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Cytometry in the Short-Wave Infrared

ACS Nano 2024年第28期18卷 18534-18547页

作者： Liu, Te-I Wang, Jhih-Shan Nguyen, Ai-Phuong Raabe, Marco Quiroz Reyes, Carlos Jose Lin, Chih-Hsin Lin, Ching-Wei Institute of Atomic and Molecular Sciences Academia Sinica Taipei City106319 Taiwan Department of Materials Science and Engineering National Taiwan University Taipei City106319 Taiwan Department of Physics University of Stuttgart Stuttgart70174 Germany Department of Chemistry National Tsing Hua University Hsinchu300044 Taiwan International Ph.D. Program in Biomedical Engineering Taipei Medical University New Taipei City235603 Taiwan Graduate Institute of Nanomedicine and Medical Engineering Taipei Medical University New Taipei City235603 Taiwan

Cytometry plays a crucial role in characterizing cell properties, but its restricted optical window (400-850 nm) limits the number of stained fluorophores that can be detected simultaneously and hampers the study and utilization of short-wave infrared (SWIR;900-1700 nm) fluorophores in cells. Here we introduce two SWIR-based methods to address these limitations: SWIR flow cytometry and SWIR image cytometry. We develop a quantification protocol for deducing cellular fluorophore mass. Both systems achieve a limit of detection of ∼0.1 fg cell-1 within a 30 min experimental time frame, using individualized, high-purity (6,5) single-wall carbon nanotubes as a model fluorophore and macrophage-like RAW264.7 as a model cell line. This high-sensitivity feature reveals that low-dose (6,5) serves as an antioxidant, and cell morphology and oxidative stress dose-dependently correlate with (6,5) uptake. Our SWIR cytometry holds immediate applicability for existing SWIR fluorophores and offers a solution to the issue of spectral overlapping in conventional cytometry. © 2024 The Authors. Published by American Chemical Society.

关键词： Oxygen

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ATP_mCNN: Predicting ATP binding sites through pretrained language models and multi-window neural networks

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Computers in Biology and Medicine 2025年 185卷 109541-109541页

作者： Le, Van-The Malik, Muhammad-Shahid Lin, Yi-Jing Liu, Yu-Chen Chang, Yan-Yun Ou, Yu-Yen Department of Computer Science and Engineering Yuan Ze University Chung-Li32003 Taiwan Graduate Program in Biomedical Informatics Yuan Ze University Chung-Li32003 Taiwan Department of Computer Sciences Karakoram International University Gilgit-Baltistan 15100 Pakistan

Adenosine triphosphate plays a vital role in providing energy and enabling key cellular processes through interactions with binding proteins. The increasing amount of protein sequence data necessitates computational methods for identifying binding sites. However, experimental identification of adenosine triphosphate-binding residues remains challenging. To address the challenge, we developed a multi-window convolutional neural network architecture taking pre-trained protein language model embeddings as input features. In particular, multiple parallel convolutional layers scan for motifs localized to different window sizes. Max pooling extracts salient features concatenated across windows into a final multi-scale representation for residue-level classification. On benchmark datasets, our model achieves an area under the ROC curve of 0.95, significantly improving on prior sequence-based models and outperforming convolutional neural network baselines. This demonstrates the utility of pre-trained language models and multi-window convolutional neural networks for advanced sequence-based prediction of adenosine triphosphate-binding residues. Our approach provides a promising new direction for elucidating binding mechanisms and interactions from primary structure. © 2024 Elsevier Ltd

关键词： Convolutional neural networks

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Development of Automated Detection Methods for Calculating Blood Vessel Width and Stenosis Rate in Cardiac Catheterization Imaging 24

Development of Automated Detection Methods for Calculating B...

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8th International Conference on Medical and Health Informatics, ICMHI 2024

作者： Huang, Hsien-Cheng Chang, Hsiao-Huang Ke, Xiang-Wei Chien, Ting-Ying Department of Computer Science and Engineering Yuan Ze University Taoyuan City Taiwan Cardiovascular Surgery Department Taipei Veterans General Hospital Taipei City Taiwan Taipei Medical University Taipei City Taiwan Graduate Program in Biomedical Informatics Yuan Ze University Taoyuan City Taiwan Innovation Center for Big Data and Digital Convergence Yuan Ze University Taoyuan City Taiwan

ISBN: (纸本)9798400716874

Coronary artery disease is the most prevalent type of heart disease and has a considerable mortality rate. In diagnosing and assessing coronary artery disease, physicians must integrate a variety of clinical information and test results to evaluate the degree of coronary artery obstruction and continually learn and improve their skills in clinical practice to ensure the most accurate assessment of patients. Currently, the use of information technology to assist medical staff allows more effective and accurate analysis of symptoms. This approach not only serves as an auxiliary standard for physician diagnosis, thereby reducing the possibility of misdiagnosis, but also significantly improves patient treatment outcomes and medical quality while reducing the time burden on physicians for diagnosing patients. This study utilized image processing techniques and thinning algorithms to automate the detection of coronary artery width and, following the recommended methods of physicians in related fields, used specific vessel widths to calculate the degree of coronary artery narrowing. This provides a more accurate and efficient assessment method for evaluating the degree of vascular constriction in patients with coronary artery disease. © 2024 Copyright ACM.

关键词： Patient treatment

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IGF1 enhances memory function in obese mice and stabilizes the neural structure under insulin resistance via AKT-GSK3β-BDNF signaling

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Biomedicine and Pharmacotherapy 2025年 183卷 117846-117846页

作者： Jo, Danbi Choi, Seo Yoon Ahn, Seo Yeon Song, Juhyun Department of Anatomy Chonnam National University Medical School Hwasun 58128 South Korea Biomedical Science Graduate Program (BMSGP) Chonnam National University Hwasun 58128 South Korea

Obesity is a prevalent metabolic disorder linked to insulin resistance, hyperglycemia, increased adiposity, chronic inflammation, and cognitive dysfunction. Recent research has focused on developing therapeutic strategies to mitigate cognitive impairment associated with obesity. Insulin growth factor-1 (IGF1) deficiency is linked to insulin resistance, glucose intolerance, and the progression of obesity-related central nervous system (CNS) disorders. In this study, we investigated the neuroprotective effects of IGF1 in two obesity models: diet-induced obesity (high-fat diet mice) and genetic obesity (ob/ob mice which is genetically deficient in leptin), and in vitro Neuro2A neuronal cells and primary cortical neurons under insulin resistance conditions. We performed RNA sequencing analysis using the cortex of high-fat diet mice injected with IGF1. Also, we detected cytokine levels in blood of high-fat diet mice injected with IGF1. In addition, we conducted the Barnes maze test as a spatial memory function test and open field test as an anxiety behavior test in ob/ob mice. We measured the levels of proteins and mRNAs related to insulin signaling, including synaptic density proteins in brain cortex of ob/ob mice. Our results showed that IGF1 injection enhanced spatial memory function and synaptic plasticity in obese mice. Furthermore, in vitro data demonstrated that IGF1 treated neurons revealed enhanced neural complexity and improved neurite outgrowth under insulin resistance condition through the AKT-GSK3β-BDNF pathway related to antidepressant, cognitive function and anti-apoptotic mechanisms. Therefore, our results provided that IGF1 have potential to alleviate cognitive impairment by promoting synaptic plasticity and neural complexity in the obese brain. © 2025 The Authors

关键词： Brain-derived neurotrophic factor (BDNF) Insulin growth factor −1 (IGF1) Neurite outgrowth Obesity Spatial memory

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Rac-maninoff and Rho-vel: The symphony of Rho-GTPase signaling at excitatory synapses

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Small GTPases 2022年第1期13卷 14-47页

作者： Duman, Joseph G. Blanco, Francisco A. Cronkite, Christopher A. Ru, Qin Erikson, Kelly C. Mulherkar, Shalaka Saifullah, Ali Bin Firozi, Karen Tolias, Kimberley F. Department of Neuroscience Baylor College of Medicine Houston TX United States Integrative Molecular and Biomedical Science Graduate Program Baylor College of Medicine Houston TX United States Department of Biochemistry and Molecular Biology Baylor College of Medicine Houston TX United States Medical Scientist Training Program Baylor College of Medicine Houston TX United States

Synaptic connections between neurons are essential for every facet of human cognition and are thus regulated with extreme precision. Rho-family GTPases, molecular switches that cycle between an active GTP-bound state and an inactive GDP-bound state, comprise a critical feature of synaptic regulation. Rho-GTPases are exquisitely controlled by an extensive suite of activators (GEFs) and inhibitors (GAPs and GDIs) and interact with many different signalling pathways to fulfill their roles in orchestrating the development, maintenance, and plasticity of excitatory synapses of the central nervous system. Among the mechanisms that control Rho-GTPase activity and signalling are cell surface receptors, GEF/GAP complexes that tightly regulate single Rho-GTPase dynamics, GEF/GAP and GEF/GEF functional complexes that coordinate multiple Rho-family GTPase activities, effector positive feedback loops, and mutual antagonism of opposing Rho-GTPase pathways. These complex regulatory mechanisms are employed by the cells of the nervous system in almost every step of development, and prominently figure into the processes of synaptic plasticity that underlie learning and memory. Finally, misregulation of Rho-GTPases plays critical roles in responses to neuronal injury, such as traumatic brain injury and neuropathic pain, and in neurodevelopmental and neurodegenerative disorders, including intellectual disability, autism spectrum disorder, schizophrenia, and Alzheimer’s Disease. Thus, decoding the mechanisms of Rho-GTPase regulation and function at excitatory synapses has great potential for combatting many of the biggest current challenges in mental health. © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

关键词： AMPA receptor Cdc42 dendritic spine LTD LTP NMDA receptor Rac1 RhoA

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A Facile NMR Method for Pre-MRI Evaluation of Trigger-Responsive T1 Contrast Enhancement

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Small Methods 2024年第10期8卷 e2301603页

作者： Jian, Cheng-Bang Wu, Ying-Yann Lin, Ming-Huang Gao, Hua-De Chen, Chong-Yan Leong, Shwee Khuan Tzou, Der-Lii M. Hwang, Dennis W. Lee, Hsien-Ming Institute of Chemistry Academia Sinica Taipei11529 Taiwan Nano Science and Technology Program Taiwan International Graduate Program Academia Sinica and National Taiwan University Taipei11529 Taiwan Department of Chemistry National Taiwan University Taipei10617 Taiwan Institute of Biomedical Sciences Academia Sinica Taipei11529 Taiwan Sustainable Chemical Science and Technology Program Taiwan International Graduate Program Academia Sinica and National Yang Ming Chiao Tung University Taipei11529 Taiwan Department of Applied Chemistry National Yang Ming Chiao Tung University Hsinchu30093 Taiwan

There is a growing interest in developing paramagnetic nanoparticles as responsive magnetic resonance imaging (MRI) contrast agents, which feature switchable T1 image contrast of water protons upon biochemical cues for better discerning diseases. However, performing an MRI is pragmatically limited by its cost and availability. Hence, a facile, routine method for measuring the T1 contrast is highly desired in early-stage development. This work presents a single-point inversion recovery (IR) nuclear magnetic resonance (NMR) method that can rapidly evaluate T1 contrast change by employing a single, optimized IR pulse sequence that minimizes water signal for "off-state" nanoparticles and allows for sensitively measuring the signal change with "switch-on" T1 contrast. Using peptide-induced liposomal gadopentetic acid (Gd3+-DTPA) release and redox-sensitive manganese oxide (MnO2) nanoparticles as a demonstration of generality, this method successfully evaluates the T1 shortening of water protons caused by liposomal Gd3+-DTPA release and Mn2+ formation from MnO2 reduction. Furthermore, the NMR measurement is highly correlated to T1-weighted MRI scans, suggesting its feasibility to predict the MRI results at the same field strength. This NMR method can be a low-cost, time-saving alternative for pre-MRI evaluation for a diversity of responsive T1 contrast systems. © 2024 Wiley-VCH GmbH.

关键词： Nuclear magnetic resonance spectroscopy

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The largest genome-wide association study for breast cancer in Taiwanese Han population

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Breast Cancer Research and Treatment 2024年第2期203卷 291-306页

作者： Hsu, Yu-Ching Chen, Hung-Lin Cheng, Chi-Fung Chattopadhyay, Amrita Chen, Pei-Shan Lin, Che-Chen Chiang, Hsiu-Yin Liu, Ting-Yuan Huang, Chi-Hao Kuo, Chin-Chi Chuang, Eric Y. Lu, Tzu-Pin Tsai, Fuu-Jen Bioinformatics Program Taiwan International Graduate Program National Taiwan University Taipei Taiwan Bioinformatics Program Institute of Statistical Science Taiwan International Graduate Program Academia Sinica Taipei Taiwan Institute of Health Data Analytics and Statistics Department of Public Health College of Public Health National Taiwan University Taipei Taiwan Big Data Center China Medical University Hospital Taichung Taiwan Center for Translational Genomic Research Department of Medical Research China Medical University Hospital Taichung Taiwan Million-Person Precision Medicine Initiative Department of Medical Research China Medical University Hospital Taichung Taiwan Division of Breast Surgery Department of Surgery China Medical University Hospital Taichung Taiwan Division of Nephrology Department of Internal Medicine China Medical University Hospital Taichung Taiwan Department of Medical Research China Medical University Hospital Taichung Taiwan Bioinformatics and Biostatistics Core Center of Genomic and Precision Medicine National Taiwan University Taipei Taiwan Graduate Institute of Biomedical Electronics and Bioinformatics National Taiwan University Taipei Taiwan Biomedical Technology and Device Research Laboratories Industrial Technology Research Institute Hsinchu Taiwan Genetic Center Department of Medical Research China Medical University Hospital Taichung Taiwan

Purpose: Breast cancer is a molecularly heterogeneous disease, and multiple genetic variants contribute to its development and prognosis. Most of previous genome-wide association studies (GWASs) and polygenic risk scores (PRSs) analyses focused on studying breast cancers of Caucasian populations, which may not be applicable to other population. Therefore, we conducted the largest breast cancer cohort of Taiwanese population to fill in the knowledge gap. Methods: A total of 152,534 Participants recruited by China Medical University Hospital between 2003 and 2019 were filtered by several patient selection criteria and GWAS quality control steps, resulting in the inclusion of 2496 cases and 9984 controls for this study. We then conducted GWAS for all breast cancers and PRS analyses for all breast cancers and the four breast cancer subtypes, including luminal A, luminal B, basal-like, and HER2-enriched. Results: The GWAS analyses identified 113 SNPs, 50 of which were novel. The PRS models for all breast cancers and the luminal A subtype showed positively correlated trends between the PRS and the risk of developing breast cancer. The odds ratios (95% confidence intervals) for the groups with the highest PRS in all breast cancers and the luminal A subtype were 5.33 (3.79–7.66) and 3.55 (2.13–6.14), respectively. Conclusion: In summary, we explored the association of genetic variants with breast cancer in the largest Taiwanese cohort and developed two PRS models that can predict the risk of developing any breast cancer and the luminal A subtype in Taiwanese women. © 2023, The Author(s), under exclusive licence to Springer science+Business Media, LLC, part of Springer Nature.

关键词： Breast cancer Genome-wide association study Polygenic risk score Taiwanese population

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Two Novel Compounds Isolated from the Marine Fungal Symbiont of Aspergillus unguis Induce Apoptosis and Cell Cycle Arrest in Breast Cancer Cells: In vitro Study

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Journal of Experimental Pharmacology 2025年 17卷 37-50页

作者： Bashari, Muhammad Hasan Agung, Mochamad Untung Kurnia Ariyanto, Eko Fuji Al Muqarrabun, Laode Muhammad Ramadhan Salsabila, Syefira Chahyadi, Agus Rosandy, Andi Rifki Afifah, Ervi Afni, Merry Atmaja, Harold Eka Putri, Tenny Utami, Fitria Subhan, Beginer Syafrizayanti Andriani, Yosie Elfahmi Department of Biomedical Sciences Faculty of Medicine Universitas Padjadjaran West Java Bandung Indonesia Department of Marine Science Faculty of Fisheries and Marine Science Universitas Padjadjaran West Java Bandung Indonesia University Center of Excellence for Nutraceuticals Bioscience and Biotechnology Research Center Bandung Institute of Technology West Java Bandung Indonesia Graduate School of Master Program Faculty of Medicine Universitas Padjadjaran Bandung Indonesia Biomedical Laboratory Faculty of Medicine Universitas Padjadjaran West Java Bandung Indonesia Department of Marine Science and Technology Faculty of Fisheries and Marine Science IPB University West Java Bogor Indonesia Biochemistry Laboratory Department of Chemistry Universitas Andalas West Sumatera Padang Indonesia Institute of Climate Adaptation and Marine Biotechnology Universiti Malaysia Terengganu Kuala Nerus Terengganu Malaysia School of Pharmacy Bandung Institute of Technology West Java Bandung Indonesia

Purpose: A promising feature of marine sponges is the potential anticancer efficacy of their secondary metabolites. The objective of this study was to explore the anticancer activities of compounds from the fungal symbiont of Aaptos suberitoides on breast cancer cells. Methods: In the present research, Aspergillus unguis, an endophytic fungal strain derived from the marine sponge A. suberitoides was successfully isolated and characterized. Subsequently, ethyl acetate extraction and isolation of chemical constituents produced was performed. The structures of the isolated compounds were identified using several spectroscopic methods, ie, UV, NMR, and mass spectrometry. Thereafter, MDA-MB-231, MCF-7 breast cancer cells and HaCat cells were treated with the isolated compounds. Not only viability, apoptosis, and cell cycle analyses were conducted, but also the mRNA expression of MCL1, BCL2L1, AKT1 and CDK2 were evaluated. Results: The extract showed cytotoxic activity in breast cancer cells. Two novel compounds were successfully isolated and identified, ie, Unguisol A (15.1 mg) and Unguisol B (97.9 mg). Both compounds share the same basic skeleton and comprise an aromatic ring which is attached to a sulphur-containing, seven-membered ring via an oxygen atom. This marked the first-time isolation of Unguisol A and Unguisol B from A. unguis, highlighting their novelty. Both compounds induced early apoptosis (p < 0.01) and cell cycle arrest at the S phase (p < 0.05) in MDA-MB-231 cells, but not in HaCat cells. Both compounds suppressed BCL2L1 and AKT1 mRNA expression (p < 0.01). Conclusion: Two novel compounds were isolated from A. unguis. Unguisol A and Unguisol B induced apoptosis in MDA-MB-231 breast cancer cells via BCL2L1 mRNA downregulation, while both compounds induced cell cycle arrest at the S phase through AKT1 mRNA downregulation. © 2025 Bashari et al.

关键词： Aspergillus unguis drug screening assays Porifera triple negative breast neoplasms

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Transferrin-Mediated Nanophotosensitizer to Enhance Phototherapy with Photoacoustic Imaging Under Hypoxia

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CCS Chemistry 2025年第4期7卷 1127-1141页

作者： Mengyao Yang Yunyoung Nah Donghyeon Oh Xingshu Li Heejeong Kim Sinyoung Park Junha Lim Aibing Chen Chulhong Kim Won Jong Kim Juyoung Yoon College of Chemical and Pharmaceutical Engineering Hebei University of Science and TechnologyShijiazhuang 050018 Department of Chemistry and Nanoscience Ewha Womans UniversitySeoul 03760 Department of Chemistry POSTECH-Catholic Biomedical Engineering InstitutePOSTECHPohang 37673 Department of Electrical Engineering Convergence IT EngineeringMechanical Engineeringand Medical Science and EngineeringMedical Device Innovation CenterPOSTECHPohang 37673 Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy College of ChemistryFuzhou UniversityFuzhou 350108 School of Interdisciplinary Bioscience and Bioengineering POSTECHPohang 37673 Graduate Program in Innovative Biomaterials Convergence Ewha Womans UniversitySeoul 03760

Various obstacles[poor tissue penetration,hypoxic tumor microenvironment,and reactive oxygen species(ROS)production quenching due to aggregation]obstruct imaging-guided high-efficiency phototherapy targeting ***,nanophthalocyanine(ZnPcN4-TF)is elaborately designed based on a synthetic phthalocyanine derivative(ZnPcN4)and nonimmunogenic transferrin(TF)through multiple noncovalent interactions for photoacoustic(PA)imaging-guided *** conjugating electron-rich amino groups effectively suppressed fluorescence and ROS generation due to the strong photoinduced electron transfer effect,ZnPcN4 became an ideal photothermal and PA imaging ***4-TF not only effectively targeted tumor sites and accumulated there,but also,surprisingly,facilitated the enhancement of ROS production via a type I process in an aggregate compared to ZnPcN4 itself,potentially due to accelerated electron ***,ZnPcN4-TF had a substantially more powerful photothermal effect than ZnPcN4 ***,this design effectively overcomes the obstacles to photodynamic therapy(aggregation-related ROS generation quenching in a hypoxic environment).Furthermore,PA imaging solves the tissue penetration challenge in optical *** study provides a broader base for designing novel photosensitizers to improve phototherapy under hypoxia.

关键词： photoacoustic imaging type I reactive oxygen species photothermal effect tumor accumulation self-assembly

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A Transparent Ultrasound Array for Real-Time Optical,Ultrasound,and Photoacoustic Imaging

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biomedical Engineering Frontiers 2022年第1期3卷 284-297页

作者： Haoyang Chen Sumit Agrawal Mohamed Osman Josiah Minotto Shubham Mirg Jinyun Liu Ajay Dangi Quyen Tran Thomas Jackson Sri-Rajasekhar Kothapalli Department of Biomedical Engineering The Pennsylvania State UniversityUniversity ParkPA 16802USA School of Electrical Engineering and Computer Science The Pennsylvania State UniversityUniversity ParkPA 16802USA Penn State Cancer Institute The Pennsylvania State UniversityHersheyPA 17033USA Graduate Program in Acoustics The Pennsylvania State UniversityUniversity ParkPA 16802USA

Objective and Impact *** imaging of ultrasound and optical contrasts can help map structural,functional,and molecular biomarkers inside living subjects with high spatial *** is a need to develop a platform to facilitate this multimodal imaging capability to improve diagnostic sensitivity and ***,combining ultrasound,photoacoustic,and optical imaging modalities is challenging because conventional ultrasound transducer arrays are optically *** a result,complex geometries are used to coalign both optical and ultrasound waves in the same field of *** elegant solution is to make the ultrasound transducer transparent to ***,we demonstrate a novel transparent ultrasound transducer(TUT)linear array fabricated using a transparent lithium niobate piezoelectric material for real-time multimodal *** TUT-array consists of 64 elements and centered at~6 MHz *** demonstrate a quad-mode ultrasound,Doppler ultrasound,photoacoustic,and fluorescence imaging in real-time using the TUT-array directly coupled to the tissue mimicking *** TUT-array successfully showed a multimodal imaging capability and has potential applications in diagnosing cancer,neurological,and vascular diseases,including image-guided endoscopy and wearable imaging.

关键词： Ultrasound specificity transparent

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