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A generalized adder for cell size homeostasis: Effects on stochastic clonal proliferation

Biophysical Journal 2025年第9期124卷 1376-1386页

作者： Nieto, César Vargas-García, César Augusto Singh, Abhyudai Department of Electrical and Computer Engineering University of Delaware Newark DE United States AGROSAVIA - Corporacion Colombiana de Investigacion Agropecuaria Cundinamarca Mosquera Colombia Department of Electrical and Computer Engineering Biomedical Engineering Mathematical Sciences Interdisciplinary Neuroscience Program University of Delaware Newark DE United States

Measurements of cell size dynamics have revealed phenomenological principles by which individual cells control their size across diverse organisms. One of the emerging paradigms of cell size homeostasis is the adder, where the cell cycle duration is established such that the cell size increase from birth to division is independent of the newborn cell size. We provide a mechanistic formulation of the adder, considering that cell size follows any arbitrary nonexponential growth law. Our results show that the main requirement to obtain an adder regardless of the growth law (the time derivative of cell size) is that cell cycle regulators are produced at a rate proportional to the growth law, and cell division is triggered when these molecules reach a prescribed threshold level. Among the implications of this generalized adder, we investigate fluctuations in the proliferation of single-cell-derived colonies. Considering exponential cell size growth, random fluctuations in clonal size show a transient increase and then eventually decay to zero over time (i.e., clonal populations become asymptotically more similar). In contrast, several forms of nonexponential cell size dynamics (with adder-based cell size control) yield qualitatively different results: clonal size fluctuations monotonically increase over time, reaching a nonzero value. These results characterize the interplay between cell size homeostasis at the single-cell level and clonal proliferation at the population level, explaining the broad fluctuations in clonal sizes seen in barcoded human cell lines. © 2025 Biophysical Society

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Comparison of Hemodynamic Circulation in Pulsatile and Nonpulsatile Extracorporeal Membrane Oxygenation Systems Using an In-Vitro Heart Model

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ASAIO Journal 2025年 2025 Apr 17页

作者： Yoo, Changyoung Jang, Hyun-Woo Kang, Seongmin Choi, Seong-Wook Interdisciplinary Program in Biohealth-Machinery Convergence Engineering Kangwon National University Chuncheon-si Korea Republic of Program of Mechanical and Biomedical Engineering College of Engineering Kangwon National University Chuncheon-si Korea Republic of

This study conducts an in-vitro experiment using a mock circulation system that mimics human circulation to assess the veno-arterial extracorporeal membrane oxygenation (ECMO) system. This study aims to compare the hemodynamic effects of centrifugal and pulsatile ECMO systems on the body using an in-vitro cardiogenic shock model. The heart model used in this study involves a contracting blood sac with inlet and outlet valves, capable of maintaining arterial pressure between 80 and 120 mm Hg while delivering a blood flow of 1.8-2 L/min, effectively replicating a cardiogenic shock model. The contraction force in the heart model was generated using a pneumatic cylinder and gradually decreased to simulate reduced cardiac function. The initial blood flow rates of both ECMO systems were maintained at 2 L/min under identical conditions for a fair comparison. Upon reducing the stroke volume of the heart to 35 ml, the ECMO system with counter-pulsation control increased the cardiac output by 10.7% and systemic circulation by 3.8% compared with the conventional ECMO system. This study demonstrates the hemodynamic benefits provided by the sustained counter-pulsation in an in-vitro weakened heart model. Pulsatile flow ECMO systems may serve as an alternative to address the limitations of continuous flow ECMO systems. © ASAIO 2025.

关键词： Heart

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Evaluating Crosslinking Efficiency and Cytocompatibility of Three Commonly Used Photoinitiators Across Different Cell-Compatible Hydrogel Platforms

SSRN

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SSRN 2025年

作者： Gavish Moscovitz, Aya Simaan Yameen, Haneen Bar-Am, Orit Seliktar, Dror The Faculty of Biomedical Engineering Technion-Israel Institute of Technology Haifa Israel The Interdisciplinary Program in Biotechnology Technion–Israel Institute of Technology Haifa Israel

biomedical hydrogels that undergo a rapid liquid-to-solid phase transition often use a photopolymerization strategy to crosslink the polymer network. In applications such as 3D bioprinting or tissue engineering that involve cell-laden hydrogels, or where in-vivo polymerization is desired (i.e., in-situ), cytotoxicity of the hydrogel crosslinking reaction becomes an important issue. There are only a few cytocompatible photoinitiators (PIs) that are commonly used for crosslinking biomedical hydrogels, including Irgacure2959 (I2959), lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) and EosinY (EY). These PIs are illuminated at 365nm, 405nm and 525nm, respectively. The photopolymerization conditions, including PI concentration and illumination intensity may affect both the cytotoxicity of the reaction and the crosslinking of the hydrogel. Herein we tested these three PIs to optimize the maximum crosslinking efficiency while minimizing cell death associated with the photochemical reaction. Testing was performed on three different types of cell-compatible hydrogels used for cell encapsulation and 3D cell growth, including a synthetic material (poly(ethylene glycol)-diacrylate, PEG-DA), a semi-synthetic material (PEG-fibrinogen, PF) and a modified biological material (methacrylated fibrinogen, FibMA). Strain-rate controlled rheology was used to characterize the crosslinking reaction efficiency, both in terms of maximum shear storage modulus, G’, and crosslinking kinetics. Viability was examined on human dermal fibroblasts in 3D culture within photopolymerized PF hydrogels crosslinked using each of the PIs. The results showed that PI concentration and the illumination intensity had significant impact on the crosslinking efficiency, with each material system demonstrating different responses to the PI parameters. Optimal photo-crosslinking conditions, considering both crosslinking efficiency and cell viability were not the same for the modified protein hydrogels, as co

关键词： Cell death

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Injectable Platelet Lysate–Thai Silk Fibroin Hydrogel for Canine Intervertebral Disc Repair: A Minimally Invasive Strategy for Sustained Growth Factor Release

SSRN

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SSRN 2025年

作者： Ratanavaraporn, Juthamas Chayatup, Kannika Boonkruephan, Sarinthorn Keeratihattayakorn, Saran Wangdee, Chalika Interdisciplinary Program of Biomedical Engineering Program Faculty of Engineering Chulalongkorn University Bangkok Thailand Biomedical Engineering Research Center Faculty of Engineering Chulalongkorn University Bangkok Thailand Research Unit Chulalongkorn University Bangkok10330 Thailand Department of Veterinary Surgery Faculty of Veterinary Science Chulalongkorn University Bangkok Thailand

Canine intervertebral disc degeneration (IVDD) is a progressive spinal disorder that compromises mobility, induces chronic pain, and reduces quality of life. Existing treatments provide only symptomatic relief and do not halt disease progression or restore disc integrity. This study aims to develop and characterize an injectable platelet lysate–Thai silk fibroin (PL–TSF) hydrogel as a minimally invasive platform for localized and sustained growth factor delivery in canine IVDD treatment. The hydrogel was formulated using PL from expired canine platelet concentrates and TSF extracted from cocoons of Thai-bred Bombyx mori silkworms. Fabricated via sonication-induced gelation, it exhibited tunable gelation kinetics and injectability through a 27-gauge spinal needle, supporting clinical feasibility for minimally invasive delivery. PL incorporation enhanced the hydrogel’s elasticity and mechanical resilience without compromising scaffold integrity. The system demonstrated biphasic degradation over 35 days. TGF-β1 release kinetics exhibited an initial burst followed by sustained release over 28 days, consistent with diffusion-controlled delivery suitable for IVD repair. Cytotoxicity testing confirmed good biocompatibility and supported the viability of canine chondrocytes. By combining mechanical support with prolonged growth factor availability, PL–TSF hydrogels address key limitations of conventional platelet-based therapies and represent a promising strategy for early-stage IVDD intervention. Further in vivo studies are warranted to confirm long-term regenerative efficacy and facilitate clinical translation in veterinary medicine. © 2025, The Authors. All rights reserved.

关键词： Gelation

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DiffEGG: Diffusion-Driven Edge Generation as a Pixel-Annotation-Free Alternative for Instance Annotation

arXiv

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arXiv 2025年

作者： Jo, Sanghyun Lee, Ziseok Lee, Wooyeol Kim, Kyungsu OGQ Seoul Korea Republic of Department of Biomedical Sciences Seoul National University Seoul Korea Republic of Department of Computer Science and Engineering Seoul National University Seoul Korea Republic of School of Transdisciplinary Innovations Interdisciplinary Program in Artificial Intelligence Seoul National University Seoul Korea Republic of

Achieving precise panoptic segmentation heavily relies on pixel-wise instance annotations, but obtaining such datasets is costly. Unsupervised instance segmentation (UIS) eliminates annotation requirements but struggles with adjacent instance merging and single-instance fragmentation, largely due to the limitations of DINO-based backbones, which lack strong instance separation cues. Weakly-supervised panoptic segmentation (WPS) reduces annotation costs by using sparse labels (e.g., points, boxes), yet these annotations remain expensive and introduce human bias and boundary errors, limiting performance. To address these challenges, we propose DiffEGG (Diffusion-Driven EdGe Generation), a fully annotation-free method that extracts instance-aware features from pretrained diffusion models to generate precise instance edge maps. DiffEGG fundamentally differs from prior UIS and WPS approaches by leveraging pretrained diffusion models as a backbone. Unlike DINO-based UIS methods, diffusion models inherently capture fine-grained, instance-aware features, enabling more precise boundary delineation. DiffEGG further enhances edge connectivity through self-supervised fine-tuning, progressively improving instance separation. For WPS, DiffEGG completely eliminates annotation costs and human bias by operating without any form of manual supervision, addressing the key limitations of prior best methods. Additionally, we introduce RIP, a post-processing technique that fuses DiffEGG’s edge maps with segmentation masks in a task-agnostic manner. This broad applicability allows DiffEGG to be seamlessly integrated into various segmentation frameworks. When applied to UIS, DiffEGG and RIP achieve an average +4.4 AP improvement over prior best UIS methods. When combined with weakly-supervised semantic segmentation (WSS), DiffEGG enables WPS without instance annotations, outperforming prior best point-supervised WPS methods by +1.7 PQ. These results demonstrate that DiffEGG’s edge maps serv

关键词： Semantic Segmentation

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Developing an explainable Deep Neural Network for stress detection using biosignals and human-engineered features

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biomedical Signal Processing and Control 2025年 109卷

作者： Lee, Hyeokjong Kim, Jaewon Han, Bohyung Park, Sang Min Chang, Jooyoung Department of Biomedical Sciences Seoul National University College of Medicine Seoul03080 Korea Republic of Department of Electrical and Computer Engineering Seoul National University Seoul08826 Korea Republic of Interdisciplinary Program in Artificial Intelligence Seoul National University Seoul08826 Korea Republic of XAIMED Co. Ltd. Seoul02738 Korea Republic of

Detecting stress is crucial for preventing long-term health issues, and recent research, particularly using the WESAD (WEarable Stress and Affect Detection) dataset, has made significant advances in this area. Deep Neural Networks (DNNs) demonstrate a key advantage by efficiently processing raw signals, unlike traditional machine learning methods that predominantly rely on human-engineered features. In our study, we enhance DNN capabilities by integrating both raw signals and human-engineered features altogether. Our model, augmented with attention mechanisms, significantly improves its performance. This approach yields state-of-the-art results, demonstrating high accuracies across various modalities in the stress classification task: 92.89% in Electrodermal Activity (EDA), 92.16% in Photoplethysmography (PPG), and 96.57% in all modalities. Explaining model decisions in biosignals is challenging compared to the image domain, where images are inherently more intuitive. Many Explainable AI (XAI) techniques, optimized for images, face difficulties when applied to biosignals. To address this, we employ human-engineered features for biosignals, grounded in the ‘Human Comprehensible Space’ concept, making explanations intuitively understandable. Furthermore, a survey conducted to statistically validate the comprehensibility of our XAI methods confirms their effectiveness in enhancing the accessibility of explanations. © 2025 Elsevier Ltd

关键词： Deep neural networks

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Autolysosomal Dysfunction in Obesity-induced Metabolic Inflammation and Related Disorders

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Current obesity reports 2025年第1期14卷 43页

作者： Lenny Yi Tong Cheong Eka Norfaishanty Saipuljumri Gavin Wen Zhao Loi Jialiu Zeng Chih Hung Lo Lee Kong Chian School of Medicine Nanyang Technological University Singapore 308232 Singapore. Program in Neuroscience & Cognitive Science University of Arizona Tucson AZ 85721 USA. School of Biomedical Sciences The University of Queensland St Lucia QLD 4072 Australia. Department of Biomedical and Chemical Engineering Syracuse University Syracuse NY 13244 USA. jzeng22@syr.edu. Interdisciplinary Neuroscience Program Syracuse University Syracuse NY 13244 USA. jzeng22@syr.edu. Interdisciplinary Neuroscience Program Syracuse University Syracuse NY 13244 USA. clo101@syr.edu. Department of Biology Syracuse University Syracuse NY 13244 USA. clo101@syr.edu.

PURPOSE OF REVIEW:Obesity is a global health crisis affecting individuals across all age groups, significantly increasing the risk of metabolic disorders such as type 2 diabetes (T2D), metabolic dysfunction-associated fatty liver disease (MAFLD), and cardiovascular diseases. The World Health Organization reported in 2022 that 2.5 billion adults were overweight, with 890 million classified as obese, emphasizing the urgent need for effective interventions. A critical aspect of obesity's pathophysiology is meta-inflammation-a chronic, systemic low-grade inflammatory state driven by excess adipose tissue, which disrupts metabolic homeostasis. This review examines the role of autolysosomal dysfunction in obesity-related metabolic disorders, exploring its impact across multiple metabolic organs and evaluating potential therapeutic strategies that target autophagy and lysosomal function. RECENT FINDINGS:Emerging research highlights the importance of autophagy in maintaining cellular homeostasis and metabolic balance. Obesity-induced lysosomal dysfunction impairs the autophagic degradation process, contributing to the accumulation of damaged organelles and toxic aggregates, exacerbating insulin resistance, lipotoxicity, and chronic inflammation. Studies have identified autophagic defects in key metabolic tissues, including adipose tissue, skeletal muscle, liver, pancreas, kidney, heart, and brain, linking autophagy dysregulation to the progression of metabolic diseases. Preclinical investigations suggest that pharmacological and nutritional interventions-such as AMPK activation, caloric restriction mimetics, and lysosomal-targeting compounds-can restore autophagic function and improve metabolic outcomes in obesity models. Autolysosomal dysfunction is a pivotal contributor to obesity-associated metabolic disorders , influencing systemic inflammation and metabolic dysfunction. Restoring autophagy and lysosomal function holds promise as a therapeutic strategy to mitigate obesi

关键词： Autophagy function Lysosomal acidification Metabolic inflammation Neurodegeneration Neuroinflammation Therapeutic strategies

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A physical picture of liquid–liquid phase separation of proteins

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Journal of Molecular Liquids 2025年 424卷

作者： Kinoshita, Masahiro Hayashi, Tomohiko Nakamura, Yuka Yoshimori, Akira Katahira, Masato Nagata, Takashi Department of Chemistry of Science Chiba University 1-33 Yayoi-cho Inage Chiba263-8522 Japan Institute of Advanced Energy Kyoto University Kyoto Uji611-0011 Japan Interdisciplinary Program of Biomedical Engineering Assistive Technology and Art and Sports Sciences Faculty of Engineering Niigata University 8050 Ikarashi 2-no-cho Nishi-ku Niigata950-2181 Japan Department of Physics Niigata University Niigata950-2181 Japan

Liquid-liquid phase separation (LLPS) of proteins, by which they assemble and partition into a protein-dense phase and a protein-dilute phase, has caught much attention due to its essential roles in a variety of biological processes. Nevertheless, its mechanism remains to be unveiled. Here we develop a physical picture covering almost all the aspects of LLPSs of diverse systems. In our view, when only the proteins are looked at, one of the two phases is liquid-like and the other is gas-like. We relate LLPS to gas–liquid phase separation (GLPS) of simple fluids wherein the pivotal quantity is kBT (kB is the Boltzmann constant and T is the absolute temperature) divided by the absolute value of the minimum of interaction potential between fluid particles. GLPS occurs only if the pivotal quantity is sufficiently small. For LLPS, the interaction potential must be replaced by the potential of mean force (PMF) between protein molecules in aqueous solution. We do not explicitly consider aqueous solution, and its influence on properties of protein molecules is incorporated in PMF. PMF can reach its deep minimum when the two protein molecules associate. A physical interpretation is given for GLPS from a statistical-mechanics point of view, and it is extended to LLPS. In the extension, we discuss not only the similarities between the two phase separations but also the physical factors to be taken into account only in LLPS due to the fact that proteins are large molecules possessing polyatomic structures and they are immersed in aqueous solution. LLPS can be categorized as a biological self-assembly process. By reconsidering the results obtained in our earlier studies on biological self-assembly processes, we specify the entropic and energetic factors driving or opposing coacervation (association) of protein molecules followed by LLPS. We clarify the differences between LLPSs of folded proteins (i.e., proteins in the native states) and intrinsically disordered proteins. There c

关键词： Alkali halides

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Porous silicon on paper sensors: Factors affecting biosensing performance

Porous silicon on paper sensors: Factors affecting biosensin...

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Frontiers in Biological Detection: From Nanosensors to Systems XVII 2025

作者： An, Huijin Laibinis, Paul E. Locke, Andrea K. Weiss, Sharon M. Interdisciplinary Material Science Program Vanderbilt University Nashville 37235 TN United States Department of Chemical and Biomolecular Engineering Vanderbilt University Nashville 37235 TN United States Department of Chemistry Vanderbilt University Nashville 37235 TN United States Department of Biomedical Engineering Vanderbilt University Nashville 37235 TN United States Department of Electrical and Computer Engineering Vanderbilt University Nashville 37235 TN United States

ISBN: (纸本)9781510684249

A paper-based biosensor integrating a functionalized porous silicon (PSi) membrane as the active sensing element for quantifiable protein detection has been developed. For similar short-time exposures to an analyte, improved molecular transport in PSi membranes when on paper leads to larger signal changes compared to traditional PSi films that remain on a silicon substrate. In this work, we discuss controlling the incubation time of the analyte and the overall testing time of the sensor by incorporating different combinations of wicking and absorbent paper beneath the PSi membrane. With this control, the PSi-on-paper sensor platform has the potential to serve as an effective low-cost rapid diagnostic test with highly sensitive, quantitative readout for a wide range of analytes. © 2025 SPIE.

关键词： optical biosensor paper-based sensor porous silicon rapid diagnostic test

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Protocol to characterize longitudinal gut motility in mice using transit time, tissue harvest, and whole-mount immunostaining

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STAR Protocols 2025年第2期6卷 103761页

作者： Frith, Mary E. Kashyap, Purna C. Linden, David R. Chang, Eugene B. Interdisciplinary Scientist Training Program University of Chicago Chicago 60637 IL United States Department of Medicine University of Chicago Chicago 60637 IL United States Division of Gastroenterology and Hepatology Department of Medicine Mayo Clinic Rochester 55905 MN United States Enteric Neuroscience Program Department of Physiology and Biomedical Engineering Mayo Clinic Rochester 55905 MN United States

Transit time is a key in vivo metric of gastrointestinal (GI) motility, which is a physiologic readout of cellular communication within the enteric system. Here, we present a protocol to characterize longitudinal gut motility in mice. We describe steps for transit testing, whole-mount immunostaining, and tissue harvest. We then detail procedures for image processing and manual cell counting. This protocol seeks to minimize inter-trial variability while assessing cellular and molecular features that may underpin motility differences between experimental conditions. For complete details on the use and execution of this protocol, please refer to Frith et al.¹ © 2025 The Authors

关键词： Metabolism Model Organisms Systems biology

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