ACS Pharmacology and Translational Science最新文献_第2页

Influence of Linker Molecules on the Biodistribution Characteristics of 99mTc-labeled Mannose Derivatives with an Isocyanide-Coordinated Group

IF 4.9

ACS Pharmacology and Translational Science Pub Date : 2025-01-29 DOI: 10.1021/acsptsci.4c0065710.1021/acsptsci.4c00657

Guangxing Yin, Yuhao Jiang, Junhong Feng, Qing Ruan, Qianna Wang, Peiwen Han and Junbo Zhang*,

{"title":"Influence of Linker Molecules on the Biodistribution Characteristics of 99mTc-labeled Mannose Derivatives with an Isocyanide-Coordinated Group","authors":"Guangxing Yin, Yuhao Jiang, Junhong Feng, Qing Ruan, Qianna Wang, Peiwen Han and Junbo Zhang*, ","doi":"10.1021/acsptsci.4c0065710.1021/acsptsci.4c00657","DOIUrl":"https://doi.org/10.1021/acsptsci.4c00657https://doi.org/10.1021/acsptsci.4c00657","url":null,"abstract":"A hallmark of cancer cells is their increased glucose demand, which is mediated by glucose transporters (GLUTs). Mannose is imported into cells via GLUTs, thereby prompting the selection of mannose as the targeting molecule for designing radioactive derivatives for tumor imaging. In this study, five 99mTc-labeled mannose derivatives were prepared and evaluated in vitro and in vivo. The derivatives were conjugated with an isonitrile group and different linkers, including (CH2)5-Dpro, (CH2)6-Dpro, (CH2)7-Dpro, (CH2)5-Lpro, and (CH2)6-Lpro. All five radioactive compounds exhibited hydrophilicity and in vitro stability. A comparative biodistribution study demonstrated that probes modified with D-proline exhibited greater uptake in tumors than those modified with L-proline. [99mTc]Tc-L1 exhibited the highest accumulation in the tumor and the most favorable tumor-to-nontarget ratios. SPECT/CT imaging results of [99mTc]Tc-L1 demonstrated clear accumulation and visualization at the tumor site. Blocking studies in cells and mice bearing S180 tumors revealed that [99mTc]Tc-L1 was transported into cancer cells via a GLUT-mediated mechanism. These findings suggest that [99mTc]Tc-L1 is a promising probe for SPECT tumor imaging and that linker molecules significantly affect biodistribution characteristics.","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 2","pages":"566–577 566–577"},"PeriodicalIF":4.9,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143402095","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}

引用次数: 0

Influence of Linker Molecules on the Biodistribution Characteristics of ^99mTc-labeled Mannose Derivatives with an Isocyanide-Coordinated Group.

IF 4.9

ACS Pharmacology and Translational Science Pub Date : 2025-01-29 eCollection Date: 2025-02-14 DOI: 10.1021/acsptsci.4c00657

Guangxing Yin, Yuhao Jiang, Junhong Feng, Qing Ruan, Qianna Wang, Peiwen Han, Junbo Zhang

{"title":"Influence of Linker Molecules on the Biodistribution Characteristics of 99mTc-labeled Mannose Derivatives with an Isocyanide-Coordinated Group.","authors":"Guangxing Yin, Yuhao Jiang, Junhong Feng, Qing Ruan, Qianna Wang, Peiwen Han, Junbo Zhang","doi":"10.1021/acsptsci.4c00657","DOIUrl":"10.1021/acsptsci.4c00657","url":null,"abstract":"A hallmark of cancer cells is their increased glucose demand, which is mediated by glucose transporters (GLUTs). Mannose is imported into cells via GLUTs, thereby prompting the selection of mannose as the targeting molecule for designing radioactive derivatives for tumor imaging. In this study, five 99mTc-labeled mannose derivatives were prepared and evaluated in vitro and in vivo. The derivatives were conjugated with an isonitrile group and different linkers, including (CH2)5-Dpro, (CH2)6-Dpro, (CH2)7-Dpro, (CH2)5-Lpro, and (CH2)6-Lpro. All five radioactive compounds exhibited hydrophilicity and in vitro stability. A comparative biodistribution study demonstrated that probes modified with D-proline exhibited greater uptake in tumors than those modified with L-proline. [99mTc]Tc-L1 exhibited the highest accumulation in the tumor and the most favorable tumor-to-nontarget ratios. SPECT/CT imaging results of [99mTc]Tc-L1 demonstrated clear accumulation and visualization at the tumor site. Blocking studies in cells and mice bearing S180 tumors revealed that [99mTc]Tc-L1 was transported into cancer cells via a GLUT-mediated mechanism. These findings suggest that [99mTc]Tc-L1 is a promising probe for SPECT tumor imaging and that linker molecules significantly affect biodistribution characteristics.","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 2","pages":"566-577"},"PeriodicalIF":4.9,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11833735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459890","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}

引用次数: 0

Novel Soluble Epoxide Hydrolase Inhibitor: Toward Regulatory Preclinical Studies.

IF 4.9

ACS Pharmacology and Translational Science Pub Date : 2025-01-29 eCollection Date: 2025-02-14 DOI: 10.1021/acsptsci.4c00629

Júlia Jarne-Ferrer, Javier Sánchez, Sandra Codony, Marion Schneider, Christa E Müller, Coral Sanfeliu, Rafael Franco, Santiago Vazquez, Christian Griñán-Ferré, Mercè Pallàs

{"title":"Novel Soluble Epoxide Hydrolase Inhibitor: Toward Regulatory Preclinical Studies.","authors":"Júlia Jarne-Ferrer, Javier Sánchez, Sandra Codony, Marion Schneider, Christa E Müller, Coral Sanfeliu, Rafael Franco, Santiago Vazquez, Christian Griñán-Ferré, Mercè Pallàs","doi":"10.1021/acsptsci.4c00629","DOIUrl":"10.1021/acsptsci.4c00629","url":null,"abstract":"Neuroinflammation is widely recognized as a key pathological hallmark of Alzheimer's disease (AD). Recently, inhibiting soluble epoxide hydrolase (sEH) has emerged as a promising therapeutic strategy for AD. sEH plays a pivotal role in neuroinflammation by hydrolyzing epoxyeicosatrienoic acids (EETs), which have anti-inflammatory and neuroprotective properties, into pro-inflammatory dihydroepoxyeicosatrienoic acids (DHETs). Furthermore, the overexpression of the enzyme in the brains of AD patients and animal models of the disease highlights its relevance as a therapeutic target. Our previous studies, using the inhibitor UB-SCG-51 demonstrated that sEH inhibition regulates neuroinflammation and other mechanisms, such as the unfolded protein response pathway, while reducing autophagy, apoptosis, and neuronal death, thereby promoting neuroprotection. Building on these findings, we evaluated the arginine salt of the compound, designated UB-SCG-74, which offers improved oral absorption compared to that of UB-SCG-51 while retaining high permeability, potency, and selectivity. In experiments using 5XFAD mice, UB-SCG-74 treatment significantly improved cognition and synaptic plasticity, outperforming donepezil, a standard AD drug, and ibuprofen, an anti-inflammatory drug. Remarkably, these benefits persisted for 4 weeks after administration cessation, suggesting lasting therapeutic effects. Safety pharmacology studies showed no toxicity, supporting the advancement of UB-SCG-74 into preclinical regulatory evaluation. Our findings further indicate that sEH inhibition engages multiple neuroprotective pathways, potentially modifying both AD symptoms and disease progression, thus reinforcing its therapeutic potential.","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 2","pages":"533-542"},"PeriodicalIF":4.9,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11833725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459972","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}

引用次数: 0

Correction to “Effective, but Safe? Physiologically Based Pharmacokinetic (PBPK)-Modeling-Based Dosing Study of Molnupiravir for Risk Assessment in Pediatric Subpopulations”

IF 4.9

ACS Pharmacology and Translational Science Pub Date : 2025-01-28 DOI: 10.1021/acsptsci.5c0005310.1021/acsptsci.5c00053

Sarang Mishra, and , Katharina Rox*,

引用次数: 0

Synaptic Vesicle 2A (SV2A) Positron Emission Tomography (PET) Imaging as a Marker of Therapeutic Response in a Mouse Model of Depression.

IF 4.9

ACS Pharmacology and Translational Science Pub Date : 2025-01-28 eCollection Date: 2025-02-14 DOI: 10.1021/acsptsci.4c00621

Cassandre Corvo, Indira Mendez-David, Sébastien Goutal, Wadad Saba, Michel Bottlaender, Fabien Caillé, Rene Hen, Romain Colle, Emmanuelle Corruble, Nicolas Tournier, Claire Leroy, Denis J David

{"title":"Synaptic Vesicle 2A (SV2A) Positron Emission Tomography (PET) Imaging as a Marker of Therapeutic Response in a Mouse Model of Depression.","authors":"Cassandre Corvo, Indira Mendez-David, Sébastien Goutal, Wadad Saba, Michel Bottlaender, Fabien Caillé, Rene Hen, Romain Colle, Emmanuelle Corruble, Nicolas Tournier, Claire Leroy, Denis J David","doi":"10.1021/acsptsci.4c00621","DOIUrl":"10.1021/acsptsci.4c00621","url":null,"abstract":"In this preclinical pilot study, we used [11C]UCB-J PET imaging to monitor the synaptic modulation in depression and after fluoxetine. PET imaging was performed in a validated mouse model of depression/anxiety (CORT model), and the effect of 5-week treatment with fluoxetine was tested. Depression/anxiety phenotype and antidepressant action of fluoxetine were confirmed using the novelty-suppressed feeding test, previously validated in the CORT model. PET data showed significant decreases of volume of distribution (V T) of [11C]UCB-J in most brain regions of CORT mice compared with controls. After 5 weeks of fluoxetine, a trend toward restoration of V T values to control levels was observed, although it reached significance only in the olfactory bulb. These preliminary data support the use of [11C]UCB-J PET imaging and the CORT model to study the synaptic modulation of antidepressants. It provides excellent translational opportunities to study the relationship between synaptic plasticity and the clinical efficacy of antidepressants.","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 2","pages":"339-345"},"PeriodicalIF":4.9,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11833719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459206","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}

引用次数: 0

Synaptic Vesicle 2A (SV2A) Positron Emission Tomography (PET) Imaging as a Marker of Therapeutic Response in a Mouse Model of Depression

IF 4.9

ACS Pharmacology and Translational Science Pub Date : 2025-01-28 DOI: 10.1021/acsptsci.4c0062110.1021/acsptsci.4c00621

Cassandre Corvo, Indira Mendez-David, Sébastien Goutal, Wadad Saba, Michel Bottlaender, Fabien Caillé, Rene Hen, Romain Colle, Emmanuelle Corruble, Nicolas Tournier, Claire Leroy* and Denis J. David,

{"title":"Synaptic Vesicle 2A (SV2A) Positron Emission Tomography (PET) Imaging as a Marker of Therapeutic Response in a Mouse Model of Depression","authors":"Cassandre Corvo, Indira Mendez-David, Sébastien Goutal, Wadad Saba, Michel Bottlaender, Fabien Caillé, Rene Hen, Romain Colle, Emmanuelle Corruble, Nicolas Tournier, Claire Leroy* and Denis J. David, ","doi":"10.1021/acsptsci.4c0062110.1021/acsptsci.4c00621","DOIUrl":"https://doi.org/10.1021/acsptsci.4c00621https://doi.org/10.1021/acsptsci.4c00621","url":null,"abstract":"In this preclinical pilot study, we used [11C]UCB-J PET imaging to monitor the synaptic modulation in depression and after fluoxetine. PET imaging was performed in a validated mouse model of depression/anxiety (CORT model), and the effect of 5-week treatment with fluoxetine was tested. Depression/anxiety phenotype and antidepressant action of fluoxetine were confirmed using the novelty-suppressed feeding test, previously validated in the CORT model. PET data showed significant decreases of volume of distribution (VT) of [11C]UCB-J in most brain regions of CORT mice compared with controls. After 5 weeks of fluoxetine, a trend toward restoration of VT values to control levels was observed, although it reached significance only in the olfactory bulb. These preliminary data support the use of [11C]UCB-J PET imaging and the CORT model to study the synaptic modulation of antidepressants. It provides excellent translational opportunities to study the relationship between synaptic plasticity and the clinical efficacy of antidepressants.","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 2","pages":"339–345 339–345"},"PeriodicalIF":4.9,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143402408","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}

引用次数: 0

Correction to "Effective, but Safe? Physiologically Based Pharmacokinetic (PBPK)-Modeling-Based Dosing Study of Molnupiravir for Risk Assessment in Pediatric Subpopulations".

IF 4.9

ACS Pharmacology and Translational Science Pub Date : 2025-01-28 eCollection Date: 2025-02-14 DOI: 10.1021/acsptsci.5c00053

Sarang Mishra, Katharina Rox

引用次数: 0

Novel Soluble Epoxide Hydrolase Inhibitor: Toward Regulatory Preclinical Studies

IF 4.9

ACS Pharmacology and Translational Science Pub Date : 2025-01-28 DOI: 10.1021/acsptsci.4c0062910.1021/acsptsci.4c00629

Júlia Jarne-Ferrer, Javier Sánchez, Sandra Codony, Marion Schneider, Christa E. Müller, Coral Sanfeliu, Rafael Franco, Santiago Vazquez, Christian Griñán-Ferré* and Mercè Pallàs*,

{"title":"Novel Soluble Epoxide Hydrolase Inhibitor: Toward Regulatory Preclinical Studies","authors":"Júlia Jarne-Ferrer, Javier Sánchez, Sandra Codony, Marion Schneider, Christa E. Müller, Coral Sanfeliu, Rafael Franco, Santiago Vazquez, Christian Griñán-Ferré* and Mercè Pallàs*, ","doi":"10.1021/acsptsci.4c0062910.1021/acsptsci.4c00629","DOIUrl":"https://doi.org/10.1021/acsptsci.4c00629https://doi.org/10.1021/acsptsci.4c00629","url":null,"abstract":"Neuroinflammation is widely recognized as a key pathological hallmark of Alzheimer’s disease (AD). Recently, inhibiting soluble epoxide hydrolase (sEH) has emerged as a promising therapeutic strategy for AD. sEH plays a pivotal role in neuroinflammation by hydrolyzing epoxyeicosatrienoic acids (EETs), which have anti-inflammatory and neuroprotective properties, into pro-inflammatory dihydroepoxyeicosatrienoic acids (DHETs). Furthermore, the overexpression of the enzyme in the brains of AD patients and animal models of the disease highlights its relevance as a therapeutic target. Our previous studies, using the inhibitor UB-SCG-51 demonstrated that sEH inhibition regulates neuroinflammation and other mechanisms, such as the unfolded protein response pathway, while reducing autophagy, apoptosis, and neuronal death, thereby promoting neuroprotection. Building on these findings, we evaluated the arginine salt of the compound, designated UB-SCG-74, which offers improved oral absorption compared to that of UB-SCG-51 while retaining high permeability, potency, and selectivity. In experiments using 5XFAD mice, UB-SCG-74 treatment significantly improved cognition and synaptic plasticity, outperforming donepezil, a standard AD drug, and ibuprofen, an anti-inflammatory drug. Remarkably, these benefits persisted for 4 weeks after administration cessation, suggesting lasting therapeutic effects. Safety pharmacology studies showed no toxicity, supporting the advancement of UB-SCG-74 into preclinical regulatory evaluation. Our findings further indicate that sEH inhibition engages multiple neuroprotective pathways, potentially modifying both AD symptoms and disease progression, thus reinforcing its therapeutic potential.","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 2","pages":"533–542 533–542"},"PeriodicalIF":4.9,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143402405","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}

引用次数: 0

Identification of a Cannabinoid Receptor 2 Allosteric Site Using Computational Modeling and Pharmacological Analysis

IF 4.9

ACS Pharmacology and Translational Science Pub Date : 2025-01-28 DOI: 10.1021/acsptsci.4c0054710.1021/acsptsci.4c00547

Zara Farooq, Pietro Delre, Stylianos Iliadis, Giuseppe Felice Mangiatordi, Marialessandra Contino, Lesley A. Howell and Peter J. McCormick*,

{"title":"Identification of a Cannabinoid Receptor 2 Allosteric Site Using Computational Modeling and Pharmacological Analysis","authors":"Zara Farooq, Pietro Delre, Stylianos Iliadis, Giuseppe Felice Mangiatordi, Marialessandra Contino, Lesley A. Howell and Peter J. McCormick*, ","doi":"10.1021/acsptsci.4c0054710.1021/acsptsci.4c00547","DOIUrl":"https://doi.org/10.1021/acsptsci.4c00547https://doi.org/10.1021/acsptsci.4c00547","url":null,"abstract":"Emerging evidence has demonstrated that cannabinoid receptor 2 (CB2) is involved in a number of diseases, such as neurodegenerative disorders and various types of cancer, making it an attractive pharmacological target. Classically, a protein active site or an orthosteric binding site, where the endogenous ligand binds to, is used as a target for the design of most small-molecule drugs. This can present challenges when it comes to phylogenetically related proteins that have similar orthosteric binding sites, such as the cannabinoid receptors. An alternative approach is to target sites that are unique to these receptors yet still impact receptor function, known as allosteric binding sites. Using an inactive-state human cannabinoid receptor 2 crystal structure (PDB ID:5ZTY), we identified a putative CB2 allosteric site using computational approaches. In vitro signaling assays using known allosteric modulators and CB2 agonists have been used to verify the in silico results. This identification opens promising avenues for the development of selective and specific CB2 ligands for therapeutic purposes.","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 2","pages":"423–434 423–434"},"PeriodicalIF":4.9,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acsptsci.4c00547","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143402392","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}

引用次数: 0

Identification of a Cannabinoid Receptor 2 Allosteric Site Using Computational Modeling and Pharmacological Analysis.

IF 4.9

ACS Pharmacology and Translational Science Pub Date : 2025-01-28 eCollection Date: 2025-02-14 DOI: 10.1021/acsptsci.4c00547

Zara Farooq, Pietro Delre, Stylianos Iliadis, Giuseppe Felice Mangiatordi, Marialessandra Contino, Lesley A Howell, Peter J McCormick

{"title":"Identification of a Cannabinoid Receptor 2 Allosteric Site Using Computational Modeling and Pharmacological Analysis.","authors":"Zara Farooq, Pietro Delre, Stylianos Iliadis, Giuseppe Felice Mangiatordi, Marialessandra Contino, Lesley A Howell, Peter J McCormick","doi":"10.1021/acsptsci.4c00547","DOIUrl":"10.1021/acsptsci.4c00547","url":null,"abstract":"Emerging evidence has demonstrated that cannabinoid receptor 2 (CB2) is involved in a number of diseases, such as neurodegenerative disorders and various types of cancer, making it an attractive pharmacological target. Classically, a protein active site or an orthosteric binding site, where the endogenous ligand binds to, is used as a target for the design of most small-molecule drugs. This can present challenges when it comes to phylogenetically related proteins that have similar orthosteric binding sites, such as the cannabinoid receptors. An alternative approach is to target sites that are unique to these receptors yet still impact receptor function, known as allosteric binding sites. Using an inactive-state human cannabinoid receptor 2 crystal structure (PDB ID:5ZTY), we identified a putative CB2 allosteric site using computational approaches. In vitro signaling assays using known allosteric modulators and CB2 agonists have been used to verify the in silico results. This identification opens promising avenues for the development of selective and specific CB2 ligands for therapeutic purposes.","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 2","pages":"423-434"},"PeriodicalIF":4.9,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11833715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459889","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}

引用次数: 0