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Advances in targeted nanotherapeutics： From bioconjugation to biomimicry

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Nano Research 2018年第10期11卷 4999-5016页

作者： Danielle M. Valcourt Jenna Harris Rachel S. Riley megan Dang Jianxin Wang Emily S. Day 161 Colburn L ab Department of Biomedical Engineering University of Delaware Newark DE 19716 USA 201 DuPont Hall Department of Materials Science & Engineering University o f Delaware Newark DE 79716 USA 4701 Ogletown Stanton Road Helen F. Graham Cancer Center & Research Institute Newark DE 19713 USA

Since the emergence of cancer nanomedicine, researchers have had intense interest in developing nanoparticles （NPs） that can specifically target diseased sites while avoiding healthy tissue to mitigate the off-target effects seen with conventional treatments like chemotherapy. Initial endeavors focused on the bioconjugation of targeting agents to NPs, and more recently, researchers have begun to develop biomimetic NP platforms that can avoid immune recognition to maximally accumulate in tumors. In this review, we describe the advantages and limitations of each of these targeting strategies. First, we review developments in bioconjugation strategies, where NPs are coated with biomolecules such as antibodies, aptamers, peptides, and small molecules to enable cell-specific binding. While bioconjugated NPs offer many exciting features and have improved pharmacokinetics and biodistribution relative to unmodified NPs, they are still recognized by the body as ＂foreign＂, resulting in their clearance by the mononuclear phagocytic system （MPS）. To overcome this limitation, researchers have recently begun to investigate biomimetic approaches that can hide NPs from immune recognition and reduce clearance by the MPS. These biomimetic NPs fall into two distinct categories： synthetic NPs that present naturally occurring structures, and NPs that are completely disguised by natural structures. Overall bioconjugated and biomimetic NPs have substantial potential to improve upon conventional treatments by reducing off-target effects through site-specific delivery. and they show great promise for future standards of care. Here, we provide a summary of each strategy, discuss considerations for their design moving forward, and highlight their potential clinical impact on cancer therapy.

关键词： targeting nanoparticles cancer biomimicry bioconjugation delivery

Use of a community-led prevention strategy to enhance behavioral changes towards Ebola virus disease prevention:a qualitative case study in Western Côte d’Ivoire

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Global Health Research and Policy 2017年第1期2卷 1-12页

作者： Lara Gautier Koffi Ange Houngbedji Jeanne Uwamaliya megan Coffee Department of Social and Preventive Medicine School of Public Health(ESPUM)University of MontrealQuébecCanada Public Health Research Institute(IRSPUM) University of MontrealQuébecCanada Centre d’Etudes en Sciences Sociales sur les Mondes Africains Américains et AsiatiquesUniversitéDenis DiderotParis-Sorbonne CitéFrance International Rescue Committee AbidjanCôte d’Ivoire International Rescue Committee 122 East 42nd StreetNew YorkNY 10168-1289USA

Background:Starting in December 2013,the Ebola virus disease(EVD)epidemic spread in West Africa through five countries(Sierra Leone,Liberia,Guinea,Nigeria,and Mali),killing over 11,300 *** partnership with Côte d’Ivoire’s Ministry of Health,the International Rescue Committee instigated a community-led strategy aimed at promoting behavior change in order to prevent potential Ebola outbreaks in the *** strategy was implemented in Western districts bordering Liberia,Guinea,and *** study aims to analyze the community-led strategy,to document lessons learned from the experience,and to capitalize on the ***:A case study in four districts of Western Côte d’Ivoire,***,Danané,Odiennéand Touba districts was carried *** data in 12 villages(i.e.,three villages per district)was collected from 62 healthcare workers,community leaders,and ordinary community *** was de-identified,coded and analyzed using a thematic ***:The community-led strategy was socially accepted in the *** though some community leaders reported that sensitization had been,at times,constrained by a lack of equipment,the people interviewed demonstrated accurate understanding of information about prevention *** practices were easily adopted,while others remained difficult to implement(e.g.,ensuring safe and dignified dead body management).Conclusion:This research demonstrates that sensitization efforts led by well-integrated and respected community leaders can be conducive of behavior *** learned from the community-led strategy could be applied to future disease outbreaks.

关键词： Community-led prevention behavior change Ebola virus Côte d’Ivoire

First complete genome sequence in Arborophila and comparative genomics reveals the evolutionary adaptation of Hainan Partridge(Arborophila ardens)

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Avian Research 2019年第1期10卷 63-70页

作者： Chuang Zhou Shuai Zheng Xue Jiang Wei Liang megan Price Zhenxin Fan Yang Meng Bisong Yue Key Laboratory of Bioresources and Ecoenvironment(Ministry of Education) College of Life SciencesSichuan University Sichuan Key Laboratory of Conservation Biology on Endangered Wildlife College of Life SciencesSichuan University Ministry of Education Key Laboratory for Ecology of Tropical Islands College of Life SciencesHainan Normal University

Background:The Hainan Partridge(Arborophila ardens,Phasianidae,Galliformes) is an endemic species of Hainan Island,China,and it is classified as globally vulnerable *** are at least 16 species in genus Arborophila and no genome sequence is ***:The whole genome of Hainan Partridge was de novo sequenced(with shotgun approach on the Illumina 2000 platform) and ***:The genome size of Arborophila ardens is about 1.05 Gb with a high N50 scaffold length of 8.28 Mb and it is the first high quality genome announced in Arborophila *** 9.19% of the genome was identified as repeat sequences and about 5.88 million heterozygous SNPs were detected.A total of 17,376 protein-coding genes were predicted and their functions were *** genome comparison between Hainan Partridge and Red Junglefowl(Gallus gallus) demonstrated a conserved genome *** phylogenetic analysis indicated that the Hainan Partridge possessed a basal phylogenetic position in Phasianidae and it was most likely derived from a common ancestor approximately 36.8 million years ago(Mya).We found that the Hainan Partridge population had experienced bottleneck and its effective population decreased from about 1,040,000 individuals 1.5 Mya to about 200,000 individuals 0.2 Mya,and then recovered to about 460,000 *** number of 1:1 orthologous genes that were predicted to have undergone positive selection in the Hainan Partridge was 504 and some environmental adaptation related categories,such as response to ultraviolet radiation were represented in GO distribution ***:We announced the first high quality genome in Arborophila genus and it will be a valuable genomic resource for the further studies such as evolution,adaption,conservation,not only on Hainan Partridge but also on Arborophila or Phasianidae species.

关键词： Hainan Partridge Arborophila ardens Comparative genomics Positive selection

Adult meerkats modify close call rate in the presence of pups

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Current Zoology 2017年第3期63卷 349-355页

作者： megan T. WYMAN Pearl R. RIVERS Coline MULLER Pauline TONI Marta B. MANSER Department of Evolutionary Biology and Environmental Studies University of Zurich Winterthurerstrasse 190 Zurich CH 8057 Switzerland Kalahari Meerkat Project Kuruman River Reserve P.O. Box 64 Van Zylsrus Northern Cape 8467 South Africa

In animals, signaling behavior is often context-dependent, with variation in the probability of emitting certain signals dependent on fitness advantages. Senders may adjust signaling rate depending on receiver identity, presence of audiences, or noise masking the signal, all of which can affect the benefits and costs of signal production. In the cooperative breeding meerkat Suricata suricatta, group members emit soft contact calls, termed as ＂close calls＂, while foraging in order to maintain group cohesion. Here, we investigated how the close calling rate during foraging was affected by the presence of pups, that produce continuous, noisy begging calls as they follow older group members. Adults decreased their overall close call rate substantially when pups were foraging with the group in comparison to periods when no pups were present. We suggest this decrease was likely due to a masking effect of the loud begging calls, which makes the close call function of maintaining group cohesion partly redundant as the centrally located begging calls can be used in- stead to maintain cohesion. There was some support that adults use close calls strategically to at- tract specific pups based on fitness advantages, that is, as the philopatric sex, females should call more than males and more to female pups than male pups. Dominant females called more than dominant males when a pup was in close proximity, while subordinates showed no sex-based dif- ferences. The sex of the nearest pup did not affect the calling rate of adults. The study shows that meerkats modify their close call production depending on benefits gained from calling and provides an example of the flexible use of one calling system in the presence of another, here contact calls versus begging calls, within the same species.

关键词： call rate communication contact calls cooperation flexibility group cohesion.

Elevated Stream Pathogenic Indicator Bacteria Concentrations in Livestock Grazing Areas across a Single National Forest

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Natural Resources 2017年第10期8卷 657-670页

作者： Lindsey Myers megan Fiske megan Layhee Central Sierra Environmental Resource Center Twain Harte CA USA

Livestock presence in proximity to forest streams has been shown to contribute pathogenic bacteria in excess of water quality standards established to protect human health. However, the degree to which livestock fecal contamination in streams on national forest lands is either a limited or a potentially widespread occurrence is still debated. This study provides additional insight into the matter. We analyzed water in small streams near known cattle grazing areas within the Stanislaus National Forest in the Sierra Nevada, California from 2012 to 2016. Fourteen stream sites were sampled before and after cattle were released onto the forest (four of these sites were sampled across multiple years) to compare indicator bacteria concentrations (fecal coliform—FC, Escherichia coli—EC) to standards established for recreational contact for surface waters. One control site was also sampled. There were 194 water quality violations of either state or federal regulatory standards for recreational contact, all of which occurred once cattle were on the forest. Mean (max) FC and EC concentrations were on orders of magnitude higher after cattle were released onto the forest [FC 1307 (30,000) and EC 1033 (17,000) MPN/100 mL] than during the time period before cattle were on the forest [FC 19 (220) and EC 17 (220) MPN/100 mL;FC, F1,210 = 105, p 1,210 = 85.5, p 0.001]. In addition, the presence of cattle, visual evidence of recent cattle-related disturbances, and sampling week were important predictor variables of FC and EC. These findings support the link between cattle presence and increased levels of stream pathogenic bacteria, and also demonstrate that stream pathogenic bacteria pollution occurs widely across the forest. This research indicates the need to consider alternative range management practices to better protect water quality and human health.

关键词： Cattle Escherichia coli Fecal Coliform Sierra Nevada Water Quality

The role of emergency incident type in identifying first responders' health exposure risks

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Journal of Safety Science and Resilience 2023年第2期4卷 167-173页

作者： Emily J.Haas Katherine N.Yoon Alexa Furek megan Casey Susan M.Moore National Personal Protective Technology Laboratory(NPPTL) National Institute for Ocupational Safety and Health(NIOSH)PittsburghPA 15236United States National Personal Protective Technology Laboratory(NPPTL) National Institute forOccupational Safety and Health(NIOSH)MorgantownWV2605United States

Fire-based emergency management service(EMS)personnel are dispatched to various incidents daily,many of which have unique occupational *** fully understand the variability of incident types and how to best pre-pare and respond,an exploration of the *** system of incident types is *** study uses potential exposure to SARS-CoV-2 as a case example to understand if and how coding categories for incident call types may be updated to improve data standardization and emergency response decision *** received emergency response incident data generated by three fire department computer-aided dispatch(CAD)systems between March and September *** incident was labeled EMS,Fire,or *** the 162,766 incidents,approximately 8.1%(n=13,144)noted potential SARS-CoV-2 exposure within their narrative descriptions of which 86.3%were coded as EMS,9.9%as Fire,and 3.9%as *** assess coding variability across incident types,researchers used the original 3-incident type variable and a new 5-incident type variable reassigned by researchers into EMS,Fire,Other,Hazmat,and Motor *** regressions compared differences in potential exposure using the 3-and 5-incident type *** evaluating the 3-incident type variable,those respond-ing to a Fire versus an EMS incident were 84%less likely to be associated with potential exposure to *** the 5-incident type variable,those responding to Fire incidents were 77%less likely to be associated with a potential exposure than those responding to EMS *** in potential exposure between the 3-and 5-incident type models show the need to understand how incident types are *** demonstrates the need for data standardization to accurately categorize incident types to improve emergency preparedness and *** have implications for incident type coding at fire department municipality and national levels.

关键词： Emergencymedical se Firefighter Incident type Surveillance Telecommunicator

Structure-specific nucleases in genome dynamics and strategies for targeting cancers

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Journal of Molecular Cell Biology 2024年第5期16卷 3-18页

作者： Haitao Sun megan Luo Mian Zhou Li Zheng Hongzhi Li R.Steven Esworthy Binghui Shen Medicinal Plant Resources and Protection Research Center Institute of Medicinal Plant DevelopmentChinese Academy of Medical SciencesPeking Union Medical CollegeBeĳing 100193China Department of Cancer Genetics and Epigenetics Beckman Research Institute of City of HopeDuarteCA 91010USA Department of Molecular and Cell Biology University of CaliforniaBerkeleyBerkeleyCA 94720USA

Nucleases are a super family of enzymes that hydrolyze phosphodiester bonds present in *** widely vary in substrates,causing differentiation in cleavage patterns and having a diversified role in maintaining genetic *** cellular evolution of prokaryotic to eukaryotic,nucleases become structure-specific in recognizing its own or foreign genomic DNA/RNA configurations as its substrates,including flaps,bubbles,and Holliday *** special structural configurations are commonly found as intermediates in processes like DNA replication,repair,and *** structure-specific nature and diversified functions make them essential to maintaining genome integrity and evolution in normal and cancer *** this article,we review their roles in various pathways,including Okazaki fragment maturation during DNA replication,end resection in homology-directed recombination repair of DNA double-strand breaks,DNA excision repair and apoptosis DNA fragmentation in response to exogenous DNA damage,and HIV life *** the nucleases serve as key points for the DNA dynamics,cellular apoptosis,and cancer cell survival pathways,we discuss the efforts in the field in developing the therapeutic regimens,taking advantage of recently available knowledge of their diversified structures and functions.

关键词： structure-specific nucleases DNA replication nuclease inhibitors synthetic lethality

Promising applications of D-amino acids in periprosthetic joint infection

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Bone Research 2023年第2期11卷 248-272页

作者： Matthew Caldwell megan Hughes Fei Wei Christopher Ngo Raven Pascua Abinaya Sindu Pugazhendhi Melanie J.Coathup Biionix Cluster&College of Medicine University of Central FloridaBlvdOrlandoFL32827USA School of Biosciences Cardiff UniversityCF103AT WalesUK Burnett School of Biomedical Sciences College of MedicineUniversity of Central Florida6900 Lake NonaBlvdOrlandoFL32827USA

Due to the rise in our aging population,a disproportionate demand for total joint arthroplasty(TJA)in the elderly is *** joint infection(PJI)represents one of the most challenging complications that can occur following TJA,and as the number of primary and revision TJAs continues to rise,an increasing PJI burden is *** advances in operating room sterility,antiseptic protocols,and surgical techniques,approaches to prevent and treat PJI remain difficult,primarily due to the formation of microbial *** difficulty motivates researchers to continue searching for an effective antimicrobial *** dextrorotatory-isoforms of amino acids(D-AAs)are essential components of peptidoglycan within the bacterial cell wall,providing strength and structural integrity in a diverse range of *** many tasks,D-AAs regulate cell morphology,spore germination,and bacterial survival,evasion,subversion,and adhesion in the host immune *** administered exogenously,accumulating data have demonstrated that D-AAs play a pivotal role against bacterial adhesion to abiotic surfaces and subsequent biofilm formation;furthermore,D-AAs have substantial efficacy in promoting biofilm *** presents D-AAs as promising and novel targets for future therapeutic *** their emerging antibacterial efficacy,their role in disrupting PJI biofilm formation,the disassembly of established TJA biofilm,and the host bone tissue response remains largely *** review aims to examine the role of D-AAs in the context of *** to date suggest that D-AA bioengineering may serve as a promising future strategy in the prevention and treatment of PJI.

关键词： prevention spite furthermore

Potentially traumatic events,coping strategies and associations with mental health and well-being measures among conflict-affected youth in Eastern Democratic Republic of Congo

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Global Health Research and Policy 2016年第1期1卷 54-71页

作者： megan Cherewick Shannon Doocy Wietse Tol Gilbert Burnham Nancy Glass Department of International Health Johns Hopkins Bloomberg School of Public Health615 N.Wolfe St.BaltimoreMD 21205USA Department of Mental Health Johns Hopkins Bloomberg School of Public Health624 N.BroadwayHH 863BaltimoreMD 21205USA Department of International Health Johns Hopkins School of NursingJohns Hopkins Center for Global Health615 N.Wolfe St.BaltimoreMD 21205USA

Background:Youth in conflict and post-conflict settings are exposed to a variety of potentially-traumatic events that impact their mental health and *** purposes of this study were to examine coping strategies among conflict-affected youth exposed to potentially-traumatic events and the relationship to psychological symptoms and well-being in the Democratic Republic of Congo(DRC).Methods:A total of 434 male and female youth(ages 10–15 years)completed data collection with a trained Congolese *** survey instrument included measures of exposure to potentially traumatic events,an adapted coping strategies checklist,and measures of psychosocial distress and *** factor analyses was used to identify coping strategies and Hierarchical regression was used to assess how coping strategies were associated with psychological symptoms including internalizing and externalizing problems and well-being outcomes including prosocial behavior and ***:Exploratory Factor analysis suggested four coping strategies;problem-focused,emotion-focused,avoidance and faith-based ***-focused coping strategies were associated with greater internalizing and externalizing problems and lower prosocial behavior in both boys and ***,when problem-focused strategies were used with emotion-focused coping strategies,the result was fewer internalizing problems in girls and fewer externalizing problems in boys and ***-focused,avoidance and faith based strategies were associated with better ***:These results suggest a complex relationship between coping strategies,psychological symptoms and well-being and contradict evidence that problem-focused strategies benefit mental health while emotion-focused strategies harm mental health,particularly in conflict and post-conflict *** results suggest coping flexibility,or use of multiple coping strategies may be particularly useful to improving mental

关键词： Conflict Trauma Coping Mental health Resilience Well-being