Inhibiting FAT1 Blocks Metabolic Bypass to Enhance Antitumor Efficacy of TCA Cycle Inhibition through Suppressing CPT1A-Dependent Fatty Acid Oxidation.

FAT atypical cadherin 1 (FAT1) is one of the most frequently mutated genes in head and neck squamous cell carcinoma (HNSCC), exhibiting the highest mutation rate across different tumor types. Although FAT1's role has attracted considerable attention, its impact on cancer metabolism and treatment resistance remains poorly understood. In this study, it is demonstrated that knockout of mutant FAT1 in HNSCC cells attenuates CPT1A-driven fatty acid oxidation (FAO) through downregulation of the transcription factor ASCL2, leading to marked suppression of tumor growth.

Smartphone language features may help identify adverse post-traumatic neuropsychiatric sequelae and their trajectories.

Language features may reflect underlying cognitive and emotional processes following a traumatic event that portend clinical outcomes. The authors sought to determine whether language features from usual smartphone use were markers associated with concurrent posttraumatic symptoms and worsening or improving posttraumatic symptoms over time following a traumatic exposure. This investigation was a secondary analysis of the Advancing Understanding of RecOvery afteR traumA study, a longitudinal study of traumatic outcomes among survivors recruited from 33 emergency departments across the United States.

Feasibility Assessment of 3D Printing-Based Tubular Tissue Flap in a Porcine Model for Long Segmental Tracheal Reconstruction.

Background: Despite advances in tissue engineering, current clinical reconstructive options for long segment tracheal defects are limited. In this study, a 3D printing based tubular tissue flap strategy was developed for long segment tracheal reconstruction.

Method: A stent-patterned airway scaffold with sufficient radial rigidity and longitudinal bending flexibility was designed and its mechanical behavior was analyzed using finite element analysis (FEA).

Antifreezing hydrogels: from mechanisms and strategies to applications.

Antifreezing hydrogels have emerged as an innovative solution for maintaining functional performance and mechanical integrity in subzero environments, offering a robust alternative to traditional water-free antifreezing materials that often fail under wet and cold conditions. These water-rich hydrogels leverage their porous, crosslinked, polymeric networks, which serve as the structural basis for implementing two parallel strategies: the incorporation of antifreezing additives (peptides/proteins, salts, ionic liquids, and organics) and the meticulous engineering of polymer systems and network structures for manipulating the water-ice phase equilibrium to significantly enhance antifreezing properties. This review synthesizes recent findings to provide a fundamental overview of the important advancements in antifreezing hydrogels, focusing on their designs, mechanisms, performances, and functional applications.

Synergistic Torso-Muscle-Controlled Detached Robotic Hand: A Novel Approach for Post-Stroke Hand Rehabilitation.

This study aimed to develop a novel rehabilitative approach for post-stroke hand movement using a simple detached robotic hand and synergistic torso muscle activities for reaching and to perform a pilot test on its functionality and feasibility. In reference to a mental practice that does not activate hand muscles, enhanced cognitive engagement would be achieved without hand activation using the externally present, visible, and audible robotic hand by activating the non-hand muscles associated with hand function. A simple and low-cost robotic hand was developed and placed distal to the hidden resting hand as if it were a functional extended hand.

A facile yeast-display approach for antibody mask discovery.

Tuning in vivo activity of protein therapeutics can improve their safety. In this vein, it is possible to add a 'mask' moiety to a protein therapeutic such that its ability to bind its target is prevented until the mask has been proteolytically removed, for instance by a tumor-associated protease. As such, new methods to isolate functional masking sequences can aid development of protein therapies.

Self-authenticating genomic materials in Escherichia coli via advanced genome signatures.

The authenticity and integrity of synthetic genomic materials containing valuable intellectual property are essential for advancing scientific knowledge and enhancing biosafety. Nevertheless, existing DNA tags and watermarks have limited efficacy due to low mutation tolerance and inadequate digital encoding capacity. Here, we present "Genome Signature", a biochemically stable and tamper-resistant DNA labeling system that enables the creation of self-authenticating genomes.

Real-world implementation of a noninvasive, AI-augmented, anemia-screening smartphone app and personalization for hemoglobin level self-monitoring.

Anemia, characterized by low blood hemoglobin (Hgb) levels, afflicts >2 billion individuals worldwide. Here, we report real-world data generated by a smartphone app that noninvasively screens for anemia using only "fingernail selfies." App data for anemia screening were obtained from >1.

Chondrogenic and chondroprotective response of composite collagen I/II-hyaluronic acid scaffolds within an inflammatory osteoarthritic environment.

Inflammation plays a key role in cartilage damage that occurs in osteoarthritis (OA). However, assessments of tissue-engineered constructs for cartilage regeneration generally do not consider their performance in the presence of inflammation. In this work, the chondrogenic differentiation potential of mesenchymal stromal cells (MSCs) was evaluated in the presence of both chondrogenic factors and inflammatory cytokines, and cartilage formation, degradative response, and inflammatory response were characterized.

Wireless Flexible Potentiometric Microsensors for Temperature-Compensated Sweat Electrolyte Monitoring.

Sweat electrolyte analysis using potentiometric systems is a promising approach for continuous health monitoring. However, despite its potential, temperature-induced measurement errors remain a critical challenge, and, to our knowledge, no study has effectively addressed this issue for accurate potentiometric sensing during physiological activities. Here, we present a temperature-compensated flexible microsensor integrated with a wireless potentiometric measurement circuit for real-time sweat analysis.

Dynamics of striatal action selection and reinforcement learning.

Spiny projection neurons (SPNs) in dorsal striatum are often proposed as a locus of reinforcement learning in the basal ganglia. Here, we identify and resolve a fundamental inconsistency between striatal reinforcement learning models and known SPN synaptic plasticity rules. Direct-pathway (dSPN) and indirect-pathway (iSPN) neurons, which promote and suppress actions, respectively, exhibit synaptic plasticity that reinforces activity associated with elevated or suppressed dopamine release.

Multiscale and recursive unmixing of spatiotemporal rhythms for live-cell and intravital cardiac microscopy.

Cardiovascular diseases remain a pressing public health issue, necessitating the development of advanced therapeutic strategies underpinned by precise cardiac observations. While fluorescence microscopy is an invaluable tool for probing biological processes, cardiovascular signals are often complicated by persistent autofluorescence, overlaying dynamic cardiovascular entities and nonspecific labeling from tissue microenvironments. Here we present multiscale recursive decomposition for the precise extraction of dynamic cardiovascular signals.

Cyclosporine A Accelerates Neurorecovery Transcriptional Trajectory in a Swine Model of Diffuse Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) is a leading cause of morbidity in children with both short- and long-term neurological, cognitive, cerebrovascular, and emotional deficits. These deficits have been attributed to ongoing pathophysiological cascades that occur acutely and persist post-injury. Given our limited understanding of the transcriptional changes associated with these pathophysiological cascades, we studied formalin-fixed paraffin-embedded (FFPE) tissues from the frontal cortex (FC) and the hippocampus + amygdala (H&A) regions of swine (N = 40) after a sagittal rapid non-impact head rotation (RNR).

Machine learning methods to predict transvalvular gradient waveform post-transcatheter aortic valve replacement using preprocedural echocardiogram.

Objective: Time-varying transvalvular pressure gradient after transcatheter aortic valve replacement indicates the effectiveness of the therapy. The objective was to develop a novel machine learning method enhanced by generative artificial intelligence and smart data selection strategies to predict the post-transcatheter aortic valve replacement gradient waveform using preprocedural Doppler echocardiogram.

Methods: A total of 110 patients undergoing transcatheter aortic valve replacement (mean age 78.

Sequential decreases in basolateral amygdala response to threat predict failure to recover from PTSD.

Amygdala hyperreactivity early-post trauma has been a demonstrable neurobiological correlate of future posttraumautic stress disorder (PTSD). The basolateral amygdala (BLA) particularly is vital for fear memory and threat processing, but BLA functional dynamics following a traumatic event are unexplored. BLA reactivity to threat may be a trait that can predict PTSD and persist over time.

Deep Learning Model of Primary Tumor and Metastatic Cervical Lymph Nodes From CT for Outcome Predictions in Oropharyngeal Cancer.

Importance: Primary tumor (PT) and metastatic cervical lymph node (LN) characteristics are highly associated with oropharyngeal squamous cell carcinoma (OPSCC) prognosis. Currently, there is a lack of studies to combine imaging characteristics of both regions for predictions of p16+ OPSCC outcomes.

Objectives: To develop and validate a computed tomography (CT)-based deep learning classifier that integrates PT and LN features to predict outcomes in p16+ OPSCC and to identify patients with stage I disease who may derive added benefit associated with chemotherapy.

Fluorescence microscopy through scattering media with robust matrix factorization.

Biological tissues, as natural scattering media, inherently disrupt structural information, presenting significant challenges for optical imaging. Complex light propagation through tissue severely degrades image quality, limiting conventional fluorescence imaging techniques to superficial depths. Extracting meaningful information from random speckle patterns is, therefore, critical for deeper tissue imaging.

Quantifying Ventricular CSF Clearance in the Human Brain Using Dynamic 18F-FDG PET: Insights into Age-Related Glymphatic Impairment.

Purpose: The glymphatic system facilitates brain waste clearance via cerebrospinal fluid (CSF) flow, and its dysfunction has been linked to aging and neurodegeneration. However, clinically accessible methods to quantify glymphatic function in humans remain limited. This study aimed to examine the potential of dynamic 18F-FDG PET for measuring ventricular CSF clearance - as a surrogate marker of glymphatic function.

Coil Combination Using OpTIMUS Results in Improved Signal-to-Noise Ratios of In Vivo MR Spectra Acquired at 7 T.

Magnetic resonance spectroscopy (MRS) enables noninvasive quantification of metabolites, but its utility in vivo can be limited by low signal-to-noise ratios (SNRs) and long acquisition times. The use of ultrahigh-field (UHF) strengths (> 3 T) combined with multichannel phased receive arrays can improve spectral SNR. A crucial step in the use of multichannel arrays is the combination of spectra acquired from individual coil channels.

A Mimetic Assay of Neutrophil Extracellular Trap Degradation Using YOYO-1-Stained DNA-Histone Surface Webs.

Neutrophil extracellular traps (NETs) are not only promising biomarkers of disease, but also potential therapeutic targets. Overproduction or the improper clearance of NETs has been linked to disease severity. In vitro NET degradation assays can reveal mechanisms and degradation efficiency differences in diseased serum samples.

40 Hz sensory stimulation enhances CA3-CA1 coordination and prospective coding during navigation in a mouse model of Alzheimer's disease.

40 Hz sensory stimulation ("flicker") has emerged as a new technique to potentially mitigate pathology and improve cognition in mouse models of Alzheimer's disease (AD) pathology. However, it remains unknown how 40 Hz flicker affects neural codes essential for memory. Accordingly, we investigate the effects of 40 Hz flicker on neural representations of experience in the hippocampus of the 5XFAD mouse model of AD by recording 1,000s of neurons during a goal-directed spatial navigation task.

Seeing Is Believing: How Does the Surface of Silver Nanocubes Change during Their Growth in an Aqueous System.

The seed-mediated growth involving cetyltrimethylammonium chloride (CTAC), silver trifluoroacetate (CFCOOAg), ascorbic acid (HAsc), and Ag seeds covered by poly(vinylpyrrolidone) (PVP) in aqueous medium is a robust route to Ag nanocubes with tunable sizes. However, mechanistic details such as changes to the surface remain elusive. Herein, we address this issue by leveraging the high sensitivity and water compatibility of surface-enhanced Raman scattering (SERS).

Advancing β-adrenoreceptor agonism for recovery after volumetric muscle loss through regenerative rehabilitation and biomaterial delivery approaches.

Volumetric muscle loss (VML) injury results in the unrecoverable loss of muscle mass and contractility. Oral delivery of formoterol, a β-adrenergic receptor agonist, produces a modest recovery of muscle mass and contractility in VML-injured mice. The objective of this study was to determine if a regenerative rehabilitation paradigm or a regenerative medicine paradigm could enhance the recovery of VML-injured muscle.

Differential Sensitivity to Interepitope Spacing in Mast Cells and B Cells Enables Design of Hypoallergenic Allergen Vaccine Immunogens.

Therapeutic allergen vaccine immunogens can trigger IgE-mediated mast cell activation, resulting in allergic reactions. Here, we report on a mode of hypoallergenic immunogen design that enables immunization against IgE-reactive peptide B cell epitopes by optimizing the distance between epitopes. Using DNA-based model immunogens, we show that mast cells and B cells exhibit idiosyncratic sensitivity to interepitope spacing, with mast cell activation being dampened by high interepitope spacing while B cells remain responsive to identical immunogen configurations.

Programming megakaryocytes to produce engineered platelets for delivering non-native proteins.

Platelets are anucleate cells naturally filled with secretory granules that store large amounts of protein to be released in response to certain physiological conditions. Cell engineering can endow platelets with the ability to deliver non-native proteins by modifying them as they develop during the cell fate process. This study presents a strategy to efficiently generate mouse platelets from pluripotent stem cells and demonstrates their potential as bioengineered protein delivery platforms.