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Signal Transduction and Targeted Therapy 2023年第3期8卷 905-907页

作者： Shao-bin Wang Yosuke Nagasaka dionne Argyle Ayami Nagasaka Praveen Yerramothu bradley dgelfand Jayakrishna Ambati Center for Advanced Vision Science University of Virginia School of MedicineCharlottesvilleVAUSA department of Ophthalmology University of Virginia School of MedicineCharlottesvilleVAUSA department of Biomedical Engineering University of Virginia School of MedicineCharlottesvilleVAUSA department of Pathology University of Virginia School of MedicineCharlottesvilleVAUSA department of Microbiology Immunologyand Cancer BiologyUniversity of Virginia School of MedicineCharlottesvilleVAUSA

dear Editor,Vascular endothelial growth factor-A(VEGFA,also known as VEGF)is a critical angiogenic factor that regulates the physiological and pathological blood vessel growth.1 Increased abundance of VEGF in the eye underlies many forms of aberrant ocular angiogenesis and resultant vision loss,including in neovascular age-related macular degeneration(nvAMd),proliferative diabetic retinopathy(PdR).

关键词： degeneration ocular release

Nucleoside reverse transcriptase inhibitors and Kamuvudines inhibit amyloid-βinduced retinal pigmented epithelium degeneration

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Signal Transduction and Targeted Therapy 2021年第5期6卷 1526-1534页

作者： Siddharth Narendran Felipe Pereira Praveen Yerramothu Ivana Apicella Shao-bin Wang Kameshwari Ambati Shuichiro Hirahara Younghee Kim Meenakshi Ambati Vidya L.Ambati Peirong Huang Akhil Varshney Yosuke Nagasaka Shinichi Fukuda Kirstie L.Baker Kenneth M.Marion Jan M.deussing Srinivas R.Sadda bradley d.gelfand Jayakrishna Ambati Center for Advanced Vision Science University of Virginia School of MedicineCharlottesvilleVAUSA department of Ophthalmology University of Virginia School of MedicineCharlottesvilleVAUSA Aravind Eye Care System MaduraiIndia departamento de Oftalmologia e Ciências Visuais Escola Paulista de MedicinaUniversidade Federal de São PauloSão PauloBrazil Center for digital Image Evaluation CharlottesvilleVAUSA doheny Eye Institute Los AngelesLos AngelesCAUSA Molecular Neurogenetics Department of Stress Neurobiology and NeurogeneticsMax Planck Institute of PsychiatryMunichGermany department of Ophthalmology David Geffen School of MedicineUniversity of California–Los AngelesLos AngelesCAUSA department of Biomedical Engineering University of Virginia School of MedicineCharlottesvilleVAUSA department of Pathology University of Virginia School of MedicineCharlottesvilleVAUSA department of Microbiology Immunologyand Cancer BiologyUniversity of Virginia School of MedicineCharlottesvilleVAUSA

Nonfibrillar amyloid-βoligomers(AβOs)are a major component of drusen,the sub-retinal pigmented epithelium(RPE)extracellular deposits characteristic of age-related macular degeneration(AMd),a common cause of global *** report that AβOs induce RPE degeneration,a clinical hallmark of geographic atrophy(GA),a vision-threatening late stage of AMd that is currently *** demonstrate that AβOs induce activation of the NLRP3 inflammasome in the mouse RPE in vivo and that RPE expression of the purinergic ATP receptor P2RX7,an upstream mediator of NLRP3 inflammasome activation,is required for AβO-induced RPE *** classes of small molecule inflammasome inhibitors—nucleoside reverse transcriptase inhibitors(NRTIs)and their antiretrovirally inert modified analog Kamuvudines—both inhibit AβOs-induced RPE *** findings crystallize the importance of P2RX7 and NLRP3 in a disease-relevant model of AMd and identify inflammasome inhibitors as potential treatments for GA.

关键词： degeneration activation upstream

Recent developments in Metallic degradable Micromotors for Biomedical and Environmental Remediation Applications

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Nano-Micro Letters 2024年第3期16卷 1-35页

作者： Sourav dutta Seungmin Noh Roger Sanchis Gual Xiangzhong Chen Salvador Pané bradley J.Nelson Hongsoo Choi department of Robotics and Mechatronics Engineering Daegu Gyeongbuk Institute of Science and Technology(DGIST)Daegu 42988Republic of Korea dGIST‑ETH Microrobotics Research Center DGISTDaegu 42988Republic of Korea Multi‑Scale Robotics Lab Institute of Robotics and Intelligent SystemsETH Zurich8092 ZurichSwitzerland Institute of Optoelectronics State Key Laboratory of Photovoltaic Science and TechnologyShanghai Frontiers Science Research Base of Intelligent Optoelectronics and PerceptionFudan UniversityShanghai 200433People’s Republic of China

Synthetic micromotor has gained substantial attention in biomedicine and environmental ***-based degradable micromotor composed of magnesium(Mg),zinc(Zn),and iron(Fe)have promise due to their nontoxic fuel-free propulsion,favorable biocompatibility,and safe excretion of degradation products Recent advances in degradable metallic micromotor have shown their fast movement in complex biological media,efficient cargo delivery and favorable biocompatibility.A noteworthy number of degradable metal-based micromotors employ bubble propulsion,utilizing water as fuel to generate hydrogen *** novel feature has projected degradable metallic micromotors for active in vivo drug delivery *** addition,understanding the degradation mechanism of these micromotors is also a key parameter for their design and *** propulsion efficiency and life span govern the overall performance of a degradable metallic *** we review the design and recent advancements of metallic degradable ***,we describe the controlled degradation,efficient in vivo drug delivery,and built-in acid neutralization capabilities of degradable micromotors with versatile biomedical ***,we discuss micromotors’efficacy in detecting and destroying environmental ***,we address the limitations and future research directions of degradable metallic micromotors.

关键词： Magnesium Zinc Iron Biodegradable microrobot Biomedical Environmental

Intravenous immune globulin suppresses angiogenesis in mice and humans

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Signal Transduction and Targeted Therapy 2016年第1期1卷 141-148页

作者： Reo Yasuma Valeria Cicatiello Takeshi Mizutani Laura Tudisco Younghee Kim Valeria Tarallo Sasha Bogdanovich Yoshio Hirano Nagaraj Kerur Shengjian Li Tetsuhiro Yasuma Benjamin J Fowler Charles B Wright Ivana Apicella Adelaide Greco Arturo Brunetti Balamurali K Ambati Sevim Barbasso Helmers Ingrid E Lundberg Ondrej Viklicky Jeanette HW Leusen J Sjef Verbeek bradley d gelfand Ana Bastos-Carvalho Sandro de Falco Jayakrishna Ambati department of Ophthalmology and Visual Sciences University of KentuckyLexingtonKYUSA department of Ophthalmology Nagoya University Graduate School of MedicineNagoyaJapan Angiogenesis Lab Institute of Genetics and Biophysics—CNRNaplesItaly Bio-Ker MultiMedica GroupNaplesItaly department of Physiology University of KentuckyLexingtonKYUSA department of Advanced Biomedical Sciences University of Naples‘Federico II’NaplesItaly CEINGE—Biotecnologie Avanzate s.c.ar.l.NaplesItaly department of Ophthalmology and Visual Sciences Moran Eye CenterUniversity of Utah School of MedicineSalt Lake CityUTUSA department of Ophthalmology Veterans Affairs Salt Lake City Healthcare SystemSalt Lake CityUTUSA Rheumatology Unit Department of MedicineKarolinska InstitutetKarolinska University HospitalStockholmSweden department of Nephrology Institute for Clinical and Experimental MedicinePrague 4Czech Republic Immunotherapy Laboratory Laboratory for Translational ImmunologyUniversity Medical Center UtrechtUtrechtThe Netherlands department of Human Genetics Leiden University Medical CenterLeidenThe Netherlands department of Biomedical Engineering University of KentuckyLexingtonKYUSA department of Microbiology Immunologyand Molecular GeneticsUniversity of KentuckyLexingtonKYUSA IRCCS MultiMedica MilanoItaly

Human intravenous immune globulin(IVIg),a purified IgG fraction composed of~60%IgG1 and obtained from the pooled plasma of thousands of donors,is clinically used for a wide range of *** biological actions of IVIg are incompletely understood and have been attributed both to the polyclonal antibodies therein and also to their IgG(IgG)Fc ***,we demonstrated that multiple therapeutic human IgG1 antibodies suppress angiogenesis in a target-independent manner via FcγRI,a high-affinity receptor for *** we show that IVIg possesses similar anti-angiogenic activity and inhibited blood vessel growth in five different mouse models of prevalent human diseases,namely,neovascular age-related macular degeneration,corneal neovascularization,colorectal cancer,fibrosarcoma and peripheral arterial ischemic *** was mediated by the Fc region of IVIg,required FcγRI and had similar potency in transgenic mice expressing human Fcγ***,IVIg therapy administered to humans for the treatment of inflammatory or autoimmune diseases reduced kidney and muscle blood vessel *** data place IVIg,an agent approved by the US Food and drug Administration,as a novel angioinhibitory drug in doses that are currently administered in the clinical *** addition,they raise the possibility of an unintended effect of IVIg on blood vessels.

关键词： doses inhibited degeneration

Human IgG1 antibodies suppress angiogenesis in a target-independent manner

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Signal Transduction and Targeted Therapy 2016年第1期1卷 158-171页

作者： Sasha Bogdanovich Younghee Kim Takeshi Mizutani Reo Yasuma Laura Tudisco Valeria Cicatiello Ana Bastos-Carvalho Nagaraj Kerur Yoshio Hirano Judit Z Baffi Valeria Tarallo Shengjian Li Tetsuhiro Yasuma Parthasarathy Arpitha Benjamin J Fowler Charles B Wright Ivana Apicella Adelaide Greco Arturo Brunetti Menotti Ruvo Annamaria Sandomenico Miho Nozaki Ryo Ijima Hiroki Kaneko Yuichiro Ogura Hiroko Terasaki Balamurali K Ambati Jeanette HW Leusen Wallace Y Langdon Michael R Clark Kathryn L Armour Pierre Bruhns J Sjef Verbeek bradley d gelfand Sandro de Falco Jayakrishna Ambati department of Ophthalmology and Visual Sciences University of KentuckyLexingtonKYUSA department of Ophthalmology and Visual Science Nagoya City University Graduate School of Medical SciencesNagoyaJapan department of Ophthalmology Nagoya University Graduate School of MedicineNagoyaJapan Angiogenesis Lab Institute of Genetics and Biophysics—CNRNaplesItaly Bio-Ker MultiMedica GroupNaplesItaly department of Advanced Biomedical Sciences University of Naples‘Federico II’NaplesItaly CEINGE—Biotecnologie Avanzate s.c.a.r.l.NaplesItaly Istituto di Biostrutture e Bioimmagini CNRNaplesItaly department of Ophthalmology and Visual Sciences Moran Eye CenterUniversity of Utah School of MedicineSalt Lake CityUTUSA department of Ophthalmology Veterans Affairs Salt Lake City Healthcare SystemSalt Lake CityUTUSA Immunotherapy Laboratory Laboratory for Translational ImmunologyUniversity Medical Center UtrechtUtrechtThe Netherlands School of Pathology and Laboratory Medicine University of Western AustraliaCrawleyWAAustralia division of Immunology Department of PathologyUniversity of CambridgeCambridgeUK department of Immunology Unit of Antibodies in Therapy and PathologyInstitut PasteurParisFrance Institut National de la Santéet de la Recherche Médicale(INSERM)U1222 ParisFrance department of Human Genetics Leiden University Medical CenterLeidenThe Netherlands department of Biomedical Engineering University of KentuckyLexingtonKYUSA department of Microbiology Immunologyand Molecular GeneticsUniversity of KentuckyLexingtonKYUSA IRCCS MultiMedica MilanoItaly department of Physiology University of KentuckyLexingtonKYUSA.

Aberrant angiogenesis is implicated in diseases affecting nearly 10%of the world’s *** most widely used antiangiogenic drug is bevacizumab,a humanized IgG1 monoclonal antibody that targets human *** bevacizumab does not recognize mouse Vegfa,it inhibits angiogenesis in *** we show bevacizumab suppressed angiogenesis in three mouse models not via Vegfa blockade but rather Fc-mediated signaling through FcγRI(Cd64)and c-Cbl,impairing macrophage *** approved humanized or human IgG1 antibodies without mouse targets(adalimumab,alemtuzumab,ofatumumab,omalizumab,palivizumab and tocilizumab),mouse IgG2a,and overexpression of human IgG1-Fc or mouse IgG2a-Fc,also inhibited angiogenesis in wild-type and FcγR humanized *** anti-angiogenic effect was abolished by Fcgr1 ablation or knockdown,Fc cleavage,IgG-Fc inhibition,disruption of Fc-FcγR interaction,or elimination of FcRγ-initated ***,bevacizumab’s Fc region potentiated its anti-angiogenic activity in humanized VEGFA ***,mice deficient in FcγRI exhibited increased developmental and pathological *** findings reveal an unexpected anti-angiogenic function for FcγRI and a potentially concerning off-target effect of hIgG1 therapies.

关键词： Cd64 angiogenesis antibodies

The silent spermatozoon： are man-made endocrine disruptors killing male fertility？

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Asian Journal of Andrology 2013年第2期15卷 165-168,I0004页

作者： bradley d Anawalt department of Medicine University of Washington Seattle WA 98195 USA

In 1992, a danish group led by Skakkebaek , reported in a meta-analysis that global mean sperm counts were fallingandthat testicular cancer, hypospadias and cryptorchidism were increasing. They hypothesized that environmental factors were the cause. Their rectaanalysis was criticized subsequently for many methodological flaws. However, their controversial metamlysls and hypothesis spurred pubfic and scientific interest in the study of male reproductive function and stimulated more rigorous scientific work in the area. Subsequent research has not convincingly supported their hypothesis, However, it is caudal to continue high quality studies of the effects of drugs and manmade pollutants on male eeproductlve function.

关键词： dETERIORATING SEMEN QUALITY SPERM COUNTS REFERENCE VALUES INFERTILE MEN NO EVIdENCE dANISH MEN HEALTHY PERIOd dECLINE OBESITY

Growth and competition among understory plants varies with reclamation soil and fertilization

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Ecological Processes 2018年第1期7卷 116-123页

作者： Jennifer Buss Kyle Stratechuk bradley d.Pinno department of Renewable Resources University of AlbertaEdmontonAlbertaCanada

Introduction:Following oil sands mining in Alberta,Canada,the main land management goal is to establish a functioning boreal forest ecosystem,including the understory plant *** of the challenges with restoring the understory is the presence of non-native species that compete with desirable native species for *** a greenhouse experiment,we studied the growth of two native understory species(Galium boreale and Vicia americana)and a non-native invasive species(Matricaria perforata)grown with either intra-or interspecific neighbors across three common land reclamation soils and a nitrogen fertilizer ***:When grown by itself,*** aboveground biomass did not differ among soil or fertilizer treatments,likely due to its ability to fix *** of *** was directly related to soil nitrogen,and it had the greatest increase in biomass with *** and biomass of *** was less than the other species,and it had the highest mortality in the nitrogen-poor *** grown together,the proportional biomass of *** and *** varied with soil treatment such that *** was dominant in the high-nitrogen forest floormineral mix treatment while *** was dominant in the low-nitrogen peat-mineral ***:Operationally,care should be taken when applying fertilizer to reclamation areas,as it may have an unwanted positive effect on growth for undesirable non-native plants at the expense of native *** terms of seed mixtures,*** may be a good option for low inorganic nitrogen resource soils and *** for high nitrogen resource soils.

关键词： Matricaria perforata Galium boreale Vicia americana Forest floor-mineral mix Peat-mineral mix Oil sands reclamation

Why is understanding the relationship of testosterone to cardiovascular risk so important？

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Asian Journal of Andrology 2018年第2期20卷 107-108页

作者： Bu B Yeap bradley d Anawalt School of Medicine University of Western Australia Perth Western Australia 6009 Australia department of Endocrinology and diabetes Fiona Stanley Hospital Perth Western Australia 6150 Australia department of Medicine University of Washington School of Medicine Seattle Washington 98195 United States

Epidemiological studies hint at a beneficial influence of endogenous circulating testosterone （T）, or its metabolite dihydrotestosterone （dHT）, such that men with lower concentrations of T or dHT appear to have po... 详细信息

关键词： AUSTRALIA POSITION STATEMENT OLdER MEN MYOCARdIAL-INFARCTION ENdOCRINE-SOCIETY THERAPY ASSOCIATION MORTALITY

Conclusions about testosterone therapy and cardiovascular risk

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Asian Journal of Andrology 2018年第2期20卷 152-153页

作者： bradley d Anawalt Bu B Yeap division of Medicine University of Washington School of Medicine Seattle Washington 98195 United States School of Medicine University of Western Australia Perth Western Australia 6009 Australia department of Endocrinology and diabetes Fiona Stanley Hospital Perth Western Australia 6150 Australia

In this issue of Asian Journal of Andrology （AJA）, several experts have reviewed L the latest data on the potential and known effects of endogenous and exogenous testosterone （T） on cardiovascular risk. In the review by Meyer and Wittert, low endogenous serum T appears to be associated with higher risk of cardiovascular disease and overall mortality in certain populations such as Klinefelter syndrome and older men,

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Where physics meets chemistry： Thin film deposition from reactive plasmas

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Frontiers of Chemical Science and Engineering 2016年第4期10卷 441-458页

作者： Andrew Michelmore Jason d. Whittle James W. bradley Robert d. Short School of Engineering University of South Australia Mawson Lakes Australia SA 5095 Future Industries Institute University of South Australia Mawson Lakes Australia SA 5095 department of Electrical Engineering and Electronics University of Liverpool Liverpool L69 3GJ UK Material Science Institute Lancaster University Lancaster LA1 4YW UK

Functionalising surfaces using polymeric thin films is an industrially important field. One technique for achieving nanoscale, controlled surface functionalization is plasma deposition. Plasma deposition has advantages over other surface engineering processes, including that it is solvent free, substrate and geometry independent, and the surface properties of the film can be designed by judicious choice of precursor and plasma conditions. despite the utility of this method, the mechanisms of plasma polymer growth are generally unknown, and are usually described by chemical （i.e., radical） pathways. In this review, we aim to show that plasma physics drives the chemistry of the plasma phase, and surface-plasma interactions. For example, we show that ionic species can react in the plasma to form larger ions, and also arrive at surfaces with energies greater than 1000 kJ·mol^-1 （〉10 eV） and thus facilitate surface reactions that have not been taken into account previously. Thus, improving thin film deposition processes requires an understanding of both physical and chemical processes in plasma.

关键词： thin films plasma physics plasma chemistry,functionalization polymer