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ExoHCR: a sensitive assay to profile PD-L1 level on tumor exosomes for immunotherapeutic prognosis

Biophysics Reports 2020年第6期6卷 290-298页

作者： Lujun Hu Wenjie Chen Shurong Zhou Guizhi Zhu College of Bioengineering Sichuan University of Science and Engineering Institute for Structural Biology Drug Discovery and DevelopmentVirginia Commonwealth University The Developmental Therapeutics Program Massey Cancer CenterVirginia Commonwealth University Center for Pharmaceutical Engineering and Sciences Department of PharmaceuticsSchool of PharmacyVirginia Commonwealth University

Cancer immunotherapy has made recent breakthrough, including immune checkpoint blockade(ICB)that inhibits immunosuppressive checkpoints such as programmed cell death protein 1(PD-1) and programmed death-ligand 1(PD-L1). However, most cancer patients do not durably respond to ICB. To predict ICB responses for patient stratification, conventional immunostaining has been used to analyze the PD-L1 expression level on biopsied tumor tissues but has limitations of invasiveness and tumor heterogeneity. Recently, PD-L1 levels on tumor cell exosomes showed the potential to predict ICB response. Here, we developed a non-invasive, sensitive, and fast assay, termed as exosome-hybridization chain reaction(ExoHCR), to analyze tumor cell exosomal PD-L1 levels. First, using a CD63-conjugated magnetic beads, we isolated exosomes from B16 F10 melanoma and CT26 colorectal cancer cells that were immunostimulated to generate PD-L1-positive exosomes. Exosomes were then incubated with a conjugate of PD-L1 antibody with an HCR trigger DNA(T), in which one a PD-L1-T conjugate carried multiple copies of T. Next, a pair of metastable fluorophore-labeled hairpin DNA(H1 and H2) were added, allowing T on a PD-L1-T to initiate HCR in situ on bead-conjugated exosome surfaces. By flow cytometric analysis of the resulting beads, relative to a PD-L1-fluorophore conjugates, ExoHCR amplified the fluorescence signal intensities for exosome detection by 3–7 times in B16 F10 cells and CT26 ***, we validated the biostability of ExoHCR in culture medium supplemented with 50% *** results suggest the potential of ExoHCR for non-invasive, sensitive, and fast PD-L1 exosomal profiling in patient stratification of cancer immunotherapy.

关键词： Exosome Hybridization chain reaction Immune checkpoint PD-L1 analysis Immunotherapy

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Unravelling Exothermic Reaction Dynamics in Polyurethane Polymerization: A Thermo-Kinetic Simulation Approach

SSRN

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SSRN 2023年

作者： Mendija, Leanne Christie C. Dingcong, Roger G. Alfeche, Fortia Louise Adeliene M. Al-Moameri, Harith H. Dumancas, Gerard G. Malaluan, Roberto M. Alguno, Arnold C. Lubguban, Arnold A. Center for Sustainable Polymers Mindanao State University Iligan Institute of Technology Iligan City9200 Philippines Material Science and Engineering Program Graduate School of Engineering Mindanao State University Iligan Institute of Technology Iligan City9200 Philippines Department of Materials Engineering Mustansiriyah University Baghdad10052 Iraq Department of Chemistry The University of Scranton ScrantonPA18510 United States Department of Chemical Engineering and Technology Mindanao State University Iligan Institute of Technology Iligan City9200 Philippines Department of Physics Mindanao State University Iligan Institute of Technology Iligan City9200 Philippines

The pursuit of sustainable polyurethane product development necessitates a profound understanding of precursor materials, particularly polyol since polyurethane properties are heavily influenced by the type of polyol employed during polyurethane production. While traditional polyurethanes are solely derived from hydroxyl functionalized polyols, the emergence of amine-hydroxyl hybrid polyols has garnered significant attention due to their potential for enhancing polyurethane product properties. These hybrid polyols are characterized by the presence of both amine and hydroxyl functional groups. However, characterizing these polyols remains a daunting challenge due to the lack of established experimental testing standards for properties, such as fractional hydroxyl and amine moieties, and thermo-kinetic parameters for amine reactions with isocyanates. To bridge these gaps, this study employed a computational simulation approach to determine the fractions of moieties in both traditional and hybrid polyols. Additionally, this study determined the thermo-kinetic parameters for exothermic isocyanate reactions with amine moieties in hybrid polyols. The computational method integrated energy balance and reaction kinetics analysis for various polyols to elucidate the influence of functional moieties on the thermo-kinetic behavior of polyurethane formations. Validation of the simulated results was conducted by comparing their experimental and simulated gel and foam temperature profiles, highlighting the direct influence of fractional moieties on polyurethane formations. The comparisons revealed an average relative error of less than 5%, indicating the accuracy and credibility of the simulation. Thus, this study represents a pivotal opportunity for advancing knowledge and driving sustainable developments in biobased polyol characterization for polyurethane production streamlining and formulation optimization. © 2023, The Authors. All rights reserved.

关键词： Polymerization

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Enhancing forensic investigations: Identifying bloodstains on various substrates through ATR-FTIR spectroscopy combined with machine learning algorithms

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Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy 2024年 308卷 123755页

作者： Wei, Chun-Ta You, Jhu-Lin Weng, Shiuh-Ku Jian, Shun-Yi Lee, Jeff Cheng-Lung Chiang, Tang-Lun School of Defense Science Chung Cheng Institute of Technology National Defense University Taoyuan 335009 Taiwan Department of Chemical and Materials Engineering Chung Cheng Institute of Technology National Defense University Taoyuan 335009 Taiwan System Engineering and Technology Program National Yang Ming Chiao Tung University Hsinchu 300093 Taiwan Department of Electronic Engineering Chien Hsin University of Science and Technology Taoyuan 320678 Taiwan Department of Material Engineering Ming Chi University of Technology New Taipei 243303 Taiwan Center for Plasma and Thin Film Technologies Ming Chi University of Technology New Taipei 243303 Taiwan Department of Criminal Investigation Taiwan Police College Taipei 116078 Taiwan

The forensic analysis of bloodstains on various substrates plays a crucial role in criminal investigations. This study presents a novel approach for analyzing bloodstains using Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR) in combination with machine learning. ATR-FTIR offers non-destructive and non-invasive advantages, requiring minimal sample preparation. By detecting specific chemical bonds in blood components, it enables the differentiation of various body fluids. However, the subjective interpretation of the spectra poses challenges in distinguishing different fluids. To address this, we employ machine learning techniques. Machine learning is extensively used in chemometrics to analyze chemical data, build models, and extract useful information. This includes both unsupervised learning and supervised learning methods, which provide objective characterization and differentiation. The focus of this study was to identify human and porcine blood on substrates using ATR-FTIR spectroscopy. The substrates included paper, plastic, cloth, and wood. Data preprocessing was performed using Principal Component Analysis (PCA) to reduce dimensionality and analyze latent variables. Subsequently, six machine learning algorithms were used to build classification models and compare their performance. These algorithms comprise Partial Least Squares Discriminant Analysis (PLS-DA), Decision Trees (DT), Logistic Regression (LR), Naive Bayes Classifier (NBC), Support Vector Machine (SVM), and Neural Network (NN). The results indicate that the PCA-NN model provides the optimal solution on most substrates. Although ATR-FTIR spectroscopy combined with machine learning effectively identifies bloodstains on substrates, the performance of different identification models still varies based on the type of substrate. The integration of these disciplines enables researchers to harness the power of data-driven approaches for solving complex forensic problems. Th

关键词： ATR-FTIR Bloodstains Forensic investigations Machine learning Substrates

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Terahertz Landau Polaritons in Nano-slots: Ultrastrong Coupling under Extreme Spatial Confinement

Terahertz Landau Polaritons in Nano-slots: Ultrastrong Coupl...

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International Conference on Infrared and Millimeter Waves

作者： Dasom Kim Sunghwan Kim Dukhyung Lee Shuang Liang Fuyang Tay Michael J. Manfra Dai-Sik Kim Junichiro Kono Department of Electrical and Computer Engineering Rice University Houston TX USA Applied Physics Graduate Program Smalley-Curl Institute Rice University Houston TX USA Department of Physics Long-wavelength Nanotechnology Laboratory and Quantum Photonics Institute Ulsan National Institute of Science and Technology (UNIST) Ulsan South Korea Department of Physics and Astronomy Purdue University West Lafayette IN USA Birck Nanotechnology Center Purdue University West Lafayette IN USA Elmore Family School of Electrical and Computer Engineering Purdue University West Lafayette IN USA School of Materials Engineering Purdue University West Lafayette IN USA Department of Physics and Astronomy Rice University Houston TX USA Department of Material Science and NanoEngineering Rice University Houston TX USA

We report ultrastrong coupling of the cyclotron resonance of a two-dimensional electron gas in a GaAs quantum well to terahertz cavity photons under extreme confinement to the nanometer scale. This was realized by an array of nano-slots fabricated close to the quantum well layer on the GaAs substrate. Our terahertz magnetospectroscopic measurements revealed two polariton branches as a function of applied magnetic field. While the photon-like part of the two polariton branches was clearly observed, the matter-like part was generally elusive. Our electromagnetic simulations quantitatively reproduce our observation for the upper-polariton branch. However, for the lower-polariton branch, our simulations predict a pronounced resonance, which was absent in experimental spectra. This discrepancy may be a consequence of the breakdown of the dipole approximation in this extreme confinement situation.

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AI-driven 3D Spatial Transcriptomics

arXiv

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arXiv 2025年

作者： Almagro-Pérez, Cristina Song, Andrew H. Weishaupt, Luca Kim, Ahrong Jaume, Guillaume Williamson, Drew F.K. Hemker, Konstantin Lu, Ming Y. Singh, Kritika Chen, Bowen Le, Long Phi Baras, Alexander S. Jiang, Sizun Bashashati, Ali Liu, Jonathan T.C. Mahmood, Faisal Department of Pathology Mass General Brigham Harvard Medical School BostonMA United States Cancer Program Broad Institute of Harvard and MIT CambridgeMA United States Data Science Program Dana-Farber Cancer Institute BostonMA United States Harvard-MIT Division of Health Sciences and Technology Massachusetts Institute of Technology CambridgeMA United States Department of Pathology Pusan National University Busan Korea Republic of Department of Pathology and Laboratory Medicine Emory University School of Medicine AtlantaGA United States Department of Computer Science & Technology University of Cambridge Cambridge United Kingdom Department of Electrical Engineering and Computer Science Massachusetts Institute of Technology CambridgeMA United States Rutgers Robert Wood Johnson Medical School New BrunswickNJ United States Department of Pathology Johns Hopkins Hospital BaltimoreMD United States Department of Biomedical Engineering Johns Hopkins Hospital BaltimoreMD United States Broad Institute of Harvard and MIT CambridgeMA United States Center for Virology and Vaccine Research Beth Israel Deaconess Medical Center Harvard Medical School BostonMA United States Department of Pathology Dana Farber Cancer Institute BostonMA United States Department of Pathology and Laboratory Medicine University of British Columbia VancouverBC Canada School of Biomedical Engineering University of British Columbia VancouverBC Canada Department of Mechanical Engineering Bioengineering Laboratory Medicine & Pathology University of Washington SeattleWA United States Harvard Data Science Initiative Harvard University CambridgeMA United States

A comprehensive three-dimensional (3D) map of tissue architecture and gene expression is crucial for illuminating the complexity and heterogeneity of tissues across diverse biomedical applications1. However, most spatial transcriptomics (ST) approaches remain limited to two-dimensional (2D) sections of tissue2–4. Although current 3D ST methods hold promise, they typically require extensive tissue sectioning, are complex, are not compatible with non-destructive 3D tissue imaging technologies, and often lack scalability5–8. Here, we present VOlumetrically Resolved Transcriptomics EXpression (VORTEX), an AI framework that leverages 3D tissue morphology and minimal 2D ST to predict volumetric 3D ST. By pretraining on diverse 3D morphology–transcriptomic pairs from heterogeneous tissue samples and then fine-tuning on minimal 2D ST data from a specific volume of interest, VORTEX learns both generic tissue-related and sample-specific morphological correlates of gene expression. This approach enables dense, high-throughput, and fast 3D ST, scaling seamlessly to large tissue volumes far beyond the reach of existing 3D ST techniques. By offering a cost-effective and minimally destructive route to obtaining volumetric molecular insights, we anticipate that VORTEX will accelerate biomarker discovery and our understanding of morphomolecular associations and cell states in complex tissues. Interactive 3D ST volumes can be viewed at https://***/. © 2025, CC BY-NC-ND.

关键词： Vortex flow

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An Approach for 3D Microprinting Soft Robotic Surgical Tools at 1.5 French Length Scales for Endovascular Interventions

An Approach for 3D Microprinting Soft Robotic Surgical Tools...

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IEEE International Conference on Soft Robotics (RoboSoft)

作者： Bailey M. Felix Olivia M. Young Jordi T. Andreou Nicholas Portwood Kieran J. Barvenik Noah Barnes Clifford R. Weiss Christopher R. Bailey Dheeraj Gandhi Miroslaw Janowski Jeremy D. Brown Eleonora Tubaldi Mark Fuge Axel Krieger Ryan D. Sochol Department of Bioengineering University of Maryland College Park MD USA Department of Mechanical Engineering University of Maryland College Park MD USA Department of Mechanical Engineering Johns Hopkins University Baltimore MD USA The Russell H. Morgan Department of Radiology and Radiological Science Division of Vascular and Interventional Radiology Johns Hopkins University School of Medicine Baltimore MD USA Department of Diagnostic Radiology and Nuclear Medicine Program in Image Guided Neurointerventions University of Maryland School of Medicine Baltimore MD USA Maryland Robotics Center University of Maryland College Park MD USA Robert E. Fischell Institute for Biomedical Devices University of Maryland College Park MD USA

A wide range of endovascular interventions rely on surgical tools such as guidewire-catheter systems for navigating through blood vessels to, for example, deliver embolic materials, stents, and/or therapeutic agents to target sites as well as biopsy tools (e.g., forceps and punch needles) for medical diagnostics. In response to the difficulties in maneuvering such endovascular instruments safely and effectively to access intended sites in the body, researchers have developed an array of soft robotic surgical tools that harness fluidic (e.g., pneumatic or hydraulic) actuation schemes to support on-demand steering and control. Despite considerable progress, scaling these tools down to the sizes required for medical procedures such as cerebral aneurysm treatment and liver chemoembolization have been hindered by manufacturing-induced constraints. To provide a pathway to overcome these miniaturization challenges, this work presents a novel additive manufacturing strategy for 3D microprinting integrated soft actuators directly atop multilumen microfluidic tubing via “Two-Photon Direct Laser Writing (DLW)”. As an exemplar, a two-actuator tip was 3D printed onto custom dual-lumen tubing-resulting in a system akin to a 1.5 French (Fr) guidewire with a steerable tip. Experimental results revealed independent actuator control via the discretized lumens, with tip bending of approximately 60° under input pressures of 130 kPa via hydraulic actuation. These results suggest that the presented strategy could be extended to achieve new classes of fluidically actuated soft robotic surgical tools at unprecedented length scales for emerging applications in minimally invasive surgery.

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Retraction notice to“Amelioration of imiquimod-induced psoriasis-like dermatitis in mice by DSW therapy inspired hydrogel”[BIOMAT 6(2021)299-311]

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Bioactive materials 2022年第1期7卷 1-1页

作者： Xiang He Bing Zhu WeiJia Xie Yu He Jian Song Yi Zhang Chi Sun Hao Li Qi Yu Tang XinXin Sun Yanni Tan Yong Liu State Key Laboratory of Powder Metallurgy Central South UniversityChangsha410083China School of Materials Science and Engineering Central South UniversityChangsha410083China Xiangya School of Medicine Central South UniversityChangsha410083China Department of Material and Chemical Engineering Zhengzhou University of Light IndustryZhengzhou450002China Department of Mechanical Engineering and Munich School of Bioengineering Technical University of Munich85748GarchingGermany Changchun Institute of Applied Chemistry Chinese Academy of SciencesChangchun130022China Center for Medical Genetics&Hunan Key Laboratory of Medical Genetics School of Life SciencesCentral South UniversityChangsha410083China A.James Clark School of Engineering University of MarylandCollege Park20742MDUnited States

This article has been retracted:please see Elsevier Policy on Article Withdrawal(https://***/about/our-business/policies/article-withdrawal).This article has been retracted at the request of all the Authors,the Editor-in-Chief and the owner of the *** article has been retracted because of the authors recently re-conducted partly the experiments and found that the anti-bacteria behavior of Rb+was not *** shown in Fig.1(see enclosed file),at a centration as high as 200 mM,the addition of single Rb+does not show anti-bacteria *** Fig.2(see enclosed file),the authors prepared a mixed solution containing Rb+,Mg2+and Zn2+with concentrations close to those(12 h)in the article,and found that the mixed solution does not show anti-bacterial effect *** two figures indicate that the anti-bacteria effect of Rb+is not conclusive,which seriously impairs the rigidity of the *** complex factors influencing the experiments with hydrogels,there might be other effects on the anti-bacteria ***,since the anti-bacteria effect of Rb+is incorrect,the authors would like to retract the published article.

关键词： please journal Elsevier

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Novel Biodegradable Ca–P/Ti–F Composite Conversion Coatings for Improving the Corrosion Resistance of Medical Magnesium materials

SSRN

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SSRN 2024年

作者： Sun, Ying-Sui Chu, Peng-Wei Cheng, An-Yu You, Jhu-Lin Chang, Tsung-Ming Jian, Shun-Yi Chi, Chun-Shang Liu, Yu-Cheng Chang, Chin-Jou School of Dental Technology College of Oral Medicine Taipei Medical University Taipei Taiwan Department of Engineering and System Science National Tsing Hua University Hsinchu300044 Taiwan Department of Chemical & Materials Engineering Chung Cheng Institute of Technology National Defense University Taoyuan335 Taiwan System Engineering and Technology Program National Chiao Tung University Hsinchu300 Taiwan Department of Material Engineering Ming Chi University of Technology New Taipei City24301 Taiwan Center for Plasma and Thin Film Technology Ming Chi University of Technology New Taipei243303 Taiwan Combination Medical Device Technology Division Medical Devices R&D Service Department Metal Industries Research & Development Centre Kaohsiung802 Taiwan

Mg and its alloys are characterized by favorable biocompatibility and nontoxicity, and these properties have stimulated considerable research interest in their application as degradable biomaterials for medical implants. However, the clinical application of these materials is restricted by their rapid degradation. Therefore, this study designed a surface modification method for Mg and Mg alloys to enable them to satisfy clinical requirements. A two-step conversion coating method was applied to pure Mg. Pure Mg samples were first coated with calcium phosphate (Ca–P), following which they were coated with titanium fluoride (Ti–F), resulting in the production of Mg samples coated with a bioactive Ca–P/Ti–F composite. The composition of the coated samples was investigated through energy-dispersive X-ray spectroscopy with transmission electron microscopy, and their morphology was characterized through scanning electron microscopy. Moreover, hydrogen evolution measurements in simulated body fluid (SBF), electrochemical impedance spectroscopy, and polarization curves were employed to evaluate the samples’ corrosion resistance. The prepared composite conversion coatings had an average thickness of approximately 350 nm, and their corroded area was less than 5% of their total area following their immersion in SBF for 72 h. Thus, the prepared Ca–P/Ti–F composite conversion coatings effectively inhibited Mg corrosion in SBF. Moreover, the attachment and differentiation of MG-63 cells on the prepared coatings were observed. © 2024, The Authors. All rights reserved.

关键词： Energy dispersive spectroscopy

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Novel anti-adhesion Al2O3-TiN ceramic surgical electrodes with low thermal damage

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Ceramics International 2025年

作者： Ren, Guiying Feng, Xiangyi Jiao, Enxiang Chang, Lebing Xiao, Duanqiang Li, Yuechuan Deng, Chengchen Zhang, Xuehai Tang, Hui Sun, Ziru Wang, Huimin Xu, Meihong Yang, Xianjin Wang, Dong Zhang, Haijun School of Materials Science and Engineering Shandong University of Technology Shandong Zibo25500 China National United Engineering Laboratory for Biomedical Material Modification Shandong Qihe251100 China Key Laboratory for Bioarcheological Science and Technology of Ministry of Education National Local Joint Engineering Laboratory for Vascular Implants Bioengineering College of Chongqing University Chongqing 400044 China Department of Interventional and Vascular Surgery Shanghai Tenth People's Hospital School of Medicine Tongji University Shanghai 200072 China

High-frequency electrodes, renowned for their superior cutting and coagulation capabilities, are a staple device in surgical procedures. Nonetheless, the challenges of soft-tissue adhesion and the potential for thermal damage during surgery remain significant and cannot be overlooked. In this study, Al2O3-TiN ceramic electrodes have been successfully fabricated to address the challenges of tissue thermal damage and adhesion that are encountered during surgical procedures. These electrodes are engineered to alleviate the aforementioned issues, enhancing the safety and efficacy of surgical interventions. The incorporation of TiN into Al2O3 ceramics confers electrical conductivity upon the material, yet it ensures that this conductivity remains below that of the 316 stainless steel electrodes. This strategic modification leads to a substantial decrease in intraoperative contact temperature at the electrode-tissue interface, with a maximum reduction of 24.7 °C compared to 316 stainless steel electrodes, thereby diminishing the incidence of thermal tissue damage. Meanwhile, the enhanced hydrophobicity of the ceramic electrode surface significantly diminishes tissue adhesion during surgical procedures, with a maximum reduction of 50 % in weight gain before and after cutting compared to 316 stainless steel electrodes, thereby mitigating the risk of tissue tearing. The present investigation introduces an innovative approach to the fabrication of high-frequency surgical electrodes, holding significant promise for translation into clinical practice. © 2025 Elsevier Ltd and Techna Group S.r.l.

关键词： Electric resistance

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Multiple Doses of Exogenous FSTL1 Delivered with an Epicardial Reservoir Improve Cardiac Function, Healing and Angiogenesis after a Myocardial Infarction

SSRN

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SSRN 2023年

作者： Varela, Claudia E. Monahan, David S. Islam, Shahrin Whyte, William Bonnemain, Jean Ngoy, Souen Fisch, Sudeshna Duffy, Garry P. Roche, Ellen T. Institute for Medical Engineering and Science Massachusetts Institute of Technology CambridgeMA United States Harvard-MIT Program in Health Sciences and Technology CambridgeMA United States University of Galway Galway Ireland Department of Mechanical Engineering Massachusetts Institute of Technology CambridgeMA United States Department of Adult Intensive Care Medicine Lausanne University Hospital University of Lausanne Lausanne Switzerland Department of Medicine Brigham & Women's Hospital Harvard Medical School BostonMA United States Advanced Materials and BioEngineering Research Centre AMBER University of Galway Galway Ireland

Epicardial delivery of human follistatin-like 1 protein (FSTL1) induces significant cardiac benefit following a myocardial infarction (MI). However, the optimal dosing regimen for maximal therapeutic benefit has not yet been elucidated. To investigate the impact of multiple FSTL1 doses, without the confounding effects of multiple surgical procedures for multidose delivery, alternative delivery strategies are needed. Here, we use an epicardial reservoir that allows non-invasive delivery of additional doses after implantation to investigate the impact of single, double, and triple FSTL1 dose regimens in a rat model of MI. Multidose delivery of FSTL1 improves ejection fraction (3 doses), fractional shortening (1, 2 and 3 doses), and chamber stiffness (2 doses) 28 days after MI. Histologically, multiple FSTL1 doses increase ventricular wall thickness (2 and 3 doses) and reduce infarct size (1, 2, and 3 doses). We also demonstrate a dose-dependent increase in blood vessel number and density in the infarct zone, with three FSTL1 doses leading to the highest improvements. This study shows that multidose delivery of FSTL1 improves cardiac function, healing, and angiogenesis following MI. The epicardial delivery platform used here may be essential in optimizing dosing regimens of various bioagent combinations for a range of clinical indications. © 2023, The Authors. All rights reserved.

关键词： Controlled drug delivery

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