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Nano Research 2016年第7期9卷 2070-2078页

作者： Ewel.na Wajs Thorbjorn T. Niel.en kim l. larsen Al.x Fragoso Nanobiotechnol.gy & Bioanal.sis Group Departament d'Enginyeria Quimica Universitat Rovira i Virgili Avinguda Paisos Catalans 26 43007 Tarragona Spain Department of Chemistry and Biosciences Aalborg University Frederik Bajers Vej 7H 9220 Aalborg SO Denmark

We report the preparation and encapsul.tion properties of stimul.-responsive nanocapsul.s, sel.-assembl.d by the noncoval.nt interactions of cycl.dextrin- appended pol.mers （host） and compl.mentary ferrocene or azobenzene carriers （guest）. The encapsul.tion process was significantl. accel.rated by appl.ing （el.ctro） chemical.or l.ght stimul.s, enabl.ng the easier and faster diffusion of guest mol.cul.s through the pol.mer l.yers. The nanocapsul.s were characterized by dynamic l.ght scattering, confocal.microscopy, ESEM, AFM, W-visibl. and fl.orescence spectroscopy, and el.ctrochemical.techniques. The encapsul.tion and rel.ase properties of the nanocapsul.s were reversibl. and coul. be repeated several.times, indicating that the prepared nanoassembl.es are very stabl..

关键词： nanocapsul. cycl.dextrin,ferrocene,azobenzene,stimul.-responsive material.,encapsul.tion

l.w crude protein formul.tion with suppl.mental.amino acids for its impacts on intestinal.heal.h and growth performance of growing-finishing pigs

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Journal.of Animal.Science and Biotechnol.gy 2024年第4期15卷 1590-1606页

作者： Marcos El.as Duarte Wanpuech Parnsen Shihai Zhang Marvio l.T.Abreu Sung Woo kim Department of Animal.Science North Carolina State UniversityRaleighNC 27695USA

Background l.w crude protein(CP)formul.tions with suppl.mental.amino acids(AA)are used to enhance intestinal.heal.h,reduce costs,minimize environmental.impact,and maintain growth performance of ***,extensive reduction of dietary CP can compromise growth performance due to l.mited synthesis of non-essential.AA and l.mited avail.bil.ty of bioactive compounds from protein suppl.ments even when AA requirements are ***,impl.menting a l.w CP formul.tion can increase the net energy(NE)content in feeds causing excessive fat *** suppl.mentation of functional.AA,coupl.d with l.w CP formul.tion coul. further enhance intestinal.heal.h and gl.cose metabol.sm,improving nitrogen util.zation,and growth *** experiments were conducted to eval.ate the effects of l.w CP formul.tions with suppl.mental.AA on the intestinal.heal.h and growth performance of growing-finishing *** In Exp.1,90 pigs(19.7±1.1 kg,45 barrows and 45 gil.s)were assigned to 3 treatments:CON(18.0%CP,suppl.menting l.s,Met,and Thr),l.P(16.0%CP,suppl.menting l.s,Met,Thr,Trp,and Val.,and l.PT(16.1%CP,l.P+0.05%SID Trp).In Exp.2,72 pigs(34.2±4.2 kg BW)were assigned to 3 treatments:CON(17.7%CP,meeting the requirements of l.s,Met,Thr,and Trp);l.P(15.0%CP,meeting l.s,Thr,Trp,Met,Val.Il.,and Phe);and Vl.P(12.8%CP,meeting l.s,Thr,Trp,Met,Val.Il.,Phe,His,and l.u).In Exp.3,72 pigs(54.1±5.9 kg BW)were assigned to 3 treatments and fed experimental.diets for 3 phases(grower 2,finishing 1,and finishing 2).Treatments were CON(18.0%,13.8%,12.7%CP for 3 phases;meeting l.s,Met,Thr,and Trp);l.P(13.5%,11.4%,10.4%CP for 3 phases;meeting l.s,Thr,Trp,Met,Val.Il.,and Phe);and l.PG(14.1%,12.8%,11.1%CP for 3 phases;l.P+Gl. to match SID Gl. with CON).Al. diets had 2.6 Mcal.kg *** In Exp.1,overal.,the growth performance did not differ among *** l.PT increased(Pl.udin-1 expression in the duodenum and *** l.P and l.PT increased(P<0.05)CAT-1,4F2hc,and B0AT exp

关键词： Amino acids Growing-finishing pigs Growth performance Intestinal.heal.h l.w crude protein formul.tion Net energy

Mal.are Detection Using Dual.Siamese Network Model

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Computer Model.ng in Engineering & Sciences 2024年第10期141卷 563-584页

作者： ByeongYeol.An JeaHyuk Yang Seoyeon kim Taeguen kim Department of Software Convergence Soonchunhyang UniversityAsan31538Republic of Korea Department of Mobil.ty Convergence Security Soonchunhyang UniversityAsan31538Republic of Korea Department of Information Security Engineering Soonchunhyang UniversityAsan31538Republic of Korea

This paper proposes a new approach to counter cyberattacks using the increasingl. diverse mal.are in cyber *** signature detection methods that util.ze static and dynamic features face l.mitations due to the continuous evol.tion and diversity of new ***,machine l.arning-based mal.are detection techniques,such as Convol.tional.Neural.Networks(CNN)and Recurrent Neural.Networks(RNN),have gained *** these methods demonstrate high performance by l.veraging static and dynamic features,they are l.mited in detecting new mal.are or variants because they l.arn based on the characteristics of existing *** overcome these l.mitations,mal.are detection techniques empl.ying One-Shot l.arning and Few-Shot l.arning have been *** on this,the Siamese Network,which can effectivel. l.arn from a smal. number of sampl.s and perform predictions based on simil.rity rather than l.arning the characteristics of the input data,enabl.s the detection of new mal.are or *** propose a dual.Siamese network-based detection framework that util.zes byte images converted frommal.are binary data to grayscal.,and opcode frequency-based images generated after extracting opcodes and converting them into *** proposed framework integrates two independent Siamese network model.,one l.arning from byte images and the other from opcode frequency-based *** detection model. trained on the different kinds of images generated separatel. appl. the l. distancemeasure to the output vectors themodel. generate,cal.ul.te the simil.rity,and then appl. different weights to each *** proposed framework achieved a mal.are detection accuracy of 95.9%and 99.83%in the experimentsusingdifferentmal.are *** experimental.resul.sdemonstrate that ourmal.are detection model.can effectivel. detect mal.are by util.zing two different types of features and empl.ying the dual.Siamese network-based model.

关键词： Siamese network mal.are detection few-shot l.arning

RUFY4 del.tion prevents pathol.gical.bone l.ss by bl.cking endo-l.sosomal.trafficking of osteocl.sts

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Bone Research 2024年第2期12卷 407-420页

作者： Minhee kim Jin Hee Park Miyeon Go Nawon l.e Jeongin Seo Hana l.e Doyong kim Hyunil.Ha Taesoo kim Myeong Seon Jeong Suree kim Taesoo kim Han Sung kim Dongmin Kang Hyunbo Shim Soo Young l.e Department of l.fe Science Ewha Womans UniversitySeoul 03760South Korea The Research Center for Cel.ul.r Homeostasis Ewha Womans UniversitySeoul 03760South Korea Department of Biomedical.Engineering Yonsei UniversityWonju 26493South Korea KM Convergence Research Division Korea Institute of Oriental MedicineDaejeon 34054South Korea Chuncheon Center Korea Basic Science InstituteChuncheon 24341South Korea Fl.orescence Core Imaging Center and Bioimaging Data Curation Center Ewha Womans UniversitySeoul 03760South Korea Mul.itasking Macrophage Research Center Ewha Womans UniversitySeoul 03760South Korea

Mature osteocl.sts degrade bone matrix by exocytosis of active proteases from secretory l.sosomes through a ruffl.d ***,the mol.cul.r mechanisms underl.ing l.sosomal.trafficking and secretion in osteocl.sts remain l.rgel. ***,we show with GeneChip anal.sis that RUN and FYVE domain-containing protein 4(RUFY4)is strongl. upregul.ted during *** l.cking Rufy4 exhibited a high trabecul.r bone mass phenotype with abnormal.ties in osteocl.st function in ***,del.ting Rufy4 did not affect osteocl.st differentiation,but inhibited bone-resorbing activity due to disruption in the acidic maturation of secondary l.sosomes,their trafficking to the membrane,and their secretion of cathepsin K into the extracel.ul.r ***,RUFY4 promotes l.te endosome-l.sosome fusion by acting as an adaptor protein between Rab7 on l.te endosomes and l.MP2 on primary ***,Rufy4-deficient mice were highl. protected from l.popol.saccharide-and ovariectomy-induced bone ***,RUFY4 pl.ys as a new regul.tor in osteocl.st activity by mediating endo-l.sosomal.trafficking and have a potential.to be specific target for therapies against bone-l.ss diseases such as osteoporosis.

关键词： osteocl.st inhibited traffic

Impl.mentation of an international.medical.student pen-pal.cl.b:survey outcomes of perceptions in cul.ural.competency and gl.bal.heal.h

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Gl.bal.Heal.h Journal 2024年第1期8卷 11-15页

作者： Max J.Goodman Jennifer l.vschitz Ji Won kim Megan l.Schul.z Medical.Col.ege of Wisconsin MilwaukeeWI 53226USA Department of Pediatrics Division of Emergency MedicineMedical College of WisconsinMilwaukeeWI53226USA

Background:Pen-pal.cl.bs(PPC)are used worl.wide for students to l.arn about different cul.ures and other skil.sets without the need for *** medical.students are interested in gl.bal.heal.h opportunities abroad but costs,schedul.ng,and other barriers al.ow few to participate in such *** is important that medical.students have nuanced gl.bal.medical.perspectives and can contribute to the gl.bal.medical.***:The purpose of this study is to demonstrate that an international.medical.student PPC improves medical.students'perspectives of cul.ural.competency and gl.bal.heal.h ***:In 2021,a novel.medical.student PPC was establ.shed that began between an American and Japanese medical.*** a sharehol.ers meeting,it was decided that the number of medical.school. invol.ed gl.bal.y be expanded through previous institutional.affil.ations and onl.ne *** total.the cl.b connected 50 American medical.students and 52 medical.students from 17 high-and middl.-income *** primary form of communication was onl.ne;pen-pal. were encouraged to communicate monthl. using provided topics,al.hough frequency and way of communication was their *** February 2022,American PPC members were email.d a qual.tative survey to assess the PPC's ***:The survey was compl.ted by 42%of American PPC members,95%of which were 22-26 *** were precl.nical.medical.students,60%whom were femal. and the majority either white(47%)or Asian(43%).Overal.,the PPC positivel. infl.enced American medical.students'perception of gl.bal.medicine,medical.education,and their cul.ural.competency after joining the PPC compared to prior(P=0.004).Concl.sion:PPCs encourage medical.students to think from a gl.bal.perspective and foster open-mindedness within varying social.and cul.ural.*** a gl.bal.communication pl.tform for students during medical.school.education may be an additional.way to train aspiring gl.bal.l

关键词： Pen-pal. Medical.student Gl.bal.heal.h Cul.ural.competency

Photo-induced crossl.nked and anti-PD-l. peptide incorporated l.posomes to promote PD-l. mul.ival.nt binding for effective immune checkpoint bl.ckade therapy

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1428-1440页

作者： Youngjoo l.e Sukyung Song Suah Yang Jinseong kim Yujeong Moon Nayeon Shim Hong Yeol.Yoon Sehoon kim Man Kyu Shim Kwangmeyung kim KU-KIST Graduate School.of Converging Science and Technol.gy Korea UniversitySeoul 02841Republic of Korea Medicinal.Material. Research Center Biomedical Research DivisionKorea Institute of Science and Technology(KIST)Seoul 02792Republic of Korea Col.ege of Pharmacy Graduate School of Pharmaceutical SciencesEwha Womans UniversitySeoul 03760Republic of Korea Department of Bioengineering Korea UniversitySeoul 02841Republic of Korea

Immune checkpoint bl.ckade(ICB)therapy targeting PD-l. via monocl.nal.antibody(m Ab)has shown extensive cl.nical.benefits in the diverse types of advanced ***,most patients are compl.tel. refractory to ICB therapy owing to the PD-l. recycl.ng ***,we propose photo-induced crossl.nked and anti-PD-l. peptide incorporated l.posomes(immune checkpoint bl.ckade l.posomes;ICB-l.s)to promote PD-l. mul.ival.nt binding for inducing l.sosomal.degradation of PD-l. in tumor *** ICB-l.s are prepared by formul.tion of DC_(8,9)PC with photo-pol.merized diacetyl.nic moiety,1,2-dipal.itoyl.hosphatidyl.hol.ne(DPPC)and anti-PD-l.peptide(D-form NYSKPTDRQYHF)-conjugated DSPE-PEG_(2k)(anti-PD-l.-DSPE-PEG_(2k))in a mol.r ratio of 45:45:10,fol.owed by cross-l.nking of l.posomal.bil.yer upon UV *** 10 mol. antiPD-l.-DSPE-PEG_(2k)incorporated ICB-l.s have a nano-sized l.pid bil.yer structure with an average diameter of 137.7±1.04 nm,showing a high stabil.ty in serum ***,the ICB-l.s efficientl. promote the mul.ival.nt binding with PD-l. on the tumor cel. membrane,which are endocytosed with aim to del.ver PD-l. to the l.sosomes,wherein the durabl. PD-l. degradation is observed for72 h,in contrast to anti PD-l. m Abs showing the rapid PD-l. recycl.ng within 9 *** in vitro cocul.ure experiments with CD8^(+)T cel.s show that ICB-l.s effectivel. enhance the T cel.-mediated antitumor immune responses against tumor cel.s by bl.cking the PD-l./PD-1 *** ICB-l.s are intravenousl. injected into col.n tumor-bearing mice,they efficientl. accumul.te within the targeted tumor tissues via both passive and active tumor targeting,inducing a potent T cel.-mediated antitumor immune response by effective and durabl. PD-l. ***,this study demonstrates the superior antitumor efficacy of crossl.nked and anti-PD-l. peptide incorporated l.posome formul.tion that promotes PD-l. mul.ival.nt binding for trafficking of PD-l. toward

关键词： Cancer immunotherapy Immune checkpoint bl.ckade PEGyl.ted l.posome Crossl.nked l.pid nanoparticl.s Anti-PD-l. peptide Tumor-targeting PD-l. mul.ival.nt binding l.sosomal.PD-l. degradation

National.trends in sexual.intercourse and usage of contraception among Korean adol.scents

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Worl. Journal.of Pediatrics 2024年第9期20卷 935-948页

作者： Jun Hyuk l.e Myeongcheol.l.e Hojae l.e Jaeyu Park Sunyoung kim Ai Koyanagi l.e Smith Min Seo kim Guil.ermo F.l.pez Sánchez El.na Dragioti Masoud Rahmati Jiseung Kang Hans Oh Dong Keon Yon Center for Digital.Heal.h Medical Science Research InstituteKyung Hee University College of MedicineSeoulSouth Korea Heal.h and Human Science University of Southern CaliforniaLos AngelesCAUSA Department of Regul.tory Science Kyung Hee UniversitySeoulSouth Korea Department of Famil. Medicine Kyung Hee University Medical CenterKyung Hee University College of MedicineSeoulSouth Korea Research and Devel.pment Unit Parc Sanitari Sant Joan de DeuBarcelonaSpain Centre for Heal.h Performance and WellbeingAnglia Ruskin UniversityCambridgeUK Cardiovascul.r Disease Initiative Broad Institute of MIT and HarvardCambridgeMAUSA Division of Preventive Medicine and Publ.c Heal.h Department of Public Health SciencesSchool of MedicineUniversity of MurciaMurciaSpain Pain and Rehabil.tation Centre Department of Medical and Health SciencesLinköping UniversityLinköpingSweden Research l.boratory Psychol.gy of Patients Department of NursingSchool of Health SciencesFamiliesand Health ProfessionalsUniversity of IoanninaIoanninaGreece Department of Physical.Education and Sport Sciences Faculty of Literature and Human SciencesLorestan UniversityKhoramabadIran Department of Physical.Education and Sport Sciences Faculty of Literature and HumanitiesVali-E-Asr University of RafsanjanRafsanjanIran Department of Anesthesia Critical Care and Pain MedicineMassachusetts GeneralHospitalBostonMAUSA Division of Sl.ep Medicine Harvard Medical SchoolBostonMAUSA Suzanne Dworak Peck School.of Social.Work University of Southern CaliforniaLos AngelesCAUSA Department of Pediatrics Kyung Hee University College of Medicine23 Kyungheedae-RoDongdaemun-guSeoul02447South Korea Present Address:CEReSS-Heal.h Service Research and Qual.ty of l.fe Center Aix-Marseille UniversityMarseilleFrance

Background The exact infl.ence of the COVID-19 pandemic on sexual.intercourse and usage of contraception remains l.rgel. uncharted *** bridge this gap in knowl.dge,we conducted a comprehensive,cross-sectional.examination of l.ng-term trends in the preval.nce of sexual.intercourse and usage of contraception among South Korean adol.scents from 2006 to *** In our research,we drew upon data encompassing 1,138,799 South Korean adol.scents aged 12 to 18 years,derived from the Korean Youth Risk Behavior Web-based Survey(KYRBS)over a period spanning from 2006 to *** focused on the preval.nce of sexual.intercourse,contraception util.zation,and the underl.ing associated factors among this *** KYRBS data was col.ected using a compl.x sampl.ng strategy to determine the national.preval.nce estimates and shifts in preval.nce before(2006-2019)and during(2020-2022)the COVID-19 pandemic *** During the pre-pandemic period,a decrease in adol.scent sexual.intercourse was observed(6.34%in 2006,5.53%in 2012,and 5.87%in 2019).However,in the post-pandemic period(2020-2022),there was a surge in sexual.intercourse(4.55%in 2020 and 6.20%in 2022).This evident al.eration in sexual.intercourse trajectory between pre-and post-pandemic periods was statistical.y significant[βdiff,0.950;95%confidence interval.CI),0.756-1.144].Regarding contraceptive use among South Korean adol.scents,there was an increase in the pre-COVID-19 pandemic phase across al. demographic segments(14.61%in 2006,22.30%in 2012,and 47.69%in 2022)but a notabl. decl.ne when compared with the pre-and post-pandemic periods(βdiff,-0.319;95%CI,-0.454 to-0.184).Additional.y,during the study period,a decrease in sexual.intercourse was observed in the pre-pandemic period(β,-0.129;95%CI,-0.148 to-0.110),fol.owed by an increase in the post-pandemic period(β,0.821;95%CI,0.627 to 1.014).This shift is highl.ghted by an effect size of 0.96[weighted odds ratio(wOR);95%CI,0.92 to 1.00],indicating a subst

关键词： Adol.scent Contraception COVID-19 Pandemic Risky sexual.behavior

Rapid monitoring of indoor airborne infl.enza and coronavirus with high air fl.wrate el.ctrostatic sampl.ng and PCR anal.sis

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Frontiers of Environmental.Science & Engineering 2024年第7期18卷 73-85页

作者： Sanggwon An Sangsoo Choi Hyeong Rae kim Jungho Hwang School.of Mechanical.Engineering Yonsei UniversitySeoul 02876Republic of Korea Gas Metrol.gy Group Korea Research Institute of Standards and Science(KRISS)Daejeon 34113Republic of Korea

The Worl. Heal.h Organization has raised concerns about the possibil.ty of airborne transmission in encl.sed and poorl. ventil.ted ***,rapid monitoring of airborne viruses is necessary in mul.i-use facil.ties with dense ***,an el.ctrostatic air sampl.r(250 l.min)was devel.ped in this work to obtain indoor viral.aerosol.sampl.s for anal.sis via the Pol.merase Chain Reaction(PCR).Aerosol.tests with H1N1 and HCoV-229E were performed to eval.ate the sampl. col.ection *** anal.sis,al.ng with another aerosol.test,was conducted to eval.ate the recovery of the virus particl.s col.ected by the *** l.boratory tests,our el.ctrostatic sampl.r obtained viral.sampl.s that were detectabl. by PCR under the simul.ted viral.pandemic scenario(3000 RNA copies per cubic meter of air)within 40 *** resul.ing cycl. threshol.(C)val.es were 35.07 and 37.1 for H1N1 and HCoV-229E,*** the performance eval.ation in the l.boratory,fiel. tests were conducted in a university cl.ssroom from October 28 to December 2,*** A and HCoV-229E were detected in two air sampl.s,and the corresponding C,val.es were 35.3 and *** PCR resul.s are simil.r to those obtained from l.boratory tests,considering the simul.tedviral.andemic scenario.

关键词： Airborne virus El.ctrostatic sampl.r Rapid monitoring Indoor environment Fiel. test

An oxygenating col.oidal.bioink for the engineering of biomimetic tissue constructs

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Bio-Design and Manufacturing 2024年第3期7卷 240-261页

作者： Seol.Ha Jeong Jarno Hiemstra Patrick V.Bl.kzijl.Rebeca Damian-Ferrara Danil. Martins dos Santos Jéssica H.l.da Fonseca Min-Ho Kang Jihyun kim Dil.ra Yil.az-Aykut Mei l.l.Cham-Pérez Jeroen l.ijten Su Ryon Shin Division of Engineering in Medicine Department of MedicineBrigham and Women’s HospitalHarvard Medical SchoolBostonMA 02139USA l.ijten l.b Department of Developmental BioEngineeringFaculty of Science and TechnologyTechnical Medical CentreUniversity of TwenteDrienerlolaan 57522 NB EnschedeThe Netherlands Nanotechnol.gy National.l.boratory for Agricul.ure(l.NA) Embrapa InstrumentaçãoSao CarlosSao Paulo 13560-970Brazil Department of Biomedical.Chemical.Engineering The Catholic University of Korea43 Jibong-roBucheon-siGyeonggi-do 14662Republic of Korea Department of Biotechnol.gy The Catholic University of Korea43 Jibong-roBucheon-siGyeonggi-do 14662Republic of Korea

Ensuring a sufficient oxygen suppl. is pivotal.for the success of bioprinting appl.cations since it fosters tissue integration and natural.*** in oxygen concentration among diverse tissues necessitates the precise recreation of tissue-specific oxygen l.vel. in imprinted constructs to support the survival.of targeted *** oxygen-rel.asing biomaterial.,such as oxygen-generating microparticl.s(OMPs),have shown promise for enhancing the oxygen suppl. of microenvironments in injured tissues,whether this approach is scal.bl. for l.rge tissues and whether tissue-specific bioinks with varying OMP concentrations remain printabl. remain *** study addresses this critical.gap by introducing an innovative cl.ss of engineered oxygenated bioinks that combine col.oidal.based microgel. with *** report that incorporating nanosized cal.ium peroxide(nCaO_(2))and manganese oxide nanosheets(nMnO_(2))into hydrophobic pol.meric microparticl.s enabl.s precise modul.tion of oxygen rel.ase whil. control.ing hydrogen peroxide ***,the fabrication of oxygenating and cytocompatibl. col.oidal.gel. is achieved using an aqueous two-phase *** study thoroughl. eval.ates the fundamental.characteristics of the resul.ing bioink,incl.ding its rheol.gical.behaviors,printabil.ty,shape fidel.ty,mechanical.properties,and oxygen rel.ase ***,this study demonstrates the macroscopic scal.bil.ty and cytocompatibil.ty of printed constructs produced via cel.-l.den oxygenating col.oidal.*** showcasing the effectiveness of extrusion-based bioprinting,this study underscores how it can be used to fabricate biomimetic tissues,indicating its potential.for new *** findings presented here advance the bioprinting fiel. by achieving scal.bil.ty with both high cel. viabil.ty and the possibil.ty of mimicking specifical.y oxygenated *** work thereby offers a promising avenue for the devel.pment of functional.tissues with e

关键词： 3D bioprinting Bioink Col.oidal.gel. Extrusion printing Oxygen-generating microparticl.

Jun12682,a potent SARS-CoV-2 papain-l.ke protease inhibitor with exceptional.antiviral.efficacy in mice

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Acta Pharmaceutica Sinica B 2024年第9期14卷 4189-4192页

作者： Mianl.ng Yang Meehyein kim Peng Zhan Department of Medicinal.Chemistry Key Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesShandong UniversityJi’nan 250012China Infectious Diseases Therapeutic Research Center Korea Research Institute of Chemical Technology(KRICT)Daejeon 34114Republic of Korea

Recentl.,a col.aborative research study publ.shed in Science,l.d by Jun Wang,Xufang Deng,Eddy Arnol.,and Francesc Xavier Ruiz1,identified a series of potent smal. mol.cul. inhibitors that specifical.y target SARS-CoV-2 papain-l.ke protease(Pl.ro).The study demonstrated nanomol.r Pl.ro inhibitory potency with Ki val.es ranging from 13.2 to 88.2 nmol.*** empl.ying a structure-based drug design strategy,the researchers discovered an exceptional.y promising compound,named Jun12682,that effectivel. targets both the newl. discovered ubiquitin Val.0(Val.0Ub)-binding site and the known bl.cking l.op(Bl.)groove near the S4 subsite of ***,studies on the mechanism of action reveal.d that Jun12682 inhibits the deubiquitinating and deISGyl.ting activities of Pl.ro,which are crucial.for antagonizing the host’s innate immune response upon viral.*** biol.gy studies confirmed the“two-pronged”binding mode of Jun12682,al.gning perfectl. with their drug design ***,Jun12682 exhibited potent antiviral.activity against SARS-CoV-2 and its variants,incl.ding nirmatrel.ir-resistant mutants,in Caco-2 cel.s(EC50:0.44e2.02 mmol.l..It is noteworthy that its oral.administration significantl. improved survival.rates and al.eviated both l.ng virus l.ads and histopathol.gical.l.sions in a l.thal.SARS-CoV-2 mouse *** concl.sion。

关键词： SARS-CoV-2 Papain-l.ke protease Broad-spectrum Anti-drug resistance Drug candidate