Hasil untuk "q-bio.TO"

Aoqi Wang, Jiajia Liu, Jianguo Wen et al.

We envision the Full-Body AI Agent as a comprehensive AI system designed to simulate, analyze, and optimize the dynamic processes of the human body across multiple biological levels. By integrating computational models, machine learning tools, and experimental platforms, this system aims to replicate and predict both physiological and pathological processes, ranging from molecules and cells to tissues, organs, and entire body systems. Central to the Full-Body AI Agent is its emphasis on integration and coordination across these biological levels, enabling analysis of how molecular changes influence cellular behaviors, tissue responses, organ function, and systemic outcomes. With a focus on biological functionality, the system is designed to advance the understanding of disease mechanisms, support the development of therapeutic interventions, and enhance personalized medicine. We propose two specialized implementations to demonstrate the utility of this framework: (1) the metastasis AI Agent, a multi-scale metastasis scoring system that characterizes tumor progression across the initiation, dissemination, and colonization phases by integrating molecular, cellular, and systemic signals; and (2) the drug AI Agent, a system-level drug development paradigm in which a drug AI-Agent dynamically guides preclinical evaluations, including organoids and chip-based models, by providing full-body physiological constraints. This approach enables the predictive modeling of long-term efficacy and toxicity beyond what localized models alone can achieve. These two agents illustrate the potential of Full-Body AI Agent to address complex biomedical challenges through multi-level integration and cross-scale reasoning.

Yayu Zhao, Ying Fei, Yunyun Cai et al.

Neuropathic pain is a chronic condition characterized by damage to and dysfunction of the peripheral or central nervous system. There are currently no effective treatment options available for neuropathic pain, and existing drugs often provide only temporary relief with potential side effects. Multilineage-differentiating stress-enduring (Muse) cells are characterized by high expansion potential, a stable phenotype and strong immunosuppression. These properties make them attractive candidates for therapeutics for neuropathic pain management. In this study, we conducted a series of experiments to evaluate the effect of Muse cells on neuropathic pain. Muse cells from different species demonstrated analgesic potential by reversing CCI-induced neuropathic pain. Protein profiling revealed a high degree of similarity between Muse cells and BMSCs. The intrathecal injection of Muse cells effectively reduced neuropathic pain in various mouse models, resulting in better analgesic effects than the administration of equivalent low doses of BMSCs. Immunohistochemical analysis and qPCR revealed the ability of Muse cells to inhibit spinal cord neuroinflammation caused by SNI. In addition, Transwell and ELISA revealed that Muse cells migrated through the injured dorsal root ganglion (DRG) via the CCR7-CCL21 chemotactic axis. In addition, the secretion of TGF-b and IL-10 by Muse cells was identified as the mechanism underlying the analgesic effect of Muse cells. The capacity of Muse cells to mitigate neuroinflammation and produce analgesic effects via the modulation of TGF-b and IL-10 underscores their potential as promising therapeutic approaches for the treatment of neuropathic pain.

Jason R. Casar, Claire A. McLellan, Cindy Shi et al.

The forces generated by action potentials in muscle cells shuttle blood, food and waste products throughout the luminal structures of the body. Although non-invasive electrophysiological techniques exist, most mechanosensors cannot access luminal structures non-invasively. Here we introduce non-toxic ingestible mechanosensors to enable the quantitative study of luminal forces and apply them to study feeding in living Caenorhabditis elegans roundworms. These optical 'microgauges' comprise NaY0.8Yb0.18Er0.02F4@NaYF4 upconverting nanoparticles embedded in polystyrene microspheres. Combining optical microscopy and atomic force microscopy to study microgauges in vitro, we show that force evokes a linear and hysteresis-free change in the ratio of emitted red to green light. With fluorescence imaging and non-invasive electrophysiology, we show that adult C. elegans generate bite forces during feeding on the order of 10 micronewtons and that the temporal pattern of force generation is aligned with muscle activity in the feeding organ. Moreover, the bite force we measure corresponds to Hertzian contact stresses in the pressure range used to lyse the bacterial food of the worm. Microgauges have the potential to enable quantitative studies that investigate how neuromuscular stresses are affected by aging, genetic mutations and drug treatments in this organ and other luminal organs.

S. J. Beck

Muzammil Kuddushi, Aatif Ali Shah, Cagri Ayranci et al.

Optically transparent wound dressings offer a range of potential applications in the biomedical field, as they allow for the monitoring of wound healing progress without having to replace the dressing. These dressings must be impermeable to water and bacteria, yet permeable to moisture vapor and atmospheric gases in order to maintain a moist environment at the wound site. This review article provides a comprehensive overview of the types of wound dressings, novel wound dressing materials, advanced fabrication techniques for transparent wound dressing materials, and the key features and applications of transparent dressings for the healing process, as well as how it can improve healing outcomes. This review mainly focuses on representing specifications of transparent polymeric wound dressing materials, such as transparent electrospun nanofibers, transparent crosslinked hydrogels, and transparent composite films/membranes. Due to the advance properties of electrospun nanofiber such as large surface area, enable efficient incorporation of antibacterial molecules, a structure similar to the extracellular matrix, and high mechanical stability, is often used in wound dressing applications. We also highlight the hydrogels or films for wound healing applications, it's promote the healing process, provide a moisture environment, and offer pain relief with their cool, high-water content, excellent biocompatibility, and bio-biodegradability.

Michelle A Bartolo, Alyssa M Taylor-LaPole, Darsh Gandhi et al.

Patient-specific computational modeling is a popular, non-invasive method to answer medical questions. Medical images are used to extract geometric domains necessary to create these models, providing a predictive tool for clinicians. However, in vivo imaging is subject to uncertainty, impacting vessel dimensions essential to the mathematical modeling process. While there are numerous programs available to provide information about vessel length, radii, and position, there is currently no exact way to determine and calibrate these features. This raises the question, if we are building patient-specific models based on uncertain measurements, how accurate are the geometries we extract and how can we best represent a patient's vasculature? In this study, we develop a novel framework to determine vessel dimensions using change points. We explore the impact of uncertainty in the network extraction process on hemodynamics by varying vessel dimensions and segmenting the same images multiple times. Our analyses reveal that image segmentation, network size, and minor changes in radius and length have significant impacts on pressure and flow dynamics in rapidly branching structures and tapering vessels. Accordingly, we conclude that it is critical to understand how uncertainty in network geometry propagates to fluid dynamics, especially in clinical applications.

Jan Lebert, Meenakshi Mittal, Jan Christoph

Scroll wave chaos is thought to underlie life-threatening ventricular fibrillation. However, currently there is no direct way to measure action potential wave patterns transmurally throughout the thick ventricular heart muscle. Consequently, direct observations of three-dimensional electrical scroll waves remains elusive. Here, we study whether it is possible to reconstruct simulated scroll waves and scroll wave chaos using deep learning. We trained encoding-decoding convolutional neural networks to predict three-dimensional scroll wave dynamics inside bulk-shaped excitable media from two-dimensional observations of the wave dynamics on the bulk's surface. We tested whether observations from one or two opposing surfaces would be sufficient, and whether transparency or measurements of surface deformations enhances the reconstruction. Further, we evaluated the approach's robustness against noise and tested the feasibility of predicting the bulk's thickness. We distinguished isotropic and anisotropic, as well as opaque and transparent excitable media as models for cardiac tissue and the Belousov-Zhabotinsky chemical reaction, respectively. While we demonstrate that it is possible to reconstruct three-dimensional scroll wave dynamics, we also show that it is challenging to reconstruct complicated scroll wave chaos and that prediction outcomes depend on various factors such as transparency, anisotropy and ultimately the thickness of the medium compared to the size of the scroll waves. In particular, we found that anisotropy provides crucial information for neural networks to decode depth, which facilitates the reconstructions. In the future, deep neural networks could be used to visualize intramural action potential wave patterns from epi- or endocardial measurements.

Chottiwatt Jittprasong

Oncolytic viruses, which may be naturally occurring or genetically engineered, are a type of virus that infects and destroy cancer cells preferentially. Owing to their selectivity, they outperform conventional chemotherapy and radiotherapy, which both have a tendency to impact non-target cells and cause unwanted adverse side effects. Oncolytic virotherapy is a type of cancer treatment in which oncolytic viruses are deliberately introduced into patients affected with cancers in order for them to infect and destroy cancer cells locally or systemically, in a manner analogous to chemotherapy but with a greater degree of selectivity. Multiple studies indicate that oncolytic virotherapy is effective in vitro but in vivo findings remain ambiguous due to the approach's primary limitation: inefficient therapeutic agent delivery to its target, which is heavily influenced by the immune system. Here, we propose overcoming this limitation by exploiting a recent discovery in cancer research: a carrier cell. By exploiting their tumor-promoting activities, mesenchymal stem cells may be employed for cancer therapy by serving as a carrier for the oncolytic viruses toward their target. This approach directly addresses the limitation of conventional oncolytic virotherapy, where oncolytic viruses are often poorly delivered after systemic administration.

Helena U. Zacharias, Christoph Kaleta, Francois Cossais et al.

Due to the aging of the world population and westernization of lifestyles, the prevalence of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD) is rapidly rising and is expected to put a strong socioeconomic burden on health systems worldwide. Due to the limited success of clinical trials of therapies against neurodegenerative diseases, research has extended its scope to a systems medicine point of view, with a particular focus on the gastrointestinal-brain axis as a potential main actor in disease development and progression. Microbiome as well as metabolome studies along the gastrointestinal-brain axis have already revealed important insights into disease pathomechanisms. Both the microbiome and metabolome can be easily manipulated by dietary and lifestyle interventions, and might thus offer novel, readily available therapeutic options to prevent the onset as well as the progression of PD and AD. This review summarizes our current knowledge on the association between microbiota, metabolites, and neurodegeneration in light of the gastrointestinal-brain axis. In this context, we also illustrate state-of-the art methods of microbiome and metabolome research as well as metabolic modeling that facilitate the identification of disease pathomechanisms. We conclude our review with therapeutic options to modulate microbiome composition to prevent or delay neurodegeneration and illustrate potential future research directions to fight PD and AD.

D. Raoult, H. Tissot-Dupont, C. Foucault et al.

R. Dearden, N. Friedman, Stuart J. Russell

M. Borselli, T. Johnson, O. Painter

Using a combination of resist reflow to form a highly circular etch mask pattern and a low-damage plasma dry etch, high-quality-factor silicon optical microdisk resonators are fabricated out of silicon-on-insulator (SOI) wafers. Quality factors as high as Q = 5x10(6) are measured in these microresonators, corresponding to a propagation loss coefficient as small as alpha ~ 0.1 dB/cm. The different optical loss mechanisms are identified through a study of the total optical loss, mode coupling, and thermally-induced optical bistability as a function of microdisk radius (5-30 microm). These measurements indicate that optical loss in these high-Q microresonators is limited not by surface roughness, but rather by surface state absorption and bulk free-carrier absorption.

S. Spillane, T. Kippenberg, K. Vahala et al.

We investigate the suitability of toroidal microcavities for strong-coupling cavity quantum electrodynamics (QED). Numerical modeling of the optical modes demonstrate a significant reduction of the modal volume with respect to the whispering gallery modes of dielectric spheres, while retaining the high-quality factors representative of spherical cavities. The extra degree of freedom of toroid microcavities can be used to achieve improved cavity QED characteristics. Numerical results for atom-cavity coupling strength g, critical atom number No, and critical photon number no for cesium are calculated and shown to exceed values currently possible using Fabry-Perot cavities. Modeling predicts coupling rates g/2π exceeding 700 MHz and critical atom numbers approaching 10^(-7) in optimized structures. Furthermore, preliminary experimental measurements of toroidal cavities at a wavelength of 852 nm indicate that quality factors in excess of 108 can be obtained in a 50-µm principal diameter cavity, which would result in strong-coupling values of (g/(2π),n(0),N-0) = (86 MHz, 4.6 x 10^(-4), 1.0 x 10^(-3)).

A. Klassen, S. Cano, A. Scott et al.

F. Bannon, J.R. Clark, C. Nguyen

Y. Akahane, T. Asano, B. Song et al.

A photonic nanocavity with a high Q factor of 100,000 and a modal volume V of 0.71 cubic wavelengths, is demonstrated. According to the cavity design rule that we discovered recently, we further improve a point-defect cavity in a two-dimensional (2D) photonic crystal (PC) slab, where the arrangement of six air holes near the cavity edges is fine-tuned. We demonstrate that the measured Q factor for the designed cavity increases by a factor of 20 relative to that for a cavity without displaced air holes, while the calculated modal volume remains almost constant.

Antonio Julià, Irene Bonafonte, Antonio Gómez et al.

In its more severe forms, COVID-19 progresses towards an excessive immune response, leading to the systemic overexpression of proinflammatory cytokines like IL6, mostly from the infected lungs. This cytokine storm can cause multiple organ damage and death. Consequently, there is a pressing need to identify therapies to treat and prevent severe symptoms during COVID-19. Based on previous clinical evidence, we hypothesized that inhibiting T cell co-stimulation by blocking CD80/86 could be an effective therapeutic strategy against progression to severe proinflammatory states. To support this hypothesis, we performed an analysis integrating blood transcriptional data we generated from rheumatoid arthritis patients treated with abatacept -- a CD80/86 co-stimulation inhibitor -- with the pathological features associated with COVID-19, particularly in its more severe forms. We have found that many of the biological processes that have been consistently associated with COVID-19 pathology are reversed by CD80/86 co-stimulation inhibition, including the downregulation of IL6 production. Also, analysis of previous transcriptional data from blood of SARS-CoV-infected patients showed that the response to abatacept has a very high level of antagonism to that elicited by COVID-19. Finally, analyzing a recent single cell RNA-seq dataset from bronchoalveolar lavage fluid cells from COVID-19 patients, we found a significant correlation along the main elements of the C80/86 axis: CD86+/80+ antigen presenting cells, activated CD4+ T cells and IL6 production. Our in-silico study provides additional support to the hypothesis that blocking of the CD80/CD86 signaling axis may be protective of the excessive proinflammatory state associated with COVID-19 in the lungs.

Giulia Montagna, Francesco Cristofaro, Lorenzo Fassina et al.

The osteoinductive property of strontium was repeatedly proven in the last decades. Compelling $\textit{in vitro}$ data demonstrated that strontium hydroxyapatite nanoparticles exert a dual action, by promoting osteoblasts-driven matrix secretion and inhibiting osteoclasts-driven matrix resorption. Recombinant human bone morphogenetic protein 2 (rhBMP2) is a powerful osteoinductive biologic, used for the treatment of vertebral fractures and critically-sized bone defects. Although effective, the use of rhBMP2 has limitations due its recombinant morphogen nature. In this study, we examined the comparison between two osteoinductive agents: rhBMP2 and the innovative strontium-substituted hydroxyapatite nanoparticles. To test their effectiveness, we independently loaded Gelfoam sponges with the two osteoinductive agents and used the sponges as agent-carriers. Gelfoam are FDA-approved biodegradable medical devices used as delivery system for musculoskeletal defects. Their porous structure and spongy morphology make them attractive in orthopedic field. The abiotic characterization of the loaded sponges, involving ion release pattern and structure investigation, was followed by $\textit{in vivo}$ implantation onto the periosteum of healthy mice and comparison of the effects induced by each implant was performed. The results demonstrated the use of sponges loaded with strontium nanoparticles as potential bone grafts might provide better outcomes for complex fractures. Strontium nanoparticles are a novel and effective non-biologic treatment for bone injuries and can be used as novel powerful therapeutics for bone regeneration.

Yannick Drif, Benjamin Roche, Pierre Valade

Climate change, which is largely linked to human activities, is already having a considerable impact on our societies. Based on current trends, climate change is expected to accelerate in the coming decades. Beyond its impact on the pace of natural disasters (floods, hurricanes, etc.), climate change may have catastrophic consequences for human life and health. One of the concerns is the increase in the transmission of viruses spread by mosquitoes. Indeed, rising temperatures have a direct positive impact on the viability of mosquitoes in ecosystems, leading to their abundance and thus the risk of exposure of human populations to these pathogens. This study quantifies the consequences of global warming on the risk of epidemics of viruses transmitted by the Aedes Albopictus mosquito in metropolitan France. This mosquito, which is a vector for the Dengue, Chikungunya and Zika viruses, among others, arrived in mainland France in 2004 and has since spread throughout the country. Thanks to the association previously established between the probability of the presence of the mosquito and the average temperature combined with a mathematical model, the probability of an epidemic and the number of people who could be infected and die during a season in each department are estimated. If there is a high degree of heterogeneity in metropolitan France, nearly 2,000 deaths per year could be expected by 2040.

P. N. Sadjang