Biomolecules最新文献

{"title":"Hexameric-Based Hierarchy in the Sizes of a Cytolysin Pore-Forming Complex.","authors":"Meijun Liu, Xintao Qin, Menglin Luo, Yi Shen, Jiabin Wang, Jielin Sun, Daniel M Czajkowsky, Zhifeng Shao","doi":"10.3390/biom15030424","DOIUrl":"10.3390/biom15030424","url":null,"abstract":"<p><p>Perfringolysin O (PFO) is a prototypical member of a large family of pore-forming toxins (PFTs) that are potent virulence factors for many pathogenic bacteria. One of the most enigmatic properties of these PFTs is how structural changes are coordinated between different subunits within a single complex. Moreover, there are conflicting data in the literature, with gel electrophoresis results apparently showing that pores are only complete rings, whereas microscopy images clearly also show incomplete-ring pores. Here, we developed a novel multi-stack gel electrophoretic assay to finely separate PFO pore complexes and found that this assay indeed resolves both complete- and incomplete-ring pores. However, unexpectedly, we found that the stoichiometries of these complexes are predominantly integral multiples of six subunits. High-resolution atomic force microscopy images of PFO pore complexes also reveal a predominant hexameric-based stoichiometry. We also observed this hexameric-based stoichiometry at the prepore stage and identified a mutant that is kinetically trapped at a hexameric state. Thus, overall, these results reveal a previously unknown hexameric-based structural hierarchy in the PFO complexes. We suggest that the structural coordination within the hexamers is different than between the hexamers and is thus a critical feature of the structural coordination of the complex as a whole.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assembly Formation of P65 Protein, Featured by an Intrinsically Disordered Region Involved in Gliding Machinery of <i>Mycoplasma pneumoniae</i>.","authors":"Masaru Yabe, Takuma Toyonaga, Miki Kinoshita, Yukio Furukawa, Tasuku Hamaguchi, Yuhei O Tahara, Munehito Arai, Katsumi Imada, Makoto Miyata","doi":"10.3390/biom15030429","DOIUrl":"10.3390/biom15030429","url":null,"abstract":"<p><p><i>Mycoplasma pneumoniae</i> is a human pathogen that glides on host cell surfaces by a repeated catch and release mechanism using sialylated oligosaccharides. At a pole, this organism forms a protrusion called an attachment organelle composed of surface structures, including an adhesin complex and an internal core structure. To clarify the structure and function of the attachment organelle, we focused on a core component, P65, which is essential for stabilization of the adjacent surface and core proteins P30 and HMW2, respectively. Analysis of its amino acid sequence (405 residues) suggested that P65 contains an intrinsically disordered region (residues 1-217) and coiled-coil regions (residues 226-247, 255-283, and 286-320). Four protein fragments and the full-length P65 were analyzed by size exclusion chromatography, analytical centrifugation, circular dichroism spectroscopy, small-angle X-ray scattering, limited proteolysis, and negative staining electron microscopy. The results showed that P65 formed a multimer composed of a central globule with 30 and 23 nm axes and four to six projections 14 nm in length. Our data suggest that the C-terminal region of P65 is responsible for multimerization, while the intrinsically disordered N-terminal region forms a filament. These assignments and roles of P65 in the attachment organelle are discussed.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Lycium barbarum</i> Glycopeptide Promotes Testosterone Synthesis and Glucose Metabolism in Leydig Cells of the Testis.","authors":"Jinlian Liang, Tianchan Peng, Jinrong Hu, Kwok Fai So, Hongyi Zhang, Guobin Chen, Yuan-Wei Zhang","doi":"10.3390/biom15030425","DOIUrl":"10.3390/biom15030425","url":null,"abstract":"<p><p><i>Lycium barbarum</i> extracts have been shown to be effective in male reproductive protection and male infertility. However, its role in enhancing testicular function, such as testosterone synthesis, and the potential mechanism remain to be understood. To elucidate the effects of <i>Lycium barbarum</i> glycopeptide (LbGp) on testosterone synthesis, we isolated primary Leydig cells (LCs) from testes and performed RNA sequencing (RNA seq) on LCs treated with LbGp. In this study, we demonstrated that LbGp promoted testosterone synthesis in LCs both in vivo and in vitro. We also demonstrated that LbGp elevated adenosine 5'-triphosphate (ATP) synthesis and cell proliferation by enhancing glucose metabolism. Mechanistically, LbGp upregulated testosterone synthesis by suppressing TGF-β pathway and enhancing the expression of steroidogenic genes: <i>Cyp11a1</i>, <i>Hsd3b1</i>, <i>Hsd17b3</i>, <i>Star</i>, and <i>Sf-1</i>. These findings indicate that LbGp plays an important role in enhancing testicular function and promoting testosterone synthesis.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Prognostic, Predictive and Clinicopathological Implications of KRT81/HNF1A- and GATA6-Based Transcriptional Subtyping in Pancreatic Cancer.","authors":"Michael Guenther, Sai Agash Surendran, Lea Margareta Steinke, Iduna Liou, Melanie Alexandra Palm, Volker Heinemann, Michael Haas, Stefan Boeck, Steffen Ormanns","doi":"10.3390/biom15030426","DOIUrl":"10.3390/biom15030426","url":null,"abstract":"<p><strong>Background: </strong>Transcriptional subtypes of pancreatic ductal adenocarcinoma (PDAC) based on the expression of hallmark genes may have prognostic implications and potential predictive functions. The two most employed subtyping markers assess the combined expression of KRT81 and HNF1A or of GATA6 alone, which can be detected by immunohistochemistry (IHC). This study aimed to determine the prognostic or predictive impact of both subtyping marker panels in two large cohorts of advanced and resected pancreatic ductal adenocarcinoma (PDAC) patients.</p><p><strong>Methods: </strong>Transcriptional subtypes were determined by combining the expression of KRT81/HNF1A or assessing GATA6 expression alone by IHC in samples of two independent PDAC patient cohorts (advanced PDAC <i>n</i> = 139 and resected PDAC <i>n</i> = 411) as well as in 57 matched primary tumors and their corresponding metastases. RNAseq-based expression data of 316 resected PDAC patients was analyzed for validation.</p><p><strong>Results: </strong>Transcriptional subtypes widely overlapped in both marker panels (χ²<i>p</i> < 0.001) but switched during disease progression in up to 31.6% of patients. They had a modest impact on the patients' prognosis in both cohorts, with longer overall survival (OS) for patients with KRT81-/HNF1A+ or GATA6+ tumors but better progression-free survival (PFS) and disease-free survival (DFS) in patients with KRT81+/GATA6- tumors treated with palliative or adjuvant gemcitabine-based chemotherapy. RNAseq expression data confirmed the findings.</p><p><strong>Conclusions: </strong>Transcriptional subtypes have differential responses to palliative and adjuvant gemcitabine-based chemotherapy and may change during disease progression. Both employed subtyping marker panels are equivalent and may be used to inform clinical therapy decisions.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization of Intra-Arterial Administration of Chemotherapeutic Agents for Glioblastoma in the F98-Fischer Glioma-Bearing Rat Model.","authors":"Juliette Latulippe, Laurent-Olivier Roy, Fernand Gobeil, David Fortin","doi":"10.3390/biom15030421","DOIUrl":"10.3390/biom15030421","url":null,"abstract":"<p><p>Glioblastoma (GBM) is a difficult disease to treat for different reasons, with the blood-brain barrier (BBB) preventing therapeutic drugs from reaching the tumor being one major hurdle. The median overall survival is only 14.6 months after the standard first line of treatment. At relapse, there is no recognized standard second-line treatment. Our team uses intra-arterial (IA) chemotherapy as a means to bypass the BBB, hence achieving an overall median survival of 25 months. However, most patients eventually fail the treatment and progress. This is why we wish to expand our portfolio of options in terms of chemotherapy agents available for IA administration. In this study, we tested topotecan, cytarabine, and new formulations of carboplatin and paclitaxel by IA administration in the F98-Fischer glioma-bearing rat model as a screening tool for identifying potential candidate drugs. The topotecan IA group showed increased survival compared to the intravenous (IV) group (29.0 vs. 23.5), whereas the IV cytarabine group survived longer than the IA group (26.5 vs. 22.5). The new formulation of carboplatin showed a significant increase in survival compared to two previous studies with the conventional form (37.5 vs. 26.0 and 30.0). As for paclitaxel, it was too neurotoxic for IA administration. Topotecan and the new formulation of carboplatin demonstrated significant results, warranting their transition for consideration in clinical trials.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scaffold Proteins in Fibrotic Diseases of Visceral Organs.","authors":"Piaopiao Sun, Liliang Yang, Keqing Yu, Jing Wang, Jie Chao","doi":"10.3390/biom15030420","DOIUrl":"10.3390/biom15030420","url":null,"abstract":"<p><p>Fibrosis, characterized by excessive extracellular matrix (ECM) deposition, disrupts tissue architecture and impairs organ function, ultimately leading to severe health consequences and even failure of vital organs such as the lung, heart, liver, and kidney. Despite significant advances in understanding the molecular mechanisms underlying fibrosis, effective therapeutic options remain limited. Emerging evidence highlights scaffold proteins as critical regulators in the progression of fibrosis. These multifunctional proteins serve as molecular platforms that organize and coordinate key signaling pathways-including those governing ECM remodeling, cytoskeletal organization, and cell migration-thereby integrating both profibrotic and antifibrotic signals. Their pivotal role in linking mechanotransduction, inflammatory, and developmental signals offers a unique therapeutic window, as targeted interventions (e.g., small-molecule inhibitors, peptides, biologics, and gene therapy) are emerging to modulate these pathways. This review synthesizes recent findings on scaffold protein functions across multiple organs and discusses novel therapeutic strategies to manage and potentially reverse fibrosis.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Purinergic Mechanisms in the Excitability of Trigeminal Afferents of Rats with Prenatal Hyperhomocysteinemia.","authors":"Elizaveta Ermakova, Svetlana Svitko, Alsu Kabirova, Egor Nevsky, Olga Yakovleva, Karina Gilizhdinova, Kseniia Shaidullova, Anton Hermann, Guzel Sitdikova","doi":"10.3390/biom15030419","DOIUrl":"10.3390/biom15030419","url":null,"abstract":"<p><p>Elevated levels of homocysteine in the blood plasma (hyperhomocysteinemia, HHCY) positively correlate with migraine symptoms in patients. Experimental studies show a higher sensitivity of rats with prenatal HHCY (pHHCY) to migraine symptoms like allodynia, photophobia, anxiety, and a higher excitability of meningeal trigeminal afferents. In the present study, the roles of purinergic mechanisms in the homocysteine-induced hyperexcitability of the trigeminal ganglion (TG) system using electrophysiological recordings from the trigeminal nerve, Ca²⁺ imaging of cells isolated from TG, and mast cell staining in meninges were investigated. Experiments were performed using rats with pHHCY born from females fed with a high-methionine-containing diet before and during pregnancy. Firstly, we found that lower concentrations of 4-aminopyridine, a K⁺-channel blocker, were able to induce an increase in the nociceptive activity of trigeminal afferents, supporting the hypothesis of the higher excitability of the trigeminal nerve of rats with pHHCY. Trigeminal afferents of rats with pHHCY were more sensitive to the exogenous application of the nonspecific agonist of purinergic ATP receptors. In neurons and satellite glial cells of TG of rats with pHHCY ATP, ADP (an agonist of metabotropic P2Y receptors) and BzATP (an agonist of ionotropic P2X with especially high potency for the P2X7 receptor) induced larger Ca²⁺ transients. The incubation of TG neurons in homocysteine for 24 h increased the ratio of neurons responding simultaneously to ATP and capsaicin. Moreover, rats with pHHCY exhibit a higher rate of degranulation of mast cells and increased response to the agonist of the P2X7 receptor BzATP application. In addition, higher levels of calcitonin gene-related peptide (CGRP) were found in rats with pHHCY. Our results suggest that chronic elevated levels of homocysteine induce the upregulation of ionotropic or metabotropic ATP receptors in neurons, satellite glial cells, and mast cells, which further provide inflammatory conditions and the sensitization of peripheral afferents underlying pain.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing Membrane Repair Using Recombinant MG53/TRIM72 (rhMG53) Reduces Neurotoxicity in Alzheimer's Disease Models.","authors":"Hannah R Bulgart, Miguel A Lopez Perez, Noah Weisleder","doi":"10.3390/biom15030418","DOIUrl":"10.3390/biom15030418","url":null,"abstract":"<p><p>Alzheimer's Disease (AD) is the most common neurodegenerative disease that involves neuronal cell death initiated by the breakdown of the plasma membrane. Amyloid beta (Aβ), a hallmark protein that contributes to AD pathogenesis, is known to interact directly with the plasma membrane and induce increased intracellular calcium levels, reactive oxygen species (ROS), and cell death. Our recent studies revealed that elevated levels of Aβ₄₂ induce a plasma membrane repair defect in neurons that compromises this conserved cellular response that would normally repair the disruption. Here, we tested if recombinant MG53/TRIM72 protein (rhMG53), a therapeutic protein known to increase plasma membrane repair capacity, could enhance membrane repair in AD neurons. rhMG53 increased plasma membrane repair in ex vivo and in vitro tissue treated with Aβ₄₂ or cerebrospinal fluid from AD patients, normalizing intracellular calcium levels, ROS, and cell death in treated cells. This study demonstrates that increasing plasma membrane repair can rescue neural cells from the neurotoxic effects of Aβ, indicating that elevating plasma membrane repair could be a viable therapeutic approach to reduce neuronal death in AD.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Plasmid System That Utilises Phosphoribosylanthranilate Isomerase to Select Against Cells Expressing Truncated Proteins.","authors":"Aditi A Ghuge, Susanne Gottfried, Anja H Schiemann, Evelyn Sattlegger","doi":"10.3390/biom15030412","DOIUrl":"10.3390/biom15030412","url":null,"abstract":"<p><p>We have generated a vector that enables the removal of plasmids coding for truncated proteins. This vector expresses a protein of interest in the yeast <i>Saccharomyces cerevisiae</i> from a galactose-inducible promoter. The gene of interest is fused in-frame to a downstream sequence coding for phosphoribosylanthranilate isomerase (PRAI), which catalyses the third step in tryptophan biosynthesis. As a consequence, only the full-length protein of interest renders the host cell tryptophan prototrophic, allowing for selection against cells expressing truncated proteins. Our proof-of-principle study demonstrates that PRAI is functional when fused C-terminally to a protein, robustly rendering cells tryptophan prototrophic. The N-terminal GST tag and C-terminal myc tag allow for tag-mediated protein purification, co-precipitation studies, determination of relative expression levels, as well as validation of full-length expression of the protein via Western blotting.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progressive Alcohol-Related Brain Atrophy and White Matter Pathology Are Linked to Long-Term Inhibitory Effects on mTOR Signaling.","authors":"Ming Tong, Camilla Homans, William Pelit, Busra Delikkaya, Suzanne M de la Monte","doi":"10.3390/biom15030413","DOIUrl":"10.3390/biom15030413","url":null,"abstract":"<p><strong>Background: </strong>Alcohol-related brain damage (ARBD) causes cognitive-behavioral impairments that can lead to dementia. White matter is a major target in ARBD. Additional research is needed to better understand the mechanisms of ARBD progression to advanced stages with permanent disability. Potential contributing factors include neuroinflammation and altered signaling through pathways that regulate cell survival, neuronal plasticity, myelin maintenance, and energy metabolism.</p><p><strong>Objectives: </strong>This study characterizes the time course-related effects of chronic heavy ethanol feeding on white matter myelin protein expression, neuroinflammation, and molecules that mediate signaling through the mechanistic target of rapamycin (mTOR) pathways.</p><p><strong>Methods: </strong>Adult Long Evans rats (8-12/group) were fed with isocaloric liquid diets containing 0% (control) or 36% ethanol. Experimental endpoints spanned from 1 day to 8 weeks. The frontal lobes were used for histopathology and molecular and biochemical analyses.</p><p><strong>Results: </strong>Chronic ethanol feeding caused significant brain atrophy that was detected within 4 weeks and sustained over the course of the study. Early exposure time points, i.e., 2 weeks or less, were associated with global increases in the expression of non-myelinating, myelinating, and astrocyte markers, whereas at 6 or 8 weeks, white matter oligodendrocyte/myelin/glial protein expression was reduced. These effects were not associated with shifts in neuroinflammatory markers. Instead, the early stages of ARBD were accompanied by increases in several mTOR proteins and phosphoproteins, while later phases were marked by inhibition of downstream mTOR signaling through P70S6K.</p><p><strong>Conclusions: </strong>Short-term versus long-term ethanol exposures differentially altered white matter glial protein expression and signaling through mTOR's downstream mediators that have known roles in myelin maintenance. These findings suggest that strategic targeting of mTOR signaling dysregulation may be critical for maintaining the functional integrity of white matter and ultimately preventing long-term ARBD-related cognitive impairment.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}