{"title":"Ginsenoside Re protects against kainate-induced neurotoxicity in mice by attenuating mitochondrial dysfunction through activation of the signal transducers and activators of transcription 3 signaling","authors":"YenNhiDoan Nguyen, JiHoon Jeong, Naveen Sharma, Ngoc KimCuong Tran, Hoang-Yen Phi Tran, Duy-Khanh Dang, JungHoon Park, Jae Kyung Byun, Sung Kwon Ko, Seung-Yeol Nah, Hyoung-Chun Kim, Eun-Joo Shin","doi":"10.1080/10715762.2024.2341885","DOIUrl":"https://doi.org/10.1080/10715762.2024.2341885","url":null,"abstract":"It was demonstrated that ginsenosides exert anti-convulsive potentials and interleukin-6 (IL-6) is protective from excitotoxicity induced by kainate (KA), a model of temporal lobe epilepsy. Ginseno...","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":"76 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140591696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Association of poly(rC)-binding protein-2 with sideroflexin-3 through TOM20 as an iron entry pathway to mitochondria","authors":"Danyang Mi, Izumi Yanatori, Hao Zheng, Yingyi Kong, Tasuku Hirayama, Shinya Toyokuni","doi":"10.1080/10715762.2024.2340711","DOIUrl":"https://doi.org/10.1080/10715762.2024.2340711","url":null,"abstract":"Iron is essential for all the lives and mitochondria integrate iron into heme and Fe-S clusters for diverse use as cofactors. Here we screened mitochondrial proteins in KU812 human chronic myelogen...","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":"18 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140591692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tássia Liz Araújo dos Santos Lessa, Thiago Macêdo Lopes Correia, Talita Costa dos Santos, Railmara Pereira da Silva, Beatriz Pereira da Silva, Maria Cláudia Magalhães Cavallini, Leonardo Silva Rocha, Albert Souza Peixoto, Beatriz S. Cugnasca, Gustavo Cervi, Thiago C. Correra, Augusto Cesar Gonçalves, William Tadeu Lara Festuccia, Thiago Mattar Cunha, Regiane Yatsuda, Amélia Cristina Mendes de Magalhães, Alcindo A. Dos Santos, Flávia Carla Meotti, Raphael Ferreira Queiroz
{"title":"A novel diselenide attenuates the carrageenan-induced inflammation by reducing neutrophil infiltration and the resulting tissue damage in mice","authors":"Tássia Liz Araújo dos Santos Lessa, Thiago Macêdo Lopes Correia, Talita Costa dos Santos, Railmara Pereira da Silva, Beatriz Pereira da Silva, Maria Cláudia Magalhães Cavallini, Leonardo Silva Rocha, Albert Souza Peixoto, Beatriz S. Cugnasca, Gustavo Cervi, Thiago C. Correra, Augusto Cesar Gonçalves, William Tadeu Lara Festuccia, Thiago Mattar Cunha, Regiane Yatsuda, Amélia Cristina Mendes de Magalhães, Alcindo A. Dos Santos, Flávia Carla Meotti, Raphael Ferreira Queiroz","doi":"10.1080/10715762.2024.2336566","DOIUrl":"https://doi.org/10.1080/10715762.2024.2336566","url":null,"abstract":"Selenium-containing compounds have emerged as promising treatment for redox-based and inflammatory diseases. This study aimed to investigate the in vitro and in vivo anti-inflammatory activity of a...","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":"69 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140591686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Upasana Ganguly, Sukhpal Singh, Aritri Bir, Arindam Ghosh, Sankha Shubhra Chakrabarti, Reena V Saini, Luciano Saso, Marco Bisaglia, Sasanka Chakrabarti
{"title":"Alpha-synuclein interaction with mitochondria is the final mechanism of ferroptotic death induced by erastin in SH-SY5Y cells","authors":"Upasana Ganguly, Sukhpal Singh, Aritri Bir, Arindam Ghosh, Sankha Shubhra Chakrabarti, Reena V Saini, Luciano Saso, Marco Bisaglia, Sasanka Chakrabarti","doi":"10.1080/10715762.2024.2336563","DOIUrl":"https://doi.org/10.1080/10715762.2024.2336563","url":null,"abstract":"Ferroptosis has been characterized as a form of iron-dependent regulated cell death accompanied by an accumulation of reactive oxygen species and lipid oxidation products along with typical morphol...","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":"55 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140602935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Free Radical ResearchPub Date : 2024-03-01Epub Date: 2024-03-27DOI: 10.1080/10715762.2024.2333074
Lu Chen, Xiaohua Yang, Kai Wang, Lina Guo, Cao Zou
{"title":"Humanin inhibits lymphatic endothelial cells dysfunction to alleviate myocardial infarction-reperfusion injury via BNIP3-mediated mitophagy.","authors":"Lu Chen, Xiaohua Yang, Kai Wang, Lina Guo, Cao Zou","doi":"10.1080/10715762.2024.2333074","DOIUrl":"10.1080/10715762.2024.2333074","url":null,"abstract":"<p><strong>Objective: </strong>Acute myocardial infarction (AMI) ranks among the top contributors to sudden death and disability worldwide. It should be noted that current therapies always cause increased reperfusion damage. Evidence suggests that humanin (HN) reduces mitochondrial dysfunction to have cardio-protective effects against MI-reperfusion injury. In this context, we hypothesized that HN may attenuate MI-reperfusion injury by alleviating lymphatic endothelial cells dysfunction through the regulation of mitophagy.</p><p><strong>Materials and methods: </strong>In this study, primary lymphatic endothelial cells were selected as the experimental model. Cells were maintained under 1% O<sub>2</sub> to induce a hypoxic phenotype. For <i>in vivo</i> experiments, the left coronary arteries of C57/BL6 mice were clamped for 45 min followed by 24 h reperfusion to develop MI-reperfusion injury. The volume of infarcted myocardium in MI-reperfusion injury mouse models were TTC staining. PCR and western blot were used to quantify the expression of autophagy-, mitophagy- and mitochondria-related markers. The fibrosis and apoptosis in the ischemic area were evaluated for Masson staining and TUNEL respectively. We also used western blot to analyze the expression of VE-Cadherin in lymphatic endothelial cells.</p><p><strong>Results: </strong>We firstly exhibited a specific mechanism by which HN mitigates MI-reperfusion injury. We demonstrated that HN effectively reduces such injury <i>in vivo</i> and also inhibits dysfunction in lymphatic endothelial cells <i>in vitro</i>. Importantly, this inhibitory effect is mediated through BNIP3-associated mitophagy.</p><p><strong>Conclusions: </strong>In conclusion, HN alleviates myocardial infarction-reperfusion injury by inhibiting lymphatic endothelial cells dysfunction, primarily through BNIP3-mediated mitophagy.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"180-193"},"PeriodicalIF":3.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140293274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Free Radical ResearchPub Date : 2024-03-01Epub Date: 2024-03-05DOI: 10.1080/10715762.2024.2325940
Ruzan M Simonyan, Sona M Feschyan, Roza A Madoyan, Gegham M Simonyan, Hasmik H Sargsyan, Madlena A Babayan, Hasmik H Yekmalyan, Magdalina M Melkonyan, Maxim A Simonyan, Ashkhen L Manukyan
{"title":"Superoxide-producing associates from gastrointestinal bacteria: stimulation of its growth by exogenous superoxide-producing complex from raspberries.","authors":"Ruzan M Simonyan, Sona M Feschyan, Roza A Madoyan, Gegham M Simonyan, Hasmik H Sargsyan, Madlena A Babayan, Hasmik H Yekmalyan, Magdalina M Melkonyan, Maxim A Simonyan, Ashkhen L Manukyan","doi":"10.1080/10715762.2024.2325940","DOIUrl":"10.1080/10715762.2024.2325940","url":null,"abstract":"<p><p>Aerobic organisms including the gut microbiota have an essential antioxidant status, as a result of which these bacteria protect organisms from various pathologies and diseases. The goal of the given investigation is (1) the isolation and purification of the isoforms of endogenous О<sub>2</sub><sup>-</sup>-producing associate from gastrointestinal bacteria (<i>Lactobacillus rhamnosus, Lactobacillus acidophilus, Bifidobacterium bifidum</i>); (2) determination of the effective concentrations of exogenous О<sub>2</sub><sup>-</sup> produced by a complex of NADPH-containing protein component and Fe(III) (NPC-Fe(III)) from raspberries on the growth of the gastrointestinal bacteria in a nutrient medium <i>in vitro</i>. Ion-exchange chromatography on cellulose DE-52 and gel filtration on Sephadex G-100 at the pH of 9.5 was used to isolate and purify the NLP-Nox isoforms. Specific maximal optical absorption spectra of the Nox isoforms were observed in a weakly opalescent aqueous solution of the NLP-Nox isoforms. The specific contents of these NLP-Nox isoforms, as well as their composition, the stationary concentration of produced О<sub>2</sub><sup>-</sup>, and the mechanism of О<sub>2</sub><sup>-</sup> production were determined. The stimulating effect on the growth of these gastrointestinal bacteria in the nutrient medium of MRS broth and MRS agar <i>in vitro</i> under the influence of О<sub>2</sub><sup>-</sup>, as a product of a new thermostable and acid-stable complex NPC-Fe(III) was determined. The NPC-Fe(III) complex, from raspberries was determined as well. Thus, for the first time, the isolation and purification of О<sub>2</sub><sup>-</sup>- producing thermostable NADPH-containing lipoprotein-NADPH oxidase (NLP-Nox) associate from gastrointestinal bacteria membranes (continuously producing О<sub>2</sub><sup>-</sup> under the aerobic conditions), and the stimulation of these bacteria growth by О<sub>2</sub><sup>-</sup> formed by the complex from raspberries were demonstrated.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"145-155"},"PeriodicalIF":3.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139996059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Biocompatibility assessment of bovine serum albumin conjugated manganese dioxide nanoparticle and their therapeutic role against microwave radiation induced haematological toxicity in male Wistar rats.","authors":"Sonali Pardhiya, Usha Singh Gaharwar, Ajith Manayil Parambil, Jay Prakash Nirala, Paulraj Rajamani","doi":"10.1080/10715762.2024.2333880","DOIUrl":"10.1080/10715762.2024.2333880","url":null,"abstract":"<p><p>Microwave (MW) radiations are widely used in communications, radar and medical treatment and thus human exposure to MW radiations have increased tremendously, raising health concerns as MW has been implicated in induction of oxidative stress condition in our body. Few metallic nanoparticles (NPs) have been shown to mimic the activity of antioxidant enzymes and hence can be applied for the modulation of adverse effects caused by MW. Present study aimed to assess the biocompatibility of Bovine serum albumin (BSA) conjugated manganese dioxide nanoparticles (MNP*) and to counteract the impact of MW on the haematological system of male Wistar rats. Experiments were conducted in two sets. Set I involved biodistribution and antioxidant activity evaluation of MNP* at different doses. Results showed a dose-dependent increase in antioxidant potential and significant biodistribution in the liver, spleen, kidney, and testis, with no organ damage, indicating its biocompatibility. Experiment set II constituted the study of separate and combined effects of MW and MNP* on haematological parameters, oxidative status, and genotoxic study in the blood of rats. MW exposure significantly altered red blood cell count, hemoglobin, packed cell volume percentage, monocyte percentage, aspartate aminotransferase, Alanine aminotransferase and uric acid. MW also induced significant DNA damage in the blood. A significant increase in lipid peroxidation and a decrease in antioxidant enzyme superoxide dismutase was also observed in MW exposed group. However, these alterations were reduced significantly when MNP* was administered. Thus, MNP* showed biocompatibility and modulatory effects against MW-induced alterations in the haematological system of rats.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"194-216"},"PeriodicalIF":3.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Andrographolide attenuates sepsis-induced acute kidney injury by inhibiting ferroptosis through the Nrf2/FSP1 pathway.","authors":"Yixin Zhang, Youcheng Zeng, Ming Huang, Guodong Cao, Liang Lin, Xiaoyue Wang, Qinghong Cheng","doi":"10.1080/10715762.2024.2330413","DOIUrl":"10.1080/10715762.2024.2330413","url":null,"abstract":"<p><p>Sepsis is a systemic inflammatory response syndrome caused by infection, which causes renal dysfunction known as sepsis-associated acute kidney injury (S-AKI). Ferroptosis is a form of lipid peroxidation dependent on iron and reactive oxygen species that differs from other forms of programmed cell death at the morphological and biochemical levels. Andrographolide (AG), a natural diterpenoid lactone compound extracted from <i>Andrographis paniculata</i>, has been shown to have therapeutic effects in kidney disease. In this study, we investigated the novel mechanism by which AG attenuates septic acute kidney injury by inhibiting ferroptosis in renal tubular epithelial cells (HK-2) through the Nrf2/FSP1 pathway. Cecum ligation and puncture (CLP)-induced septic rats and lipopolysaccharide (LPS)-induced HK-2 cells were used for <i>in vivo</i> and <i>in vitro</i> experiments. Firstly, in septic rats and HK-2 cells, AG effectively decreased the levels of kidney injury indicators, including blood creatinine, urea nitrogen, and markers of kidney injury such as neutrophil gelatinase-associated lipid transport protein and kidney injury molecule-1 (KIM-1). In addition, AG prevented ferroptotosis, by avoiding the accumulation of iron and lipid peroxidation, and an increase in SLC7A11 and GPX4 in AG-treated HK-2 cells. Furthermore, AG attenuated mitochondrial damage, including mitochondrial swelling, outer membrane rupture, and a reduction in mitochondrial cristae in LPS-treated HK-2 cells. Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, significantly inhibited LPS-induced ferroptosis in HK-2 cells. Importantly, our results confirm that Nrf2/FSP1 is an important pathway for ferroptosis resistance. Nrf2 siRNA hindered the effect of AG in attenuating acute kidney injury and inhibiting ferroptosis. These findings demonstrate that Nrf2/FSP1-mediated HK-2 ferroptosis is associated with AG, alleviates septic acute kidney injury, and indicates a novel avenue for therapeutic interventions in the treatment of acute kidney injury in sepsis.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"156-169"},"PeriodicalIF":3.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140119205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Inhibition of glutamine metabolism increases sensitivity to plasma-activated medium-induced cytotoxicity.","authors":"Shu Tanaka, Sae Hayashi, Tomohiro Otsuka, Tetsuro Kamiya, Kenji Ishikawa, Hirokazu Hara","doi":"10.1080/10715762.2024.2332343","DOIUrl":"10.1080/10715762.2024.2332343","url":null,"abstract":"<p><p>Non-thermal atmospheric pressure plasma (NTP), an ionized gas containing electrons, ions, radicals, and photons, has various biological effects, including wound healing and anticancer effects. Plasma-activated medium (PAM), which is prepared by irradiating medium with NTP, preferentially kills cancer cells. Large amounts of reactive oxygen species (ROS) and reactive nitrogen species (RNS) included in PAM are closely related to its anticancer effects. The precise mechanism of PAM-induced cytotoxicity is not fully understood; however, PAM exposure has been reported to reduce cellular energy metabolism. Glutamine (Gln) is an important amino acid as an energy source in cancer cells. Gln is converted to glutamate by glutaminase (GLS), and is utilized to synthesize ATP and glutathione (GSH). Expression levels of GLS have been shown to be higher in certain types of cancers. In this study, we examined the effects of GLS inhibition on PAM cytotoxicity using breast cancer MDA-MB-231 cells. Pretreatment with BPTES, a glutaminase 1 (GLS1) inhibitor, dose-dependently enhanced PAM-induced cell death. PAM-induced ROS production and γ-H2AX formation, a DNA damage marker, were increased in cells pretreated with BPTES compared with PAM alone. BPTES pretreatment enhanced a PAM-induced decrease in intracellular GSH, indicating the possibility that BPTES reduces the antioxidant capacity of MDA-MB-231 cells. In addition, BPTES pretreatment enhanced PAM-induced loss of the mitochondrial membrane potential and reduction of ATP production. Moreover, GLS1 knockdown promoted PAM-induced cell death. Taken together, the combination of GLS1 inhibitors such as BPTES is considered to be useful for enhancing the cytotoxic effects of PAM against cancer cells.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"170-179"},"PeriodicalIF":3.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140174139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"<i>Brca2<sup>(p.T1942fs/+)</sup></i> dissipates ovarian reserve in rats through oxidative stress in follicular granulosa cells.","authors":"Hideaki Tanaka, Yashiro Motooka, Yuki Maeda, Reina Sonehara, Tomoko Nakamura, Hiroaki Kajiyama, Tomoji Mashimo, Shinya Toyokuni","doi":"10.1080/10715762.2024.2320405","DOIUrl":"10.1080/10715762.2024.2320405","url":null,"abstract":"<p><p>Pathogenic variants of <i>BRCA1/2</i> constitute hereditary breast and ovarian cancer (HBOC) syndrome, and <i>BRCA1/2</i> mutant is a risk for various cancers. Whereas the clinical guideline for HBOC patients has been organized for the therapy and prevention of cancer, there is no recommendation on the female reproductive discipline. Indeed, the role of <i>BRCA1/2</i> pathogenic variants in ovarian reserve has not been established due to the deficiency of appropriate animal models. Here, we used a rat model of <i>Brca2<sup>(p.T1942fs/+)</sup></i> mutant of <i>Sprague-Dawley</i> strain with <i>CRISPR-Cas9</i> editing to evaluate ovarian reserve in females. Fertility and ovarian follicles were evaluated and anti-Müllerian hormone (AMH) was measured at 8-32 weeks of age with a comparison between the wild-type and the mutant rats (MUT). MUT revealed a significantly smaller number of deliveries with fewer total pups. Furthermore, MUT showed a significant decrease in primordial follicles at 20 weeks and a low AMH level at 28 weeks. RNA-sequencing of the ovary at 10 weeks detected acceleration of the DNA damage repair pathway, which was accompanied by oxidative stress-induced DNA double-strand breaks, a decrease in PTEN, and an increase in mTOR in follicular granulosa cells. In conclusion, <i>Brca2<sup>(p.T1942fs/+)</sup></i> dissipates primordial follicles <i>via</i> early activation of granulosa cells through oxidative stress, leading to earlier termination of fertility.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"130-143"},"PeriodicalIF":3.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139939903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}