Biotechnology Reports最新文献

{"title":"Production and characterization of rNGFSP: a recombinant fusion immunogen eliciting dual anti-NGF and anti-Substance P therapeutic antibodies for Degenerative Joint Disease","authors":"Valentina Varela ,&nbsp;Monique Costa ,&nbsp;Cecilia Maciel ,&nbsp;Joaquín Barbeito ,&nbsp;Exequiel E. Barrera ,&nbsp;Erica Gutierre ,&nbsp;Agustín Correa ,&nbsp;Melania Elgue ,&nbsp;Sebastián Carrasco ,&nbsp;Magdalena Domínguez Larrosa ,&nbsp;María Pereira ,&nbsp;Josefina Correa ,&nbsp;Nadia Crosignani ,&nbsp;Joseph S. Beckman ,&nbsp;Luis Barbeito ,&nbsp;Emiliano Trias","doi":"10.1016/j.btre.2026.e00946","DOIUrl":"10.1016/j.btre.2026.e00946","url":null,"abstract":"<div><div>Anti-NGF monoclonal antibodies have recently been approved for treating degenerative joint disease, including osteoarthritis pain, in dogs and cats. However, their widespread use is limited by high cost and the requirement for repeated injections. Nerve Growth Factor and Substance P play central roles in the initiation and maintenance of inflammation and chronic pain in OA. There is a pressing need for new, safe, cost-effective therapies that target the underlying mechanisms of OA chronic pain. Here, we designed and produced a novel recombinant fusion protein, termed rNGFSP, which functions as an immunogen due to its unique molecular structure combining amino acid sequences from NGF and SP in a non-native conformation. When formulated and administered as a vaccine, rNGFSP elicits dual anti-NGF and anti-SP therapeutic antibodies in the host. rNGFSP was produced in <em>E. coli</em> and purified from inclusion bodies using metal affinity chromatography under denaturing conditions. Mass spectrometry confirmed the expected molecular weight (17.5 kDa) and preserved amino acid sequence. Structural prediction using Alphafold2 revealed rNGFSP presented a non-natural folding, but a preserved NGF core and a flexible SP tail, supporting antigenic presentation. Vaccination of mice, rabbits, horses, and dogs, showed that rNGFSP elicited cross-reactive IgG antibodies against the native conformations of NGF and SP. Furthermore, immunoglobulins elicited in vaccinated dogs neutralized the biological activity of NGF and SP in cell cultures, suggesting a therapeutic potential. These findings support rNGFSP as a promising vaccine candidate simultaneously targeting endogenous NGF and SP species, providing a cost-effective alternative to monoclonal antibodies.</div></div>","PeriodicalId":38117,"journal":{"name":"Biotechnology Reports","volume":"49 ","pages":"Article e00946"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976932","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":"Development of anti-dengue virus D8 neutralizing monoclonal antibody production in Nicotiana benthamiana","authors":"Gunt Niyompun ,&nbsp;Kaewta Rattanapisit ,&nbsp;Janejira Jaratsittisin ,&nbsp;Pipob Suwanchaikasem ,&nbsp;Rochanawan Sootichote ,&nbsp;Pichamon Sittikul ,&nbsp;Pannamthip Pitaksajjakul ,&nbsp;Pongrama Ramasoota ,&nbsp;Waranyoo Phoolcharoen","doi":"10.1016/j.btre.2026.e00951","DOIUrl":"10.1016/j.btre.2026.e00951","url":null,"abstract":"<div><div>Dengue is a life-threatening mosquito-borne viral disease ranging from mild symptoms to severe hemorrhagic fever. In this study, a recombinant anti-dengue D8 monoclonal antibody was produced in <em>Nicotiana benthamiana</em> and characterized for protein integrity and glycosylation by LC-MS. The plant-derived antibody lacked plant-specific β1,2-xylose and core α1,3-fucose residues, displaying a mammalian-like glycan profile. Functional evaluation showed potent cross-neutralizing activity against all four dengue virus serotypes (DENV1–DENV4), with the strongest activity against DENV4 (FRNT50 &lt; 1 µg/mL), followed by DENV2 (5.82 µg/mL), DENV3 (9.49 µg/mL), and DENV1 (28.68 µg/mL), comparable to the mammalian-produced counterpart. The antibody also bound strongly to NS1 proteins of all serotypes, especially DENV2, and demonstrated higher reactivity than mammalian-derived anti-NS1 antibodies. Collectively, our results provide proof-of-concept that a glycoengineered plant platform can generate a functional D8 antibody with mammalian-like glycosylation, robust NS1 binding, and cross-neutralizing activity against DENV1–4, prompting further evaluation in Fc-dependent assays and in vivo models.</div></div>","PeriodicalId":38117,"journal":{"name":"Biotechnology Reports","volume":"49 ","pages":"Article e00951"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147327584","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":"Insulin Resistance, Anti-inflammatory, and Antioxidant In vitro Activity of Heterologously Expressed Arenin from Dryophytes arenicolor","authors":"Enrique Hidalgo-Vázquez ,&nbsp;Marilena Antunes-Ricardo ,&nbsp;Jesús Hernández-Pérez ,&nbsp;Jorge Benavides","doi":"10.1016/j.btre.2026.e00947","DOIUrl":"10.1016/j.btre.2026.e00947","url":null,"abstract":"<div><div>Amphibian-derived peptides are promising therapeutics for metabolic dysfunction, oxidative stress, and immune imbalance. We investigated arenin, a Kunitz-type peptide from <em>Dryophytes arenicolor</em>, produced heterologously in <em>E. coli</em>, for anti-metabolic, antioxidant, and immunomodulatory activities. In insulin-resistant hepatocytes, arenin increased glucose uptake from 23.97 ± 2.79% (IR control) to 51.38 ± 2.95% at 250 µg/mL. Arenin also reduced intracellular reactive oxygen species (ROS) in a time-dependent manner. The most significant early effect (20 min) occurred at higher doses (500–1000 µg/mL), whereas at 24 h the effect shifted to lower–intermediate concentrations (15.62–250 µg/mL), with 15.62 µg/mL yielding the lowest ROS levels (15.78 ± 1.66%). In macrophages, nitric oxide (NO) production showed a concentration-dependent, multi-layered response, indicating immunomodulation. These data position arenin as a multifunctional bioactive capable of improving metabolic homeostasis, strengthening antioxidant defenses, and tuning innate immune responses, laying groundwork for peptide-based interventions against metabolic disturbances.</div></div>","PeriodicalId":38117,"journal":{"name":"Biotechnology Reports","volume":"49 ","pages":"Article e00947"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037778","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":"Indole-alkaloid–rich fraction of Ervatamia coronaria leaf extract regresses breast cancer by inducing apoptotic cell death","authors":"Chirantan Majumder ,&nbsp;Anirban Manna ,&nbsp;Satyajit Halder ,&nbsp;Somesh Roy ,&nbsp;Subhash C Mandal ,&nbsp;Kuladip Jana ,&nbsp;Mahadeb Pal","doi":"10.1016/j.btre.2025.e00937","DOIUrl":"10.1016/j.btre.2025.e00937","url":null,"abstract":"<div><div>Current anti-breast cancer therapies often cause severe toxicity to normal cells and promote chemoresistance, while their exorbitant costs limit their accessibility to many patients. This underscores the need for safer, effective, and affordable alternative treatment strategies. In this study, we evaluated the anti-breast cancer potential of an alkaloid-rich dichloromethane fraction of <em>Ervatamia coronaria</em> (DFE) leaf extract, identified by LC-MS to contain eight indole-alkaloids as its major constituents. Using 4T1 cell-induced tumour allografts in BALB/c mice, alongside cell-based assays including cell viability, scratch assay, immunoblotting, immunohistochemistry, and scanning electron microscopy, we investigated its mechanisms of action. DFE treatment induced cell cycle arrest in the sub-G1 phase, triggering apoptosis, with little effect on normal cells. Mechanistically, elevated mitochondrial ROS were identified as the primary driver of toxicity, as pre-treatment with NAC reversed DFE’s effects. Additionally, DFE downregulated AKT signalling in breast cancer cells. Importantly, DFE significantly reduced 4T1 tumour growth in vivo, both alone and in combination with doxorubicin, without exerting significant toxicity on healthy mice. These findings support further evaluation of DFE in clinical models.</div></div>","PeriodicalId":38117,"journal":{"name":"Biotechnology Reports","volume":"49 ","pages":"Article e00937"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145651946","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":"Cyanobacterium-Penicillium co-flocculation under erythromycin treatment: increased CO2 capture and biomass production in an organic compound-free co-cultivation","authors":"Jidapa Leksingto ,&nbsp;Panutchaya Pichaiyotinkul ,&nbsp;Kobkul Boorachokwiwat ,&nbsp;Janine Kaewbai-ngam ,&nbsp;Nichaphat Kanoksinwuttipong ,&nbsp;Nannaphat Sukkasam ,&nbsp;Tanakarn Monshupanee","doi":"10.1016/j.btre.2025.e00943","DOIUrl":"10.1016/j.btre.2025.e00943","url":null,"abstract":"<div><div>Photoautotrophic cyanobacteria convert CO₂ into bioproducts. However, efficient cell harvesting remains a major obstacle. Auto-bioflocculation offers a promising solution. In cultures of <em>Synechocystis</em> sp. PCC 6803, <em>Synechocystis</em> co-flocculated with natural fungal contaminant (identified as <em>Penicillium</em> sp.) into spherical clusters with internal hollow spaces—but only in the presence of erythromycin (EM), and not without EM. Optimized co-cultivation of <em>Synechocystis</em> and <em>Penicillium</em> for five days in BG11 medium (lacking organic compounds) supplemented with 5 µM EM resulted in complete biomass co-flocculation, yielding up to 2.0 g/L. This corresponds to atmospheric CO₂ capture rate of 0.50 g/L/day, representing a 7.9-fold increase in biomass and a 7.0-fold enhancement in CO₂ capture compared to axenic <em>Synechocystis</em> culture. Protein was the major component of the flocculated biomass, accounting for 39–61 % of dry weight. Increasing EM concentrations (from 0.3 to 10 µM) led to an increase in floc diameter from 0.5 to 1.9 mm. Scaling the culture volume from 100 to 200–1000 mL changed the surface texture of the co-flocculates from relatively smooth to rough with thorn-like structures. Transcriptomic analysis indicated that co-flocculation was associated with upregulation of genes involved in S-layer protein synthesis, molecular chaperones, exopolysaccharide polymerization, and pilin regulation. Genes related to minor pilin proteins, pili function, and capsular polysaccharide synthesis were downregulated. Differentially expressed genes between smooth-surfaced and rough-surfaced co-flocs were reported. This bio-flocculation demonstrates low-energy, organic-free strategy that boosts CO₂ capture, highlighting strong potential for carbon-negative bioprocesses. The protein-rich co-flocs offer opportunities for downstream use in animal feed or biorefinery.</div></div>","PeriodicalId":38117,"journal":{"name":"Biotechnology Reports","volume":"49 ","pages":"Article e00943"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145925437","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":"Plant-produced monoclonal antibodies recognize the native circumsporozoite protein on Plasmodium falciparum sporozoites","authors":"Kanokporn Thiganta ,&nbsp;Kaewta Rattanapisit ,&nbsp;Pipob Suwanchaikasem ,&nbsp;Wanlapa Roobsoong ,&nbsp;Christine Joy I. Bulaon ,&nbsp;Waranyoo Phoolcharoen","doi":"10.1016/j.btre.2025.e00944","DOIUrl":"10.1016/j.btre.2025.e00944","url":null,"abstract":"<div><div>Malaria is primarily caused by <em>Plasmodium</em> parasites and remains a major global health threat due to drug resistance and limited vaccine efficacy. Monoclonal antibodies (mAbs) targeting the conserved NANP repeat region of the circumsporozoite protein (PfCSP), such as MS-1797, represent a promising prophylactic strategy. Here, we demonstrate the plant-based production of MS-1797 in glycoengineered <em>Nicotiana benthamiana</em> ΔXF. Two variants were generated: MS-01 (original MS-1797) and MS-02 (MS-1797-SEKDEL), which yielded up to 457.3 µg/g fresh weight and 415.7 µg/g FW at 6 days post-infiltration. The plant-derived mAbs were obtained in high purity (&gt;90%) and displayed either human core glycans or high mannose structures. Notably, both MS-01 and MS-02 retained antigen specificity <em>in vitro</em> and bound native PfCSP on sporozoites by immunofluorescence assay. These results establish the feasibility of producing functional anti-malarial mAbs in plants and highlight their potential use as affordable reagents for malaria research, diagnostics, and future prophylactic interventions.</div></div>","PeriodicalId":38117,"journal":{"name":"Biotechnology Reports","volume":"49 ","pages":"Article e00944"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145925423","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":"Integrating multi-omics data: Methods and applications in human complex diseases","authors":"Pasquale Sibilio ,&nbsp;Enrico De Smaele ,&nbsp;Paola Paci ,&nbsp;Federica Conte","doi":"10.1016/j.btre.2025.e00938","DOIUrl":"10.1016/j.btre.2025.e00938","url":null,"abstract":"<div><div>Over the past few decades, technological advancements and declining costs of high-throughput data generation have revolutionized biomedical research, enabling the collection of large-scale datasets across multiple omics layers—including genomics, transcriptomics, proteomics, metabolomics, and epigenomics. The analysis and integration of these datasets provides global insights into biological processes and holds great promise in elucidating the myriad molecular interactions associated with human diseases, particularly multifactorial ones such as cancer, cardiovascular, and neurodegenerative disorders. However, integrating multi-omics data presents significant challenges due to high dimensionality and heterogeneity. This review explores computational methods for integrating multi-omics data, with a particular focus on network-based approaches that offer a holistic view of relationships among biological components in health and disease. Furthermore, this review showcases a selection of recent, successful applications of multi-omics data integration, moving beyond theoretical methods to demonstrate their transformative potential in biomarker discovery, patient stratification, and guiding therapeutic interventions in specific human diseases.</div></div>","PeriodicalId":38117,"journal":{"name":"Biotechnology Reports","volume":"48 ","pages":"Article e00938"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145578651","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":"Plant growth-promoting traits of Rhizophora mangle-associated bacteria and their effects on tomato (Solanum lycopersicum)","authors":"Lucumi-Banguero Ruby Stella,&nbsp;Bustos-Barona María Alejandra,&nbsp;López-Velázquez Ximena Andrea,&nbsp;Aguirre-Ramírez Elkin,&nbsp;Benítez-Campo Neyla","doi":"10.1016/j.btre.2025.e00923","DOIUrl":"10.1016/j.btre.2025.e00923","url":null,"abstract":"<div><div>Mangrove ecosystems harbor a remarkable microbial diversity that plays essential roles in nutrient recycling and transformation, contributing to soil fertility and quality. However, the exploration of this microbiota as a source of plant growth-promoting bacteria (PGPB) remains at an early stage. In this study, bacterial strains associated with the rhizosphere of <em>Rhizophora mangle</em> from Colombian Pacific mangroves were characterized and their effects on <em>Solanum lycopersicum</em> var. <em>cerasiforme</em> were evaluated. Strains were isolated using nitrogen-free media and identified through 16S rRNA gene sequencing. Key plant growth-promoting (PGP) functions were assessed, including biological nitrogen fixation (confirmed by the presence of the <em>nifH</em> gene), indole-3-acetic acid (IAA) production, siderophore synthesis, and phosphate and potassium solubilization. All isolates fixed nitrogen and produced IAA; 50 % synthesized siderophores, 72 % solubilized potassium, and 90.9 % solubilized phosphate. A factorial analysis of mixed data (FAMD) was used to select four functionally promising strains: <em>Raoultella terrigena</em> RFN53, <em>Klebsiella variicola</em> RFN55, <em>Cellulosimicrobium</em> sp. RFN73, and <em>Klebsiella</em> sp. RFN75, which were evaluated in independent paired greenhouse trials. Inoculation with <em>Cellulosimicrobium</em> sp. RFN73, as well as the combinations RFN53+RFN55 and RFN73+RFN75, significantly enhanced plant growth, increasing plant height, leaf area, and biomass accumulation (<em>p</em> &lt; 0.05) compared to the control. These findings highlight the potential of <em>R. mangle</em>-associated bacteria as biofertilizers and underscore the importance of including safety assessments and detailed functional characterization to ensure their responsible use in sustainable agricultural systems.</div></div>","PeriodicalId":38117,"journal":{"name":"Biotechnology Reports","volume":"48 ","pages":"Article e00923"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145266566","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":"Structural and functional properties of neodymium-doped hydroxyapatite nanoparticles for biomedical applications","authors":"K.Sai Manogna ,&nbsp;K. Kusuma ,&nbsp;G.Rajasekhara Reddy ,&nbsp;B.Deva Prasad Raju ,&nbsp;N.John Sushma","doi":"10.1016/j.btre.2025.e00916","DOIUrl":"10.1016/j.btre.2025.e00916","url":null,"abstract":"<div><div>Neodymium (Nd³⁺) doped hydroxyapatite nanoparticles (Han: Nd³⁺ NPs) were synthesized and systematically characterized to evaluate their structural and functional properties for biomedical applications. X-ray diffraction (XRD) confirmed the crystalline phase retention post-doping, while x-ray photoelectron spectroscopy (XPS) revealed the successful incorporation of Nd³⁺ ions. The doping altered the optical and electronic properties, potentially enhancing bioactivity and imaging capabilities. Preliminary cytotoxicity assessments on MCF7 and 4T1 breast cancer cell lines indicated dose-dependent effects, with IC50 values of 36.13 µg/mL and 64.38 µg/mL, respectively. The study concludes that Han: Nd³⁺ NPs offer promise as multifunctional platforms for cytotoxic response and structural stability, with potential for future application in imaging and targeted breast cancer therapy.</div></div>","PeriodicalId":38117,"journal":{"name":"Biotechnology Reports","volume":"48 ","pages":"Article e00916"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144890162","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":"Consolidated bioprocessing of inulin-containing feedstock to succinic acid by newly isolated Enterobacter sp. GAP1","authors":"Marcin Podleśny ,&nbsp;Tomasz Szymczak ,&nbsp;Jagoda Kucharska ,&nbsp;Monika Szymajda","doi":"10.1016/j.btre.2025.e00929","DOIUrl":"10.1016/j.btre.2025.e00929","url":null,"abstract":"<div><div>The novel <em>Enterobacter</em> sp. GAP1 strain was found to ferment inulin-containing carbohydrates in Jerusalem artichoke (JA) without the need for acidic or enzymatic pretreatment prior to fermentation. The GAP1 strain also possesses an efficient ability to produce succinic acid (SA). Using inulin as a carbon source in a liquid medium produced 29.4 g/L of SA. Using ground and dried JA tubers resulted in a SA concentration of 17.9 g/L, while adding freshly squeezed JA tuber juice resulted in a concentration of 24.7 g/L. In addition to tests using liquid media, the possibility of producing SA under conditions of limited water availability was also investigated, achieving a concentration of 27.7 g/L. Notably, the use of the <em>Enterobacter</em> sp. GAP1 strain is the first reported instance of a consolidated bioprocess for producing SA from inulin-containing materials both submerged and semi-solid state fermentation approach.</div></div>","PeriodicalId":38117,"journal":{"name":"Biotechnology Reports","volume":"48 ","pages":"Article e00929"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145362596","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}