简介：Oxaliplatin,ananticancerdrugcommonlyusedtotreatcolorectalcancerandothertumors,hasanumberofserioussideeffects,mostnotablyneuropathyandototoxicity.Togaininsightsintoitsototoxicprofile,oxaliplatinwasappliedtoratcochlearorgancultures.Consistentwithitneurotoxicpropensity,oxaliplatinselectivelydamagednervefibersataverylowdose1μM.Incontrast,thedoserequiredtodamagehaircellsandspiralganglionneuronswas50foldhigher(50μM).Oxailiplatin-inducedcochlearlesionsinitial-lyincreasedwithdose,butunexpectedlydecreasedatveryhighdoses.Thisnon-lineardoseresponsecouldberelatedtodepressedoxaliplatinuptakeviaactivetransportmechanisms.Previousstudieshavedemon-stratedthataxonaldegenerationinvolvesbiologicallyactiveprocesseswhichcanbegreatlyattenuatedbynicotinamideadeninedinucleotide(NAD+).TodetermineifNAD+wouldprotectspiralganglionaxonsandthehaircellsfromoxaliplatindamage,cochlearculturesweretreatedwithoxaliplatinaloneatdosesof10μMor50μMrespectivelyascontrolsorcombinedwith20mMNAD+.Treatmentwith10μMoxaliplatinfor48hoursresultedinminordamagetoauditorynervefibers,butsparedcochlearhaircells.However,whencochlearculturesweretreatedwith10μMoxaliplatinplus20mMNAD+,mostauditorynervefiberswereintact.50μMoxaliplatindestroyedmostofspiralganglionneuronsandcochlearhaircellswithapop-toticcharacteristicsofcellfragmentations.However,50μMoxaliplatinplus20mMNAD+treatmentgreat-lyreducedneuronaldegenerationsandhaircellmissing.TheresultssuggestedthatNAD+providessignifi-cantprotectionagainstoxaliplatin-inducedneurotoxicityandototoxicity,whichmaybeduetoitsactionsofantioxidant,antiapoptosis,andenergysupply.

简介：Precisebaseeditingishighlydesiredinplantfunctionalgenomicresearchandcropmolecularbreeding.Inthisstudy,weconstructedarice-codonoptimizedadeninebaseeditor(ABE)-nCas9toolthatinducedtargetedA·TtoG·Cpointmutationofakeysinglenucleotidepolymorphismsiteinanimportantagriculturalgene.Combinedwiththemodifiedsingle-guideRNAvariant,ourplantABEtoolcanefficientlyachieveadeninebaseeditinginthericegenome.

简介：ＳＹＮＴＨＥＳＩＳＡＮＤＡＮＴＩ－ＨＵＭＡＮＩＭＭＵＮＯＤＥＦＩＣＩＥＮＣＹＶＩＲＵＳ－１（ＨＩＶ－１）ＡＣＴＩＶＩＴＹＯＦ９－（２－ＰＨＯＳＰＨＯＮＹＬＭＥＴＨＯＸＹＥＴＨＹＬ）ＡＤＥＮＩＮＥ（１）ＡＮＤＩＴＳＲＥＧＩＯＩＳＯＭＥＲ３－（２－ＰＨＯ...