MRA and Doppler ultrasound of laryngeal blood flow under hormonal and hydration modulation

BMC Research Notes · 2026-04-03

OBJECTIVE: Phonation is a complex process requiring an appropriate tissue environment of the vocal folds, with laryngeal blood flow serving as one factor that contributes to tissue homeostasis. Effects of dehydration and reproductive hormone cycling to blood flow and vascular dynamics are described in the literature, but there is a gap in our understanding how these factors may influence the laryngeal blood supply directly. The present study has used a mild systemic dehydration and hormone manipulation paradigm in rats to evaluate the related impacts to the superior thyroid artery using Doppler ultrasound and time-of-flight magnetic resonance angiography. RESULTS: This study provides evidence that hormone status can modify the manifestation of mild systemic dehydration as reflected in bodyweight loss. The imaging methods employed did not reliably identify perturbations to blood flow related to either hydration or hormone status, which we attribute to their practical resolution with respect to the superior thyroid artery and subtlety of the hypothesized effects.

Smart Wearable Ozone Therapy System for Managing Multidrug‐Resistant Wound Infections

Advanced Therapeutics · 2026-03-01

ABSTRACT Multidrug‐resistant (MDR) bacterial infections represent a critical challenge in wound care, leading to treatment failure, prolonged healing, and increased morbidity and mortality worldwide. Among MDR pathogens, Pseudomonas aeruginosa is particularly problematic due to its adaptive resistance mechanisms, underscoring the urgent need for alternative, non‐antibiotic therapeutic strategies. Ozone has demonstrated potent antimicrobial efficacy while promoting wound healing and exhibiting a low propensity for resistance development; however, conventional ozone delivery systems are bulky, poorly suited for ambulatory use, and pose risks of environmental leakage and unintended exposure. To address these limitations, we have developed a smart wearable ozone therapy system capable of precise, localized ozone delivery directly to the wound bed. The platform integrates on‐demand ozone generation, real‐time sensing, and controlled air circulation within a compact, reusable unit, coupled to a disposable wound interface patch via double‐lumen tubing. Embedded sensors continuously regulate ozone concentrations within therapeutic windows while detecting leakage and triggering automatic shutdown to ensure patient and environmental safety. System characterization demonstrated that localized low‐level ozone exposure (75 ppm), when combined with Vancomycin (400 µg·mL − 1 ), eradicated planktonic bacterial cultures to undetectable levels within 4 h while maintaining minimal cytotoxicity toward mammalian cells. For the first time, this fully integrated wearable platform was validated in a Pseudomonas aeruginosa– infected porcine wound model, achieving approximately 90% bacterial reduction after four consecutive daily 6 h treatments and accelerating wound closure by nearly threefold compared with silver dressings or topical antibiotic treatment alone. These results establish a safe, effective, and translationally viable wearable ozone therapy system for the management of MDR‐infected wounds.

Positive allosteric modulator of SERCA pump NDC-1171 attenuates cardiac functional decline in mouse model of Duchenne muscular dystrophy

bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-09

Abstract Progressive cardiomyopathy is the leading cause of death in Duchenne muscular dystrophy (DMD). Dysregulation of calcium handling has been implicated in cardiomyopathy progression in DMD. Here we describe a therapeutic approach to improve calcium homeostasis in a mouse model of DMD using the novel therapeutic NDC-1171, which is a positive allosteric modulator of the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) pump. We synthesized NDC-1171 and treated 4-week-old D2. mdx mice (n=9) via oral gavage. A group of D2. mdx mice (n=9) and a group of DBA/2J mice (n=9; background strain) received a vehicle on the same schedule. We used ultrasound to assess left ventricular function, followed by a treadmill exhaustion test and a 4-paw grip strength test to assess skeletal muscle function. NDC-1171 attenuated cardiac functional decline in D2. mdx mice. At 16 weeks of age, left ventricular ejection fraction (LVEF) was significantly preserved in mice treated with NDC-1171 (57.7□±□0.5%) compared to mice treated with a vehicle (50.7□±□0.9%, p □<□0.05), though remained lower than background strain controls (62.4□±□0.6%). In contrast, functional behavior testing revealed no significant improvement in skeletal muscle function with treatment. These data suggest that treatment with the SERCA pump modulator NDC-1171 helps preserve cardiac function in a murine model of DMD, even as skeletal muscle function was impaired. Future work will be needed to determine if the benefits of this novel SERCA activator translate to large animal and clinical studies, but these initial results are promising and could help guide development of future treatments for pediatric patients with muscular dystrophy.

Evaluation of Elastin Composition and Organization in Murine Abdominal Aortic Aneurysms

Proceedings of IMPRS · 2026-03-30

Background and Hypothesis: The prevalence of aortic aneurysms has increased dramatically over the past 20 years, with over 35 million cases of abdominal aortic aneurysms (AAAs) in 2019 alone. However, AAAs with intraluminal thrombus (ILT) development remain understudied. Elastin is a key component of the aorta that gives it distensibility. Here, we evaluated the organization of aortic elastin with and without ILT. Methods: AAAs were induced in mice by topically applying elastase to the aorta. β-aminopropionitrile was added to drinking water to promote AAA expansion. After 8 weeks aortas were extracted and stained with Movat’s Pentachrome. Images at the largest aortic diameter were collected at 100 μm zoom and separated into 4 quadrants around the lumen. Manual counting was used to determine the number of elastin fibers in the aortic wall. ImageJ’s color segmentation was used to find extracellular matrix component composition of each aortic layer. Results: We found samples without ILT on average had 2.7 more distinct elastin sheets compared to ILT samples. Color segmentation findings showed 7% less elastin in the tunica media in samples with ILT. Further, color segmentation showed there was a statistically significant increase in the amount of proteoglycans in the tunica media in samples with ILT. Conclusion: We found ILT forming aneurysms had fewer intact elastin fibers and greater proteoglycan deposition, indicating more detrimental breakdown of the tunica media compared to samples without ILT. Clinical Implications: Our findings suggest AAA patients with ILT are at higher risk for more severe cases of aortic wall degradation, suggesting special monitoring following identification of ILT. Further Considerations: A larger sample size is needed to identify a statistically significant difference in elastin between groups. Future work should compare changes in aortic wall composition in male and female mice to improve our understanding of pathophysiological differences observed between genders.

Molecular changes, histopathology, and ultrasonic vocalization acoustic profiles of systemically dehydrated rats

PLoS ONE · 2025-04-22

Systemic hydration is known to promote optimal functioning of bodily systems-including the vocal folds. The impact of systemic dehydration on the biology of the vocal folds and the downstream effects of dehydration on voice output are not well understood. An in vivo rat model of systemic dehydration was employed to investigate vocal fold gene expression, histological changes, and acoustic changes in vocalization. Ultrasonic vocalizations (USVs) were recorded every day for 5 days (baseline), in male and female Long-Evans rats (N = 36, ages: 3-4 months) using an anticipatory reward paradigm. Next, rats were dehydrated (N = 18) using a published water-restriction model for 5 days or euhydrated (N = 18) and provided ad libitum access to water for 5 days. USVs were recorded daily during the dehydration/euhydration period. The USV variables were averaged at baseline and following dehydration/euhydration for individual animals, and the difference between these time periods was used for statistical analysis. USV analysis included total USV count, complexity ratio, duration (s), frequency range (kHz), and maximum intensity (dB). At the end of dehydration/euhydration, animals were euthanized, and kidney and vocal fold tissue samples were dissected and processed for histology and gene expression analysis. Compared to euhydrated rats, dehydrated male and female rats had significantly up-regulated gene expression of kidney renin (male p = 0.047; female p = 0.018), indicating physiologic dehydration. There were no statistically significant differences in the USV acoustic profile or histopathology between the two groups. Differential expression (p < 0.05) of several genes related to extracellular matrix remodeling, inflammatory responses, and water ion transport in the vocal folds was present. Our results indicate that mild systemic dehydration impacts gene expression in the vocal fold mucosa; however, these gene expression changes are not evident in the acoustic profile of vocalizations.

AnnotateAnyCell: Open-Source AI Framework for Efficient Annotation in Digital Pathology

bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-03

A bstract Manual annotation of histopathological whole slide images remains a critical bottleneck for computational pathology and clinical AI deployment, requiring prohibitive expert time at scale. Here we present an open-source semi-supervised framework combining active contrastive learning with iterative human-in-the-loop feedback for efficient cellular annotation and classification. The pipeline integrates Cellpose segmentation, UMAP-based latent space visualization, and contrastive learning with pseudolabel propagation, evaluated on five whole slide images of canine invasive urothelial carcinoma across low, intermediate, and high histological grades at 40× magnification. Latent space clustering-guided annotation required 47 minutes compared to 63 minutes for sequential annotation, a 25% reduction (95% CI 18–32%). Classification accuracy reached 96.3% ± 1.2% for mitotic figures and 98.3% ± 1.4% for nucleoli using 1,075 labeled samples, with nucleoli classification achieving 95.5% ± 1.5% accuracy from only 215 samples. Inter-annotator agreement was high for chromatin ( κ = 1.00) and nucleoli ( κ = 0.95) but moderate for mitotic figures ( κ = 0.58) and nuclear shape ( κ = 0.36), reflecting intrinsic morphological ambiguity in these categories. This framework substantially reduces annotation burden while achieving expert-level accuracy for well-defined morphological features, providing a scalable path toward AI-assisted diagnostics in resource-constrained pathology settings.

LAP-Hsp60 complex modulates epithelial tight junction barrier

Research Square · 2025-05-14 · 1 citations

Reshaping lipid metabolism with long-term alternate day feeding in type 2 diabetes mice

npj Metabolic Health and Disease · 2025-02-03 · 2 citations

Strategies to improve metabolic health include calorie restriction, time restricted eating and fasting several days per week or month. These approaches have demonstrated benefits for individuals experiencing obesity, metabolic syndrome, and prediabetes. However, their impact on established diabetes remains incompletely studied. The chronicity of type 2 diabetes (T2D) requires that interventions must be undertaken for extended periods of time, typically the entire lifetime of the individual. In this study, we examined the impact of intermittent fasting (IF), with an every-other-day protocol for a duration of 6 months in a murine model of T2D, the db/db (D) mouse on metabolism and liver steatosis. We compared D-IF mice with diabetic ad-libitum (AL; D-AL), control-IF (C-IF) and control-AL (C-AL) cohorts. We demonstrated using lipidomic, microbiome, metabolomic and liver transcriptomic studies that chronic IF improved carbohydrate utilization and glucose homeostasis without weight loss and reduced white adipose tissue inflammation and significantly impacted lipid metabolism in the liver. Microbiome studies and predicted functional analysis of gut microbiota showed that IF increased beneficial bacteria involved in sphingolipid (SL) metabolism. The metabolomic studies showed that oxidation of lipid species and ceramide levels were reduced in D-IF compared to D-AL. The liver lipidomic analysis and liver microarray confirmed a reduction in overall lipid content in D-IF mice compared to D-AL mice, especially in the feeding state as well as an overall reduction in oxidized lipids and ceramides. These studies support that long-term IF can improve glucose homeostasis and dramatically altered lipid metabolism in the absence of weight loss.

AMPK‐Dependent Epigenetic Regulation of Metabolism Mediates the Anti‐Cancer Action of Pterostilbene in Hepatocellular Carcinoma

Molecular Nutrition & Food Research · 2025-09-01 · 4 citations

Disrupted metabolism, often implicated in hepatocellular carcinoma (HCC), is linked to aberrant epigenetic patterns. Dietary polyphenols, including pterostilbene (PTS), have been demonstrated to remodel epigenetic landscapes and restore metabolic homeostasis by regulating the activity of AMP-activated protein kinase (AMPK), a protein recently shown to orchestrate a diverse set of networks to epigenetically mediate transcription. We therefore explored the mechanistic involvement of AMPK in the epigenetic effects of PTS in HCC. We incorporated PTS into a choline-deficient amino acid defined HCC-inducing diet (CDAA) in male Fisher-344 rats and found significant attenuation in HCC development compared to CDAA alone. Transcriptomics by RNA-sequencing revealed PTS-upregulated targets, that were enriched in key metabolic processes, including the folate (Aldh1l1), methionine (Bhmt), and sarcosine (Dmdgh) cycles. PTS-mediated gene upregulation was linked to lower levels of histone H3-methylation at lysine 27 (H3K27me3) at gene promoters. Mechanistic studies in HCC HepG2 cells revealed that AMPK inhibition abolished epigenetic gene activation in response to PTS, which was accompanied by diminished binding of H3K27me3-demethylase KDM6A at promoters of PTS-target genes. Our findings provide evidence for new disease vulnerabilities that arise from epigenetic/metabolic changes and constitute novel opportunities for preventative and therapeutic success in HCC.

Murine Abdominal Aortic Aneurysm Intraluminal Thrombus Composition and Structure

bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-30

Abstract An abdominal aortic aneurysm (AAA) is a dilation of the aortic wall in the abdomen. Many AAA patients develop intraluminal thrombus (ILT), but the role of ILT in AAA progression and rupture is not well understood. To evaluate ILT in AAAs, we induced AAAs in male C57Bl6/J mice (n=25) via surgical application of topical elastase (5 µL of 5 or 10 mg/mL) to the abdominal aorta below the renal arteries and administration of β-aminopropionitrile (BAPN, 0.2%) drinking water. We collected weekly/biweekly ultrasound images over 56 days. Mice were euthanized and histology images were collected. We semi-quantitatively assessed elastin degradation and inflammation from Movat’s pentachrome and H&amp;E-stained samples, respectively. Mice with ILT had more significant expansion over the length of the study (beginning at day 14, p&lt;0.05). From histology, ILT samples showed more elastin disorganization and greater inflammation. From scanning electron microscopy, we were able to confirm the presence of layered sheets of fibrin and abnormally shaped red blood cells (polyhedrocytes) within the ILT deposits. In this model, elastase causes aortic injury by degrading elastin fibrils in the aortic wall, reducing the ability of the aorta to contract during high-pressure blood flow. Further damage to the extracellular matrix is likely driven by subsequent inflammation. Here we observed tissue samples with greater acute-on-chronic inflammation were correlated with more elastin damage, and therefore greater aortic expansion. Further, larger aortic expansions were correlated with slower blood flow, likely due to increased cross-sectional area. Thus, increased aortic expansion and damage to the aortic wall may be more likely to create hemodynamic conditions that are conducive to the initiation of ILT deposition: endothelial damage and reduced blood flow. Understanding the relationship between ILT formation, aortic wall degradation, and inflammation could help refine therapeutic strategies for treating AAAs. Abstract Figure