Journal of Biomaterials Science, Polymer Edition最新文献

{"title":"Advancements in nanotechnology for PARP inhibitor delivery: a comprehensive review of diverse nanosystems, their mechanisms, and therapeutic applications across cancer and beyond.","authors":"Bassam M Abualsoud, Majid Alhomrani, Abdulhakeem S Alamri, Walaa F Alsanie, Suhas Ballal, Girish Chandra Sharma, T Krithiga, Abhayveer Singh, Arun Kumar, Deepak A","doi":"10.1080/09205063.2025.2534698","DOIUrl":"https://doi.org/10.1080/09205063.2025.2534698","url":null,"abstract":"<p><p>Poly (ADP-ribose) polymerase (PARP) inhibitors have appeared as a transformative class of anticancer agents, particularly for tumors with homologous recombination deficiencies such as BRCA1/2-mutated breast, ovarian, prostate, and pancreatic cancers. Despite their clinical success, challenges such as poor bioavailability, systemic toxicity, and acquired resistance have limited their broader application. Nanotechnology-based drug delivery systems offer a promising strategy to overcome these limitations by enhancing the solubility, stability, and tumor-specific accumulation of PARP inhibitors while reducing off-target effects. This review explores the mechanism of action of PARP inhibitors, including their role in DNA repair and synthetic lethality, and discusses their therapeutic applications. Furthermore, recent progresses in delivery systems, including lipid-based, polymeric, inorganic, and hybrid nanosystems, are examined with a focus on their design, functionality, and impact on drug efficacy. Recent studies demonstrating improved drug retention, enhanced tumor targeting, and controlled release mechanisms are highl'hted, along with potential strategies to overcome resistance. The integration of multifunctional and stimuli-responsive nanosystems further enhances the therapeutic potential of PARP inhibitors. Continued innovation in nanomedicine holds the potential to optimize PARP inhibitor therapy and expand its clinical utility in personalized cancer treatment. Future directions include addressing translational challenges, scalability, and regulatory considerations for clinical applications.</p>","PeriodicalId":15195,"journal":{"name":"Journal of Biomaterials Science, Polymer Edition","volume":" ","pages":"1-62"},"PeriodicalIF":3.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144663850","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 new developed nano-curcumin containing dental hemostatic material; <i>in vitro</i> and the clinical assessments.","authors":"Leila Chodari, Sina Taghilou, Shadi Mohammadpour Asl, Mohammad Ali Ghavimi, Hamid Taghilou, Solmaz Maleki Dizaj, Simin Sharifi","doi":"10.1080/09205063.2025.2528493","DOIUrl":"https://doi.org/10.1080/09205063.2025.2528493","url":null,"abstract":"<p><p>Curcumin has antioxidant, anti-inflammatory, and cardiovascular protective effects. This study aimed to develop and evaluate an innovative biodegradable hemostatic gelatinous sponge containing curcumin nanoparticles for use in dentistry. This research investigated the efficacy and safety of this material in both <i>in vitro</i> tests and some clinical settings. The novel sponge was prepared <i>via</i> the freeze-drying method. It was characterized by common approaches. The biocompatibility and biological effects of the new sponge were evaluated <i>in vitro</i>. In the next step, thirty-eight patients who needed dental extraction on two teeth were selected for clinical assessment. The prepared sponge was placed inside the cavity of the experimental group. On the control side, the teeth were extracted normally. All patients were studied for pain, swelling, repair of the extracted site, clot quantity, and the occurrence of dry sockets. Results revealed a porous structure with micro- and nanosized pores and a 12-day degradation period. The produced sponge could absorb blood 38 times its weight. It showed no toxic effect. In the clinical study, pain reduction was larger in the experimental group compared to the control group. The extracted site was normal in terms of repair and clot formation. Finally, there was no dry socket in any of the experimental and control groups. The abovementioned advantages may make the new sponge more effective in tooth extraction and other surgical applications in dentistry.</p>","PeriodicalId":15195,"journal":{"name":"Journal of Biomaterials Science, Polymer Edition","volume":" ","pages":"1-14"},"PeriodicalIF":3.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649581","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":"Synergistic evaluation of anti-diabetic and hypolipidemic effects of <i>Alangium salvifolium</i> and <i>Ocimum sanctum</i> extracts.","authors":"Deepak Jain, Pankaj Sharma, Vinay Jain","doi":"10.1080/09205063.2025.2527254","DOIUrl":"https://doi.org/10.1080/09205063.2025.2527254","url":null,"abstract":"<p><p>In this study, <i>Alangium salvifolium</i> and <i>Ocimum sanctum</i> extracts were investigated for their antioxidant, antidiabetic and hypolipidemic activities individually and in combined form. HPLC, LC-MS and UPLC phytochemicals profiling identified phenolics and flavonoids as major bioactives. Antioxidant assays showed significant DPPH and ABTS radical scavenging activities, with the combined formulation (1:1 ratio) 91.2 and 89.6% inhibition was achieved respectively. Antidiabetic activities were first investigated <i>in vitro</i> with the ability of the combination to inhibit both α-amylase (IC₅₀ = 38.4 µg/mL) and α-glucosidase (IC₅₀ = 45.2 µg/mL) having the strongest inhibitory effects. The hypolipidemic activity included inhibition of lipid peroxidation (78.5%); pancreatic lipase inhibition (70.2%). The bioactives were further molecular docked to find strong binding affinities with PPARγ, DPP-IV, and HMG-CoA reductase. Results were confirmed statistically different (<i>p</i> < 0.05) between treated and control groups. These results suggest that the extracts can exhibit synergy as natural therapeutics in diabetes and lipid disorders.</p>","PeriodicalId":15195,"journal":{"name":"Journal of Biomaterials Science, Polymer Edition","volume":" ","pages":"1-29"},"PeriodicalIF":3.6,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637118","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":"Nanostructured Ox-MWCNT-PPy-Au electrochemical sensor for ultralow detection of retrorsine and evaluation of its cytotoxic effects on liver cells.","authors":"Ezgi Zekiye Akturk, Muath Njjar, Melek Tunc Ata, Ahmet Kaya, Abdullah Akdogan, Canan Onac","doi":"10.1080/09205063.2025.2529535","DOIUrl":"https://doi.org/10.1080/09205063.2025.2529535","url":null,"abstract":"<p><p>This study presents the development of a novel retrorsine (RTS)-imprinted sensor utilizing oxidized multi-walled carbon nanotubes (Ox-MWCNTs), polypyrrole (PPy), and gold nanoparticles (AuNPs), employing square wave voltammetry for the sensitive and selective detection of RTS which causes oxidative-stress and DNA damage. The fabricated Ox-MWCNT-PPy-AuNP sensor demonstrated a surface-area of (0.218 cm²) is 4.25 times larger than a bare glassy carbon electrode, with a low charge transfer resistance (10.9 Ω), enhancing electron transfer kinetics. The sensor showed excellent sensitivity in detecting retrorsine, with a limit of detection of 0.035 nM in synthetic matrices and -0.030 nM in HepaRG cell culture medium. Toxicity assays in HepaRG cells revealed dose-dependent oxidative-stress, with glutathione levels decreasing from 23.08 ± 0.21 µmol/10⁹ to 21.21 ± 0.02 µmol/10⁹ at 35 µM retrorsine. Concurrently, GSSG levels increased from 1.32 ± 0.26 µmol/10⁹ to 2.22 ± 0.02 µmol/10⁹. DNA-damage assessed <i>via</i> comet assay, showed significant increases in tail-moment (2.53 µm) and tail-migration (16.13 µm). Oxidative DNA-damage, indicated by 8-OHdG levels, increased significantly from 0.29 ± 0.02 ng.mL^- (control) to 0.47 ± 0.07 ng.mL^- at 35 µM retrorsine. These findings demonstrate the sensor's effectiveness for retrorsine detection and its applicability in toxicological studies. The integration of nanomaterial engineering and molecular imprinting provides a highly sensitive, selective, and eco-friendly solution for monitoring toxic agents and assessing their biological impacts.</p>","PeriodicalId":15195,"journal":{"name":"Journal of Biomaterials Science, Polymer Edition","volume":" ","pages":"1-31"},"PeriodicalIF":3.6,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608463","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":"Oral sustained release expandable dosage forms: innovations, challenges, and future directions.","authors":"Phool Chandra, Sani Pratap Singh, Vaibhav Rastogi, Mayur Porwal, Neetu Sachan","doi":"10.1080/09205063.2025.2528935","DOIUrl":"https://doi.org/10.1080/09205063.2025.2528935","url":null,"abstract":"<p><p>Oral sustained-release dosage forms have gained considerable attention for their ability to enhance therapeutic outcomes and improve patient compliance. Among these, expandable drug delivery systems represent a significant innovation, offering extended gastric retention and controlled drug release through size-based retention strategies. These systems expand in the stomach after administration, delaying gastric emptying and enabling prolonged drug action. This review presents a consolidated overview of key expandable mechanisms-such as swelling, unfolding, floating, and mucoadhesion-along with a detailed discussion on formulation strategies, polymeric materials, and <i>in vivo</i> behavior. Special emphasis is placed on recent advancements in smart polymers, 3D printing, and novel fabrication techniques. The review also explores clinical applications, manufacturing challenges, safety concerns, and future research directions. By integrating scientific, technical, and translational insights, this paper aims to highlight the potential of expandable dosage forms in advancing oral drug delivery technologies.</p>","PeriodicalId":15195,"journal":{"name":"Journal of Biomaterials Science, Polymer Edition","volume":" ","pages":"1-30"},"PeriodicalIF":3.6,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608464","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":"Janus-loaded Zn²⁺ composite film dressing based on chitin from <i>Periplaneta americana</i> effectively promotes wound healing.","authors":"Yang Qing, Ailian Zhu, Ling He, Hujing Zhang, Xi Wang, Chunyan Xiao, Qiang Fu, Qin Song","doi":"10.1080/09205063.2025.2524871","DOIUrl":"https://doi.org/10.1080/09205063.2025.2524871","url":null,"abstract":"<p><p>This study compared the application-specific benefits of PAC (<i>Periplaneta americana</i> chitin) and SC (Shrimp chitin) blended with PEG (Polyethylene Glycol) in innovative wound-dressing materials. By preparing SC/PEG and PAC/PEG porous blended membranes, it was found that PAC/PEG has better breathability, degradability. Based on this, we developed a Janus PAC/PEG@Zn0.3 composite film dressing for wound healing. After crosslinking PAC with PEG, a hydrophilic layer was formed through phase separation and selective dissolution, loaded with Zn²⁺, and combined with a hydrophobic PCL (Polycaprolactone) membrane using a simple coating technique. This composite film has the characteristics of being moist, breathable, and stretchable, and exhibits good biodegradability and compatibility. The addition of Zn²⁺ enhanced the hemostatic and antibacterial properties of the film. The mouse wound healing experiment showed that the dressing promoted collagen deposition and capillary generation, accelerating wound healing. Overall, the Janus PAC/PEG@Zn0.3 composite film is a wound dressing with promising application prospects.</p>","PeriodicalId":15195,"journal":{"name":"Journal of Biomaterials Science, Polymer Edition","volume":" ","pages":"1-29"},"PeriodicalIF":3.6,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600570","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":"Dual drug delivery of Paclitaxel and Curcumin via hyaluronic acid functionalized nanoparticles for improved breast cancer therapy.","authors":"Joyceline Praveena, Yuvraj Rallapalli, Keerthana Suresh Kizhakkanoodan, Divakarareddy Vemanna Paladugulu, Sriprasad Acharya, Bharath Raja Guru","doi":"10.1080/09205063.2025.2525668","DOIUrl":"https://doi.org/10.1080/09205063.2025.2525668","url":null,"abstract":"<p><p>Breast cancer has high mortality rate among women. Though paclitaxel is one of the important drugs used, but frequent use will lead to drug resistance. Nuclear factor kappa B (NFƘB) a transcription factor will be up regulated with frequent use of paclitaxel, and this increases drug resistance in cancer cells. Usage of curcumin will down regulate the NFƘB and using both the drugs in combination with different mechanisms of action has shown synergistic effects and reduces NFƘB expression in cancer cells. To reduce the systemic toxicity, low intracellular uptake and low bioavailability, nano-based therapeutics were used. To improve the targeting ability of the drug to the cancer cells, Hyaluronic acid (HA) is used as a targeting moiety on the surface of the nanoparticles (NP). The study focuses on formulating a Hyaluronic acid (HA) surface functionalized Poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) encapsulated with Paclitaxel (PTX) or Curcumin (CUR) to target CD44v expressed on breast cancer cells. HA surface functionalized NPs encapsulated with only PTX or in combination with CUR were treated against MCF-7 breast cancer cells. We found that HA surface functionalized NPs with combination of PTX and CUR has substantially increased cytotoxicity compared to non-surface functionalized NPs and free drugs and 2.5-fold increased cellular uptake of NPs compared to free drugs. We also found that NFKB activity reduces significantly with the use of CUR with PTX. From the results, we can conclude that combination of drugs in HA surface functionalized NPs will be useful for breast cancer therapy.</p>","PeriodicalId":15195,"journal":{"name":"Journal of Biomaterials Science, Polymer Edition","volume":" ","pages":"1-24"},"PeriodicalIF":3.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600569","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":"Nano-polyplexes from a cationic modification of poly(γ-glutamic acid).","authors":"Porochista Dorost, Montserrat García-Alvarez, Antxon Martínez de Ilarduya","doi":"10.1080/09205063.2025.2527221","DOIUrl":"https://doi.org/10.1080/09205063.2025.2527221","url":null,"abstract":"<p><p>In this study, a cationic biopolymer has been developed through the chemical modification of a biodegradable and biocompatible polymer such as poly(γ-glutamic acid) (PGGAH). A series of PGGAH_xTMEA_y copolymers with varying degrees of cationic groups incorporation (11-95%) were synthesized by partial esterification of carboxylate side groups of PGGAH with 2-bromoethyl trimethylammonium bromide (BrETABr). The copolymers were thoroughly characterized using ¹H NMR, FTIR, TGA, and GPC analyses. It was found that the degree of esterification had a pronounced effect on the thermal stability, and DNA-binding capacity of the copolymers. Higher degrees of modification were shown to enhance the excellent potential for DNA complexation, forming polyplex nanoaggregates with sizes in the range of 80-220 nm at various ammonium-to-phosphate (N/P) ratios. The stability, size, and surface charge of these polyplexes were monitored over two weeks in aqueous solutions using dynamic light scattering (DLS). Enhanced stability in polyplex formation was exhibited by copolymers with higher degrees of modification, which maintained consistent particle sizes across different N/P ratios. This study provides valuable insights into the development of efficient DNA delivery systems based on a new cationically modified poly(γ-glutamic acid) derivative.</p>","PeriodicalId":15195,"journal":{"name":"Journal of Biomaterials Science, Polymer Edition","volume":" ","pages":"1-15"},"PeriodicalIF":3.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584014","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":"Recent advances in conducting tissue engineering based on conducting polymers.","authors":"Büşra Oktay, Haya Akkad, Esma Ahlatcıoğlu Özerol","doi":"10.1080/09205063.2025.2527910","DOIUrl":"https://doi.org/10.1080/09205063.2025.2527910","url":null,"abstract":"<p><p>Conductive tissue engineering has emerged as a revolutionary approach to addressing the limitations of traditional regenerative therapies by integrating electrical and mechanical properties into biomaterials. This field focuses on mimicking the natural microenvironment of excitable tissues, such as nerves, cardiac, and skeletal muscles, to enhance cellular functions and facilitate tissue repair. Conducting polymers (CP), including polypyrrole, polyaniline, and PEDOT, have been widely utilized for their exceptional electrical conductivity, biocompatibility, and tunable properties. The incorporation of these polymers into electroactive scaffolds has demonstrated significant potential in promoting cell proliferation, differentiation, and alignment, while also enabling functional recovery through electrical stimulation. Applications in nerve regeneration have shown promise in restoring synaptic connections, while in cardiac and skeletal muscle tissues, conductive scaffolds aid in synchronized contractions and structural reinforcement. Despite these advancements, challenges such as optimizing conductivity, achieving long-term biocompatibility, and scaling production remain key areas of focus. This review thoroughly examines the use of conducting polymers for different tissue types such as neural, cardiac, and muscular tissues in light of the most recent literature. By addressing key topics such as electrical stimulation, multifunctional scaffold systems, biological responses, and emerging research trends, this study presents a holistic and up-to-date contribution to the field. Future directions aim to refine scaffold designs, enhance electrical stimulation protocols, and explore translational potential, paving the way for advanced regenerative therapies.</p>","PeriodicalId":15195,"journal":{"name":"Journal of Biomaterials Science, Polymer Edition","volume":" ","pages":"1-33"},"PeriodicalIF":3.6,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567473","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":"Hyaluronic acid and K-carrageenan metal ionic cross-linked polymers: a promising injectable hydrogels for prolonged chemotherapeutic drug delivery.","authors":"Hadeia Mashaqbeh, Rania Hamed, Rana Obaidat, Ali Hmedat, Raffa Aburayya, Sara Hijazi, Yazan Akkam","doi":"10.1080/09205063.2025.2524059","DOIUrl":"https://doi.org/10.1080/09205063.2025.2524059","url":null,"abstract":"<p><p>Hydrogel-based drug delivery technologies have garnered considerable interest in the biomedical field, aiming to overcome the challenges associated with conventional treatments. This investigation reports a novel injectable hydrogel composed of non-chemically modified hyaluronic acid and κ-carrageenan, crosslinked using a Fe(III)-ethylenediaminetetraacetic acid (EDTA) complex for the delivery of a chemotherapeutic agent. The system exhibits shear-thinning behavior, possessing both appropriate rheological and drug-release properties, thereby eliminating the need for chemical or thermoresponsive additives. This study examines this system in the context of chemotherapeutic delivery, providing a novel approach to achieving biocompatibility, structural flexibility, injectability, and prolonged release properties. The developed hydrogels were evaluated <i>in vitro</i> for their ability to deliver the model drug daunorubicin (DNR). Physicochemical characterizations of hydrogels, including FTIR, DSC, and SEM analysis, were carried out. Furthermore, the rheological properties, <i>in vitro</i> release, swelling, degradation, and cytotoxicity of the developed hydrogels were evaluated. Homopolymer hydrogels of metal ion crosslinked HA, KCG, and hybrid hydrogels of HA-KCG were developed and evaluated. All studied hydrogels can control DNR release; compared to homopolymer hydrogels, the HA-KCG hybrid hydrogels showed a better swelling ratio, a slower degradation rate, and a higher capability to prolong DNR release over 16 days. In addition, the evaluated hydrogels exhibit shear-thinning properties and diverse viscoelastic properties, as well as enhanced DNR cytotoxic activities. Overall, Injectable self-healing hydrogels of HA and KCG interpenetrating polymer networks (IPNs) produced by metal ionic crosslinking were successfully created, exhibiting shear-thinning ability and thixotropic properties, making them a potential candidate for localized chemotherapeutic drug delivery.</p>","PeriodicalId":15195,"journal":{"name":"Journal of Biomaterials Science, Polymer Edition","volume":" ","pages":"1-30"},"PeriodicalIF":3.6,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560240","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}