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Cytoplasmic DNA: sources, sensing, and role in aging and disease

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四川生理科学杂志 2024年第4期46卷 89-89页

作者： karl N Miller Aging Cancer and Immuno-oncology Program Sanford Burnham Prebys Medical Discovery Institute La Jolla CA 92037 USA Department of Physiology and Biomedical Engineering Mayo Clinic Rochester MN 55905 USA

Endogenous cytoplasmic DNA(cytoDNA)species are emerging as key mediators of inflammation in diverse physiological and pathological *** the role of endogenous cytoDNA in innate immune activation is well established,the cytoDNA species themselves are often poorly characterized and difficult to distinguish,and their mechanisms of formation,scope of function and contribution to disease are incompletely understood.

关键词： endogenous inflammation incomplete

Monogenic deficiency in murine intestinal Cdc42 leads to mucosal inflammation that induces crypt dysplasia

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Genes & Diseases 2024年第1期11卷 413-429页

作者： Dongsheng Zhang Wenjuan Tang Haitao Niu William Tse Hai-Bin Ruan Helmut Dolznig Thomas Knosel friedrich karl-Heinz Madeleine Themanns Jiang Wang Mingquan Song Lee Denson Lukas Kenner Richard Moriggl Yi Zheng Xiaonan Han Division of Hematology and Oncology Division of Cancer BiologyDepartment of MedicineMetroHealth Medical Center(MHMC)Case Western Reserve University(CWRU)School of MedicineClevelandOH 44109USA Cancer Genomics and Epigenomics Program Case Comprehensive Cancer CenterCase Western Reserve University(CWRU)ClevelandOH 44106USA Division of Gastroenterology Hepatology and NutritionCincinnati Children’s Hospital Medical Center(CCHMC)CincinnatiOH 45229USA Children’s Hospital of fudan University Shanghai 201102China School of Medicine Jinan UniversityGuangzhouGuangdong 510632China Laboratory Animal Science(ILAS) Chinese Academy of Medical Science(CAMS)and Peking Union Medical College(PUMC)Beijing 100006China Department of Integrative Biology and Physiology University of Minnesota Medical SchoolMinneapolisMI 55455USA Institute of Medical Genetics Medical University of ViennaVienna 1040Austria Institute of Pathology Ludwig-Maximilians-University MunichMunich 80539Germany Institute of Biochemistry II University Hospital JenaJena 07743Germany Laboratory Animal Pathology University of Veterinary Medicine ViennaVienna 1210Austria Department of Pathology University of CincinnatiCincinnatiOH 45221USA Department of Gastroenterology The Affiliated Hospital of Qingdao UniversityQingdaoShandong 266005China Department of Pathology Medical University of ViennaVienna 1040Austria Ludwig Boltzmann Institute for Cancer Research Vienna 1090Austria Medical University of Vienna Vienna 1040Austria Institute of Animal Breeding and Genetics University of Veterinary Medicine ViennaVienna 1210Austria Division of Experimental Hematology CCHMCCincinnatiOH 45229USA

CDC42 controls intestinal epithelial(IEC)stem cell(IESC)*** aberrant CDC42 initiates intestinal inflammation or neoplasia is *** utilized models of inflam-matory bowel diseases(IBD),colorectal cancer,aging,and IESC injury to determine the loss of intestinal Cdc42 upon inflammation and *** specimens were collected to determine the levels of CDC42 in IBD or colorectal ***42 floxed mice were crossed with Villin-Cre,Villin-CreERT2 and/or Lgr5-eGfP-IRES-CreERT2,or Bmi1-CreERT2 mice to generate Cdc42 deficient ***,colitis,aging,and intestinal organoid were used to evaluate CDC42 upon mucosal inflammation,IESC/progenitor regenerative capacity,and IEC *** studies revealed that increased CDC42 in colorectal cancer correlated with lower survival;in contrast,lower levels of CDC42 were found in the inflamed IBD *** Cdc42 depletion significantly reduced Lgr5+IEsCs,increased progenitors'hyperplasia,and induced mucosal inflammation,which led to crypt *** Cdc42 depletion markedly enhanced irra-diation-or chemical-induced *** or inhibition of Cdc42 reduced colonic Lgr5+IESC *** conclusion,depletion of Cdc42 reduces the IESC regeneration and IEC repair,leading to prolonged mucosal *** monogenic loss of Cdc42 in-duces mucosal inflammation,which could result in intestinal neoplasia in the context of aging.

关键词： Cell divisioncycle 42(CDC42) Colitis Colorectal cancer(CRC) Inflammatory bowel diseases(IBD) Intestinal epithelial cell(IEC) Intestinal epithelial stem cell(IESC) Irradiation

An active self-cleaning surface system for photovoltaic modules using anisotropic ratchet conveyors and mechanical vibration

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Microsystems & Nanoengineering 2020年第1期6卷 413-424页

作者： Di Sun karl f.Bohringer Department of Electrical and Computer Engineering University of WashingtonSeattleWA 98195USA Institute for Nano-Engineered Systems University of WashingtonSeattleWA 98195USA

The purpose of this work is to develop an active self-cleaning system that removes contaminants from a solar module surface by means of an automatic,water-saving,and labor-free *** output efficiency of a solar module can be degraded over time by dust accumulation on top of the cover glass,which is often referred to as“soiling”.This paper focuses on creating an active self-cleaning surface system using a combination of microsized features and mechanical *** features,which are termed anisotropic ratchet conveyors(ARCs),consist of hydrophilic curved rungs on a hydrophobic *** different ARC systems have been designed and fabricated with self-assembled monolayer(SAM)silane and fluoropolymer thin film(Cytop).fabrication processes were established to fabricate these two systems,including patterning Cytop without degrading the original Cytop *** droplet transport characteristics,including anisotropic driving force,droplet resonance mode,cleaning mechanisms,and system power consumption,were studied with the help of a high-speed camera and custom-made test *** droplet can be transported on the ARC surface at a speed of 27 mm/s and can clean a variety of dust particles,either water-soluble or *** transmission was measured to show that Cytop can improve transmittance by 2.5~3.5%across the entire visible wavelength ***-time demonstrations of droplet transport and surface cleaning were performed,in which the solar modules achieved a 23 percentage-point gain after cleaning.

关键词： anisotropic cleaning remove

Superior antibody and membrane protein‑specific T‑cell responses to CoronaVac by intradermal versus intramuscular routes in adolescents

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World Journal of Pediatrics 2024年第4期20卷 353-370页

作者： Jaime S.Rosa Duque Samuel M.S.Cheng Carolyn A.Cohen Daniel Leung Xiwei Wang Xiaofeng Mu Yuet Chung Tsun Ming Lau Manni Wang Wenyue Zhang Yanmei Zhang Howard H.W.Wong Leo C.H.Tsang Sara Chaothai Tsz Chun Kwan John K.C.Li karl C.K.Chan Leo L.H.Luk Jenson C.H.Ho Wing Yan Li Amos M.T.Lee Jennifer H.Y.Lam Sau Man Chan Wilfred H.S.Wong Issan Y.S.Tam Masashi Mori Sophie A.Valkenburg Malik Peiris Wenwei Tu Yu Lung Lau Department of Paediatrics and Adolescent Medicine The University of Hong KongHong KongChina School of Public Health The University of Hong KongHong KongChina HKU‑Pasteur Research Pole School of Public HealthThe University of Hong KongHong KongChina Research Institute for Bioresources and Biotechnology Ishikawa Prefectural UniversityNonoichiJapan Department of Microbiology and Immunology Peter Doherty Institute for Infectionand ImmunityUniversity of MelbourneMelbourneVICAustralia Center for Immunology and Infection C2i Hong KongChina

Background Optimising the immunogenicity of COVID-19 vaccines to improve their protection against disease is *** dosing by intradermal(ID)administration has been shown to be equally immunogenic as intramuscular(IM)administration for several vaccines,but the immunogenicity of ID inactivated whole severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)at the full dose is *** study(NCT04800133)investigated the superiority of antibody and T-cell responses of full-dose CoronaVac by ID over IM administration in *** Participants aged 11–17 years received two doses of IM or ID vaccine,followed by the 3rd dose 13–42 days *** and cellular immunogenicity outcomes were measured post-dose 2(IM-CC versus ID-CC)and post-dose 3(IMCCC versus ID-CCC).Doses 2 and 3 were administered to 173 and 104 adolescents,*** Spike protein(S)immunoglobulin G(IgG),S-receptor-binding domain(RBD)IgG,S IgG fcγreceptor IIIa(fcγRIIIa)-binding,SNM[sum of individual(S),nucleocapsid protein(N),and membrane protein(M)peptide pool]-specific interleukin-2(IL-2)+CD4^(+),SNM-specific IL-2^(+)CD8^(+),S-specific IL-2^(+)CD8^(+),N-specific IL-2^(+)CD4^(+),N-specific IL-2^(+)CD8^(+)and M-specific IL-2^(+)CD4^(+)responses fulfilled the superior and non-inferior criteria for ID-CC compared to IM-CC,whereas IgG avidity was *** ID-CCC,S-RBD IgG,surrogate virus neutralisation test,90%plaque reduction neutralisation titre(PRNT90),PRNT50,S IgG avidity,S IgG fcγRIIIa-binding,M-specific IL-2^(+)CD4^(+),interferon-γ+CD8^(+)and IL-2^(+)CD8^(+)responses were superior and non-inferior to *** estimated vaccine efficacies were 49%,52%,66%and 79%for IM-CC,ID-CC,IM-CCC and ID-CCC,*** ID groups reported more local,mild adverse *** This is the first study to demonstrate superior antibody and M-specific T-cell responses by ID inactivated SARSCoV-2 vaccination and serves as the basis for future research to improve the

关键词： CoronaVac Coronavirus disease 2019 Immunity Intradermal Vaccine

Is PAWP the ＂real＂ sperm factor？

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Asian Journal of Andrology 2015年第3期17卷 444-446页

作者： Michail Nomikos karl Swann f Anthony Lai Institute of Molecular and Experimental Medicine School of Medicine Cardiff University Cardiff UK

Mammalian embryo development is initiated by intracellular Ca2＋ oscillations that result in oocyte activation following gamete membrane fusion. It is widely believed that oocyte Ca2＋ oscillations are triggered by a sperm-specific protein, phospholipase C-zeta （PLCζ） that activates InsP3 production leading to repetitive Ca2. release from intracellular stores. However, a recent report in the fASEB Journal by Aarabi et al. challenges this view by proposing postacrosomal WW domain-binding protein （PAWP） as another sperm-derived protein that can also initiate Ca2＋ oscillations and zygotic development at fertilization. Here we discuss these new findings and examine the evidence suggesting PAWP as the ＂real＂ sperm factor.

关键词： PHOSPHOLIPASE-C-ZETA DOMAIN-BINDING-PROTEIN CA2+ OSCILLATIONS OOCYTE ACTIVATION EGG ACTIVATION CALCIUM OSCILLATIONS PLC-ZETA RELEASE fERTILIZATION INITIATE

Multimodal 4-arylchromene derivatives with microtubule-destabilizing,anti-angiogenic,and MYB-inhibitory activities

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Cancer Drug Resistance 2023年第1期6卷 59-77页

作者： Leonhard H.f.Kohler Sebastian Reich Maria Yusenko karl-Heinz Klempnauer Gerrit Begemann Rainer Schobert Bernhard Biersack Organic Chemistry Laboratory University of BayreuthBayreuth 95440Germany Institute for Biochemistry Westfalische-Wilhelms-UniversitatMunster 48149Germany Developmental Biology University of BayreuthBayreuth 95440Germany

Aim:Efficient and readily available anticancer drugs are sought as treatment *** this reason,chromene derivatives were prepared using the one-pot reaction and tested for their anticancer and anti-angiogenic ***:2-Amino-3-cyano-4-(aryl)-7-methoxy-4H-chromene compounds(2A-R)were repurposed or newly synthesized via a three-component reaction of 3-methoxyphenol,various aryl aldehydes,and *** performed assays to study the inhibition of tumor cell growth[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromid(MTT)assay],effects on microtubules(immunofluorescence),cell cycle(flow-activated cell sorting analysis),angiogenesis(zebrafish model),and MYB activity(luciferase reporter assay).fluorescence microscopy was applied for localization studies via copper-catalyzed azide-alkyne click reaction of an alkyne-tagged drug ***:Compounds 2A-C and 2f exhibited robust antiproliferative activities against several human cancer cell lines(50%inhibitory concentrations in the low nanomolar range)and showed potent MYB *** alkyne derivative 3 was localized in the cytoplasm after only 10 min of *** microtubule disruption and G2/M cell-cycle arrest were observed,where compound 2f stood out as a promising microtubule-disrupting *** study of anti-angiogenic properties showed that 2A was the only candidate with a high potential to inhibit blood vessel formation in ***:The close interplay of various mechanisms,including cell-cycle arrest,MYB inhibition,and anti-angiogenic activity,led to identifying promising multimodal anticancer drug candidates.

关键词： Chromene pyran anticancer drugs microtubule angiogenesis MYB inhibition

MEMS-actuated metasurface Alvarez lens

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Microsystems & Nanoengineering 2020年第1期6卷 334-344页

作者： Zheyi Han Shane Colburn Arka Majumdar karl f.Bohringer Department of Electrical and Computer Engineering University of WashingtonSeattleWashington 98195USA Institute for Nano-Engineered Systems University of WashingtonSeattleWashington 98195USA Department of Physics University of WashingtonSeattleWashington 98195USA Department of Bioengineering University of WashingtonSeattleWashington 98195USA

Miniature lenses with a tunable focus are essential components for many modern applications involving compact optical *** several tunable lenses have been reported with various tuning mechanisms,they often face challenges with respect to power consumption,tuning speed,fabrication cost,or production *** this work,we have adapted the mechanism of an Alvarez lens–a varifocal composite lens in which lateral shifts of two optical elements with cubic phase surfaces give rise to a change in the optical power–to construct a miniature,microelectromechanical system(MEMS)-actuated metasurface Alvarez *** based on an electrostatic MEMS generates fast and controllable actuation with low power *** utilization of metasurfaces–ultrathin and subwavelength-patterned diffractive optics–as optical elements greatly reduces the device volume compared to systems using conventional freeform *** entire MEMS Alvarez metalens is fully compatible with modern semiconductor fabrication technologies,granting it the potential to be mass-produced at a low unit *** the reported prototype operating at 1550 nm wavelength,a total uniaxial displacement of 6.3µm was achieved in the Alvarez metalens with a direct-current(DC)voltage application up to 20V,which modulated the focal position within a total tuning range of 68µm,producing more than an order of magnitude change in the focal length and a 1460-diopter change in the optical *** MEMS Alvarez metalens has a robust design that can potentially generate a much larger tuning range without substantially increasing the device volume or energy consumption,making it desirable for a wide range of imaging and display applications.

关键词： electrostatic optics adapted

Costs and cost-effectiveness of HIV early infant diagnosis in low- and middle-income countries: a scoping review

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Infectious Diseases of Poverty 2022年第4期11卷 9-28页

作者： Kira Elsbernd karl MfEmmert-fees Amanda Erbe Veronica Ottobrino Arne Kroid Till Barnighausen Benjamin P Geisler Stefan Kohler Division of Infectious Diseases and Tropical Medicine Faculty of MedicineLudwig Maximilians UniversityMunichGermany Institute for Medical Information Processing Biometryand Epidemiology(IBE)Faculty of Medicine Ludwig Maximilian UniversityMunichGermany Department of Sports and Health Sciences Technical University of MunichMunichGermany Institute of Health Economics and Health Care Management Helmholtz Zentrum MunchenMunichGermany Heidelberg Institute of Global Health Heidelberg UniversityHeidelbergGermany Department of Health Management and Health Economics University of OsloOsloNorway German Center for Infection Research(DZif) Partner SiteMunichGermany Massachusetts General Hospital/Harvard Medical School BostonMAUSA Institute of Social Medicine Epidemiology and HealthEconomicsCharite-Universitatsmedizin BerlinBerlinGermany

Background:Continuing progress in the global pediatric human immunodeficiency virus(HIV)response depends on timely identification and care of infants with *** countries scale-out improvements to HIV early infant diagnosis(EID),economic evaluations are needed to inform program design and *** scoping review aimed to summarize the available evidence and discuss practical implications of cost and cost-effectiveness analyses of HIV ***:We systematically searched bibliographic databases(Embase,MEDLINE and EconLit)and grey literature for economic analyses of HIV EID in low-and middle-income countries published between January 2008 and June *** extracted data on unit costs,cost savings,and incremental cost-effectiveness ratios as well as outcomes related to health and the HIV EID care process and summarized results in narrative and tabular *** converted unit costs to 2021 USD for easier comparison of costs across ***:After title and abstract screening of 1278 records and full-text review of 99 records,we included 29 studies:17 cost analyses and 12 model-based cost-effectiveness *** costs were 21.46-51.80 USD for point-of-care EID tests and 16.21-42.73 USD for laboratory-based EID *** cost-effectiveness analyses stated at least one of the interventions evaluated to be *** studies reported costs of EID testing strategies;however,few studies assessed the same intervention or reported costs in the same way,making comparison of costs across studies *** data availability of context-appropriate costs and outcomes of children with HIV as well as structural heterogeneity of cost-effectiveness modelling studies limits generalizability of economic analyses of HIV ***:The available cost and cost-effectiveness evidence for EID of HIV,while not directly comparable across studies,covers a broad range of interventions and suggests most interventions designed to improve EID are cost

关键词： Cost effectiveness Diagnostics Low-and middle-income countries Point of care Early infant diagnosis Health systems

Maximizing recovery time between knock-out races improves sprint cross-country skiing performance

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Journal of Sport and Health Science 2022年第1期11卷 21-29页

作者： Kerry McGawley Coline Van Waerbeke karl-Johan Westberg Erik P.Andersson Swedish Winter Sports Research Centre Department of Health SciencesMid Sweden UniversityOstersund 83125Sweden

Background:In a sprint cross-country(XC)ski competition,the difference in recovery times separating the first and the second semi-final(Sf)heats from the final(f)may affect *** aim of the current study was to compare the effects of longer *** recovery periods prescribed between the 3 knock-out races of a simulated sprint XC ski competition involving a prologue(P),quarter-final(Qf),Sf,and ***:Eleven well-trained XC ski athletes completed 2 simulated sprint XC ski competitions on a treadmill involving 4×883-m roller-ski bouts at a 4°incline using the gear 3 ski-skating *** first 3 bouts were completed at a fixed speed(PfIX,QffIX,and SffIX)corresponding to~96%of each individual’s previously determined maximal *** final bout was performed as a self-paced sprint time trial(fSTT).Test conditions differed by the time durations prescribed between the QffIX,SffIX,and fSTT,which simulated real-world XC ski competition conditions using maximum(MAX-REC)or minimum(MIN-REC)recovery ***:The fSTT was completed 5.4±5.5 s faster(p=0.009)during MAX-REC(179.2±18.1 s)compared to MIN-REC(184.6±20.0 s),and this was linked to a significantly higher power output(p=0.010)and total metabolic rate(p=0.009).The pre fSTT blood lactate(BLa)concentration was significantly lower during MAX-REC compared to MIN-REC(2.5±0.8 mmol/L vs.3.6±1.6 mmol/L,respectively;p=0.027),and the pre-to-post fSTT increase in BLa was greater(8.8±2.1 mmol/L vs.7.1±2.3 mmol/L,respectively;p=0.024).No other differences for MAX-REC ***-REC reached significance(p>0.05).Conclusion:Performance in a group of well-trained XC skiers is negatively affected when recovery times between sprint heats are minimized which,in competition conditions,would occur when selecting the last Qf *** result is combined with a higher pre-race BLa concentration and a reduced rise in BLa concentration under shorter recovery *** findings may help inform decision making when

关键词： Energetics Repeated sprints Roller skiing Simulated competition Tactics