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ALS-linked C9orf72 dipeptide repeats inhibit starvation-induced autophagy through modulating bCL2–bECN1 interaction

Acta Pharmaceutica Sinica b 2024年第5期14卷 2026-2038页

作者： Shiqiang Xu Qilian ma Junwen Shen Ningning Li Shan Sun Nana Wang Yang Chen Chunsheng Dong Kin Yip Tam Jochen h.m.Prehn hongfeng Wang Zheng Ying Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences Soochow UniversitySuzhou 215123China mOE Key Laboratory of Geriatric Diseases and Immunology College of Pharmaceutical SciencesSuzhou Medical College of Soochow UniversitySuzhou 215123China Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development Soochow UniversitySuzhou 215123China Dept.of Physiology&medical Physics and FUTURE-NEURO Research Centre Royal College of Surgeons in IrelandDublin D02 YN77Ireland Faculty of health Sciences University of MacaoTaipaMacao 999078China Insititutes of biology and medical Science Soochow UniversitySuzhou 215123China

Growing evidences indicate that dysfunction of autophagy contributes to the disease pathogenesis of amyotrophic lateral sclerosis(ALS)and frontotemporal dementia(FTD),two neurodegenerative disorders.The GGGGCC·GGCCCC repeat RNA expansion in chromosome 9 open reading frame 72(C9orf72)is the most genetic cause of both ALS and FTD.According to the previous studies,GGGGCC·GGCCCC repeat undergoes the unconventional repeat-associated non-ATG translation,which produces dipeptide repeat(DPR)proteins.Although there is a growing understanding that C9orf72 DPRs have a strong ability to harm neurons and induce C9orf72-linked ALS/FTD,whether these DPRs can affect autophagy remains unclear.In the present study,we find that poly-GR and poly-PR,two arginine-containing DPRs which display the most cytotoxic properties according to the previous studies,strongly inhibit starvation-induced autophagy.moreover,our data indicate that arginine-rich DPRs enhance the interaction between bCL2 and bECN1/beclin 1 by inhibiting bCL2 phosphorylation,therefore they can impair autophagic clearance of neurodegenerative disease-associated protein aggregates under starvation condition in cells.Importantly,our study not only highlights the role of C9orf72 DPR in autophagy dysfunction,but also provides novel insight that pharmacological intervention of autophagy using SW063058,a small molecule compound that can disrupt the interaction between bECN1 and bCL2,may reduce C9orf72 DPR-induced neurotoxicity.

关键词： Amyotrophic lateral sclerosis Frontotemporal dementia C9orf72 Autophagy bCL2 bECN1/beclin 1 Dipeptide repeat Neurodegeneration

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Single atom Cu-N-C catalysts for the electro-reduction of CO_(2) to CO assessed by rotating ring-disc electrode

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Journal of Energy Chemistry 2024年第1期88卷 169-182,I0004页

作者： S.Pérez-Rodríguez m.Gutiérrez-Roa C.Giménez-Rubio D.Ríos-Ruiz P.Arévalo-Cid m.V.martínez-huerta A.Zitolo m.J.Lázaro D.Sebastián Instituto de Carboquímica(CSIC) Miguel Luesma Castán 450018 ZaragozaSpain Instituto de Catálisis y Petroleoquímica(CSIC) Marie Curie 228049 MadridSpain Synchrotron SOLEIL L’Orme des MerisiersDépartementale 12891190France

The electrochemical CO_(2) reduction reaction(CO_(2)RR) to controllable chemicals is considered as a promising pathway to store intermittent renewable energy. herein, a set of catalysts based on copper-nitrogendoped carbon xerogel(Cu-N-C) are successfully developed varying the copper amount and the nature of the copper precursor, for the efficient CO_(2)RR. The electrocatalytic performance of Cu-N-C materials is assessed by a rotating ring-disc electrode(RRDE), technique still rarely explored for CO_(2)RR. For comparison, products are also characterized by online gas chromatography in a h-cell. The as-synthesized Cu-NC catalysts are found to be active and highly CO selective at low overpotentials(from -0.6 to -0.8 V vs.RhE) in 0.1 m KhCO_(3), while h_(2) from the competitive water reduction appears at larger overpotentials(-0.9 V vs. RhE). The optimum copper acetate-derived catalyst containing Cu-N_(4) moieties exhibits a CO_(2)-to-CO turnover frequency of 997 h^(-1) at -0.9 V vs. RhE with a h_(2)/CO ratio of 1.8. These results demonstrate that RRDE configuration can be used as a feasible approach for identifying electrolysis products from CO_(2)RR.

关键词： Cu-N-C Carbon xerogel Rotating ring disc electrode Carbon dioxide reduction reaction Carbon monoxide

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Global prevalence and gender inequalities in at least 60 min of self-reported moderate-to-vigorous physical activity 1 or more days per week:An analysis with 707,616 adolescents

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Journal of Sport and health Science 2024年第5期13卷 709-716页

作者： Raphael h.O.Araujo AndrúO.Werneck Clarice L.martins Luciana L.barboza Rafael m.Tassitano Nicolas Aguilar-Farias Gilmar m.Jesus Robinson Ramírez-Véelez Riki Tesler Adewale L.Oyeyemi Ellen C.m.Silva Robert G.Weaver mark S.Tremblay Javier brazo-Sayavera Grégore I.mielke Danilo R.P.Silva Graduation Program in health Sciences Londrina State University(UEL)Londrina 86057-970Brazil Center for Epidemiological Research in Nutrition and health Department of NutritionSchool of Public HealthUniversidade de Sao Paulo(USP)Sao Paulo 01246-904Brazil Department of Physical Education Federal University of ParaıbaParaıba 58051-900Brazil Research Centre of Physical Activity Health and LeisureFaculty of SportsLaboratory for Integrative and Translational Research in Population Health(ITR)University of PortoPorto 4500Portugal Postgraduate Program in Physical Education University of BrasıliaBrasılia 70910-900Brazil Department of Kinesiology and Community health University of Illinois at Urbana-ChampaignChampaignIL 61801-3841USA Department of Physical Education Sports and RecreationUniversidad de La FronteraTemuco 4680000Chile Department of health State University of Feira de SantanaFeira de Santana 44036-900Brazil Navarrabiomed Hospital Universitario de Navarra(HUN)Navarra Institute for Health Research(IdiSNA)Universidad Publica de Navarra(UPNA)Pamplona 31006Spain Facultad de Ciencias de la Educacion Unidad Central del Valle del Cauca(UCEVA)TuluaValle del Cauca 763022Colombia health management Department Faculty of Heath sciencesAriel UniversityAriel 40700Israel College of health Solutions Arizona State UniversityPhoenixAZ 85004USA Arnold School of Public health University of South CarolinaColumbiaSC 29208USA healthy Active Living and Obesity Research Group Children’s Hospital of Eastern Ontario Research InstituteOttawaON K1H 8L1Canada Department of Pediatrics University of OttawaOttawaON K1H 8L1Canada Department of health Sciences Carleton UniversityOttawaON K1S 5B6Canada Department of Sports and Computer Science Universidad Pablo de Olavide(UPO)Seville 41013Spain Centro Universitario Regional Noreste Universidad de la RepublicaRivera 40000Uruguay School of Public health The University of QueenslandBrisbaneQLD 4006Australia Department of Physical Education

background:Guidelines recommend that adolescents should accumulate an average of 60 min per day of moderate-to-vigorous physical activity(mVPA).however,using only this cut-off could hide important information.For instance,from a population-level point of view,increasing physical activity for those with no or low physical activity could provide more health benefits than increasing physical activity for those with intermediate levels.Also,including a more sensitive cut-point of≥1 days per week could be an additional strategy for identifying those with low access/opportunities for physical activity practice.Thus,the current study aims to estimate the prevalence of≥60 min of mVPA≥1 days per week among adolescents globally,and to describe any relevant gender inequalities.methods:We used representative datasets from 146 countries/territories collected between 2003 and 2019.mVPA was self-reported.Participants were grouped into younger(≤14 years old)and older(>14 years old)adolescents.Crude Poisson regression models were used to identify the relative differences in≥60 min of mVPA≥1 days per week between boys and girls,and random-effects meta-analysis models were used to identify the pooled estimates.Analyses were stratified by country and region.Results:Approximately 80%of both younger and older adolescents reported≥60 min of mVPA≥1 days per week.This prevalence was≥94%in Europe and Central Asia and North America,while the estimates for the other regions werehe prevalence of≥60 min of mVPA≥1 days per week was higher among boys than girls,with the largest differences occurring among the oldest adolescents(Prevalence ratio_(≤14y)=1.04(95%confidence interval(95%CI)):1.03-1.04)vs.Prevalence ratio_(>14y)=1.09(95%CI:1.08-1.10)).Conclusion:Approximately 8 out of 10 adolescents reported accumulating≥60 min of mVPA≥1 days per week,with notable differences between regions.Gender differences were observed in several countries,especially among the oldest adolescents.Priorities for physical activity promotion among adolescents

关键词： Global School-based Student health Survey health behaviour Among School-aged Children survey Inequality Surveillance Youth

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Development of an active-site titrant for SARS-CoV-2 main protease as an indispensable tool for evaluating enzyme kinetics

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Acta Pharmaceutica Sinica b 2024年第5期14卷 2349-2357页

作者： Rabea Voget Julian breidenbach Tobias Claff Alexandra hingst Katharina Sylvester Christian Steinebach Lan Phuong Vu Renato h.Weiße Ulrike bartz Norbert Sträter Christa E.müller michael Gütschow Pharmaceutical Institute Pharmaceutical&Medicinal ChemistryUniversity of BonnBonn 53121Germany Institute of bioanalytical Chemistry Center for Biotechnology and BiomedicineLeipzig UniversityLeipzig 04103Germany Department of Natural Sciences University of Applied Sciences Bonn-Rhein-SiegRheinbach 53359Germany

A titrant for the SARS-CoV-2 main protease(m^(pro))was developed that enables,for the first time,the exact determination of the concentration of the enzymatically active m^(pro) by active-site titration.The covalent binding mode of the tetrapeptidic titrant was elucidated by the determination of the crystal structure of the enzyme–titrant complex.Four fluorogenic substrates of m^(pro),including a prototypical,internally quenched Dabcyl-EDANS peptide,were compared in terms of solubility under typical assay conditions.by exploiting the new titrant,key kinetic parameters for the m^(pro)-catalyzed cleavage of these substrates were determined.

关键词： COVID-19 SARS-CoV-2 main protease Peptide nitriles Fluorogenic substrates Active-site titration X-ray crystallography Inner filter effect

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由超拍电子伏特加速器产生的超高能伽马射线气泡

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Science bulletin 2024年第4期69卷 449-457页

作者： LhAASO Collaboration Zhen Cao Chuandong Gao Cong Li Ruo-Yu Liu Ruizhi Yang 不详 Key Laboratory of Particle Astrophyics&Experimental Physics Division&Computing Center Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China University of Chinese Academy of Sciences Beijing 100049China TIANFU Cosmic Ray Research Center ChengduChina Institute of Frontier and Interdisciplinary Science Shandong UniversityQingdao 266237China School of Astronomy and Space Science Nanjing UniversityNanjing 210023China University of Science and Technology of China Hefei 230026China

We report the detection of aγ-ray bubble spanning at least 100deg2 in ultra-high energy(UhE)up to a few PeV in the direction of the star-forming region Cygnus X,implying the presence super PeVatron(s)accelerating protons to at least 10 PeV.A log-parabola form with the photon indexΓ(E)=(2.71±0.02)+(0.11±0.02)×log10(E/10 TeV)is found fitting the gamma-ray energy spectrum of the bubble well.UhE sources,“hot spots”correlated with very massive molecular clouds,and a quasi-spherical amorphousγ-ray emitter with a sharp central brightening are observed in the bubble.In the core of~0.5°,spatially associating with a region containing massive Ob association(Cygnus Ob2)and a microquasar(Cygnus X-3),as well as previously reported multi-TeV sources,an enhanced concentration of UhEγ-rays is observed with 2 photons at energies above 1 PeV.The general feature of the bubble,the morphology,and the energy spectrum,are reasonably reproduced by the assumption of a particle accelerator in the core,continuously injecting protons into the ambient medium.

关键词： Cosmic rays γ-rays Interstellar medium Star cluster

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Philippine retinoblastoma initiative multi-eye center study 2010-2020

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International Journal of Ophthalmology(English edition) 2024年第1期17卷 144-156页

作者： Roland Joseph D.Tan Gary John V.mercado Patricia E.Cabrera Paulita Pamela P.Astudillo Rolando Enrique D.Domingo Josept mari S.Poblete Charmaine Grace m.Cabebe Adriel Vincent R.Te melissa Anne S.Gonzales Jocelyn G.Sy beltran Alexis A.Aclan Jayson T.So Fatima G.Regala Kimberley Amanda K.Comia Josemaria m.Castro mara Augustine S.Galang Aldous Dominic C.Cabanlas benedicto Juan E.Aguilar Gabrielle S.Evangelista Jo michael maniwan Andrei P.martin Calvin Y.martinez John Alfred h.Lim Rena Ivy bascuna Rachel m.Ng Kevin b.Agsaoay Kris Zanna A.Acluba-Arao Ellaine Rose V.Apostol beatriz m.Prieto Department of Ophthalmology and Visual Sciences Philippine General HospitalManila 1000Philippines Department of Ophthalmology Baguio General Hospital and Medical CenterBaguio City 2600Philippines Department of Ophthalmology Manila Doctors HospitalManila 1000Philippines Department of Ophthalmology Rizal Medical CenterPasig City 1600Philippines Department of Ophthalmology Jose B.Lingad Memorial Regional HospitalPampanga 2000Philippines Department of Ophthalmology Southern Philippines Medical CenterDavao City 8000Philippines Department of Ophthalmology East Avenue Medical CenterQuezon City 1100Philippines Department of Ophthalmology Northern Mindanao Medical CenterCagayan de Oro City 9000Philippines Department of Ophthalmology Cebu Velez General HospitalCebu City 6000Philippines Legazpi Eye Center Legazpi City 4500Philippines Department of Ophthalmology Cagayan Valley Medical CenterTuguegarao City 3500Philippines

AIm:To provide a comprehensive and more representative national data on the disease,especially on treatment options and outcomes,and to determine access of retinoblastoma patients from Luzon,Visayas and mindanao to eye care,and determine if access is associated with delay in consultation,staging and outcomes.mEThODS:Cohort study of retinoblastoma patients seen in eleven institutions located in the three major areas of the Philippines namely Luzon,Vizayas and mindanao from 2010-2020.RESULTS:Totally 636 patients,involving 821 eyes,were included.majority(57%)were from Luzon and were seen in institutions in Luzon(72%).Annually,58±10 new cases were seen with 71%having unilateral disease.median delay of consultation remained long at 9(3,17)mo,longest in patients with unilateral disease(Phose from the Visayas(Pbased on the International Retinoblastoma Staging System,only 35%of patients had Stage 1 while 47%already had extraocular disease.Enucleation was the most common treatment received by 484 patients while intravenous chemotherapy was received by 469.There were 250(39%)patients alive,195(31%)dead,85(13%)abandoned,17(3%)refused and 89(14%)with no data.CONCLUSION:This study presents the largest cohort of retinoblastoma patients in the Philippines in terms of patients’and participating institutions’number and geographical location and type of institution(private and public).It also presents more comprehensive data on the treatments used and outcomes(survival,globe salvage,and vision retention rates).Delay in consultation was still long among patients leading to advanced disease stage and lower survival rate.Despite increasing capacity to diagnose and manage retinoblastoma in the country,the delay of consultation remains long primarily due to accessibility issues to eye care institutions especially in the Visayas and financial concerns.The delay was still significant that overall survival rate remain low.

关键词： retinoblastoma Philippines clinical profile

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Isochrone Fitting of Galactic Globular Clusters—Ⅵ. high-latitude Clusters NGC 5024 (m53), NGC 5053, NGC 5272 (m3), NGC 5466, and NGC7099 (m30)

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Research in Astronomy and Astrophysics 2024年第6期 172-192页

作者： G.A.Gontcharov S.S.Savchenko A.A.marchuk C.J.bonatto O.S.Ryutina m.Yu.Khovritchev V.b.Il'in A.V.mosenkov D.m.Poliakov A.A.Smirnov Central (Pulkovo) Astronomical Observatory Russian Academy of Sciences Saint Petersburg State University Special Astrophysical Observatory Russian Academy of Sciences Departamento de Astronomia Instituto de Física UFRGS Av.Bento Gon?alves Saint Petersburg University of Aerospace Instrumentation Department of Physics and Astronomy Brigham Young University

We fit various color–magnitude diagrams(CmDs) of the high-latitude Galactic globular clusters NGC 5024(m53),NGC 5053, NGC 5272(m3), NGC 5466, and NGC 7099(m30) by isochrones from the Dartmouth Stellar Evolution Database and bag of Stellar Tracks and Isochrones for α–enrichment [α/Fe] = +0.4. For the CmDs, we use data sets from hubble Space Telescope, Gaia, and other sources utilizing, at least, 25 photometric filters for each cluster. We obtain the following characteristics with their statistical uncertainties for NGC 5024, NGC 5053,NGC 5272, NGC 5466, and NGC 7099, respectively: metallicities [Fe/h] =-1.93 ± 0.02,-2.08 ± 0.03,-1.60 ± 0.02,-1.95 ± 0.02, and-2.07 ± 0.04 dex with their systematic uncertainty 0.1 dex; ages 13.00 ± 0.11,12.70 ± 0.11, 11.63 ± 0.07, 12.15 ± 0.11, and 12.80 ± 0.17 Gyr with their systematic uncertainty 0.8 Gyr;distances(systematic uncertainty added) 18.22 ± 0.06 ± 0.60, 16.99 ± 0.06 ± 0.56, 10.08 ± 0.04 ± 0.33, 15.59 ±0.03 ± 0.51, and 8.29 ± 0.03 ± 0.27 kpc; reddenings E(b-V) = 0.023 ± 0.004, 0.017 ± 0.004, 0.023 ± 0.004,0.023 ± 0.003, and 0.045 ± 0.002 mag with their systematic uncertainty 0.01 mag; extinctions AV= 0.08 ± 0.01,0.06 ± 0.01, 0.08 ± 0.01, 0.08 ± 0.01, and 0.16 ± 0.01 mag with their systematic uncertainty 0.03 mag, which suggest the total Galactic extinction AV= 0.08 across the whole Galactic dust to extragalactic objects at the North Galactic Pole. The horizontal branch morphology difference of these clusters is explained by their different metallicity, age, mass-loss efficiency, and loss of low-mass members in the evolution of the core-collapse cluster NGC 7099 and loose clusters NGC 5053 and NGC 5466.

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Universal basis underlying temperature, pressure and size induced dynamical evolution in metallic glass-forming liquids

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Chinese Physics b 2024年第1期33卷 134-142页

作者：张华平范蓓蓓吴佳琦李茂枝 Department of Physics Beijing Key Laboratory of Opto-electronic Functional Materials&Micro-nano DevicesRenmin University of ChinaBeijing 100872China Songshan Lake materials Laboratory Dongguan 523808China Key Laboratory of Quantum State Construction and manipulation Renmin University of ChinaBeijing 100872China

The dramatic temperature-dependence of liquids dynamics has attracted considerable scientific interests and efforts in the past decades, but the physics of which remains elusive. In addition to temperature, some other parameters, such as pressure, loading and size, can also tune the liquid dynamics and induce glass transition, which makes the situation more complicated. here, we performed molecular dynamics simulations for Ni_(50)Zr_(50) bulk liquid and nanodroplet to study the dynamics evolution in the complex multivariate phase space, especially along the isotherm with the change of pressure or droplet size. It is found that the short-time Debye–Waller factor universally determines the long-time relaxation dynamics no matter how the temperature, pressure or size changes. The basic correlation even holds at the local atomic scale. This finding provides general understanding of the microscopic mechanism of dynamic arrest and dynamic heterogeneity.

关键词： metallic glass-forming liquids structure relaxation dynamical heterogeneity Debye–Waller factor

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Interaction of photons with silver and indium nuclei at energies up to 20 meV

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Chinese Physics C 2024年第2期48卷 135-140页

作者： J.h.Khushvaktov m.A.Demichev D.L.Demin S.A.Evseev m.I.Gostkin V.V.Kobets F.A.Rasu-lova S.V.Rozov E.T.Ruziev A.A.Solnyshkin T.N.Tran E.A.Yakushev b.S.Yuldashev Joint Institute for Nuclear Research(JINR) DubnaRussia Institute of Nuclear Physics of the Academy of Sciences of the Republic of Uzbekistan(INP ASRU) TashkentUzbekistan Institute of Physics of the Vietnam Academy of Science and Technology(IP VAST) HanoiVietnam

The yields of photonuclear reactions in the 107Ag,113In,and 115In nuclei were measured.monte Carlo simulations were performed using the Geant4 code,and the results were compared with the experimental values.The isomeric ratios of the yields in the reactions 107Ag(γ,n)106m,gAg and 113In(γ,m)112m,gIn were determined,and the cross sections for the reactions 107Ag(γ,n)106gAg and 107Ag(γ,2n)105Ag at an energy of 20 meV were calculated based on the experimental data.

关键词： 107Ag(γ,n)10mgAg and I13In(γ,n)12m-2In reactions cross section yield isomeric ratio simula-tion Geant4 TALYS

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Well-Posedness of Stochastic Continuity Equations on Riemannian manifolds

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Chinese Annals of mathematics,Series b 2024年第1期45卷 81-122页

作者： Luca GALImbERTI Kenneth h.KARLSEN Department of mathematical Sciences NTNU Norwegian University of Science and TechnologyN-7491 TrondheimNorway Department of mathematics University of OsloP.O.Box 1053BlindernN-0316 OsloNorway

The authors analyze continuity equations with Stratonovich stochasticity,■ρ+divh[ρo(u(t,x)+∑_(i=1)^(N)a_(i)(x)w_(i)(t))]=0defined on a smooth closed Riemannian manifold m with metric h.The velocity field u is perturbed by Gaussian noise terms Wi(t),:WN(t)driven by smooth spatially dependent vector fields a1(x),...,aN(x)on m.The velocity u belongs to L_(t)^(1)W_(x)^(1,2)with divh u bounded in Lf,for p>d+2,where d is the dimension of m(they do not assume div_(h) u∈L_(t,x)^(∞)).For carefully chosen noise vector fields ai(and the number N of them),they show that the initial-value problem is well-posed in the class of weak L^(2) solutions,although the problem can be ill-posed in the deterministic case because of concentration effects.The proof of this“regularization by noise”result is based on a L^(2) estimate,which is obtained by a duality method,and a weak compactness argument.

关键词： Stochastic continuity equation Riemannian manifold hyperbolic equa-tion Non-smooth velocity field Weak solution Existence Uniqueness

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