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SSRN 2023年

作者： Ayad, Nadia M.E. Lakins, Johnathon N. Ghagre, Ajinkya Ehrlicher, Allen J. Weaver, Valerie M. Graduate Program in Bioengineering University of California San Francisco University of California Berkeley San FranciscoCA94143 United States Center for Bioengineering and Tissue Regeneration Department of Surgery University of California San Francisco San FranciscoCA94143 United States Department of Bioengineering McGill University MontrealQCH3A 0E9 Canada Department of Bioengineering Department of Anatomy and Cell Biology Department of Biomedical Engineering Department of Mechanical Engineering Centre for Structural Biology Rosalind and Morris Goodman Cancer Institute McGill University MontrealQCH3A 1A3 Canada Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research University of California San Francisco San FranciscoCA94143 United States UCSF Comprehensive Cancer Center Helen Diller Family Cancer Research Center University of California San Francisco San FranciscoCA94143 United States Department of Bioengineering and Therapeutic Sciences Department of Radiation Oncology University of California San Francisco San FranciscoCA94143 United States

The role of morphogenetic forces in cell fate specification is an area of intense interest. Our prior studies suggested that the development of high cell-cell tension in human embryonic stem cells (hESC) colonies permits the Src-mediated phosphorylation of junctional β-catenin that accelerates its release to potentiate Wnt-dependent signaling critical for initiating mesoderm specification. Using an ectopically expressed nonphosphorylatable mutant of β-catenin (Y654F), we now provide direct evidence that impeding tension-dependent Src-mediated β-catenin phosphorylation impedes the expression of Brachyury (T) and the epithelial-to-mesenchymal transition (EMT) necessary for mesoderm specification. Addition of exogenous Wnt3a or inhibiting GSK3β activity rescued mesoderm expression, emphasizing the importance of force dependent Wnt signaling in regulating mechanomorphogenesis. Our work provides a framework for understanding tension-dependent β-catenin/Wnt signaling in the self-organization of tissues during developmental processes including gastrulation. © 2023, The Authors. All rights reserved.

关键词： Tissue

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CELL-E 2: translating proteins to pictures and back with a bidirectional text-to-image transformer 23

CELL-E 2: translating proteins to pictures and back with a b...

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Proceedings of the 37th International Conference on Neural Information Processing Systems

作者： Emaad Khwaja Yun S. Songt Aaron Agarunov Bo Huang UC Berkeley - UCSF Joint Bioengineering Graduate Program and Computer Science Division UC Berkeley CA Department of Statistics UC Berkeley CA and Computer Science Division UC Berkeley CA Department of Pathology Memorial Sloan Kettering Cancer Center Department of Pharmaceutical Chemistry UCSF San Francisco CA and Department of Biochemistry and Biophysics UCSF San Francisco CA and Chan Zuckerberg Biohub - San Francisco San Francisco CA

We present CELL-E 2, a novel bidirectional transformer that can generate images depicting protein subcellular localization from the amino acid sequences (and vice versa). Protein localization is a challenging problem that requires integrating sequence and image information, which most existing methods ignore. CELL-E 2 extends the work of CELL-E, not only capturing the spatial complexity of protein localization and produce probability estimates of localization atop a nucleus image, but also being able to generate sequences from images, enabling de novo protein design. We train and finetune CELL-E 2 on two large-scale datasets of human proteins. We also demonstrate how to use CELL-E 2 to create hundreds of novel nuclear localization signals (NLS). Results and interactive demos are featured at https://***/CELL-E_2/.

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Consistency and variation in the placement of cortical folds: A perspective

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Brain Multiphysics 2023年 5卷

作者： Nagehan Demirci Fatemeh Jafarabadi Xincheng Wang Shuolun Wang Maria A. Holland Bioengineering Graduate Program University of Notre Dame Notre Dame IN 46556 USA Department of Aerospace and Mechanical Engineering University of Notre Dame Notre Dame IN 46556 USA

Cortical folds, known as gyri and sulci, are prominent features of the human brain that play a crucial role in its function. These folds exhibit both consistency and variation within and across individuals and species, presenting a scientific challenge to our understanding of the underlying mechanisms. In this perspective paper, we summarize current knowledge about fold development and placement. We discuss the temporal and anatomical differences between primary, secondary, and tertiary folds, highlighting the consistency of primary folds and the increasing variation in later-developing folds. We explore the biological and mechanical factors that influence fold placement, including gene expression, tissue growth, axonal tension, curvature, thickness, and stiffness, which likely work together in a complex, coupled manner. We also highlight the need for advanced computational modeling approaches to unravel the mechanisms of precise placement of primary folds and further our understanding of brain complexity. Statement of significance: Understanding the factors driving both the consistency and variation in fold patterns is essential for unraveling the functional implications and potential links to neurological and psychiatric disorders. Ultimately, gaining deeper insights into fold development and placement could have significant implications for our fundamental understanding of the brain, as well as mental health research and clinical applications.

关键词： Cortical folding Gyri Sulci Neurodevelopment Comparative neuroanatomy

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Pioneering Astaxanthin-Tumor Cell Membrane Nanoparticles for Innovative Targeted Drug Delivery on Melanoma

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International journal of nanomedicine 2024年 19卷 2395-2407页

作者： Jui-Jen Chang Yi-Chen Wang Shu-Hui Yang Ju-Yu Wu Ming-Wei Chang Hui-Min David Wang Department of Medical Research China Medical University Hospital China Medical University Taichung 40447 Taiwan. Graduate Institute of Integrated Medicine China Medical University Taichung 40447 Taiwan. Division of Cardiology Department of Internal Medicine Kaohsiung Armed Forces General Hospital Kaohsiung City 802 Taiwan. Institute of Medical Science and Technology National Sun Yat-sen University Kaohsiung 807 Taiwan. Graduate Institute of Biomedical Engineering National Chung Hsing University Taichung 402 Taiwan. Bachelor Program of Biotechnology National Chung Hsing University Taichung 402 Taiwan. Doctoral Program in Tissue Engineering and Regenerative Medicine National Chung Hsing University Taichung 402 Taiwan. Nanotechnology and Integrated Bioengineering Centre University of Ulster Belfast BT15 1AB Northern Ireland UK. Graduate Institute of Medicine College of Medicine Kaohsiung Medical University Kaohsiung 807 Taiwan. Department of Medical Laboratory Science and Biotechnology China Medical University Taichung 404 Taiwan. Center of Applied Nanomedicine National Cheng Kung University Tainan 701 Taiwan.

Background:Recently, the use of the tumor or its secretions as drug carriers has gradually become popular, with the advantages of high biocompatibility and enhanced drug delivery to specific cells. Melanoma is the most malignant tumor of all skin cancers; it is the most metastatic and, therefore, the most difficult to treat. The main purpose of this study is to develop nanovesicles with tumor cell membrane secretion properties to encapsulate target substances to enhance the therapeutic effect of cancer. Methods:Astaxanthin was selected as an anticancer drug due to our previous research finding that astaxanthin has extremely high antioxidant, anti-ultraviolet damage, and anti-tumor properties. The manufacturing method of the astaxanthin nanovesicle carrier is to mix melanoma cells and astaxanthin in an appropriate ratio and then remove the genetic material and inflammatory factors of cancer cells by extrusion. Results:In terms of results, after the co-culture of astaxanthin nanovesicles and melanoma cancer cells, it was confirmed that the ability of astaxanthin nanovesicles to inhibit the growth and metastasis of melanoma cancer cells was significantly better than the same amount of astaxanthin alone, and it had no effect on normal Human cells are also effective. There was no apparent harm on normal cells, indicating the ability of the vesicles to be selectively transported. Conclusion:Our findings illustrated the potential of astaxanthin nanovesicles as an anticancer drug.

关键词： astaxanthin melanoma nanoparticle

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Methodological Properties of Transcutaneous Electrical Nerve Stimulation (TENS) Equipment Used for Analgesia in Humans: a Systematic Review

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SN Comprehensive Clinical Medicine 2021年第6期3卷 1363-1372页

作者： Guimarães, Igor Batista Volpini Lana, Mariana Ribeiro de Aquino, Mariana Rodrigues Carvalho Cavalheiro, Jessé Mendonça Alves, Davi Neiva Vimieiro, Claysson Bruno Santos Associação Mineira de Reabilitação Orthotics for Humans Laboratory (OhLab) Child Rehabilitation Center Belo Horizonte Brazil Graduate Program in Mechanical Engineering Bioengineering Laboratory Labbio Universidade Federal de Minas Gerais Belo Horizonte Brazil Faculty of Engineering and Architecture Biomedical Engineering Department Universidade FUMEC Belo Horizonte Brazil Graduate Program in Mechanical Engineering Pontifícia Universidade Católica de Minas Gerais Belo Horizonte Brazil

Pain is considered a public health problem due to its high economic cost, high prevalence, and great impact on the quality of life of patients and their families. Transcutaneous electrical nerve stimulation (TENS) has been shown to be a safe, inexpensive option with satisfactory results in improving pain control. However, the success of this therapy presents as key factors the parameters used, among them the intensity and duration of treatment. However, little is known about the validation of such equipment. To perform a systematic review of the equipment available for the application of electrostimulation as a therapeutic resource for analgesia, which had their methodological properties tested. A systematic literature search was conducted for all relevant scientific articles in the SCIELO, Medline/PubMed, PEDRo, and EBSCO databases. A total of 318 articles were found. Sixty-six were duplicate studies, 252 were selected by title, 72 by abstract, 5 by text full reading, and finally only 2 were included, since the others did not meet the pre-established inclusion criteria. The evidence gathered in this study shows that the performance evaluation of commercially available electrostimulation equipment may be a responsibility of the national regulatory agency. Our findings reinforce the importance of greater availability of information about the regulatory processes of these devices and the verification of the parameters of the regulated devices, so that the achievement of therapeutic goals is not compromised.

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An exact mathematical description of computation with transient spatiotemporal dynamics in a complex-valued neural network

arXiv

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arXiv 2023年

作者： Budzinski, Roberto C. Busch, Alexandra N. Mestern, Samuel Martin, Erwan Liboni, Luisa H.B. Pasini, Federico W. Mináč, Ján Coleman, Todd Inoue, Wataru Muller, Lyle E. Department of Mathematics Western University LondonON Canada Western Institute for Neuroscience Western University LondonON Canada Western Academy for Advanced Research Western University LondonON Canada Graduate Program in Neuroscience Western University London Canada Huron University College LondonON Canada Department of Bioengineering Stanford University StanfordCA United States Robarts Research Institute Western University London Canada Department of Physiology and Pharmacology Western University London Canada

We study a complex-valued neural network (cv-NN) with linear, time-delayed interactions. We report the cv-NN displays sophisticated spatiotemporal dynamics, including partially synchronized "chimera" states. We then use these spatiotemporal dynamics, in combination with a nonlinear readout, for computation. The cv-NN can instantiate dynamics-based logic gates, encode shortterm memories, and mediate secure message passing through a combination of interactions and time delays. The computations in this system can be fully described in an exact, closed-form mathematical expression. Finally, using direct intracellular recordings of neurons in slices from neocortex, we demonstrate that computations in the cv-NN are decodable by living biological neurons. These results demonstrate that complex-valued linear systems can perform sophisticated computations, while also being exactly solvable. Taken together, these results open future avenues for design of highly adaptable, bio-hybrid computing systems that can interface seamlessly with other neural networks. © 2023, CC BY.

关键词： Linear systems

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The type 1 diabetes immune niche: Immunomodulatory biomaterial design considerations for beta cell transplant therapies

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Journal of Immunology and Regenerative Medicine 2022年 17卷

作者： Claire E. Hilburger Matthew J. Rosenwasser Derfogail Delcassian Department of Bioengineering University of California Berkeley CA 94720 USA UC Berkeley-UC San Francisco Graduate Program in Bioengineering University of California Berkeley CA 94720 USA

Islet transplantation is a promising therapy for a subset of people with Type 1 diabetes (T1D). However, beta cell transplant clinical trials have largely failed to maintain long-term normal glycemia in transplant recipients. This is broadly due to immune rejection of the transplanted islets themselves or the devices in which these cells are encapsulated. As an autoimmune condition, the T1D host presents a uniquely challenging immunological niche for the transplant of additional beta cells. An understanding of the autoimmune environment is crucial for the development of successful beta cell transplant therapies. Here, we provide an overview of the immune cell pathways leading to autoimmune T1D, and the resulting immune niche. Next, we examine biomaterial platforms that can be used for cell transplantation, and describe those that seek to modulate the immune environment to mitigate immune rejection. These approaches include delivery of localized immune cues, co-transplantation with immunomodulatory cells, strategies to engineer islets ex-vivo, and antigen-specific immunomodulation to generate operational tolerance. Finally, we describe therapies which seek to prevent T1D progression which could be repurposed to support beta cell transplantation and future immunoengineering design considerations for successful islet transplantation therapies.

关键词： Immunomodulation Islet transplantation Operational tolerance Biomaterials T1D Diabetes

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Systematic analysis of siRNA and mRNA features impacting fully chemically modified siRNA efficacy

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Nucleic acids research 2025年第12期53卷

作者： Sarah M Davis Samuel Hildebrand Hannah J MacMillan Kathryn R Monopoli Julianna Buchwald Jacquelyn Sousa David Cooper Socheata Ly Dimas Echeverria Nicholas McHugh Chantal Ferguson Andrew Coles Vignesh N Hariharan Daniel O'Reilly Qi Tang Raymond Furgal Ken Yamada Julia F Alterman James W Gilbert Emily Knox Yamilett Pineda Caitlyn N Weston Christina E Baer Athma A Pai Anastasia Khvorova Morningside Graduate School of Biomedical Sciences T.H. Chan School of Medicine Interdisciplinary Graduate Program RNA Therapeutics Institute Program in Molecular Medicine Systems Biology Biochemistry and Molecular Biotechnology Microbiology and Physiological Systems MD/PhD Program University of Massachusetts Chan Medical School Worcester MA 01655 United States. Quantitative and Computational Biosciences and Bioengineering Program University of Massachusetts Chan Medical School and Worcester Polytechnic Institute Worcester MA 01655 United States.

Chemically modified small interfering RNAs (siRNAs) are a promising drug class that silences disease-causing genes via mRNA degradation. Both siRNA-specific features (e.g. sequence, modification pattern, and structure) and target mRNA-specific factors contribute to observed efficacy. Systematically defining the relative contributions of siRNA sequence, structure, and modification pattern versus the native context of the target mRNA is necessary to inform design considerations and facilitate the widespread application of this therapeutic platform. To address this, we synthesized a panel of ∼1260 differentially modified siRNAs and evaluated their silencing efficiency against therapeutically relevant mRNAs (APP, BACE1, MAPT, and SNCA) using both reporter-based and native expression assays. Our results demonstrate that the siRNA modification pattern (e.g. level of 2'-O-methyl content) significantly impacts efficacy, while structural features (e.g. symmetric versus asymmetric configurations) do not. Furthermore, we observed substantial differences in the number of effective siRNAs identified per target. These target-specific differences in hit rates are largely mitigated when efficacy is tested in the context of a reporter assay, confirming that native mRNA-specific features influence siRNA performance. Key target-specific factors, including exon usage, polyadenylation site selection, and ribosomal occupancy, partially explained efficacy variability. These insights led to a proposed framework of parameters for optimizing therapeutic siRNA design.

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Capillary regression leads to sustained local hypoperfusion by inducing constriction of upstream transitional vessels

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Proceedings of the National Academy of Sciences of the United States of America 2024年第37期121卷 e2321021121-e2321021121页

作者： Bonney, Stephanie K. Nielson, Cara D. Sosa, Maria J. Bonnar, Orla Shih, Andy Y. Center for Developmental Biology and Regenerative Medicine Seattle Children’s Research Institute Seattle 98101 WA United States Graduate Program in Neuroscience University of Washington Seattle 98195 WA United States MassGeneral Institute for Neurodegenerative Disease Massachusetts General Hospital Harvard Medical School Boston 02129 MA United States Department of Pediatrics University of Washington Seattle 98195 WA United States Department of Bioengineering University of Washington Seattle 98195 WA United States

In the brain, a microvascular sensory web coordinates oxygen delivery to regions of neuronal activity. This involves a dense network of capillaries that send conductive signals upstream to feeding arterioles to promote vasodilation and blood flow. Although this process is critical to the metabolic supply of healthy brain tissue, it may also be a point of vulnerability in disease. Deterioration of capillary networks is a feature of many neurological disorders and injuries and how this web is engaged during vascular damage remains unknown. We performed in vivo two-photon microscopy on young adult mural cell reporter mice and induced focal capillary injuries using precise two-photon laser irradiation of single capillaries. We found that ~59% of the injuries resulted in regression of the capillary segment 7 to 14 d following injury, and the remaining repaired to reestablish blood flow within 7 d. Injuries that resulted in capillary regression induced sustained vasoconstriction in the upstream arteriole-capillary transition (ACT) zone at least 21 days postinjury in both awake and anesthetized mice. The degree of vasomotor dynamics was chronically attenuated in the ACT zone consequently reducing blood flow in the ACT zone and in secondary, uninjured downstream capillaries. These findings demonstrate how focal capillary injury and regression can impair the microvascular sensory web and contribute to cerebral hypoperfusion. Copyright © 2024 the Author(s).

关键词： capillary cerebral blood flow microbleed pericyte two-photon imaging

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Clinical anthropometrics and body composition from 3D whole-body surface scans (vol 70, pg 1265, 2016)

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EUROPEAN JOURNAL OF CLINICAL NUTRITION 2021年第3期75卷 574-574页

作者： Ng, B. K. Hinton, B. J. Fan, B. Kanaya, A. M. Shepherd, J. A. Department of Radiology and Biomedical Imaging University of California San Francisco San Francisco USA The UC Berkeley—UCSF Graduate Program in Bioengineering San Francisco USA Department of Medicine University of California San Francisco San Francisco USA

A Correction to this paper has been published: https://***/10.1038/s41430-020-00808-y

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