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Genome and clonal hematopoiesis stability contrasts with immune,cfDNA,mitochondrial,and telomere length changes during short duration spaceflight

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Precision Clinical Medicine 2024年第1期7卷 1-13页

作者： J.Sebastian Garcia-Medina Karolina Sienkiewicz S.Anand Narayanan Eliah G.Overbey Kirill Grigorev Krista A.Ryon Marissa Burke Jacqueline Proszynski Braden Tierney Caleb M.Schmidt Nuria Mencia-Trinchant Remi Klotz Veronica Ortiz Jonathan Foox christopher chin Deena Najjar Irina Matei Irenaeus Chan Carlos Cruchaga Ashley Kleinman JangKeun Kim Alexander Lucaci Conor Loy Omary Mzava Iwijn De Vlaminck Anvita Singaraju Lynn E.Taylor Julian C.Schmidt Michael A.Schmidt Kelly Blease Juan Moreno Andrew Boddicker Junhua Zhao Bryan Lajoie Andrew Altomare Semyon Kruglyak Shawn Levy Min Yu Duane C.Hassane Susan M.Bailey Kelly Bolton Jaime Mateus christopher E.Mason Department of Physiology and Biophysics Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine Weill Cornell MedicineNew YorkNY 10021USA Department of Immunology Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA Department of Stem Cell Biology and Regenerative Medicine Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033USA Space Exploration Technologies Corporation HawthomeCA 90250USA Sovaris Aerospace BoulderCO 80302USA Advanced Pattern Analysis&Human Performance Group BoulderCO 80302USA Children's Cancer and Blood Foundation Laboratories Departments of Pediatrics and Cell and Developmental BiologyDrukier Institute for Children's HealthMeyer Cancer CenterWeill Cornell MedicineNew YorkNY 10021USA Meyer Cancer Center Weill Cornell MedicineNew YorkNY 10065USA Department of Nutrition and Integrative Physiology Florida State UniversityTallahasseeFL 32306USA Department of Systems Engineering Colorado State UniversityFort CollinsCO 80523USA Element Biosciences San DiegoCA 10055USA Department of Environmental and Radiological Health Sciences Colorado State UniversityFort CollinsCO 80523USA Cell and Molecular Biology Program Colorado State UniversityFort CollinsCO 80523USA BioAstra Inc New YorkNYUSA Washington University St Louis Oncology Division St.LouisMO 63100USA Meinig School of Biomedical Engineering Cornell UniversityIthacaNY 14853USA The Feil Family Brain and Mind Research Institute Weill Cornell MedicineNY 10021USA WorldQuant Initiative for Quantitative Prediction Weill Cornell MedicineNew YorkNY 10021USA

Background The Inspiration4(I4)mission,the first all-civilian orbital flight mission,investigated the physiological effects of short-duration spaceflight through a multi-omic *** advances,there remains much to learn about human adaptation to spaceflight's unique challenges,including microgravity,immune system perturbations,and radiation *** To provide a detailed genetics analysis of the mission,we collected dried blood spots pre-,during,and post-flight for DNA *** length was measured by quantitative PCR,while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations.A robust bioinformatic pipeline was used for data analysis,including variant calling to assess mutational *** Telomere elongation occurred during spaceflight and shortened after return to ***-free DNA analysis revealed increased immune cell signatures *** significant clonal hematopoiesis of indeterminate potential(CHIP)or whole-genome instability was *** long-term gene expression changes across immune cells suggested cellular adaptations to the space environment persisting months *** Our findings provide valuable insights into the physiological consequences of short-duration spaceflight,with telomere dynamics and immune cell gene expression adapting to spaceflight and persisting after return to *** sequencing data will serve as a reference point for studying the early development of CHIP in astronauts,an understudied phenomenon as previous studies have focused on career *** study will serve as a reference point for future commercial and non-commercial spaceflight,low Earth orbit(LEO)missions,and deep-space exploration.

关键词： genomes clonal hematopoiesis stability immune mitochondria ribosomes spaceflight

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Role of the histone methyltransferases Ezh2 and Suv4-20h1/Suv4-20h2 in neurogenesis

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Neural Regeneration Research 2023年第3期18卷 469-473页

作者： christopher T.Rhodes chin-Hsing Annie Lin Eunice Kennedy Shriver National Institute of Child Health and Human Development(NICHD) National Institutes of Health(NIH)BethesdaMDUSA Department of Integrative Biology University of Texas at San AntonioSan AntonioTXUSA University of Texas at San Antonio Neurosciences Institute San AntonioTXUSA

Mechanisms regulating neurogenesis involve broad and complex processes that represent intriguing therapeutic targets in the field of regenerative *** influential factor guiding neural stem cell proliferation and cellular differentiation during neurogenesis are epigenetic *** present an overview of epigenetic mechanisms including chromatin structure and histone modifications;and discuss novel roles of two histone modifiers,Ezh2 and Suv4-20h1/Suv4-20h2(collectively referred to as Suv4-20h),in neurodevelopment and *** review will focus on broadly reviewing epigenetic regulatory components,the roles of epigenetic components during neurogenesis,and potential applications in regenerative medicine.

关键词： adult neurogenesis epigenetic Ezh2 histone co-regulation histone modification neurodevelopment neurogenesis regenerative medicine Suv4-20h

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Current status and future of targeted peptide receptor radionuclide positron emission tomography imaging and therapy of gastroenteropancreatic-neuroendocrine tumors

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World Journal of Gastroenterology 2022年第17期28卷 1768-1780页

作者： Neil Grey Michael Silosky christopher H Lieu Bennett B chin Radiology-Nuclear Medicine University of Colorado School of MedicineAnschutz Medical CampusAuroraCO 80045United States Department of Radiology University of Colorado School of MedicineAnschutz Medical CampusAuroraCO 80045United States Medical Oncology University of Colorado School of MedicineAnschutz Medical CampusAuroraCO 80045United States

Theranostics is the highly targeted molecular imaging and therapy of *** peptide receptor radionuclide therapy has taken the lead in demonstrating the safety and effectiveness of this molecular approach to treating ***,well-differentiated gastroenteropancreatic neuroendocrine tumors may be most effectively imaged and treated with DOTATATE *** review the current practice,safety,advantages,and limitations of DOTATATE based ***,we briefly describe the exciting new areas of development and future directions of gastroenteropancreatic neuroendocrine tumor theranostics.

关键词： DOTATATE Theranostics Gastroenteropancreatic neuroendocrine tumors 68Ga DOTATATE 177Lu DOTATATE Review

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Online AUV Path Replanning Using Quantum-Behaved Particle Swarm Optimization with Selective Differential Evolution

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Computer Modeling in Engineering & Sciences 2020年第10期125卷 33-50页

作者： Hui Sheng Lim christopher K.H.chin Shuhong Chai Neil Bose National Centre for Maritime Engineering and Hydrodynamics Australian Maritime CollegeUniversity of TasmaniaLauncestonTAS7250Australia Memorial University of Newfoundland St.John’sNLA1C 5S7Canada

This paper presents an online AUV(autonomous underwater vehicle)path planner that employs path replanning approach and the SDEQPSO(selective differential evolution-hybridized quantum-behaved particle swarm optimization)algorithm to optimize an AUV mission conducted in an unknown,dynamic and cluttered ocean *** proposed path replanner considered the effect of ocean currents in path optimization to generate a Pareto-optimal path that guides the AUV to its target within minimum *** optimization was based on the onboard sensor data measured from the environment,which consists of a priori unknown dynamic obstacles and spatiotemporal *** sensor arrangements for the forward-looking sonar and horizontal acoustic Doppler current profiler(H-ADCP)were considered in 2D and 3D *** on the simulation results,the SDEQPSO path replanner was found to be capable of generating a time-optimal path that offered up to 13%reduction in travel time compared to the situation where the vehicle simply followed a path with the shortest *** proposed replanning technique also showed consistently better performance over a reactive path planner in terms of solution quality,stability,and computational *** of the replanner was verified under stochastic process using the Monte Carlo *** generated path fulfilled the vehicle’s safety and physical constraints,while intelligently exploiting ocean currents to improve the vehicle’s efficiency.

关键词： Autonomous underwater vehicle path planning particle swarm optimization sonar detection Monte Carlo methods

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Ecological connectivity in fragmented agricultural landscapes and the importance of scattered trees and small patches

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Ecological Processes 2021年第1期10卷 274-289页

作者： Darrel chin Fung Tiang Andrew Morris Mathew Bell christopher NGibbins Badrul Azhar Alex MLechner School of Environmental and Geographical Sciences University of Nottingham MalaysiaJalan Broga43500 SemenyihSelangorMalaysia MidCoast Council 2 Biripi WayTareeNSW 2430Australia Faculty of Forestry&Environment Universiti Putra Malaysia43400 SerdangSelangorMalaysia Lincoln Centre for Water and Planetary Health School of GeographyUniversity of LincolnLincoln LN67TSUK

Background:Fragmentation and habitat loss can restrict species movement and reduce connectivity,negatively impacting *** the overall connectivity of an area can inform better management of human modified *** connectivity modelling methods seldom incorporate fine-scale movement patterns associated with movement between fine-scaled structural connectivity elements such as scattered trees,roadside corridors and small patches of *** study aims to characterise connectivity within the Karuah-Myall catchments,a typical woodland ecosystem that is fragmented by agriculture,using least-cost path analysis and a graph-theoretic approach;it focuses on how fine-scaled vegetation such as scattered trees support *** mapped scattered(and paddock)trees within this agricultural landscape where the main human modified land use was *** modelled connectivity for a general representative woodland species using an interpatch dispersal distance and gap crossing threshold,and resistance from different land cover *** gap crossing distance threshold was used to model movement between fine-scaled vegetation *** compared the least-cost paths modelled with and without scattered ***:Our results show that by excluding scattered trees,least-cost paths across the cleared pasture landscape did not reflect the types of movement patterns typically observed from field studies,such as those associated with a foray-search strategy used by small and medium mammals and *** modelling also shows that the KaruahMyall catchments are well connected and provide value to biodiversity beyond the catchment borders,by connecting coastal vegetation to the Great Eastern Ranges national wildlife corridor ***:Connectivity models that exclude fine-scale landscape features such as scattered trees and small,linear patches risk misrepresenting connectivity *** of regional-scale connectivity can b

关键词： Scattered trees Landscape connectivity Gap crossing Fragmentation Agricultural landscape

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Design and in vivo characterization of kidney-targeting multimodal micelles for renal drug delivery

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Nano Research 2018年第10期11卷 5584-5595页

作者： Jonathan Wang christopher Poon Deborah chin Sarah Milkowski Vivian Lu Kenneth R. Hallows Eun Ji Chung Department of Biomedical Engineering University of Southern California Los Angeles CA 90089 USA Division of Nephrology and Hypertension Department of Medicine Keck School of Medicine University of Southern California Los Angeles CA 90033 USA USC/UKRO Kidney Research Center Keck School of Medicine University of Southern California Los Angeles CA 90033 USA Norris Comprehensive Cancer Center University of Southern California Los Angeles CA 90033 USA Department of Stem Cell Biology and Regenerative Medicine University of Southern California Los Angeles CA 90033 USA Mork Family Department of Chemical Engineering and Materials Science University of Southern California Los Angeles CA 90089 USA

One in three Americans is at risk for developing chronic kidney disease （CKD） and end-stage renal disease （ESRD）, leading to the need for dialysis or a kidney transplant. Small-molecule drugs have been proposed as therapies to manage kidney diseases, but high dosages are often required to achieve therapeutic efficacy, generating off-target side effects, some of which are lethal. To address these limitations, we developed a novel kidney-targeting multimodal micelle （KM） system for drug delivery applications. SpecificaU~ we incorporated the kidney-targeting peptide （Lysine-Lysine-Glutamic acid-Glutamic acid-Glutamic acid）3-Lysine）（（KKEEE）3K） into micelles. This peptide binds to megalin, a multi-ligand cell surface receptor present on renal tubule cells. When incubated with human kidney proximal tubule cells, KMs were found to be biocompatible in vitro. In vivo, KMs showed higher accumulation in the kidneys as compared to a non-targeted （NT） control upon intravenous injection in wild-type C57BL/6J mice. Histological evaluation showed no signs of tissue damage, while blood urea nitrogen （BUN） and creatinine levels were within normal ranges, validating the preservation of kidney health upon micelle administration. To our knowledge, this is the first utilization of （KKEEE）BK in a nanoparticle formulation, and our study offers strong evidence that this novel nanoparticle platform can be used as a candidate drug delivery carrier to direct therapeutics to diseased tissue in CKD.

关键词： micelle kidney disease renal targeting biodistribution nanoparticle

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The mTORC1 complex in pre-osteoblasts regulates whole-body energy metabolism independently of osteocalcin

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Bone Research 2021年第1期9卷 109-125页

作者： Pawanrat Tangseefa Sally K.Martin Peck Yin chin James Breen Chui Yan Mah Paul A.Baldock Gary A.Wittert Amanda J.Page christopher G.Proud Stephen Fitter Andrew C.W.Zannettino Adelaide Medical School Faculty of Health and Medical ScienceUniversity of AdelaideAdelaide5005 SAAustralia Cancer Program Precision Medicine ThemeSouth Australian Health and Medical Research InstituteAdelaide5000 SAAustralia Research Centre for Reproductive Health School of Paediatrics and Reproductive HealthUniversity of AdelaideAdelaide5005 SAAustralia Computational&Systems Biology program Precision Medicine ThemeSouth Australian Health and Medical Research InstituteAdelaide5000 SAAustralia Robinson Research Institute University of AdelaideAdelaideSA 5005Australia Bioinformatics Hub University of AdelaideAdelaideSA 5005Australia Freemasons Foundation Centre for Men’s Health University of AdelaideAdelaide5005 SAAustralia Skeletal Metabolism Group Garvan Institute of Medical ResearchSydney2010 NSWAustralia Nutrition Diabetes&Metabolism ProgramLifelong Health ThemeSouth Australian Health and Medical Research InstituteAdelaide5000 SAAustralia School of Biological Sciences University of AdelaideAdelaide5005 SAAustralia Central Adelaide Local Health Network AdelaideSAAustralia

Overnutrition causes hyperactivation of mTORC1-dependent negative feedback loops leading to the downregulation of insulin signaling and development of insulin *** osteoblasts(OBs),insulin signaling plays a crucial role in the control of systemic glucose *** utilized mice with conditional deletion of Rptor to investigate how the loss of mTORC1 function in OB affects glucose metabolism under normal and overnutrition dietary *** to the controls,chow-fed Rptorob−/−mice had substantially less fat mass and exhibited adipocyte ***,upon feeding with high-fat diet,mice with pre-and post-natal deletion of Rptor in OBs were protected from diet-induced obesity and exhibited improved glucose metabolism with lower fasting glucose and insulin levels,increased glucose tolerance and insulin *** leanness and resistance to weight gain was not attributable to changes in food intake,physical activity or lipid absorption but instead was due to increased energy expenditure and greater whole-body substrate ***-seq revealed an increase in glycolysis and skeletal insulin signaling pathways,which correlated with the potentiation of insulin signaling and increased insulin-dependent glucose uptake in Rptorknockout ***,these findings point to a critical role for the mTORC1 complex in the skeletal regulation of wholebody glucose metabolism and the skeletal development of insulin resistance.

关键词： metabolism mTORC1 homeostasis

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Novel insights into the role of anti-inflammatory IL-38 in immunity against infection

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Cellular & Molecular Immunology 2022年第11期19卷 1322-1324页

作者： Xun Gao Guoqiu Wu Miranda Sin-Man Tsang Danqi Huang christopher Wai-Kei Lam Chun Kwok Wong Department of Chemical Pathology The Chinese University of Hong KongHong KongChina Center of Clinical Laboratory Medicine Zhongda HospitalSoutheast UniversityNanjingChina Institute of chinese Medicine and State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants The Chinese University of Hong KongHong KongChina Faculty of Medicine and State Key Laboratory of Quality Research in chinese Medicines Macao University of Science and TechnologyMacaoChina Li Dak Sum Yip Yio chin R and D Centre for chinese Medicine The Chinese University of Hong KongHong KongChina

Since the identification and cloning of interleukin(IL)-38 in 2001,a plethora of studies have focused on its essential roles as a novel IL-1 family cytokine in both innate and acquired *** on the shared traits with IL-36 receptor antagonist(IL-36Ra)and IL-1 receptor antagonist(IL-1Ra),IL-38 constitutes one of the most important anti-inflammatory cytokines within the IL-36 subfamily and thus elicits its antagonistic effects through binding to IL-36 receptor(IL-36R)and to IL-R1 with a relatively low affinity[1,2].IL-38 has been proven to bind to X-linked interleukin-1 receptor accessory protein-like 1(IL1RAPL1)[1],and IL1RAPL1 therefore serves as a novel receptor of IL-38.

关键词： immunity antagonist insight

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Meteorin-β/Meteorin like/IL-41 attenuates airway inflammation in house dust mite-induced allergic asthma

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Cellular & Molecular Immunology 2022年第2期19卷 245-259页

作者： Xun Gao Ting-Fan Leung Gary Wing-Kin Wong Wing-Hung Ko Mengyun Cai Ellie Jiayi He Ida Miu-Ting Chu Miranda Sin-Man Tsang Ben Chung-Lap Chan Jiawei Ling Xiao Fan Liwei Lu christopher Wai-Kei Lam Chun-Kwok Wong Department of Chemical Pathology The Chinese University of Hong KongHong KongChina Department of Paediatrics The Chinese University of Hong KongHong KongChina School of Biomedical Sciences The Chinese University of Hong KongHong KongChina Emory College of Arts and Sciences Emory UniversityAtlantaGAUSA Institute of chinese Medicine and State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants The Chinese University of Hong KongHong KongChina Department of Pathology and Shenzhen Institute of Research and Innovation The University of Hong KongHong KongChina Faculty of Medicine and State Key Laboratory of Quality Research in chinese Medicines Macao University of Science and TechnologyMacaoChina Li Dak Sum Yip Yio chin R&D Centre for chinese Medicine The Chinese University of Hong KongHong KongChina

We sought to examine the regulatory effect of Meteorin-β(Metrnβ)/Meteorin like(Metrnl)/IL-41 on lung inflammation in allergic *** found that Metrnβwas elevated significantly in asthmatic patients and in mice with allergic asthma induced by house dust mite(HDM)*** exposure to HDM,Metrnβwas secreted predominantly by airway epithelial cells and inflammatory cells,including macrophages and *** increased Metrnβeffectively blocked the development of airway hyperreactivity(AHR)and decreased inflammatory cell airway infiltration and type 2 cytokine production,which was associated with downregulated DC-mediated adaptive immune ***,Metrnβimpaired the maturation and function of bone marrow-derived dendritic cells in *** mice adoptively transferred with dendritic cells isolated from Metrnβ-treated allergic mice displayed decreased AHR,airway inflammation,and lung ***βalso displayed anti-inflammatory properties in immunodeficient SCID mice with allergic asthma and in in vitro 3D ALI airway ***,blockade of Metrnβby anti-Metrnβantibody treatment promoted the development of allergic *** results revealed the unappreciated protective roles of Metrnβin alleviating DC-mediated Th2 inflammation in allergic asthma,providing the novel treatment strategy of therapeutic targeting of Metrnβin allergic asthma.

关键词： Metrnβ Eosinophils Dendritic cells Allergic asthma Air-liquid interface

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Adverse Skin Reactions to Personal Protective Equipment Among Health-Care Workers During COVID-19 Pandemic: A Multicenter Cross-sectional Study in Indonesia

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International Journal of Dermatology and Venereology 2020年第4期3卷 211-218页

作者： christopher Paulus Mario Roren Regina Stefani Tania Clarissa Jayadi Nana Novia Cucunawangsih Cucunawangsih Faculty of Medicine Pelita Harapan UniversityBanten 15811Indonesia Department of Dermatology and Venereology Faculty of MedicinePelita Harapan UniversityBanten 15811Indonesia Department of Microbiology Faculty of MedicinePelita Harapan UniversityBanten 15811Indonesia

Objective:Health-care workers(HCWs)in Indonesia have been participating in the war against the coronavirus disease-2019 since March *** since HCWs were exposed to the regular use of personal protective equipment(PPE)with varying levels and maintain hand hygiene more as recommended by the World Health *** skin reactions to PPE in Indonesia has yet to be *** study aimed to study the prevalence and characteristics-,possible risk factors-,and suggest possible solutions towards adverse skin reactions to PPE among HCWs in a multi-center setting of ***:A cross-sectional survey was conducted online among HCWs in the Siloam Hospitals Group of Banten *** of Banten Province were surveyed from June 1 to August 31,*** data was obtained using avalidated online survey questionnaire including(1)demographic characteristics;(2)occupational-related characteristics;(3)adverse skin ***:A response rate of 40.2%was obtained and 200 valid respondents were *** mean age of respondents was(26.94±7.23)years *** skin reactions(66.5%)were reported primarily in female(73.7%)working as doctors(82.7%)of a non-referral center for coronavirus disease-2019(60.2%)wearing level 2 and 3 PPE(43.6% and 37.6%,respectively).The cheeks and chin was the most common site involved(69.9%)with dryness/tightness(63.9%)and acne(77.4%)as the highest symptoms and signs ***,age group classification,level of PPE worn,hand hygiene frequency,and duration of PPE worn daily were factors considerably associated with adverse skin reactions to PPE(P<0.05).Conclusions:Adverse skin reactions to PPE are common among HCWs in *** strengthening of the skin condition and awareness on adverse skin reactions should be advocated.

关键词： adverse skin reactions health-care workers PPE COVID-19 Indonesia

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