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The role of input imaging combination and ADC threshold on segmentation of acute ischemic stroke lesion using U-Net

European Radiology 2023年第9期33卷 6157-6167页

作者： Li, Ya-Hui Lin, Shao-Chieh Chung, Hsiao-Wen Chang, Chia-Ching Peng, Hsu-Hsia Huang, Teng-Yi Shen, Wu-Chung Tsai, Chon-Haw Lo, Yu-Chien Lee, Tung-Yang Juan, Cheng-Hsuan Juan, Cheng-En Chang, Hing-Chiu Liu, Yi-Jui Juan, Chun-Jung Graduate Institute of Biomedical Electronics and Bioinformatics National Taiwan University Taipei Taiwan Department of Medical Imaging China Medical University Hsinchu Hospital No. 199 Sec. 1 Xinglong Rd. Zhubei City Hsinchu County 302 Hsinchu Taiwan Ph.D. Program in Electrical and Communication Engineering Feng Chia University Taichung Taiwan Department of Electrical Engineering National Taiwan University Taipei Taiwan Department of Management Science National Yang Ming Chiao Tung University Hsinchu Taiwan Department of Biomedical Engineering and Environmental Sciences National Tsing Hua University Hsinchu Taiwan Department of Electrical Engineering National Taiwan University of Science and Technology Taipei Taiwan Department of Radiology School of Medicine College of Medicine China Medical University Taichung Taiwan Department of Medical Imaging Medical University Hospital Taichung Taiwan Department of Neurology China Medical University Hospital Taichung Taiwan Cheng Ching Hospital Taichung Taiwan Master’s Program of Biomedical Informatics and Biomedical Engineering Feng Chia University Taichung Taiwan Department of Automatic Control Engineering Feng Chia University No. 100 Wenhwa Rd. Seatwen Taichung 40724 Taiwan Department of Biomedical Engineering The Chinese University of Hong Kong ERB1112 11/F William M.W. Mong Engineering Building N.T Shatin Hong Kong Multi-Scale Medical Robotics Center The Chinese University of Hong Kong N.T Shatin Hong Kong Department of Biomedical Engineering National Defense Medical Center Taipei Taiwan Department of Computer Science and Information Engineering National Taiwan University Taipei Taiwan

Background: To evaluate the effect of the weighting of input imaging combo and ADC threshold on the performance of the U-Net and to find an optimized input imaging combo and ADC threshold in segmenting acute ischemic stroke (AIS) lesion. Methods: This study retrospectively enrolled a total of 212 patients having AIS. Four combos, including ADC-ADC-ADC (AAA), DWI-ADC-ADC (DAA), DWI-DWI-ADC (DDA), and DWI-DWI-DWI (DDD), were used as input images, respectively. Three ADC thresholds including 0.6, 0.8 and 1.8 × 10^–3 mm²/s were applied. Dice similarity coefficient (DSC) was used to evaluate the segmentation performance of U-Nets. Nonparametric Kruskal–Wallis test with Tukey–Kramer post-hoc tests were used for comparison. A p <.05 was considered statistically significant. Results: The DSC significantly varied among different combos of images and different ADC thresholds. Hybrid U-Nets outperformed uniform U-Nets at ADC thresholds of 0.6 × 10^–3 mm²/s and 0.8 × 10^–3 mm²/s (p <.001). The U-Net with imaging combo of DDD had segmentation performance similar to hybrid U-Nets at an ADC threshold of 1.8 × 10^–3 mm²/s (p =.062 to 1). The U-Net using the imaging combo of DAA at the ADC threshold of 0.6 × 10^–3 mm²/s achieved the highest DSC in the segmentation of AIS lesion. Conclusions: The segmentation performance of U-Net for AIS varies among the input imaging combos and ADC thresholds. The U-Net is optimized by choosing the imaging combo of DAA at an ADC threshold of 0.6 × 10^–3 mm²/s in segmentating AIS lesion with highest DSC. Key Points: • Segmentation performance of U-Net for AIS differs among input imaging combos. • Segmentation performance of U-Net for AIS differs among ADC thresholds. • U-Net is optimized using DAA with ADC = 0.6 × 10^–3mm²/s. © 2023, The Author(s), under exclusive licence to European Society of Radiology.

关键词： Deep Learning Diffusion Magnetic Resonance Imaging Ischemic Stroke Neural Networks, Computer Retrospective Study

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Titania Nanosheets Generates Peroxynitrite for S-Nitrosylation and Enhanced p53 Function in Lung Cancer Cells

Research Square

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Research Square 2021年

作者： Soonnarong, Rapeepun Tungsukruthai, Sucharat Nutho, Bodee Rungrotmongkol, Thanyada Vinayanuwattikun, Chanida Maluangnont, Tosapol Chanvorachote, Pithi Interdisciplinary Program of Pharmacology Graduate School Chulalongkorn University Bangkok Thailand Cell-based Drug and Health Products Development Research Unit Chulalongkorn University Bangkok Thailand Departments of Pharmacology and Physiology Faculty of Pharmaceutical Sciences Bangkok Thailand Department of Pharmacology Faculty of Science Mahidol University Bangkok Thailand Biocatalyst and Environmental Biotechnology Reseach Unit Department of Biochemistry Faculty of Science Chulalongkorn University Bangkok Thailand Program in Bioinformatics and Computational Biology Graduate School Chulalongkorn University Bangkok Thailand Division of Medical Oncology Department of Medicine Chulalongkorn University Bangkok Thailand College of Materials Innovation and Technology King Mongkut’s Institute of Technology Ladkrabang Bangkok Thailand

Background: Metal oxide nanomaterials are increasingly being exploited in cancer therapy thanks to their unique properties, which can enhance the efficacy of current cancer therapies. However, the nanotoxicity and mechanism of Ti0.8O2 nanosheets for specific site-targeting strategies in NSCLC have not yet been investigated. Methods: The effects of Ti0.8O2 nanosheets on cytotoxicity in NSCLC cells and normal cells were examined. The apoptosis characteristics, including condensed and fragmented nuclei, as assessed by positive staining with annexin V. The cellular uptake of the nanosheets and the induction of stress fiber were assessed via transmission electron microscopy (TEM) and scanning electron microscopy (SEM) analyses, respectively. We also evaluated the expression of protein in death mechanism to identify the molecular mechanisms behind the toxicity of these cells. We investigated the relationship between S-nitrosylation and the increase in p53 stability by molecular dynamics. Results: Ti0.8O2 nanosheets caused cytotoxicity in several lung cancer cells, but not in normal cells. The nanosheets could enter lung cancer cells and exert an apoptosis induction. Results for protein analysis further indicated the activation of p53, increased Bax, decreased Bcl-2 and Mcl-1, and activation of caspase-3. The nanosheets also exhibited a substantial apoptosis effect in drug-resistant metastatic primary lung cancer cells, and it was found that the potency of the nanosheets was dramatically higher than that of cisplatin and etoposide. In terms of their mechanism of action, we found that the mode of apoptosis induction was through the generation of cellular ONOO− mediated the S-nitrosylation of p53 at C182. Molecular dynamics analysis further showed that the S-nitrosylation of one C182 stabilized the p53 dimer. Consequently, this nitrosylation of the protein led to an upregulation of p53 through its stabilization. Conclusions: Taking all the evidence together, we provided info

关键词： Molecular dynamics

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Universal mechanical response of metallic glasses during strain-rate-dependent uniaxial compression

arXiv

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arXiv 2022年

作者： Jin, Weiwei Datye, Amit Schwarz, Udo D. Shattuck, Mark D. O'Hern, Corey S. Department of Mechanical Engineering and Materials Science Yale University New HavenCT06520 United States Department of Chemical and Environmental Engineering Yale University New HavenCT06520 United States Benjamin Levich Institute Physics Department The City College of New York New YorkNY10031 United States Department of Physics Yale University New HavenCT06520 United States Department of Applied Physics Yale University New HavenCT06520 United States Graduate Program in Computational Biology and Bioinformatics Yale University New HavenCT06520 United States

Experimental data on the compressive strength σmax versus strain rate Ε eng for metallic glasses undergoing uniaxial compression shows significantly different behavior for different alloys. For some metallic glasses, σmax decreases with increasing Ε eng, for others, σmax increases with increasing Ε eng, and for others σmax versus Ε eng is nonmonotonic. Using numerical simulations of metallic glasses undergoing uniaxial compression at nonzero strain rate and temperature, we show that they obey a universal relation for the compressive strength versus temperature, which determines their mechanical response. At low Ε eng, increasing strain rate leads to increases in temperature and decreases in σmax∗, whereas at high Ε eng, increasing strain rate leads to decreases in temperature and increases in σmax∗. This non-monotonic behavior of σmax∗ versus temperature causes the nonmonotonic behavior of σmax∗ versus Ε eng. Variations in the internal dissipation change the characteristic strain rate at which the nonmonotonic behavior occurs. These results are general for a wide range of metallic glasses with different atomic interactions, damping coefficients, and chemical compositions. © 2022, CC BY.

关键词： Strain rate

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The complete chloroplast genome ofArtocarpus altilis(Moraceae) and phylogenetic relationships

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Mitochondrial DNA Part B 2021年第8期6卷 2291-2293页

作者： Ueric José Borges de Souza Raíssa Nunes dos Santos Renisson Neponuceno de Araújo Filho Gil Rodrigues dos Santos Renato Almeida Sarmento Fabien De Bellis Fabrício Souza Campos a Laboratory of Bioinformatics & Biotechnology Federal University of Tocantins Gurupi Brazil b Department of Forestry Engineering Federal University of Tocantins Gurupi Brazil c Laboratory of Phytopathology Federal University of Tocantins Gurupi Brazil b Department of Forestry Engineering Federal University of Tocantins Gurupi Brazild Post-Graduate Program in Plant Production Federal University of Tocantins Gurupi Brazil e CIRAD UMR AGAP Institute Montpellier Francef UMR AGAP Institute University of Montpellier CIRAD INRAE L’Institut Agro Montpellier France

The chloroplast (cp) is an essential organelle in higher plants. The genes of the plastome are well suited to infer phylogenetic relationships among taxa. In this study, we report the assembly of the cp genome ofArtocarpus altilisand its phylogeny among species from Moraceae family. The cp genome ofA. altiliswas 160,822 base pair (bp) in length, comprising one large single-copy region of 88,692 bp, one small single-copy region of 19,290 bp, and a pair of inverted repeat regions (IRs) of 26,420 bp. A total of 113 different genes were predicted, including 79 protein-coding genes, 30tRNA genes, and fourrRNA genes. The phylogenetic analysis of 19 species belonging to the Moraceae family confirmed the phylogenetic proximity of the genusArtocarpusandMorusand the genetic similarity ofA. camansiandA. altilis.

关键词： Plastid genome plastome phylogenetic relationships

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Buparlisib and ponatinib inhibit aggressiveness of cholangiocarcinoma cells via suppression of IRS1-related pathway by targeting oxidative stress resistance

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Biomedicine and Pharmacotherapy 2024年 180卷 117569-117569页

作者： Kaewlert, Waleeporn Sakonsinsiri, Chadamas Lert-itthiporn, Worachart Mahalapbutr, Panupong Ali, Saba Rungrotmongkol, Thanyada Jusakul, Apinya Armartmuntree, Napat Pairojkul, Chawalit Feng, Guofei Ma, Ning Pinlaor, Somchai Murata, Mariko Thanan, Raynoo Department of Biochemistry Faculty of Medicine Khon Kaen University Khon Kaen 40002 Thailand Cholangiocarcinoma Research Institute Khon Kaen University Khon Kaen 40002 Thailand Center of Excellence in Structural and Computational Biology Department of Biochemistry Faculty of Science Chulalongkorn University Bangkok 10330 Thailand Program in Bioinformatics and Computational Biology Graduated School Chulalongkorn University Bangkok 10330 Thailand The Center for Research and Development of Medical Diagnostic Laboratories Faculty of Associated Medical Sciences Khon Kaen University Khon Kaen 40002 Thailand Department of Medical Science Amnatcharoen Campus Mahidol University Amnat Charoen 37000 Thailand Department of Pathology Faculty of Medicine Khon Kaen University Khon Kaen 40002 Thailand Department of Environmental and Molecular Medicine Mie University Graduate School of Medicine Mie 514-8507 Japan Graduate School of Health Science Suzuka University of Medical Science Suzuka Mie 510-0226 Japan Department of Parasitology Faculty of Medicine Khon Kaen University Khon Kaen 40002 Thailand

Cholangiocarcinoma (CCA) is an oxidative stress-driven liver cancer with bile duct epithelial cell phenotypes and currently lacks effective treatments, making targeted drug therapy urgently needed. Oxidative stress plays a critical role in CCA carcinogenesis, involving cells with oxidative stress resistance via upregulation of the PI3K and MEKK3 signaling pathways. In this study, we investigated the antineoplastic efficacy of a PI3K inhibitor (buparlisib) and a multi-tyrosine kinase inhibitor (ponatinib) on CCA. The cytotoxicity of the drug combination was studied in vitro using CCA cell lines and in vivo using CCA xenograft models. It was found that the drug combination suppressed growth, colony formation, and migration abilities of CCA cells and induced oxidative damage, cell cycle arrest, and autophagy by suppressing MEKK3 and YAP1 through inhibition of insulin receptor substrate 1 (IRS1) signaling. Moreover, the drugs would potentially bind to the IRS1 protein, significanly decreasing IRS1 phosphorylation. Additionally, the drug combination significantly diminished the expression of YAP1, the cell proliferation marker and an antioxidant regulator, and increased oxidative stress-responsive markers in the xenograft model. In conclusion, targeting oxidative stress resistance with combined buparlisib and ponatinib suppressed tumor growth and migration by repressing IRS1-related pathways and ultimately inducing oxidative damage, suggesting the potential for targeted therapy and clinical trials in CCA patients over the use of a single drug. © 2024 The Authors

关键词： Anti-cancer Bile duct cancer Buparlisib Insulin receptor substrate 1 Ponatinib Targeted therapy

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IDH1 fine-tunes cap-dependent translation initiation

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Journal of Molecular Cell Biology 2019年第10期11卷 816-828页

作者： Lichao Liu JYuyang Lu Fajin Li Xudong Xing Tong Li Xuerui Yang Xiaohua Shen Tsinghua-Peking Center for Life Sciences School of Medicine and School of Life SciencesTsinghua UniversityBeijing 100084China MOE Key Laboratory of Bioinformatics Center for Synthetic Systems BiologySchool of Life SciencesTsinghua UniversityBeijing 100084China Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program School of Life SciencesTsinghua UniversityBeijing 100084China

The metabolic enzyme isocitrate dehydrogenase 1(IDH1)catalyzes the oxidative decarboxylation of isocitrate to a-ketoglutarate(a-KG).Its mutation often leads to aberrant gene expression in ***1 was reported to bind thousands of RNA transcripts in a sequence-dependent manner;yet,the functional significance of this RNA-binding activity remains ***,we report that IDH1 promotes mRNA translation via direct associations with polysome mRNA and translation *** proteomic analysis in embryonic stem cells(ESCs)revealed strikingenrichmentof ribosomal proteins and translation regulators in IDH1-bound protein *** performed ribosomal profiling and analyzed mRNA transcripts that are associated with actively translating ***,knockout of IDH1 in ESCs led to significant downregulation of polysome-bound mRNA in IDH1 targets and subtle upregulation of ribosome densities at the start codon,indicating inefficient translation initiation upon loss of *** IDH1 to a luciferase mRNA via the MS2-MBP system promotes luciferase translation,independently of the catalytic activity of ***,IDH1 fails to enhance luciferase translation driven by an internal ribosome entry ***,these results reveal an unforeseen role of IDH1 in fine-tuning cap-dependent translation via the initiation step.

关键词： IDH1 proteomic interactome translation regulation RNA-binding protein

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Sex-specific interactive effect of melamine and DEHP on a marker of early kidney damage in Taiwanese adults: A national population-based study from the Taiwan Biobank

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Ecotoxicology and Environmental Safety 2023年第1期263卷 115208页

作者： Li, Sih-Syuan Chen, Jia-Jen Su, Ming-Wei Lin, Chien-Wei Chen, Chu-Chih Wang, Yin-Han Liu, Chia-Chu Tsai, Yi-Chun Hsieh, Tusty-Jiuan Wu, Ming-Tsang Wu, Chia-Fang Research Center for Precision Environmental Medicine Kaohsiung Medical University Kaohsiung Taiwan Taiwan Biobank Academia Sinica Taipei Taiwan Division of Biostatistics and Bioinformatics Institute of Population Health Sciences National Health Research Institutes Taiwan Department of Urology Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung Taiwan Division of Nephrology Department of Internal Medicine Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung Taiwan Graduate Institute of Medicine College of Medicine Kaohsiung Medical University Kaohsiung Taiwan Department of Family Medicine Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung Taiwan Ph.D. Program in Environmental and Occupational Medicine Kaohsiung Medical University Kaohsiung Taiwan Department of Public Health Kaohsiung Medical University Kaohsiung Taiwan International Master Program of Translational Medicine National United University Miaoli Taiwan

Taiwan had the high incidence of chronic kidney disease (CKD) worldwide. Our objective was to examine associations between daily exposure of phthalates and melamine, two common nephrotoxins, and kidney damage risk in a well-established nationwide cohort. Study subjects were from Taiwan Biobank (TWB) with existing data of questionnaire and biochemical examinations. Average daily intake (ADI) levels of melamine and seven parental phthalates, including DEHP (di-2-ethylhexylphthalate), DiBP (Dibutyl phthalate), DnBP (Di-n-butyl phthalate), BBzP (Butyl benzyl phthalate), DEP (Diethyl phthalate), and DMP (Dimethyl phthalate) were estimated using a creatinine excretion-based model from urine melamine and 10 phthalate metabolites. Urine microalbumin to creatinine ratio (ACR) was used to represent for the outcome of kidney damage. Two statistical strategies were used: First, a weighted quantile sum (WQS) regression model to select the most important exposure variables of ADI levels of phthalates and melamine associated with ACR;Second, to examine effects of those most important exposure variables on ACR in multivariable linear regression models. In total, 1153 eligible adults were left for analyses. Of them, 591 (51.3%) and 562 (48.7%) were men and women, respectively, with a median age of 49 years old. By WQS, a significant and positive association was found between ADI of melamine and phthalates and ACR (β = 0.14, p = 0.002). ADI levels of melamine had the highest weight (0.57), followed by DEHP (0.13). Next, examining the two most important exposures in association with ACR, we found that the higher the melamine and DEHP intakes, the higher the ACR levels were found. An interaction effect was also found between melamine and DEHP intakes on urine ACR (p = 0.015). This result was more prominent in men (p = 0.008) than in women (p = 0.651). Environmental co-exposure of melamine and DEHP can potentially affect ACR in the community-dwelling Taiwanese adult population. © 2023 T

关键词： Chronic kidney disease (CKD) Interactive effect Melamine Phthalates Renal dysfunction Sex

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Elimination of senescent cells by β-galactosidase-targeted prodrug attenuates inflammation and restores physical function in aged mice

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细胞研究（英文版） 2020年第7期30卷 574-589页

作者： Yusheng Cai Huanhuan Zhou Yinhua Zhu Qi Sun Yin Ji Anqi Xue Yuting Wang Wenhan Chen Xiaojie Yu Longteng Wang Han Chen Cheng Li Tuoping Luo Hongkui Deng The MOE Key Laboratory of Cell Proliferation and Differentiation College of Life Sciences Peking-Tsinghua Center for Life Sciences and School of Basic Medical Sciences State Key Laboratory of Natural and Biomimetic Drugs Peking University Health Science Center Peking University Beijing 100191 China State Key Laboratory of Chemical Oncogenomics School of Chemical Biology & Biotechnology Peking University Shenzhen Graduate School Shenzhen Guangdong 518055 China Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary Studies Peking University Beijing 100871 China Key Laboratory of Bioorganic Chemistry and Molecular Engineering Ministry of Education and Beijing National Laboratory for Molecular Science College of Chemistry and Molecular Engineering Peking University Beijing 100871 China School of Life Sciences Joint Graduate Program of Peking-Tsinghua-NIBS Peking University Beijing 100871 China School of Life Sciences Center for Bioinformatics Center for Statistical Science Peking University Beijing 100871 China

Cellular senescence,a persistent state of cell cycle arrest,accumulates in aged organisms,contributes to tissue dysfunction,and drives age-related *** clearance of senescent cells is expected to decrease chronic,low-grade inflammation and improve tissue repair capacity,thus attenuating the decline of physical function in aged ***,selective and effective clearance of senescent cells of different cell types has proven ***,we developed a prodrug strategy to design a new compound based on the increased activity of lysosomalβ-galactosidase (β-gal),a primary characteristic of senescent *** prodrug SSK1 is specifically activated by β-gal and eliminates mouse and human senescent cells independently of senescence inducers and cell *** aged mice,our compound effectively cleared senescent cells in different tissues,decreased the senescence-and age-associated gene signatures,attenuated low-grade local and systemic inflammation,and restored physical *** results demonstrate that lysosomalβ-gal can be effectively leveraged to selectively eliminate senescent cells,providing a novel strategy to develop anti-aging interventions.

关键词： Apoptosis Senescence

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Study of enhancer-promoter interactome during mouse embryonic development with H3K4me3 PLAC-seq

Study of enhancer-promoter interactome during mouse embryoni...

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第十八次中国暨国际生物物理大会

作者： Miao Yu Rongxin Fang Ivan Juric Nathan Zemke Armen Abnousi Rong Hu Ming Hu Bing Ren School of Life Sciences Fudan University Ludwig Institute for Cancer Research Bioinformatics and Systems Biology Graduate Program University of California Department of Quantitative Health Sciences Lerner Research Institute Cleveland Clinic Foundation Center for Epigenomics Department of Cellular and Molecular Medicine University of California

Formation of long-range chromatin loops is a crucial step in transcriptional activation of target genes by distal enhancers. Mapping such structural features can help define target genes for enhancers and annotate non-coding sequence variants linked to human ***, we developed Proximity Ligation-Assisted ChIP-seq (PLAC-seq), which detects high-resolution long-range chromatin interactions at selected genomic regions through combination of in situ Hi-C and chromatin IP. We also developed a computational method, MAPS (Model-based Analysis of PLAC-seq and HiChIP) to process the data from such experiments and identify long-range chromatin interactions with high reproducibility and precision. By application of H3K4me3 PLAC-seq in mouse fetal tissues we identify182,403 long-range chromatin interactions at 10kb resolution. Through integrative analysis with RNA-seq, ATAC-seq and ChIP-seq data, we are able to link the genes with their potential regulatory enhancers.

关键词： Study of enhancer-promoter interactome during mouse embryonic development with H3K4me3 PLAC-seq

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Real-time Weed Identification Using Machine Learning and Image Processing in Oil Palm Plantations

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IOP Conference Series: Earth and Environmental Science 2022年第1期998卷

作者： Erick Firmansyah Teddy Suparyanto Alam Ahmad Hidayat Bens Pardamean Agricultural Engineering Department Institute of Agricultural STIPER Yogyakarta 55282 Indonesia Bioinformatics and Data Science Research Center Bina Nusantara University Jakarta Indonesia 11480 Computer Science Department BINUS Graduate Program – Master of Computer Science Bina Nusantara University Jakarta Indonesia 11480

The effectiveness and efficiency of the operation of oil palm plantations are considered to be the most crucial factor to develop the productivity and profitability of the palm oil business. One of the major obstacles for the plants to optimally produce crops based on their capacity is caused by the presence of noxious weeds in the plantation area. However, weed control via chemical processes may potentially harm the surrounding environment if it is not properly managed. Therefore, an automatic system to assist the farmers to identify and control the weeds is required to minimize harmful impacts on the environment. Machine Learning (ML) and Artificial Intelligence (AI)-based systems provide powerful tools to perform such tasks. In this work, we aim for an ML-based system design to perform an automatic weed recognition task. The methodology can provide an effort for environmental sustainability in oil palm plantations. The weed identification involves the description, the local names, and tolerance class of the weeds as well as suggestions to control them. The flow of this work consists of weed and herbicide data acquisition, data labeling, model configurations, and data training. Further, the proposed system can be adopted as an android-based application in mobile devices that can deploy the trained model to predict weed category in both real-time and non-real-time tasks.

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