease enzyme, is a crucial part of the renin-angiotensin-aldosterone system (RAAS) that regulates blood pressure. However, numerous renin inhibitors, including Aliskiren, Zankiren, Enalkiren, Fasidotril, and Remikiren, are in the clinical arena of managing hypertension, but they are associated with numerous drawbacks. The important one includes modest efficacy in contrast to other antihypertensive agents, which reduces their use as monotherapy; secondly, the related side effects, including hyperkalemia and renal impairment. Thus, considering the unmet need to identify new renin inhibitors, we applied the drug repurposing technique on an 1880 US FDA-approved small molecules database. The research was achieved by performing the structure-based virtual screening (SBVD) on FDA-approved drugs, which was well supported by molecular docking, dynamics, and mechanics studies. This work identified Panobinostat as a possible lead renin inhibitor. The in vitro Elisa-based assay revealed Panobinostat has the potential to inhibit the renin enzyme at the half-maximal concentration (IC₅₀) of 201.27 nM, while standard renin inhibitor Aliskiren portrayed an IC₅₀ of 162.22 nM. The comparable potency to clinical renin inhibitors presents this HDAC inhibitor as a dual-functioning ligand. The findings are significant and well correlated with the plethora of evidence suggesting the role of HDACs in regulating RAAS and cardiovascular functions via the post-translational level modulation of chromatins' structures and functions.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning-based QSAR and molecular modeling identify promising PTP1B modulators from Ocimum gratissimum for type 2 diabetes therapy.","authors":"Oludare M Ogunyemi, Esther O Adeyeye, Oladimeji S Macaulay, Babatunde A Olabuntu, J Achem, Gideon A Gyebi, Charles O Olaiya, Saheed Sabiu","doi":"10.1007/s11030-025-11255-x","DOIUrl":"https://doi.org/10.1007/s11030-025-11255-x","url":null,"abstract":"<p><p>Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of insulin signaling and a promising therapeutic target for the treatment of type 2 diabetes mellitus. Ocimum gratissimum (African basil) has been traditionally used and reported to enhance insulin sensitivity and promote glucose uptake, however, the molecular basis and active constituents responsible for these biological activities remain poorly characterized. The study focused on bioprospecting O. gratissimum for PTP1B inhibitors through machine learning (ML) and molecular modeling. Predictive ML models were developed using a curated IC₅₀ bioactivity dataset of known PTP1B inhibitors from the ChEMBL database. Among 42 algorithms assessed, the Random Forest Regressor (RFR) exhibited the best performance and identified 49 compounds (pIC₅₀ > 5) out of 156-screened phytochemicals. Molecular docking and 100-ns molecular dynamics (MD) simulations revealed luteolin, isovitexin, and morin as top binders, forming stable hydrogen bonds and hydrophobic interactions with key catalytic residues (CYS215 and ARG221) of PTP1B. Structural dynamics analysis further revealed the stability and conformational flexibility of the flavonoid-PTP1B complexes, while Molecular Mechanics-Poisson-Boltzmann Surface Area (MM-PBSA) binding free energy calculations supported their strong and favorable binding affinities in a dynamic environment. Overall, these findings suggest that luteolin, isovitexin, and morin may serve as potent, non-covalent PTP1B inhibitors, offering mechanistic insight into the insulin-sensitizing potential of O. gratissimum and supporting its ethnopharmacological use in diabetes management. Further experimental validation is recommended to explore and confirm their therapeutic relevance.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}