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LPA_(1) antagonist-derived LNPs deliver A20 mRNA and promote anti-fibrotic activities

Nano Research 2024年第10期17卷 9095-9102页

作者： Jingyue Yan Diana D.Kang Chang Wang Xucheng Hou Shi Du Siyu Wang Yonger Xue Zhengwei Liu Haoyuan Li Yichen Zhong Binbin Deng David W.McComb Yizhou Dong division of Pharmaceutics&Pharmacology College of PharmacyThe Ohio State UniversityColumbusOH 43210USA Icahn Genomics Institute Precision Immunology InstituteDepartment of Immunology and ImmunotherapyDepartment of Oncological SciencesTisch Cancer InstituteBiomedical Engineering and Imaging InstituteFriedman Brain InstituteIcahn School of Medicine at Mount SinaiNew YorkNY 10029USA Center for Electron Microscopy and Analysis The Ohio State UniversityColumbusOH 43212USA Department of Materials Science and Engineering The Ohio State UniversityColumbusOH 43210USA

Activated fibroblasts are major mediators of pulmonary *** are generally found in the connective tissue but upon activation can generate excess extracellular matrix(ECM)in the lung interstitial ***,fibroblasts are one of the most targeted cells for treating idiopathic pulmonary fibrosis(IPF).Here,we develop an anti-fibrotic platform that can modulate both the lysophosphatidic acid receptor 1(LPA_(1))and the inflammatory pathway through tumor necrosis factorα-induced protein 3(TNFAIP3,also known as A20)in ***,we synthesized a series of LPA_(1) antagonists,AM095 and AM966,derived amino lipids(LA lipids)which were formulated into LA-lipid nanoparticles(LA-LNPs)encapsulating ***,LA5-LNPs,with AM966 head group and biodegradable acetal lipid tails,showed efficient A20 mRNA delivery to lung fibroblasts in vitro(80.2%±1.5%)and ex vivo(17.2%±0.4%).When treated to primary mouse lung fibroblasts(MLF),this formulation inhibited fibroblast migration and collagen production,thereby slowing the progression of ***,LA5-LNPs encapsulated with A20 mRNA is a novel platform offering a potential approach to regulate fibroblast activation for the treatment of IPF.

关键词： lysophosphatidic acid receptor 1(LPA_(1))antagonist tumor necrosis factorα-induced protein 3(A20) lung fibrosis lipid nanoparticles mRNA

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Comprehensive analysis of the potential pathogenesis of COVID-19 infection and liver cancer

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 436-457页

作者： Yao Rong Ming-Zheng Tang Song-Hua Liu Xiao-Feng Li Hui Cai First Clinical Medical College Gansu University of Chinese MedicineLanzhou 730000Gansu ProvinceChina General Surgery Clinical Medical Center Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina Key Laboratory of Molecular diagnostics and Precision Medicine for Surgical Oncology in Gansu Province Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina NHC Key Laboratory of Diagnosis and therapy of Gastrointestinal Tumor Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina

BACKGROUND A growing number of clinical examples suggest that coronavirus disease 2019(COVID-19)appears to have an impact on the treatment of patients with liver cancer compared to the normal population,and the prevalence of COVID-19 is significantly higher in patients with liver ***,this mechanism of action has not been *** sets for COVID-19(GSE180226)and liver cancer(GSE87630)were obtained from the Gene Expression Omnibus *** identifying the common differentially expressed genes(DEGs)of COVID-19 and liver cancer,functional enrichment analysis,protein-protein interaction network construction and scree-ning and analysis of hub genes were ***,the validation of the differential expression of hub genes in the disease was performed and the regulatory network of transcription factors and hub genes was *** Of 518 common DEGs were obtained by screening for functional *** hub genes including aurora kinase B,cyclin B2,cell division cycle 20,cell division cycle associated 8,nucleolar and spindle associated protein 1,etc.,were further identified from DEGs using the“cytoHubba”*** enrichment analysis of hub genes showed that these hub genes are associated with P53 signalling pathway regulation,cell cycle and other functions,and they may serve as potential molecular markers for COVID-19 and liver ***,we selected 10 of the hub genes for in vitro expression validation in liver cancer *** Our study reveals a common pathogenesis of liver cancer and *** common pathways and key genes may provide new ideas for further mechanistic studies.

关键词： COVID-19 Liver cancer Differentially expressed genes Hub genes Pathogenesis

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Delphi study for developing a checklist of adverse events associated with acupotomy

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Journal of Integrative Medicine 2024年第5期22卷 579-587页

作者： Hyungsun Jun Haebeom Lee Sang-Hoon Yoon Chan-Young Kwon Damin Jeon Jun-Hwan Lee Jungtae Leem Department of diagnostics College of Korean Medicine Wonkwang University 7Days Inc. Chung-Yeon Korean Medicine Clinic Department of Oriental Neuropsychiatry Dong-Eui University College of Korean Medicine Chonnam National University Hwasun Hospital KM Science Research division Korea Institute of Oriental Medicine Department of Korean Convergence Medical Science KIOM School University of Science & Technology (UST) Department of Physical Medicine and Rehabilitation Spaulding Rehabilitation Hospital Harvard Medical School Research Center of Traditional Korean Medicine College of Korean Medicine Wonkwang University

Background: Acupotomy, a more invasive procedure than acupuncture, involves the use of a thicker needle with an integrated knife at the tip, necessitating safety research. We aimed to define relevant adverse events(AEs) and create a standardized form of the ACUPOtomy-related AEs CHECKlist(ACUPOCHECK).Methods: Before conducting the Delphi process, a systematic review and pilot prospective study were conducted to gather information on previously reported AEs. Using these data, pilot versions of the ACUPOCHECK and Delphi questionnaires were developed. The Delphi questionnaire involved selecting types of AE for inclusion, establishing separate criteria for acupotomy-related AEs, and achieving a consensus on AE assessment. Thirteen Korean doctors with experience in acupotomy or AE research were recruited to participate in each Delphi round. Consensus was considered to have been reached if the critical value for the content validity ratio met or exceeded ***: The final ACUPOCHECK was developed using four rounds of the Delphi method and one face-toface consensus meeting. It included 12 local AEs(pain, hemorrhage, bruise, hematoma, edema, pruritus,rash, infection, nerve damage, dysesthesia, movement impairment, and pneumothorax) and 14 systemic AEs(disease aggravation, needle fatigue, sleepiness, procedural nausea, procedural vomiting, procedural headache, procedural dizziness, sweating, procedural shock, syncope, dyspnea, procedural pain, sleep disorder, and postprocedural infection). Separate criteria were established for pain, hemorrhage and bruising: pain was defined as pain that occurrs during daily activities and persists for longer than 72 h,hemorrhage as bleeding that continues for ≥ 3 min despite pressure application, and bruising as having a bruise with a diameter of ≥ 3 cm. Open-ended descriptions were allowed for AEs not covered by the checklist, and severity and causality were assessed using the Common Terminology Criteria for Adverse Events and modif

关键词： Acupotomy Delphi technique Patient safety Safety management Adverse event

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Supercritical fluid technology:A game-changer for biomacromolecular nanomedicine preparation and biomedical application

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Chinese Chemical Letters 2024年第7期35卷 89-99页

作者： Yating Zheng Yulan Huang Jing Luo Xuqi Peng Xiran Gui Gang Liu Yang Zhang State Key Laboratory of Vaccines for Infectious Diseases Xiang An Biomedicine LaboratoryNational Innovation Platform for Industry-Education Integration in Vaccine ResearchState Key Laboratory of Molecular Vaccinology and Molecular DiagnosticsCenter for Molecular Imaging and Translational MedicineSchool of Public HealthXiamen UniversityXiamen 361102China Shen Zhen Research Institute of Xiamen University Shenzhen 518057China division of Urology and Department of Surgery Brigham and Women's HospitalHarvard Medical SchoolBostonMA 02115United States Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province(IKKEM) Xiamen 361102China

Biomacromolecules are attractive in biomedical applications as therapeutic agents and potential drug carriers due to their natural active components,good biocompatibility,and high ***,their large relative molecular weight,complex structure,susceptibility to degradation,and poor stability limit their *** can address these issues by improving the therapeutic value,bioavailability,permeability,and absorption of biomacromolecules while regulating their retention time in the ***,compelling evidence has been reported that supercritical fluid(SCF)technology has emerged as an alternative that maintains the integrity of biomacromolecules and reduces environmental *** this review,we highlight a set of unique nanosizing strategies based on SCF technology for biomacromolecular nanomedicine,and extensively discuss their characteristics and *** particular,the protein-based,nucleic acid-based,and polysaccharide-based nanomedicine preparations via SCF technology and their biomedical applications are summarized,and the potential for industrial production of biomacromolecular drugs is also *** further provide perspectives on the opportunities and challenges in this excellent field of biomacromolecular drugs nanotechnology.

关键词： Biomacromolecules Supercritical fluid technology Therapeutic proteins Gene therapy Nanomedicine

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Viral-host molecular interactions and metabolic modulation:Strategies to inhibit flaviviruses pathogenesis

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World Journal of Virology 2024年第4期13卷 41-50页

作者： Zeeshan Ahmad Khan Mukesh Kumar Yadav Dong-Woo Lim Hojun Kim Jing-Hua Wang AbuZar Ansari Biohealth Products Research Center(BPRC) Research Center for Agedlife Redesign(RCAR)Department of Physical TherapyINJE UniversityGimhae 5084South Korea Department of Microbiology Central University of PunjabBathinda 151401India Department of diagnostics College of Korean MedicineDongguk UniversityGoyang 10326South Korea division of Rehabilitation Medicine of Korean Medicine Department of Oriental Rehabilitation MedicineDongguk UniversityIlsan HospitalGoyang 10326South Korea Institute of Oriental Medicine Dongguk UniversityGoyang 10326South Korea Department of Obstetrics and Gynecology Ewha Womans UniversitySeoul 07985South Korea

Flaviviruses,which include globally impactful pathogens,such as West Nile virus,yellow fever virus,Zika virus,Japanese encephalitis virus,and dengue virus,contribute significantly to human *** the ongoing emergence and resurgence of flavivirus-mediated pathogenesis,the absence of specific therapeutic options remains a challenge in the prevention and treatment of flaviviral *** the intricate processes of fusion,transcription,replication,and maturation,the complex interplay of viral and host metabolic interactions affects *** interactions involve metabolic molecules,such as amino acids,glucose,fatty acids,and nucleotides,each playing a pivotal role in the replication and maturation of *** viral-host metabolic molecular interactions hijack and modulate the molecular mechanisms of host metabolism.A comprehensive understanding of these intricate metabolic pathways offers valuable insights,potentially unveiling novel targets for therapeutic interventions against flaviviral *** review emphasizes promising avenues for the development of therapeutic agents that target specific metabolic molecules,such as amino acids,glucose,fatty acids,and nucleotides,which interact with flavivirus replication and are closely linked to the modulation of host *** clinical limitations of current drugs have prompted the development of new inhibitory strategies for flaviviruses based on an understanding of the molecular interactions between the virus and the host.

关键词： Flavivirus Nonstructural proteins Virus-host interaction Metabolism Inhibitors Vaccines

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Liver cell cancer surveillance practice in Nigeria:Pitfalls and future prospects

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World Journal of Hepatology 2024年第10期16卷 1132-1141页

作者： Yusuf Musa Ijeoma M Ifeorah Abubakar Sadiq Maiyaki Rahama Mohammad Almustapha Yussuf Abdulkadir Maisuna Habib Tijjani Saleh Abdulmumini Yakubu division of Gastroenterology and Hepatology Department of Internal MedicineFederal Teaching Hospital KatsinaKatsina 820101Nigeria Department of Medical Laboratory Sciences College of Medicine University of Nigeria Enugu CampusEnugu 400102Nigeria division of Gastroenterology and Hepatology Department of Internal MedicineFaculty of Clinical SciencesCollege of Health SciencesUsmanu Danfodiyo UniversitySokoto 840283Nigeria division of Gastroenterology and Hepatology Department of Internal MedicineUsmanu Danfodiyo University Teaching Hospital SokotoSokoto 840101Nigeria Infection Prevention and Control Unit Department of Community MedicineFederal Teaching HospitalKatsina 820101KatsinaNigeria division of Gastroenterology and Hepatology Department of Internal MedicineBayero University KanoKano 700101Nigeria division of Gastroenterology and Hepatology Department of Internal MedicineAminu Kano Teaching HospitalKano 700101Nigeria division of Gastroenterology and Hepatology Department of Internal MedicineUsmanu Danfodiyo UniversitySokoto 840283Nigeria division of Gastroenterology and Hepatology Department of Internal MedicineUsmanu Danfodiyo University Teaching HospitalSokoto 840283Nigeria

Hepatocellular carcinoma(HCC)is a disease of public health concern in Nigeria,with chronic hepatitis B and C infections contributing most to the disease *** the increasing incidence of HCC,surveillance practices for early diagnosis and possible cure are not deeply rooted in the *** article aims to review the current status of HCC surveillance in Nigeria,stressing the encounters,breaches,and potential *** factors,such as limited tools for screening and diagnostics,insufficient infrastructure,and low cognizance among the doctors,and the general public affect the surveillance practices for HCC in ***,the lack of standardized guidelines and protocols for HCC surveillance further intensifies the suboptimal diagnosis and ***,there are opportunities for refining surveillance practices in the *** would be achieved through boosted public health sensitization campaigns,integrating HCC screening into routine clinical services,and leveraging technological developments for early detection and ***,collaboration between government agencies,healthcare providers,and international organizations can facilitate the development of comprehensive HCC surveillance programs person-alized to the Nigerian ***,HCC surveillance practice faces substantial *** addressing the drawbacks and leveraging prospects,Nigeria can improve HCC surveillance,with subsequent improved outcomes for individuals at risk of developing the disease.

关键词： Hepatocellular cancer Surveillance Alpha-fetoprotein Ultrasonography Des-gamma-carboxy prothrombin Early disease Intermediate disease Late disease Advance disease

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Splenic lymphangiomatosis showing rapid growth during lactation:A case report

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World Journal of Gastroenterology 2010年第9期16卷 1155-1157页

作者： Rosalia Patti Emilio Iannitto Gaetano Di Vita General Surgery Unit Department of Surgical and Oncological SciencesUniversity of Palermo Haematological division University of Palermo

Splenic lymphangiomatosis is a very rare condition that,from 1990 to date,has been described only nine *** the present report,we describe the first case of splenic lymphangiomatosis with rapid growth during lactation in a 35-year-old *** also underline the difficultly in making an accurate preoperative diagnosis,despite more modern imaging *** splenectomy was considered to be the treatment needed,both to make a definitive diagnosis and to exclude the presence of malignancy.

关键词： Lymphangiomatosis Spleen Lactation

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Identification of telomere maintenance gene variations related to lung adenocarcinoma risk by genome-wide association and whole genome sequencing analyses

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Cancer Communications 2024年第2期44卷 287-293页

作者： Kouya Shiraishi Atsushi Takahashi Yukihide Momozawa Yataro Daigo Syuzo Kaneko Takahisa Kawaguchi Hideo Kunitoh Shingo Matsumoto Hidehito Horinouchi Akiteru Goto Takayuki Honda Kimihiro Shimizu Masahiro Torasawa Daisuke Takayanagi Motonobu Saito Akira Saito Yuichiro Ohe Shun-ichi Watanabe Koichi Goto Masahiro Tsuboi Katsuya Tsuchihara Sadaaki Takata Tomomi Aoi Atsushi Takano Masashi Kobayashi Yohei Miyagi Kazumi Tanaka Hiroyuki Suzuki Daichi Maeda Takumi Yamaura Maiko Matsuda Yoko Shimada Takaaki Mizuno Hiromi Sakamoto Teruhiko Yoshida Yasushi Goto Tatsuya Yoshida Taiki Yamaji Makoto Sonobe Shinichi Toyooka Kazue Yoneda Katsuhiro Masago Fumihiro Tanaka Megumi Hara Nobuo Fuse Satoshi S.Nishizuka Noriko Motoi Norie Sawada Yuichiro Nishida Kazuki Kumada Kenji Takeuchi Kozo Tanno Yasushi Yatabe Kuniko Sunami Tomoyuki Hishida Yasunari Miyazaki Hidemi Ito Mitsuhiro Amemiya Hirohiko Totsuka Haruhiko Nakayama Tomoyuki Yokose Kazuyoshi Ishigaki Toshiteru Nagashima Yoichi Ohtaki Kazuhiro Imai Ken Takasawa Yoshihiro Minamiya Kazuma Kobayashi Kenichi Okubo Kenji Wakai Atsushi Shimizu Masayuki Yamamoto Motoki Iwasaki Koichi Matsuda Johji Inazawa Yuichi Shiraishi Hiroyoshi Nishikawa Yoshinori Murakami Michiaki Kubo Fumihiko Matsuda Yoichiro Kamatani Ryuji Hamamoto Keitaro Matsuo Takashi Kohno division of Genome Biology National Cancer Center Research InstituteTokyoJapan Department of Clinical Genomics National Cancer Center Research InstituteTokyoJapan Laboratory for Statistical Analysis Center for Integrative Medical SciencesRIKENYokohamaJapan Department of Genomic Medicine Research InstituteNational Cerebral and Cardiovascular CenterOsakaJapan Laboratory for Genotyping Development Center for Integrative Medical SciencesRIKENYokohamaJapan Center for Antibody and Vaccine therapy Research HospitalInstitute of Medical ScienceThe University of TokyoTokyoJapan Department of Medical Oncology and Cancer Center and Center for Advanced Medicine against CancerShiga University of Medical ScienceOtsuJapan division of Medical AI Research and Development National Cancer Center Research InstituteTokyoJapan Center for Genomic Medicine Graduate School of MedicineKyoto UniversityKyotoJapan Department of Medical Oncology Japanese Red Cross Medical CenterTokyoJapan Department of Thoracic Oncology National Cancer Center Hospital EastJapan Department of Thoracic Oncology National Cancer Center HospitalTokyoJapan Department of Cellular and Organ Pathology Graduate School of MedicineAkita UniversityAkitaJapan Department of Respiratory Medicine Tokyo Medical and Dental UniversityBunkyo-kuTokyoJapan division of General Thoracic Surgery Department of SurgeryShinshu University School of MedicineMatsumotoNaganoJapan Department of General Surgical Science Division of General Thoracic SurgeryGunma University Graduate School of MedicineIntegrative Center of General SurgeryGunma University HospitalGunmaJapan Department of Gastrointestinal Tract Surgery Fukushima Medical University School of MedicineFukushimaJapan StaGen Co. LtdTokyoJapan division of Thoracic Surgery National Cancer Center HospitalTokyoJapan Department of Thoracic Surgery National Cancer Center Hospital EastChibaJapan division of Translational Informatics Exploratory Oncology Research and Clinical Trial Center(EPOC

Dear editor,Lung carcinoma is responsible for the highest fatal-ity rate among cancer-related deaths globally,with lung adenocarcinoma(LADC)emerging as the prevailing sub-type.

关键词： adenocarcinoma lung Lung

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New perspectives on biology,disease progression,and therapy response of head and neck cancer gained from single cell RNA sequencing and spatial transcriptomics

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Oncology Research 2024年第1期32卷 1-17页

作者： GERWIN HELLER THORSTEN FUEREDER ALEXANDER MICHAEL GRANDITS ROTRAUD WIESER division of Oncology Department of Medicine IMedical University of ViennaVienna1090Austria Ludwig Boltzmann Institute for Hematology and Oncology Medical University of ViennaVienna1090Austria

Head and neck squamous cell carcinoma(HNSCC)is one of the most frequent cancers *** main risk factors are consumption of tobacco products and alcohol,as well as infection with human papilloma *** therapeutic options comprise surgery,radiation,chemotherapy,targeted therapy through epidermal growth factor receptor inhibition,and immunotherapy,but outcome has remained unsatisfactory due to recurrence rates of~50%and the frequent occurrence of second *** availability of the human genome sequence at the beginning of the millennium heralded the omics era,in which rapid technological progress has advanced our knowledge of the molecular biology of malignant diseases,including HNSCC,at an unprecedented ***,microarray-based methods,followed by approaches based on next-generation sequencing,were applied to study the genetics,epigenetics,and gene expression patterns of bulk *** recently,the advent of single-cell RNA sequencing(scRNAseq)and spatial transcriptomics methods has facilitated the investigation of the heterogeneity between and within different cell populations in the tumor microenvironment(e.g.,cancer cells,fibroblasts,immune cells,endothelial cells),led to the discovery of novel cell types,and advanced the discovery of cell-cell communication within *** review provides an overview of scRNAseq,spatial transcriptomics,and the associated bioinformatics methods,and summarizes how their application has promoted our understanding of the emergence,composition,progression,and therapy responsiveness of,and intercellular signaling within,HNSCC.

关键词： Head and neck squamous cell carcinoma Tumor microenvironment Immunotherapy Gene expression Omics

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Study of plasma parameters of coaxial plasma source using triple Langmuir probe and Faraday cup diagnostics

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Plasma Science and Technology 2024年第4期26卷 94-100页

作者： Sunil KANCHI Rohit SHUKLA Archana SHARMA Pulsed Power and Electromagnetics division Bhabha Atomic Research CentreVisakhapatnam 531011India Homi Bhabha National Institute Mumbai 400085India Beam Technology Development Group Bhabha Atomic Research CentreMumbai 400085India

Coaxial plasma guns are a type of plasma source that produces plasma which propagates radially and axially controlled by the shape of the ground electrode, which has attracted much interest in several applications. In this work, a 120° opening angle of CPG nozzle is used as a plasma gun configuration that operates at the energy of 150 J. The ionization of polyethylene insulator between the electrodes of the gun produces a cloud of hydrogen and carbon *** triple Langmuir probe and Faraday cup are used to measure plasma density and plasma temperature. These methods are used to measure the on-axis and off-axis plasma divergence of the coaxial plasma gun. The peak values of ion densities measured at a distance of 25 mm on-axis from the plasma gun are(1.6±0.5)×10^(19)m^(-3)and(2.8±0.6)×10^(19)m^(-3)for hydrogen and carbon plasma respectively and the peak temperature is 3.02±0.5 eV. The mean propagation velocity of plasma is calculated using the transit times of plasma at different distances from the plasma gun and is found to be 4.54±0.25 cm/μs and 1.81±0.18 cm/μs for hydrogen and carbon plasma respectively. The Debye radius is obtained from the measured experimental data that satisfies the thin sheath approximation. The shot-to-shot stability of plasma parameters facilitates the use of plasma guns in laboratory experiments. These types of plasma sources can be used in many applications like plasma opening switches, plasma devices, and as plasma sources.

关键词： coaxial plasma source triple Langmuir probe Faraday cup plasma density plasma temperature

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