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Structural Aspects of Mycobacterium tuberculosis DNA Gyrase Targeted by Novel Bacterial Topoisomerase Inhibitors.
IF 3.5 3区 医学
ACS Medicinal Chemistry Letters Pub Date : 2024-11-22 eCollection Date: 2024-12-12 DOI: 10.1021/acsmedchemlett.4c00447
Maja Kokot, Martina Hrast Rambaher, Lipeng Feng, Lesley A Mitchenall, David M Lawson, Anthony Maxwell, Tanya Parish, Nikola Minovski, Marko Anderluh
{"title":"Structural Aspects of <i>Mycobacterium tuberculosis</i> DNA Gyrase Targeted by Novel Bacterial Topoisomerase Inhibitors.","authors":"Maja Kokot, Martina Hrast Rambaher, Lipeng Feng, Lesley A Mitchenall, David M Lawson, Anthony Maxwell, Tanya Parish, Nikola Minovski, Marko Anderluh","doi":"10.1021/acsmedchemlett.4c00447","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.4c00447","url":null,"abstract":"<p><p>In this Letter, we present a small series of novel bacterial topoisomerase inhibitors (NTBIs) that exhibit both potent inhibition of <i>Mycobacterium tuberculosis</i> DNA gyrase and potent antimycobacterial activity. The disclosed crystal structure of <i>M. tuberculosis</i> DNA gyrase in complex with DNA and compound <b>5</b> from this NBTI series reveals the binding mode of an NBTI in the GyrA binding pocket and confirms the presence and importance of halogen bonding for the excellent on-target potency. In addition, we have shown that compound <b>5</b> is a promising <i>M. tuberculosis</i> DNA gyrase inhibitor, with an IC<sub>50</sub> for <i>M. tuberculosis</i> gyrase of 0.096 μM, and it has potent activity against <i>M. tuberculosis</i>, with an IC<sub>50</sub> of 0.165 μM.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"15 12","pages":"2164-2170"},"PeriodicalIF":3.5,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Structural Aspects of Mycobacterium tuberculosis DNA Gyrase Targeted by Novel Bacterial Topoisomerase Inhibitors
IF 3.5 3区 医学
ACS Medicinal Chemistry Letters Pub Date : 2024-11-22 DOI: 10.1021/acsmedchemlett.4c0044710.1021/acsmedchemlett.4c00447
Maja Kokot, Martina Hrast Rambaher, Lipeng Feng, Lesley A Mitchenall, David M Lawson, Anthony Maxwell, Tanya Parish, Nikola Minovski* and Marko Anderluh*, 
{"title":"Structural Aspects of Mycobacterium tuberculosis DNA Gyrase Targeted by Novel Bacterial Topoisomerase Inhibitors","authors":"Maja Kokot,&nbsp;Martina Hrast Rambaher,&nbsp;Lipeng Feng,&nbsp;Lesley A Mitchenall,&nbsp;David M Lawson,&nbsp;Anthony Maxwell,&nbsp;Tanya Parish,&nbsp;Nikola Minovski* and Marko Anderluh*,&nbsp;","doi":"10.1021/acsmedchemlett.4c0044710.1021/acsmedchemlett.4c00447","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.4c00447https://doi.org/10.1021/acsmedchemlett.4c00447","url":null,"abstract":"<p >In this Letter, we present a small series of novel bacterial topoisomerase inhibitors (NTBIs) that exhibit both potent inhibition of <i>Mycobacterium tuberculosis</i> DNA gyrase and potent antimycobacterial activity. The disclosed crystal structure of <i>M. tuberculosis</i> DNA gyrase in complex with DNA and compound <b>5</b> from this NBTI series reveals the binding mode of an NBTI in the GyrA binding pocket and confirms the presence and importance of halogen bonding for the excellent on-target potency. In addition, we have shown that compound <b>5</b> is a promising <i>M. tuberculosis</i> DNA gyrase inhibitor, with an IC<sub>50</sub> for <i>M. tuberculosis</i> gyrase of 0.096 μM, and it has potent activity against <i>M. tuberculosis</i>, with an IC<sub>50</sub> of 0.165 μM.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"15 12","pages":"2164–2170 2164–2170"},"PeriodicalIF":3.5,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acsmedchemlett.4c00447","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142850965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Potential Therapeutic Benefit of the Selective Inhibitors of Casitas B Cell Lymphoma-b (CBL-B) in Cancer Immunotherapy
IF 3.5 3区 医学
ACS Medicinal Chemistry Letters Pub Date : 2024-11-19 DOI: 10.1021/acsmedchemlett.4c0053310.1021/acsmedchemlett.4c00533
Ahmed F. Abdel-Magid*, 
{"title":"Potential Therapeutic Benefit of the Selective Inhibitors of Casitas B Cell Lymphoma-b (CBL-B) in Cancer Immunotherapy","authors":"Ahmed F. Abdel-Magid*,&nbsp;","doi":"10.1021/acsmedchemlett.4c0053310.1021/acsmedchemlett.4c00533","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.4c00533https://doi.org/10.1021/acsmedchemlett.4c00533","url":null,"abstract":"<p >The invention in this patent application relates to 1,6-dihydro-7<i>H</i>-pyrrolo[2,3-<i>c</i>]pyridin-7-one derivatives represented generally by formula 1. These compounds are inhibitors of the E3 ubiquitin ligase, casitas B-lineage lymphoma proto-oncogene-b (CBL-B), and may be useful for the treatment of immunosuppression-associated diseases and disorders such as cancer and chronic viral infections.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"15 12","pages":"2085–2087 2085–2087"},"PeriodicalIF":3.5,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142850791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Potential Therapeutic Benefit of the Selective Inhibitors of Casitas B Cell Lymphoma-b (CBL-B) in Cancer Immunotherapy.
IF 3.5 3区 医学
ACS Medicinal Chemistry Letters Pub Date : 2024-11-19 eCollection Date: 2024-12-12 DOI: 10.1021/acsmedchemlett.4c00533
Ahmed F Abdel-Magid
{"title":"Potential Therapeutic Benefit of the Selective Inhibitors of Casitas B Cell Lymphoma-b (CBL-B) in Cancer Immunotherapy.","authors":"Ahmed F Abdel-Magid","doi":"10.1021/acsmedchemlett.4c00533","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.4c00533","url":null,"abstract":"<p><p>The invention in this patent application relates to 1,6-dihydro-7<i>H</i>-pyrrolo[2,3-<i>c</i>]pyridin-7-one derivatives represented generally by formula 1. These compounds are inhibitors of the E3 ubiquitin ligase, casitas B-lineage lymphoma proto-oncogene-b (CBL-B), and may be useful for the treatment of immunosuppression-associated diseases and disorders such as cancer and chronic viral infections.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"15 12","pages":"2085-2087"},"PeriodicalIF":3.5,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Inhibition of the Binding of Interleukin 17A with Interleukin 17A Receptor as a Treatment for Immune System and Inflammation Disorders, Cancer, and Neurodegenerative Diseases.
IF 3.5 3区 医学
ACS Medicinal Chemistry Letters Pub Date : 2024-11-19 eCollection Date: 2024-12-12 DOI: 10.1021/acsmedchemlett.4c00532
Ahmed F Abdel-Magid
{"title":"Inhibition of the Binding of Interleukin 17A with Interleukin 17A Receptor as a Treatment for Immune System and Inflammation Disorders, Cancer, and Neurodegenerative Diseases.","authors":"Ahmed F Abdel-Magid","doi":"10.1021/acsmedchemlett.4c00532","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.4c00532","url":null,"abstract":"<p><p>The invention in this patent application relates to <i>N</i>-(2-amino-2-oxoethyl)heteroarylcarboxamide derivatives, represented herein generally by formula 1. These compounds are inhibitors of the binding of interleukin 17A (IL-17A) with its receptor IL-17RA and may potentially be used for the treatment of diseases or disorders associated with IL-17A activity, which include psoriasis, ankylosing spondylitis, psoriatic arthritis and rheumatoid arthritis, cancer, and neurodegenerative disorders.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"15 12","pages":"2088-2090"},"PeriodicalIF":3.5,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Inhibition of the Binding of Interleukin 17A with Interleukin 17A Receptor as a Treatment for Immune System and Inflammation Disorders, Cancer, and Neurodegenerative Diseases
IF 3.5 3区 医学
ACS Medicinal Chemistry Letters Pub Date : 2024-11-19 DOI: 10.1021/acsmedchemlett.4c0053210.1021/acsmedchemlett.4c00532
Ahmed F. Abdel-Magid*, 
{"title":"Inhibition of the Binding of Interleukin 17A with Interleukin 17A Receptor as a Treatment for Immune System and Inflammation Disorders, Cancer, and Neurodegenerative Diseases","authors":"Ahmed F. Abdel-Magid*,&nbsp;","doi":"10.1021/acsmedchemlett.4c0053210.1021/acsmedchemlett.4c00532","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.4c00532https://doi.org/10.1021/acsmedchemlett.4c00532","url":null,"abstract":"<p >The invention in this patent application relates to <i>N</i>-(2-amino-2-oxoethyl)heteroarylcarboxamide derivatives, represented herein generally by formula 1. These compounds are inhibitors of the binding of interleukin 17A (IL-17A) with its receptor IL-17RA and may potentially be used for the treatment of diseases or disorders associated with IL-17A activity, which include psoriasis, ankylosing spondylitis, psoriatic arthritis and rheumatoid arthritis, cancer, and neurodegenerative disorders.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"15 12","pages":"2088–2090 2088–2090"},"PeriodicalIF":3.5,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142850792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Novel Triazines as NLRP3 Inhibitors for Treating Multiple Diseases
IF 3.5 3区 医学
ACS Medicinal Chemistry Letters Pub Date : 2024-11-18 DOI: 10.1021/acsmedchemlett.4c0055210.1021/acsmedchemlett.4c00552
Ram W. Sabnis*, 
{"title":"Novel Triazines as NLRP3 Inhibitors for Treating Multiple Diseases","authors":"Ram W. Sabnis*,&nbsp;","doi":"10.1021/acsmedchemlett.4c0055210.1021/acsmedchemlett.4c00552","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.4c00552https://doi.org/10.1021/acsmedchemlett.4c00552","url":null,"abstract":"<p >Provided herein are novel triazines as NLRP3 inhibitors, pharmaceutical compositions, use of such compounds in treating multiple diseases, and processes for preparing such compounds.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"15 12","pages":"2099–2100 2099–2100"},"PeriodicalIF":3.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Novel Triazines as NLRP3 Inhibitors for Treating Multiple Diseases.
IF 3.5 3区 医学
ACS Medicinal Chemistry Letters Pub Date : 2024-11-18 eCollection Date: 2024-12-12 DOI: 10.1021/acsmedchemlett.4c00552
Ram W Sabnis
{"title":"Novel Triazines as NLRP3 Inhibitors for Treating Multiple Diseases.","authors":"Ram W Sabnis","doi":"10.1021/acsmedchemlett.4c00552","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.4c00552","url":null,"abstract":"<p><p>Provided herein are novel triazines as NLRP3 inhibitors, pharmaceutical compositions, use of such compounds in treating multiple diseases, and processes for preparing such compounds.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"15 12","pages":"2099-2100"},"PeriodicalIF":3.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Discovery of 4-(5-Membered)Heteroarylether-6-methylpicolinamide Negative Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 5.
IF 3.5 3区 医学
ACS Medicinal Chemistry Letters Pub Date : 2024-11-18 eCollection Date: 2024-12-12 DOI: 10.1021/acsmedchemlett.4c00481
Elizabeth S Childress, Rory A Capstick, Katherine E Crocker, Miranda L Ledyard, Aaron M Bender, Mallory A Maurer, Natasha B Billard, Hyekyung P Cho, Alice L Rodriguez, Colleen M Niswender, Weimin Peng, Jerri M Rook, Sichen Chang, Anna L Blobaum, Olivier Boutaud, Analisa Thompson Gray, Carrie K Jones, P Jeffrey Conn, Andrew S Felts, Craig W Lindsley, Kayla J Temple
{"title":"Discovery of 4-(5-Membered)Heteroarylether-6-methylpicolinamide Negative Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 5.","authors":"Elizabeth S Childress, Rory A Capstick, Katherine E Crocker, Miranda L Ledyard, Aaron M Bender, Mallory A Maurer, Natasha B Billard, Hyekyung P Cho, Alice L Rodriguez, Colleen M Niswender, Weimin Peng, Jerri M Rook, Sichen Chang, Anna L Blobaum, Olivier Boutaud, Analisa Thompson Gray, Carrie K Jones, P Jeffrey Conn, Andrew S Felts, Craig W Lindsley, Kayla J Temple","doi":"10.1021/acsmedchemlett.4c00481","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.4c00481","url":null,"abstract":"<p><p>This Letter details our efforts to develop novel, non-acetylene-containing metabotropic glutamate receptor subtype 5 (mGlu<sub>5</sub>) negative allosteric modulators (NAMs) with improved pharmacological properties. This endeavor involved replacing the ether-linked pyrimidine moiety, a metabolic liability, with various 5-membered heterocycles. From this exercise, we identified <b>VU6043653</b>, a highly brain penetrant and selective mGlu<sub>5</sub> NAM which displayed moderate potency against both human and rat mGlu<sub>5</sub>. Moreover, <b>VU6043653</b> has overall improved pharmacological and drug metabolism and pharmacokinetic profiles when compared to its predecessor compounds. Most notably, <b>VU6043653</b> exhibits low predicted human hepatic clearance, a clean cytochrome P450 profile, and minimal inhibition of the dopamine transporter.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"15 12","pages":"2210-2219"},"PeriodicalIF":3.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Discovery of 4-(5-Membered)Heteroarylether-6-methylpicolinamide Negative Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 5
IF 3.5 3区 医学
ACS Medicinal Chemistry Letters Pub Date : 2024-11-18 DOI: 10.1021/acsmedchemlett.4c0048110.1021/acsmedchemlett.4c00481
Elizabeth S. Childress, Rory A. Capstick, Katherine E. Crocker, Miranda L. Ledyard, Aaron M. Bender, Mallory A. Maurer, Natasha B. Billard, Hyekyung P. Cho, Alice L. Rodriguez, Colleen M. Niswender, Weimin Peng, Jerri M. Rook, Sichen Chang, Anna L. Blobaum, Olivier Boutaud, Analisa Thompson Gray, Carrie K. Jones, P. Jeffrey Conn, Andrew S. Felts, Craig W. Lindsley* and Kayla J. Temple*, 
{"title":"Discovery of 4-(5-Membered)Heteroarylether-6-methylpicolinamide Negative Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 5","authors":"Elizabeth S. Childress,&nbsp;Rory A. Capstick,&nbsp;Katherine E. Crocker,&nbsp;Miranda L. Ledyard,&nbsp;Aaron M. Bender,&nbsp;Mallory A. Maurer,&nbsp;Natasha B. Billard,&nbsp;Hyekyung P. Cho,&nbsp;Alice L. Rodriguez,&nbsp;Colleen M. Niswender,&nbsp;Weimin Peng,&nbsp;Jerri M. Rook,&nbsp;Sichen Chang,&nbsp;Anna L. Blobaum,&nbsp;Olivier Boutaud,&nbsp;Analisa Thompson Gray,&nbsp;Carrie K. Jones,&nbsp;P. Jeffrey Conn,&nbsp;Andrew S. Felts,&nbsp;Craig W. Lindsley* and Kayla J. Temple*,&nbsp;","doi":"10.1021/acsmedchemlett.4c0048110.1021/acsmedchemlett.4c00481","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.4c00481https://doi.org/10.1021/acsmedchemlett.4c00481","url":null,"abstract":"<p >This Letter details our efforts to develop novel, non-acetylene-containing metabotropic glutamate receptor subtype 5 (mGlu<sub>5</sub>) negative allosteric modulators (NAMs) with improved pharmacological properties. This endeavor involved replacing the ether-linked pyrimidine moiety, a metabolic liability, with various 5-membered heterocycles. From this exercise, we identified <b>VU6043653</b>, a highly brain penetrant and selective mGlu<sub>5</sub> NAM which displayed moderate potency against both human and rat mGlu<sub>5</sub>. Moreover, <b>VU6043653</b> has overall improved pharmacological and drug metabolism and pharmacokinetic profiles when compared to its predecessor compounds. Most notably, <b>VU6043653</b> exhibits low predicted human hepatic clearance, a clean cytochrome P450 profile, and minimal inhibition of the dopamine transporter.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"15 12","pages":"2210–2219 2210–2219"},"PeriodicalIF":3.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acsmedchemlett.4c00481","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142850490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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