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Overcoming Cytosolic Delivery Barriers of Proteins Using Denatured Protein-Conjugated Mesoporous Silica Nanoparticles

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ACS Applied Materials and Interfaces 2023年第1期15卷 432-451页

作者： Dembélé, Julien Liao, Jou-Hsuan Liu, Tsang-Pai Chen, Yi-Ping Graduate Institute of Biomedical Materials & Tissue Engineering College of Biomedical Engineering Taipei Medical University Taipei11031 Taiwan Laboratory of Toxicology Environment and Health Doctorate School of Health University Joseph Ki-Zerbo Ouaga03 BP 7021 Burkina Faso Department of Chemistry National Taiwan University Taipei10617 Taiwan Department of Surgery Mackay Memorial Hospital Taipei10449 Taiwan Graduate Institute of Nanomedicine and Medical Engineering Taipei Medical University Taipei11031 Taiwan International PhD Program in Biomedical Engineering College of Biomedical Engineering Taipei Medical University Taipei11031 Taiwan

Intracellular delivery of therapeutic proteins has increased advantages over current small-molecule drugs and gene therapies, especially in therapeutic efficacies for a broad spectrum of diseases. Hence, developing the protein therapeutics approach provides a needed alternative. Here, we designed a mesoporous silica nanoparticle (MSN)-mediated protein delivery approach and demonstrated effective intracellular delivery of the denatured superoxide dismutase (SOD) protein, overcoming the delivery challenges and achieving higher enzymatic activity than native SOD-conjugated MSNs. The denatured SOD-conjugated MSN delivery strategy provides benefits of reduced size and steric hindrance, increased protein flexibility without distorting its secondary structure, exposure of the cell-penetrating peptide transactivator of transcription for enhanced efficient delivery, and a change in the corona protein composition, enabling cytosolic delivery. After delivery, SOD displayed a specific activity around threefold higher than in our previous reports. Furthermore, the in vivo biosafety and therapeutic potential for neuron therapy were evaluated, demonstrating the biocompatibility and the effective antioxidant effect in Neuro-2a cells that protected neurite outgrowth from paraquat-induced reactive oxygen species attack. This study offers an opportunity to realize the druggable possibility of cytosolic proteins using MSNs. © 2022 American Chemical Society.

关键词： Peptides

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Fast interactive multi-region cardiac segmentation with linearly ordered labels

Fast interactive multi-region cardiac segmentation with line...

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2012 9th IEEE International Symposium on biomedical Imaging: From Nano to Macro, ISBI 2012

作者： Rajchl, M. Yuan, J. Ukwatta, E. Peters, P.M. Robarts Research Institute Imaging Laboratories London ON Canada Biomedical Engineering Graduate Program University of Western Ontario London ON Canada

ISBN: (纸本)9781457718588

We present a novel and fast interactive approach to multi-modality cardiac image segmentation, which employs the linearly ordered surfaces as an additional constraint. We show using such a geometrical constraint helps to significantly reduce user interaction and improve the accuracy of segmentation results at the same time. We solve the proposed multiregion segmentation problem with the order constraints by means of convex optimization, resulting in a fast and reliable flow maximization approach which implicitly embeds the linear order prior without introducing extra computation load. In this regard, a new fully parallelized continuous max-flow algorithm is proposed and implemented using GPGPU to segment a 3D volume within one second. We demonstrate our results over pathological trans-esophageal echocardiogram, cardiac CT and delayed enhancement MRI data sets. © 2012 IEEE.

关键词： Magnetic resonance imaging

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Reconstruction algorithms for interior and exterior spherical radon transform-based ultrasound imaging

Reconstruction algorithms for interior and exterior spherica...

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Medical Imaging 2009: Ultrasonic Imaging and Signal Processing

作者： Vaidyanathan, Ravi Shankar Lewis, Matthew A. Ambartsoumian, Gaik Aktosun, Tuncay Graduate Program in Biomedical Engineering UTSouthwestern Medical Center United States Dept. of Mathematics UT Arlington United States

ISBN: (纸本)9780819475169

This work is concerned with the numerical implementation of a reconstruction algorithm developed to recover a function from its spherical means over spheres centered on a circle. The algorithm is experimentally verified by simulations using numerical phantoms. In the scheme of tomography, acoustic waves are generated by illuminating an object with a short burst of radio-frequency waves. In applications, like breast cancer imaging, which use modalities like photo-acoustic tomography (PAT) that model the acoustic pressures as spherical means, data are measured on the detectors located in a circle surrounding the object. This is then used to reconstruct the absorption density inside the object. In contrast, applications like bore hole tomography and improved Intravascular Ultra Sound (IVUS) imaging for prostate cancer, which use modalities like Radial Reflection Diffraction Tomography (RRDT), a ring of detectors placed exterior to the object, collect the acoustic waves as back-scattered field. This work uses a single algorithm to reconstruct functions from data collected using these two different techniques ? one, by placing the object inside the ring of detectors, and the other, by placing the object exterior to the ring of detectors. The algorithm then draws a comparison between the two reconstructions. The case of bistatic ultrasound imaging, where the elliptical Radon transform is appropriate, is also discussed. © 2009 SPIE.

关键词： Radon

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Downsizing and soft X-ray tomography for cellular uptake of interpenetrated metal-organic frameworks

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Journal of Materials Chemistry B 2024年第25期12卷 6079-6090页

作者： Yu, Yu-Sheng Liang, Yung-Yi Hsieh, Chia-Chun Lin, Zi-Jing Cheng, Po-Hsiu Cheng, Chih-Chan Chen, Shu-Ping Lai, Lee-Jene Wu, Kevin C.-W. National Taiwan University Department of Chemical Engineering Taipei Taiwan National Health Research Institute Institute of Biomedical Engineering and Nanomedicine Miaoli Taiwan Hsinchu Taiwan International Graduate Program of Molecular Science and Technology Taiwan International Graduate Program Academia Sinica Taipei Taiwan National Taiwan University Taipei Taiwan

Metal-organic frameworks (MOFs) are porous materials with potential in biomedical applications such as sensing, drug delivery, and radiosensitization. However, how to tune the properties of the MOFs for such applications remains challenging. Herein, we synthesized two MOFs, Zr-PEB and Hf-PEB. Zr-PEB can be classified as porous interpenetrated zirconium frameworks (PIZOFs) and Hf-PEB is its analogue. We controlled their sizes while maintaining their crystal structure by employing a coordination modulation strategy. They were designed to serve as sensitizer for X-ray therapy and as potential drug carriers. Comprehensive characterizations of the MOFs' properties have been conducted, and the in vitro biological impacts have been studied. Since viability assay showed that Hf-PEB was more biocompatible compared to Zr-PEB, the cellular uptake of Hf-PEB by cells was evaluated using both fluorescence microscopy and soft X-ray tomography (SXT), and the three-dimensional structure of Hf-PEB in cells was observed. The results revealed the potential of Zr-PEB and Hf-PEB as nanomaterials for biomedical applications and demonstrated that SXT is an effective tool to assist the development of such materials. © 2024 The Royal Society of Chemistry.

关键词： Organometallics

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CHITOSAN-COLLAGEN COMPOSITE SCAFFOLDS FOR GROWTH DIRECTION GUIDANCE OF PC12 AXONS

CHITOSAN-COLLAGEN COMPOSITE SCAFFOLDS FOR GROWTH DIRECTION G...

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ASME 2024 International Design engineering Technical Conferences and Computers and Information in engineering Conference, IDETC-CIE 2024

作者： Tsai, Po-Yu Lin, Ying-Ting Wang, Gou-Jen Graduate Institute of Biomedical Engineering National Chung-Hsing University Taichung Taiwan PhD Program in Tissue Engineering and Regenerative Medicine National Chung-Hsing University Taichung Taiwan Department of Mechanical Engineering Graduate Institute of Biomedical Engineering National Chung-Hsing University Taichung Taiwan

ISBN: (纸本)9780791888421

In this study, nerve conduits of chitosan and collagen composites with biocompatibility and biodegradability were fabricated. The effects of material composition and surface morphology on the axonal growth and directionality of rat epinephric pheochromocytoma PC12 were investigated. The cells were separated by a PDMS structure to simulate nerve injury, and the growth of axons of PC12 cells was observed under the separation of large gaps. At the same time, mitochondria extracted from osteosarcoma cybrid cells (C2-GFP) were added to the culture to investigate the effect of healthy mitochondria on axon differentiation and growth. The experimental results showed that the chitosan-collagen composite film can promote the growth of PC12 axons more effectively than the pure chitosan film. Cell culture results at different groove widths also showed that smaller grooves resulted in more axon numbers and longer axon lengths. Nerve injury simulation experiments showed that the nerve repair could be almost completed after 12 days of culture. Copyright © 2024 by ASME.

关键词： Mitochondria

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Fabrication of versatile poly(xylitol sebacate)-co-poly(ethylene glycol) hydrogels through multifunctional crosslinkers and dynamic bonds for wound healing

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Acta Biomaterialia 2023年 170卷 344-359页

作者： Yeh, Ying-Yu Lin, Yi-Yun Wang, Ting-Teng Yeh, Yu-Jia Chiu, Ting-Hsiang Wang, Reuben Bai, Meng-Yi Yeh, Yi-Cheun Institute of Polymer Science and Engineering National Taiwan University Taipei Taiwan Institute of Biomedical Engineering National Taiwan University Taipei Taiwan Biomedical Engineering Program Graduate Institute of Applied Science and Technology National Taiwan University of Science and Technology Taipei Taiwan Institute of Food Safety and Health National Taiwan University Taipei Taiwan Graduate Institute of Biomedical Engineering National Taiwan University of Science and Technology Taipei Taiwan Adjunct Appointment to the Department of Biomedical Engineering National Defense Medical Center Taipei Taiwan Program National Taiwan University Taipei Taiwan GIP-TRIAD Master's Degree in Agro-Biomedical Science National Taiwan University Taipei Taiwan

Poly(polyol sebacate) (PPS) polymer family has been recognized as promising biomaterials for biomedical applications with their characteristics of easy production, elasticity, biodegradation, and cytocompatibility. Poly(xylitol sebacate)-co-poly(ethylene glycol) (PXS-co-PEG) has been developed to fabricate PPS-based hydrogels;however, current PXS-co-PEG hydrogels presented limited properties and functions due to the limitations of the crosslinkers and crosslinking chemistry used in the hydrogel formation. Here, we fabricate a new type of PXS-co-PEG hydrogels through the use of multifunctional crosslinkers as well as dynamic bonds. In our design, polyethyleneimine-polydopamine (PEI-PDA) macromers are utilized to crosslink aldehyde-functionalized PXS-co-PEG (APP) through imine bonds and hydrogen bonds. PEI-PDA/APP hydrogels present multiple functional properties (e.g., fluorescent, elastomeric, biodegradable, self-healing, bioadhesive, antioxidant, and antibacterial behaviors). These properties of PEI-PDA/APP hydrogels can be fine-tuned by changing the PDA grafting degrees in the PEI-PDA crosslinkers. Most importantly, PEI-PDA/APP hydrogels are considered promising wound dressings to promote tissue remodeling and prevent bacterial infection in vivo. Taken together, PEI-PDA/APP hydrogels have been demonstrated as versatile biomaterials to provide multiple tailorable properties and desirable functions to expand the utility of PPS-based hydrogels for advanced biomedical applications. Statement of significance: Various strategies have been developed to fabricate poly(polyol sebacate) (PPS)-based hydrogels. However, current PPS-based hydrogels present limited properties and functions due to the limitations of the crosslinkers and crosslinking chemistry used in the hydrogel formation. This work describes that co-engineering crosslinkers and interfacial crosslinking is a promising approach to synthesizing a new type of poly(xylitol sebacate)-co-poly(ethylene glycol) (PXS-co-

关键词： Polyols

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Comparison of Fetal Heart Rate Detection Using Envelope Extraction and Shannon Energy

Comparison of Fetal Heart Rate Detection Using Envelope Extr...

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2019 International Seminar on Application for Technology of Information and Communication, iSemantic 2019

作者： Setiawan, Agung W. Sujatmiko, Wahyu Biomedical Engineering Research Group School of Electrical Engineering and Informatics ITB Bandung Indonesia Graduate Program in Electrical Engineering School of Electrical Engineering and Informatics ITB Bandung Indonesia

ISBN: (纸本)9781728138329

Heart rate monitoring is widely used as a general procedure to examine fetal health condition. Fetal heart rate can be used to identified possibilities of fetal anomaly and warn the obstetrician to provide immediate intervention before any further abnormalities. The purpose of this research is to compare fetal heart rate detection result using envelope extraction and Shannon energy envelope method. There are 115 fetal phonocardiography and maternal phonocardiography that is used in this research. The dataset was obtained from Hafez Hospital, Shiraz University of Medical Science. Envelope extraction method can be used to detect fetal heart rate signal with 89.2% accuracy for all fetal phonocardiography signal while Shannon energy envelope method can be used to detect fetal heart rate signal with 88.3% accuracy for all fetal phonocardiography signal. © 2019 IEEE.

关键词： Phonocardiography

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Tumor ploidy determination in low-pass whole genome sequencing and allelic copy number visualization using the Constellation Plot

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Genome biology 2025年第1期26卷 132页

作者： Sarah H Johnson James B Smadbeck Roman M Zenka Michael T Barrett Athanasios Gaitatzes Arnav Solanki Angela B Florio Mitesh J Borad John C Cheville George Vasmatzis Biomarker Discovery Program Mayo Clinic Rochester MN 55905 USA. Center for Individualized Medicine Mayo Clinic Rochester MN 55905 USA. Quantitative Health Sciences Mayo Clinic Rochester MN 55905 USA. Hematology/Oncology Mayo Clinic Scottsdale AZ 85259 USA. Center for Digital Health Mayo Clinic Rochester MN 55905 USA. Department of Electrical and Computer Engineering University of Minnesota Minneapolis MN 55455 USA. Mayo Clinic Graduate School of Biomedical Sciences Rochester MN 55905 USA. Anatomic Pathology Mayo Clinic Rochester MN 55905 USA. Biomarker Discovery Program Mayo Clinic Rochester MN 55905 USA. Vasmatzis.George@mayo.edu. Department of Molecular Medicine Mayo Clinic Rochester MN 55905 USA. Vasmatzis.George@mayo.edu.

Ploidy determination across the genome has been challenging for low-pass-WGS tumor-only samples. We present BACDAC, a method that calculates tumor ploidy down to 1.2X effective tumor coverage. Allele fraction patterns displayed in the Constellation Plot verify tumor ploidy and reveal subclonal populations. BACDAC outputs a metric, 2NLOH, that when combined with ploidy better distinguishes near-diploid from high-ploidy tumors. Validated using TCGA, BACDAC had good agreement with other methods and 88% agreement with experimental methods. Discrepancies occur mainly when BACDAC predicts diploidy with subclones rather than high-ploidy. Applied to 653 low-pass-WGS samples spanning 12 cancer subtypes, BACDAC calls 40% as high-ploidy.

关键词： Loss of heterozygosity Next generation sequencing Ploidy Whole genome doubling

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A Novel SERS Substrate Containing Silver Nanoparticle-Deposited Photoresist Microcone Array for Sensitive Biosensing

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IEEE Sensors Journal 2024年第2期24卷 1398-1404页

作者： Lin, Ying-Ting Wang, Sheng-Hsiang Tseng, Yu-Hsin Lin, Ze-Cheng Chen, Jyun-Tu Chang, Cheng-Chung Wang, Gou-Jen National Chung Hsing University Program in Tissue Engineering and Regenerative Medicine Taichung40227 Taiwan National Chung Hsing University Department of Mechanical Engineering Taichung40227 Taiwan Graduate Institute of Biomedical Engineering National Chung Hsing University Taichung40227 Taiwan

In this study, we developed a novel surface-enhanced Raman scattering (SERS) substrate formed by depositing silver nanoparticles (AgNPs) on a silver thin film-coated photoresist (PR) microcone array. The semiconductor photolithographic process was adopted for fabricating the PR microcone array. The hotspot enhancement effect of the SERS substrates was optimized by adjusting the concentration of the trisodium citrate, which was used as a reducing agent and a stabilizing agent for the synthesis of AgNPs. Experimental results showed that the proposed SERS substrate could detect the indicating peaks of Rhodamine 6G (R6G) at a relatively low concentration of 10-12 M. A standard detection curve for HbA1c detection with a linear detection range of 5000-20000 ng/mL with good linearity of 0.994 and a limit of detection (LOD) of 850.2 ng/mL was further established by adding HbA1c agent to artificial blood to simulate a real environmental condition. Recovery rate detection experiments confirmed the reproducibility of the established standard detection curve. © 2001-2012 IEEE.

关键词： Silver nanoparticles

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The biomedical engineer - The roles he can play

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Science 1971年第4013期174卷 1001-1003页

作者： Bronzino, Joseph D. Biomedical Engineering Program Rensselaer Polytechnic Institute Graduate Center Troy NY United States Department of Engineering Trinity College Hartford CT 06106 United States

The interdisciplinary exposure necessary for these new professionals depends upon their specific roles.

关键词： Bioengineering Nursing students Medical schools biomedical technology Medical students Physicians Human resources Health care administration Entrepreneurs

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