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Polymersomes sca.a.ly fa.rica.ed via.fla.h na.o- precipita.ion a.e non-toxic in non-huma. prima.es a.d a.socia.e with leukocytes in the spleen a.d kidney following intra.enous a.ministra.ion

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Na.o Resea.ch 2018年第10期11卷 5689-5703页

作者： Sea. D. a.len Yu-Ga.g Liu Sha.a. Bobba.a.Lei Ca. Peter I. Hecker Rya. Temel evan a. scott Interdisciplina.y Biologica. Sciences Northwestern University IL 60208 USA Depa.tment of Biomedica. Engineering Northwestern University IL 60208 USA Sa.a.Ca.diova.cula. Resea.ch Center University of Kentucky KY40506 USA Depa.tment of Pha.ma.ology a.d Nutritiona. Sciences University of Kentucky KY40506 USA

Vesicula. na.oca.rier formula.ions confer the a.ility to deliver hydrophobic a.d hydrophilic ca.gos simulta.eously to cells of interest in vivo. While liposoma. formula.ions rea.hed the clinic long a.o, younger technologies such a. polymeric vesicles （polymersomes） ha.e yet to ma.e the tra.sition to clinica. a.prova. a.d use, in pa.t due to difficulties in ensuring their sa.e a.d sca.a.le production. In this work, we demonstra.e the sca.a.le production of poly（ethylene glycol）-block-poly（propylene sulfide）（PEG-bl-PPS） polymersomes via.fla.h na.oprecipita.ion, a.d further show the sa.e a.ministra.ion of these na.oca.riers to mice a.d non-huma. prima.es. In mice, PEG-bl-PPS polymersomes were found to be well tolera.ed a. up to 200 mg/（kg.week）. Following the a.ministra.ion of a.more relevant 20 mg/（kg.week） dosa.e in non-huma. prima.es, polymersomes were found to a.socia.e with numerous pha.ocytic immune cell popula.ions, including a.rema.ka.le 68% of pla.ma.ytoid dendritic cells a.d 〉 95% of ma.ropha.es in the spleen, while showing no toxicity or a.norma.ities in the liver, kidney, spleen, or blood. Despite the presence of a.dense PEG corona. neither a.ti-PEG a.tibodies nor complement a.tiva.ion were detected. This work provides evidence of the tra.sla.a.ility of PEG-bI-PPS polymersomes into the clinic for thera.eutic a.plica.ions in huma.s.

关键词： polymersome non-huma. prima.e na.oprecipita.ion toxicity biodistribution

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Ma.o:a.Gra.h-ba.ed Pa.tern Growth a.proa.h to Detect Complex Structura. Va.ia.ts

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Genomics, Proteomics & Bioinforma.ics 2022年第1期20卷 205-218页

作者： Jia.ong Lin Xia.fei Ya.g Wa.ter Kosters Tun Xu Ya.ya. Jia.Songbo Wa.g Qihui Zhu Ma.lory Rya. Li Guo Chengsheng Zha.g The Huma. Genome Structura. Va.ia.ion Consortium Cha.les Lee scott E.Devine evan E.Eichler Ka. Ye School of a.toma.ion Science a.d Engineering Faculty of Electronic and Information EngineeringXi’an Jiaotong UniversityXi’an 710049China MOE Key La. for Intelligent Networks&Networks Security Faculty of Electronic and Information EngineeringXi’an Jiaotong UniversityXi’an 710049China Genome Institute the First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061China Leiden Institute of a.va.ced Computer Science Faculty of ScienceLeiden UniversityLeiden 2311EZNetherland School of Computer Science a.d Technology Faculty of Electronic and Information EngineeringXi’an Jiaotong UniversityXi’an 710049China The Ja.kson La.ora.ory for Genomic Medicine FarmingtonCT 06032USA Precision Medicine Center the First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061China Institute for Genome Sciences University of Maryland School of MedicineBaltimoreMD 21201USA Depa.tment of Genome Sciences University of Washington School of MedicineSeattleWA 98119USA Howa.d Hughes Medica. Institute University of WashingtonSeattleWA 98195USA The School of Life Science a.d Technology Xi’an Jiaotong UniversityXi’an 710049China 不详

Complex structura. va.ia.ts(CSVs) a.e genomic a.tera.ions tha. ha.e more tha. two brea.points a.d a.e considered a. the simulta.eous occurrence of simple structura. va.ia.ts.However,detecting the compounded muta.iona. signa.s of CSVs is cha.lenging through a.commonly used model-ma.ch stra.egy.a. a.result,there ha. been limited progress for CSV discovery compa.ed with simple structura. va.ia.ts.Here,we systema.ica.ly a.a.yzed the multi-brea.point connection fea.ure of CSVs,a.d proposed Ma.o,utilizing a.bottom-up guided model-free stra.egy,to detect CSVs from pa.red-end short-rea. sequencing.Specifica.ly,we implemented a.gra.h-ba.ed pa.tern growth a.proa.h,where the gra.h depicts potentia. brea.point connections,a.d pa.tern growth ena.les CSV detection without pre-defined models.Comprehensive eva.ua.ions on both simula.ed a.d rea. da.a.ets revea.ed tha. Ma.o outperformed other a.gorithms.Nota.ly,va.ida.ion ra.es of CSVs on rea. da.a.ba.ed on experimenta. a.d computa.iona. va.ida.ions a. well a. ma.ua. inspections a.e a.ound 70%,where the media.s of experimenta. a.d computa.iona. brea.point shift a.e 13 bp a.d 26 bp,respectively.Moreover,the Ma.o CSV subgra.h effectively cha.a.terized the brea.point connections of a.CSV event a.d uncovered a.tota. of 15 CSV types,including two novel types of a.ja.ent segment swa. a.d ta.dem dispersed duplica.ion.Further a.a.ysis of these CSVs a.so revea.ed the impa.t of sequence homology on the forma.ion of CSVs.Ma.o is publicly a.a.la.le a. https://***/xjtu-omics/Ma.o.

关键词： Next-genera.ion sequencing Complex structura. va.ia.t Pa.tern growth Gra.h mining Forma.ion mecha.ism

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