Biomolecules & Therapeutics最新文献

{"title":"Understanding the Unfolded Protein Response (UPR) Pathway: Insights into Neuropsychiatric Disorders and Therapeutic Potentials.","authors":"Pitna Kim","doi":"10.4062/biomolther.2023.181","DOIUrl":"10.4062/biomolther.2023.181","url":null,"abstract":"<p><p>The Unfolded Protein Response (UPR) serves as a critical cellular mechanism dedicated to maintaining protein homeostasis, primarily within the endoplasmic reticulum (ER). This pathway diligently responds to a variety of intracellular indicators of ER stress with the objective of reinstating balance by diminishing the accumulation of unfolded proteins, amplifying the ER's folding capacity, and eliminating slow-folding proteins. Prolonged ER stress and UPR irregularities have been linked to a range of neuropsychiatric disorders, including major depressive disorder, bipolar disorder, and schizophrenia. This review offers a comprehensive overview of the UPR pathway, delineating its activation mechanisms and its role in the pathophysiology of neuropsychiatric disorders. It highlights the intricate interplay within the UPR and its profound influence on brain function, synaptic perturbations, and neural developmental processes. Additionally, it explores evolving therapeutic strategies targeting the UPR within the context of these disorders, underscoring the necessity for precision and further research to effective treatments. The research findings presented in this work underscore the promising potential of UPR-focused therapeutic approaches to address the complex landscape of neuropsychiatric disorders, giving rise to optimism for improving outcomes for individuals facing these complex conditions.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"32 2","pages":"183-191"},"PeriodicalIF":3.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10902702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139970903","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}

{"title":"Erratum to \"Small Molecule Inhibitors of Middle East Respiratory Syndrome Coronavirus Fusion by Targeting Cavities on Heptad Repeat Trimers\" [Biomol Ther 28(4), 311-319 (2020)].","authors":"Mahmoud Kandeel, Mizuki Yamamoto, Abdulla Al-Taher, Aya Watanabe, Kentaro Oh-Hashi, Byoung Kwon Park, Hyung-Joo Kwon, Jun-Ichiro Inoue, Mohammed Al-Nazawi","doi":"10.4062/biomolther.2024.001","DOIUrl":"10.4062/biomolther.2024.001","url":null,"abstract":"","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"32 2","pages":"262-265"},"PeriodicalIF":3.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10902707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139982270","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}

{"title":"Association between <i>LEPR</i> Genotype and Gut Microbiome in Healthy Non-Obese Korean Adults.","authors":"Yoon Jung Cha, In Ae Chang, Eun-Heui Jin, Ji Hye Song, Jang Hee Hong, Jin-Gyu Jung, Jung Sunwoo","doi":"10.4062/biomolther.2023.116","DOIUrl":"10.4062/biomolther.2023.116","url":null,"abstract":"<p><p>The <i>LEPR</i> (leptin receptor) genotype is associated with obesity. Gut microbiome composition differs between obese and non-obese adults. However, the impact of <i>LEPR</i> genotype on gut microbiome composition in humans has not yet been studied. In this study, the association between <i>LEPR</i> single nucleotide polymorphism (rs1173100, rs1137101, and rs790419) and the gut microbiome composition in 65 non-obese Korean adults was investigated. Leptin, triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels were also measured in all participants. Mean ± SD (standard deviation) of age, body mass index, and leptin hormone levels of participants was 35.2 ± 8.1 years, 21.4 ± 1.8 kg/m², and 7989.1 ± 6687.4 pg/mL, respectively. Gut microbiome analysis was performed at the phylum level by 16S rRNA sequencing. Among the 11 phyla detected, only one showed significantly different relative abundances between <i>LEPR</i> genotypes. The relative abundance of Candidatus Saccharibacteria was higher in the G/A genotype group than in the G/G genotype group for the rs1137101 single nucleotide polymorphism (<i>p</i>=0.0322). Participant characteristics, including body mass index, leptin levels, and other lipid levels, were similar between the rs1137101 G/G and G/A genotypes. In addition, the relative abundances of Fusobacteria and Tenericutes showed significant positive relationship with plasma leptin concentrations (<i>p</i>=0.0036 and <i>p</i>=0.0000, respectively). In conclusion, <i>LEPR</i> genotype and gut microbiome may be associated even in normal-weight Korean adults. However, further studies with a greater number of obese adults are needed to confirm whether <i>LEPR</i> genotype is related to gut microbiome composition.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"146-153"},"PeriodicalIF":3.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10259986","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}

{"title":"Current Development Status of Cytokines for Cancer Immunotherapy.","authors":"Kyoung Song","doi":"10.4062/biomolther.2023.196","DOIUrl":"10.4062/biomolther.2023.196","url":null,"abstract":"<p><p>Cytokines influence the overall cancer immune cycle by triggering tumor antigen expression, antigen presenting, immune cell priming and activation, effector immune cell recruitment and infiltration to cancer, and cancer killing in the tumor microenvironment (TME). Therefore, cytokines have been considered potential anti-cancer immunotherapy, and cytokine-based anti-cancer therapies continue to be an active area of research and development in the field of cancer immunotherapy, with ongoing clinical trials exploring new strategies to improve efficacy and safety. In this review, we examine past and present clinical developments for major anticancer cytokines, including interleukins (IL-2, IL-15, IL-12, IL-21), interferons, TGF-beta, and GM-CSF. We identify the current status and changes in the technology platform being applied to cytokine-based immune anti-cancer therapeutics. Through this, we discuss the opportunities and challenges of cytokine-based immune anti-cancer treatments in the current immunotherapy market and suggest development directions to enhance the clinical use of cytokines as immuno-anticancer drugs in the future.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"32 1","pages":"13-24"},"PeriodicalIF":3.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039474","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}

{"title":"Effect of Various Pathological Conditions on Nitric Oxide Level and L-Citrulline Uptake in Motor Neuron-Like (NSC-34) Cell Lines.","authors":"Shashi Gautam, Sana Latif, Young-Sook Kang","doi":"10.4062/biomolther.2023.110","DOIUrl":"10.4062/biomolther.2023.110","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder that causes progressive paralysis. L-Citrulline is a non-essential neutral amino acid produced by L-arginine via nitric oxide synthase (NOS). According to previous studies, the pathogenesis of ALS entails glutamate toxicity, oxidative stress, protein misfolding, and neurofilament disruption. In addition, L-citrulline prevents neuronal cell death in brain ischemia; therefore, we investigated the change in the transport of L-citrulline under various pathological conditions in a cell line model of ALS. We examined the uptake of [¹⁴C]L-citrulline in wild-type (hSOD1wt/WT) and mutant NSC-34/ SOD1^G93A (MT) cell lines. The cell viability was determined via MTT assay. A transport study was performed to determine the uptake of [¹⁴C]L-citrulline. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was performed to determine the expression levels of rat large neutral amino acid transported 1 (rLAT1) in ALS cell lines. Nitric oxide (NO) assay was performed using Griess reagent. L-Citrulline had a restorative effect on glutamate induced cell death, and increased [¹⁴C]L-citrulline uptake and mRNA levels of the large neutral amino acid transporter (LAT1) in the glutamate-treated ALS disease model (MT). NO levels increased significantly when MT cells were pretreated with glutamate for 24 h and restored by co-treatment with L-citrulline. Co-treatment of MT cells with L-arginine, an NO donor, increased NO levels. NSC-34 cells exposed to high glucose conditions showed a significant increase in [¹⁴C]L-citrulline uptake and LAT1 mRNA expression levels, which were restored to normal levels upon co-treatment with unlabeled L-citrulline. In contrast, exposure of the MT cell line to tumor necrosis factor alpha, lipopolysaccharides, and hypertonic condition decreased the uptake significantly which was restored to the normal level by co-treating with unlabeled L-citrulline. L-Citrulline can restore NO levels and cellular uptake in ALS-affected cells with glutamate cytotoxicity, pro-inflammatory cytokines, or other pathological states, suggesting that L-citrulline supplementation in ALS may play a key role in providing neuroprotection.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"32 1","pages":"154-161"},"PeriodicalIF":3.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039476","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}

{"title":"Immunological Mechanisms in Cutaneous Adverse Drug Reactions.","authors":"Ai-Young Lee","doi":"10.4062/biomolther.2023.170","DOIUrl":"10.4062/biomolther.2023.170","url":null,"abstract":"<p><p>Adverse drug reactions (ADRs) are an inherent aspect of drug use. While approximately 80% of ADRs are predictable, immune system-mediated ADRs, often unpredictable, are a noteworthy subset. Skin-related ADRs, in particular, are frequently unpredictable. However, the wide spectrum of skin manifestations poses a formidable diagnostic challenge. Comprehending the pathomechanisms underlying ADRs is essential for accurate diagnosis and effective management. The skin, being an active immune organ, plays a pivotal role in ADRs, although the precise cutaneous immunological mechanisms remain elusive. Fortunately, clinical manifestations of skin-related ADRs, irrespective of their severity, are frequently rooted in immunological processes. A comprehensive grasp of ADR morphology can aid in diagnosis. With the continuous development of new pharmaceuticals, it is noteworthy that certain drugs including immune checkpoint inhibitors have gained notoriety for their association with ADRs. This paper offers an overview of immunological mechanisms involved in cutaneous ADRs with a focus on clinical features and frequently implicated drugs.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"32 1","pages":"1-12"},"PeriodicalIF":3.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039479","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}

{"title":"Contribution of HSP90 Cleavage to the Cytotoxic Effect of Suberoylanilide Hydroxamic Acid <i>In Vivo</i> and the Involvement of TXNIP in HSP90 Cleavage.","authors":"Sangkyu Park, Dongbum Kim, Haiyoung Jung, In Pyo Choi, Hyung-Joo Kwon, Younghee Lee","doi":"10.4062/biomolther.2023.104","DOIUrl":"10.4062/biomolther.2023.104","url":null,"abstract":"<p><p>Heat shock protein (HSP) 90 is expressed in most living organisms, and several client proteins of HSP90 are necessary for cancer cell survival and growth. Previously, we found that HSP90 was cleaved by histone deacetylase (HDAC) inhibitors and proteasome inhibitors, and the cleavage of HSP90 contributes to their cytotoxicity in K562 leukemia cells. In this study, we first established mouse xenograft models with K562 cells expressing the wild-type or cleavage-resistant mutant HSP90β and found that the suppression of tumor growth by the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) was interrupted by the mutation inhibiting the HSP90 cleavage <i>in vivo</i>. Next, we investigated the possible function of thioredoxin interacting protein (TXNIP) in the HSP90 cleavage induced by SAHA. TXNIP is a negative regulator for thioredoxin, an antioxidant protein. SAHA transcriptionally induced the expression of TXNIP in K562 cells. HSP90 cleavage was induced by SAHA also in the thymocytes of normal mice and suppressed by an anti-oxidant and pan-caspase inhibitor. When the thymocytes from the TXNIP knockout mice and their wild-type littermate control mice were treated with SAHA, the HSP90 cleavage was detected in the thymocytes of the littermate controls but suppressed in those of the TXNIP knockout mice suggesting the requirement of TXNIP for HSP90 cleavage. We additionally found that HSP90 cleavage was induced by actinomycin D, β-mercaptoethanol, and p38 MAPK inhibitor PD169316 suggesting its prevalence. Taken together, we suggest that HSP90 cleavage occurs also <i>in vivo</i> and contributes to the anti-cancer activity of various drugs in a TXNIP-dependent manner.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"32 1","pages":"115-122"},"PeriodicalIF":3.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039473","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}

{"title":"Exploring the Potential of Rosemary Derived Compounds (Rosmarinic and Carnosic Acids) as Cancer Therapeutics: Current Knowledge and Future Perspectives.","authors":"Fazila Sirajudeen, Lara J Bou Malhab, Yasser Bustanji, Moyad Shahwan, Karem H Alzoubi, Mohammad H Semreen, Jalal Taneera, Waseem El-Huneidi, Eman Abu-Gharbieh","doi":"10.4062/biomolther.2023.054","DOIUrl":"10.4062/biomolther.2023.054","url":null,"abstract":"<p><p>Cancer is a global health challenge with high morbidity and mortality rates. However, conventional cancer treatment methods often have severe side effects and limited success rates. In the last decade, extensive research has been conducted to develop safe, and efficient alternative treatments that do not have the limitations of existing anticancer medicines. Plant-derived compounds have shown promise in cancer treatment for their anti-carcinogenic and anti-proliferative properties. Rosmarinic acid (RA) and carnosic acid (CA) are potent polyphenolic compounds found in rosemary (<i>Rosmarinus officinalis</i>) extract. They have been extensively studied for their biological properties, which include anti-diabetic, anti-inflammatory, antioxidant, and anticancer activities. In addition, RA and CA have demonstrated effective anti-proliferative properties against various cancers, making them promising targets for extensive research to develop candidate or leading compounds for cancer treatment. This review discusses and summarizes the anti-tumor effect of RA and CA against various cancers and highlights the involved biochemical and mechanistic pathways.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"32 1","pages":"38-55"},"PeriodicalIF":3.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039478","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}

{"title":"Rosmarinic Acid Inhibits Ultraviolet B-Mediated Oxidative Damage via the AKT/ERK-NRF2-GSH Pathway <i>In Vitro</i> and <i>In Vivo</i>.","authors":"Mei Jing Piao, Pattage Madushan Dilhara Jayatissa Fernando, Kyoung Ah Kang, Pincha Devage Sameera Madushan Fernando, Herath Mudiyanselage Udari Lakmini Herath, Young Ree Kim, Jin Won Hyun","doi":"10.4062/biomolther.2023.179","DOIUrl":"10.4062/biomolther.2023.179","url":null,"abstract":"<p><p>Rosmarinic acid (RA) is a phenolic ester that protects human keratinocytes against oxidative damage induced by ultraviolet B (UVB) exposure, however, the mechanisms underlying its effects remain unclear. This study aimed to elucidate the cell signaling mechanisms that regulate the antioxidant activity of RA and confirm its cyto-protective role. To explore the signaling mechanisms, we used the human keratinocyte cell line HaCaT and SKH1 hairless mouse skin. RA enhanced glutamate-cysteine ligase catalytic subunit (GCLC) and glutathione synthetase (GSS) expression in HaCaT cells in a dose- and time-dependent manner. Moreover, RA induced nuclear factor erythroid-2-related factor 2 (NRF2) nuclear translocation and activated the signaling kinases protein kinase B (AKT) and extracellular signal-regulated kinase (ERK). Treatment with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, the ERK inhibitor U0126, and small interfering RNA (siRNA) gene silencing suppressed RA-enhanced GCLC, GSS, and NRF2 expression, respectively. Cell viability tests showed that RA significantly prevented UVB-induced cell viability decrease, whereas the glutathione (GSH) inhibitors buthionine sulfoximine, LY294002, and U0126 significantly reduced this effect. Moreover, RA protected against DNA damage and protein carbonylation, lipid peroxidation, and apoptosis caused by UVB-induced oxidative stress in a concentration-dependent manner in SKH1 hairless mouse skin tissues. These results suggest that RA protects against UVB-induced oxidative damage by activating AKT and ERK signaling to regulate NRF2 signaling and enhance GSH biosynthesis. Thus, RA treatment may be a promising approach to protect the skin from UVB-induced oxidative damage.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"32 1","pages":"84-93"},"PeriodicalIF":3.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039492","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}

{"title":"Intermittent Fasting Modulates Immune Response by Generating Tregs via TGF-β Dependent Mechanisms in Obese Mice with Allergic Contact Dermatitis.","authors":"Sang-Chul Han, Jung-Il Kang, Youn Kyung Choi, Hye-Jin Boo, Weon-Jong Yoon, Hee-Kyoung Kang, Eun-Sook Yoo","doi":"10.4062/biomolther.2023.053","DOIUrl":"10.4062/biomolther.2023.053","url":null,"abstract":"<p><p>People with obesity maintain low levels of inflammation; therefore, their exposure to foreign antigens can trigger an excessive immune response. In people with obesity or allergic contact dermatitis (ACD), symptoms are exacerbated by a reduction in the number of regulatory T cells (Tregs) and IL-10/TGF-β-modified macrophages (M2 macrophages) at the inflammatory site. Benefits of intermittent fasting (IF) have been demonstrated for many diseases; however, the immune responses regulated by macrophages and CD4⁺T cells in obese ACD animal models are poorly understood. Therefore, we investigated whether IF suppresses inflammatory responses and upregulates the generation of Tregs and M2 macrophages in experimental ACD animal models of obese mice. The IF regimen relieved various ACD symptoms in inflamed and adipose tissues. We showed that the IF regimen upregulates Treg generation in a TGF-β-dependent manner and induces CD4⁺T cell hypo-responsiveness. IF-M2 macrophages, which strongly express TGF-β and inhibit CD4⁺T cell proliferation, directly regulated Treg differentiation from CD4⁺T cells. These results indicate that the IF regimen enhances the TGF-β-producing ability of M2 macrophages and that the development of Tregs keeps mice healthy against ACD exacerbated by obesity. Therefore, the IF regimen may ameliorate inflammatory immune disorders caused by obesity.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"136-145"},"PeriodicalIF":3.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9754651","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}