MedChemComm最新文献

{"title":"Nitroreductase-activatable photosensitizers for selective antimicrobial photodynamic therapy†","authors":"Matthew T. Tung, Tianyi Ma, Ivonne Rebeca Lopez-Miranda, Joshua N. Milstein and Andrew A. Beharry","doi":"10.1039/D4MD00890A","DOIUrl":"10.1039/D4MD00890A","url":null,"abstract":"<p >Antimicrobial photodynamic therapy (aPDT) utilizes light, oxygen and a photosensitizer (PS) to enact cell death <em>via</em> the production of reactive oxygen species (ROS). This mechanism of cell death, <em>via</em> oxidative stress, has allowed aPDT to be effective against antibiotic-resistant bacterial strains, with the development of resistance being minimal as no specific pathway is targeted. While promising, as ambient light can activate PSs, damage to mammalian tissues can occur, leading to drug-induced photosensitivity. To mitigate this, we developed a nitroreductase-activatable PS containing a quenching group that inhibits fluorescence and ROS. Upon reaction with nitroreductase, the quenching group can be liberated, restoring fluorescence and ROS production. As nitroreductase is not present in healthy mammalian tissues but expressed in many bacteria, photosensitivity of mammalian cells can be reduced. Herein, the synthesis and photophysical characterization of the nitroreductase-activatable PS, <strong>DB2</strong>, is described. <strong>DB2</strong> was quenched compared to the free PS, <strong>DB1</strong>, and activation both <em>in vitro</em> by purified nitroreductase and in the gram-positive bacterial strain, <em>Bacillus subtilis</em>, was confirmed by fluorescence recovery. Cell viability studies in <em>B. subtilis</em> showed low dark toxicity and an IC<small>₅₀</small> of 0.16 μM under 10-minute irradiation (530 nm, 42 mW cm<small>⁻²</small>). Minimal toxicity was observed under the same conditions in mammalian cell cultures demonstrating the potential of <strong>DB2</strong> to mitigate photosensitivity and provide a promising approach for aPDT.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 5","pages":" 2133-2141"},"PeriodicalIF":3.597,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586543","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":"Towards catalytic fluoroquinolones: from metal-catalyzed to metal-free DNA cleavage†","authors":"Moshe N. Goldmeier, Alina Khononov, Tomasz Pieńko, Valery Belakhov, Feng-Chun Yen, Limor Baruch, Marcelle Machluf and Timor Baasov","doi":"10.1039/D4MD00984C","DOIUrl":"10.1039/D4MD00984C","url":null,"abstract":"<p >A library of eight new fluoroquinolone–nuclease conjugates containing a guanidinoethyl or aminoethyl auxiliary pendant on the 1,4,7-triazacyclononane (TACN) moiety was designed and synthesized to investigate their potential as catalytic antibiotics. The Cu(<small>II</small>) complexes of the designer structures showed significant <em>in vitro</em> hydrolytic and oxidative DNA cleavage activity and good antibacterial activity against both Gram-negative and Gram-positive bacteria. The observed activity of all the Cu(<small>II</small>)–TACN–ciprofloxacin complexes was strongly inhibited in the presence of Cu(<small>II</small>)-chelating agents, thereby demonstrating “vulnerability” under physiological conditions. However, selected TACN–ciprofloxacin conjugates in their metal-free form efficiently cleaved plasmid DNA under physiological conditions. The lead compound <strong>1</strong> showed good DNase activity which was retained in the presence of strong metal chelators and exhibited excellent antibacterial activity against both Gram-negative and Gram-positive bacteria. Density functional theory calculations combined with quantum mechanics/molecular mechanics simulations suggest a general base–general acid mechanism for the hydrolytic DNA cleavage mechanism by compound <strong>1</strong>.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 6","pages":" 2576-2591"},"PeriodicalIF":3.597,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754375","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":"Development of p300-targeting degraders with enhanced selectivity and onset of degradation†","authors":"Graham P. Marsh, Mark S. Cooper, Sean Goggins, Stephen J. Reynolds, Dean F. Wheeler, Joel O. Cresser-Brown, Robert E. Arnold, Emily G. Babcock, Gareth Hughes, Darko Bosnakovski, Michael Kyba, Samuel Ojeda, Drew A. Harrison, Christopher J. Ott and Hannah J. Maple","doi":"10.1039/D4MD00969J","DOIUrl":"10.1039/D4MD00969J","url":null,"abstract":"<p >p300 and CBP are paralogous epigenetic regulators that are considered promising therapeutic targets for cancer treatment. Small molecule p300/CBP inhibitors have so far been unable to differentiate between these closely related proteins, yet selectivity is desirable in order to probe their distinct cellular functions. Additionally, in multiple cancers, loss-of-function <em>CREBBP</em> mutations set up a paralog dependent synthetic lethality with p300, that could be exploited with a selective therapeutic agent. To address this, we developed p300-targeting heterobifunctional degraders that recruit p300 through its HAT domain using the potent spiro-hydantoin-based inhibitor, iP300w. Lead degrader, BT-O2C, demonstrates improved selectivity and a faster onset of action compared to a recently disclosed A 485-based degrader in HAP1 cells and is cytotoxic in CIC::DUX4 sarcoma (CDS) cell lines (IC<small>₅₀</small> = 152–221 nM), significantly reducing expression of CDS target genes (ETV1, ETV4, ETV5). Taken together, our results demonstrate that BT-O2C represents a useful tool degrader for further exploration of p300 degradation as a therapeutic strategy.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 5","pages":" 2049-2060"},"PeriodicalIF":3.597,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650271","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":"Betaine–salicylic acid cocrystal for enhanced skincare and acne treatment†","authors":"Zhenyuan Wang, Mi Wang, Qingsheng Tao, Yufei Li, Hao Wang, Mei Zhang, Xueli Liu and Jiaheng Zhang","doi":"10.1039/D5MD00001G","DOIUrl":"10.1039/D5MD00001G","url":null,"abstract":"<p >Salicylic acid (SA) is a natural lipophilic active ingredient commonly used in cosmetics and skin disease treatments, offering benefits such as exfoliation, anti-inflammation effects, antibacterial properties, oil control, and acne alleviation. However, its poor water solubility, low bioavailability, and potential side effects, such as allergies, irritation, and dryness, hinder its widespread application. In this study, we prepared a betaine–salicylic acid (BeSA) cocrystal and systematically characterized its crystal structure, biological activity, and clinical efficacy. The results showed that BeSA has significantly lower irritancy and cytotoxicity than SA, but exhibits excellent anti-inflammatory and antioxidant properties as well as high moisturizing and anti-acne efficacy, making it a potential alternative to SA. Further, quantum chemical calculations and molecular docking simulations were conducted to investigate the intrinsic mechanisms underlying the excellent bioactivity of BeSA cocrystals. This study introduces an innovative solution for safer and more effective skincare formulations based on SA and offers theoretical guidance regarding material engineering and further material optimization, which has crucial implications for both industry and academia.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 4","pages":" 1705-1714"},"PeriodicalIF":3.597,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543024","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":"Application of a bivalent “click” approach to target tyrosyl-DNA phosphodiesterase 1 (TDP1)†","authors":"Xue Zhi Zhao, Wenjie Wang, Md Rasel Al Mahmud, Keli Agama, Yves Pommier and Terrence R. Burke","doi":"10.1039/D4MD00824C","DOIUrl":"10.1039/D4MD00824C","url":null,"abstract":"<p >Although inhibiting the DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1) synergizes with topoisomerase type I (TOP1) inhibitors in anticancer therapy, development of TDP1 inhibitors has been highly challenging. This may be due to the open and shallow nature of the TDP1 catalytic site and the necessity of competing with a large and highly extended substrate. The toolbox available to chemical biologists for studying TDP1 could be significantly enhanced by introducing the ability to selectively eliminate TDP1 using protein degraders. Our current work starts from phenyl imidazopyridine-based TDP1 inhibitors previously developed from small molecule microarrays (SMMs). Using crystal structures of lead inhibitors bound to TDP1, we designed and synthesized a series of bivalent proteolysis-targeting chimeras (PROTACs). The focus of our current work is to explore synthetic approaches that permit installation of E3 ligase-targeting functionality, while retaining the TDP1 binding. We employed copper-catalyzed azide–alkyne cycloaddition (CuAAC) “click” reactions to assemble PROTAC constituents with 1,2,3-triazole-containing linkers. With the addition of the relatively large parts of the linkers and E3-targeting moieties, we retained the ability to inhibit TDP1. The successful development of TDP1-directed PROTACS would yield a new therapeutic class that could potentially enhance the efficacy and selectivity of TOP1 inhibitors including those used as payloads in antibody drug conjugates (ADCs).</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 5","pages":" 1969-1985"},"PeriodicalIF":3.597,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483535","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, synthesis and biological evaluation of 2H-[1,4]oxazino-[2,3-f]quinazolin derivatives as potential EGFR inhibitors for non-small cell lung cancer†","authors":"Linchang Huang, Ying Zhang, Peng Liu, Lihong Lan, Lifang Yang, Bo Wang, Tingting Cao, Liming Hu and Xuemei Qin","doi":"10.1039/D4MD01016G","DOIUrl":"10.1039/D4MD01016G","url":null,"abstract":"<p >Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have emerged as the first-line treatment for patients with EGFR-mutant non-small cell lung cancer (NSCLC). A series of 2<em>H</em>-[1,4]oxazino[2,3-<em>f</em>]quinazolin derivatives were synthesized and evaluated as irreversible EGFR-TKIs for the treatment of NSCLC. Most of the synthesized compounds demonstrated strong inhibitory activity against the EGFR kinase and the tested cancer cells. Notably, compound <strong>4a</strong> exhibited considerable inhibitory effects against the EGFR kinase and the EGFR<small>^L858R/T790M</small> mutant NCI-H1975 cancer cells. Compound <strong>4a</strong> was found to suppress cell proliferation, colony formation, cell invasion, and migration, while also inducing G0/G1 phase arrest of the cell cycle in NCI-H1975 cells. Compound <strong>4a</strong> was docked into the active pocket of the EGFR mutant to ascertain the probable binding conformation. Overall, compound <strong>4a</strong> was identified as a promising irreversible EGFR-TKI for the treatment of NSCLC.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 5","pages":" 2231-2239"},"PeriodicalIF":3.597,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650268","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":"Design and synthesis of 2-phenyl-1H-benzo[d]imidazole derivatives as 17β-HSD10 inhibitors for the treatment of Alzheimer's disease†","authors":"Xiaohan Liu, Bin Zhou, Yan Chen, Jinyuan Lin, Chenwen Shao, Liuzeng Chen, Banfeng Ruan, Xingxing Zhang and Yong Qian","doi":"10.1039/D4MD00861H","DOIUrl":"10.1039/D4MD00861H","url":null,"abstract":"<p >It has been reported that 17β-HSD10 plays a key role in Alzheimer's disease. Here, a total of 44 2-phenyl-1<em>H</em>-benzo[<em>d</em>]imidazole derivatives were designed and synthesized as novel 17β-HSD10 inhibitors based on rational design and SAR studies. Among them, compound <strong>33</strong> (<em>N</em>-(4-(1,4,6-trimethyl-1<em>H</em>-benzo[<em>d</em>] imidazol-2-yl)phenyl)cyclohexanecarboxamide) showed high inhibitory efficacy (17β-HSD10 IC<small>₅₀</small> = 1.65 ± 0.55 μM) and low toxicity (HepaRG IC<small>₅₀</small> &gt;100 μM). The Morris water maze experiment revealed that compound <strong>33</strong> could alleviate cognitive impairment induced by scopolamine in mice. This study facilitates the further development of more potent 17β-HSD10 inhibitors for the treatment of Alzheimer's disease.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 6","pages":" 2467-2486"},"PeriodicalIF":3.597,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754350","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":"Pyrazolo[3,4-d]pyrimidine-based neplanocin analogues identified as potential de novo pharmacophores for dual-target HBV inhibition†","authors":"Mohan Kasula, Masaaki Toyama, Ramakrishnamraju Samunuri, Ashok Kumar Jha, Mika Okamoto, Masanori Baba and Ashoke Sharon","doi":"10.1039/D4MD00932K","DOIUrl":"10.1039/D4MD00932K","url":null,"abstract":"<p >The discovery of selective and potent inhibitors through <em>de novo</em> pathways is essential to combat drug resistance in chronic hepatitis B (CHB) infections. Recent studies have highlighted that neplanocin A (NepA) derivatives are biologically selective inhibitors of the hepatitis B virus (HBV). In this study, we designed, synthesized, and evaluated various pyrazolo[3,4-<em>d</em>]pyrimidine-based NepA analogues (<strong>4a–h</strong>) for their anti-HBV activity. Notably, analogue <strong>4g</strong> demonstrated significant activity against HBV replication, with EC<small>₅₀</small> (HBV DNA) = 0.96 μM, CC<small>₅₀</small> &gt; 100 μM and EC<small>₅₀</small> (HBsAg) = 0.82 μM, showing selective inhibition of HBsAg secretion. The SAR analysis concluded that replacing the polar 4-NH<small>₂</small> group with –CH<small>₃</small> also acted as a weak H-bonding donor, and the presence of 3-iodo was found to be desirable for the activity/toxicity profile. The nucleoside analogues exhibited a distinct mechanism of action compared to existing nucleoside analogues for the selective inhibition of HBsAg secretion. Based on these findings, compound <strong>4g</strong> represents a promising lead molecule for the development of new anti-HBV agents with unique mechanisms of action.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 4","pages":" 1740-1745"},"PeriodicalIF":3.597,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483611","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":"Transmembrane protease serine 2 (TMPRSS2) inhibitors screened from an Fv-antibody library for preventing SARS-CoV-2 infection","authors":"Jaeyong Jung, Jeong Soo Sung, Soonil Kwon, Hyung Eun Bae, Min-Jung Kang, Joachim Jose, Misu Lee and Jae-Chul Pyun","doi":"10.1039/D4MD00992D","DOIUrl":"10.1039/D4MD00992D","url":null,"abstract":"<p >Fv-antibodies targeting the transmembrane protease serine 2 (TMPRSS2) were screened from an Fv-antibody library for inhibiting SARS-CoV-2 infection. Fv-antibodies were derived from the variable region of heavy-chain immunoglobulin G (IgG), which consisted of three complementarity-determining regions (CDRs) and frame regions (FRs). The Fv-antibody library was prepared through site-directed mutagenesis of CDR3 region. The proteolytic cleavage site (S2′ site) of TMPRSS2 on the spike protein (SP) of SARS-CoV-2 was used as a screening probe for the library. Two Fv-antibodies were screened and subsequently expressed as soluble recombinant proteins. The binding affinities of the expressed Fv-antibodies were estimated using a surface plasmon resonance (SPR) biosensor. The two expressed Fv-antibodies specifically bound to the active site of TMPRSS2 which interacts with S2′ site in the proprotein convertase (PPC) region. The neutralizing activities of the two expressed Fv-antibodies were demonstrated using a cell-based infection assay with pseudo-viruses that expressed the SP of four types of SARS-CoV-2 variants: Wu-1 (D614), Delta (B.1.617.2), Omicron (BA.2), and Omicron (BA.4/5). Additionally, a docking simulation was performed to analyze the interaction between the screened Fv-antibodies and the active sites of TMPRSS2.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 4","pages":" 1758-1765"},"PeriodicalIF":3.597,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483624","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":"Donepezil-based rational design of N-substituted quinazolinthioacetamide candidates as potential acetylcholine esterase inhibitors for the treatment of Alzheimer's disease: in vitro and in vivo studies†","authors":"Ahmed A. Al-Karmalawy, Ahmed F. Mohamed, Heba Nasr Shalaby, Ayman Abo Elmaaty, Riham A. El-Shiekh, Mohamed A. Zeidan, Radwan Alnajjar, Abdullah Yahya Abdullah Alzahrani, Mohammed H. AL Mughram, Moataz A. Shaldam and Haytham O. Tawfik","doi":"10.1039/D4MD00778F","DOIUrl":"10.1039/D4MD00778F","url":null,"abstract":"<p >Alzheimer's disease (AD) stands as one of the most outstanding progressive neurodegenerative disorders. Obviously, acetylcholine esterase (AChE) is the primary enzyme responsible for breaking down acetylcholine (ACh) with a much more prominent effect than butyrylcholine esterase (BuChE). Hence, novel quinazoline derivatives (<strong>3a–p</strong>) were designed and synthesized as AChE inhibitors for AD treatment. The newly synthesized quinazoline derivatives (<strong>3a–p</strong>) were pursued for their inhibitory potential towards both AChE and BuChE. Notably, compound <strong>3e</strong> displayed the highest inhibitory potential towards AChE (IC<small>₅₀</small> = 9.26 nM) surpassing donepezil (IC<small>₅₀</small> = 16.43 nM). On the other side, compound <strong>3e</strong> effectively negated the decline in memory acquisition and retention instigated by ICV administration of streptozotocin (STZ) in mice, an effect that was comparable to that produced by donepezil. Moreover, compound <strong>3e</strong>, reduced BACE1 by 51.08% (<em>p</em> &lt; 0.0001), Aβ42 by 52.47% (<em>p</em> &lt; 0.0001), and p(Ser199)-tau by 69.16% (<em>p</em> &lt; 0.0001) compared to STZ mice. Such effects were similar to those of donepezil which reduced all 3 parameters by 57.53%, 58.5%, and 66.78%, respectively, compared to STZ mice. Furthermore, molecular docking studies showed that the superimposition view clarified the similar binding mode of both <strong>3e</strong> and the co-crystallized donepezil at the AChE binding pocket. Moreover, the docked complexes (<strong>3e</strong>-AChE and <strong>3e</strong>-BuChE) were further subject to molecular dynamics simulations for 100 ns. In addition, eligible pharmacokinetic profiles as well as feasible BBB penetration were anticipated for compound <strong>3e</strong> using ADME and BBB permeation prediction studies. Accordingly, the synthesized compounds, in particular compound <strong>3e</strong>, can be treated as promising lead compounds for AD treatment with future further optimization.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 5","pages":" 2078-2097"},"PeriodicalIF":3.597,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543021","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}