Rejuvenation research最新文献

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Hormetic effect of 3-Bromopyruvate on age-induced alterations in erythrocyte membrane transporters and oxidative biomarkers in rats. 3-溴吡喃酸酯对大鼠红细胞膜转运蛋白和氧化生物标志物年龄诱导变化的激素作用。
IF 2.6 4区 医学
Rejuvenation research Pub Date : 2022-04-04 DOI: 10.1089/rej.2021.0060
J. Arya, Raushan Kumar, Shambhoo Sharan Tripathi, S. Rizvi
{"title":"Hormetic effect of 3-Bromopyruvate on age-induced alterations in erythrocyte membrane transporters and oxidative biomarkers in rats.","authors":"J. Arya, Raushan Kumar, Shambhoo Sharan Tripathi, S. Rizvi","doi":"10.1089/rej.2021.0060","DOIUrl":"https://doi.org/10.1089/rej.2021.0060","url":null,"abstract":"3-bromopyruvate (3-BP) is a glycolytic inhibitor and a potential calorie restriction mimic that shows a variety of beneficial effects in several aging model systems. A chronic low dose of 3-BP was given to male Wistar rats for four weeks. The effect of 3-BP on age-dependent alteration on the activities of various transporters/exchangers and redox biomarkers (protein carbonyl (PC), sialic acid (SA), sulfhydryl group (-SH), intracellular calcium ion [Ca2+]i, and osmotic fragility) was studied. In aged rats, 3-BP treatment increases the membrane-bound activities of Na+/K+-ATPase (NKA) and Ca2+-ATPase (PMCA), along with levels of -SH and SA. It also exerts a concomitant decrease in Na+/H+ exchanger (NHE) activity and the levels of [Ca2+]i, PC, and osmotic fragility in aged groups. 3-BP can be considered as a potential anti-aging agent that induces a hormetic effect leading to amelioration of age-dependent impairment of membrane-bound ATPases and alterations in the redox biomarker level.","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2022-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46254395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 1
Mechanisms and Minimization of False Discovery of Metabolic Bioorthogonal Noncanonical Amino Acid Proteomics. 代谢生物正交非规范氨基酸蛋白质组学的机制和最小化错误发现。
IF 2.6 4区 医学
Rejuvenation research Pub Date : 2022-04-01 DOI: 10.1089/rej.2022.0019
Chao Liu, Nathan Wong, Etsuko Watanabe, William Hou, Leonardo Biral, Jonalyn DeCastro, Melod Mehdipour, Kiana Aran, Michael J Conboy, Irina M Conboy
{"title":"Mechanisms and Minimization of False Discovery of Metabolic Bioorthogonal Noncanonical Amino Acid Proteomics.","authors":"Chao Liu,&nbsp;Nathan Wong,&nbsp;Etsuko Watanabe,&nbsp;William Hou,&nbsp;Leonardo Biral,&nbsp;Jonalyn DeCastro,&nbsp;Melod Mehdipour,&nbsp;Kiana Aran,&nbsp;Michael J Conboy,&nbsp;Irina M Conboy","doi":"10.1089/rej.2022.0019","DOIUrl":"https://doi.org/10.1089/rej.2022.0019","url":null,"abstract":"<p><p>Metabolic proteomics has been widely used to characterize dynamic protein networks in many areas of biomedicine, including in the arena of tissue aging and rejuvenation. Bioorthogonal noncanonical amino acid tagging (BONCAT) is based on mutant methionine-tRNA synthases (MetRS) that incorporates metabolic tags, for example, azidonorleucine [ANL], into newly synthesized proteins. BONCAT revolutionizes metabolic proteomics, because mutant MetRS transgene allows one to identify cell type-specific proteomes in mixed biological environments. This is not possible with other methods, such as stable isotope labeling with amino acids in cell culture, isobaric tags for relative and absolute quantitation and tandem mass tags. At the same time, an inherent weakness of BONCAT is that after click chemistry-based enrichment, all identified proteins are assumed to have been metabolically tagged, but there is no confirmation in mass spectrometry data that only tagged proteins are detected. As we show here, such assumption is incorrect and accurate negative controls uncover a surprisingly high degree of false positives in BONCAT proteomics. We show not only how to reveal the false discovery and thus improve the accuracy of the analyses and conclusions but also approaches for avoiding it through minimizing nonspecific detection of biotin, biotin-independent direct detection of metabolic tags, and improvement of signal to noise ratio through machine learning algorithms.</p>","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":"25 2","pages":"95-109"},"PeriodicalIF":2.6,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9063144/pdf/rej.2022.0019.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9220010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 2
Correction to: Persistence of Long-Term Memory in Vitrified and Revived Caenorhabditis elegans, by Vita-More, et al. Rejuvenation Res.2015;18(5):458-463; doi:10.1089/rej.2014.1636. Vita-More等人对“玻璃化和复活秀丽隐杆线虫的长期记忆持久性”的更正。复兴Res.2015; 18 (5): 458 - 463;doi: 10.1089 / rej.2014.1636。
IF 2.6 4区 医学
Rejuvenation research Pub Date : 2022-04-01 DOI: 10.1089/rej.2014.1636.correx
{"title":"<i>Correction to:</i> Persistence of Long-Term Memory in Vitrified and Revived Caenorhabditis elegans, by Vita-More, et al. Rejuvenation Res.2015;18(5):458-463; doi:10.1089/rej.2014.1636.","authors":"","doi":"10.1089/rej.2014.1636.correx","DOIUrl":"https://doi.org/10.1089/rej.2014.1636.correx","url":null,"abstract":"","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":"25 2","pages":"118-119"},"PeriodicalIF":2.6,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9063216/pdf/rej.2014.1636.correx.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9678930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
On the Road to More Effective Rejuvenation Research. 在更有效的复兴研究之路上。
IF 2.6 4区 医学
Rejuvenation research Pub Date : 2022-04-01 DOI: 10.1089/rej.2022.29006.irc
Irina Conboy
{"title":"On the Road to More Effective Rejuvenation Research.","authors":"Irina Conboy","doi":"10.1089/rej.2022.29006.irc","DOIUrl":"https://doi.org/10.1089/rej.2022.29006.irc","url":null,"abstract":"","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":"25 2 1","pages":"57-58"},"PeriodicalIF":2.6,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48781250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Carnosine improves cognitive impairment through promoting SIRT6 expression and inhibiting ER stress in a diabetic encephalopathy model. 在糖尿病脑病模型中,肌肽通过促进SIRT6表达和抑制内质网应激改善认知障碍。
IF 2.6 4区 医学
Rejuvenation research Pub Date : 2022-03-18 DOI: 10.1089/rej.2022.0002
Dong Peng, Xia Qing, L. Guan, Hong-ying Li, Lijun Qiao, Yun-bo Chen, Ye-Feng Cai, Qi Wang, Shi-Jie Zhang
{"title":"Carnosine improves cognitive impairment through promoting SIRT6 expression and inhibiting ER stress in a diabetic encephalopathy model.","authors":"Dong Peng, Xia Qing, L. Guan, Hong-ying Li, Lijun Qiao, Yun-bo Chen, Ye-Feng Cai, Qi Wang, Shi-Jie Zhang","doi":"10.1089/rej.2022.0002","DOIUrl":"https://doi.org/10.1089/rej.2022.0002","url":null,"abstract":"Diabetic encephalopathy is one of complications of diabetes mellitus. Carnosine is a dipeptide composed of β-alanine and L-histidine. Study has shown that carnosine could ameliorate cognitive impairment in animal model with diabetes mellitus. However, the mechanism remains unclear. An animal model of type 2 diabetes (db/db mice) was used in this study. The animals were treated with 0.9 % saline or carnosine (100 mg/kg) for 8 weeks. Morris water maze was tested after drug administration. Oxidative stress-related factors malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), and pro-inflammatory factors inducible nitric oxide synthase (iNOS) were measured. Synapse-related protein postsynapticdensity 95 (PSD95) and brain-derived neurotrophic factor (BDNF) were detected by western blot. Besides, the expressions of sirtuin 6 (SIRT6), binding immunoglobulin protein (BIP), protein kinase R-like endoplasmic reticulum kinase (PERK), phospho-protein kinase R-like endoplasmic reticulum kinase (P-PERK), inositol-requiring enzyme-1α (IRE1α), phospho-inositol-requiring enzyme-1α (P-IRE1α), activating transcription factor 6 (ATF6), C/EBP-homologous protein (CHOP) in the hippocampus of the brain were detected. The results showed that treatment with carnosine ameliorated cognitive impairment in db/db mice. Carnosine reduced neuronal oxidative stress damage and iNOS expression in db/db mice. Meanwhile, carnosine relieved neurodegeneration in the hippocampus of db/db mice. Furthermore, carnosine promoted the expression of SIRT6 and reduced the expressions of endoplasmic reticulum (ER) related factors (BIP, P-PERK, P-IRE1α, ATF6, CHOP). In conclusion, these data suggested that the protective effect of carnosine against diabetic encephalopathy might be related to SIRT6/ER stress pathway.","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2022-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44165737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 4
It is time to work on the extension of body growth and reproductive stages. 是时候研究身体生长和生殖阶段的延长了。
IF 2.6 4区 医学
Rejuvenation research Pub Date : 2022-03-16 DOI: 10.1089/rej.2022.0017
W. Gu
{"title":"It is time to work on the extension of body growth and reproductive stages.","authors":"W. Gu","doi":"10.1089/rej.2022.0017","DOIUrl":"https://doi.org/10.1089/rej.2022.0017","url":null,"abstract":"There are three major changes for the human lifespan in the past half decade: the decreased age of sexual maturity, slight increase in age of menopause/ andropause, and a trend of increase in life expectancy. The ages of puberty and menopause are the transitions in life stages, such that early puberty leads to loss and late menopause leads to gain the lifespan. So far, the strategies for increased lifespan have been largely focused on the post-reproductive stage. These approaches are challenging and may at some point reach a plateau. It might be interesting to expand this focus to potentially delaying the puberty and extending the period of body growth, which might yield longer reproductive stages as well as the longer and healthier lifespan.","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2022-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42650843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 4
Different expression of miRNA in the subcutaneous and visceral adipose tissue of obese subjects. 肥胖者皮下和内脏脂肪组织中miRNA的不同表达。
IF 2.6 4区 医学
Rejuvenation research Pub Date : 2022-03-16 DOI: 10.1089/rej.2022.0004
D. Lacedonia, N. Tartaglia, G. Scioscia, P. Soccio, G. Pavone, G. Moriondo, C. Gallo, M. F. Foschino Barbaro, A. Ambrosi
{"title":"Different expression of miRNA in the subcutaneous and visceral adipose tissue of obese subjects.","authors":"D. Lacedonia, N. Tartaglia, G. Scioscia, P. Soccio, G. Pavone, G. Moriondo, C. Gallo, M. F. Foschino Barbaro, A. Ambrosi","doi":"10.1089/rej.2022.0004","DOIUrl":"https://doi.org/10.1089/rej.2022.0004","url":null,"abstract":"Obesity is a pathology characterized by an excessive accumulation of adipose tissue and it is a condition associated with complex alterations affecting different organs and systems. Obesity has great influences on cardiovascular and respiratory morbidity and mortality and impairs the multiple aspects of metabolism. Since micro-RNAs (miRNAs) are thought to play a role in the regulation of various pathological processes, in this complex framework, the investigation of these classes of noncoding regulatory RNA seems to be promising. Selected group of obese subjects was recruited. We analysed the expression of seven miRNAs from obese adipose tissue supposed to have a role in the pathogenesis of cardiovascular and respiratory disease related to obesity and we compared it with the expression of the same miRNAs in a group of non-obese controls. In the current study what emerged is miR-27b and miR-483 significant down-regulation in subcutaneous adipose tissue from obese group compared with non-obese ones. For visceral adipose tissue, a significant decrease in miR-27b and miR-223 expression was observed in obese group. Moreover, a different expression of miR-26a and miR-338 in the obese group was found. Those findings could help the individuation of previously unknown key players in the development of different diseases usually associated with obesity, such as cardiovascular and pulmonary diseases.","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2022-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47334987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 4
Protective Efficacy of Spilanthes acmella Murr. Extracts and Bioactive Constituents in Neuronal Cell Death. 牡丹的保护作用。神经元细胞死亡的提取物和生物活性成分。
IF 2.6 4区 医学
Rejuvenation research Pub Date : 2022-02-01 DOI: 10.1089/rej.2021.0002
Wilasinee Suwanjang, Chayanit Sirisuwat, Sujittra Srisung, Chartchalerm Isarankura-Na-Ayudhya, Supitcha Pannengpetch, Supaluk Prachayasittikul
{"title":"Protective Efficacy of <i>Spilanthes acmella</i> Murr. Extracts and Bioactive Constituents in Neuronal Cell Death.","authors":"Wilasinee Suwanjang,&nbsp;Chayanit Sirisuwat,&nbsp;Sujittra Srisung,&nbsp;Chartchalerm Isarankura-Na-Ayudhya,&nbsp;Supitcha Pannengpetch,&nbsp;Supaluk Prachayasittikul","doi":"10.1089/rej.2021.0002","DOIUrl":"https://doi.org/10.1089/rej.2021.0002","url":null,"abstract":"<p><p><i>Spilanthes acmella</i> Murr., a well-known Thai traditional medicine, has been used for treatment of toothache, rheumatism, and fever. Diverse pharmacological activities of <i>S. acmella</i> Murr. have been reported. In this study, antioxidative and neuroprotective effects of <i>S. acmella</i> Murr. extracts as well as bioactive scopoletin, vanillic acid, and <i>trans</i>-ferulic acid found in the aerial parts of this plant species have been described. Protective effect of <i>S. acmella</i> Murr. extracts and bioactive compounds on dexamethasone-induced neuronal cell death was investigated. Different plant crude ethyl acetate (EtOAc) and methanol (MeOH) extracts including pure compounds of <i>S. acmella</i> Murr. were evaluated in human neuroblastoma SH-SY5Y cells. Cytotoxic effects were performed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Mechanisms involved in the antioxidant effects of <i>S. acmella</i> Murr. regarding the activation of antioxidant marker proteins such as superoxide dismutase 2 (SOD2) and sirtuin 3 (SIRT3) were determined using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) assay, Western blot analysis, and immunocytochemistry. Dexamethasone significantly caused the decrease of SH-SY5Y cell viability. Conversely, the increases in reactive oxygen species (ROS), autophagy, and apoptosis were observed in dexamethasone-treated cells. <i>S. acmella</i> Murr. MeOH and EtOAc extracts, as well as the bioactive compounds, reversed the toxic effect of dexamethasone by increasing the cell viability, SIRT3 protein expression but reducing the ROS, autophagy, and apoptosis. This study demonstrated that <i>S. acmella</i> Murr. may exert its protective effects against ROS through SOD2 and SIRT3 signaling pathways in dexamethasone-induced neurotoxicity. <i>S. acmella</i> Murr. may be a candidate therapy for neuroprotection.</p>","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":"25 1","pages":"2-15"},"PeriodicalIF":2.6,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39693300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 1
Angiotensin II-Induced Erythrocyte Senescence Contributes to Oxidative Stress. 血管紧张素ii诱导的红细胞衰老有助于氧化应激。
IF 2.6 4区 医学
Rejuvenation research Pub Date : 2022-02-01 Epub Date: 2022-01-28 DOI: 10.1089/rej.2021.0054
Chenglin Huang, Jing Gao, Tong Wei, Weili Shen
{"title":"Angiotensin II-Induced Erythrocyte Senescence Contributes to Oxidative Stress.","authors":"Chenglin Huang,&nbsp;Jing Gao,&nbsp;Tong Wei,&nbsp;Weili Shen","doi":"10.1089/rej.2021.0054","DOIUrl":"https://doi.org/10.1089/rej.2021.0054","url":null,"abstract":"<p><p>Oxidative stress may be an important cause of erythrocyte senescence. Angiotensin II (Ang II) has recently been shown to promote vascular cell senescence. However, its effects on erythrocytes remain unclear. This study aims at investigating the role of Ang II in regulating erythrocyte lifespan through oxidative stress. Experiments were performed in C57/BL6J mice infused with Ang II (1500 ng/kg per minute) or saline for 7 days. After Ang II infusion, we found that Ang II increased erythrocyte number, hemoglobin, and red blood cell distribution width. These differences were accompanied by a decrease in glutathione (GSH) and an increase in malondialdehyde (MDA) concentration. <i>In vitro</i>, after 24 hours of Ang II treatment, erythrocytes showed reduced surface expression of CD47 and increased phosphatidylserine exposure. In parallel, Ang II reduced the levels of antioxidant enzymes, including Cu/ZnSOD, catalase, and peroxidase 2 (PRDX2). These effects were reversed by the addition of the antioxidant N-acetyl-L-cysteine or the Ang II type 1 (AT1) receptor blocker losartan. In addition, Ang II treatment increased pro-inflammatory oxylipin, including hydroxyeicosatetraenoic acids (HETEs) and dihydroxyoctadecenoic acids (DiHOMEs), in the erythrocyte membranes. Collectively, Ang II induced erythrocyte senescence and susceptibility to eryptosis, partially due to enhanced oxidative stress.</p>","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":"25 1","pages":"30-38"},"PeriodicalIF":2.6,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39886570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 5
Changing of the Guard: Our First Editorial. 换岗:我们的第一篇社论。
IF 2.6 4区 医学
Rejuvenation research Pub Date : 2022-02-01 DOI: 10.1089/rej.2022.29005.irc
Irina Conboy
{"title":"Changing of the Guard: Our First Editorial.","authors":"Irina Conboy","doi":"10.1089/rej.2022.29005.irc","DOIUrl":"https://doi.org/10.1089/rej.2022.29005.irc","url":null,"abstract":"","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":"25 1","pages":"1"},"PeriodicalIF":2.6,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39931462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
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