Advances in biological regulation最新文献

{"title":"A coordinated paracrine islet cell network regulating β-cell Ca²⁺ dynamics.","authors":"Philip Tröster, Montse Visa, Martin Köhler, Per-Olof Berggren","doi":"10.1016/j.jbior.2026.101184","DOIUrl":"https://doi.org/10.1016/j.jbior.2026.101184","url":null,"abstract":"<p><p>Pulsatile insulin secretion originates from oscillations in cytosolic free Ca²⁺ in pancreatic islet β-cells. Decades of work have identified multiple determinants of these oscillations, including glucose metabolism, ion channels, ER Ca²⁺ handling, cellular heterogeneity, and paracrine and neurohormonal signaling. Yet their relative contributions under physiological conditions remain unresolved because each experimental preparation preserves only a subset of these regulatory layers. Here, we review evidence that intercellular paracrine signaling, in addition to cell-autonomous β-cell machinery, is an important determinant of oscillation frequency and coordination. Simultaneous Ca²⁺ imaging of α-cells and β-cells reveals tightly coordinated activity, with α-cells following β-cells after a conserved ∼20-s delay. Perturbation of glucagon signaling further indicates that α-cell signaling can modulate β-cell oscillation frequency. Complementing these findings, in vivo imaging of islets engrafted in the anterior chamber of the eye shows that α-cell expansion enhances β-cell Ca²⁺ coordination in a glucagon-receptor-dependent manner. Extending this circuit to δ-cells, somatostatin limits oscillation frequency primarily by suppressing α-cell glucagon release, thereby enabling the δ-cell-α-cell-β-cell paracrine circuit to shift β-cell oscillations between fast, mixed, and slow regimes. Importantly, a glycemia-dependent slow-to-fast transition is lost in diabetic mice and rescued by GLP-1 receptor agonism. Under anesthesia-free conditions, however, islets in awake animals occupy a slow, highly synchronized oscillatory regime in which glucose modulates amplitude, period, and plateau fraction without altering network coordination. Together, these findings suggest that the δ-cell-α-cell-β-cell circuit represents an important regulatory layer shaping β-cell Ca²⁺ oscillations alongside intrinsic β-cell mechanisms and extrinsic physiological inputs. β-cell dysfunction may therefore involve not only altered oscillation frequency and coordination, but also disrupted paracrine regulation by glucagon and somatostatin.</p>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":" ","pages":"101184"},"PeriodicalIF":2.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apolipoprotein CIII as a therapeutic target in obesity-associated metabolic dysfunction.","authors":"Ismael Valladolid-Acebes, Per-Olof Berggren, Lisa Juntti-Berggren","doi":"10.1016/j.jbior.2026.101183","DOIUrl":"https://doi.org/10.1016/j.jbior.2026.101183","url":null,"abstract":"<p><p>Apolipoprotein CIII (apoCIII) is a major regulator of lipid metabolism and increased levels are related to higher risk of cardiovascular disease. Increasing evidence, however, suggests that apoCIII may also play an important role in obesity-associated metabolic dysfunction and type 2 diabetes (T2D). ApoCIII inhibits lipoprotein lipase and hepatic lipases and impairs the hepatic clearance of triglyceride-rich lipoproteins, thereby promoting hypertriglyceridemia. In addition, apoCIII has been implicated in inflammatory processes that may contribute to metabolic and vascular disease. Importantly, insulin and glucose regulate apoCIII expression, providing a mechanistic link between apoCIII and the metabolic disturbances associated with obesity and diabetes. In this review, we summarize current evidence concerning the relationship between apoCIII and obesity-associated metabolic dysfunction. Diet-induced and genetic models of obesity exhibit elevated circulating apoCIII levels as well as increased apoCIII expression in pancreatic islets. Elevated apoCIII is associated with impaired lipid metabolism, adipose tissue dysfunction, inflammation, insulin resistance, and disturbed glucose homeostasis. Conversely, pharmacological reduction of apoCIII using antisense oligonucleotides improves the metabolic dysfunctions. These effects appear to involve mechanisms extending beyond triglyceride lowering, including enhanced lipoprotein clearance, increased hepatic fatty-acid oxidation and ketogenesis, and increased thermogenic activity in adipose tissue. Preliminary clinical evidence suggests that apoCIII reduction may also improve lipid and glucose metabolism and insulin sensitivity in individuals with obesity, T2D, and hypertriglyceridemia. ApoCIII therefore represents a potential therapeutic target in obesity-associated metabolic disease. Further clinical studies are needed to establish the efficacy, safety, and long-term metabolic effects of targeted apoCIII lowering in obesity and diabetes in humans.</p>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":" ","pages":"101183"},"PeriodicalIF":2.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transient phospholipid asymmetry as a regulatory switch coupling exocytosis to compensatory endocytosis.","authors":"Margherita Caputo, Olga Gubar, Petra Tóth, Emma Darracq, Sylvette Chasserot-Golaz, Stéphane Ory, Stéphane Gasman, Nicolas Vitale","doi":"10.1016/j.jbior.2026.101187","DOIUrl":"https://doi.org/10.1016/j.jbior.2026.101187","url":null,"abstract":"<p><p>Plasma membrane phospholipid asymmetry is usually described as a homeostatic arrangement that preserves surface identity. In secretory cells, however, this arrangement is briefly and locally relaxed when intracellular calcium rises. Evidence from adrenal chromaffin cells and cerebellar synapses now places this transient remodeling at a specific point in the vesicle cycle: it is largely dispensable for membrane fusion, yet it is required for efficient compensatory endocytosis. In both systems, loss of phospholipid scramblase 1 (PLSCR1) prevents stimulus-dependent phosphatidylserine exposure without substantially reducing the initial exocytic response. The consequences emerge during membrane retrieval, with defective recapture of secretory-granule membrane proteins in chromaffin cells, delayed synaptic-vesicle endocytosis in neurons, and a failure to sustain neurotransmission during high-frequency activity. These findings shift the emphasis from phosphatidylserine exposure as a passive correlate of secretion to lipid asymmetry as a dynamic regulatory variable. Several non-exclusive mechanisms may account for this effect. Scrambling may relax leaflet stress, lower membrane stiffness, accelerate lateral diffusion, preserve the identity of recently fused vesicular membrane, and reorganize electrostatic interactions that govern actin and endocytic protein recruitment. At the same time, the molecular status of PLSCR1 remains unsettled. Its direct lipid-translocating activity has not been established in intact cells, and it may instead act through oligomerization, an unidentified transporter, or a signaling scaffold. This review integrates the neuroendocrine and synaptic evidence, identifies the strongest mechanistic inferences, and outlines experiments needed to distinguish lipid transport from lipid-dependent signaling in the coupling of exocytosis to endocytosis.</p>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":" ","pages":"101187"},"PeriodicalIF":2.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BNIP3/NIX-mediated mitophagy versus Parkin-mediated mitophagy: mechanistic differences and functional implications.","authors":"Satoshi Waguri, Shun-Ichi Yamashita, Ritsuko Arai, Tomotake Kanki","doi":"10.1016/j.jbior.2026.101186","DOIUrl":"https://doi.org/10.1016/j.jbior.2026.101186","url":null,"abstract":"<p><p>Mitophagy is a form of selective autophagy in which an isolation membrane (IM or phagophore) sequesters damaged or superfluous mitochondria for lysosomal degradation. Recent advances in receptor-mediated mitophagy, particularly the BNIP3/NIX-mediated mitophagy, have highlighted the importance of this pathway in mitochondrial regulation across various biological settings, along with the well-established Parkin-mediated pathway. Parkin-mediated mitophagy senses mitochondrial damage through loss of membrane potential, whereas BNIP3/NIX-mediated mitophagy plays an important role in basal or physiologically induced mitochondrial turnover, thereby contributing to mitochondrial quality control and remodeling. These two pathways employ distinct sets of molecules to recruit the autophagy machinery to the mitochondria and exhibit different IM dynamics that are closely linked to mitochondrial fission and segregation. In this review, we first provide an updated overview of the autophagy process and then compare these two major forms of mitophagy, with particular emphasis on the molecular mechanisms of mitophagy initiation and IM dynamics. We also discuss the functional implications of these mechanistic differences in physiological and pathological context.</p>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":" ","pages":"101186"},"PeriodicalIF":2.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DGIST: A standardized image-based spatial quantification workflow for neurogenesis in the dentate gyrus","authors":"Jinhee Lee,&nbsp;Wonyoung Lee,&nbsp;Yoichi Kosodo","doi":"10.1016/j.jbior.2026.101173","DOIUrl":"10.1016/j.jbior.2026.101173","url":null,"abstract":"<div><div>The adult hippocampus generates new neurons in the dentate gyrus (DG), where neural stem cells (NSCs) in the subgranular zone differentiate into neuronal and astroglial lineages. Accurate quantification of adult NSCs is critical for assessing neurogenic potential, yet most current methods rely on manual, density-based measurements in limited regions of the DG. These approaches may introduce bias due to morphological variability among tissue sections. To overcome these challenges, we developed the Dentate Gyrus Image-based Spatial quantification Tool (DGIST), an ImageJ/Fiji-based workflow that integrates BioVoxxel and MorphoLibJ plug-ins for cell-based quantification throughout the entire DG. Applied to <em>in vivo</em> datasets, DGIST quantifies age-dependent changes in marker-defined NSC and astroglial populations. Our results demonstrate that DGIST provides a reproducible method for quantifying marker-defined populations in the adult neurogenic niche.</div></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"101 ","pages":"Article 101173"},"PeriodicalIF":2.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148696912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three-dimensional genome architecture: from contacts to mechanisms.","authors":"Peter Hoboth, Martin Sztacho","doi":"10.1016/j.jbior.2026.101171","DOIUrl":"https://doi.org/10.1016/j.jbior.2026.101171","url":null,"abstract":"<p><p>Three-dimensional genome architecture (3DGA) is an active, self-reinforcing system in which chromatin biochemical state and spatial organization are reciprocally coupled. Thus, 3DGA provides a physical substrate through which past regulatory events are encoded, maintained, and re-established, as a form of cellular memory. Understanding how 3DGA arises and persists requires the integration of three complementary approaches, each illuminating aspects of 3DGA that the others cannot fully capture. Chromosome conformation capture and its derivatives, culminating in Hi-C, have generated genome-wide maps of chromatin contacts revealing compartments, topologically associating domains, and loops, but report ensemble-averaged contact frequencies that obscure the variability and dynamics realized in individual nuclei. Super-resolution microscopy and chromatin tracing directly resolve the spatial geometry of chromatin in single cells, revealing that the structural features inferred from Hi-C are probabilistic and heterogeneous rather than fixed, and capturing the transient, stochastic nature of enhancer-promoter contacts. Biochemical reconstitution together with single-molecule approaches define the causal mechanisms underlying the organizational features of 3DGA, but operate on material removed from its native cellular context. We discuss how the integration of these three approaches has shifted our view of 3DGA from a passive correlate of gene expression to a dynamic memory machine.</p>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":" ","pages":"101171"},"PeriodicalIF":2.7,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complex role of mTOR signaling pathway in glioblastoma and its stem cells","authors":"Austin B. Carpenter,&nbsp;Ariel Sacknovitz,&nbsp;Simon Hanft,&nbsp;Chirag D. Gandhi,&nbsp;Meena Jhanwar-Uniyal","doi":"10.1016/j.jbior.2025.101143","DOIUrl":"10.1016/j.jbior.2025.101143","url":null,"abstract":"<div><div>Mechanistic target of rapamycin (mTOR: aka mammalian target of rapamycin), a serine threonine kinase, functions by forming two multiprotein complexes designated mTORC1 and mTORC2. This signaling cascade of PI3K/AKT/mTOR is often upregulated due to frequent loss of the tumor suppressor PTEN, a phosphatase that functions antagonistically to PI3K. mTORC1 is sensitive to nutrients and mTORC2 is regulated via PI3K and growth factor signaling. Aberrant signaling of mTOR is shown to be associated with tumorigenesis of numerous malignancies including glioblastoma (GBM). mTORC1 and mTORC2 activate downstream substrates that execute cellular and metabolic functions. Experimental models have provided evidence of the existence of cancer stem cells (CSCs), also known as tumor-initiating cells within the tumor mass, that may play an active role in development, progression and reformation of GBM. In addition, presence of highly infiltrative CSCs in the peritumoral region of GBM may appear to play an important role in recurrence of disease. Since rapamycin and its analogues are less effective in treatment of GBM, the use of ATP-competitive dual inhibitors of mTORC1 and mTORC2 have been increasingly investigated. These attempt to suppress GBM growth by pharmacodynamically inhibiting phosphorylation of the mTORC1 substrates S6K Ser235/236 and 4E-BP1 Thr37/46. These inhibitors also cause down-regulation of mTORC2 substrate AKT Ser473. These reactions result in reduction of cell growth and migration. Notably, these inhibitors of mTOR also alter self-renewal and growth of CSC of GBM. The aim of this review is to reiterate the use of mTOR inhibitors in the treatment of GBM and its stem cells associated with progression and recurrence of the disease. In addition, understanding the peritumor area of GBM is a crucial means to control the recurrence of the disease.</div></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"100 ","pages":"Article 101143"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145736285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ecnomotopic expression of olfactory receptors is affected by human apolipoproteins A-IMilano and A-II: evidence from liver microarray analyses","authors":"Amedeo Amedei ,&nbsp;Cinzia Parolini","doi":"10.1016/j.jbior.2026.101158","DOIUrl":"10.1016/j.jbior.2026.101158","url":null,"abstract":"<div><div>Olfactory receptors (ORs) are seven transmembrane domains G protein-coupled receptors (GPCRs) located in the olfactory sensory neurons (OSNs) of the nasal olfactory epithelium. Although OR expression was initially hypothesized to be restricted to the OSNs, an ecnomotopic expression has been identified and associated with the modulation of different physiological functions, such as glucose and lipid metabolism, hypoxia sensing, wound healing and sperm chemiotaxis. However, the role of most ORs in non-olfactory tissues is still a matter of debate, as well as their specific ligands and mechanisms of action. High-density lipoproteins (HDL) are heterogenous, and multifunctional nanoparticles constituted primarily of proteins and lipids. Their main structural protein, namely, apolipoprotein A-I (A-I) has been recognized as the major determinant of the biological activities of HDL. Recently, our group, by using unique mouse models and microarray methodology, has demonstrated that human A-II (hA-II) and A-I_Milano (A-I_M), a molecular variant of A-I, strongly modulate the hepatic expression of different genes involved in lipid metabolism and immune/inflammatory pathways. Therefore, aiming at investigating the impact of these apolipoproteins on the hepatic expression of mouse ORs (Olfrs), we have performed a new bioinformatic analysis of the differentially expressed genes (DEGs) found in the liver of hA-II/A-I k-in versus hA-II/A-I_M k-in; A-I_M k-in versus hA-II/A-I_M k-in; A-I k-in versus A-I_M k-in; A-I k-in versus hA-II/A-I k-in mice. Our results suggest that the presence of A-I_M, either alone or in combination with hA-II, is critical for the efficient trafficking and functional expression of Olfrs at the cell surface. Moreover, co-expression of hA-II with A-I resulted in down-regulation of previously uncharacterized Olfrs genes an up-regulation of several known Olfrs, which are likely responsive to short-chain fatty acids and signal through the cAMP/CREB pathway.</div></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"100 ","pages":"Article 101158"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146130834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adrenergic receptor activation shapes circadian clock gene oscillations in HL-1 cardiomyocyte cell line","authors":"Elena Crecca ,&nbsp;Martina Pinna ,&nbsp;Maria Rita Assenza ,&nbsp;Andrea M. Isidori ,&nbsp;Federica Barbagallo","doi":"10.1016/j.jbior.2026.101159","DOIUrl":"10.1016/j.jbior.2026.101159","url":null,"abstract":"<div><div>Circadian rhythms are physiological, biochemical and behavioural processes with a 24-h period molecularly regulated by clock genes. Cardiovascular physiology is subject to circadian variations in heart rate, blood pressure and contractility to optimize its function according to the rest-activity phases. Adrenergic receptors (ARs), activated by endogenous catecholamine hormones, are crucial in the regulation of cardiac functions; however, controllable <em>in vitro</em> models to study the intrinsic cardiomyocyte circadian clock with minimal systemic timing cues remain limited. Here, we use HL-1 cardiomyocyte cell line (HL-1 cells), in which serum shock induces synchronized oscillations of core clock gene transcripts compared with unsynchronized cultures. Different ARs activators onto HL-1 cells were applied under non-synchronized or synchronized conditions and circadian oscillation of representative clock genes was determined. We show that alpha- and beta-AR activation differentially modulates clock gene mesor, amplitude and phase. These findings support HL-1 cells as a convenient <em>in vitro</em> platform to investigate interactions between adrenergic signaling and cardiomyocyte clock gene oscillations.</div></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"100 ","pages":"Article 101159"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146130820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An integrative multi-cohort transcriptomic study reveals cell cycle– and adhesion-related hub genes as diagnostic biomarkers for pulmonary arterial hypertension","authors":"Jiajia Zou ,&nbsp;Guojiao Rao ,&nbsp;Xiaomin Hou ,&nbsp;Zhifa Zheng ,&nbsp;Mengjie Xu ,&nbsp;Xian Li ,&nbsp;Yan Gao ,&nbsp;Yiwei Shi ,&nbsp;Xiaojiang Qin","doi":"10.1016/j.jbior.2026.101145","DOIUrl":"10.1016/j.jbior.2026.101145","url":null,"abstract":"<div><div>Pulmonary arterial hypertension (PAH) is a progressive and fatal vascular disorder for which reliable and non-invasive diagnostic biomarkers remain limited. This study aims to screen and verify the hub genes related to PAH by integrating bioinformatics and experimental verification. We analyzed four GEO datasets (GSE117261, GSE24988, GSE53408, GSE113439) to identify differentially expressed genes and co-expressed modules. Functional enrichment analysis revealed the pathways related to vascular smooth muscle contraction and organ development. Protein-protein interaction network analysis screened out 4 hub genes. These genes showed different expression dysfunctions in the training set, an independent validation set and a Single-cell sequencing dataset (GSE33463, GSE228644), and demonstrated good diagnostic value through ROC curve analysis. Crucially, in the nicotine-induced PAH mouse model, RT-qPCR experiments confirmed the significant upregulation of these 4 genes. Our research results have established CDK1, TPX2, IGF1 and VCAM1 as robust polygenic markers related to PAH, providing potential evidence for clarifying their molecular mechanisms and developing non-invasive diagnostic tools.</div></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"100 ","pages":"Article 101145"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146023238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}