Recent uci_eng_bme items

Charge readout electronics for the DUNE horizontal drift far detector: design and performance in ProtoDUNE-HD

Tue, 15 Sep 2026 00:00:00 +0000

DUNE (Deep Underground Neutrino Experiment) is a long-baseline neutrino oscillation experiment currently under construction, whose far detectors will be the largest liquid argon time projection chambers ever built. This detector design calls for custom-built cryogenic front-end electronics to meet its performance requirements. This paper describes the charge readout electronics that will be used in the DUNE horizontal drift (HD) far detector and presents performance results using data from the ProtoDUNE-HD detector, a 770 ton liquid argon time projection chamber operated at the CERN Neutrino Platform in 2024 that served as the final prototype of the DUNE HD design.

A standardized data specification for reproducible, verifiable structured light and multispectral image sets

Fri, 11 Sep 2026 00:00:00 +0000

Spatial Frequency Domain Imaging (SFDI) is a quantitative wide-field imaging technique that uses light and diffuse optical spectroscopic principles to rapidly generate tissue optical property images. However, SFDI datasets present significant workflow challenges: they can be large (on the order of gigabytes), contain multiple image formats, and require computationally intensive processing. Additionally, SFDI images typically require calibration measurements, further complicating data organization. The proliferation of calibration data, imaging data, and processing options creates technical overhead and leads to reproducibility issues. While multiple "Open SFDI"initiatives exist, no standardized storage format has emerged, making the replication of published SFDI research difficult. Commercial solutions like Modulim's directory-based format contain trade secrets and lack open-source processing options. We are developing an open standard for SFDI images, extensible to multispectral...

Characterization of global and region-specific transcriptomic alterations in the bladder following acute partial bladder outlet obstruction in female mini-swine.

Thu, 10 Sep 2026 00:00:00 +0000

Partial bladder outlet obstruction (pBOO) is a fibroproliferative disorder that results in poorly compliant, high-pressure bladders due to lower urinary tract occlusion. The mechanisms governing pBOO-induced bladder remodeling remain poorly understood. The goals of the present study were to profile global and region-specific transcriptomes of porcine bladders in response to pBOO using RNA sequencing and to identify genes and pathways differentially affected in the bladder dome and trigone by obstructive injury. Nine adult female Yucatan mini-swine were randomized and divided into either nonsurgical controls (n = 5) or those subjected to pBOO for 4 weeks (n = 4). Post-pBOO swine demonstrated bladder smooth muscle hypertrophy as well as significant declines in bladder capacity (35% ± 7% of baseline) and compliance (38% ± 10% of baseline). The global transcriptome of obstructed bladders revealed enrichment of processes related to loss of urothelial barrier function, immune activation,...

Mapping Polyamide–DNA Interactions in Human Cells Reveals a New Design Strategy for Effective Targeting of Genomic Sites

Wed, 9 Sep 2026 00:00:00 +0000

Targeting the genome with sequence-specific synthetic molecules is a major goal at the interface of chemistry, biology, and personalized medicine. Pyrrole/imidazole-based polyamides can be rationally designed to target specific DNA sequences with exquisite precision in vitro; yet, the biological outcomes are often difficult to interpret using current models of binding energetics. To directly identify the binding sites of polyamides across the genome, we designed, synthesized, and tested polyamide derivatives that enabled covalent crosslinking and localization of polyamide-DNA interaction sites in live human cells. Bioinformatic analysis of the data reveals that clustered binding sites, spanning a broad range of affinities, best predict occupancy in cells. In contrast to the prevailing paradigm of targeting single high-affinity sites, our results point to a new design principle to deploy polyamides and perhaps other synthetic molecules to effectively target desired genomic sites...

Axonal theta oscillations evoke bursting in target hippocampal subregions.

Wed, 9 Sep 2026 00:00:00 +0000

OBJECTIVE: Local field potentials (LFPs) measured in the extracellular matrix of the brain are postulated to arise from the integration of synaptic ionic currents and spread by volume conduction. However, there is a lack of consensus on whether these spatiotemporal voltage gradients are just an epiphenomenon of spiking or if the LFPs play a functional role in information processing. APPROACH: To examine a potential functional role of LFPs in information processing, we developed a microfluidic device that allows neurons from the hippocampal formation to self-wire through microfluidic channels, effectively isolating the activity of single axons between subregions of the network. RESULTS: We recorded spontaneous theta-band activity (4-10 Hz) in these axons whose power spectra were independent of simultaneous spiking activity. The highest theta amplitudes above noise were seen intermittently in a sparse set of axons from the CA3 into the CA1. Source neurons for the axonal theta were...

Breaking the age-related redox spiral for regeneration.

Wed, 9 Sep 2026 00:00:00 +0000

Breaking the age-related redox spiral for regeneration.

Maternal allostatic load in pregnancy is prospectively associated with child adiposity and metabolic function across infancy and early childhood.

Wed, 26 Aug 2026 00:00:00 +0000

BACKGROUND: Empirical evidence suggests that the origins of obesity and metabolic dysfunction can be traced to stress-related exposures in prenatal life. The aim of the present study was to examine the prospective association of a composite, multi-system measure of maternal biological stress in pregnancy -- allostatic load (AL) -- with offspring adiposity and insulin resistance across infancy and early childhood. METHODS: In N = 55 mother-child dyads, maternal allostatic load was operationalized as a latent variable representing the following components: pre-pregnancy BMI, cortisol, interleukin-6, C-reactive protein, homeostasis model assessment of insulin resistance (HOMA-IR), free fatty acids, and systolic/diastolic blood pressure. Offspring percent total (%FM) and abdominal (%AbFM) fat were quantified with dual-energy X-ray absorptiometry at birth (newborn), 6-mo, and ∼5 yrs age, and HOMA-IR was quantified at ∼5 yrs age. Generalized estimating equation modeling was used to...

Microdystrophins partially rescue deficits of Duchenne muscular dystrophy iPSC-cardiomyocytes

Wed, 26 Aug 2026 00:00:00 +0000

Duchenne muscular dystrophy (DMD) is a severe muscle wasting disease caused by the lack of dystrophin. Dilated cardiomyopathy is the leading cause of death in DMD patients. Smaller variants of dystrophin, called microdystrophins, amenable to packaging into adeno-associated virus (AAV), have been shown to be effective in improving skeletal muscle function in animal models. However, the functional benefit of these microdystrophins in the DMD heart remains unclear. To determine the efficacy of microdystrophin gene therapy, we compared three microdystrophin variants in DMD cardiomyocytes (CMs) differentiated from human induced pluripotent stem cells (iPSCs). We used three DMD lines of different genetic backgrounds and benchmarked against controls expressing full-length dystrophin. We also tested a dystrophin variant, minidystrophin, which is larger than the microdystrophins. Our results show that microdystrophins partially rescue disease phenotypes; however, the results are variable...

Optimized hip-knee-ankle exoskeleton assistance at a range of walking speeds

Sat, 22 Aug 2026 00:00:00 +0000

Abstract Background Effective autonomous exoskeletons will need to be useful at a variety of walking speeds, but we do not know how optimal exoskeleton assistance should change with speed. Optimal exoskeleton assistance may increase with speed similar to biological torque changes or a well-tuned assistance profile may be effective at a variety of speeds. Methods We optimized hip-knee-ankle exoskeleton assistance to reduce metabolic cost for three participants walking at 1.0 m/s, 1.25 m/s and 1.5 m/s. We measured metabolic cost, muscle activity, exoskeleton assistance and kinematics. We performed two tailed paired t-tests to determine significance. Results Exoskeleton assistance reduced the metabolic cost of walking compared to wearing the exoskeleton with no torque applied by 26%, 47% and 50% at 1.0, 1.25 and 1.5 m/s, respectively. For all three participants, optimized exoskeleton ankle torque was the smallest for slow walking, while hip and knee torque changed slightly with...

Two Faces of Mitral Stenosis: Uncovering Structural and Hemodynamic Signatures of Rheumatic and Mitral Annular Calcification–Induced Disease

Thu, 13 Aug 2026 00:00:00 +0000

BACKGROUND: Mitral annular calcification (MAC) is common and associated with increased cardiovascular risk and, when severe, mitral stenosis (MS). MAC-related MS differs anatomically and hemodynamically from rheumatic MS (RMS), challenging standard diagnostic methods. This study compares structural and flow characteristics, including kinetic energy losses, across MAC-related MS, RMS, and normal mitral valves, and evaluates the applicability of conventional diagnostic metrics in MAC. METHODS: Three-dimensional transesophageal echocardiographic data sets from 70 patients (22 normal mitral valves, 26 RMS valves, 22 MAC valves) were used to obtain linear, area, and volumetric measurements for valve comparison. Representative valves from each group were converted into 3-dimensional silicone models for in vitro testing in a heart flow simulator. Transmitral flow was assessed with particle image velocimetry, flow energetics were quantified, and coefficients of contraction...

From Polymer Structure to Valve Function: A Multiscale Evaluation of Polycarbonate Polyurethanes for Polymeric Mitral Valves

Thu, 13 Aug 2026 00:00:00 +0000

PurposePolymeric heart valves (PHVs) offer the potential to combine the durability of mechanical valves with the favorable hemodynamics of bioprosthetic valves; however, establishing clear relationships between polymer properties and valve-level function remains a key challenge. This study evaluates polycarbonate-based polyurethanes as candidate scaffold materials for polymeric mitral valves through a multiscale structure–function approach.MethodsTwo aromatic polycarbonate-based thermoplastic polyurethanes, Carbothane AC-4095A (CB95-AC) and QuadraSil ARCS 90A (Qsil), were characterized using rheological, mechanical, and spectroscopic analyses. Trileaflet valve scaffolds were fabricated and evaluated using particle image velocimetry (PIV), pressure–flow measurements, and accelerated wear testing (AWT) up to 50 million cycles. Preliminary in vivo performance was assessed following implantation of a CB95-AC valve in an ovine model.ResultsQsil exhibited higher solution viscosity,...

Microfluidic Precision Engineered Artificial GARP Presenting Cells for Regulatory T-Cell Induction

Thu, 30 Jul 2026 00:00:00 +0000

PurposeThe incidence of autoimmune diseases has increased in Western societies, highlighting the need for novel treatment strategies. Current therapies, including biologics, are limited by high costs, potential adverse effects, and often lack specificity and long-term efficacy. Regulatory T cells (Tregs) are crucial for maintaining immune tolerance and represent a promising target for autoimmune disease therapies. However, current methods for inducing Tregs, such as in vitro cytokine combinations and in vivo antigen-specific approaches, face challenges in stability and effectiveness. This research aims to develop an innovative artificial cell platform to enhance Treg induction for autoimmune disease treatment.MethodsThis study developed artificial GARP-presenting cells (aGPCs), an innovative artificial cell platform designed to mimic natural cellular functions and enhance Treg induction. We evaluated aGPC efficacy in inducing Tregs both in vitro and in vivo, comparing results...

Correlating ultrasonic communication with behavior in a small-scale rat colony living in a naturalistic habitat

Thu, 30 Jul 2026 00:00:00 +0000

Traditional studies of rat communication have focused on a few individuals in simplified laboratory settings, leaving colony-level vocal-behavioral dynamics largely unexplored. Here, we examined the nocturnal lives of a rat colony housed in an enhanced naturalistic habitat (ENH). Using infrared cameras and ultrasound microphones, we recorded 18,412 ultrasonic vocalizations (USVs) alongside social behaviors. Analyses revealed structurally distinct USVs not previously characterized statistically or behaviorally. Notably, 22 kHz calls-typically associated with aversion-occurred across multiple social behaviors lacking obvious aversive context. Brief exposure to cat hair elicited uniquely modified 22 kHz calls as rats fled to their burrows, remaining hidden for two days. The introduction of an unfamiliar caged rat, and the disruption of the colony's social structure then showed how social stressors alter vocal-behavioral dynamics. These findings reveal the structured and context-sensitive...

Heart–Lung Interactions in Pulmonary Hypertension due to Heart Failure With Preserved Ejection Fraction

Wed, 29 Jul 2026 00:00:00 +0000

Pulmonary hypertension associated with heart failure with preserved ejection fraction (PH-HFpEF) is a common and high-risk clinical condition characterized by the convergence of pulmonary vascular dysfunction and right ventricular (RV) stress. Despite its prevalence, the pathophysiological mechanisms of development and progression of PH-HFpEF remain largely unknown. Consequently, there are no current therapies that target PH-HFpEF other than optimization of treatment for HFpEF and some limited adaptation of therapies for pulmonary artery hypertension (PAH). This review examines PH-HFpEF through the lens of heart-lung interactions, integrating evidence across hemodynamic, molecular, and cellular scales. We highlight how chronic venous pressure overload, impaired pulmonary vascular reserve, and increased pulsatile load reshape RV afterload and contribute to RV-pulmonary arterial uncoupling, particularly during physiological stress such as exercise. We further discuss how endothelial...

Stronger pre-surgical functional connectivity networks are associated with improved surgical outcome in temporal lobe epilepsy

Wed, 15 Jul 2026 00:00:00 +0000

OBJECTIVE: This study investigates the network differences in pre-surgical resting-state EEG between individuals with unilateral temporal lobe epilepsy who become seizure-free and those who continue to have seizures after epilepsy surgery. METHODS: We retrospectively identified 15 individuals with unilateral TLE who were seizure-free (SF) after epilepsy surgery and 13 who continued to have seizures post-surgery (nSF). Functional connectivity was measured using cross-correlation techniques on clips of resting-state scalp EEG that were free of any visually apparent epileptiform abnormalities. RESULTS: Stronger pre-surgical functional connectivity was associated with favorable post-surgical outcomes. The SF group demonstrated significantly higher connectivity strength, particularly in cross-hemispheric and intra-hemispheric networks involving the ictal hemisphere (P = 0.02). Functional connectivity strength predicted post-surgical seizure freedom with 75 % accuracy...

Prediction of treatment response in infantile epileptic spasms syndrome using EEG phase–amplitude coupling

Wed, 15 Jul 2026 00:00:00 +0000

OBJECTIVE: Treatment selection for infantile epileptic spasms syndrome (IESS) is complex and multifaceted, and currently no electroencephalogram (EEG) biomarkers can guide this decision by predicting treatment response. We tested the predictive value of phase-amplitude coupling (PAC) as IESS patients are known to have elevated PAC. METHODS: We analyzed retrospective EEG recordings from 40 IESS patients, before and after treatment, and 20 healthy controls. Patients were classified as responders (n = 25) or nonresponders (n = 15) based on short-term treatment outcomes. We measured PAC in each EEG using modulation index (MI) and mean vector length (MVL) and analyzed the relationship between pre- and posttreatment values and the ability of pretreatment values to predict response. RESULTS: MI and MVL values decreased with treatment in almost all subjects. However, nonresponders had significantly higher pretreatment MI than responders (p < 0.05), suggesting utility for predicting...

Physiological ripples during sleep in scalp electroencephalogram of healthy infants

Wed, 15 Jul 2026 00:00:00 +0000

Physiological ripples during sleep in scalp electroencephalogram of healthy infants

EEG functional connectivity as a marker of evolution from infantile epileptic spasms syndrome to Lennox–Gastaut syndrome

Wed, 15 Jul 2026 00:00:00 +0000

OBJECTIVE: Timely diagnosis and effective treatment of Lennox-Gastaut syndrome (LGS) improve prognosis and lower health care costs, but the transition from infantile epileptic spasms syndrome (IESS) to LGS is highly variable and insidious. Objective biomarkers are needed to monitor this progression and guide clinical decision-making. METHODS: We retrospectively collected longitudinal EEG data at the Children's Hospital of Orange County from 15 children who were diagnosed with IESS and later with LGS between 2012 and 2021. Electroencephalography studies were from IESS and LGS diagnoses, between the two diagnoses, and following LGS diagnosis. Functional connectivity networks were calculated using a cross-correlation-based method and assessed relative to diagnostic timepoint, treatment response, and the presence of clinical markers of disease, age, and amplitude of interictal spikes. RESULTS: Connectivity strength was high at LGS diagnosis and decreased after favorable response to...

Semi-autonomous liquid handling via on-chip pneumatic digital logic

Sun, 28 Jun 2026 00:00:00 +0000

This report presents a liquid-handling chip capable of executing metering, mixing, incubation, and wash procedures largely under the control of on-board pneumatic circuitry. The only required inputs are four static selection lines to choose between the four machine states, and one additional line for power. State selection is simple: constant application of vacuum to an input causes the device to execute one of its four liquid handling operations. Programmed control of 31 valves, including fast coordinated cycling for peristaltic pumping, is accomplished by pneumatic digital logic circuits built out of microfluidic valves and channels rather than electronics, eliminating the need for the off-chip control machinery that is typically required for integrated microfluidics.

SCREENING FOR EARLY LIFE UNPREDICTABILITY IN PEDIATRIC PRIMARY CARE IDENTIFIES CHILD OBESITY RISK

Thu, 18 Jun 2026 00:00:00 +0000

SCREENING FOR EARLY LIFE UNPREDICTABILITY IN PEDIATRIC PRIMARY CARE IDENTIFIES CHILD OBESITY RISK

Limbic‐predominant age‐related TDP‐43 encephalopathy, but Not Alzheimer's Disease, neuropathological changes are associated with Physical Performance Decline in the Oldest Old: Insights from The 90+ Study

Thu, 18 Jun 2026 00:00:00 +0000

AbstractBackground

To examine physical performance longitudinal trajectories in relation to Alzheimer's Disease Neuropathological Changes (ADNC) and Limbic‐predominant age‐related TDP‐43 encephalopathy neuropathological changes (LATE‐NC) at autopsy. ADNC and LATE‐NC have similar cognitive presentations, but it is unclear whether physical presentation is similar as well.

Method

Participants were from The 90+ Study, a longitudinal study of aging among individuals 90 years and older with evaluations every 6 months. We used 4 physical performance measures including gait speed, the Five Times Sit to Stand test (5XSST), grip strength, balance, and a composite summing the 4 measures. Each measure was scored from 0 (unable to perform) to 4 (best performance), the composite from 0 to 16. Neuropathological changes from brain autopsies were dichotomized: ADNC as intermediate/high versus none/low and LATE‐NC as present versus absent. To examine the longitudinal association of ADNC...

ESPRESSO: Spatiotemporal omics based on organelle phenotyping reveals dynamic cell state transitions

Wed, 17 Jun 2026 00:00:00 +0000

ESPRESSO: Spatiotemporal omics based on organelle phenotyping reveals dynamic cell state transitions

Integrated Strain–Flow Analysis for Early Assessment of Right Ventricular Dysfunction in Pulmonary Arterial Hypertension

Thu, 21 May 2026 00:00:00 +0000

PurposeEarly detection of right ventricular (RV) dysfunction is essential in pulmonary arterial hypertension (PAH) but remains challenging using conventional echocardiography. This study investigates the feasibility of a noninvasive, physics-based framework using three-dimensional (3D) echocardiography that integrates myocardial strain and volumetric flow analysis to characterize RV mechanical performance across stages of PAH.MethodsA prospective pilot study (N = 15) enrolled healthy controls, PAH patients with preserved RV size, and PAH patients with RV dysfunction. Deformation was evaluated by principal strain analysis and by conventional (longitudinal, circumferential) components. Hemodynamic metrics included hemodynamic forces and energetic properties that were derived using a physics-informed volumetric echocardiographic particle image velocimetry (V-Echo-PIV) method applied to contrast-enhanced acquisitions.ResultsDeformation analysis revealed that longitudinal...

Hippocampal ensembles represent sequential relationships among discrete nonspatial events

Thu, 7 May 2026 00:00:00 +0000

ABSTRACT The hippocampus is critical to the temporal organization of our experiences, including the ability to remember past event sequences and predict future ones. Although this fundamental capacity is conserved across modalities and species, its underlying neuronal mechanisms remain poorly understood. Here we recorded hippocampal ensemble activity as rats remembered a sequence of nonspatial events (5 odor presentations unfolding over several seconds), using a task with established parallels in humans. Using novel statistical methods and deep learning techniques, we then identified new forms of sequential organization in hippocampal activity linked with task performance. We discovered that sequential firing fields (“time cells”) provided temporal information within and across events in the sequence, and that distinct types of task-critical information (stimulus identity, temporal order, and trial outcome) were also sequentially differentiated within event presentations. Finally,...

Ultrasound-Integrated Urinary Catheter for Minimally-Invasive Cervical & Fetal Monitoring

Fri, 24 Apr 2026 00:00:00 +0000

Over 4 million births occur in the United States annually, and nearly all laboring mothers undergo multiple manual exams to assess cervical dilation and effacement as part of labor progression. Assessing cervical dilation is a critical part of labor management. However, manual cervical exam poses a risk of infection that can lead to maternal and fetal complications, and these exams are subjective with variability rates as high as 50%. Our innovation leverages the anatomical proximity of the bladder and uterus to obtain labor metrics. 75% of mothers receive an epidural for pain management and are unable to feel their lower body, resulting in the need for a urinary catheter to drain the bladder. We propose an ultrasound-integrated urinary catheter to provide continuous, objective measurements of both cervical dilation and fetal vitals while seamlessly integrating into the existing standard for labor management. The ultrasound-integrated urinary catheter could transform obstetric...

Evaluating synthesized speech intelligibility in noise

Fri, 24 Apr 2026 00:00:00 +0000

Humans can modify their speech to improve intelligibility in noisy environments. With the advancement of speech synthesis technology, machines may also synthesize voices that remain highly intelligible in noise condition. This study evaluates both the subjective and objective intelligibility of synthesized speech in speech-shaped noise from three major speech synthesis platforms. It was found that synthesized voices have a similar intelligibility range to human voices, and some synthesized voices were more intelligible than human voices. It was also found that two modern automatic speech recognition systems recognized 10% more words than human listeners.

Detrended fluctuation analysis of amygdala-hippocampal beta synchrony reveals network rigidity in depression associated with temporal lobe epilepsy.

Thu, 23 Apr 2026 00:00:00 +0000

Objective Depressive symptoms are common in individuals with temporal lobe epilepsy (TLE), yet the network dynamics linking limbic circuitry to mood disturbance in TLE remain poorly understood. Here, we investigated whether the temporal organization of amygdala-hippocampal beta synchrony reflects depressive symptom burden in individuals with TLE undergoing intracranial EEG (iEEG) monitoring. Approach We analyzed iEEG recordings from 14 adults with TLE who underwent intracranial monitoring as part of routine pre-surgical evaluation. Dynamic functional connectivity (dFC) in the beta band was calculated between the amygdala and the hippocampus, and the temporal structure of the dFC was quantified using detrended fluctuation analysis. Random permutation of epochs was performed to assess the influence of interictal epileptiform discharges (IEDs) on the network dynamics. We additionally extracted the ultra-slow fluctuations in dFC and assessed whether the timing of the IEDs was phase-locked...

NeoFusion: Fully Mechanical Syringe Pump for Low-Resource Countries

Wed, 22 Apr 2026 00:00:00 +0000

There are approximately 6,500 newborn deaths each day. Despite many of these deaths being preventable by proper access to quality healthcare, the world continues to see a health crisis that disproportionately impacts low-and-middle income countries (LMICs), with about 98% of newborn deaths occurring in these regions. The WHO has identified syringe pumps as necessary medical devices because they can gradually deliver precise amounts of medication, fluids, nutrients, and electrolytes to neonates. However, the majority of syringe infusion pumps currently on the market depend on electricity, which can be unreliable in areas lacking proper infrastructure. Our solution, NeoFusion, does not require electricity and is fully mechanical, powered by the potential energy stored in a spring. Preliminary trials with our prototype achieved accurate and adjustable flow rates. In future designs, we will incorporate a visual and auditory alarm system for occlusions.

Flapping-Wing Micro-Air-Vehicle Project (FMMAV)

Wed, 22 Apr 2026 00:00:00 +0000

We are a student-led research team dedicated to bridging the gap between natural flight and modern engineering by studying the complex aerodynamics of flapping wings. Our project focuses on evolving our quadflapper and novel prototypes into high-performance aerial vehicles that challenge the efficiency of traditional propeller drones.

SimuMed Solutions: Developing Accurate Simulation Models for Groin-to-Right Heart Catheterization to Enhance R&D Testing

Wed, 15 Apr 2026 00:00:00 +0000

Cardiovascular disease affects nearly 50% of adults in the United States, with many requiring right heart catheterization as part of their diagnosis or treatment. A common approach for this procedure is the groin-to-right heart catheterization, which involves inserting a catheter through the femoral vein into the right atrium, allowing access to the interatrial septum. While transradial access (via the arm or wrist) has become increasingly popular due to a lower risk of complications such as major bleeding or stroke, femoral access (via the groin) remains necessary in cases requiring larger catheters or more complex procedures. However, the femoral access approach carries a higher risk of bleeding and vascular injury due to its deeper access site and the potential for excessive insertion force. Therefore, there is a critical need to develop realistic, high-fidelity testing models that simulate the femoral access procedure to enhance procedural safety and outcomes. These models...

Evaluating the potential of acupuncture for Alzheimer’s disease treatment: A meta-analysis and systematic review of mouse model studies

Wed, 8 Apr 2026 00:00:00 +0000

Acupuncture is an ancient practice that was developed within the framework of traditional Chinese medicine. While acupuncture has been recently proposed as a therapy for Alzheimer’s disease (AD), acupuncture effects are not well understood in terms of neural mechanisms. Here, we review and examine the studies that used AD mouse models and analyze the experiments where researchers administered electroacupuncture (EA) to AD mice to assess the potential therapeutic impact of acupuncture on disease pathology and cognitive function in controlled laboratory settings. We analyzed 29 relevant PubMed articles published between January 2014 and July 2025. Our results reveal that EA significantly reduces both amyloid-beta (Aβ) and phosphorylated tau (p-tau) levels and neuroinflammatory biomarkers, including molecular signatures for activated microglia and astrocytes in the brain. EA also enhances cognitive functions. While no study directly compared acupoint strategies, the indirect comparisons...

Expanding the Spectrum of Central Sensitivity Syndrome: Integrating Otologic Migraine as Otologic Central Sensitivity Syndrome

Wed, 1 Apr 2026 00:00:00 +0000

Objective: To propose that migraine-related symptoms such as dizziness, sudden hearing loss, tinnitus, and vertigo-when occurring without headache-should be recognized as manifestations of central sensitivity syndrome (CSS), and to explore the implications of this reclassification for clinical practice and patient care. Data sources: PubMed Central and Google Scholar. Review methods: A search of the literature was performed using PubMed and Google Scholar. Search terms included combinations of keywords such as "migraine", "vertigo", "tinnitus", "dizziness", "sudden hearing loss", "central sensitivity syndrome", and "central sensitization". Conclusions: Non-headache migraine symptoms show significant overlap with characteristics of CSS, including central nervous system hyperexcitability and dysregulation. Neuroimaging and clinical data support this connection, suggesting these symptoms may be better understood within the CSS framework. Recognizing this...

JAK2 inhibition with baricitinib stunts growth and postnatal development in juvenile rats

Thu, 26 Mar 2026 00:00:00 +0000

The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway has recently emerged as an important regulator of musculoskeletal development. Inhibition of the pathway with small-molecule JAK inhibitors (jakinibs) may improve tendon development and healing. The goal of the present study was to characterize the effects of blocking JAK1 and 2 during a key postnatal musculoskeletal growth phase in Sprague-Dawley rats (postnatal day (PND) 7-28). We administered vehicle or baricitinib via chow (3 mg, or 10 mg/kg BW/day), which blocks JAK1 and JAK2, for 21 days and characterized the resulting systemic and musculoskeletal effects. We found a striking reduction in overall growth of the juvenile rats with baricitinib treatment, with a reduction in body weight of ∼30% for males and ∼20% for females at PND 28. The spleen was smaller in size with baricitinib treatment, even after normalization to body weight. Bone and tendon similarly showed decreases in mechanical...

Collagen remodeling in murine melanoma therapy response through second-harmonic generation imaging

Mon, 16 Mar 2026 00:00:00 +0000

The study by Heaton et al. marks a significant advancement in understanding the role of collagen remodeling within the melanoma tumor microenvironment during immunotherapy. Using in vivo second-harmonic generation imaging, the authors quantitatively tracked dynamic changes in collagen morphology in a preclinical melanoma model, revealing a shift toward a healthier phenotype associated with treatment. These findings enhance our understanding of tumor extracellular matrix dynamics and highlight the potential of optical imaging technologies to guide and optimize cancer immunotherapy. This commentary will explore these findings, contextualize them within the broader field of tumor immunology, and discuss their implications for improving immunotherapy strategies in melanoma and other cancers.

Spatial and temporal evaluations of the liquid argon purity in ProtoDUNE-SP

Mon, 16 Mar 2026 00:00:00 +0000

Liquid argon time projection chambers (LArTPCs) rely on highly pure argon to ensure that ionization electrons produced by charged particles reach readout arrays. ProtoDUNE Single-Phase (ProtoDUNE-SP) was an approximately 700-ton liquid argon detector intended to prototype the Deep Underground Neutrino Experiment (DUNE) Far Detector Horizontal Drift module. It contains two drift volumes bisected by the cathode plane assembly, which is biased to create an almost uniform electric field in both volumes. The DUNE Far Detector modules must have robust cryogenic systems capable of filtering argon and supplying the TPC with clean liquid. This paper will explore comparisons of the argon purity measured by the purity monitors with those measured using muons in the TPC from October 2018 to November 2018. A new method is introduced to measure the liquid argon purity in the TPC using muons crossing both drift volumes of ProtoDUNE-SP. For extended periods on the timescale of weeks, the drift...

MEASUREMENT OF PULSATILE FLOW IN THE TEETH USING LASER SPECKLE IMAGING

Fri, 13 Mar 2026 00:00:00 +0000

MEASUREMENT OF PULSATILE FLOW IN THE TEETH USING LASER SPECKLE IMAGING

Treatment of age-related decreases in GTP levels restores endocytosis and autophagy

Wed, 11 Mar 2026 00:00:00 +0000

Age-related declines in neuronal bioenergetic levels may limit vesicular trafficking and autophagic clearance of damaged organelles and proteins. Age-related ATP depletion would impact cognition dependent on ionic homeostasis, but limits on proteostasis powered by GTP are less clear. We used neurons isolated from aged 3xTg-AD Alzheimer’s model mice and a novel genetically encoded fluorescent GTP sensor (GEVAL) to evaluate live GTP levels in situ. We report an age-dependent reduction in ratiometric measurements of free/bound GTP levels in living hippocampal neurons. Free GTP colocalized in the mitochondria decreased with age accompanied by the accumulation of free GTP-labeled vesicular structures. The energy dependence of autophagy was demonstrated by depletion of GTP with rapamycin stimulation, while bafilomycin inhibition of autophagy raised GTP levels. Twenty-four-hour supplementation of aged neurons with the NAD precursor nicotinamide and the Nrf2 redox modulator EGCG restored...

Secondary Macular Hole Closure With Sub-Tenon Triamcinolone Acetonide

Wed, 25 Feb 2026 00:00:00 +0000

Purpose: To evaluate the efficacy and safety of sub-Tenon triamcinolone acetonide in the management of secondary full-thickness macular holes after vitreoretinal surgeries or traumatic injury. Methods: This case series includes 3 patients with secondary macular holes. All patients were treated with 40 mg sub-Tenon triamcinolone acetonide injections for macular holes. Results: Postinjection, the macular holes closed in 2 months, 2 weeks, and 1 month, respectively. Vision improved in all cases. The third patient experienced a significant increase in intraocular pressure, effectively managed with topical medications. No recurrence was observed at follow-up. Conclusions: Sub-Tenon triamcinolone acetonide is a promising therapeutic option for the management of secondary macular holes less than 200 µm in diameter, demonstrating efficacy in promoting hole closure and improving visual outcomes.

Dense sampling for mapping pituitary growth dynamics before, during, and after pregnancy.

Tue, 17 Feb 2026 00:00:00 +0000

Pregnancy represents a period of profound endocrine activity and neural reorganization. While recent evidence highlights pituitary volume as a biomarker of endocrine dynamics during pregnancy, its precise trajectory (timing and relative magnitude of effect) across human pregnancy remains undescribed. Three healthy women (59 total observations) underwent T1-weighted MRI before conception (5 baseline observations), during pregnancy (38 total observations, spanning gestational weeks 1-36), and up to 1 year postpartum (16 total observations). Anterior and posterior pituitary lobes were manually delineated at every visit. A longitudinal pipeline co-registered each scan to all other intra-subject scans, propagated their labels, and generated majority-vote ensembles for objective and regularized volume estimates. Person-centered z-scores were computed, and generalized additive mixed models (GAMMs) with random intercepts estimated nonlinear volume trajectories. The anterior lobe followed...

Multiplexed bioluminescence microscopy via phasor analysis

Thu, 12 Feb 2026 00:00:00 +0000

Bioluminescence imaging with luciferase–luciferin pairs is a well-established technique for visualizing biological processes across tissues and whole organisms. Applications at the microscale, by contrast, have been hindered by a lack of detection platforms and easily resolved probes. We addressed this limitation by combining bioluminescence with phasor analysis, a method commonly used to distinguish spectrally similar fluorophores. We built a camera-based microscope equipped with special optical filters to directly assign phasor locations to unique luciferase–luciferin pairs. Six bioluminescent reporters were easily resolved in live cells, and the readouts were quantitative and instantaneous. Multiplexed imaging was also performed over extended time periods. Bioluminescent phasor further provided direct measures of resonance energy transfer in single cells, setting the stage for dynamic measures of cellular and molecular features. The merger of bioluminescence with phasor analysis...

A Novel, Low-Cost, 3D-Printed Motorized Injector for Retinal Sheet Transplantation

Wed, 11 Feb 2026 00:00:00 +0000

Retinal transplantation offers promise for restoring vision in advanced retinal degeneration. However, manual delivery of retinal sheets is often hindered by imprecise placement and collateral tissue damage resulting from instrument instability. We introduce a novel, 3D-printed, motorized retinal sheet injector designed to enhance placement accuracy and minimize tissue injury. The motorized injector features an Arduino-controlled foot pedal with three discrete actuator positions (“Min”, “Mid”, “Max”). When compared via frame-by-frame motion analysis, the motorized system reduced tip variance by approximately threefold over manual methods. In addition, in in vitro gelatin trials, the motorized injector achieved significantly higher placement accuracy versus the manual injector, which suffered from occasional complete misplacements. The novel motorized retinal sheet injector markedly improves stability and placement accuracy relative to manual methods, potentially reducing complications...

Landscape expansion microscopy reveals interactions between membrane and phase-separated organelles.

Wed, 4 Feb 2026 00:00:00 +0000

Landscape expansion microscopy (land-ExM) is a light microscopy technique that visualizes both the lipid and protein ultrastructural context of cells. Achieving this level of detail requires both superresolution and a high signal-to-noise ratio. Although expansion microscopy (ExM) provides superresolution, obtaining high signal-to-noise images of both proteins and lipids remains challenging. land-ExM overcomes this limitation by using self-retention trifunctional anchors to significantly enhance protein and lipid signals in expanded samples. This improvement enables the accurate visualization of diverse membrane organelles and phase separations, as well as the 3D visualization of their contact sites. As a demonstration, we revealed triple-organellar contact sites among the stress granule, the nuclear tunnel, and the nucleolus. Overall, land-ExM offers a high-contrast superresolution platform that advances our understanding of how cells spatially coordinate interactions between...

Frequency and leg stiffness adaptation in human vertical hopping before, during and after added load.

Fri, 30 Jan 2026 00:00:00 +0000

Terrestrial animal gaits often use spring-like mechanics to enhance movement economy through elastic energy cycling. Hopping is a relatively simple, constrained task, yet retains essential features of bouncing gaits, requiring cyclic regulation of limb stiffness and generation of high muscle forces to support body weight and enable elastic energy cycling. We investigated how humans adjust hopping frequency and leg stiffness before, during, and after experiencing added load. Eighteen participants hopped bipedally for 90 seconds per trial, with hop frequency and height unconstrained, while kinematic, ground reaction force, and ankle muscle electromyographic (EMG) data were collected. We analysed mechanics across four conditions: initial body weight (BWi), two added mass trials (+10% and +20% BW), and final body weight (BWf). With added mass, participants increased leg stiffness and maintained a consistent hopping frequency (∼2.15 Hz); yet, when returning to BWf, the elevated leg...

Neutralizing Monoclonal Antibody Use and COVID-19 Infection Outcomes

Wed, 28 Jan 2026 00:00:00 +0000

Importance: Evidence on the effectiveness and safety of COVID-19 therapies across a diverse population with varied risk factors is needed to inform clinical practice. Objective: To assess the safety of neutralizing monoclonal antibodies (nMAbs) for the treatment of COVID-19 and their association with adverse outcomes. Design, Setting, and Participants: This retrospective cohort study included 167 183 patients from a consortium of 4 health care systems based in California, Minnesota, Texas, and Utah. The study included nonhospitalized patients 12 years and older with a positive COVID-19 laboratory test collected between November 9, 2020, and January 31, 2022, who met at least 1 emergency use authorization criterion for risk of a poor outcome. Exposure: Four nMAb products (bamlanivimab, bamlanivimab-etesevimab, casirivimab-imdevimab, and sotrovimab) administered in the outpatient setting. Main Outcomes and Measures: Clinical and SARS-CoV-2 genomic sequence data and propensity-adjusted...

Differences in 10–20 Hz ‘shock’ attenuation emerge between injured and uninjured runners across a 30-minute run

Wed, 28 Jan 2026 00:00:00 +0000

Running is associated with high rates of injury. One mechanism that has been proposed to contribute to running injury is greater exposure to 10-20 Hz frequencies. Typically, these frequencies are attenuated (decreased in power) as they travel up the body, however, attenuation may be compromised as runners become fatigued. Here, we report the first ever comparison of 10-20 Hz frequency attenuation in injured and uninjured runners across a fatiguing run. Thirty-one runners (16 uninjured; 15 previously injured; 14 female; 17 male; age 31.6 ± 12.6 years) ran overground for 30-minutes while accelerations were measured at the tibia, gastrocnemius, sacrum, and head using tri-axial inertial measurement units. Power spectral density was calculated at each location and transfer functions between locations were used to quantify attenuation. Across the 30-minute run, fatigue was recorded using Borg's rating of perceived exertion and percent maximum heart rate. Between-group...

Analysis of yeast's ORF upstream regions by parallel processing, microarrays, and computational methods.

Wed, 28 Jan 2026 00:00:00 +0000

We use a network of workstations to compute all pairwise alignments of the 500 bp upstream regions of 6,225 yeast ORFs (Open Reading Frames). We correlate the alignments with DNA microarray expression data from budding yeast cells over an oxidative stress time course. We confirm on a genomic scale that, in general, genes with extremely similar upstream regions have similar activity levels, even when located on different chromosomes. As the difference in upstream regions increases, the correlation rapidly drops towards zero. Divergent ORFs with overlapping upstream regions do not seem to be correlated in any way. The pairwise alignments coupled with the expression data, together with other computational techniques, suggest a few new putative regulatory binding sites that can be tested experimentally. Finally, we investigate the inherent symmetry present in the two strands of the yeast genome. We show that it extends at least all the way up to 9-mers and is likely to result from...

The Influence of Social Determinants on Receiving Outpatient Treatment with Monoclonal Antibodies, Disease Risk, and Effectiveness for COVID-19

Wed, 28 Jan 2026 00:00:00 +0000

The Influence of Social Determinants on Receiving Outpatient Treatment with Monoclonal Antibodies, Disease Risk, and Effectiveness for COVID-19

Subcutaneous Lactate Correlates With Arterial Lactate in Severe Combined Trauma and Shock in Swine

Mon, 26 Jan 2026 00:00:00 +0000

INTRODUCTION: Changes in blood lactate (Lac) carry prognostic value in pathologic processes and guide decision-making on therapeutic interventions. This feasibility study evaluated a new wearable continuous lactate monitor (CLM) currently undergoing preclinical validation in severe combat-relevant porcine trauma models. PURPOSE: Assess the performance of CLM compared to arterial blood gas (ABG) analysis. HYPOTHESIS: CLM-derived Lac values correlate with ABG Lac. METHODS: Female Yorkshire swine (50-60 kg, N = 6) were anesthetized, mechanically ventilated, subjected to a combination of the following injuries: bilateral pulmonary contusion (PC), traumatic brain injury (TBI), or hemorrhagic shock (HEM): (PC N = 3, PC + TBI N = 1; PC + HEM N = 1; PC + TBI + HEM N = 1). Animals were managed with immediate application of veno-venous extracorporeal life support. Two CLMs were placed in the skin of the lower abdomen. ABG analysis was performed using a GEM Premier 4000 [Werfen, Bedford,...

Label-free human skin imaging with enhanced molecular contrast via time-resolved fluorescence and advanced phasor analysis

Mon, 26 Jan 2026 00:00:00 +0000

Current state-of-the-art clinical skin imaging using label-free multiphoton microscopy (MPM) faces challenges due to limited molecular specificity, which hampers the accurate characterization of skin tissues because of overlapping fluorescence signals from multiple molecular components. In this study, we present a novel approach to enhance molecular contrast in MPM clinical skin imaging by leveraging advanced strategies to effectively unmix the various endogenous fluorophores present in the skin with the performance capabilities of a recently developed imaging platform for in vivo time-resolved fluorescence imaging of human skin. By identifying phasor positions of key endogenous skin fluorophores – such as keratin, melanin, free NADH, and protein-bound NADH – we effectively perform multicomponent unmixing in different skin types and conditions, including those with varying levels of pigmentation and metabolic states. The phasor analysis allows for the mapping and quantification...

Two-step regression analysis approach to assess burn wound severity using spatial frequency domain imaging

Mon, 26 Jan 2026 00:00:00 +0000

Significance: Prompt care is essential for burn wound recovery. Spatial frequency domain imaging (SFDI) has previously shown promise in predicting healing outcomes across burn severity grades. This study builds on that by demonstrating calibrated reflectance images ( ) from SFDI can estimate thermally induced collagen denaturation depth (CDD), a histology-based metric of burn severity linked to healing outcomes. These findings may simplify future hardware design by clarifying contrast sources in SFDI. Aim: To develop predictive models for: 1) Day-1 postburn CDD using SFDI and 2) Day-28 healing outcomes using day-1 CDD. Approach: Using a previously reported graded-severity porcine burn model ( ) with eight contact durations (5 to 40 s), we collected SFDI and color images on days 0, 1, 3, 7, 14, 21, and 28. Histological analysis using Picrosirius red staining and polarization microscopy was performed on days 1, 7, 14, 21, and 28 to assess CDD. Healing outcomes were clinically...

Multidimensional mapping of stimulation-responsive regulatory elements and candidate causal variants in T cell activation.

Mon, 12 Jan 2026 00:00:00 +0000

Genome-wide association studies (GWASs) have elucidated numerous noncoding variants linked to immune-related disorders, yet the intricate context-specific mechanisms governing their effects remain poorly defined. Here, we leverage CD4⁺ T cell activation as a model to integrate multilayered genomic data and interrogate the dynamic regulatory mechanisms underpinning these genetic associations. We have applied a cistromic strategy to systematically identify and prioritize stimulation-responsive cis-regulatory elements (CREs) and key genes essential for T cell activation. Using capture Hi-C and tiling CRISPR activation screening at the CD28 locus, we reveal a pivotal CRE harboring a causal small insertion variant, rs5837875, that modulates CD28 activation in an allele-specific manner. Mechanistically, we demonstrate that ZNF384 mediates stimulation-responsive chromatin looping between the rs5837875-containing enhancer and the CD28 promoter, culminating...

Modeling the interplay of sex hormones in cardiac hypertrophic signaling

Fri, 26 Dec 2025 00:00:00 +0000

Biological sex plays a crucial role in the outcomes of cardiac health and therapies. Sex hormones are known to strongly influence cardiac remodeling through intracellular signaling pathways, yet their underlying mechanisms remain unclear. To address this need, we developed and validated a logic-based systems biology model of cardiomyocyte hypertrophy that, for the first time, incorporates the effects of both estradiol (E2) and testosterone (T) alongside well-established hypertrophic stimuli (Strain, angiotensin II (AngII), and endothelin-1 (ET-1)). We qualitatively validated the model to literature data with 82% agreement. Quantitative validation was done by simulating the impact of the inputs (E2, T, Strain, AngII, and ET-1) on cardiac hypertrophy, captured as change in CellArea. We perturbed the validated model to examine the differential response to hypertrophy and identify changes in influential and sensitive downstream nodes for a pre-menopausal female, post-menopausal female,...

Regional and Sexual Dimorphism in Murine Skeletal Responses to Osteocytic HIF Pathway Modulation

Wed, 24 Dec 2025 00:00:00 +0000

Hypoxia-inducible factors (HIFs) are transcription factors stabilized under hypoxia and degraded under normoxia by the E3 ubiquitin ligase Von Hippel-Lindau (Vhl). In osteocytes, the central orchestrators of bone homeostasis, Vhl and HIFs promote an osteoanabolic transcriptional program. In this study, we assessed unique impacts of osteocytic Vhl deletion versus individual HIF-α paralog stabilization on bone structure, mineralization, and mechanics as a function of sex and skeletal region. Microcomputed tomography revealed that osteocytic Vhl deletion robustly increased trabecular bone mass in both sexes and at both axial and appendicular regions, while HIF-2α accumulation increased femoral metaphyseal bone mass in both sexes while enhancing vertebral bone mass only in males. Vhl deletion paradoxically reduced mineral heterogeneity in male vertebrae, despite raising peak and mean calcium content in both sexes. In contrast, HIF-2α stabilization impaired cortical mineralization...

Impact of common variants on brain gene expression from RNA to protein to schizophrenia risk

Sat, 20 Dec 2025 00:00:00 +0000

Genetic variants influencing gene expression have been extensively studied at the transcriptional level. How these variants affect downstream processes remains unclear. We quantitated ribosome occupancy in prefrontal cortex samples from the BrainGVEX cohort and integrated these data with transcriptomic and proteomic profiles from the same individuals. Through cis-QTL mapping, we identified genetic variants associated with transcript level (eQTLs), ribosome occupancy (rQTLs), and protein level (pQTLs). Notably, only 34% of eQTLs have their effects propagated to the protein levels, suggesting widespread post-transcriptional attenuation. Using both a gene-based approach and a variant-based approach we identified omics-specific QTLs that associated with brain disorder GWAS signals and found the majority of them to be driven predominantly by transcriptional regulation. Consistently, using a TWAS approach, we identified 74 SCZ risk genes across the three omics layers, 52 were discovered...

Medicare’s Bundled Payments For Care Improvement Initiative Maintained Quality Of Care For Vulnerable Patients

Fri, 19 Dec 2025 00:00:00 +0000

The Bundled Payments for Care Improvement (BPCI) initiative established four models to test whether linking payments for an episode of care could reduce Medicare payments while maintaining or improving quality. Evaluations concluded that model 2, the largest, generally lowered payments without reducing quality for the average beneficiary, but these global results could mask adverse findings among vulnerable subpopulations. We analyzed changes in emergency department visits, unplanned hospital readmissions, and all-cause mortality within ninety days of hospital discharge among beneficiaries with one or more of three vulnerable characteristics-dementia, dual eligibility for Medicare and Medicaid, and recent institutional care-in 105,458 beneficiary episodes in the period October 2013-December 2016. The results for twelve types of medical and surgical BPCI episodes were evaluated relative to results in matched comparison groups. Our findings suggest that BPCI model 2 did...

Two-visit Repeatability Of VL and PFC Hemoglobin Thresholds In Ramp Exercise

Fri, 19 Dec 2025 00:00:00 +0000

Two-visit Repeatability Of VL and PFC Hemoglobin Thresholds In Ramp Exercise

Short-wave infrared (SWIR) spectroscopy and imaging of biological tissues: a decade of advancements (2016-2025)

Fri, 19 Dec 2025 00:00:00 +0000

Significance: Short-wave infrared (SWIR) light has recently gained popularity in tissue spectroscopy and imaging applications for a wide range of biomedical applications, primarily due to advancements in hardware (e.g., cameras). Aim: We aim to provide a detailed review of SWIR-based biomedical optics studies from the past decade, during which there has been a proliferation of SWIR-based tissue-optics studies. Approach: We report literature occurring after the publication of our previous (2015) review of this space, describing next-generation SWIR-based techniques that hold significant promise for enhanced in vivo tissue characterization and clinical translation. Results: Interest from the biophotonics field in SWIR technology is typically attributable to (1) the capability of SWIR light to provide greater sensitivity to chromophores such as water and lipids, with absorption peaks not as prominent in the visible-to-near-infrared (VIS-NIR) spectral region, and (2) the...

Early detection of coronary artery disease using low-dose CT perfusion: An experimental western fat diet study

Wed, 3 Dec 2025 00:00:00 +0000

PURPOSE: To evaluate changes in myocardial blood flow (MBF) and coronary flow reserve (CFR) over time in a swine model fed a Western diet (WD) using a novel low-dose myocardial CT perfusion technique. MATERIALS AND METHODS: Ten swine with low-density lipoprotein receptor mutations were fed a WD starting at week 0 and imaged after 12, 16, 17, 18, 19, or 23 weeks of WD exposure (mean ± SD: 17.1 ± 3.25 weeks; range 12-23 weeks) using a 320-slice CT scanner under rest and adenosine-induced stress (240 μg/kg/min). Peripheral contrast injection (370 mgI/mL, 0.5 mL/kg, 5 mL/s) with a diluted chaser (30:70 contrast/saline) was followed by bolus tracking and a single-volume scan acquired at peak aortic enhancement (100 kVp, 200 mA). A first-pass analysis model derived MBF (mL/min/g) from bolus-tracking and scan data. Rest and stress MBF were used to compute CFR. Correlations between WD duration and both stress MBF and CFR were assessed....

Real-time tracking of the Bragg peak during proton therapy via 3D protoacoustic Imaging in a clinical scenario

Wed, 3 Dec 2025 00:00:00 +0000

Proton radiotherapy favored over X-ray photon therapy due to its reduced radiation exposure to surrounding healthy tissues, is highly dependent on the accurate positioning of the Bragg peak. Existing methods like PET and prompt gamma imaging to localize Bragg peak face challenges of low precision and high complexity. Here we introduce a 3D protoacoustic imaging with a 2D matrix array of 256 ultrasound transducers compatible with 256 parallel data acquisition channels provides real-time imaging capability (up to 75 frames per second with 10 averages), achieving high precision (5 mm/5% Gamma index shows accuracy better than 95.73%) at depths of tens of centimeters. We have successfully implemented this method in liver treatment with 5 pencil beam scanning and in prostate cancer treatment on a human torso phantom using a clinical proton machine. This demonstrates its capability to accurately identify the Bragg peak in practical clinical scenarios. It paves the way for adaptive radiotherapy...

Early life environment moderates association of body composition and internalizing problems in adolescence

Mon, 24 Nov 2025 00:00:00 +0000

Metabolic and depressive disorders are major chronic global health concerns, often co-occurring and mutually reinforcing each other. Thus, understanding risk and protective factors underlying their development is crucial for identifying effective preventive strategies. Participants included N = 10,446 participants (31,418 observations) from the Adolescent Brain Cognitive Development Study aged 10-15 years. Primary outcomes were internalizing problem scores, and random slopes quantifying the within-person coupling between waist-to-height ratio and internalizing problems. Predictors included early-life adversity measures and potentially protective environments measured at the family, community, peer, and school level. Early-life adversity and protective environment scores were examined as moderators of the coupling between body composition and internalizing problems. Early-life adversity was significantly associated with the magnitude of within-person coupling (random slope); individuals...

Assessment of mitochondrial viability under calcium Stress: Insights for mitochondrial transplantation

Thu, 20 Nov 2025 00:00:00 +0000

Mitochondrial transplantation has emerged as a promising cardioprotective strategy for ischemia-reperfusion injury, aiming to restore bioenergetic function by delivering healthy mitochondria to damaged tissue. However, conflicting reports exist regarding whether mitochondria can survive exposure to the calcium-rich extracellular environment, such as the bloodstream, prior to cellular uptake. Resolving this question is essential for advancing the therapeutic use of mitochondria in clinical settings. Isolated mitochondria from L6 rat skeletal muscle cells were incubated with physiologic (1.3 mM), sub-physiologic (0.65 mM), and supraphysiologic (2.6 mM) concentrations of calcium. Mitochondrial membrane potential was assessed using MitoTracker™ Red FM fluorescence, and structural integrity was evaluated using impedance-based Coulter counter analysis over a 12-hour time course. Mitochondria exposed to 1.3 mM calcium retained 90-95 %...

The inherent fragility of collective proliferative control

Thu, 20 Nov 2025 00:00:00 +0000

Tissues achieve and maintain their sizes through active feedback, whereby cells collectively regulate proliferation and differentiation to facilitate homeostasis and the ability to respond to disturbances. One of the best understood feedback mechanisms-renewal control-achieves remarkable feats of robustness in determining and maintaining desired sizes. Yet in a variety of biologically relevant situations, we show that stochastic effects should cause rare but catastrophic failures of renewal control. We define the circumstances under which this occurs and raise the possibility that such events account for important non-genetic steps in the development of cancer. We further suggest that the spontaneous stochastic reversal of these events could explain cases of cancer normalization or dormancy following treatment. Indeed, we show that the kinetics of post-treatment recurrence for many cancers are often better fit by a model of stochastic re-emergence due to the loss of collective...

Consensus guidelines for cellular label-free optical metabolic imaging: ensuring accuracy and reproducibility in metabolic profiling

Wed, 19 Nov 2025 00:00:00 +0000

Significance: Cellular metabolism plays a central role in health and disease, making its study critical for advancing diagnostics and therapies. Label-free optical metabolic imaging using endogenous fluorescence from reduced nicotinamide adenine dinucleotide (phosphate) [NAD(P)H] and flavin adenine dinucleotide (FAD) provides nondestructive, high-resolution insights into metabolic function and heterogeneity from the sub-cellular to the tissue level. Standardized approaches are essential to ensure reproducibility and comparability across studies. Aim: We aim to establish a consensus framework for the acquisition, calibration, and reporting of microscopic imaging metabolic function assessments based on fluorescence intensity and lifetime measurements of NAD(P)H and FAD. Approach: We present best practices for calibrating, analyzing, and reporting fluorescence intensity-based optical redox ratios and fluorescence lifetime data using multiexponential fitting and phasor analysis. Guidelines...

Autoimmune antibodies and systemic inflammatory markers are prevalent and associated with cognition in individuals aged 90+

Tue, 11 Nov 2025 00:00:00 +0000

BackgroundWhile recent studies have found associations between markers of autoimmunity/inflammation and cognitive performance in individuals aged 60-90, these findings remain unexplored in individuals aged 90 and above.ObjectiveTo examine the prevalence of autoimmune antibodies and raised inflammatory markers and their associations with cognition in participants aged 90 + .MethodsWe included participants with serological testing from The 90+ Study, a community-based longitudinal study in southern California. For measures of autoimmunity, we evaluated antinuclear, antineutrophil cytoplasmic (ANCA), rheumatoid factor, double stranded DNA, antithyroglobulin, and thyroid peroxidase antibodies. For inflammatory markers, we examined interleukin-6 (IL-6) and erythrocyte sedimentation rate (ESR). To examine the relationship between autoimmune antibodies and inflammatory markers with cognitive performance, we ran linear mixed effects models.ResultsAmong 201 participants (mean age 94.8...

Complementary biomolecular coassemblies direct energy transport for cardiac photostimulators

Wed, 8 Oct 2025 00:00:00 +0000

Charge and energy transport within living systems are fundamental processes that enable the autonomous function of excitable cells and tissues. To date, localized control of these transport processes has been enabled by genetic modification approaches to render light sensitivity to cells. Here, we present peptidic nanoassemblies as constituents of a cardiac biomaterial platform that leverages complementary sequence interactions to direct photoinduced energy transport at the cellular interface. Photophysical characterizations and conductivity measurements confirm the occurrence of energy/charge transfer and photocurrent generation upon optical excitation in both dry and electrolytic environments. Comparing an electrostatic sequence pair against a sequence-matched donor-acceptor coassembly, we demonstrate that the sequence design with charge complementarity shows more prominent photocurrent behavior. With the flanking bioadhesive units, the primary and stem cell-derived cardiomyocytes...

Optimizing automated detection of high frequency oscillations using visual markings does not improve SOZ localization

Tue, 7 Oct 2025 00:00:00 +0000

OBJECTIVE: High frequency oscillations (HFOs) are a biomarker of the seizure onset zone (SOZ) and can be visually or automatically detected. In theory, one can optimize an automated algorithm's parameters to maximize SOZ localization accuracy; however, there is no consensus on whether or how this should be done. Therefore, we optimized an automated detector using visually identified HFOs and evaluated the impact on SOZ localization accuracy. METHODS: We detected HFOs in intracranial EEG from 20 patients with refractory epilepsy from two centers using (1) unoptimized automated detection, (2) visual identification, and (3) automated detection optimized to match visually detected HFOs. RESULTS: SOZ localization accuracy based on HFO rate was not significantly different between the three methods. Across patients, visually optimized detector settings varied, and no single set of settings produced universally accurate SOZ localization. Exploratory analysis suggests that, for many patients,...

Label-free multiphoton microscopy of human skin: longitudinal studies capturing cell dynamics

Wed, 1 Oct 2025 00:00:00 +0000

This study presents recent advances in an imaging platform developed by our lab, the fast large area multiphoton exoscope (FLAME), a microscope designed for clinical skin imaging. Its dual-scanning modality enables reliable, cellular-scale imaging of the same skin locations over extended time periods across areas up to 1 cm². Enabling fluorescence lifetime imaging microscopy, this device, for the first time in vivo, allows detailed longitudinal tracking of cellular dynamics in human skin, such as responses to injury, significantly advancing the capabilities of dermatological research. By overcoming previous limitations in large-area, high-resolution skin imaging, FLAME opens new opportunities for monitoring therapy responses, tracking cellular dynamics, and understanding skin biology at the cellular level.

Multivariate Linear Regression Approach to Predicting Burn Depth Using Spatial Frequency Domain Imaging

Wed, 1 Oct 2025 00:00:00 +0000

We applied multivariate linear regression to spatial frequency domain imaging (SFDI) data to predict burn depth, as determined by histological grading. To reduce the variable space, we preliminarily employed the minimum redundancy maximum relevance algorithm.

Fast large-area multiphoton exoscope for label-free in vivo imaging of immune cells in human skin

Wed, 1 Oct 2025 00:00:00 +0000

Fast large-area multiphoton exoscope for label-free in vivo imaging of immune cells in human skin

Highly multiplexed spectral FLIM via physics informed data analysis

Wed, 1 Oct 2025 00:00:00 +0000

Spectral fluorescence lifetime imaging (S-FLIM) allows for the simultaneous deconvolution of signal from multiple fluorophore species by leveraging both spectral and lifetime information. However, existing analyses still face multiple difficulties in decoding information collected from typical S-FLIM experiments. These include: using information from pre-calibrated spectra in environments that may differ from the cellular context in which S-FLIM experiments are performed; limitations in the ability to deconvolute species due to overlapping spectra; high photon budget requirements, typically about a hundred photons per pixel per species. Yet information on the spectra themselves are already encoded in the data and do not require pre-calibration. What is more, efficient photon-by-photon analyses are possible reducing both the required photon budget and making it possible to use larger budgets in order to discriminate small differences in spectra to resolve spatially co-localized...

CDCP1/mitochondrial Src axis increases electron transport chain function to promote metastasis in triple-negative breast cancer

Wed, 1 Oct 2025 00:00:00 +0000

BackgroundTriple-negative type of breast cancer (TNBC) has limited therapeutic options and frequently metastasizes, leading to low survival rates. Oxidative phosphorylation (OXPHOS) is a driver of TNBC metastasis, but the signaling underlying this metabolic change is poorly understood.MethodsWe performed metabolic assays and assessed migratory and metastatic potential in cells with manipulated CDCP1/mitochondrial Src signaling.ResultsWe show that the pro-metastatic cell surface protein CUB-domain containing protein 1 (CDCP1) activates Src kinase localized in mitochondria, which potently induces OXPHOS and TNBC migration. Genetic targeting of either CDCP1 or mitochondrial Src, as well as pharmacological inhibition of Src reduce OXPHOS in vitro. We further show that mitochondrial Src increases OXPHOS by stimulating Complex I activity in the electron transport chain. Importantly, rescuing Complex I activity in cells devoid of CDCP1/mitochondrial Src signaling restores both OXPHOS...

An open, integrated platform for multiplexed bioluminescence microscopy

Wed, 1 Oct 2025 00:00:00 +0000

We report an imaging package to democratize all-in-one bioluminescence and fluorescence microscopy. The platform comprises three tools: PhasorViewer, a visualization suite to design experiments and identify optimal probe combinations; PhasorScope, an open-source, cost-effective microscopy framework to upgrade conventional microscopes; and PhasorAnalysis, a dedicated, user-friendly analysis pipeline to quantify phasor imaging data. We demonstrate the utility of the platform for multiplexed, simultaneous fluorescence and bioluminescence imaging with readily accessible optical reporters.

In Vitro Validation of Dynamic Light Scattering Imaging on Fluid Phantoms

Wed, 1 Oct 2025 00:00:00 +0000

Dynamic Light Scattering Imaging (DLSI) quantifies fluid flow and scattering by estimating correlation time and scattering ratios. This study demonstrates DLSI's sensitivity to volumetric flow and flow dynamics, optimizing parameter settings for biomedical imaging applications.

Single-cell spatial transcriptomics reveals distinct patterns of dysregulation in non-neuronal and neuronal cells induced by the Trem2R47H Alzheimer’s risk gene mutation

Thu, 11 Sep 2025 00:00:00 +0000

The R47H missense mutation of the TREM2 gene is a known risk factor for development of Alzheimer’s Disease. In this study, we analyze the impact of the Trem2R47H mutation on specific cell types in multiple cortical and subcortical brain regions in the context of wild-type and 5xFAD mouse background. We profile 19 mouse brain sections consisting of wild-type, Trem2R47H, 5xFAD and Trem2R47H; 5xFAD genotypes using MERFISH spatial transcriptomics, a technique that enables subcellular profiling of spatial gene expression. Spatial transcriptomics and neuropathology data are analyzed using our custom pipeline to identify plaque and Trem2R47H-induced transcriptomic dysregulation. We initially analyze cell type-specific transcriptomic alterations induced by plaque proximity. Next, we analyze spatial distributions of disease associated microglia and astrocytes, and how they vary between 5xFAD and Trem2R47H; 5xFAD mouse models. Finally, we analyze the impact of the Trem2R47H mutation on...

An AAV capsid proposed as microglia-targeting directs genetic expression in forebrain excitatory neurons

Wed, 10 Sep 2025 00:00:00 +0000

A newly developed capsid AAV-MG1.2 was reported to mediate specific microglial transduction. However, we find that AAV-MG1.2 actually enables specific genetic access to excitatory neurons in forebrain regions including hippocampal formation and visual cortex but does not confer expression in microglia or astrocytes in vivo. Furthermore, we find that AAV-MG1.2 specifically labels the deep layer of the CA1 pyramidal layer in a titer-dependent manner. We show that AAV-MG1.2-Cre can be used to genetically target excitatory neurons for cell-type-specific neural circuit mapping studies. We also find that AAV-MG1.2 conserves specificity for excitatory neurons in rat hippocampus. Thus, the AAV-MG1.2 presents a useful viral-genetic tool for targeting excitatory neurons in the forebrain across different species.

Regulation of feather length: FGF/IGF signaling and NOTCH/YAP modulation of progenitor cell topology

Fri, 29 Aug 2025 00:00:00 +0000

The regulation of organ size is a fundamental biological question. This study investigates how feather length is regulated in chickens. We found that collar bulge stem cell zones vary in size: main sickle > lesser sickle > contour feathers. During growth, IGF and FGF9 signaling are highly expressed, while BMP, WIF1, and FGF18 increase toward growth termination. Functional assays show that insulin-like growth factor/fibroblast growth factor signaling promotes feather elongation via tyrosine kinase receptor signaling. Single-cell RNA sequencing analysis reveals accelerated differentiation of keratinocytes in short contour feathers compared to long sickle feathers. In Phoenix chickens, superlong main sickle feathers exhibit specialized stem cell zones with enhanced DLL1 expression and expanded intermediate-layer cell clusters with dynamic interactions involving NOTCH1/DLL1, YAP1, and WNT signaling in progenitor...

Retinal progenitor cells (jCell) for retinitis pigmentosa

Wed, 27 Aug 2025 00:00:00 +0000

Objective: To assess the safety and tolerability of intravitreal injection of human retinal progenitor cells (RPCs) at multiple dose levels in adults with non-syndromic retinitis pigmentosa (RP). Design: A prospective, multicenter, open-label, single-arm, Phase I/IIa safety study of RPCs in adults with RP (n = 28). Two patient cohorts were studied: Cohort 1: BCVA no better than 20/200 and no worse than Hand Motions, and Cohort 2: BCVA no better than 20/40 and no worse than 20/200). Subjects: Adults (n = 28) with a clinical diagnosis of RP confirmed by electroretinogram, consenting to gene mutation typing for genes involved in inherited retinal degenerations and related disorders, and willing to undergo human leukocyte antigen (HLA) typing. Methods: Subjects, who were not selected for genotype, were divided across the two vision cohorts with each receiving a single intravitreal injection of one of: 0.5, 1.0, 2.0, or 3.0 × 10⁶ allogeneic RPCs. Initially,...

A pan-beta-coronavirus vaccine bearing conserved and asymptomatic B- and T-cell epitopes protects against highly pathogenic Delta and highly transmissible Omicron SARS-CoV-2 variants

Wed, 27 Aug 2025 00:00:00 +0000

Over the last five years of the COVID-19 pandemic, the repetitive mutations and deletions in the SARS-CoV-2 genome, primarily targeting the Spike gene, resulted in the emergence of multiple viral variants and sub-variants. The non-updated mismatched Spike-based sub-unit vaccines are less effective due to the ability of these SARS-CoV-2 variants and sub-variants to evade vaccine-induced humoral immunity. To reduce reliance on neutralizing antibodies and prevent potential mismatches between circulating variants, sub-variants, and the vaccines, we have identified highly conserved Spike and non-Spike viral epitopes associated with protective asymptomatic B- and T-cell immune responses, respectively. We demonstrated that unvaccinated asymptomatic patients with COVID-19 recognized these conserved B- and T-cell epitopes. Using the mRNA-LNP-based antigen delivery system, we developed a multi-epitope vaccine that incorporates the conserved B-cell epitopes, CD4⁺ T-cell epitopes,...

Supernova pointing capabilities of DUNE

Fri, 15 Aug 2025 00:00:00 +0000

The determination of the direction of a stellar core collapse via its neutrino emission is crucial for the identification of the progenitor for a multimessenger follow-up. A highly effective method of reconstructing supernova directions within the Deep Underground Neutrino Experiment (DUNE) is introduced. The supernova neutrino pointing resolution is studied by simulating and reconstructing electron-neutrino charged-current absorption on and elastic scattering of neutrinos on electrons. Procedures to reconstruct individual interactions, including a newly developed technique called “brems flipping,” as well as the burst direction from an ensemble of interactions are described. Performance of the burst direction reconstruction is evaluated for supernovae happening at a distance of 10 kpc for a specific supernova burst flux model. The pointing resolution is found to be 3.4 degrees at 68% coverage for a perfect interaction-channel classification and a fiducial mass of 40 kton,...

PyRESP: A flexible program for polarizable force field parameterizations

Wed, 13 Aug 2025 00:00:00 +0000

PyRESP: A flexible program for polarizable force field parameterizations

Improved temporal speckle contrast model for slow and fast dynamic: effect of temporal correlation among neighboring pixels

Tue, 5 Aug 2025 00:00:00 +0000

Significance

Speckle contrast analysis, whether spatial or temporal, is a valuable optical technique extensively utilized in medical and engineering domains owing to its simplicity, affordability, and noninvasive nature. It relies on statistical analysis of the dynamic speckle pattern produced by the sample under examination, offering insights into the sample's dynamics. However, challenges persist in precisely measuring temporal speckle contrast, particularly for slow dynamic samples. Existing mathematical models fail to accurately reflect the experimental data, which could result in misinterpretation of the analyzed results.

Aim

To overcome these constraints, we present a mathematical model that incorporates the correlation between adjacent pixels. We specifically concentrate on temporal correlation, i.e., the relationship between neighboring frames, to compute the temporal speckle contrast.

Approach

We theoretically replicate the statistical analysis typically...

Combined XA/CT Imaging for Bone Density and Elasticity Evaluation: A Simulation Study

Tue, 5 Aug 2025 00:00:00 +0000

Osteoporosis is a significant public health concern that affects old adults and individuals with certain medical conditions. In this work, we demonstrate the proof of the principle of combining the emerging new radiological imaging technique, X-ray-induced acoustic (XA) imaging, and X-ray computed tomography (CT) for bone density and elasticity evaluation. This combined method is intended for use in single scanner that can perform both XA imaging and CT imaging simultaneously for the purpose of providing accurately registered anatomical localization of structures seen in the CT image to extract the elasticity information in XA imaging. We demonstrate that our nonlinear optimization algorithm can acquire the speed of sound information for bone. By combining the speed of sound and density information from CT, we can calculate the elasticity with an error of less than 1%. We conclude that using CT information as prior information is a feasible way to obtain elasticity information...

CDC42-effector interaction inhibitors alter patterns of vessel arborization in skin and tumors in vivo

Tue, 5 Aug 2025 00:00:00 +0000

Skin tumors require a vascular supply to grow beyond 1 mm in depth, yet existing anti-angiogenesis agents are largely ineffective at treating melanoma tumors arising in skin. Using an approach that integrates antibody infusion, optical tissue clearing, multiphoton imaging, and vessel tracing, we identified the CDC42 GTPase RhoJ as a critical regulator of skin vessel arborization. Small molecules that target both RhoJ and CDC42 (CDC42 interaction inhibitors), but not those that target only CDC42 (CASIN), inhibit vessel branching in mouse skin in vivo and vascular organoids in vitro. This anti-vascular effect was not limited to skin, as CDC42 interaction inhibitors blocked melanoma tumor vascularization and inhibited tumor growth to a similar degree as Braf inhibitors. Taken together, this work identifies small molecules that target RhoJ as selective tumor anti-vascular agents. RhoJ-targeting drugs have a particular proclivity for blocking skin vascularization, nominating...

Harnessing Dark Core Skyrmions for Optical Trapping and Imaging

Tue, 5 Aug 2025 00:00:00 +0000

Dark core Skyrmions are three-dimensional dark regions surrounded by vectorial light, created using polarization-dependent wavefront shaping, enabling enhanced uniformity, stability. We discuss their utility in microscopy and optical trapping.

Uncovering minimal pathways in melanoma initiation

Tue, 5 Aug 2025 00:00:00 +0000

Melanomas are genetically heterogeneous, displaying mitogen-activated protein kinase mutations and homozygous loss of tumor suppressor genes. Mouse models combining such mutations produce fast-growing tumors. In contrast, rare, slow-growing tumors arise in mice combining Braf activation with heterozygous loss of Pten. Here we show that similar tumors can arise in albino mice bearing only a Braf mutation. Incidence kinetics suggest a stochastic event underlies tumorigenesis in tumors that arise with only a Braf mutation, yet de novo mutations or structural variants that could explain the incidence of most tumors could not be found. Single-cell transcriptomics of tumors identify a cell type resembling “neural crest-like” cells in human and mouse melanomas. These exist in normal mouse skin, expand upon Braf activation, and persist through serial transplantation; analyses of gene expression suggest they serve as precursors of malignant cells. This state may serve as an intermediate...

Enhancing burn wound classification with ensemble learning using spatial frequency domain imaging applied to in-vivo porcine skin

Tue, 5 Aug 2025 00:00:00 +0000

Assessing burn severity is crucial for appropriate care and treatment to reduce the risk of scarring and infection. Currently, practitioners rely on visual and tactile assessments, which can be subjective and potentially misleading. A more objective method recently employed in a swine model involves spatial frequency domain imaging (SFDI), a wide-field, noninvasive technique that deduces tissue optical properties using light propagation models. Recent studies have advanced this approach by using machine learning (ML) algorithms to predict burn severity from calibrated reflectance data o btained via SFDI, e liminating t he need f or l ight propagation m odels. Data from a porcine model of graded burns was collected using two distinct SFDI systems: the Reflect RS a nd Clarifi RS (Modulim Inc.). The Reflect R S o perates w ith e ight wavelengths f rom 4 70-850 nm modulated a t s ix spatial frequencies, five f rom 0 t o 0 .2/mm a t e qual i ncrements a nd a nother a t 0 .122/mm, w...

Light Scattering Induced by Orbital Angular Momentum Beams in Microparticle Suspensions

Tue, 5 Aug 2025 00:00:00 +0000

We explore the propagation of optical vortices and the conservation of orbital angular momentum (OAM) in scattering media by analyzing the phase characteristics and mode composition of scattered vortex beams. Using micro-sized polystyrene particles across varying concentrations and optical path lengths, we investigate how light scattering depends on the optical properties and thickness of the media.

Polarized microscopy with picrosirius red: potential for reproducible burn depth grading

Tue, 5 Aug 2025 00:00:00 +0000

This research explores the challenges in accurately classifying burn severity and the limitations associated with traditional histology-based model training. Histology, often considered the gold standard for determining burn wound severity, typically employs stains like Hematoxylin and Eosin (H&E) and Masson's Trichrome. However, these methods can yield inconsistent results due to subjective interpretation and variability among professionals who interpret histology. The study investigates the use of Picrosirius Red (PSR) staining combined with polarized microscopy as a potential tool for producing consistent, reproducible, and computer-aided grading of burn histology severity. By analyzing collagen denaturation in burn tissues, preliminary data demonstrates a proportional correlation between the depth of collagen damage and burn contact time. The findings suggest that PSR staining enhances visibility of collagen alterations, potentially leading to more objective assessments...

Improved temporal speckle contrast model for slow and fast dynamic: effect of temporal correlation among neighboring pixels

Sat, 2 Aug 2025 00:00:00 +0000

Significance: Speckle contrast analysis, whether spatial or temporal, is a valuable optical technique extensively utilized in medical and engineering domains owing to its simplicity, affordability, and noninvasive nature. It relies on statistical analysis of the dynamic speckle pattern produced by the sample under examination, offering insights into the sample's dynamics. However, challenges persist in precisely measuring temporal speckle contrast, particularly for slow dynamic samples. Existing mathematical models fail to accurately reflect the experimental data, which could result in misinterpretation of the analyzed results. Aim: To overcome these constraints, we present a mathematical model that incorporates the correlation between adjacent pixels. We specifically concentrate on temporal correlation, i.e., the relationship between neighboring frames, to compute the temporal speckle contrast. Approach: We theoretically replicate the statistical analysis typically conducted...

Multiscale analysis of equatorial sclera anisotropy: Revealing discrepancies in fiber orientation and mechanical properties

Thu, 31 Jul 2025 00:00:00 +0000

The sclera, the eye's primary load-bearing tissue, substantially influences the globe's response to intraocular pressure. Although the mechanical properties of the anterior and posterior segments have been extensively studied, the equatorial sclera's properties remain underexplored, limiting our understanding of ocular conditions like myopia, ocular trauma, and glaucoma. Traditional studies that rely solely on fiber orientation to explain scleral mechanics may overlook the tissue's complex biomechanical behavior. To address this gap, we conducted a comprehensive investigation using ultrasonic elastography, optical coherence elastography, and polarizing light microscopy to analyze the equatorial sclera's anisotropic properties. Our findings reveal a counterintuitive result: Mechanical anisotropy in the equatorial sclera contradicts preferred fiber orientation. This integrated approach not only challenges prevailing models of scleral biomechanics but also provides fundamental insights...

Dorsal root ganglion-targeted analgesic delivery for effective relief of neuropathic pain

Thu, 31 Jul 2025 00:00:00 +0000

Neuropathic pain is a devastating experience for patients and its treatment remains challenging. Dorsal root ganglion (DRG) is currently an important therapeutic target and DRG-targeted analgesic delivery through systemic injection is however not reported. Herein, a disintegrin and metalloproteinase protein 8 (ADAM8), a membrane-anchored protein primarily recognized as a cancer biomarker, is found to be de novo and persistently upregulated in the DRG neurons in spared nerve injury (SNI) and chemotherapy-induced neuropathic pain (CINP), two neuropathic pain models with distinct mechanisms. We thus designed a DRG-targeted delivery strategy using lipid nanoparticles (LNPs), aiming to effectively deliver conventional analgesics to the DRG to improve analgesic effect through blocking pain signal transduction from the periphery to central nervous system. In vitro and in vivo results revealed that LNPs extended the duration of action of the free analgesic from less than...

Intracoronary Optical Coherence Tomography: Technological Innovations and Clinical Implications in Cardiology

Thu, 31 Jul 2025 00:00:00 +0000

Purpose of ReviewTo provide the most up-to-date clinical evidence of intracoronary optical coherence tomography (OCT), and clinical implications to guide future imaging research in cardiology.Recent FindingsIntracoronary OCT has demonstrated advanced system performance and high reproducibility in analyzing atherosclerotic lesions. It is an attractive tool due to its capability for functional classification and superior imaging resolution, enabling precise and reliable tissue assessments. Compared to traditional angiography, OCT has been associated with improved long-term clinical outcomes and serves as an effective tool for optimizing stent selection and post-intervention evaluation. The development of OCT variations and the combination of various intravascular imaging modalities further enhance its diagnostic capabilities, allowing a comprehensive assessment of complex vulnerable lesions and improving risk stratification for patients. SummaryCurrent and evolving system development...

Non‐Uniform Electric Field Manipulation of Chromogenic Peptide Amphiphile Assemblies

Tue, 29 Jul 2025 00:00:00 +0000

This work investigates the influence of dielectrophoretic forces on the structural features and the resulting aggregates of a chromogenic model system, peptide-diacetylene (D₃GV-DA) amphiphiles. Here, we systematically investigate how non-uniform electric fields impact the (i) peptide-directed supramolecular assembly stage and (ii) topochemical photopolymerization stage of polydiacetylenes (PDAs) in a quadrupole-based dielectrophoresis (DEP) device, as well as the (iii) manipulation of D₃GV-DA aggregates in a light-induced DEP (LiDEP) platform. The conformation-dependent chromatic phases of peptide-PDAs are utilized to probe the chain-level effect of DEP exposure after the supramolecular assembly or after the topochemical photopolymerization stage. Steady-state spectroscopic and microscopy analyses show that structural features such as the chirality and morphologies of peptidic 1-D nanostructures are mostly conserved upon DEP exposure, but applying mild,...

Selective Induction of Molecular Assembly to Tissue‐Level Anisotropy on Peptide‐Based Optoelectronic Cardiac Biointerfaces

Tue, 29 Jul 2025 00:00:00 +0000

The conduction efficiency of ions in excitable tissues and of charged species in organic conjugated materials both benefit from having ordered domains and anisotropic pathways. In this study, a photocurrent-generating cardiac biointerface is presented, particularly for investigating the sensitivity of cardiomyocytes to geometrically comply to biomacromolecular cues differentially assembled on a conductive nanogrooved substrate. Through a polymeric surface-templated approach, photoconductive substrates with symmetric peptide-quaterthiophene (4T)-peptide units assembled as 1D nanostructures on nanoimprinted polyalkylthiophene (P3HT) surface are developed. The 4T-based peptides studied here can form 1D nanostructures on prepatterned polyalkylthiophene substrates, as directed by hydrogen bonding, aromatic interactions between 4T and P3HT, and physical confinement on the nanogrooves. It is observed that smaller 4T-peptide units that can achieve a higher degree of assembly order within...

Light-triggered cardiac microphysiological model

Tue, 29 Jul 2025 00:00:00 +0000

Light is recognized as an accurate and noninvasive tool for stimulating excitable cells. Here, we report on a non-genetic approach based on organic molecular phototransducers that allows wiring- and electrode-free tissue modulation. As a proof of concept, we show photostimulation of an in vitro cardiac microphysiological model mediated by an amphiphilic azobenzene compound that preferentially dwells in the cell membrane. Exploiting this optical based stimulation technology could be a disruptive approach for highly resolved cardiac tissue stimulation.

Concentration-Driven Assembly and Sol–Gel Transition of π‑Conjugated Oligopeptides

Tue, 29 Jul 2025 00:00:00 +0000

Advances in supramolecular assembly have enabled the design and synthesis of functional materials with well-defined structures across multiple length scales. Biopolymer-synthetic hybrid materials can assemble into supramolecular structures with a broad range of structural and functional diversity through precisely controlled noncovalent interactions between subunits. Despite recent progress, there is a need to understand the mechanisms underlying the assembly of biohybrid/synthetic molecular building blocks, which ultimately control the emergent properties of hierarchical assemblies. In this work, we study the concentration-driven self-assembly and gelation of π-conjugated synthetic oligopeptides containing different π-conjugated cores (quaterthiophene and perylene diimide) using a combination of particle tracking microrheology, confocal fluorescence microscopy, optical spectroscopy, and electron microscopy. Our results show that π-conjugated oligopeptides self-assemble into β-sheet-rich...

Energy transfer within responsive pi-conjugated coassembled peptide-based nanostructures in aqueous environments

Tue, 29 Jul 2025 00:00:00 +0000

Steady-state and time-resolved photophysical measurements demonstrate energy transfer within π-conjugated peptide nanostructures composed of oligo-(p-phenylenevinylene)-based donor units and quaterthiophene-based acceptor units in completely aqueous environments. These peptide-based assemblies encourage energy migration along the stacking axis, thus resulting in the quenching of donor emission peaks along with the development of new spectral features reminiscent of acceptor emission. These spectral changes were observed even at minute amounts of the acceptor (starting at 1 mol%), suggesting that exciton migration is involved in energy transport and supporting a funnel-like energy transduction mechanism. The reversibility of nanostructure formation and the associated photophysical responses under different conditions (pH, temperature) were also studied. This unique material design incorporates two different semiconducting units coassembled within peptide nanostructures and...

Endothelial extracellular vesicles contain protective proteins and rescue ischemia-reperfusion injury in a human heart-on-chip

Tue, 29 Jul 2025 00:00:00 +0000

Extracellular vesicles (EVs) derived from various stem cell sources induce cardioprotective effects during ischemia-reperfusion injury (IRI). These have been attributed mainly to the antiapoptotic, proangiogenic, microRNA (miRNA) cargo within the stem cell-derived EVs. However, the mechanisms of EV-mediated endothelial signaling to cardiomyocytes, as well as their therapeutic potential toward ischemic myocardial injury, are not clear. EV content beyond miRNA that may contribute to cardioprotection has not been fully illuminated. This study characterized the protein cargo of human vascular endothelial EVs (EEVs) to identify lead cardioactive proteins and assessed the effect of EEVs on human laminar cardiac tissues (hlCTs) exposed to IRI. We mapped the protein content of human vascular EEVs and identified proteins that were previously associated with cellular metabolism, redox state, and calcium handling, among other processes. Analysis of the protein landscape of human cardiomyocytes...

Looking both ways: Electroactive biomaterials with bidirectional implications for dynamic cell–material crosstalk

Tue, 29 Jul 2025 00:00:00 +0000

Cells exist in natural, dynamic microenvironmental niches that facilitate biological responses to external physicochemical cues such as mechanical and electrical stimuli. For excitable cells, exogenous electrical cues are of interest due to their ability to stimulate or regulate cellular behavior via cascade signaling involving ion channels, gap junctions, and integrin receptors across the membrane. In recent years, conductive biomaterials have been demonstrated to influence or record these electrosensitive biological processes whereby the primary design criterion is to achieve seamless cell-material integration. As such, currently available bioelectronic materials are predominantly engineered toward achieving high-performing devices while maintaining the ability to recapitulate the local excitable cell/tissue microenvironment. However, such reports rarely address the dynamic signal coupling or exchange that occurs at the biotic-abiotic interface, as well as the distinction between...

Mussel-inspired 3D fiber scaffolds for heart-on-a-chip toxicity studies of engineered nanomaterials

Tue, 29 Jul 2025 00:00:00 +0000

Due to the unique physicochemical properties exhibited by materials with nanoscale dimensions, there is currently a continuous increase in the number of engineered nanomaterials (ENMs) used in consumer goods. However, several reports associate ENM exposure to negative health outcomes such as cardiovascular diseases. Therefore, understanding the pathological consequences of ENM exposure represents an important challenge, requiring model systems that can provide mechanistic insights across different levels of ENM-based toxicity. To achieve this, we developed a mussel-inspired 3D microphysiological system (MPS) to measure cardiac contractility in the presence of ENMs. While multiple cardiac MPS have been reported as alternatives to in vivo testing, most systems only partially recapitulate the native extracellular matrix (ECM) structure. Here, we show how adhesive and aligned polydopamine (PDA)/polycaprolactone (PCL) nanofiber can be used to emulate the 3D native ECM environment of...