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PRX Life 2025年第1期3卷 013018-013018页

作者： Alex T. Grigas Zhuoyi Liu Jack A. Logan Mark D. Shattuck Corey S. O'Hern Graduate Program in Computational Biology and Biomedical Informatics Yale University New Haven Connecticut 06520 USA Integrated Graduate Program in Physical and Engineering Biology Yale University New Haven Connecticut 06520 USA Department of Mechanical Engineering Yale University New Haven Connecticut 06520 USA Benjamin Levich Institute and Physics Department The City College of New York New York New York 10031 USA Department of Physics Yale University New Haven Connecticut 06520 USA Department of Applied Physics Yale University New Haven Connecticut 06520 USA

Proteins fold to a specific functional conformation with a densely packed core that controls their stability. Despite their importance, we lack a quantitative explanation for why all protein cores, regardless of their overall fold, possess the same average packing fraction 〈ϕ〉≈0.55. However, important developments in the physics of jamming in particulate systems can shed light on the packing of protein cores. Here, we extend the framework of jamming to describe core packing in collapsed polymers, as well as in all-atom models of folded proteins. First, we show in a spherical bead-spring polymer model (with and without bond-angle constraints) that as the hydrophobic interactions increase relative to thermal fluctuations, a jamming-like transition occurs when the core packing fraction exceeds ϕc with the same power-law scaling behavior for the potential energy Vr, excess contact number ΔN, and characteristic frequency of the vibrational density of states ω* versus Δϕ=ϕ−ϕc as that for jammed particulate systems. Then, we develop an all-atom model for proteins and find that, above ϕc∼0.55, protein cores undergo a jamming-like transition, but with anomalous power-law scaling for Vr, ΔN, and ω* versus Δϕ. The all-atom protein model remains close to the native protein structure during jamming and accurately refolds from partially unfolded states.

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Wireless, self‑powered phototrophic algaerobot‑infused nanotherapeutic hydrogels for enhanced diabetic wound healing

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Chemical Engineering Journal 2025年 515卷

作者： Wei-Yung Huang Jiunn-Horng Kang Yan-Ting Chen Jia-Wei Liang Lan Pham Hoai Hoang Hieu Trung Nguyen Andrew E.-Y. Chuang Graduate Institute of Biomedical Materials and Tissue Engineering International Ph.D. Program in Biomedical Engineering College of Biomedical Engineering Taipei Medical University New Taipei City 23561 Taiwan International Ph.D. Program in Medicine College of Medicine Taipei Medical University Taipei 110 Taiwan Department of Physical Medicine and Rehabilitation School of Medicine College of Medicine Taipei Medical University No.250 Wuxing Street Xinyi District Taipei 110 Taiwan Department of Physical Medicine and Rehabilitation Taipei Medical University Hospital Taipei 110 Taiwan Graduate Institute of Nanomedicine and Medical Engineering College of Biomedical Engineering Taipei Medical University Taipei 110 Taiwan Department of Orthopedics and Trauma Faculty of Medicine University of Medicine and Pharmacy at Ho Chi Minh City Ho Chi Minh City 700000 Viet Nam Cell Physiology and Molecular Image Research Center Taipei Medical University-Wan Fang Hospital Taipei 11696 Taiwan Precision Medicine and Translational Cancer Research Center Taipei Medical University Hospital Taipei 11031 Taiwan

Diabetic wounds present a significant clinical challenge due to impaired immunity, hypoxia, poor neovascularization, and chronic inflammation, often resulting in severe complications such as amputation. Conventional therapies, including hyperbaric oxygen, antioxidants, and electrical stimulation, face limitations in delivering sustained and safe oxygen, hydrogen, and electrical stimulation to the wound site. This study introduces a groundbreaking approach by integrating phototrophic algae robots (AR) into a methylcellulose (MC) hydrogel, combined with platelet-derived extracellular vesicles (pEVs) and conductive glycol chitosan-polypyrrole nanoparticles (GCS-PPy NPs), forming a multifunctional composite system (MC-pEV-AR-GCS-PPy NPs). This advanced composite addresses the limitations of traditional treatments by integrating continuous, self-powered hydrogen and oxygen generation, electrical stimulation, and hyperthermia, all triggered by light-activated, electromagnetically driven mechanisms. Photosynthetic algae robots offer a sustainable solution for the generation of hydrogen and oxygen, effectively targeting the prevalent issues of hypoxia and the deficit frequently encountered in diabetic wounds. This innovative approach improves therapeutic outcomes through the integration of electrochemical processes and nanophototherapeutics, creating a multimodal platform. This platform not only promotes tissue regeneration and angiogenesis but also alleviates hypoxic conditions, modulates immune responses, and addresses key challenges associated with chronic wound healing. Incorporating pEVs amplifies the regenerative potential of the system, accelerating wound healing and promoting tissue regeneration. This self-powered platform not only reduces inflammation and suppresses M1 macrophage bioactivity but also regulates immune responses, creating an optimized healing environment. The MC-pEV-AR-GCS-PPy NPs composite represents a promising translational approach to diabetic wo

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Acoustofluidic bioassembly induced morphogenesis for therapeutic tissue fabrication

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Nature Communications 2025年第1期16卷 1-19页

作者： Kang, Byungjun Jeong, Eunseon Han, Seung Yeop Heo, Jeong Hyun Lee, Yunam Choi, Suah Choi, Yunjung Kang, Donyoung Hwang, Youn-Hoo Lee, Jiin Seo, Jung Hwa Kim, Jinyoung Jeong, Inhea Kim, Enji Lee, Juyoung Kim, Dae-Eun Park, Jang-Ung Cho, Sung-Rae Jin, Yoonhee Cho, Seung-Woo Lee, Hyungsuk School of Mechanical Engineering Yonsei University Seoul 03722 South Korea Department of Biotechnology Yonsei University Seoul 03722 South Korea Department of Biomaterials Science and Engineering Yonsei University Seoul 03722 South Korea Department of Physiology Yonsei University College of Medicine Seoul 03722 South Korea Department and Research Institute of Rehabilitation Medicine Yonsei University College of Medicine Seoul 03722 South Korea Graduate Program of Biomedical Engineering Yonsei University College of Medicine Seoul 03722 South Korea Department of Materials Science and Engineering Yonsei University Seoul 03722 South Korea Center for Nanomedicine Institute for Basic Science (IBS) Seoul 03722 South Korea Department of Neurosurgery Yonsei University College of Medicine Seoul 03722 South Korea Graduate Program of Nano Biomedical Engineering (NanoBME) Advanced Science Institute Yonsei University Seoul 03722 South Korea Rehabilitation Institute of Neuromuscular Disease Yonsei University College of Medicine Seoul 03722 South Korea Department of Rehabilitation Medicine Graduate School of Medical Science Brain Korea 21 Project Yonsei University College of Medicine Seoul 03722 South Korea Brain research institute Yonsei University College of Medicine Seoul 03722 South Korea

To build in vitro tissues for therapeutic applications, it is essential to replicate the spatial distribution of cells that occurs during morphogenesis in vivo. However, it remains technically challenging to simultaneously regulate the geometric alignment and aggregation of cells during tissue fabrication. Here, we introduce the acoustofluidic bioassembly induced morphogenesis, which is the combination of precise arrangement of cells by the mechanical forces produced by acoustofluidic cues, and the morphological and functional changes of cells in the following in vitro and in vivo cultures. The acoustofluidic bioassembly can be used to create tissues with regulated nano-, micro-, and macro-structures. We demonstrate that the neuromuscular tissue fabricated with the acoustofluidic bioassembly exhibits enhanced contraction dynamics, electrophysiology, and therapeutic efficacy. The potential of the acoustofluidic bioassembly as an in situ application is demonstrated by fabricating artificial tissues at the defect sites of living tissues. The acoustofluidic bioassembly induced morphogenesis can provide a pioneering platform to fabricate tissues for biomedical applications. © The Author(s) 2025.

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O63: Leveraging global and local genomic data to guide equitable carrier screening: From Genome Aggregation Database (gnomAD) to Qatar Genome

Genetics in Medicine Open

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Genetics in medicine Open 2025年 3卷 102632-102632页

作者： Aarabi, Mahmoud Mbarek, Hamdi Bashar, Aryan Soman, Vishal Al-Mulla, Hajer Nkrumah, Esther Schmitz, Matthew Darabi, Helia Wang, John Kiehl, Paris Sethi, Rahil Saad, Chadi Rajkovic, Aleksandar Yatsenko, Svetlana Chandran, Uma Departments of Pathology and Obstetrics Gynecology and Reproductive Sciences University of Pittsburgh School of Medicine； Medical Genetics and Genomics Laboratories University of Pittsburgh Medical Center (UPMC) Pittsburgh PA Qatar Genome Program Qatar Foundation； Qatar Precision Health Institute Doha Qatar Data Science Graduate Program University of Colorado Boulder Boulder CO Department of Biomedical Informatics University of Pittsburgh School of Medicine Pittsburgh PA Joan H. Marks Graduate Program in Human Genetics Sarah Lawrence College New York NY Temerty Faculty of Medicine University of Toronto Toronto ON Canada Medical Genetics and Genomics Laboratories University of Pittsburgh Medical Center (UPMC) Department of Pediatrics University of Pittsburgh School of Medicine Pittsburgh PA Department of Microbiology Immunology and Pathology Colorado State University Fort Collins CO Department of Pathology and Institute of Human Genetics University of California San Francisco San Francisco CA Department of Pathology Stanford University School of Medicine Stanford CA

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Targeted tumor coating with antigenic, CTL-recognizable peptides via Annexin A5 chimeric constructs following chemotherapy redirects adaptive CD8+ T cell immunity for tumor clearance

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Cellular & Molecular Immunology 2021年第6期18卷 1578-1580页

作者： Tae Heung Kang Andrew Yang Yachea Tsai Louise Ferrall Chien-Fu Hung Institute of Biomedical Science and Technology Konkuk UniversitySeoulSouth Korea Genetics and Genomics Graduate Program Baylor College of MedicineHoustonTXUSA Medical Scientist Training Program Baylor College of MedicineHoustonTXUSA Department of Pathology Johns Hopkins UniversityBaltimoreMDUSA Department of Oncology Johns Hopkins UniversityBaltimoreMDUSA

A common drawback of many cancer immunotherapies,including immune checkpoint blockade,is their reliance on the expression of immunogenic tumor antigens by cancer cells for immune recognition and clearance,which limits their efficacy against cancers with weak antigenicity.1 To overcome this obstacle,we and others have explored strategies to harness the immune responses against nontumor antigens and redirect those immune responses to target tumor cells.2,3,4,5 In particular,we have pioneered a therapeutic strategy fusing tumor-targeting proteins with known antigenic peptide epitopes not naturally expressed by tumor cells,which are flanked by peptide sequences that can be recognized and cleaved by proteases overexpressed in most cancers.2,3 This strategy facilitates the targeted delivery of immunogenic peptides into tumor foci,the release of immunogenic peptides into the tumor microenvironment(TME)via tumor protease cleavage,and subsequent loading of these peptides onto major histocompatibility complex class 1(MHC-I)on the tumor cell surface,allowing the recognition of coated tumor cells by the respective peptide-specific cytotoxic CD8+T lymphocytes(CTLs)for elimination.

关键词： immunity overcome coating

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Microenvironmental regulation of stem cells injected in the area at risk of neurodegenerative diseases

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BIOCELL 2022年第10期46卷 2231-2234页

作者： JU HYUNG LEE IL-KWON KIM SANG WOO KIM SOYEON LIM SEAHYOUNG LEE KI-CHUL HWANG BYEONG-WOOK SONG Graduate Program of Biomedical Engineering Yonsei UniversitySeoul03722Korea Institute for Bio-Medical Convergence College of MedicineCatholic Kwandong UniversityGangwon-do25601Korea Department for Medical Science College of MedicineCatholic Kwandong UniversityGangwon-do25601Korea

The complex mechanism of degenerative diseases and the non-specific modulation of regenerative targets aretopics that need to be elucidated in order to advance the use of stem cells in improvement of neurodegenerative *** pre-transplantation through post-transplantation, there are many changes in the conditions, both inside andoutside of the stem cells that have not been carefully considered. This has hindered development in the field of celltherapy and regeneration. This viewpoint highlights the potential implications of intracellular and extracellularalterations of stem cells in transplanted areas at risk of neurodegenerative disease.

关键词： Cell therapy Microenvironment Neurodegenerative disease Stem cells

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Impact of DNA-binding position variants on yeast gene expression

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Nucleic Acids Research 2009年第21期37卷 6991-7001页

作者： Swamy, Krishna B.S. Cho, Chung-Yi Chiang, Sufeng Tsai, Zing Tsung-Yeh Tsai, Huai-Kuang Institute of Information Science National Yang-Ming University Taiwan Bioinformatics Program Taiwan International Graduate Program National Yang-Ming University Taiwan Institute of Biomedical Informatics National Yang-Ming University Taiwan Research Center for Information Technology Innovation Academia Sinica Taipei 115 Taiwan

Transcription factors (TFs) regulate gene expression by binding to specific binding sites (TFBSs) in gene promoters. TFBS motifs may contain one or more variable positions. Although the prevailing assumption is that nucleotide variants at such positions are functionally equivalent, there is increasing evidence that such variants play a role in regulation of gene expression. In this article, we propose a method for studying the relationship between the expression of target genes and nucleotide variants in TFBS motifs at a genome-wide scale in Saccharomyces cerevisiae, especially the combinatorial effects of variants at two positions. Our analysis shows that nucleotide variations in more than one-third of variable positions and in 20% of dependent position pairs are highly correlated to gene expression. We define such positions as 'functional'. However, some positions are only functional as dependent pairs, but not individually. In addition, a significant proportion of the functional positions have been well conserved across all yeast-related species studied. We also find that some positions require the presence of co-occurring TFs, while others maintain their functionality in the absence of a co-occurring TF. Our analysis supports the importance of nucleotide variants at variable positions of TFBSs in gene regulation. © The Author(s) 2009. Published by Oxford University Press.

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Melatonin modulates adiponectin expression on murine colitis with sleep deprivation

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World Journal of Gastroenterology 2016年第33期22卷 7559-7568页

作者： Tae Kyun Kim Young Sook Park Haing-Woon Baik Jin Hyun Jun Eun Kyung Kim Jae Woong Sull Ho Joong Sung Jin Woo Choi Sook Hee Chung Myung Chan Gye Ju Yeon Lim Jun Bong Kim Seong Hwan Kim Department of Gastroenterology Eulji University School of MedicineEulji Hospital Department of Biochemistry and Molecular Biology Eulji University School of Medicine Departemnt of Biomedical Laboratory Science Graduate School of Health ScienceEulji University Departemnt of Senior Healthcare BK21 plus ProgramGraduate SchoolEulji University Department of Pathology Eulji University School of Medicine Department of Gastroenterology Ajou University School of Medicine Department of Life Science and Institute of Natural Sciences Hanyang University

AIM To determine adiponectin expression in colonic tissue of murine colitis and systemic cytokine expression after melatonin treatments and sleep *** The following five groups of C57BL/6 mice were used in this study:(1) group Ⅰ,control;(2) group Ⅱ,2% DSS induced colitis for 7 d;(3) group Ⅲ,2% DSS induced colitis and melatonin treatment;(4) group Ⅳ,2% DSS induced colitis with sleep deprivation(SD) using specially designed and modified multiple platform water baths; and(5) group V,2% DSS induced colitis with SD and melatonin treatment. Melatonin(10 mg/kg) or saline was intraperitoneally injected daily to mice for 4 d. The body weight was monitored daily. The degree of colitis was evaluated histologically after sacrificing the mice. Immunohistochemical staining and Western blot analysis was performed using anti-adiponectin antibody. After sampling by intracardiac punctures,levels of serum cytokines were measured by ELISA. RESULTS Sleep deprivation in water bath exacerbated DSS induced colitis and worsened weight loss. Melatonin injection not only alleviated the severity of mucosal injury,but also helped survival during stressful condition. The expression level of adiponectin in mucosa was decreased in colitis,with the lowest level observed in colitis combined with sleep deprivation. Melatonin injection significantly(P < 0.05) recovered the expression of adiponectin. The expression levels of IL-6 and IL-17 were increased in the serum of mice with DSS colitis but decreased after melatonin injection. CONCLUSION This study suggested that melatonin modulated adiponectin expression in colonic tissue and melatonin and adiponectin synergistically potentiated antiinflammatory effects on colitis with sleep deprivation.

关键词： Colitis Melatonin Adiponectin Sleep deprivation

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Enhancing Interstitial Lung Disease Diagnoses Through Multimodal AI Integration of Histopathological and CT Image Data

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Respirology 2025年第0期 2025 Apr 2页

作者： Lami, Kris Ozasa, Mutsumi Che, Xiangqian Uegami, Wataru Kato, Yoshihiro Zaizen, Yoshiaki Tsuyama, Naoko Mori, Ichiro Ichihara, Shin Yoon, Han-Seung Egashira, Ryoko Kataoka, Kensuke Johkoh, Takeshi Kondo, Yasuhiro Attanoos, Richard Cavazza, Alberto Marchevsky, Alberto M. Schneider, Frank Augustyniak, Jaroslaw Wojciech Almutrafi, Amna Fabro, Alexandre Todorovic Brcic, Luka Roden, Anja C. Smith, Maxwell Moreira, Andre Fukuoka, Junya Department of Pathology Informatics Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan Department of Respiratory Medicine Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan Strategic AI Group Future Corporation Tokyo Japan Department of Pathology Kameda Medical Center Kamogawa Japan Division of Respirology Neurology and Rheumatology Department of Medicine Kurume University School of Medicine Kurume Japan Division of Pathology Cancer Institute Japanese Foundation for Cancer Research Tokyo Japan Department of Pathology International University of Health and Welfare Narita Japan Department of Surgical Pathology Sapporo Kosei General Hospital Sapporo Japan Department of Radiology Saga University Saga Japan Department of Respiratory Medicine and Allergy Tosei General Hospital Seto Japan Department of Radiology Kansai Rosai Hospital Amagasaki Japan Department of Thoracic Surgery Kitasato University School of Medicine Kanagawa Japan Department of Cellular Pathology Cardiff University Cardiff United Kingdom Pathology Unit Azienda USL/IRCCS di Reggio Emilia Reggio Emilia Italy Department of Pathology Cedars-Sinai Medical Center Los Angeles CA United States Department of Pathology and Laboratory Medicine Emory University Atlanta GA United States Institut for Pathology Spandau Berlin Germany Department of Anatomical Pathology King Fahad Medical City Riyadh Saudi Arabia Department of Pathology and Legal Medicine Ribeirão Preto Medical School University of São Paulo São Paulo Brazil Diagnostic and Research Institute of Pathology Medical University of Graz Graz Austria Department of Laboratory Medicine and Pathology Mayo Clinic Rochester MN United States Department of Laboratory Medicine and Pathology Mayo Clinic Scottsdale AZ United States Department of Pathology NYU Grossman School of Medicine New York NY United States

Background and Objective: The diagnosis of interstitial lung diseases (ILDs) often relies on the integration of various clinical, radiological, and histopathological data. Achieving high diagnostic accuracy in ILDs, particularly for distinguishing usual interstitial pneumonia (UIP), is challenging and requires a multidisciplinary approach. Therefore, this study aimed to develop a multimodal artificial intelligence (AI) algorithm that combines computed tomography (CT) and histopathological images to improve the accuracy and consistency of UIP diagnosis. Methods: A dataset of CT and pathological images from 324 patients with ILD between 2009 and 2021 was collected. The CT component of the model was trained to identify 28 different radiological features. The pathological counterpart was developed in our previous study. A total of 114 samples were selected and used for testing the multimodal AI model. The performance of the multimodal AI was assessed through comparisons with expert pathologists and general pathologists. Results: The developed multimodal AI demonstrated a substantial improvement in distinguishing UIP from non-UIP, achieving an AUC of 0.92. When applied by general pathologists, the diagnostic agreement rate improved significantly, with a post-model κ score of 0.737 compared to 0.273 pre-model integration. Additionally, the diagnostic consensus rate with expert pulmonary pathologists increased from κ scores of 0.278–0.53 to 0.474–0.602 post-model integration. The model also increased diagnostic confidence among general pathologists. Conclusion: Combining CT and histopathological images, the multimodal AI algorithm enhances pathologists' diagnostic accuracy, consistency, and confidence in identifying UIP, even in cases where specialised expertise is limited. (Figure presented.). © 2025 The Author(s). Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.

关键词： CT histopathology interstitial lung disease multimodal AI UIP

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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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