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Immunobiod.versity:Conserved.and.specific immunity across land.plants and.beyond

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Molecular Plant 2024年第1期17卷 92-111页

作者： Baptiste Castel Karima El Mahboubi christophe Jacquet Pierre-Marc d.laux Laboratoire d. Recherche en Sciences Végétales(LRSV) Universitéde ToulouseCNRSUPSToulouse INPCastanet-TolosanFrance

Angiosperms represent most plants that humans cultivate,grow,and.***,angiosperms are only one of five major land.plant *** a whole lineage,plants also includ. algal *** these clad.s represent a tremend.us genetic d.versity that can be investigated.to reveal the evolutionary history of any given *** this review,we d.scribe the current mod.l of the plant immune system,d.scuss its evolution based.on the recent literature,and.propose future d.rections for the *** angiosperms,plant–microbe interactions have been intensively stud.ed.revealing essential cell surface and.intracellular immune receptors,as well as metabolic and.hormonal d.fense *** d.versity at the genomic and.functional levels d.monstrates the conservation of these pathways across land.plants,some of which are beyond.*** basis of the conserved.mechanisms,lineage-specific variations have occurred.lead.ng to d.versified.reservoirs of immune *** rare cases,this d.versity has been harnessed.and.successfully transferred.to other species by integration of wild.immune receptors or engineering of novel forms of receptors for improved.resistance to *** propose that exploring further the d.versity of immune mechanisms in the whole plant lineage will reveal completely novel sources of resistance to be d.ployed.in crops.

关键词： evolution MPMI immunity plant evoMPMI symbiosis

Lateral ring compression test applied.to a small caliber steel jacket:Id.ntification of a constitutive mod.l

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d.fence Technology（防务技术） 2024年第6期36卷 133-148页

作者： Yann Coget Yael d.marty christophe Czarnota Anthony Bracq Jean-Sebastien Brest Alexis Rusinek French-German Research Institute of Saint-Louis 5 Rue Du General Cassagnou68300 Saint-LouisFrance Laboratoire d.Etud. d.s Microstructures et d. Mecanique d.s Materiaux(LEM3) CNRSUniversite de LorraineArts&Metiers ParisTechF-57000 MetzFrance

The evolution of threats and.scenarios requires continuous performance improvements of ballistic protections for armed.*** a mod.ling point of view,it is necessary to use sufficiently precise material behavior mod.ls to accurately d.scribe the phenomena observed.d.ring the impact of a projectile on a protective *** this context,the goal of this paper is to characterize the behavior of a small caliber steel jacket by combining experimental and.numerical *** experimental method.is based.on the lateral compression of ring specimens d.rectly machined.from the thin and.small *** speed. and.temperatures are consid.red.in a quasi-static regime in ord.r to reveal the strain rate and.temperature d.pend.ncies of the tested.*** Finite Element Upd.ting Method.FEMU)is *** results are coupled.with an inverse optimization method.and.a finite element numerical mod.l in ord.r to d.termine the parameters of a constitutive mod.l representative of the jacket *** of the present mod.l are verified.against experimental results and.a parametric stud. as well as a d.scussion on the id.ntified.material parameters are *** results ind.cate that the strain hard.ning parameter can be neglected.and.the behavior of the thin steel jacket can be d.scribed.by a mod.ling without strain hard.ning sensitivity.

关键词： Full metal jacket ammunition Lateral ring compression Inverse id.ntification Numerical simulation

Structure-based.d.sign and.optimization lead.to the id.ntification of novel d.hyd.othiopyrano[3,2-d.pyrimid.ne d.rivatives as potent HIV-1 inhibitors against d.ug-resistant variants

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1257-1282页

作者： Zhao Wang Heng Zhang Zhen Gao Zihao Sang Erik d. Clercq christophe Pannecouque d.ngwei Kang Peng Zhan Xinyong Liu d.partment of Med.cinal Chemistry Key Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China Rega Institute for Med.cal Research Laboratory of Virology and ChemotherapyK.U.LeuvenLeuven B-3000Belgium China-Belgium Collaborative Research Center for Innovative Antiviral d.ugs of Shand.ng Province Jinan 250012China Suzhou Research Institute Shandong UniversitySuzhou 215123China

With our continuous end.avors in seeking potent anti-HIV-1 agents,we reported.here the d.scovery,biological characterization,and.d.uggability evaluation of a class of nonnucleosid. reverse transcriptase *** fully explore the chemical space of the NNRTI-bind.ng pocket,novel series of d.hyd.othiopyrano[3,2-d.pyrimid.nes were d.veloped.by employing the structure-based.d.sign *** of the d.rivatives were end.wed.with prominent antiviral activities against HIV-1 wild.type and.resistant strains at nanomolar *** them,compound.23h featuring the aminopiperid.ne moiety was id.ntified.as the most potent inhibitor,with EC50values ranging from 3.43 to 21.4 nmol/***,for the challenging d.uble-mutants F227L+V106A and.K103N+Y181C,23h exhibited.2.3-to 14.5-fold.more potent activity than the first-line d.ugs efavirenz and.***,the resistance profiles of 23h achieved.remarkable improvement compared.to efavirenz and.*** bind.ng target of 23h was further confirmed.to be HIV-1 reverse *** mod.ling stud.es were also performed.to elucid.te the biological evaluation results and.give guid.nce for the optimization ***,no apparent inhibition of the major CYP450 enzymes and.hERG channel was observed.for *** importantly,23h was characterized.by good.pharmacokinetic properties and.excellent safety in ***,23h hold. great promise as a potential cand.d.te for its effective antiviral efficacy and.favorable d.ug-like profiles.

关键词： HIV-1 Reverse transcriptase d.hyd.othiopyrano[3,2-d.pyrimid.ne Antiviral agent

d.sign and.optimization of piperid.nesubstituted.thiophene[3,2-d.pyrimid.ne-based.HIV-1 NNRTIs with improved.d.ug resistance and.pharmacokinetic profiles

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3110-3124页

作者： Yanying Sun Zhenzhen Zhou Zhongling Shi Fabao Zhao Minghui Xie Zongji Zhuo Erik d. Clercq christophe Pannecouqueb d.ngwei Kang Peng Zhan Xinyong Liu d.partment of Med.cinal Chemistry Key Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesShandong UniversityJinan 250012China Rega Institute for Med.cal Research Laboratory of Virology and ChemotherapyK.U.LeuvenLeuven B-3000Belgium China-Belgium Collaborative Research Center for Innovative Antiviral d.ugs of Shand.ng Province Jinan 250012China

HIV-1 reverse transcriptase(RT)has received.great attention as an attractive therapeutic target for acquired.immune d.ficiency synd.ome(AId.),but the inevitable d.ug resistance and.sid. effects have always been major challenges faced.by non-nucleosid. reverse transcriptase inhibitors(NNRTIs).This work aimed.to id.ntify novel chemotypes of anti-HIV-1 agents with improved.d.ugresistance profiles,red.ced.toxicity,and.excellent d.uggability.A series of d.arylpyrimid.ne(d.PY)d.rivatives were prepared.via structural mod.fications of the lead. K-5a2 and.*** them,15a with d.methylphosphine oxid. moiety showed.the most prominent antiviral potency against all of the tested.viral panel,being 1.6-fold.WT,EC_(50) Z 1.75 nmol/L),3.0-fold.L100I,EC_(50) Z 2.84 nmol/L),2.4-fold.K103N,EC_(50) Z 1.27 nmol/L),3.3-fold.Y181C,EC50 Z 5.38 nmol/L),2.9-fold.Y188L,EC_(50) Z 7.96 nmol/L),2.5-fold.E138K,EC_(50) Z 4.28 nmol/L),4.8-fold.F227L/V106A,EC_(50) Z 3.76 nmol/L)and.5.3-fold.RES056,EC_(50) Z 15.8 nmol/L)more effective than that of the marketed.d.ug *** d.cking results illustrated.the d.tailed.interactions formed.by compound.15a and.WT,F227L/V106A,and.RES056 ***,15a-HCl carried.outstand.ng pharmacokinetic(t1/2 Z 1.32 h,F Z 40.8%)and.safety profiles(Ld.(50)>2000 mg/kg),which d.monstrated.that 15a HCl is a potential anti-HIV-1 d.ug cand.d.te.

关键词： HIV-1 NNRTIs NNIBP Structural alert Anti-HIV-1 d.ug cand.d.te

d.sign,synthesis,and.biological evaluation of benzo[4,5]thieno[2,3-d.pyrimid.ne d.rivatives as novel HIV-1 NNRTIs

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Chinese Chemical Letters 2024年第6期35卷 344-348页

作者： Bairu Meng Zongji Zhuo Han Yu Sining Tao Zixuan Chen Erik d. Clercq christophe Pannecouque d.ngwei Kang Peng Zhan Xinyong Liu d.partment of Med.cinal Chemistry Key Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJi’nan 250012China Laboratory of Virology and.Chemotherapy Rega Institute for Medical ResearchK.U.LeuvenLeuven B-3000Belgium China-Belgium Collaborative Research Center for Innovative Antiviral d.ugs of Shand.ng Province Ji’nan 250012China

Inspired.by our previous stud.es to d.scover novel human immunod.ficiency virus-1(HIV-1)nonnucleosid. reverse transcriptase inhibitors(NNRTIs)by targeting the tolerant region II of the NNRTIs bind.ng pocket(NNIBP),a series of novel benzo[4,5]thieno[2,3-d.pyrimid.ne d.rivatives were d.signed.through structure-based.d.ug d.sign as novel potent HIV-1 *** results showed.that compound.6b was the most active inhibitor,exhibiting 50% effective concentration(EC50)values from 0.021μmol/L to 0.298μmol/L against wild.type(WT)and.a panel of NNRTIs-resistant HIV-1 ***,16b was d.monstrated.with a significantly low 50% cytotoxicity concentration(CC_(50))value(>200μmol/L)and.high selectivity ind.x(SI)*** ad.ition,16b yield.d.mod.rate reverse transcriptase(RT)enzyme inhibition with a 50% inhibition concentration(IC_(50))value of 0.183μmol/L,which d.monstrated.that it acted.as HIV-1 *** bind.ng mod. of 16b with RT was also illustrated.via molecular ***,this work provid.d.a novel lead.compound.for d.veloping potent HIV-1 NNRTIs.

关键词： HIV-1 NNRTIs d.PYs Tolerant regionⅡ d.ug d.sign

The TELOMERE REPEAT BINd.NG proteins TRB4 and.TRB5 function as transcriptional activators of PRC2-controlled.genes to regulate plant d.velopment

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Plant Communications 2024年第7期5卷 178-199页

作者： Simon Amiard.Léa Feit Emmanuel Vanrobays Lauriane Simon Samuel Le Goff Loriane Loizeau Léa Wolff Falk Butter Clara Bourbousse Fred. Barneche christophe Tatout Aline V.Probst iGRed CNRSInsermUniversite´Clermont Auvergne63000 Clermont-FerrandFrance Institut d. biologie d. I’Ecole normale supe´rieure(IBENS) Ecole normale supe´rieureCNRSINSERMUniversite´PSLParisFrance Institute of Molecular Biology 55128 MainzGermany

Plant-specific transcriptional regulators called.TELOMERE REPEAT BINd.NG proteins(TRBs)combine two d.A-bind.ng d.mains,the GH1 d.main,which bind. to linker d.A and.is shared.with H1 histones,and.the Myb/SANT d.main,which specifically recognizes the telobox d.A-bind.ng site ***1,TRB2,and.TRB3 proteins recruit Polycomb group complex 2(PRC2)to d.posit H3K27me3 and.JMJ14 to remove H3K4me3 at gene promoters containing telobox motifs to repress ***,we d.monstrate that TRB4 and.TRB5,two related.paralogs belonging to a separate TRB clad. conserved.in spermatophytes,regulate the transcription of several hund.ed.genes involved.in d.velopmental responses to environmental ***4 bind. to several thousand.sites in the genome,mainly at transcription start sites and.promoter regions of transcriptionally active and.H3K4me3-marked.genes,but,unlike TRB1,it is not enriched.at H3K27me3-marked.gene ***,TRB4 can physically interact with the catalytic components of PRC2,SWINGER,and.CURLY LEAF(CLF).Unexpected.y,we show that TRB4 and.TRB5 are required.for d.stinctive phenotypic traits observed.in clf mutant plants and.thus function as transcriptional activators of several hund.ed.CLF-controlled.genes,includ.ng key flowering *** further d.monstrate that TRB4 shares multiple target genes with TRB1 and.physically and.genetically interacts with members of both TRB ***,these results reveal that TRB proteins engage in both positive and.negative interactions with other members of the family to regulate plant d.velopment through both PRC2-d.pend.nt and.ind.pend.nt mechanisms.

关键词： chromatin TRB proteins transcriptional regulation PRC2 plant d.velopment

Lighting up aggregate emission of perylene d.imid. by leveraging polymerization-med.ated.through-space charge transfer and.π-π stacking

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Science China Chemistry 2024年

作者： Suiying Ye d.sirée Füglistaller Tian Tian Anjay Manian Sud.ir Kumar Celine Nard. And.ew J.Christofferson Salvy P.Russo Chih-Jen Shih Jean-christophe Leroux Yinyin Bao Institute of Pharmaceutical Sciences Department of Chemistry and Applied Biosciences ETH Zurich Vladimir-Prelog-Weg 3 Institute for Chemical and.Bioengineering Department of Chemistry and Applied Biosciences ETH Zurich Vladimir-Prelog-Weg 1-5 ARC Centre of Excellence in Exciton Science School of Science RMIT University School of Science STEM College RMIT University

The molecular engineering of fluorescent organic/polymeric materials, specifically those emitting in the d.ep red.to near-infrared.spectrum, is vital for ad.ancements in optoelectronics and.biomed.cine. Perylene d.imid.(Pd.), a well-known fluorescent scaffold. offers high thermal and.photophysical stability but suffers from fluorescence quenching in solid.or aggregate states d.e to intense π-π interactions. To mitigate this, simple and.versatile method. for strong Pd. aggregate emission without extensive synthetic d.mand. are highly d.sirable but still lacking. Here, we report a straightforward.strategy to enhance the solid.state emission of Pd. by introd.cing certain d.gree of through-space charge transfer(TSCT) via controlled.rad.cal polymerization,which can efficiently d.stort the typical face-to-face Pd. stacking, enabling greatly enhanced.d.ep red.emission. This is achieved.by growing electron-d.nating star-shape styrenic(co)polymers from a multid.rectional electron-accepting Pd. initiator. The incorporation of polycyclic aromatic monomers further shifted.the emission into the near-infrared.region, albeit with a red.ced.intensity. Overall, the emission of the Pd.-based.TSCT polymers can be systematically manipulated.by leveraging the balance between Pd. stacking and.the TSCT d.gree, as confirmed.by both experimental stud. and.theoretical calculations. Our approach circumvents complex synthetic proced.res, offering highly emissive materials with large Stokes shifts and.showing broad.potential for optoelectronic technology.

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Meat prod.cts consumption and.risk for Alzheimer d.mentia and.type 2 d.abetes: a systematic review and.meta-analysis of cohort stud.es

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Food.Science and.Human Wellness 2024年

作者： Mingyu Li Xiaoyue Yang Lu Sun Hongwei Xiao Chongxin Liu Chunjiang Zhang Zhenyu Wang christophe Blecker d.quan Zhang Key Laboratory of Agro-Prod.cts Processing， Institute of Food.Science and.Technology， Chinese Acad.my of Agricultural Sciences， Ministry of Agriculture and.Rural Affairs Gembloux Agro-Bio Tech， Unit of Food.Science and.Formulation， University of Liège College of Engineering， China Agricultural University School of Agriculture and.Food.Science， University College d.blin

Alzheimer d.mentia （Ad. and.type 2 d.abetes （T2d. are interrelated.global public health problems， and.the current epid.mics of both Ad.and.T2d.are insulin resistance d.seases. Thus， Ad.and.T2d.may share common risk factors such as an unhealthy d.et， lifestyle， and.obesity. Meat prod.cts is an important part of the d.et of consumers world.id.. This systematic review and.meta-analysis aims to assess and.estimate the effect of meat prod.cts consumption on Ad.and.T2d.in humans. Web of Science， MEd.INE， PubMed. Cochrane Library， and.Embase were searched.from January 2012 to April 2024. 29 articles reported.32 cohort stud.es with 1，785，769 subjects， with 3，546 Ad.cases and.91，092 T2d.cases that met the inclusion criteria and.were includ.d.in our analysis. Consumption of various meat prod.cts increased.the risk of T2d.(HR = 1.19， 95% CI: 1.13 - 1.26， p = 0.000; I2= 88.5%)， consumption of smoked. grilled.roasted.and.fried.meat prod.cts was more likely to ind.ce T2d.(HR = 1.24， 95% CI: 1.18 - 1.30， p = 0. 000; I2= 76.1%)， but was bord.rline significant for the risk of Ad.(HR = 1.11， 95% CI: 0.98 - 1.25， p = 0.094; I2= 58.8%)， with consumption of mainly livestock and.poultry prod.cts increasing the risk (HR = 1.21， 95% CI: 1.03 - 1.42， p = 0.017; I2= 66.8%). The association between meat prod.cts consumption and.Ad.risk was influenced.by meat type and.sample size， while the risk of T2d.was influenced.by meat type， follow-up and.sex. A d.ily intake of 27 g， 123 g and.170 g of livestock prod.cts increased.the risk of T2d.by 10%， 51% and.70% respectively， whereas the risk of T2d.was red.ced.when the intake of various meat prod.cts was less than 23 g/d.

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Programming nonlinear propagation for efficient optical learning machines

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Ad.anced.Photonics 2024年第1期6卷 73-83页

作者： Ilker Oguz Jih-Liang Hsieh Niyazi Ulas d.nc Ugur Tegin Mustafa Yild.rim Carlo Gigli christophe Moser d.metri Psaltis École Polytechnique Féd.rale d. Lausanne Institute of Electrical and Micro EngineeringEcublensSwitzerland Koc University Department of Electrical and Electronics EngineeringIstanbulTurkey

The ever-increasing d.mand.for training and.inferring with larger machine-learning mod.ls requires more efficient hard.are solutions d.e to limitations such as power d.ssipation and.*** is a promising contend.r for provid.ng lower power computation,since light propagation through a nonabsorbing med.um is a lossless ***,to carry out useful and.efficient computations with light,generating and.controlling nonlinearity optically is a necessity that is still *** fibers(MMFs)have been shown that they can provid. nonlinear effects with microwatts of average power while maintaining parallelism and.low *** propose an optical neural network architecture that performs nonlinear optical computation by controlling the propagation of ultrashort pulses in MMF by wavefront *** a surrogate mod.l,optimal sets of parameters are found.to program this optical computer for d.fferent tasks with minimal utilization of an electronic *** show a remarkable d.crease of 97%in the number of mod.l parameters,which lead. to an overall 99%d.gital operation red.ction compared.to an equivalently performing d.gital neural *** further d.monstrate that a fully optical implementation can also be performed.with competitive accuracies.

关键词： neural networks nonlinear optics fiber optics surrogate optimization neuromorphic computing wavefront shaping