MedChemComm最新文献

{"title":"Design and synthesis of novel 8-(azaindolyl)-benzoazepinones as potent and selective ROCK inhibitors†","authors":"Daniele Pala, David Clark, Christine Edwards, Elisa Pasqua, Laura Tigli, Barbara Pioselli, Piotr Malysa, Fabrizio Facchinetti, Fabio Rancati and Alessandro Accetta","doi":"10.1039/D4MD00313F","DOIUrl":"10.1039/D4MD00313F","url":null,"abstract":"<p >We report the characterization of potent and selective ROCK inhibitors identified through a core-hopping strategy. A virtual screening workflow, combining ligand- and structure-based methods, was applied on a known series of ROCK inhibitors bearing an acetamido-thiazole scaffold. The most promising replacement of the central core was represented by a benzoazepinone ring, which was selected as a starting point for a subsequent chemical exploration. The overall design approach exploited previous SARs available for congeneric series and crystallographic information to optimize the hinge-binding group as well as the terminal aromatic moiety interacting with the glycine-rich loop. The introduction of elongated and flexible charged groups led to compound <strong>15</strong>, which exhibited sub-nanomolar potencies in biochemical and cellular assays, as well as a remarkable selectivity over PKA. HDX studies not only supported the postulated binding mode of compound <strong>15</strong> but also confirmed the crucial role of specific ROCK peptide segments in driving ligand selectivity.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 11","pages":" 3862-3879"},"PeriodicalIF":3.597,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rational design of NT-PSMA heterobivalent probes for prostate cancer theranostics†","authors":"Santo Previti, Sacha Bodin, Emmanuelle Rémond, Delphine Vimont, Elif Hindié, Clément Morgat and Florine Cavelier","doi":"10.1039/D4MD00491D","DOIUrl":"10.1039/D4MD00491D","url":null,"abstract":"<p >Targeting the prostate-specific membrane antigen (PSMA) with radiopharmaceuticals for imaging and/or therapy has demonstrated significant advancement in the management of prostate cancer patients. However, PSMA targeting remains unsuccessful in prostate cancers with low expression of PSMA, which account for 15% of cases. The neurotensin receptor-1 (NTS<small>₁</small>) has been highlighted as a suitable oncotarget for imaging and therapy of PSMA-negative prostate cancer lesions. Therefore, heterobivalent probes targeting both PSMA and NTS<small>₁</small> could improve the prostate cancer management. Herein, we report the development of a branched hybrid probe (<strong>JMV 7489</strong>) designed to target PSMA and/or NTS<small>₁</small> bearing relevant pharmacophores and DOTA as the chelating agent. The new ligand was synthesized with a hybrid approach, which includes both syntheses in batch and in the solid phase. Saturation binding experiments were next performed on HT-29 and PC3-PIP cells to derive <em>K</em><small>_d</small> and <em>B</em><small>_max</small> values. On the PC3-PIP cells, [<small>⁶⁸</small>Ga]Ga-<strong>JMV 7489</strong> displayed good affinity towards PSMA (<em>K</em><small>_d</small> = 53 ± 17 nM; <em>B</em><small>_max</small> = 1393 ± 29 fmol/10<small>⁶</small> cells) in the same range as the corresponding reference monomer. A lower affinity value towards NTS<small>₁</small> was depicted (<em>K</em><small>_d</small> = 157 ± 71 nM; <em>B</em><small>_max</small> = 241 ± 42 fmol/10<small>⁶</small> cells on PC3-PIP cells; <em>K</em><small>_d</small> = 246 ± 1 nM; <em>B</em><small>_max</small> = 151 ± 44 fmol/10<small>⁶</small> cells on HT-29 cells) and, surprisingly, it was also the case for the corresponding monomer [<small>⁶⁸</small>Ga]Ga-<strong>JMV 7089</strong>. These results indicate that the DOTA macrocycle and the linker are critical elements to design heterobivalent probes targeting PSMA and NTS<small>₁</small> with high affinity towards NTS<small>₁</small>.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 12","pages":" 4153-4158"},"PeriodicalIF":3.597,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11451938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing of USFDA-approved drugs to identify leads for inhibition of acetylcholinesterase enzyme: a plausible utility as an anti-Alzheimer agent","authors":"Kapil Kumar Goel, Sandhya Chahal, Devendra Kumar, Shivani Jaiswal, Nidhi Nainwal, Rahul Singh, Shriya Mahajan, Pramod Rawat, Savita Yadav, Prachi Fartyal, Gazanfar Ahmad, Vibhu Jha and Ashish Ranjan Dwivedi","doi":"10.1039/D4MD00461B","DOIUrl":"10.1039/D4MD00461B","url":null,"abstract":"<p >In the quest to identify new anti-Alzheimer agents, we employed drug repositioning or drug repositioning techniques on approved USFDA small molecules. Herein, we report the structure-based virtual screening (SBVS) of 1880 USFDA-approved drugs. The <em>in silico</em>-based identification was followed by calculating Prime MMGB-SA binding energy and molecular dynamics simulation studies. The cumulative analysis led to identifying domperidone as an identified hit. Domperidone was further corroborated <em>in vitro</em> using anticholinesterase-based assessment, keeping donepezil as a positive control. The analysis revealed that the identified lead (domperidone) could induce an inhibitory effect on AChE in a dose-dependent manner with an IC<small>₅₀</small> of 3.67 μM as compared to donepezil, which exhibited an IC<small>₅₀</small> of 1.37 μM. However, as domperidone is known to have poor BBB permeability, we rationally proposed new analogues utilizing the principles of bioisosterism. The bioisostere-clubbed analogues were found to have better BBB permeability, affinity, and stability within the catalytic domain of AChE <em>via</em> molecular docking and dynamics studies. The proposed bioisosteres may be synthesized in the future. They may plausibly be explored for their implication in the developmental progress of new anti-Alzheimer agent achieved <em>via</em> repurposing techniques in future.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 12","pages":" 4138-4152"},"PeriodicalIF":3.597,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of selective LATS inhibitors via scaffold hopping: enhancing drug-likeness and kinase selectivity for potential applications in regenerative medicine†","authors":"Guldana Issabayeva, On-Yu Kang, Seong Yun Choi, Ji Young Hyun, Seong Jun Park, Hei-Cheul Jeung and Hwan Jung Lim","doi":"10.1039/D4MD00492B","DOIUrl":"10.1039/D4MD00492B","url":null,"abstract":"<p >Due to its essential roles in cell proliferation and apoptosis, the precise regulation of the Hippo pathway through LATS presents a viable biological target for developing new drugs for cancer and regenerative diseases. However, currently available probes for selective and highly drug-like inhibition of LATS require further improvement in terms of both activity, selectivity and drug-like properties. Through scaffold hopping aided by docking studies and AI-assisted prediction of metabolic stabilities, we successfully identified an advanced LATS inhibitor demonstrating potent kinase activity, exceptional selectivity against other kinases, and superior oral pharmacokinetic profiles.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 12","pages":" 4080-4089"},"PeriodicalIF":3.597,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11428031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142353065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the therapeutic potential of genetically engineered probiotic Zbiotics (ZB183) for non-alcoholic steatohepatitis (NASH) management via modulation of the cGAS-STING pathway†","authors":"Maha Saad, Walaa Ibrahim, Amany Helmy Hasanin, Aya Magdy Elyamany and Marwa Matboli","doi":"10.1039/D4MD00477A","DOIUrl":"10.1039/D4MD00477A","url":null,"abstract":"<p >NAFLD/NASH has emerged as a global health concern with no FDA-approved treatment, necessitating the exploration of novel therapeutic elements for NASH. Probiotics are known as an important adjunct therapy in NASH. Zbiotics (ZB183) is the first commercially available genetically engineered probiotic. Herein, we aimed to evaluate the potential therapeutic effects of Zbiotics administration on NASH management by modulating the cGAS-STING-signaling pathway-related RNA network. <em>In silico</em> data analysis was performed and three DEGs (MAPK3/EDN1/TNF) were selected with their epigenetic modulators (miR-6888-5p miRNA, and lncRNA RABGAP1L-DT-206). The experimental design included NASH induction with an HSHF diet in Wistar rats and Zbiotics administration in NASH rats in comparison to statin treatment. Liver functions and lipid profile were assessed. Additionally, the expression levels of the constructed molecular network were assessed using RT-PCR. Moreover, the Zbiotics effects in NASH were further validated with histopathological examination of liver and colon samples. Also, immunohistochemistry staining of hepatic TNF-α and colonic occludin was assessed. Oral administration of Zbiotics for four weeks downregulated the expression of the cGAS-STING-related network (MAPK3/EDN1/TNF/miR-6888-5p miRNA/lncRNA RABGAP1L-DT-206) in NASH models. Zbiotics also ameliorated hepatic inflammation and steatosis, as evidenced by a notable improvement in NAS score and decreased hepatic TNF-α levels. Furthermore, Zbiotics exhibited favorable effects on colon health, including increased crypt length, reduced inflammatory cell infiltration, and restoration of colonic mucosa occludin expression. In conclusion, our findings suggest that Zbiotics has potential therapeutic effects on NASH <em>via</em> modulating the gut–liver axis and the cGAS-STING signaling pathway.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 11","pages":" 3817-3836"},"PeriodicalIF":3.597,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DC-derived whole cell cytokine nano-regulator for remodelling extracellular matrix and synergizing tumor immunotherapy†","authors":"Jingsong Lu, Ying Li, Xiaohan Gao, Sumei Chen, Zeping Jin, Xiaoxiao Guo, Wensheng Xie, Zhenhu Guo, Yen Wei and Lingyun Zhao","doi":"10.1039/D4MD00496E","DOIUrl":"10.1039/D4MD00496E","url":null,"abstract":"<p >A smart dendritic cell (DC)-derived whole cell cytokine (DWC) nano-regulator of TCPs was developed for tumor cytokine-immunotherapy. The DWCs were purified from activated DC-cultured media and applied as a nano-dosage form. It was found that TCPs could remodel extracellular matrices <em>via</em> the elimination of fibronectin and type I collagen (Col-I) in tumor tissues, as well as the inhibition of α-SMA expression in cancer associated fibroblasts (CAFs). Furthermore, after local TCP treatment, significant tumor inhibition could be achieved combined with radiotherapy.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 12","pages":" 4090-4099"},"PeriodicalIF":3.597,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142353062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Replacement of nitro function by free boronic acid in non-steroidal anti-androgens†","authors":"Petr Šlechta, Roman Viták, Pavel Bárta, Kateřina Koucká, Monika Berková, Diana Žďárová, Andrea Petríková, Jiří Kuneš, Vladimír Kubíček, Martin Doležal, Radek Kučera and Marta Kučerová-Chlupáčová","doi":"10.1039/D4MD00343H","DOIUrl":"10.1039/D4MD00343H","url":null,"abstract":"<p >A new series of potential flutamide-like antiandrogens has been designed and synthesized to treat prostate cancer. This new series results from our research, which has been aimed at discovering new compounds that can be used for androgen deprivation treatment. The antiandrogens were designed and synthesized by varying the acyl part, linker, and substitution of the benzene ring in the 4-nitro-3-trifluoromethylanilide scaffold of non-steroidal androgens. In addition, the characteristic feature of the nitro group was replaced by a boronic acid functionality. Compound <strong>9a</strong> was found to be more effective against LAPC-4 than the standard antiandrogens flutamide, hydroxyflutamide, and bicalutamide. Moreover, it exhibited lower toxicity against the non-cancerous cell line HK-2. The initial <em>in silico</em> study did not show evidence of covalent bonding to the androgen receptor, which was confirmed by an NMR binding experiment with arginine methyl ester. The structure–activity relationships discovered in this study could provide directions for further research on non-steroidal antiandrogens.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 12","pages":" 4018-4038"},"PeriodicalIF":3.597,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11428147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142353067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strong in vitro anticancer activity of copper(ii) and zinc(ii) complexes containing naturally occurring lapachol: cellular effects in ovarian A2780 cells†‡","authors":"Sara Stocchetti, Ján Vančo, Jan Belza, Zdeněk Dvořák and Zdeněk Trávníček","doi":"10.1039/D4MD00543K","DOIUrl":"10.1039/D4MD00543K","url":null,"abstract":"<p >Copper(<small>II</small>) and zinc(<small>II</small>) complexes with lapachol (HLap) of the composition [M(Lap)<small>₂</small>(N–N)] and [Cu(Lap)(H<small>₂</small>O)(terpy)]NO<small>₃</small> (<strong>4</strong>), where M = Cu (<strong>1–3</strong>) or Zn (for <strong>5–7</strong>), and N–N stands for bathophenanthroline (<strong>1</strong> and <strong>5</strong>), 5-methyl-1,10-phenanthroline (<strong>2</strong> and <strong>6</strong>), 2,2′-bipyridine (<strong>3</strong>), 2,2′;6′,2′′-terpyridine (terpy, <strong>4</strong>) and 1,10-phenanthroline (<strong>7</strong>), were synthesised and characterised. Complexes <strong>1–5</strong> revealed strong <em>in vitro</em> antiproliferative effects against A2780, A2780R, MCF-7, PC-3, A549 and HOS human cancer lines and MRC-5 normal cells, with IC<small>₅₀</small> values above 0.5 μM, and reasonable selectivity index (SI), with SI &gt; 3.8 for IC<small>₅₀</small>(MRC-5)/IC<small>₅₀</small>(A2780). Considerable time-dependent cytotoxicity in A2780 cells was observed for complexes <strong>6</strong> and <strong>7</strong>, with IC<small>₅₀</small> &gt; 50 μM (24 h) to <em>ca.</em> 4 μM (48 h). Cellular effects of complexes <strong>1</strong>, <strong>5</strong> and <strong>7</strong> in A2780 cells were investigated by flow cytometry revealing that the most cytotoxic complexes (<strong>1</strong> and <strong>5</strong>) significantly perturbed the mitochondrial membrane potential and the interaction with mitochondrial metabolism followed by the triggering of the intracellular pathway of apoptosis.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 12","pages":" 4180-4192"},"PeriodicalIF":3.597,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11451940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rationally modified SNX-class Hsp90 inhibitors disrupt extracellular fibronectin assembly without intracellular Hsp90 activity†","authors":"Gciniwe S. Mathenjwa, Abir Chakraborty, Abantika Chakraborty, Ronel Muller, Mathew P. Akerman, Moira L. Bode, Adrienne L. Edkins and Clinton G. L. Veale","doi":"10.1039/D4MD00501E","DOIUrl":"10.1039/D4MD00501E","url":null,"abstract":"<p >Despite Hsp90's well documented promise as a target for developing cancer chemotherapeutics, its inhibitors have struggled to progress through clinical trials. This is, in part, attributed to the cytoprotective compensatory heat shock response (HSR) stimulated through intracellular Hsp90 inhibition. Beyond its intracellular role, secreted extracellular Hsp90 (eHsp90) interacts with numerous pro-oncogenic extracellular clients. This includes fibronectin, which in the tumour microenvironment enhances cell invasiveness and metastasis. Through the rational modification of known Hsp90 inhibitors (SNX2112 and SNX25a) we developed four Hsp90 inhibitory compounds, whose alterations restricted their interaction with intracellular Hsp90 and did not stimulate the HSR. Two of the modified cohort (compounds <strong>10</strong> and <strong>11</strong>) were able to disrupt the assembly of the extracellular fibronectin network at non-cytotoxic concentrations, and thus represent promising new tool compounds for studying the druggability of eHsp90 as a target for inhibition of tumour invasiveness and metastasis.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 10","pages":" 3609-3615"},"PeriodicalIF":3.597,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/md/d4md00501e?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and synthesis of novel multi-target tetrabromophthalimides as CBS and Topo-II inhibitors and DNA intercalators†","authors":"Marwa Abdel-Motaal, Dalal Ali Aldakhili, Ayman B. Farag, Ayman Abo Elmaaty, Marwa Sharaky, Nadia A. Mohamed, Saad Shaaban, Abdullah Yahya Abdullah Alzahrani and Ahmed A. Al-Karmalawy","doi":"10.1039/D4MD00585F","DOIUrl":"10.1039/D4MD00585F","url":null,"abstract":"<p >Microtubules are highly dynamic structures and constitute a crucial component of the cellular cytoskeleton. Besides, topoisomerases (Topo) play a fundamental role in maintaining the appropriate structure and organization of DNA. On the other hand, dual mechanism drug candidates for cancer treatment primarily aim to enhance the efficacy of cancer treatment and potentially overcome drug resistance. Hence, this work was tailored to design and synthesize new multi-target tetrabromophthalimide derivatives (<strong>2a–2k</strong>) that are capable of inhibiting the colchicine binding site (CBS) and topoisomerase II (Topo-II). The conducted <em>in vitro</em> studies showed that compound <strong>2f</strong> showed the lowest IC<small>₅₀</small> value (6.7 μg mL<small>⁻¹</small>) against the MDA-MB-468 cancer cell line. Additionally, compound <strong>2f</strong> prompted upregulation of pro-apoptotic markers (caspases 3, 7, 8, and 9, Bax and p53). Moreover, some anti-apoptotic proteins (MMP2, MMP9, and BCL-2) were downregulated by compound <strong>2f</strong> treatment. Besides, the colchicine binding assay showed that compounds <strong>2f</strong> and <strong>2k</strong> displayed promising inhibitory potential with IC<small>₅₀</small> values of 1.92 and 4.84 μg mL<small>⁻¹</small>, respectively, in comparison with colchicine (1.55 μg mL<small>⁻¹</small>). Furthermore, the Topo-II inhibition assay displayed the prominent inhibitory potential of compound <strong>2f</strong> with an IC<small>₅₀</small> value of 15.75 μg mL<small>⁻¹</small>, surpassing the IC<small>₅₀</small> of etoposide (20.82 μg mL<small>⁻¹</small>). Cell cycle analysis revealed that compound <strong>2f</strong> induced cell cycle arrest at both the G0–G1 and G2–M phases. The new candidates were docked against both the CBS (PDB ID: 5XIW) and Topo-II (PDB ID: 5CDP) targets to investigate their binding interactions and affinities as well. Accordingly, the synthesized compounds could serve as promising multi-target anticancer candidates with eligible apoptotic activity.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 11","pages":" 3800-3816"},"PeriodicalIF":3.597,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}