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Macrophage-targeted single walled carbon nanotubes stimulate phagocytosis via pH-dependent drug release

Nano Research 2021年第3期14卷 762-769页

作者： Yapei Zhang jianqin Ye Niloufar Hosseini-Nassab Alyssa Flores Irina Kalashnikova Sesha Lakshmi Paluri Mozhgan Lotfi nicholas j.leeper Bryan Ronain Smith Department of Biomedical Engineering Michigan State UniversityEast LansingMI48824USA Institute for Quantitative Health Science and Engineering Michigan State UniversityEast LansingMI48824USA Department of Surgery Division of Vascular SurgeryStanford University School of MedicineStanfordCA94305USA Department of Medicine Division of Cardiovascular MedicineStanford University School of MedicineStanfordCA94305USA Stanford Cardiovascular Institute StanfordCA94305USA Department of Radiology Stanford University School of MedicineStanfordCA94305USA

Atherosclerotic cardiovascular disease is the leading cause of mortality in the world.A driving feature of atherosclerotic plaque formation is dysfunctional *** the“don’t eat me”molecule CD47 is upregulated in atherosclerotic plaque cores,CD47-blocking strategies can stimulate the efferocytic clearance of apoptotic cells and thereby help prevent the progression of plaque ***,these therapies are generally costly and,in clinical and murine trials,they have resulted in side effects including anemia and ***,we developed and characterized an intracellular phagocytosis-stimulating treatment in the CD47-SIRPα*** loaded a novel monocyte/macrophage-selective nanoparticle carrier system with a small molecule enzymatic inhibitor that is released in a pH-dependent manner to stimulate macrophage efferocytosis of apoptotic cell debris via the CD47-SIRPαsignaling *** demonstrated that single-walled carbon nanotubes(SWNTs)can selectively deliver tyrosine phosphatase inhibitor 1(TPI)intracellularly to macrophages,which potently stimulates efferocytosis,and chemically characterized the ***,SWNT-delivered TPI can stimulate macrophage efferocytosis,with the potential to reduce or prevent atherosclerotic disease.

关键词： macrophages phagocytosis single-walled carbon nanotubes tyrosine phosphatase 1(SHP1)inhibitor atherosclerosis

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Classical bovine spongiform encephalopathy and chronic wasting disease:two sides of the prion coin

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Animal Diseases 2024年第1期4卷 1-18页

作者： nicholas j.Haley juergen A.Richt Department of Microbiology and Immunology College of Graduate StudiesMidwestern UniversityGlendaleAZUSA Department of Diagnostic Medicine/Pathobiology College of Veterinary MedicineKansas State UniversityManhattanKSUSA

Transmissible spongiform encephalopathies(TSEs)are a group of progressive and ultimately fatal neurologic diseases of man and animals,all resulting from the propagated misfolding of the host's normal cellular prion *** diseases can be spontaneous,heritable,anthropogenic/iatrogenic,or in some cases horizontally transmissible,and include such notable TSEs as bovine spongiform encephalopathy(BSE)of cattle and chronic wasting disease(CWD)of *** they are both unequivocally protein misfolding disorders,they differ markedly in their pathogenesis,transmissibility,and zoonotic *** the BSE epidemic has largely abated over the past three decades following global feed bans on ruminant meat and bone meal,CWD,which is readily transmitted through various forms of excreta,has rapidly expanded from its original endemic zone to encompass much of North America,along with recently identified foci in *** importantly,although the classical form of BSE has proven transmissible to humans consuming contaminated beef or beef products,so far there have been no conclusive reports on the zoonotic transmission of cWD to *** underlying basis for these differences-whether host or agent directed-are not well understood,though may be due to inherent differences in the three-dimensional structure of the misfolded BSE or CWD prion proteins or the expression levels and tissue distribution of respective cellular prion *** the uncontrolled geographic spread of CWD,it is imperative that we improve our understanding of the factors governing prion disease pathogenesis,transmission,and zoonotic potential.

关键词： Prion Bovine Spongiform Encephalopathy Chronic Wasting Disease Transmission Pathogenesis Zoonosis

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HDPairFinder:A data processing platform for hydrogen/deuterium isotopic labeling-based nontargeted analysis of trace-level amino-containing chemicals in environmental water

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journal of Environmental Sciences 2024年第2期136卷 583-593页

作者： Tingting Zhao Kristin Carroll Caley B.Craven nicholas j.P.Wawryk Shipei Xing jian Guo Xing-Fang Li Tao Huan Department of Chemistry Faculty of ScienceUniversity of British ColumbiaVancouver Campus2036 Main MallVancouverBritish ColumbiaV6T 1Z1Canada Division of Analytical and Environmental Toxicology Department of Laboratory Medicine and PathologyFaculty of Medicine and DentistryUniversity of AlbertaEdmontonAlberta T6G 2G3Canada

The combination of hydrogen/deuterium(H/D)formaldehyde-based isotopic methyl labeling with solid-phase extraction and high-performance liquid chromatography–high resolution mass spectrometry(HPLC-HRMS)is a powerful analytical solution for nontargeted analysis of trace-level amino-containing chemicals in water *** the huge amount of chemical information generated in HPLC-HRMS analysis,identifying all possible H/Dlabeled amino chemicals presents a significant challenge in data *** address this,we designed a streamlined data processing pipeline that can automatically extract H/D-labeled amino chemicals from the raw HPLC-HRMS data with high accuracy and ***,we developed a cross-correlation algorithm to correct the retention time shift resulting from deuterium isotopic effects,which enables reliable pairing of H-and D-labeled ***,we implemented several bioinformatic solutions to remove false chemical features generated by in-source fragmentation,salt adduction,and natural13C ***,we used a data mining strategy to construct the AMINES library that consists of over 38,000 structure-disjointed primary and secondary amines to facilitate putative compound ***,we integrated these modules into a freely available R program,*** rationale of each module was justified and its performance tested using experimental H/D-labeled chemical standards and authentic water *** further demonstrated the application of HDPairFinder to effectively extract N-containing contaminants,thus enabling the monitoring of changes of primary and secondary N-compounds in authentic water *** is a reliable bioinformatic tool for rapid processing of H/D isotopic methyl labeling-based nontargeted analysis of water samples,and will facilitate a better understanding of N-containing chemical compounds in water.

关键词： Isotope labeling Nontargeted analysis Reactive N-compounds HPLC-HRMS Source water

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Olympic Games and 24-hour movement behaviors:A match worth making

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journal of Sport and Health Science 2024年第6期13卷 728-731页

作者： Mark S.Tremblay nicholas Kuzik Markus j.Duncan Diego Augusto Santos Silva CHEO Research Institute OttawaON K1H 8L1Canada Department of Pediatrics University of OttawaOttawaON K1H 8L1Canada Federal University of Santa Catarina FlorianopolisSanta Catarina 88040-900Brazil

The Olympic motto,“Faster,Higher,Stronger—Together”,represents the pursuit of athletic excellence,united as a global community.“Excellence,respect and friendship”are the Olympic *** the motto and values are multifaceted and holistic in nature,and all-encompassing in their reach while recognizing no single entity rises above the ***,these foundational statements anchor the Olympic movement in its quest to build a better world through sport.

关键词： movement Together pursuit

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Towards precision 24-hour movement behavior recommendations—The next new paradigm?

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journal of Sport and Health Science 2024年第6期13卷 743-748页

作者： Mark S.Tremblay Markus j.Duncan nicholas Kuzik Diego Augusto Santos Silva Valerie Carson CHEO Research Institute OttawaON K1H 8L1Canada Department of Pediatrics University of OttawaOttawaON K1H 8L1Canada Federal University of Santa Catarina Santa Catarina 88040900Brazil Faculty of Kinesiology Sportand RecreationUniversity of AlbertaEdmontonAB T6G 2H9Canada

*** The importance of physical activity(PA)for health is unequivocal.^(1)Accordingly,population-based recommendations for exercise,and more recently public health guidelines for PA,have been developed and released by authoritative groups for many decades.^(2)Such guidelines emerged with leadership from the exercise physiology discipline and were rooted in,and loyal to,the importance of moderate-to-vigorous intensity PA(MVPA)or exercise.

关键词： movement behavior exercise

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Considerations for the use of porcine organ donation models in preclinical organ donor intervention research

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Animal Models and Experimental Medicine 2024年第3期7卷 283-296页

作者： Frazer I.Heinis Shaheed Merani nicholas W.Markin Kim F.Duncan Michael j.Moulton Lance Fristoe William E.Thorell Raechel A.Sherrick Tami R.Wells Matthew T.Andrews Marian Urban School of Natural Resources Institute of Agriculture and Natural ResourcesUniversity of Nebraska-LincolnLincolnNebraskaUSA Division of Transplantation and Vascular Surgery Department of SurgeryUniversity of Nebraska Medical CenterOmahaNebraskaUSA Department of Anesthesiology University of Nebraska Medical CenterOmahaNebraskaUSA Division of Cardiothoracic Surgery Department of SurgeryUniversity of Nebraska Medical CenterOmahaNebraskaUSA Clinical Perfusion Nebraska Medicine-Nebraska Medical CenterOmahaNebraskaUSA Department of Neurosurgery University of Nebraska Medical CenterOmahaNebraskaUSA Nutrition and Health Sciences College of Education and Human SciencesUniversity of Nebraska-LincolnLincolnNebraskaUSA Department of Comparative Medicine University of Nebraska Medical CenterOmahaNebraskaUSA

Use of animal models in preclinical transplant research is essential to the optimization of human allografts for clinical *** models of organ donation and preservation help to advance and improve technical elements of solid organ recovery and facilitate research of ischemia-reperfusion injury,organ preservation strategies,and future donor-based *** considerations include cost,public opinion regarding the conduct of animal research,translational value,and relevance of the animal model for clinical *** present an overview of two porcine models of organ donation:donation following brain death(DBD)and donation following circulatory death(DCD).The cardiovascular anatomy and physiology of pigs closely resembles those of humans,making this species the most appropriate for pre-clinical *** are also considered a potential source of organs for human heart and kidney *** is imperative to minimize animal loss during procedures that are surgically *** present our experience with these models and describe in detail the use cases,procedural approach,challenges,alternatives,and limitations of each model.

关键词： animal model brain death circulatory death organ transplantation

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Breaking the biotrophic interfacial complex:How genome editing can lead to rice blast resistance

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Molecular Plant 2023年第8期16卷 1243-1245页

作者： Vincent Were nicholas j.Talbot The Sainsbury Laboratory University of East AngliaNorwich Research ParkNorwich NR47UHUK

Genome editing is a transformational technology—by precisely altering the coding or regulatory sequence of a specific gene,it is now possible to change specific traits within a wide variety of *** a consequence,plant breeding can be taken to a new level of precision,and many countries are moving rapidly to adopt new legislation to permit genome editing(Greenwood et al.,2023).However,genome editing has so far seldom been used to develop disease-resistant *** is because plant immunity often depends on single dominant resistance genes,which encode immune receptors that recognize secreted effectors deployed by plant pathogens(jones and Dangl,2006).In this context,genetic modification has proven to be a much more powerful technology so far to introduce these genes from distinct varieties,or even different species,to develop disease resistant crop species(Greenwood et al.,2023),especially when multiple disease-resistance loci can be introduced together to provide more durable resistance(Luo et al.,2021).Genome editing can be used in an innovative way to resurrect previously effective resistance genes(Contreras et al.,2023),but it has been less effective at introducing new forms of disease resistance to crops.

关键词： breeding resistance editing

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Putting PLX5622 into perspective:microglia in central nervous system viral infection

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Neural Regeneration Research 2023年第6期18卷 1269-1270页

作者： Alanna G.Spiteri nicholas j.C.King Viral Immunopathology Laboratory InfectionImmunity and Inflammation Research ThemeSchool of Medical SciencesFaculty of Medicine and HealthThe University of SydneySydneyNSWAustralia Sydney Cytometry The University of Sydney and Centenary InstituteSydneyNSWAustralia Ramaciotti Facility for Human Systems Biology The University of Sydney and Centenary InstituteSydneyNSWAustralia Charles Perkins Centre The University of SydneyAustralia The University of Sydney Institute for Infectious Diseases The University of SydneySydneyNSWAustralia The University of Sydney Nano Institute the University of SydneySydneyNSWAustralia

Elucidating the exact contribution of microglia to central nervous system(CNS)pathology has historically been extremely *** resident parenchymal myeloid cells are considered to have critical roles as frontline responders during pathogen invasion and CNS ***,understanding the precise temporal kinetics of microglial function is central to the evolution of novel therapeutics for disease intervention and/or resolution(Spiteri et al.,2022a).The development of PLX5622,a colony-stimulating factor 1 receptor(CSF-1R)inhibitor typically formulated into a rodent chow for simple oral administration has facilitated exploration of microglial functions in disease(Spangenberg et al.,2019).

关键词： invasion system precise

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Shedding light on neurons:optical approaches for neuromodulation

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National Science Review 2022年第10期9卷 34-54页

作者： Shan jiang Xiang Wu nicholas j.Rommelfanger Zihao Ou Guosong Hong Department of Materials Science and Engineering Stanford University Wu Tsai Neurosciences Institute Stanford University Department of Applied Physics Stanford University

Today’ s optical neuromodulation techniques are rapidly evolving,benefiting from advances in photonics,genetics and materials *** this review,we provide an up-to-date overview of the latest optical approaches for *** begin with the physical principles and constraints underlying the interaction between light and neural *** then present advances in optical neurotechnologies in seven modules:conventional optical fibers,multifunctional fibers,optical waveguides,light-emitting diodes,upconversion nanoparticles,optical neuromodulation based on the secondary effects of light,and unconventional light sources facilitated by ultrasound and magnetic *** conclude our review with an outlo ok on new methods and mechanisms that afford optical neuromodulation with minimal invasiveness and footprint.

关键词： optical neuromodulation optogenetics neural interfaces

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Role of c-Myc in lung cancer:Progress,challenges,and prospects

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Chinese Medical journal Pulmonary and Critical Care Medicine 2023年第3期1卷 129-138页

作者： nicholas j.Wallbillich Hua Lu Department of Biochemistry and Molecular Biology Tulane University School of Medicine1430 Tulane AvenueNew OrleansLA 70112USA Tulane Cancer Center Tulane University School of Medicine1700 Tulane AvenueNew OrleansLA 70112USA

Lung cancer remains the leading cause of cancer-related deaths *** the recent advances in cancer therapies,the 5-year survival of non-small cell lung cancer(NSCLC)patients hovers around 20%.Inherent and acquired resistance to therapies(including radiation,chemotherapies,targeted drugs,and combination therapies)has become a significant obstacle in the successful treatment of NSCLC.c-Myc,one of the critical oncoproteins,has been shown to be heavily associated with the malignant cancer phenotype,including rapid proliferation,metastasis,and chemoresistance across multiple cancer *** c-Myc proto-oncogene is amplified in small cell lung cancers(SCLCs)and overexpressed in over 50%of NSCLCs.c-Myc is known to actively regulate the tran-scription of cancer stemness genes that are recognized as major contributors to tumor progression and therapeutic resistance;thus,targeting c-Myc either directly or indirectly in mitigation of the cancer stemness phenotype be-comes a promising approach for development of a new strategy against drug resistant lung *** review will summarize what is currently known about the mechanisms underlying c-Myc regulation of cancer stemness and its involvement in drug resistance and offer an overview on the current progress and future prospects in therapeutically targeting c-Myc in both SCLC and NSCLC.

关键词： Cancer dormancy Cancer stem cells c-Myc Drug resistance Epidermal growth factor receptor Lung cancer Non-small cell lung cancer Small cell lung cancer

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