Denisse Gardea-Gutiérrez, Manuel Román-Aguirre, Berenice E Oseguera-Guerra, Raúl Loera-Valencia, Silvia L Montes-Fonseca
{"title":"Improved application of the inverse emulsion method for generating flexible asymmetric liposomes for DNA plasmid delivery.","authors":"Denisse Gardea-Gutiérrez, Manuel Román-Aguirre, Berenice E Oseguera-Guerra, Raúl Loera-Valencia, Silvia L Montes-Fonseca","doi":"10.1080/08982104.2025.2521067","DOIUrl":"10.1080/08982104.2025.2521067","url":null,"abstract":"<p><p>The design of vehicles for transdermal gene delivery is at the forefront of molecular medicine, facilitating targeted therapies. Reports suggest that flexible liposomes can be a good alternative for transdermal delivery, and asymmetric liposomes may enhance gene delivery efficiency. This study aims to create flexible asymmetric-type liposomes with high encapsulation of DNA and high deformability rates. The synthesis of asymmetric liposomes was standardized using the inverse emulsion method, with lipids DOTMA (1,2-di-O-octadecenyl-3-trimethylammonium propane) and DOPE (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine) as the inner layer, DSPC (1,2-distearoyl-sn-glycero-3-phosphocholine) lipid as the outer layer, cholesterol as a stabilizing component, and Span 80 and ethanol as components that promote flexibility. The pIRES2-EGFP plasmid was used as the encapsulated genetic material. Asymmetric liposomes were characterized using transmission electron microscopy (TEM), encapsulation efficiency percentage (%EE), and the deformability index determined by the extrusion method. Results indicate that the asymmetric liposomes possess a well-defined bilayer, with bilayer deformability varying depending on the components used; for instance, liposomes containing flexible components exhibit a more deformable bilayer than those made solely of lipids. The average size of the liposomes was below 200 nm, and the %EE ranged from 75% to 90%. The liposomes containing Span 80 surfactant exhibited the highest flexibility index. This technique successfully produced asymmetric liposomes with appropriate encapsulation of the DNA plasmid without degradation during the process. Future studies are expected to evaluate the cytotoxicity, transfection, and skin permeation.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"446-454"},"PeriodicalIF":4.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A dual-action liposome-peptide formulation synergistically counteracts a gain-of-function p53 mutant.","authors":"Sneha Ghosh Chaudhary, Swati Bhowmick, Samriddhi Bhattacharya, Siddhartha Roy, Nahid Ali","doi":"10.1080/08982104.2025.2555179","DOIUrl":"10.1080/08982104.2025.2555179","url":null,"abstract":"<p><p>Inactivation of p53 tumor suppressor functions, often through missense mutations, is essential for carcinogenesis. A sub-class of such p53 missense mutations gains new functions, including drug resistance and enhanced proliferation, in addition to its loss of function. Among the most frequent gain-of-function p53 mutants, R273H occurs in tumors of many tissue origins and imparts aggressive character and resistance to drugs to the tumor. Tumors bearing p53R273H are generally resistant to all available therapies, and need for novel interventions are urgently needed. Interaction of p53R273H with Positive Coactivator 4 (PC4), an abundant chromatin-associated protein, is essential for acquiring the gain-of-function properties. Previously, we developed a chemically modified peptide, NLS-p53(380-386), targeting PC4 that abrogated the interaction of p53R273H with PC4 and reversed many of its gain-of-function properties. We earlier demonstrated that cationic phosphatidylcholine-stearylamine (PC-SA) liposomes possess inherent anti-tumor properties. To improve efficacy, pharmacokinetics, and delivery, we entrapped the PC4-targeted peptide into PC-SA liposome. We synthesized the NLS-p53(380-386) peptide and entrapped in PC-SA liposome. We used MTT assay, confocal microscopy, flow cytometry, qRT-PCR, and western blotting to investigate the biological effects of the p53-entrapped PC-SA. Pretreatment with the PC-SA liposome entrapped peptide enhanced the chemosensitivity of widely used anticancer drug doxorubicin in cell lines bearing p53R273H mutation. The doxorubicin-induced cell-killing effect was much more enhanced when pretreated with the liposome-entrapped peptide than when pretreated with either the free peptide or the liposome alone. The liposome-encapsulated peptide is a promising formulation for developing therapies targeting tumors bearing the p53R273H.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"490-502"},"PeriodicalIF":4.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hadi Sardarabadi, Seyed Mohammad Zarei, Masoumeh Dolati, Mohammad Hasan Darvishi, Mahdi Tavakolizadeh, Fatemeh Zohrab, Hamidreza Javadi
{"title":"Mito-phytosomal nanocarriers of <i>purslane</i> extract augments apoptosis in A549 cells.","authors":"Hadi Sardarabadi, Seyed Mohammad Zarei, Masoumeh Dolati, Mohammad Hasan Darvishi, Mahdi Tavakolizadeh, Fatemeh Zohrab, Hamidreza Javadi","doi":"10.1080/08982104.2025.2521718","DOIUrl":"10.1080/08982104.2025.2521718","url":null,"abstract":"<p><p>To enhance the anticancer effects of the purslane extract, we developed a phytosomal nanocarrier with mitochondrial targeting capabilities. Initially, a phytosomal carrier was prepared and subsequently functionalized with a Szeto-Schiller (SS) peptide as, a mitochondrial-penetrating peptide, via a DSPE-PEG (2000)-malamide crosslinker. High-performance liquid chromatography analysis was conducted to quantify the amounts of quercetin and apigenin in the hydroalcoholic extract and the fractionated isolates obtained from diethyl ether, chloroform, ethyl acetate, butanol, and water. The results indicated that both polyphenols were present in the hydroalcoholic extract, with apigenin being more abundant in the ethyl acetate fraction. Dynamic light scattering measurements revealed an average particle size of 112.2 ± 6.758 nm, a narrow polydispersity index of 0.26 ± 0.005, and a zeta potential of -30.67 ± 2.894 mV. Scanning electron microscopy confirmed that the phytosomal carrier exhibited a spherical and intact morphology. The encapsulation efficiency and loading capacity of the phytosomes were found to be 97% and 12.19%, respectively, for the ethyl acetate isolate. The in vitro drug release profile demonstrated a biphasic pattern, characterized by an initial burst release followed by prolonged sustained release. Cytotoxicity assays conducted on A549 and HFF cell lines revealed that the mitochondria-targeted phytosomal nanocarrier exhibited significant apoptotic effects (69.6%) on A549 cells, showing no significant toxicity toward HFF cells when compared with phosphatidylcholine, conventional phytosomal nanocarriers, and ethyl acetate-targeted phytosomal nanocarriers. The findings from this study represent a crucial advancement in the standardization of plant extracts and the development of herbal nanomedicine using targeted phytosomes.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"455-468"},"PeriodicalIF":4.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lea Pašalić, Barbara Pem, Andreja Jakas, Ana Čikoš, Nikolina Groznica, Tihana Mlinarić, Matilde Accorsi, Agustín Mangiarotti, Rumiana Dimova, Danijela Bakarić
{"title":"Peptide interaction with mixed lipid bilayers alters packing and hydrocarbon chain conformations.","authors":"Lea Pašalić, Barbara Pem, Andreja Jakas, Ana Čikoš, Nikolina Groznica, Tihana Mlinarić, Matilde Accorsi, Agustín Mangiarotti, Rumiana Dimova, Danijela Bakarić","doi":"10.1080/08982104.2025.2576099","DOIUrl":"10.1080/08982104.2025.2576099","url":null,"abstract":"<p><p>Cell-penetrating peptides (CPPs) with a cationic-hydrophobic character are recognized as carriers for delivering various therapeutics and diagnostic agents across cell membranes and into the cells. Among the most studied CPPs, nona-arginine (R9) exhibits superior penetration compared to its equally charged counterpart, nona-lysine (K9). This indicates that penetration ability relies not only on charge but also on the structure, distribution, and concentration of peptides, as well as the composition of lipid membranes. However, interactions of heptapeptides composed of arginine (R), lysine (K), and phenylalanine (F) residues with membranes remain poorly explored. This study sheds light on the interaction of R5F2/K5F2 on lipid membranes containing a zwitterionic lipid (phosphatidylcholine; PC) and an anionic lipid (either phosphatidylglycerol, PG or phosphatidylserine, PS) in the 90:10 molar ratio. Using differential scanning calorimetry (DSC) and temperature-dependent UV-Vis spectroscopy, we observed peptide interaction-induced changes that stabilize a particular phase of lipid bilayers, as well as their effect on the melting of the latter in terms of cooperative unit size (CUS). The distinct interaction of R5F2/K5F2 on DPPC+DPPG and DPPC+DPPS lipid bilayers revealed that the changes in lipid packing and hydrocarbon chain conformations are peptide-specific features. The peptide-induced formation of vacancies in the non-polar bilayer part is consistent with partial membrane leakage observed in giant unilamellar vesicles. This study provides new insights into the peptide-lipid interactions underlying the functionality of CPPs.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"548-565"},"PeriodicalIF":4.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145345454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Protease encapsulated liposomes for twin benefits: a green approach to unhairing and soft leather production.","authors":"Bruntha Arunachalam, Aruna Dhathathreyan, Thanikaivelan Palanisamy","doi":"10.1080/08982104.2025.2504019","DOIUrl":"10.1080/08982104.2025.2504019","url":null,"abstract":"<p><p>Rising ecological concerns are driving industries, including leather manufacturing, to adopt more sustainable practices. A major focus is transitioning from traditional chemical-based methods to bio-based alternatives. Enzyme-based unhairing has emerged as a potential replacement for the conventional lime-sulfide process. However, it faces challenges such as poor enzyme stability under harsh processing conditions, high cost, and possible grain damage resulting from uncontrolled enzymatic activity. Herein, we propose using egg-derived L-α-phosphatidylcholine (EPC) liposomes as protective carriers to encapsulate protease, aiming to improve its stability and efficacy during the unhairing process. Protease-loaded EPC liposomes (EPC+Pro) were synthesized and characterized for their size, zeta potential, thermal behavior, and morphology. The average size of EPC+Pro liposomes was 386 ± 10 nm with a zeta potential of -46 ± 0.1 mV. When applied to goat skin, EPC+Pro liposomes enabled complete (100%) hair removal within 3 h, while the unhairing process using free protease required 5 h to achieve comparable results. Beyond ensuring quick and efficient hair removal, EPC+Pro demonstrated a dual function by acting as a natural fatliquor, markedly enhancing the softness of leather with low fatliquor consumption. The treated leather showed a softness of 5.13 ± 0.2 mm, higher than the 4.26 ± 0.3 mm observed with free protease treatment. Overall, EPC+Pro treated leather demonstrated superior physical properties. This study highlights the potential of protease-encapsulated liposomes as a dual-functional, efficient, and sustainable solution for enzymatic unhairing, offering improved process efficiency, enhanced leather quality, and reduced chemical usage for commercial leather processing.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"370-381"},"PeriodicalIF":4.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kanza Rahali, Atabak Ghanizadeh Tabriz, Dennis Douroumis
{"title":"Quality by design (QbD) liposomes engineering using 3D printed Tesla microfluidic arrays.","authors":"Kanza Rahali, Atabak Ghanizadeh Tabriz, Dennis Douroumis","doi":"10.1080/08982104.2025.2504018","DOIUrl":"10.1080/08982104.2025.2504018","url":null,"abstract":"<p><p>Microfluidic arrays have been successfully implemented for the design and development of liposome nanoparticles. In this study we have applied a Quality by Design (QbD) approach to investigate the effect of 3D printed Tesla microfluidic designs (direct and serpentine shape) on the liposome nanoparticles in comparison with conventional ultrasonication methodology. Critical processing parameters (CPP) such as the shape, length and channel width of the Tesla arrays were also studied. Furthermore, the effect of critical material attributes (CMA), including the length of the phosphatidylcholine (PC) carbon chain and the lipid:cholesterol ratio on the produced nanoparticles was investigated. The obtained findings revealed that both CPP and CMA play a key role in the formation of liposome nanoparticles. The liposome size was decreasing with a descending order for plain array > Tesla <sub>(serpentine)</sub> > Tesla <sub>(direct)</sub> > ultrasonication. However, improved Tesla arrays with narrow channel width (200 μm) produced the smallest liposome particle size (74 nm). The PC carbon chain length was critical for the obtained particle size where Lipoid S75 produced smaller nanoparticles when compared to Lipoid E80. The increase of cholesterol content resulted in liposome size reduction and decreased zeta-potential.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"357-369"},"PeriodicalIF":4.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Preparation of chitosan-modified Moringa A liposomes and its protective effect on acute alcoholic liver injury.","authors":"Xiaowen Wang, Xia Jiang, Jinjing Yang, Michael Adu-Frimpong, Mingjie Gong, Qinyang Hua, Tingyuan Li, Jiaying Li, Pengfei Pan, Elmurat Toreniyazov, Xia Cao, Jiangnan Yu, Qilong Wang, Ximing Xu","doi":"10.1080/08982104.2025.2516033","DOIUrl":"10.1080/08982104.2025.2516033","url":null,"abstract":"<p><p>Moringa A (MA), the hepatoprotective components of <i>Moringa oleifera</i> Lam. seeds, are metabolized and eliminated quickly in the body. In this study, cholesterol-modified chitosan (CH-CS) was used as a polymer carrier to prepare chitosan-modified MA liposomes (MA-CLs) in order to slow down the release of MA, prolong its circulation time, and improve the oral bioavailability of MA in comparison with common MA liposomes (MA-Ls). The particle size (PS) of MA-CLs was 218.25 ± 1.07 nm, with a polydispersity index (PDI) of 0.143 ± 0.005 and a zeta potential (ZP) of 30.64 ± 0.29 mV. The encapsulation efficiency (EE) was 85.17 ± 1.70%, while the drug loading (DL) was 7.92 ± 0.16%. In contrast, the PS of MA-Ls was 232.06 ± 1.36 nm, with a PDI of 0.215 ± 0.009 and a ZP of -14.21 ± 0.33 mV. The EE and DL of MA-Ls were 71.34 ± 0.60% and 8.39 ± 0.07%, respectively. These results indicated that MA liposomes could effectively mitigate the burst release of MA, thereby enhancing its oral bioavailability. Furthermore, the performance of MA-CLs was superior to that of MA-Ls. ELISA kits demonstrated that, both MA and MA liposomes groups significantly reduced the levels of ach detection index in mice. Specifically, the therapeutic effect followed the order: MA-CLs > MA-Ls > MA, thus exhibiting a concentration-dependent manner. Histopathological analysis of liver sections revealed that MA and its formulations alleviated hepatocyte swelling and necrosis, thereby protecting the liver from alcohol-induced damage. This study found that MA has a protective effect on the liver, while MA-CLs hold promise as a therapeutic agent for prevention of acute alcoholic liver injury (ALI).</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"406-422"},"PeriodicalIF":4.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amna Naz, Sadia Haider, Malik Ihsan Ullah Khan, Rabia Khokhar, Mavra Rubab, Muhammad Farooq, Attia Afzal, Muhammad Sarfraz
{"title":"<i>In vitro</i> anticancer activity and biodistribution analysis of optimized hybrid nanoparticulate system co-loaded with apigenin and oleanolic acid.","authors":"Amna Naz, Sadia Haider, Malik Ihsan Ullah Khan, Rabia Khokhar, Mavra Rubab, Muhammad Farooq, Attia Afzal, Muhammad Sarfraz","doi":"10.1080/08982104.2025.2577195","DOIUrl":"10.1080/08982104.2025.2577195","url":null,"abstract":"<p><p>This study addresses the limitations of traditional cancer therapies-such as high toxicity and non-selectivity-by developing a novel nanoparticulate system co-loaded with plant-derived compounds, apigenin (APG) and oleanolic acid (OA). These naturally occurring phytochemicals are known for their anticancer properties but face clinical challenges due to poor solubility and limited efficacy. The Apigenin and Oleanolic Acid Nanoparticulate System (AONS) was refined and optimized using the Box-Behnken statistical design approach, resulting in nanoparticles with a mean diameter of 169 nm and size homogeneity. A validated HPLC technique was employed to simultaneously quantify both apigenin and oleanolic acid in the developed formulation as well as in various biological matrices. <i>In vitro</i> drug release was enhanced at acidic pH (5.5), mimicking the tumor microenvironment. AONS showed strong physicochemical stability under refrigerated storage. Cytotoxicity tests on HepG2, MDA-MB-231, and U87 glioma cells demonstrated significantly improved anticancer activity compared to control, free drugs, or individual nanoformulations. Cellular uptake studies confirmed efficient internalization in U87 cells, and ELISA results indicated apoptosis via activation of the p53 pathway. Biodistribution analysis revealed prolonged systemic drug retention with AONS (up to 72 hours), surpassing the short circulation time of free drugs. Notably, LC-MS data confirmed that the nanoparticle system could cross the blood-brain barrier, highlighting its therapeutic potential for treating brain cancers.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"566-589"},"PeriodicalIF":4.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145390413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pintu Prajapati, Aneri Desai, Pranav Shah, Veerashakar Pulusu, Anzarul Haque, Mohd Abul Kalam, Shailesh Shah
{"title":"Comparative <i>in-vivo</i> and <i>in-vitro</i> characterization of Donepezil loaded Lactoferrin linked PEG coated and uncoated nanocarriers as intranasal drug delivery system.","authors":"Pintu Prajapati, Aneri Desai, Pranav Shah, Veerashakar Pulusu, Anzarul Haque, Mohd Abul Kalam, Shailesh Shah","doi":"10.1080/08982104.2025.2573681","DOIUrl":"10.1080/08982104.2025.2573681","url":null,"abstract":"<p><p>Alzheimer's disease treatment faces challenges with conventional oral formulations of donepezil (DNP). This study aims to develop and characterize DNP-loaded Lactoferrin (LCF)-linked PEG-coated nano-carriers for intranasal delivery. The formulation was developed using a Quality by Design (QbD) approach integrated with molecular docking. A novel micelle-enhanced spectrofluorimetric method was developed and validated for <i>in-vitro</i> and <i>in-vivo</i> characterization of the nano-carriers. The method was optimized using Analytical Quality by Design (AQbD) principles. In-vivo pharmacokinetic and bio-distribution studies were conducted in rats to compare the developed formulation with uncoated NLCs and conventional dosage forms. The LCF-PEG-coated NLCs showed improved brain targeting efficiency compared to uncoated NLCs and conventional formulations. The spectrofluorimetric method demonstrated high sensitivity and reliability for both <i>in-vitro</i> and <i>in-vivo</i> analyses. The developed DNP-loaded LCF-PEG-coated NLCs show promise as an effective intranasal delivery system for Alzheimer's disease treatment. The novel spectrofluorimetric method offers a sustainable and efficient alternative to conventional LC-MS/MS techniques for characterizing DNP formulations.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"619-635"},"PeriodicalIF":4.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145426951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}