Recent Patents on Nanotechnology最新文献

{"title":"Recent Patents and Potential Applications of Homogenisation Techniques in Drug Delivery Systems.","authors":"Harpreet Kaur Khanuja,&nbsp;Harish Dureja","doi":"10.2174/1872210515666210719120203","DOIUrl":"https://doi.org/10.2174/1872210515666210719120203","url":null,"abstract":"<p><strong>Background: </strong>The term homogenise means \"to force or provide coalesce\". Homogenisation is a process to attain homogenous particle size. The objective of the homogenisation process is to use fluid force to split the fragments or tiny particles contained in the fluids into very small dimensions and form a sustainable dispersion suitable for further production.</p><p><strong>Methods: </strong>The databases were collected through Scopus, google patent, science web, google scholar, PubMed on the concept of homogenisation. The data obtained were systematically investigated.</p><p><strong>Results: </strong>The present study focus on the use of the homogenisation in drug delivery system. The aim of homogenisation process is to achieve the particle size in micro-and nano- range as it affects the different parameters in the formulation and biopharmaceutical profile of the drug. The particle size reduction plays a key role in influencing drug dissolution and absorption. The reduced particle size enhances the stability and therapeutic efficacy of the drug. Homogenization technology ensures to achieve effective, clinically efficient and targeted drug delivery with the minimal side effect.</p><p><strong>Conclusion: </strong>Homogenization technology has been shown to be an efficient and easy method of size reduction to increase solubility and bioavailability, stability of drug carriers. This article gives an overview of the process attributes affecting the homogenization process, the patenting of homogeniser types, design, the geometry of valves and nozzles and its role in drug delivery.</p>","PeriodicalId":49324,"journal":{"name":"Recent Patents on Nanotechnology","volume":"17 1","pages":"33-50"},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10720325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Review of the Latest Advances in Nanoparticle-Mediated Processes for Hexavalent Chromium Remediation from Water Bodies.","authors":"Subhadeep Biswas,&nbsp;Mohammad Danish,&nbsp;Anjali Pal","doi":"10.2174/1872210516666220314153635","DOIUrl":"https://doi.org/10.2174/1872210516666220314153635","url":null,"abstract":"<p><p>Hexavalent chromium (Cr(VI)) is a well-known carcinogen, and hence its removal from aqueous media is an important area of research in the field of environmental engineering. Adsorptive removal and catalytic reduction are the two most common techniques applied for this purpose. In this regard, nanoparticle-mediated technology has contributed significantly. In the current review article, a systematic investigation has been carried out to find the latest developments that took place in the domain of Cr(VI) removal by nanotechnology. The major portion deals with the advancement and application of the new-age materials, such as carbon nanotubes (CNTs), g-C₃N₄, MXenes, zero-valent iron (ZVI), and their composites, for the Cr(VI) remediation purpose. Various interesting mechanisms, as proposed by different research groups, have been covered. Applications of the nanocomposites in the real wastewater scenario have also been highlighted. Different characterization techniques often conducted in order to get insight into Cr(VI) removal process have been mentioned. Some patents related to this field have been discussed. Lastly, the future scope of the nanomaterials, current challenges, feasibility of using these nanomaterials in large-scale treatment plants, etc., have been addressed before concluding the article.</p>","PeriodicalId":49324,"journal":{"name":"Recent Patents on Nanotechnology","volume":"17 4","pages":"327-339"},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9572971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PLGA Nanoparticles and Transdermal Delivery.","authors":"Lalit Kumar","doi":"10.2174/1872210516666220127125041","DOIUrl":"https://doi.org/10.2174/1872210516666220127125041","url":null,"abstract":"<jats:sec>\u0000<jats:title />\u0000<jats:p />\u0000</jats:sec>","PeriodicalId":49324,"journal":{"name":"Recent Patents on Nanotechnology","volume":"17 1","pages":"3-4"},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10825536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanocapsules: An Emerging Drug Delivery System.","authors":"Deepika Purohit,&nbsp;Pawan Jalwal,&nbsp;Deeksha Manchanda,&nbsp;Sapna Saini,&nbsp;Ravinder Verma,&nbsp;Deepak Kaushik,&nbsp;Vineet Mittal,&nbsp;Manish Kumar,&nbsp;Tanima Bhattacharya,&nbsp;Md Habibur Rahman,&nbsp;Rohit Dutt,&nbsp;Parijat Pandey","doi":"10.2174/1872210516666220210113256","DOIUrl":"https://doi.org/10.2174/1872210516666220210113256","url":null,"abstract":"<p><strong>Background: </strong>Controlled drug release and site-specific delivery of drugs make nanocapsules the most approbative drug delivery system for various kinds of drugs, bioactive, protein, and peptide compounds. Nanocapsules (NCs) are spherical shape microscopic shells consisting of a core (solid or liquid) in which the drug is positioned in a cavity enclosed by a distinctive polymeric membrane.</p><p><strong>Objectives: </strong>The main objective of the present patent study is to elaborate on various formulation techniques and methods of nanocapsules (NCs). The review also spotlights various biomedical applications as well as on the patents of NCs to date.</p><p><strong>Methods: </strong>The review was extracted from the searches performed using various search engines such as PubMed, Google Patents, Medline, Google Scholars, etc. In order to emphasize the importance of NCs, some published patents of NCs have also been reported in the review.</p><p><strong>Results: </strong>NCs are tiny magical shells having incredible reproducibility. Various techniques can be used to formulate NCs. The pharmaceutical performance of the formulated NCs can be judged by evaluating their shape, size, entrapment efficiency, loading capacity, etc., using different analytical techniques. Their main applications are found in the field of agrochemicals, genetic manipulation, cosmetics, hygiene items, strategic distribution of drugs to tumors, nanocapsule bandages to combat infection, and radiotherapy.</p><p><strong>Conclusion: </strong>In the present review, our team made a deliberate effort to summarize the recent advances in the field of NCs and focus on new patents related to the implementation of NCs delivery systems in the area of some life-threatening disorders like diabetes, cancer, and cardiovascular diseases.</p>","PeriodicalId":49324,"journal":{"name":"Recent Patents on Nanotechnology","volume":"17 3","pages":"190-207"},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9180854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanomaterial Gas Sensors for Biosensing Applications: A Review.","authors":"Kurmendra","doi":"10.2174/1872210515666211129115229","DOIUrl":"https://doi.org/10.2174/1872210515666211129115229","url":null,"abstract":"<p><strong>Background: </strong>Nanomaterial is one of the most used materials for various gas sensing applications to detect toxic gases, human breath, and other specific gas sensing. One of the most important applications of nanomaterial based gas sensors is biosensing applications. In this review article, the gas sensors for biosensing are discussed on the basis of crystalline structure and different categories of nanomaterial.</p><p><strong>Methods: </strong>In this paper, firstly, rigorous efforts have been made to find out research questions by going through a structured and systematic survey of available peer reviewed high quality articles in this field. The papers related to nanomaterial based biosensors are then reviewed qualitatively to provide substantive findings from the recent developments in this field.</p><p><strong>Results: </strong>In this mini-review article, firstly, classifications of nanomaterial gas sensors have been presented on the basis of the crystalline structure of nanomaterial and different types of nanomaterial available for biosensing applications. Further, the gas sensors based on nanomaterial for biosensing applications are collected and reviewed in terms of their performance parameters such as sensing material used, target gas component, detection ranges (ppm-ppb), response time, operating temperature and method of detection, etc. The different nanomaterials possess slightly different sensing and morphological properties due to their structure; therefore, it can be said that a nanomaterial must be selected carefully for a particular application. The 1D nanomaterials show the best selectivity and sensitivity for gases available in low concentration ranges due to their miniaturised structure compared to 2D and 3D nanomaterials. However, these 2D and 3D nanomaterials also so good sensing properties compared to bulk semiconductor materials. The polymer and nanocomposites which are also discussed in this patent article have opened the door for future research and have great potential for new generation gas sensors for detecting biomolecules.</p><p><strong>Conclusion: </strong>These nanomaterials extend great properties towards sensing the application of different gases for a lower concentration of particular gas particles. Nano polymer and nanocomposites have great potential to be used as gas sensors for the detection of biomolecules.</p>","PeriodicalId":49324,"journal":{"name":"Recent Patents on Nanotechnology","volume":"17 2","pages":"104-118"},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10664398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Detailed Insight into Nanostructured Lipid Carriers: A Versatile Drug Delivery System.","authors":"Samarjit Ghosh,&nbsp;Triveni Tiwari,&nbsp;Upendra Nagaich,&nbsp;Neha Jain","doi":"10.2174/1872210516666220523121733","DOIUrl":"https://doi.org/10.2174/1872210516666220523121733","url":null,"abstract":"<p><p>The advent of technology provides a solution to various drug delivery-related problems by undertaking the development of a better drug delivery system, i.e., nano-sized drug delivery systems as they have shown huge prospects for effective delivery of drugs in the body. Nanostructured lipid carriers (NLCs) are such type of novel drug delivery system in which lipids of both solid and liquid types are used as a core for the disorganized matrix, which prevents the solid lipid crystallization and increases drug payload. They are generally composed of solid and liquid lipids, emulsifiers, drugs, and other various additives, which are selected based on purity, chemical stability, the concentration of materials required, compatibility, biodegradability, processing type, cost, and their regulatory status. Placing bioactives into nanostructured lipid carriers (NLCs) has enhanced pharmacokinetic characteristics by increasing therapeutic functionality and prolonging release from these carrier systems. In our opinion, the search involves two steps viz. fabrication strategies, production methods, and the impact of various types of substances on them, as well as the release mechanism and targeting modalities. In addition to other applications, the use of NLCs in gene therapy has marked a promising path for new and better drug delivery systems. Further development of various dosage forms using NLCs, like NLC based hydrogels, is being done for improving the overall aesthetic properties, leading to the desired therapeutic effect of the incorporated active. This review highlights several elements of NLCs, such as structural model and types, excipients utilized, factors affecting NLC production, preparation techniques, characterization, current applications, patents, challenges, and opportunities.</p>","PeriodicalId":49324,"journal":{"name":"Recent Patents on Nanotechnology","volume":"17 4","pages":"284-306"},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9566451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced Anti-Proliferative Effect of Carboplatin in Ovarian Cancer Cells Exploiting Chitosan-Poly (Lactic Glycolic Acid) Nanoparticles.","authors":"Fatima Redah Alassaif,&nbsp;Eman Redah Alassaif,&nbsp;Amit Kumar Kaushik,&nbsp;Jeevitha Dhanapal","doi":"10.2174/1872210516666220111160341","DOIUrl":"https://doi.org/10.2174/1872210516666220111160341","url":null,"abstract":"<p><strong>Objective: </strong>The present article aimed to enhance the therapeutic efficacy of carboplatin (CP) using the formulation of chitosan-poly (lactic glycolic acid) nanoparticles (CS-PLGA NPs).</p><p><strong>Methods: </strong>Nanoparticles were synthesized by an ionic gelation method and were characterized for their morphology, particle size, and surface potential measurements by TEM and zeta sizer. This study was highlighted for the evaluation of drug entrapment, loading and in vitro drug release capabilities of the prepared nanoparticles by spectrophotometric analysis. The stability study was also conducted after 3 months for their particle size, zeta potential, drug loading and encapsulation efficiencies. Further, ovarian cancer cell line PEO1 was used to evaluate the toxicity and efficacy of nano-formulation by MTT assay. Additionally, the study was evaluated for apoptosis using flow cytometric analysis.</p><p><strong>Results: </strong>The CS-PLGA-CP NPs were uniform and spherical in shape. The particle size and zeta potential of CS-PLGA-CP NPs were measured to be 156 ±6.8 nm and +52 ±2.4 mV, respectively. High encapsulation (87.4 ± 4.5%) and controlled retention capacities confirmed the efficiency of the prepared nanoparticles in a time and dose-dependent manner. The cytotoxicity assay results also showed that CS-PLGA-CP NPs have a high efficiency on PEO1 cells compared to the free drug. The flow cytometric result showed 64.25% of the PEO1 cells were apoptotic, and 8.42% were necrotic when treated with CS-PLGA-CP NPs.</p><p><strong>Conclusion: </strong>Chitosan-PLGA combinational polymeric nanoparticles were not only steady but also non-toxic. Our experiments revealed that the chitosan-PLGA nanoparticles could be used as a challenging vehicle candidate for drug delivery for the therapeutic treatment of ovarian cancer.</p>","PeriodicalId":49324,"journal":{"name":"Recent Patents on Nanotechnology","volume":"17 1","pages":"74-82"},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9217287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Green Synthesis of Silver Nanoparticles of <i>Vernonia cinerea</i> Leaf Extract and their <i>In vitro</i> Cytotoxicity Activity against Neuroblastoma SHSY-5Y Cell Lines, Antimicrobial and Antioxidant Studies.","authors":"Narahari N Palei,&nbsp;S Navaneetha Krishnan,&nbsp;R Jayaraman,&nbsp;S Hemanth Reddy,&nbsp;Anna Balaji,&nbsp;Malay K Samanta,&nbsp;Bibhash C Mohanta","doi":"10.2174/1872210516666220520144453","DOIUrl":"https://doi.org/10.2174/1872210516666220520144453","url":null,"abstract":"<p><strong>Background: </strong>Green syntheses of silver nanoparticles using plant extracts have potential anti- cancer, antimicrobial, and antioxidant properties, among other aspects. The aim of the present patent study was to synthesize silver nanoparticles (AgNPs) using Vernonia cinerea plant extract.</p><p><strong>Methods: </strong>The AgNPs were successfully prepared and characterized using UV-Vis Spectrophotometer, particle size, Zeta potential, Transmission electron microscopy (TEM), Energy-dispersive x-ray analysis (EDAX), X-ray diffraction (XRD), and Fourier transform infrared (FTIR) spectrometry. The in vitro cytotoxicity study was performed using neuroblastoma SHSY-5Y cell lines. Moreover, antimicrobial and antioxidant activity studies were also performed for AgNPs.</p><p><strong>Results: </strong>The size of AgNPs determined through the dynamic light scattering (DLS) technique was 49.5 nm and the zeta potential was -36.8 mV. The synthesized AgNPs were checked using UV-Visible spectroscopy at ƛmax 439 nm. The color was changed from green to dark brown, indicating the formation of AgNPs. The TEM study revealed that the nanoparticles were spherical in shape. The XRD pattern of AgNPs produced in this experiment was apparently crystalline. The results of FTIR study revealed that the majority of the obtained peaks correspond to the polyphenols, triterpenoids, and alkaloids which were abundant in the corresponding to the V. cinerea leaf extract and support to the formation of AgNPs. The cytotoxicity effect of the V. cinerea plant extract and biosynthesized AgNPs was found to be dosedependent. From the results of antimicrobial studies, it was reported that the gram negative bacteria were found to be more susceptible compared to the gram positive bacteria. Moreover, the results of antioxidant study revealed that the AgNPs showed good antioxidant activity (77.21%) in comparison to the V. cinerea plant extract (56.13%).</p><p><strong>Conclusion: </strong>Based on the results, it could be concluded that the green synthesized silver nanoparticles showed promising anticancer, antioxidant, and anti-bacterial activities as compared to the plain V. cineria plant extract.</p>","PeriodicalId":49324,"journal":{"name":"Recent Patents on Nanotechnology","volume":"17 3","pages":"270-280"},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9524788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Discursive Review of Recent Development and Patents on Glycerosomes.","authors":"Singh Ragini,&nbsp;Fatima Zeeshan,&nbsp;Srivastava Dipti,&nbsp;Awasthi Himani","doi":"10.2174/1872210516666220328124450","DOIUrl":"https://doi.org/10.2174/1872210516666220328124450","url":null,"abstract":"<p><strong>Background: </strong>To achieve a target-based drug delivery with minimal side effects, novel drug delivery systems are being continuously explored. Vesicular systems are one such system that can ameliorate the bioavailability of the encapsulated drug by delivering the drug at the targeted site and can minimize the side effect.</p><p><strong>Objective: </strong>The objective of this patent review is to provide a vivid description of glycerosomes and their applications. Glycerosomes are sphere-shaped versatile vesicles consisting of one or more phospholipid bilayers similar to liposomes but contain a high concentration of glycerol, which modifies the liposome bilayer fluidity. Glycerosomes can encapsulate both hydrophobic and hydrophilic drugs, which makes them the promising vehicle in the field of drug delivery.</p><p><strong>Conclusion: </strong>Most of the glycerosome formulations prepared were targeted for topical delivery and in particular, a cutaneous route where they have shown promising results. These vesicles are biocompatible and due to the high glycerol concentration, they have improved spreadability and penetrability. It is therefore imperative to explore the other topical routes such as ocular, vaginal, nasal, and rectal for delivery of drugs.</p>","PeriodicalId":49324,"journal":{"name":"Recent Patents on Nanotechnology","volume":"17 3","pages":"183-189"},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9384528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preparation of Bismuth Tungstate/Preoxidized Acrylonitrile/Acrylic Acid Copolymer Composite Nanofiber Membrane and Its Photocatalytic Properties.","authors":"Yinchun Fang,&nbsp;Xinhua Liu,&nbsp;Hongzhang Li,&nbsp;Yanchun Liu","doi":"10.2174/1872210516666220513094531","DOIUrl":"https://doi.org/10.2174/1872210516666220513094531","url":null,"abstract":"<p><strong>Background: </strong>In this patent article, a novel bismuth tungstate/preoxidized acrylonitrile/ acrylic acid (AN/AA) copolymer composite nanofiber membrane was prepared, which was used as the visible light catalyst.</p><p><strong>Methods: </strong>AN/AA copolymer was synthesized, which was electrospun with bismuth nitrate and sodium tungstate to prepare the composite nanofiber. Then the composite nanofiber was preoxidized to prepare the bismuth tungstate/preoxidized AN/AA composite nanofiber membrane containing adsorption moiety and photocatalytic active moiety.</p><p><strong>Results: </strong>The photocatalytic activity of bismuth tungstate/preoxidized AN/AA composite nanofiber membrane with different preoxidized temperature, heating rate, and holding time by catalytic degradation of methylene blue was investigated. The optimal preoxidized conditions were as follows: the preoxidized temperature was heated to 200 °C with the heating rate of 1°C/min and the holding time at this temperature was 12 h. The chemical structure and morphology of the composite nanofiber membrane were characterized by FTIR, XRD, and SEM.</p><p><strong>Conclusion: </strong>The bismuth tungstate/preoxidized AN/AA composite nanofiber membrane obtained good photocatalytic properties and reusability under visible light. The degradation rate of methylene blue by this visible light catalyst could reach 90.24% for 4.5 h, and the degradation rate remained 81.53% for 4.5 h after 5 reuses.</p>","PeriodicalId":49324,"journal":{"name":"Recent Patents on Nanotechnology","volume":"17 2","pages":"144-149"},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10655330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}