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Aspect oriented programs: Issues and perspective

Journal of Electrical Systems and Information Technology 2018年第3期5卷 562-575页

作者： Sk. Riazur Raheman Hima Bindu Maringanti Amiya Kumar Rath Ph.D. Scholar Computer Science & IT North Orissa University Baripada Odisha 757003 India Professor & Head Dept. of Computer Application North Orissa University Baripada Odisha 757003 India Professor Dept. of Computer Science & Engineering VSSUT Burla Odisha 768018 India

Aspect oriented programming (AOP) helps programmers for separating crosscutting concerns. All programming methodologies support split up and encapsulation of concerns. In object-oriented programming (OOP) crosscutting aspects are distributed among objects. It is hard to attain crosscutting in OOP as it is scattered in different objects. In AOP crosscutting concerns are addressed using one entity called aspect. This paper discusses varieties of existing slicing techniques of AOP. Also, we discuss a novel method to calculate dynamic slice of AOP. To represent AOP Aspect Oriented System dependence Graph (AOSdG) is used. The complexity of this new approach is equal or improved as related to certain prevailing approaches.

关键词： Aspect AOP Slicing Crosscutting AOSdG

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Plasma-derived Nanoclusters for Site-Specific Multimodality photo/Magnetic Thrombus Theranostics

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Advanced Healthcare Materials 2023年第28期12卷 2301504-2301504页

作者： Liu, Chia-Hung Liu, Ming-Che Jheng, Pei-Ru Yu, Jiashing Fan, Yu-Jui Liang, Jia-Wei Hsiao, Yu-Cheng Chiang, Chih-Wei Bolouki, Nima Lee, Jyh-Wei Hsieh, Jang-Hsing Mansel, Bradley W Chen, Yan-Ting Nguyen, Hieu Trung Chuang, Er-Yuan Department of Urology School of Medicine College of Medicine Taipei Medical University 250 Wu-Hsing Street Taipei11031 Taiwan TMU Research Center of Urology and Kidney Taipei Medical University 250 Wu-Hsing Street Taipei11031 Taiwan Department of Urology Shuang Ho Hospital Taipei Medical University 291 Zhongzheng Road Zhonghe District New Taipei City23561 Taiwan Clinical Research Center Taipei Medical University Hospital Taipei11031 Taiwan School of Dental Technology College of Oral Medicine Taipei Medical University Taipei11031 Taiwan Graduate Institute of Biomedical Materials and Tissue Engineering International Ph.D. Program in Biomedical Engineering Graduate Institute of Biomedical Optomechatronics School of Biomedical Engineering Research Center of Biomedical Device Innovation Entrepreneurship Education Center College of Interdisciplinary Studies Taipei Medical University Taipei11031 Taiwan Department of Chemical Engineering College of Engineering National Taiwan University Taipei106 Taiwan Department of Orthopedics Taipei Medical University Taipei11031 Taiwan Department of Orthopedics Taipei Medical University Hospital Taipei11031 Taiwan Department of Physical Electronics Faculty of Science Masaryk University Brno60177 Czech Republic Department of Materials Engineering Ming Chi University of Technology New Taipei City24301 Taiwan Center for Plasma and Thin Film Technologies Ming Chi University of Technology New Taipei City24301 Taiwan National Synchrotron Radiation Research Center Hsinchu Science Park Hsinchu30076 Taiwan Department of Orthopedics and Trauma Faculty of Medicine University of Medicine and Pharmacy at Ho Chi Minh City Ho Chi Minh City700000 Viet Nam Cell Physiology and Molecular Image Research Center Taipei Medical University Wan Fang Hospital Taipei11696 Taiwan Precision Medicine and Translational Cancer Research Center Taipei Medical University Hospital Taipei11031 Taiwan

Traditional thrombolytic therapeutics for vascular blockage are affected by their limited penetration into thrombi, associated off-target side effects, and low bioavailability, leading to insufficient thrombolytic efficacy. It is hypothesized that these limitations can be overcome by the precisely controlled and targeted delivery of thrombolytic therapeutics. A theranostic platform is developed that is biocompatible, fluorescent, magnetic, and well-characterized, with multiple targeting modes. This multimodal theranostic system can be remotely visualized and magnetically guided toward thrombi, noninvasively irradiated by near-infrared (NIR) phototherapies, and remotely activated by actuated magnets for additional mechanical therapy. Magnetic guidance can also improve the penetration of nanomedicines into thrombi. In a mouse model of thrombosis, the thrombosis residues are reduced by ≈80% and with no risk of side effects or of secondary embolization. This strategy not only enables the progression of thrombolysis but also accelerates the lysis rate, thereby facilitating its prospective use in time-critical thrombolytic treatment. © 2023 Wiley-VCH GmbH.

关键词： diseases

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Guardians of the Mitochondria: Space Mitochondria 2.0 Systemic Analysis Reveals Bioenergetic dysregulation Across Species

SSRN

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SSRN 2025年

作者： Guarnieri, Joseph W. Maghsoudi, Zeynab Kim, JangKeun Bya, phi Widjaja, Gabrielle A. Barker, Richard Burke, Marissa Cen, Zimu Fazelinia, Hossein Tsoy, Sergey Tiersky, Rachel Peczak, Anna Kim, Jihan Kim, Ye-Ah Haltom, Jeffrey Almeida, Michael Garris, Alex day, Sarah Sanchez-Hodge, Rebekah Zilberman, Aleeza H. Allen, Noah G. Kubik, Angela J. Blaber, Elizabeth A. Mathyk, Begum Harris, Frederick C. Singh, Kanhaiya Sen, Chandan K. Innes, Lucinda Ali, Nilufar Berliner, Aaron J. Kar, Upendra K. Overbey, Eliah Giunta, Simona Podrabsky, Jason E. Neal, Matthew d. Billiar, Timothy R. Headley, Colwyn Meydan, Cem Tasoula, Alexia Szewczyk, Nathaniel Ikeda, Yasutaka Gotoh-Katoh, Aina Schisler, Jonathan C. Kim, Man S. Schwartz, Robert E. Wallace, douglas C. Mason, Christopher E. Nguyen, Tin Beheshti, Afshin Children’s Hospital of Philadelphia PhiladelphiaPA United States Computer Science and Engineering University of Nevada Reno RenoNV United States Department of Physiology and Biophysics and WorldQuant Initiative for Quantitative Prediction Weill Cornell Medicine New YorkNY United States Computer Science and Software Engineering University of Auburn AL United States Purdue University Department of Agricultural and Biological engineering IN United States Department of Neurosurgery Houston Methodist Research Institute HoustonTX United States Department of Medicine Division of Gastroenterology and Hepatology Weill Cornell Medicine New YorkNY United States Kyung Hee University Hospital at Gangdong Kyung Hee University Seoul Korea Republic of McAllister Heart Institute Department of Pharmacology The University of North Carolina at Chapel Hill Chapel HillNC United States Shirley Ann Jackson Ph.D. Center for Biotechnology and Interdisciplinary Studies Department of Biomedical Engineering Rensselaer Polytechnic Institute TroyNY United States Division of Reproductive Endocrinology and Infertility Department of Obstetrics and Gynecology University of South Florida Morsani College of Medicine TampaFL United States Center for Space Biomedicine McGowan Institute for Regenerative Medicine Department of Surgery University of Pittsburgh School of Medicine PittsburghPA United States Department of Biological Science Boise State University BoiseID United States Department of Radiation Oncology Weill Cornell Medicine New YorkNY United States BerkeleyCA United States University of Pittsburgh School of Medicine PittsburghPA United States The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine Weill Cornell Medicine New YorkNY United States BioAstra Inc New YorkNY United States Center for STEM University of Austin AustinTX78701 United States Laboratory of Genome Evolution Department of Biology and Biotechnology Charle

Spaceflight imposes unique stressors that disrupt mitochondrial function, vital for energy production and immune regulation. Our multi-omics analysis (proteomics, bisulfite sequencing, RNA-seq, and single-nuclei RNA/ATAC-seq) on astronauts, rodents, and model organisms (flies, worms, plants) revealed progressive impairment of mitochondrial oxidative phosphorylation (OXphOS) during spaceflight, with delayed recovery post-return across species. In rodents, radiation ≥10.34 mGy activated persistent mitochondrial stress pathways across multiple organs except in the spleen, with older and male C57BL/6 mice most affected. Astronaut data from the NASA Twins Study, JAXA, and Inspiration4 missions showed prolonged mitochondrial dysfunction, with OXphOS suppression and TCA cycle inhibition lasting up to 82 days. Bisulfite sequencing confirmed lasting epigenetic changes in OXphOS genes. Lastly, Kaempferol, an antioxidant and mitochondrial activator, mitigated radiation-induced liver atrophy in mice and preserved liver function in human organoids. This cross-species study underscores the need for targeted therapies to protect mitochondrial biogenesis during long-duration space missions. © 2025, The Authors. All rights reserved.

关键词： Mammals

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Persistence and dynamic structures of diverse cephalosporinase genes in nontyphoidal Salmonella in cross-sectional surveillance in Taiwan

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International Journal of Antimicrobial Agents 2023年第4期62卷 106944-106944页

作者： Lee, Yuarn-Jang Chang, Yu-Chu Lee, I-Hui Ho, Kuo-Hao Fang, Shiuh-Bin Lauderdale, Tsai-Ling Chen, Ting-Wen Chen, Ku-Chung Huang, Chih-Hung Huang, Tzu-Wen Division of Infectious Diseases Department of Internal Medicine Shuang Ho Hospital Taipei Medical University New Taipei City Taiwan Division of Infectious Diseases Department of Internal Medicine School of Medicine College of Medicine Taipei Medical University Taipei Taiwan Department of Biochemistry and Molecular Cell Biology School of Medicine College of Medicine Taipei Medical University Taipei Taiwan International Ph.D. Program for Cell Therapy and Regeneration Medicine College of Medicine Taipei Medical University Taipei Taiwan Department of Microbiology and Immunology School of Medicine College of Medicine Taipei Medical University Taipei Taiwan Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei Taiwan Division of Pediatric Gastroenterology and Hepatology Department of Pediatrics Shuang Ho Hospital Taipei Medical University New Taipei City Taiwan Department of Medical Research Shuang Ho Hospital Taipei Medical University New Taipei City Taiwan Department of Pediatrics School of Medicine College of Medicine Taipei Medical University Taipei Taiwan Master Program in Clinical Pharmacogenomics and Pharmacoproteomics College of Pharmacy Taipei Medical University Taipei Taiwan National Institute of Infectious Diseases and Vaccinology National Health Research Institutes Zhunan Taiwan Institute of Bioinformatics and Systems Biology National Yang Ming Chiao Tung University Hsinchu Taiwan Department of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu Taiwan Center for Intelligent Drug Systems and Smart Bio-devices (IDS2B) National Yang Ming Chiao Tung University Hsinchu Taiwan Department of Chemical Engineering and Biotechnology Institute of Chemical Engineering National Taipei University of Technology Taipei Taiwan

Objectives: Nontyphoidal Salmonella (NTS) is a major foodborne pathogen causing from acute gastroenteritis to bacteraemia, particularly in paediatric and elderly patients. Antimicrobial resistance of NTS, especially resistance to extended-spectrum cephalosporins, has emerged over the past decades. Methods: Thirteen NTS isolates resistant to ceftriaxone or cefotaxime were collected from a teaching hospital in Taipei, and another three from a tertiary hospital, in New Taipei City, Taiwan, from September 2018 to december 2019. Ten other archived isolates from 2000 to 2017 were also obtained. Complete genomes of the 26 isolates were obtained. Serovars, sequence types, resistomes, genetic relatedness, and sequence comparison of plasmids were analyzed. Results: Serogroups B, C2 and E were significantly associated with ampicillin resistance. Over 90% of these 26 isolates are susceptible to carbapenems and colistin. Genomic epidemiology of these isolates shows that bla_CMY-2-harbouring isolates in different serovars were prevalent over two decades, presumably resulting from highly mobile IncI1 plasmid harbouring bla_CMY-2. One type of the IncI1 plasmids contained a mobile element, IS26, which might be involved in the acquisition of antimicrobial resistance genes. Two emerging serovars, S. Goldcoast ST358 harbouring bla_CTX-M-55 on IncHI2 plasmids and S. Anatum ST64 harbouring bla_dHA-1 on IncA/C₂ plasmids persisted in Taiwan, possibly through the clonal spread. Integration of complete or partial plasmid sequences into host chromosomes or multiplications of the antimicrobial resistance genes also appears to be mediated by IS26, in the two emerging clones. Conclusion: The dynamic movement of cephalosporinase genes mediated by IS26 in NTS is of great concern. © 2023 The Authors

关键词： Amplification Chromosome integration Epidemiology Foodborne pathogen Insertion sequence Whole-genome sequencing

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Hydrophone by combining a fiber grating and silicon thin-film

Hydrophone by combining a fiber grating and silicon thin-fil...

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Optical Fiber Sensors, OFS 2018

作者： Chang, Hung-Ying Li, Jia-Guan Chen, Chi-Fang Liu, Wen-Fung Fu, Ming-Yue Ph.D. Program of Electrical and Communications Engineering Feng-Chia University Taichung40724 Taiwan Department of Electrical Engineering Feng-Chia University Taichung40724 Taiwan Department of Engineering Science and Ocean Engineering National Taiwan University Taipei106 Taiwan Center for General Education Air Force Academy Kaohsiung City82047 Taiwan

This study proposed a hydrophone by using an FBG in conjunction with a packaging for detecting the acoustic wave under water due to that the acoustic wave pushes thin-film to cause the grating wavelength shift. ©... 详细信息

ISBN: (纸本)9781943580507

关键词： Hydrophones

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Electronic nose in differentiating and ascertaining clinical status among patients with pulmonary nontuberculous mycobacteria: A prospective multicenter study

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The Journal of infection 2023年第3期87卷 255-258页

作者： Meng-Rui Lee Hung-Ling Huang Wei-Chang Huang Shang-Yu Wu Pang-Chun Liu Jui-Ching Wu Meng-Hsuan Cheng Chau-Chyun Sheu Kea-Tiong Tang Jann-Yuan Wang Chao-Chi Ho Jin-Yuan Shih Inn-Wen Chong Department of Internal Medicine National Taiwan University Hospital Taipei Taiwan. Department of Internal Medicine Kaohsiung Municipal Ta-Tung Hospital Kaohsiung Taiwan Division of Pulmonary and Critical Care Medicine Department of Internal Medicine Kaohsiung Medical University Hospital Kaohsiung Taiwan Department of Internal Medicine Kaohsiung Medical University Hospital Kaohsiung Taiwan Graduate Institute of Medicine College of Medicine Kaohsiung Medical University Kaohsiung Taiwan. Division of Chest Medicine Department of Internal Medicine Taichung Veterans General Hospital Taichung Taiwan Department of Post-Baccalaureate Medicine College of Medicine National Chung Hsing University Taichung Taiwan Mycobacteria Center of Excellence Department of Internal Medicine Taichung Veterans General Hospital Taichung Taiwan School of Medicine Chung Shan Medical University Taichung 402 Taiwan Ph.D. Program in Translational Medicine National Chung Hsing University Taichung 402 Taiwan Department of Medical Technology Jen-Teh Junior College of Medicine Nursing and Management Miaoli Taiwan. Department. of Electrical Engineering National Tsing Hua University Hsinchu Taiwan. Division of Pulmonary and Critical Care Medicine Department of Internal Medicine Kaohsiung Medical University Hospital Kaohsiung Taiwan Department of Internal Medicine Kaohsiung Medical University Hospital Kaohsiung Taiwan. Department. of Electrical Engineering National Tsing Hua University Hsinchu Taiwan. Electronic address: kttang@ee.nthu.edu.tw. Department of Internal Medicine National Taiwan University Hospital Taipei Taiwan. Electronic address: jywang@ntu.edu.tw. Graduate Institute of Medicine College of Medicine Kaohsiung Medical University Kaohsiung Taiwan Department of Respiratory Therapy Kaohsiung Medical University Hospital Kaohsiung Taiwan Department of Biological Science & Technology National Chiao Tung University Hsin-Chu Taiwan.

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Technology dictates algorithms: Recent developments in read alignment

arXiv

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arXiv 2020年

作者： Alser, Mohammed Rotman, Jeremy Taraszka, Kodi Shi, Huwenbo Baykal, Pelin Icer Yang, Harry Taegyun Xue, Victor Knyazev, Sergey Singer, Benjamin d. Balliu, Brunilda Koslicki, david Skums, Pavel Zelikovsky, Alex Alkan, Can Mutlu, Onur Mangul, Serghei Computer Science Department ETH Zürich Zürich8092 Switzerland Computer Engineering Department Bilkent University Bilkent Ankara 06800 Turkey Department of Computer Science University of California Los Angeles Los AngelesCA90095 United States Department of Epidemiology Harvard T.H. Chan School of Public Health MA02115 United States Program in Medical and Population Genetics Broad Institute of MIT and Harvard CambridgeMA02142 United States Department of Computer Science Georgia State University AtlantaGA30302 United States Bioinformatics Interdepartmental Ph.D. Program University of California Los Angeles Los AngelesCA90095 United States Division of Pulmonary and Critical Care Medicine Northwestern University Feinberg School of Medicine ChicagoIL60611 United States Department of Biochemistry & Molecular Genetics Northwestern University Feinberg School of Medicine United States Simpson Querrey Center for Epigenetics Northwestern University Feinberg School of Medicine ChicagoIL60611 United States Department of Computational Medicine University of California Los Angeles Los AngelesCA90095 United States Computer Science and Engineering Pennsylvania State University University ParkPA16801 United States Biology Department Pennsylvania State University University ParkPA16801 United States The Huck Institutes of the Life Sciences Pennsylvania State University University ParkPA16801 United States The Laboratory of Bioinformatics I.M. Sechenov First Moscow State Medical University Moscow119991 Russia Bilkent-Hacettepe Health Sciences and Technologies Program Ankara Turkey Department of Clinical Pharmacy School of Pharmacy University of Southern California Los AngelesCA90089 United States

Massively parallel sequencing techniques have revolutionized biological and medical sciences by providing unprecedented insight into the genomes of humans, animals, and microbes. Modern sequencing platforms generate enormous amounts of genomic data in the form of nucleotide sequences or reads. Aligning reads onto reference genomes enables the identification of individual-specific genetic variants and is an essential step of the majority of genomic analysis pipelines. Aligned reads are essential for answering important biological questions, such as detecting mutations driving various human diseases and complex traits as well as identifying species present in metagenomic samples. The read alignment problem is extremely challenging due to the large size of analyzed datasets and numerous technological limitations of sequencing platforms, and researchers have developed novel bioinformatics algorithms to tackle these difficulties. Importantly, computational algorithms have evolved and diversified in accordance with technological advances, leading to today’s diverse array of bioinformatics tools. Our review provides a survey of algorithmic foundations and methodologies across 107 alignment methods published between 1988 and 2020, for both short and long reads. We provide rigorous experimental evaluation of 11 read aligners to demonstrate the effect of these underlying algorithms on speed and efficiency of read aligners. We separately discuss how longer read lengths produce unique advantages and limitations to read alignment techniques. We also discuss how general alignment algorithms have been tailored to the specific needs of various domains in biology, including whole transcriptome, adaptive immune repertoire, and human microbiome studies. Copyright © 2020, The Authors. All rights reserved.

关键词： Bioinformatics

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Arrival time estimation and reminders on public bus system 7

Arrival time estimation and reminders on public bus system

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2017 7th International Workshop on computer science and Engineering, WCSE 2017

作者： Lin, Bo-Wei Huang, ding-Ray Yang, Yun-Chung Huang, Yi-Chin Kiong, Ye Chin Lin, Jim-Min Tsai, Ming-Fong Department of Information Engineering and Computer Science Feng Chia University Taichung Taiwan Industrial Ph.D. Program of Internet of Things Feng Chia University Taichung Taiwan

ISBN: (纸本)9789811136719

The public bus service, which is one of the most frequently used public transportation methods, is an indispensable part of public lifestyle. Hence, government and companies have integrated the public bus service with smart device applications, enabling the public to check information such as bus schedules and instant information at any time. Their aim is to improve the efficiency of the public bus service. Unfortunately, their efforts have faced a variety of problems, such as the distrust of the public regarding the provided information, traffic situation, and unexpected incidents which disturb the bus schedule. In order to overcome the mentioned problems, a smart bus stop signboard system will be designed. The smart signboard will show the current position of the bus and provides a reservation service, which the public may access using smart devices. The proposed system allows bus drivers to obtain information about a particular bus stop to determine whether they should drive to that bus stop. Because the traffic situation and the embarkment and disembarkment of passengers affects the arrival time of the bus, the proposed system will take the change in the number of bus passengers and travel time into account in order to predict the arrival time of the bus.

关键词： Travel time

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Association between parental well-being and preschooler stress measured as hair cortisol concentration: A prospective cohort study

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Stress and health : journal of the International Society for the Investigation of Stress 2024年第5期40卷 e3462页

作者： Yun-Shiang Kang Ling-Chu Chien Jian-Pei Huang Yen-Tzu Fan Wen-Yi Lin Pairote Chakranon Heng-Kien Au Yi-Yung Chen Hsing Jasmine Chao Pilyoung Kim Yi-Hua Chen School of Public Health College of Public Health Taipei Medical University Taipei Taiwan. Neuroscience Research Center Taipei Medical University Taipei Taiwan. Nutrition Research Center Taipei Medical University Hospital Taipei Taiwan. Department of Obstetrics and Gynecology Mackay Memorial Hospital Taipei Taiwan. Graduate Institute of Environmental Engineering National Taiwan University Taipei Taiwan. Ph.D. Program for Neural Regenerative Medicine College of Medical Science and Technology Taipei Medical University Taipei Taiwan. Department of Obstetrics and Gynecology Taipei Medical University Hospital Taipei Taiwan. Department of Obstetrics and Gynecology School of Medicine College of Medicine Taipei Medical University Taipei Taiwan. Department of Psychology College of Arts Humanities and Social Sciences University of Denver Denver Colorado USA. Department of Psychology Ewha Womans University Seoul South Korea. Research Center of Health Equity College of Public Health Taipei Medical University Taipei Taiwan.

Hair cortisol concentration (HCC) is a valuable biomarker for evaluating chronic stress in preschoolers. However, few studies have explored early life HCC and its associated factors. This prospective cohort study analysed the HCC in children aged 6-48 months and its associations with parental HCC as well as positive and negative parental mental health outcomes. We used data from the ongoing Longitudinal Examination Across Prenatal and Postpartum Health in Taiwan (LEAPP-HIT) project, conducted in Taipei between 2020 and 2024. Hair samples were collected from both parents and children in 177 families (91 samples obtained during pregnancy and 86 during the postpartum period). The parents also completed self-reported questionnaires. Multiple linear regression was conducted to analyse the data. We observed a significant positive correlation between parents' and preschoolers' HCC. Furthermore, maternal depression (adjusted beta coefficient [aβ] = 0.09, 95% confidence interval [CI] = 0.02, 0.16) and perceived stress (aβ = 0.15, 95% CI = 0.02, 0.26) were positively associated with preschoolers' HCC. By contrast, higher maternal eudaimonia was associated with lower HCC in preschoolers (aβ = -0.11, 95% CI = -0.20, -0.01). For parents, maternal depression, anxiety, and perceived stress were independently associated with an increased HCC during the postnatal period, whereas maternal eudaimonia was negatively associated with HCC. Our results indicate that both mothers and fathers affect children's responses to stress. Assessment of cortisol stress hormone concentrations through hair samples can be a key means of detecting preschoolers' stress levels and enabling early intervention.

关键词： anxiety eudaimonia fathers hair cortisol concentration perceived stress preschoolers

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SENP2 restrains the generation of pathogenic Th17 cells in mouse models of colitis

Communications biology

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Communications biology 2023年第1期6卷 629页

作者： Tsan-Tzu Yang Ming-Feng Chiang Che-Chang Chang Shii-Yi Yang Shih-Wen Huang Nan-Shih Liao Hsiu-Ming Shih Wei Hsu Kuo-I Lin Graduate Institute of Immunology College of Medicine National Taiwan University Taipei 10002 Taiwan. Genomics Research Center Academia Sinica Taipei 11529 Taiwan. The Ph.D. Program for Translational Medicine College of Medical Science and Technology Taipei Medical University Taipei 11031 Taiwan. Institute of Molecular Biology Academia Sinica Taipei 11529 Taiwan. Institute of Biomedical Sciences Academia Sinica Taipei 11529 Taiwan. Forsyth Institute Harvard School of Dental Medicine Harvard Stem Cell Institute Harvard University Cambridge MA 02142 USA. Graduate Institute of Immunology College of Medicine National Taiwan University Taipei 10002 Taiwan. kuoilin@gate.sinica.edu.tw. Genomics Research Center Academia Sinica Taipei 11529 Taiwan. kuoilin@gate.sinica.edu.tw.

The molecular mechanisms contributing to the regulation of Th17-mediated inflammation remain underexplored. We here report a SUMO-specific protease (SENP)2-mediated pathway induced in pathogenic Th17 cells that restricts the pathogenesis of inflammatory colitis. SENP2 regulates the maturation of small ubiquitin-like modifiers (SUMO) and recycles SUMO from the substrate proteins. We find higher levels of SENP2 in pathogenic Th17 cells. By deleting Senp2 in T-cell lineages in mice, we demonstrate that the lack of Senp2 exacerbates the severity of experimental colitis, which is linked to elevated levels of GM-CSFIL-17A pathogenic Th17 cells and more severe dysbiosis of the intestinal microbiome. Adoptive transfer experiments demonstrate the cell-autonomous effect of Senp2 in restraining Th17 differentiation and colitis. The enzymatic activity of SENP2 is important for deSUMOylation of Smad4, which reduces Smad4 nuclear entry and Rorc expression. Our findings reveal a SENP2-mediated regulatory axis in the pathogenicity of Th17 cells.

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