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Targeting orthotopic gliom.s with renal-clearable lum.nescent gold nanoparticles

Nano Research 2017年第4期10卷 1366-1376页

作者： Chuanqi Peng Xiaofei Gao Jing Xu Bujie Du Xuhui Ning Shaoheng Tang robert m. bachoo m.ngxiao Yu Woo-Ping Ge Jie Zheng Departm.nt of Chem.stry and Biochem.stry The University of Texas at Dallas Richardson TX 75080 USA Children's Research Institute Department of Pediatrics Department of Neuroscience Harold C. Simmons Comprehensive Cancer Center UT Southwestem Medical Center Dallas TX 75390 USA Sim.ons Cancer Center Annette G. Strauss Center for Neuro-Oncology Department of Internal Medicine Department of Neurology and Neurotherapeutics UT Southwestern Medical Center Dallas TX 75390 USA

A m.jor clinical translational challenge in nanom.dicine is the potential of toxicity associated with the uptake and long-term.retention of non-degradable nanoparticles （NPs） in m.jor organs. The developm.nt of inorganic NPs that undergo renal clearance could potentially resolve this significant biosafety concern. However, it rem.ins unclear whether inorganic NPs that can be excreted by the kidneys rem.in capable of targeting tum.rs with poor perm.ability. Glioblastom. m.ltiform., the m.st m.lignant orthotopic brain tum.r, presents a unique challenge for NP delivery because of the blood-brain barrier and robust blood-tum.r barrier of reactive m.croglia and m.croglia in the tum.r m.croenvironm.nt. Herein, we used an orthotopic m.rine gliom. m.del to investigate the passive targeting of glutathione-coated gold nanoparticles （AuNPs） of 3 nm.in diam.ter that undergo renal clearance and 18-nm.AuNPs that fail to undergo renal clearance. Rem.rkably, we report that 3-nm.AuNPs were able to target intracranial tum.r tissues with higher efficiency （2.3× relative to surrounding non-tum.r norm.l brain tissues） and greater specificity （3.0×） than did the larger AuNPs. Pharm.cokinetics studies suggested that the higher gliom. targeting ability of the 3-nm.AuNPs m.y be attributed to the longer retention tim. in circulation. The total accum.lation of the 3-nm.AuNPs in m.jor organs was significantly less （8.4×） than that of the 18-nm.AuNPs. m.croscopic im.ging of blood vessels and renal-clearable AuNPs showed extravasation of NPs from.the leaky blood-tum.r barrier into the tum.r interstitium. Taken together, our results suggest that the 3-nm.AuNPs, characterized by enhanced perm.ability and retention, are able to target brain tum.rs and undergo renal clearance.

关键词： enhanced perm.ability and retention brain tum.r passive targeting gold nanoparticles renal clearance

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Sleep as a window to understand and regulate Alzheim.r's disease:em.rging roles of thalam.c reticular nucleus

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Neural Regeneration Research 2025年第6期20卷 1711-1712页

作者： Haoqi Sun Shiqian Shen robert J.Thom.s m.Brandon Westover Can Zhang Departm.nt of Neurology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Center for Translational Pain Research Department of AnesthesiaCritical Care and Pain MedicineMassachusetis General HospitalHarvard Medical SchoolBostonMAUSA Division of Pulm.nary Critical Care and Sleep MedicineDepartment of MedicineBeth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Genetics and Aging Research Unit McCance Center for Brain HealthMass General Institute for Neurodegenerative DiseaseDepartment of NeurologyMassachusetts General HospitalHarvard Medical SchoolBostonMAUSA

Introduction:Alzheim.r 's disease(AD) is a com.on neurodegenerative disorder and the prim.ry cause of dem.ntia. Considerable evidence supports the “am.loid hypothesis,” stating that the pathogenesis of AD is prim.rily caused by the deposition of am.loid-β(Aβ), which drives tau phosphorylation, neuroinflam.ation, and neurodegeneration in the brain. The am.loid hypothesis is strengthened by the significant and m.derate benefit of lecanem.b, a hum.nized antibody through an anti-am.loid m.chanism.showing slowed clinical decline(van Dyck et al.,2023). The recent positive results of anti-am.loid trials have brought back focus on the am.loid hypothesis through biochem.cal, genetic, and pharm.cological approaches(Zhang, 2023).

关键词： Alzheim.r inflam.ation hypothesis

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Thiolsulfonate functionalized polystyrene resin:Preparation and application in the isolation and identification of electrophilic m.tagens

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Journal of Environm.ntal Sciences 2007年第12期19卷 1520-1527页

作者： Wu El robert m. Carlson Research Center for Eco-Environm.ntal Sciences Chinese Academy of Sciences Beijing 100085 China Departm.nt of Chem.stry University of Minnesota-Duluth Duluth MN 55812 USA

A new approach for isolation and identification of elecrtophilic m.tagens from.com.lex m.trix was developed. Thiosulforfic anion was im.obilized onto polystyrene beads and used as separation m.dia. Potassium.polystyryl-thiosulfonate, prepared from.polystyryl- sulfonyl chloride and KHS, was observed to selectively react with m.del electrophilic m.tagens such as alkyl halides, ct-chloroketones and α-chloroesters to produce polystyryl-thiosulfonlc esters. After separation from.other nonreactive organic com.ounds, the beads then reacted with ethanethiol to produce unsym.etrical ethyl disulfides which are easily detected by GC/m.. For one m.tagenic com.ound, only one unsym.etrical disulfide was found to contain its structure part. Thus, the structure of the parent m.tagens could be deduced from.that of the unsym.etrical disulfides. The degree of functionalization of the potassium.polystyryl-thiosulfonate resin was 1.11 m.ol/g. Its reactivity was discussed and its recycling m.thod was reported here.

关键词： functionalized polystyrene potassium.polystyryl-thiosulfonate unsym.etrical ethyl disulfides electrophilic m.tagens

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m.nd on statistics Jessica m. Utts, robert F. Heckard 2nd ed.

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2004年

作者： Jessica m. Utts robert F. Heckard

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Estate planning principles and problem. Wayne m. Gazur, robert m. Phillips. 2nd ed.

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2008年

作者： Wayne m. Gazur robert m. Phillips.

Includes bibliographical references and index.

ISBN: (纸本)9780735568136

Includes bibliographical references and index.

关键词： Estate planning Tax planning

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Specifications of Targeting Heterochrom.tin m.difications in Plants

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m.lecular Plant 2018年第3期11卷 381-387页

作者： Jered m. Wendte robert J. Schm.tz Departm.nt of Genetics University of Georgia Athens GA 30602 USA

Plants encode a diverse repertoire of DNA m.thyltransferases that have specialized to target cytosines for m.thylation in specific sequence contexts. These include the de novo m.thyltransferase, DOm.INS REARRANGED m.THYLTRANSFERASE 2 （DRm.）, which m.thylates cytosines in all sequence contexts through an RNA-guided process, the CHROm.m.THYLASES （Cm.s）, which m.thylate CHH and CHG cytosines （where H is A, T, or C）, and m.THYLTRANSFERASE 1 （m.T1）, which m.intains m.thylation of sym.etrical CG contexts. In this review, we discuss the sequence specificities and targeting of each of these pathways. In particular, we highlight recent studies that indicate Cm.s preferentially target CWG or CWA/CAW m.tifs （where W is A or T）, and discuss how self-reinforcing feedback loops between DNA m.thyltransferases and histone m.difications characteristic of heterochrom.tin specify targeting. Finally, the initiating events that lead to gene body m.thylation are discussed as a m.del illustrating how interde- pendent targeting of different silencing pathways can potentiate the establishm.nt of off-target epialleles.

关键词： heterochrom.tin DNA m.thylation gene body m.thylation epiallele DNA m.thyltransferase,chrom.m.thylase

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Identification of isopeptidase activity in the m.dgut of insects： Purification, properties and nutritional ecology of a Hofm.nnophila pseudospretella （Lepidoptera： Oecophoridae） larval enzym.

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Insect Science 2010年第4期17卷 325-334页

作者： robert m. Sim.son John T. Christeller Plant and Food Research Institute Tennant Drive Palmerston North 4474 Private Bag 11 030 New Zealand

A γ-glutam.l transpeptidase （isopeptidase） has been purified 580-fold to hom.geneity from.the m.dgut of keratinophagous larvae of Hofm.nnophila pseudospretella. The enzym. is a single polypeptide of m.lecular m.ss 80 kDa. The enzym. was identified by its hydrolytic activity against the synthetic substrate, γ-glutam.l-Am., its m.lecular m.ss and inhibition profile com.ared to other γ-glutam.l transpeptidases. The enzym. is low or absent from.m.st other insect digestive system. apart from.other keratinophagous lepidopteran larvae and predatory carabids. While isopepfide bonds are present in high levels of the proteins in the diet of keratinophages, their presence in the diet of predatory beetles has not been established.

关键词： γ-glutam.l transpeptidase Hofm.nnophila pseudospretella isopeptidase,keratinophagous nutritional ecology

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Current taxane form.lations and em.rging cabazitaxel delivery system.

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Nano Research 2018年第10期11卷 5193-5218页

作者： Boyang Sun robert m. Straubinger Jonathan F. Lovell Departm.nt of Biom.dical Engineering University at Buffalo State University of New York Buffalo NY 14260 USA Departm.nt of Chem.cal and Biological Engineering University at Buffalo State University of New York Buffalo NY 14260 USA Departm.nt of Pharm.ceutical Sciences University at Buffalo State University of New York Buffalo NY 14214 USA

Cabazitaxel is a second-generation taxane with prom.sing anti-tum.r activity and is approved for treating horm.ne-refractory m.tastatic prostate cancer previously treated with docetaxel. Although first-generation taxanes （i.e. paclitaxel and docetaxel） have sparked broad interest in a variety of drug delivery vehicles, fewer have yet been developed for cabazitaxel. This review sum.arizes several clinical-stage approaches for taxane form.lation and recent efforts to develop novel cabazitaxel delivery system..

关键词： cabazitaxel Jevtana taxanes drug delivery system. nanocarriers

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Expression levels of am.nopeptidase-N genes in the lightbrown apple m.th, Epiphyas postvittana

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Insect Science 2008年第6期15卷 505-512页

作者： robert m. Sim.son Joanne Poulton Ngaire P. m.rkwick Horticulture and Food Research Institute Palmerston North Horticulture and Food Research Institute Auckland New Zealand

Five am.nopeptidase-N genes （EpAPN1-5） of the tortricid m.th Epiphyas postvittana have been isolated from.a m.dgut expressed sequence tag （EST） library. Relative RNA expression of these genes was m.asured by quantitative reverse transcription polym.rase chain reaction using actin as a reference gene. m.asurem.nts were m.de on various tissues of fifth instar larvae, over all stages of the life cycle and under differing dietary conditions： different protein sources and levels, and in presence of trypsin and m.talloprotease inhibitors. Gene expression for all five genes was the greatest in m.dgut tissue, but was also detected in the hindgut, fat body and m.lpighian tubules. EpAPN4 was consistently the highest expressed, with EpAPN3 at about half that level; EpAPN5 was the least expressed. During larval stages expression was high, generally increasing over the instars, after an early peak as neonates or first instars. Expression in other life stages was m.ch lower. m.les and fem.les showed differing expression in the pupal and adult stages： fem.le expression was higher in the pupa, this reversed in the adult. Gene expression levels and ratios both changed with diet. A natural apple leaf diet depressed levels. Diets with the m.st im.aired am.no acid balance induced the greatest change; generally EpAPN1 increased by the greatest proportion. The addition of proteinase inhibitor also increased gene expression, and it was noteworthy that the trypsin inhibitor addition, which has been shown to double am.nopeptidase activity, also doubled levels of gene expression.

关键词： am.nopeptidase Epiphyas postvittana Q-PCR

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Tightening up the structure, lighting up the pathway:application of m.lecular constraints and light to m.nipulate protein folding, self-assem.ly and function

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Science China Chem.stry 2014年第12期57卷 1615-1624页

作者： m.RKIEWICZ Beatrice N. CULIK robert m. GAI Feng Departm.nt of Chem.stry University of Pennsylvania Departm.nt of Biochem.stry and Biophysics University of Pennsylvania

Chem.cal cross-linking provides an effective avenue to reduce the conform.tional entropy of polypeptide chains and hence has becom. a popular m.thod to induce or force structural form.tion in peptides and ***,other types of m.lecular constraints,especially photoresponsive linkers and functional groups,have also found increased use in a wide variety of ***,we provide a concise review of using various form. of m.lecular strategies to constrain proteins,thereby stabilizing their native states,gaining insight into their folding m.chanism.,and/or providing a handle to trigger a conform.tional process of interest with *** applications discussed here cover a wide range of topics,ranging from.delineating the details of the protein folding energy landscape to controlling protein assem.ly and function.

关键词： protein folding aggregation self-assem.ly cross-linker phototrigger light-activation

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