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第11届世界华人药物化学研讨会（ISCMC 2018）

作者： Huiju Tseng Liangchieh Chen Changyi Liu Yunyi Huang Chengchung Yen Jingru Weng Yehlin Lu Wenchi Hou Tony Eight Lin Ihorng Pan Kuokuei Huang Weijan Huang Kaicheng Hsu Program in Biotechnology Research and Development College of PharmacyTaipei Medical University Graduate Institute of Pharmacognosy College of PharmacyTaipei Medical University School of Pharmacy College of PharmacyTaipei Medical University Graduate Institute of Cancer Biology and Drug Discovery College of Medical Science and TechnologyTaipei Medical University Department of Marine Technology and Resources College of Marine SciencesSun Yat-sen University Herbal Medicinal Product Div. Industrial Technology Research Institute Ph.D.Program for the Clinical Drug Discovery from Botanical Herbs College of PharmacyTaipei Medical University School of Pharmacy “Defense Medical Center”

Alzheimer's disease(AD) is a progressive neurodegenerative disorder with multiple ***-amyloid(AB) self-aggregation and overexpression of class IIa histone deacetylases(HDACs) are strongly implicated with AD *** this study,a series of novel diarylheptanoid derivatives were designed,synthesized and evaluated for use as dual Aβ self-aggregation and class IIa HDAC *** these compounds,4 j,5 c and Se displayed effective inhibitions for AB self-aggregation,HDACS activity and HDAC7 activity with IC50 values of < 10 μ*** compounds contain three common features:(1) a catechol or pyrogallol moiety,(2) a carbonyl linker and(3) an aromatic ring that can function as an HDAC cap and create hydrophobic interactions with Aβ***,compounds 4 j,5 c and 5 e showed no significant cytotoxicity to human neuroblastoma SH-SY5 Y cells and also exhibited neuroprotective effect against H2O2-induced ***,these promising in vitro data highlighted compounds 4 j,5 c and 5 e as lead compounds that are worthy for further investigation.

关键词： Alzheimer's disease Aβ aggregation Histone deacetylase Isoform-selective inhibitors Dual inhibitors

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Metabolomics and Network Biology for sensitive monitoring of how growth environment changes affect the physiology of industrial-scale perfusion cultures

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IFAC Proceedings Volumes 2013年第31期46卷 227-232页

作者： S.I. Vernardis C.T. Goudar M.I. Klapa Metabolic Engineering and Systems Biology Laboratory Institute of Chemical Engineering Foundation for Research and Technology-Hellas Patras GR- 265 04 Greece Cell Culture Development Global Biological Development Bayer HealthCare 800 Dwight Way Berkeley CA 94710 Interdepartmental Graduate Program in “Informatics in Life Sciences” Medical School University of Patras Greece & Current Address: Cell Science and Technology AMGEN Inc. Thousand Oaks CA 91320 USA Secondary Affiliation: Depts of Chemical & Biomolecular Eng and Bioengineering University of Maryland College Park MD 20742 USA

Metabolomic analysis can indeed enhance the prime variable dataset for the monitoring of perfusion cultures by providing a higher resolution view of the metabolic state. Metabolic profiles can capture physiological state shifts over the course of the perfusion cultures and indicate a metabolic “signature” of the phase transitions, which is not observable from prime variable data. Notably, metabolomics provides orthogonal (to prime variables) evidence that all cultures follow this same metabolic state shift with cell age, independently of bioreactor scale. Additionally, this analysis can increase the information content of process development experiments by helping better understand the impact of changes in bioreactor operating conditions on cell physiology. In this context, metabolic profiling could be integrated into the monitoring of cell physiology in perfusion cultures.

关键词： industrial cell culture engineering GC-MS metabolomics perfusion cultures multivariate statistical analysis metabolic network reconstruction growth environmental variations

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Small-scale fisheries (SSF) management and conservation schemes and their application in the Philippines

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Marine Policy 2024年 161卷

作者： Barboza, Anna Macusi, Edison D. Borazon, Elaine Q. Santos, Mudjekeewis D. Muallil, Richard N. Nallos, Ivy M. International Master of Science in Marine Biological Resources Program University of Ghent Belgium Faculty of Agriculture and Life Sciences Davao Oriental State University Davao Oriental Mati City Philippines International Graduate Program of Education and Human Development (IGPEHD) College of Social Sciences National Sun Yat-sen University Kaohsiung 804 Taiwan National Fisheries Research and Development Institute (NFRDI) Metro Manila Quezon City 1008 Philippines Mindanao State University (MSU) Tawi-Tawi College of Technology and Oceanography Tawi-Tawi Bongao Philippines

To reach balance and harmony, current demand, growth, and sustainability, there is a need to include economic, social, cultural, and biological principles for a holistic approach in fisheries management. However, despite the combined efforts, severe challenges still threaten the sustainability of small-scale fisheries in the Philippines. This study carried out a systematic review of the literature published from 1998 to 2021 in the Philippines. This timeframe was selected to align with the implementation of the Philippines Fisheries Code of 1998 (Republic Act 8550) and its subsequent amendment as Republic Act 10654 in 2015, which legally recognized sustainable fisheries by local governments from 1998 onwards. The literature search came out with a total of 775 articles from Web of science and 345 from SCOPUS, after duplicates were removed, 207 literature were included in the synthesis. The main issues that came out are on fishing, reef, livelihood, catch and protected areas. In the Philippines, the reliance of fishers on their livelihood remains a limiting factor in the effectiveness of management plans as pressure from the increasing population of highly fishery-dependent coastal communities, food insecurity, and catch demand can render tactics ineffective. The root issues are larger and systemic, but stem from a lack of sustainable financing to support the viability of established fishery management schemes. Marine conservation programs require consideration of the economic impacts and creating alternatives to diversify income sources so that other larger drivers of unsustainable fisheries can be addressed. © 2024 Elsevier Ltd

关键词： Ecosystem-based management Fisheries management Philippines PRISMA Small-scale fisheries (SSF)

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Timing of Epinephrine Alters the Hemodynamics of Children with Traumatic Hospital Cardiac Arrest

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Journal of Emergency Medicine 2017年第3期53卷 434-435页

作者： Lin, Y.R. Syue, Y.J. Buddhakosai, W. Lu, H.E. Chang, C.F. Chang, C.Y. Chen, C.H. Chen, W.L. Li, C.J. Department of Emergency Medicine Changhua Christian Hospital Changhua Taiwan School of Medicine Kaohsiung Medical University Kaohsiung Taiwan School of Medicine Chung Shan Medical University Taichung Taiwan Department of Anesthesiology Kaohsiung Chang Gung Memorial Hospital Chang Gung University College of Medicine Kaohsiung Taiwan Department of Biological Science and Technology National Chiao Tung University Hsinchu Taiwan Interdisciplinary Graduate Program in Genetic Engineering Graduate School Kasetsart University Bangkhen campus Bangkok Thailand Bioresource Collection and Research Center Food Industry Research and Development Institute Hsinchu Taiwan Department of Emergency Medicine Kaohsiung Chang Gung Memorial Hospital Chang Gung University College of Medicine Kaohsiung Taiwan Department of Public Health College of Health Science Kaohsiung Medical University Kaohsiung Taiwan

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A re-evaluation of the Chaetothyriales using criteria of comparative biology

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Fungal Diversity 2020年第4期103卷 47-85页

作者： Yu Quan Lucia Muggia Leandro F.Moreno Meizhu Wang Abdullah M.S.Al-Hatmi Nickolas da Silva Menezes Dongmei Shi Shuwen Deng Sarah Ahmed Kevin D.Hyde Vania A.Vicente Yingqian Kang JBenjamin Stielow Sybren de Hoog Centre of Expertise in Mycology of Radboud University Medical Centre/Canisius Wilhelmina Hospital NijmegenThe Netherlands Key Laboratory of Environmental Pollution Monitoring and Disease Control Ministry of Education of Guizhou&Key Laboratory of Medical Microbiology and ParasitologySchool of Basic Medical SciencesGuizhou Medical UniversityGuiyangChina College of Food and Pharmaceutical Engineering Guizhou Institute of TechnologyGuiyangChina Department of Life Sciences University of TriesteTriesteItaly Amsterdam Medical Center AmsterdamThe Netherlands Foundation Atlas of Clinical Fungi HilversumThe Netherlands Ministry of Health Directorate General of Health ServicesIbriOman Postgraduate Program in Microbiology Parasitology and PathologyBiological SciencesDepartment of Basic PathologyFederal University of ParanaCuritibaBrazil Department of Dermatology&Laboratory of Medical Mycology Jining No.1 People’s HospitalJiningShandongChina Department of Medical Microbiology People’s Hospital of Suzhou National New&Hi-Tech Industrial Development ZoneSuzhouChina Center of Excellence in Fungal Diversity Mae Fah Luang UniversityChiang RaiThailand Thermo Fisher Diagnostics Specialty Diagnostics GroupLandsmeerThe Netherlands Guizhou Academy of Tobacco Science GuiyangChina Engineering Bioprocess and Biotechnology Post-graduation Program Department of Bioprocess Engineering and BiotechnologyFederal University of ParanaCuritibaBrazil

Chaetothyriales is an ascomycetous order within *** order is particularly known through the black yeasts and filamentous relatives that cause opportunistic infections in *** species in the order are consistently *** and habitats of species are highly diverse,and often rather extreme in terms of exposition and *** are defined on the basis of evolutionary history,which is reconstructed by time of divergence and concepts of comparative biology using stochastical character mapping and a multi-rate Brownian motion model to reconstruct ecological ancestral character *** is hypothesized to be with a rock-inhabiting life *** disparity increased significantly in late Jurassic,probably due to expansion of cytochromes followed by colonization of vacant *** diversification took place subsequently,but at a low level of innovation resulting in strong niche conservatism for extant *** are ecologically different in degrees of *** of the clades has adapted ant domatia,which are rich in *** derived families,similar processes have enabled survival in domesticated environments rich in creosote and toxic hydrocarbons,and this ability might also explain the pronounced infectious ability of vertebrate hosts observed in these *** systems of morphological classification poorly correspond with recent phylogenetic *** are hypothesized to have low competitive ability against neighboring microbes,which interferes with their laboratory isolation on routine *** dataset is unbalanced in that a large part of the extant biodiversity has not been analyzed by molecular methods,novel taxonomic entities being introduced at a regular *** study comprises all available species sequenced to date for LSU and ITS,and a nomenclatural overview is provided.A limited number of species could not be assigned to any extant family.

关键词： Black yeasts Phylogeny Ecology Ancestral reconstruction Evolution Nomenclature

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Transdermal nanolipoplex simultaneously inhibits subcutaneous melanoma growth and suppresses systemically metastatic melanoma by activating host immunity

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Nanomedicine: Nanotechnology, Biology, and Medicine 2023年 47卷 102628-102628页

作者： Chen, Chia-Hung Weng, Tzu-Han Chuang, Cheng-Hsun Huang, Kai-Yao Huang, Sih-Cheng Chen, Pin-Rong Huang, Hsiao-Hsuan Huang, Ling-Ya Shen, Pei-Chun Chuang, Po-Ya Huang, Hsiao-Yen Wu, Yi-Syuan Chang, Hao-Chiun Weng, Shun-Long Liao, Kuang-Wen Department of Medical Research Hsinchu MacKay Memorial Hospital Hsinchu City30071 Taiwan Dependent of Medical Education MacKay Memorial Hospital Taipei10449 Taiwan Institute of Molecular Medicine and Bioengineering National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan Department of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan Industrial Development Graduate Program of College of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan Institute of Bioinformatics and Systems Biology National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan Department of Medicine MacKay Medical College New Taipei City25245 Taiwan Department of Obstetrics and Gynecology Hsinchu MacKay Memorial Hospital Hsinchu City30071 Taiwan MacKay Junior College of Medicine Nursing and Management Taipei City11260 Taiwan Drug Development and Value Creation Research Center College of Dental Medicine Kaohsiung Medical University School of Dentistry Graduate Institute of Medicine College of Medicine Center for Cancer Research Kaohsiung Medical University Kaohsiung City80708 Taiwan Center for Intelligent Drug Systems and Smart Bio-devices National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan Department of Biotechnology and Bioindustry Sciences National Cheng Kung University Tainan City70101 Taiwan Ph.D. Degree Program of Biomedical Science and Engineering National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan

Benefit for clinical melanoma treatments, the transdermal neoadjuvant therapy could reduce surgery region and increase immunotherapy efficacy. Using lipoplex (Lipo-PEG-PEI-complex, LPPC) encapsulated doxorubicin (DOX) and carrying CpG oligodeoxynucleotide;the transdermally administered nano-liposomal drug complex (LPPC-DOX-CpG) would have high cytotoxicity and immunostimulatory activity to suppress systemic metastasis of melanoma. LPPC-DOX-CpG dramatically suppressed subcutaneous melanoma growth by inducing tumor cell apoptosis and recruiting immune cells into the tumor area. Animal studies further showed that the colonization and growth of spontaneously metastatic melanoma cells in the liver and lung were suppressed by transdermal LPPC-DOX-CpG. Furthermore, NGS analysis revealed IFN-γ and NF-κB pathways were triggered to recruit and activate the antigen-presenting-cells and effecter cells, which could activate the anti-tumor responses as the major mechanism responsible for the therapeutic effect of LPPC-DOX-CpG. Finally, we have successfully proved transdermal LPPC-DOX-CpG as a promising penetrative carrier to activate systemic anti-tumor immunity against subcutaneous and metastatic tumor. © 2022

关键词： Tumors

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A Hydrogeochemical Approach to Conserve Coastal Groundwater-Dependent Ecosystems

SSRN

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SSRN 2024年

作者： Dyring, Madeleine Hofmann, Harald McDougall, Andrew Marshall, Sharon Cendón, Dioni I. Stanton, David Hamer, Ned Rodhe, Melissa M. The University of Queensland School of the Environment BrisbaneQLD Australia Commonwealth Scientific and Industrial Research Organisation Environment BrisbaneQLD Australia Department of Regional Development Manufacturing and Water BundabergQLD Australia Australian Nuclear Science and Technology Organisation Lucas Heights Sydney Australia University of New South Wales School of Biological Earth and Environmental Sciences SydneyNSW Australia 3D Environmental BrisbaneQLD Australia California Water Program The Nature Conservancy SacramentoCA United States Rohde Environmental Consulting LLC SeattleWA United States SUNY College of Environmental Science and Forestry SyracuseNY United States

Site-focused hydrogeological studies are often touted as a fundamental requirement for the effective conservation of groundwater-dependent ecosystems (GDEs) as they unveil important detail about processes that threaten groundwater and connected ecosystems. We used a hydrogeochemical and isotopic approach to characterise groundwater source, movement and recharge in a highly complex coastal dune system, the Cooloola Sand Mass in south-east Queensland, Australia. For a relatively small area (620 km2), Cooloola contains a large variety of GDEs including wetlands, fens, lakes, and streams. GDEs within Cooloola are exposed to a myriad of threats including over-abstraction, saltwater intrusion and climatic drying. Conservation approaches are broadly applied to these valuable habitats, where greater hydrological understanding could inform management actions. Major ions, trace elements, stable water isotopes (δ18O and δ2H) from 83 sites, as well as isotope tracers (3H and 14C) from 12 sites were used to characterise groundwater sources, movement, recharge processes and estimate mean residence time (MRT). Estimated MRTs ranged from 12 to 100 years, with recharge of the regional aquifer reliant on high monthly rainfall totals (>150 – 200 mm) associated with La Niña phases across eastern Australia. Results highlight the complex nature of the groundwater system with GDEs depending solely on the regional aquifer, shallow perched aquifers, or a mix of both sources. Each of these sources are exposed to different threats depending on recharge mechanisms, coastal proximity and surrounding land-use. © 2024, The Authors. All rights reserved.

关键词： Hydrogeology

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technology Roadmap for Flexible Sensors

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ACS NANO 2023年第6期17卷 5211-5295页

作者： Luo, Yifei Abidian, Mohammad Reza Ahn, Jong-Hyun Akinwande, Deji Andrews, Anne M. Antonietti, Markus Bao, Zhenan Berggren, Magnus Berkey, Christopher A. Bettinger, Christopher John Chen, Jun Chen, Peng Cheng, Wenlong Cheng, Xu Choi, Seon-Jin Chortos, Alex Dagdeviren, Canan Dauskardt, Reinhold H. Di, Chong-an Dickey, Michael D. Duan, Xiangfeng Facchetti, Antonio Fan, Zhiyong Fang, Yin Feng, Jianyou Feng, Xue Gao, Huajian Gao, Wei Gong, Xiwen Guo, Chuan Fei Guo, Xiaojun Hartel, Martin C. He, Zihan Ho, John S. Hu, Youfan Huang, Qiyao Huang, Yu Huo, Fengwei Hussain, Muhammad M. Javey, Ali Jeong, Unyong Jiang, Chen Jiang, Xingyu Kang, Jiheong Karnaushenko, Daniil Khademhosseini, Ali Kim, Dae-Hyeong Kim, Il-Doo Kireev, Dmitry Kong, Lingxuan Lee, Chengkuo Lee, Nae-Eung Lee, Pooi See Lee, Tae-Woo Li, Fengyu Li, Jinxing Liang, Cuiyuan Lim, Chwee Teck Lin, Yuanjing Lipomi, Darren J. Liu, Jia Liu, Kai Liu, Nan Liu, Ren Liu, Yuxin Liu, Yuxuan Liu, Zhiyuan Liu, Zhuangjian Loh, Xian Jun Lu, Nanshu Lv, Zhisheng Magdassi, Shlomo Malliaras, George G. Matsuhisa, Naoji Nathan, Arokia Niu, Simiao Pan, Jieming Pang, Changhyun Pei, Qibing Peng, Huisheng Qi, Dianpeng Ren, Huaying Rogers, John A. Rowe, Aaron Schmidt, Oliver G. Sekitani, Tsuyoshi Seo, Dae-Gyo Shen, Guozhen Sheng, Xing Shi, Qiongfeng Someya, Takao Song, Yanlin Stavrinidou, Eleni Su, Meng Sun, Xuemei Takei, Kuniharu Tao, Xiao-Ming Tee, Benjamin C. K. Thean, Aaron Voon-Yew Trung, Tran Quang Wan, Changjin Wang, Huiliang Wang, Joseph Wang, Ming Wang, Sihong Wang, Ting Wang, Zhong Lin Weiss, Paul S. Wen, Hanqi Xu, Sheng Xu, Tailin Yan, Hongping Yan, Xuzhou Yang, Hui Yang, Le Yang, Shuaijian Yin, Lan Yu, Cunjiang Yu, Guihua Yu, Jing Yu, Shu-Hong Yu, Xinge Zamburg, Evgeny Zhang, Haixia Zhang, Xiangyu Zhang, Xiaosheng Zhang, Xueji Zhang, Yihui Zhang, Yu Zhao, Siyuan Zhao, Xuanhe Zheng, Yuanjin Zheng, Yu-Qing Zheng, Zijian Zhou, Tao Zhu, Bowen Zhu, Ming Zhu, Rong Zhu, Yangzhi Zhu, Yong Zou, Guijin Chen, Xiaodong 08-03 Innovis Singapore 138634 Republic of Singapore Innovative Centre for Flexible Devices (iFLEX) School of Materials Science and Engineering Nanyang Technological University Singapore 639798 Singapore Department of Biomedical Engineering University of Houston Houston Texas 77024 United States School of Electrical and Electronic Engineering Yonsei University Seoul 03722 Republic of Korea Department of Electrical and Computer Engineering The University of Texas at Austin Austin Texas 78712 United States Microelectronics Research Center The University of Texas at Austin Austin Texas 78758 United States Department of Chemistry and Biochemistry California NanoSystems Institute and Department of Psychiatry and Biobehavioral Sciences Semel Institute for Neuroscience and Human Behavior and Hatos Center for Neuropharmacology University of California Los Angeles Los Angeles California 90095 United States Colloid Chemistry Department Max Planck Institute of Colloids and Interfaces 14476 Potsdam Germany Department of Chemical Engineering Stanford University Stanford California 94305 United States Laboratory of Organic Electronics Department of Science and Technology Campus Norrköping Linköping University 83 Linköping Sweden Wallenberg Initiative Materials Science for Sustainability (WISE) and Wallenberg Wood Science Center (WWSC) SE-100 44 Stockholm Sweden Department of Materials Science and Engineering Stanford University Stanford California 94301 United States Department of Biomedical Engineering and Department of Materials Science and Engineering Carnegie Mellon University Pittsburgh Pennsylvania 15213 United States Department of Bioengineering University of California Los Angeles Los Angeles California 90095 United States School of Chemistry Chemical Engineering and Biotechnology Nanyang Technological University Singapore 637457 Singapore Nanobionics Group Department of Chemical and Biological Engineering Monash University Clayton Australia 3800 Monash

Humans rely increasingly on sensors to address grand challenges and to improve quality of life in the era of digitalization and big data. For ubiquitous sensing, flexible sensors are developed to overcome the limitations of conventional rigid counterparts. Despite rapid advancement in bench-side research over the last decade, the market adoption of flexible sensors remains limited. To ease and to expedite their deployment, here, we identify bottlenecks hindering the maturation of flexible sensors and propose promising solutions. We first analyze continued...challenges in achieving satisfactory sensing performance for real-world applications and then summarize issues in compatible sensor-biology interfaces, followed by brief discussions on powering and connecting sensor networks. Issues en route to commercialization and for sustainable growth of the sector are also analyzed, highlighting environmental concerns and emphasizing nontechnical issues such as business, regulatory, and ethical considerations. Additionally, we look at future intelligent flexible sensors. In proposing a comprehensive roadmap, we hope to steer research efforts towards common goals and to guide coordinated development strategies from disparate communities. Through such collaborative

关键词： soft materials mechanics engineering flexible electronics conformable sensors bioelectronics human-machine interfaces body area sensor networks technology translation sustainable electronics

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A flexible liposomal polymer complex as a platform of specific and regulable immune regulation for individual cancer immunotherapy

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Journal of Experimental and Clinical Cancer Research 2023年第1期42卷 29-29页

作者： Chen, Chia-Hung Weng, Tzu-Han Huang, Hsiao-Hsuan Huang, Ling-Ya Huang, Kai-Yao Chen, Pin-Rong Yeh, Kuang-Yu Huang, Chi-Ting Chien, Yu-Tzu Chuang, Po-Ya Lin, Yu-Ling Tsai, Nu-Man Liu, Shih-Jen Su, Yu-Cheng Weng, Shun-Long Liao, Kuang-Wen Department of Medical Research Hsinchu MacKay Memorial Hospital Hsinchu City 30071 Taiwan Department of Dermatology MacKay Memorial Hospital Taipei City 10449 Taiwan Industrial Development Graduate Program of College of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu City 30068 Taiwan Institute of Bioinformatics and Systems Biology National Yang Ming Chiao Tung University Hsinchu City 30068 Taiwan Department of Medicine MacKay Medical College New Taipei City 25245 Taiwan Institute of Molecular Medicine and Bioengineering National Yang Ming Chiao Tung University Hsinchu City 30068 Taiwan Department of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu City 30068 Taiwan Agricultural Biotechnology Research Center Academia Sinica Taipei 11529 Taiwan Department of Medical Laboratory and Biotechnology Chung Shan Medical University Taichung City 40201 Taiwan Department of Pathology and Clinical Laboratory Chung Shan Medical University Hospital Taichung City 40201 Taiwan National Institute of Infectious Diseases and Vaccinology National Health Research Institutes Miaoli 350401 Taiwan Department of Obstetrics and Gynecology Hsinchu MacKay Memorial Hospital Hsinchu City 30071 Taiwan MacKay Junior College of Medicine Nursing and Management Taipei City 11260 Taiwan Graduate Institute of Medicine College of Medicine Kaohsiung Medical University Kaohsiung City 80708 Taiwan College of Dental Medicine Kaohsiung Medical University School of Dentistry Kaohsiung City 80708 Taiwan Department of Biotechnology and Bioindustry Sciences National Cheng Kung University Tainan City 70101 Taiwan Center for Intelligent Drug Systems and Smart Bio-Devices National Yang Ming Chiao Tung University Hsinchu City 30068 Taiwan

Background: The applicability and therapeutic efficacy of specific personalized immunotherapy for cancer patients is limited by the genetic diversity of the host or the tumor. Side-effects such as immune-related adverse events (IRAEs) derived from the administration of immunotherapy have also been observed. Therefore, regulatory immunotherapy is required for cancer patients and should be developed. Methods: The cationic lipo-PEG-PEI complex (LPPC) can stably and irreplaceably adsorb various proteins on its surface without covalent linkage, and the bound proteins maintain their original functions. In this study, LPPC was developed as an immunoregulatory platform for personalized immunotherapy for tumors to address the barriers related to the heterogenetic characteristics of MHC molecules or tumor associated antigens (TAAs) in the patient population. Here, the immune-suppressive and highly metastatic melanoma, B16F10 cells were used to examine the effects of this platform. Adsorption of anti-CD3 antibodies, HLA-A2/peptide, or dendritic cells’ membrane proteins (MP) could flexibly provide pan-T-cell responses, specific Th1 responses, or specific Th1 and Th2 responses, depending on the host needs. Furthermore, with regulatory antibodies, the immuno-LPPC complex properly mediated immune responses by adsorbing positive or negative antibodies, such as anti-CD28 or anti-CTLA4 antibodies. Results: The results clearly showed that treatment with LPPC/MP/CD28 complexes activated specific Th1 and Th2 responses, including cytokine release, CTL and prevented T-cell apoptosis. Moreover, LPPC/MP/CD28 complexes could eliminate metastatic B16F10 melanoma cells in the lung more efficiently than LPPC/MP. Interestingly, the melanoma resistance of mice treated with LPPC/MP/CD28 complexes would be reversed to susceptible after administration with LPPC/MP/CTLA4 complexes. NGS data revealed that LPPC/MP/CD28 complexes could enhance the gene expression of cytokine and chemokine pathways to st

关键词： Costimulatory molecules Immunotherapy LPPC personalized cancer therapy Tumor heterogenicity

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MiR34 contributes to spinal muscular atrophy and AAV9-mediated delivery of MiR34a ameliorates the motor deficits in SMA mice

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Molecular therapy. Nucleic acids 2023年 32卷 144-160页

作者： Tai-Heng Chen Shih-Hsin Chang Yu-Fu Wu Ya-Ping Yen Fang-Yu Hsu Yen-Chung Chen Yang Ming Ho-Chiang Hsu Yi-Ching Su Sheng-Tang Wong Jui-Hung Hung Shih-Hwa Chiou Yuh-Jyh Jong Jun-An Chen PhD Program in Translational Medicine Kaohsiung Medical University Kaohsiung 80708 and Academia Sinica Taipei 11529 Taiwan. Institute of Molecular Biology Academia Sinica Taipei 11529 Taiwan. Department of Pediatrics Kaohsiung Medical University Kaohsiung 80708 Taiwan. School of Post-Baccalaureate Medicine Kaohsiung Medical University Kaohsiung 80708 Taiwan. Neuroscience Program of Academia Sinica Academia Sinica Taipei 11529 Taiwan. Department of Computer Science National Yang Ming Chiao Tung University Hsinchu 30093 Taiwan. Institute of Pharmacology School of Medicine National Yang Ming Chiao Tung University Taipei 11221 Taiwan. Innovative Cellular Therapy Center Department of Medical Research Taipei Veterans General Hospital Taipei 11217 Taiwan. Department of Laboratory Medicine Kaohsiung Medical University Kaohsiung 80708 Taiwan. Translational Research Center of Neuromuscular Diseases Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung 80708 Taiwan. Graduate Institute of Clinical Medicine College of Medicine Kaohsiung Medical University Kaohsiung 80708 Taiwan. Drug Development and Value Creation Research Center Kaohsiung Medical University Kaohsiung 80708 Taiwan. Department of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu 30093 Taiwan.

Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by the selective loss of spinal motor neurons (MNs) and concomitant muscle weakness. Mutation of is known to cause SMA, and restoring SMN protein levels via antisense oligonucleotide treatment is effective for ameliorating symptoms. However, this approach is hindered by exorbitant costs, invasive procedures, and poor treatment responses of some patients. Here, we seek to circumvent these hurdles by identifying reliable biomarkers that could predict treatment efficacy. We uncovered that MiR34 exhibits consistent downregulation during SMA progression in both human and rodent contexts. Importantly, family-knockout mice display axon swelling and reduced neuromuscular junction (NMJ) endplates, recapitulating SMA pathology. Introducing MiR34a via scAAV9 improved the motor ability of SMNΔ7 mice, possibly by restoring NMJ endplate size. Finally, we observed a consistent decreasing trend in MiR34 family expression in the cerebrospinal fluid (CSF) of type I SMA patients during the loading phase of nusinersen treatment. Baseline CSF MiR34 levels before nusinersen injection proved predictive of patient motor skills 1 year later. Thus, we propose that MiR34 may serve as a biomarker of SMA since it is associated with the pathology and can help evaluate the therapeutic effects of nusinersen.

关键词： ASO MT: Non-coding RNAs MiR34 SMA biomarker microRNA nusinersen spinal muscular atrophy

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