This study establishes a proof of concept that electrical bioimpedance spectroscopy (EBS) can characterize volume-dependent structural variations in adipose tissue. This comes as a part of broader initiative to improve pharmacokinetic modeling accuracy in obese patients by providing better understanding of adipose tissue structural properties that influence drug distribution. To do so, an ex vivo porcine adipose tissue sample was subjected to a controlled progressive volume reduction, with impedance measured after each step. The data were fitted using a double Cole–Cole model to capture multiple dispersion mechanisms. The results revealed three distinct structural patterns: (1) large samples (Samples 10–9) exhibited a homogeneous structure with loosely arranged adipocytes, where conduction occurred predominantly through extracellular pathways; (2) intermediate samples exhibited transitional dielectric features reflecting the shift from fluid-rich to compact tissue organization; (3) small samples were compact and homogeneous, characterized by tightly packed adipocytes and minimal interstitial fluid. Cole–Cole parameters varied non-linearly with volume, reflecting underlying structural transitions in tissue organization. Time-domain relaxation curves reflected compartmentalization of fat tissue into fast-relaxing aqueous pathways and slow-relaxing lipid-rich domains. These findings establish that impedance-derived parameters capture structural components, including adipocyte density and interstitial fluid content, that directly influence drug distribution. This offers a pathway to integrate structural markers into pharmacokinetic frameworks. • Bioimpedance spectroscopy captures volume-dependent adipose tissue structure. • Cole–Cole parameters exhibit non-linear relationships with adipose tissue volume. • Extracted parameters reflect tissue characteristics relevant to drug distribution.

Microneedle-based theranostics for melanoma: Advances and outlook.

A pressure-assistive microneedles module for interstitial fluid extraction and In situ detection of biomarkers.

Pulmonary lymphatics play multiple essential roles in lung homeostasis through interstitial fluid removal, traffic of immune cells, and antigen presentation. This highly branching vascular bed comprises initial capillaries, pre-collecting vessels, and collecting lymphatics, and it is lined by characteristic lymphatic endothelial cells (LECs). These cells are distinct from blood endothelial cells in their structure, molecular markers (e.g., PROX1, LYVE-1, VEGFR-3), and responsiveness to inflammatory and mechanical stimuli. In health, LECs preserve barrier integrity, promote immune surveillance, and support unidirectional lymph flow. However, during pulmonary inflammation or injury, LECs may undergo phenotypic changes that impair function and promote local coagulation. This review consolidates current knowledge on pulmonary lymphatic vessel structure and function and LEC biology, with a focus on their involvement in inflammation and coagulation pathways. We examine how cigarette smoke disrupts LEC homeostasis, leading to endothelial injury, procoagulant factor upregulation [e.g., tissue factor, plasminogen activator inhibitor-1 (PAI-1)], and fibrin-rich thrombosis in lung lymphatics. Although vaping induces oxidative stress and vascular inflammation, its effects on the pulmonary lymphatic system have not been clearly explained. Based on pathological features shared with smoking, we propose potential mechanisms by which e-cigarette aerosols may contribute to lymphatic endothelial dysfunction and altered coagulation in lungs. Given the increasing prevalence of vaping, further research using in vitro, in vivo, and human studies is needed to elucidate how inhaled toxicants alter LEC function and to identify novel targets for preserving lymphatic health in lung disease.

Reprogramming tumor microenvironment of pancreatic cancer by CAF-targeted sonodynamic therapy combined with chemotherapy.

Ultra-robust spin-assisted infiltration for large-area, highly ordered, defect-free titanium dioxide and tin dioxide inverse opal frameworks toward efficient ultraviolet-visible photodetection.

Brain tumors disrupt the glymphatic system-a critical network for cerebrospinal and interstitial fluid circulation via the perivascular spaces (PVS)-yet the extent and underlying mechanisms of this dysfunction remain poorly defined. In a prospective study, 104 brain tumor patients (40 high-grade gliomas, 26 metastases, and 38 meningiomas) and 30 age- and sex-matched healthy controls underwent advanced MRI assessments to quantify white matter PVS volume fraction (PVSVF-WM), free water fraction (FW-WM), and the DTI-ALPS index. All tumor groups exhibited significantly elevated PVSVF-WM (p < .001) and reduced DTI-ALPS index, indicating PVS dilation and impaired glymphatic function, while FW-WM showed significant group differences, with the lowest values observed in patients with high-grade glioma (p < .001). Tumor volume showed a strong positive correlation with PVSVF-WM (ρ = 0.674, p < .001) and a negative correlation with the DTI-ALPS index (ρ = -0.482, p < .001). Moreover, in gliomas, Ki67 expression correlated positively with PVSVF-WM (ρ = 0.563, p < .001) and negatively with the DTI-ALPS index (ρ = -0.482, p = .002), whereas in metastases, p53 expression correlated positively with the DTI-ALPS index (ρ = 0.569, p = .002). These findings demonstrate that brain tumors alter the PVS network, leading to glymphatic dysfunction, with the degree of disruption being modulated by tumor burden and molecular characteristics. The innovative MRI-based metrics used in this study provide valuable insights into tumor-associated glymphatic alterations and may inform the development of tailored therapeutic interventions.

Unified stability conditions for explicit finite-difference Biot-type poroelastodynamics: Non-dimensional design maps for time step selection in brain fluid transport.

A comparison of inkjet-printed amperometric and transistor-based biosensors towards continuous glucose monitoring

The aging brain depends on coordinated fluid transport, immune surveillance, and clearance of metabolic byproducts to preserve cognitive and physiological homeostasis. While peripheral lymphatic decline is well established, growing evidence implicates brain-draining lymphatic pathways, particularly meningeal lymphatic vessels and their downstream drainage to deep cervical lymph nodes, as an aging-sensitive axis that intersects with neuroinflammation and neurodegenerative vulnerability. Here, we systematically analyzed peer-reviewed studies published between 2003 and 2025 that examined age-related changes in intracranial and cervical lymphatic circuits across human imaging, histopathology, and experimental models. Ninety-six studies met the inclusion criteria. Four themes emerged. First, aging is associated with coordinated lymphatic remodeling across peripheral and central compartments, including reduced vessel integrity, stromal remodeling, and involution of draining lymph nodes. Second, meningeal lymphatic vessels exhibit age-related, region-specific structural and molecular alterations that may coincide with impaired cerebrospinal and interstitial fluid handling and altered immune regulation. Third, advanced magnetic resonance imaging, including contrast-enhanced and non-contrast approaches, reveals reproducible age-associated changes in dural and cervical lymphatic-related signals across the lifespan, while remaining an indirect proxy for flow and transport. Fourth, early therapeutic efforts suggest that brain-draining lymphatic function may be modifiable. These approaches include augmenting meningeal lymphangiogenic signaling with VEGF-C or its cofactor; and, in selected translational settings. Collectively, the evidence supports meningeal and cervical lymphatic decline as a plausible, potentially modifiable contributor to aging-related brain vulnerability across disorders such as Alzheimer's disease and Parkinson's disease, while underscoring the need for more direct functional measurements and longitudinal human studies.

Ageing and the lymphatic system: Implications for immunity, brain health, and possible therapeutic interventions.

Spondylodiscitis is a severe infection associated with considerable morbidity and mortality. The prevalence of gram-negative infections is on the rise, posing significant therapeutic challenges. Cefepime/enmetazobactam constitutes a novel antibiotic combination that offers broad-spectrum activity against resistant gram-negative organisms. However, its pharmacokinetic profile within spinal tissues remains unknown. To dynamically assess unbound steady-state concentrations of cefepime/enmetazobactam in healthy vertebral cancellous bone, intervertebral disc, and paravertebral muscle after both short-term and continuous infusions. 16 pigs were randomised to receive either short-term infusion (3 doses of 2g/0.5g cefepime/enmetazobactam administered over 2h, repeated every 8h) or continuous infusion (1g/0.25g loading dose administered over 15min, followed by 6g/1.5g administered over 15h and 45min). Steady state was assumed during the third dosing interval (16-24h). Microdialysis was employed to sample interstitial fluid from spondylodiscitis-relevant tissues: vertebral cancellous bone, intervertebral disc and paravertebral muscle, at steady state for 8h. The unbound concentrations of cefepime and enmetazobactam were quantified by LC-MS/MS. The primary endpoint was to determine the time above relevant MIC (T > MIC) for cefepime (0.125, 4, 8, and 32 mg/L) and the time above relevant concentration threshold (T > Ct) for enmetazobactam (2 and 8 mg/L). For both cefepime and enmetazobactam, there were no differences in T > MIC and T > Ct when comparing dosing regimens, applying the conventional targets of MIC 0.125, 4, and 8 mg/L, and Ct of 2 mg/L. Only when applying the aggressive targets of MIC 32 mg/L and Ct 8 mg/L did continuous infusion yield longer T > MIC and T > Ct compared with short-term infusion in both the vertebral cancellous bone and intervertebral disc. Both cefepime and enmetazobactam consistently reached theoretically effective unbound steady-state tissue levels in relevant target tissues for spondylodiscitis, irrespective of the dosing regimen.

Exercise-induced muscle damage (EIMD) triggers a coordinated cascade of molecular responses that drive tissue repair and physiological adaptation. Recent advances in analytical chemistry have enabled multi-omics profiling to capture these complex processes across genomic, transcriptomic, proteomic, and metabolomic layers. This review critically examines the analytical strategies underlying EIMD omics research, emphasizing how modern separation and detection technologies have expanded the depth and resolution of biomolecular measurements. We outline the strengths and trade-offs of invasive and non-invasive biospecimens, highlighting how blood, urine, interstitial fluid, and sweat provide complementary insights into systemic and local muscle responses. Central to this workflow are chemometric and bioinformatic tools that enable dimensionality reduction, feature selection, and predictive modeling, transforming high-dimensional molecular data into actionable biomarkers. Case studies illustrate how metabolite panels and protein signatures can discriminate muscle damage states, reveal pathway dynamics, and support early detection of physiological stress. By linking analytical innovation with data integration, multi-omics approaches are reshaping how exercise stress, adaptation, and recovery are understood. This synthesis also acknowledges current controversies positioning multi-omics as both a powerful scientific tool and a frontier for precision exercise medicine.

The hypothalamic-pituitary-adrenal (HPA) axis is the key homeostatic system regulating the response to surgical stress. Imbalances in HPA axis hormones increase morbidity and mortality in children after cardiac surgery. Despite this, the physiology of the HPA axis in children undergoing cardiac surgery is poorly understood, leading to controversies in clinical practice. To characterise dynamic HPA axis responses in children undergoing cardiac surgery and to determine age- and procedure-related differences in cortisol and cortisone physiology. We recruited children (0-18 years) undergoing cardiac surgery with cardiopulmonary bypass or cardiac catheterisation. Tissue-free cortisol and cortisone were sampled every 20 minutes for up to 24 hours via microdialysis, alongside serum adrenocorticotropic hormone (ACTH), cortisol, cortisol-binding globulin (CBG), and inflammatory markers. We developed dynamic markers to quantify age- and procedure-dependent differences in hormonal responses and built a mathematical model to explain them. Neonates undergoing surgery showed higher free cortisol and cortisone AUC and peak concentrations than catheterisation patients. Neonates had higher peaks of cortisol and cortisone than older children undergoing surgery. The much higher tissue cortisone levels observed in neonates can be explained by enzymatic interconversion between cortisol and cortisone, likely due to persistent foetal high 11-βHSD2 activity and reduced 11-βHSD1 activity.Low post-operative blood cortisol and CBG values in neonates resulted in high free cortisol peaks in interstitial fluid during and after surgery. Neonates differ physiologically, with higher free cortisol levels that more readily diffuse into interstitial tissues, with implications for perioperative management.

VEGF/VEGFR targeting-induced vascular normalization: a key strategy to reverse cold tumor phenotype and potentiate immunotherapy in gynecologic cancers.

This study was aimed to determine whether sub-tenon triamcinolone acetonide (STTA) injections influence interstitial fluid (ISF) glucose fluctuations in patients with diabetic macular edema (DME) and assess whether age affects the glycemic response. This prospective study included 18 patients with DME receiving STTA injections. ISF glucose was monitored using a continuous glucose monitoring system. Glucose data were evaluated over a 7-day period before and after STTA injection. Time in range (TIR), time above range (TAR), and time below range (TBR) were recorded before and after STTA injection; differences before and after injection were calculated and compared by age (< 70 vs. ≥ 70 years). Results showed a non-significant trend toward an increase in average ISF glucose (from 156.3 ± 55.4mg/dL to 163.5 ± 50.6mg/dL; p = 0.055). TAR rose from 28.0% to 33.3% (p < 0.05), whereas TBR decreased from 3.42% to 0.9% (p < 0.05); TIR remained unchanged. ΔISF glucose was 15.8 ± 11.3mg/dL and 1.5 ± 13.2mg/dL in those aged ≥ 70 and < 70 years, respectively (p = 0.08). Patients aged ≥ 70 years showed increased ΔTAR (12.0% vs. 0.8%) and reduced ΔTBR (-4.8% vs. - 0.9%) (p < 0.05). STTA injections may increase TAR, especially in older patients, highlighting the need for close glucose monitoring.

The lymphatic system maintains physiological homeostasis through constant immunosurveillance, immune cell trafficking, and regulation of interstitial fluid flow. Lymphatic dysfunction is associated with a wide range of pathologies, including cancer metastasis and lymphedema. Aberrant lymphatic structure also contributes to chronic wounds and transplanted organ rejection. These functional and structural deficits have inspired strategies for lymphatic vasculature modulation and tissue engineering to regulate immune functions during disease and injury rehabilitation. Lymphangiogenesis-the process of lymphatic vessel growth- is central to the success of these strategies and has broad potential if harnessed for therapeutic intervention and tissue integration. Here we review the opportunities and obstacles for biomolecular pathway modulation, nanotechnology, and tissue engineering to promote or inhibit lymphangiogenesis.

Hydrocephalus is a complex neurological disorder traditionally thought to result from excessive cerebrospinal fluid (CSF) production, obstruction of CSF outflow, or impaired absorption. However, these classical theories have limitations in explaining key phenomena observed in certain clinical subtypes, such as normal pressure hydrocephalus. Recent advances in neuro-fluid dynamics have introduced the concept of the glymphatic system, a functional network in the brain that facilitates the exchange of CSF and interstitial fluid (ISF) along perivascular pathways and mediates the clearance of metabolic waste. This new perspective offers a fresh lens for understanding CSF circulation and fluid homeostasis. This review aims to reexamine the pathogenesis of hydrocephalus from the perspective of glymphatic dysfunction and, by integrating anatomical, physiological, and imaging evidence, explore its theoretical implications and clinical relevance.

Microneedle (MN) technology is an appealing route for treating skin cancers, but remains many challenges, such as accommodating multiple theranostic functionalities and configuring personalized sensing, particularly given that MNs typically collect sample volumes from microliters to milliliters, necessitating suitable trace analysis techniques. In this study, we developed a versatile, multilayer, detachable MN administration system capable of simultaneous photocontrolled drug delivery therapy that operated based on real-time in situ conditions monitored by droplet-based PCR (dPCR). The detachable MN consisted of an innermost poly (ethylene glycol) diacrylate extraction layer, an outer gelatin methacryloyl drug-loaded layer containing Vemurafenib and black phosphorus (BP), and a polyvinyl alcohol connection layer designed for thermal detachment. The outer layer enabled light-responsive drug release through BP's photothermal properties, achieving 78% release within 24h. Subsequently, the significant mechanical strength and swelling characteristics facilitated the effective extraction of approximately 26µL of interstitial fluid within 10min. Both in vitro and in vivo studies on melanoma demonstrated the platform's capability to enhance therapeutic efficacy while minimizing systemic toxicity. It enabled dPCR-based monitoring of MCAM and BRAF genes, including the drug-resistant V600E polymorphism, with detection limits of 223copies/µL, along with digital proximity ligation assay detection of the protein markers IL-6, VEGF, and Ki-67 at 0.64pg/mL. This well-designed biosystem highlighted its capability to interact with the pathophysiological environment, providing a preclinical proof-of-concept for minimally invasive theranostics in superficial tumors.

The heme catabolism pathway is often elevated in aggressive cancers; however, the impact of this pathway and some of its byproducts on the tumor microenvironment remain largely unknown. In human breast cancers, tumor expression of the heme catabolizing enzyme heme oxygenase-1 (HO-1/HMOX1) is positively associated with macrophage abundance. In mouse mammary tumors, knockdown of Hmox1 significantly decreased tumor growth and lung metastasis. Analysis of mammary tumor interstitial fluid compared to matching plasma revealed that the heme metabolite bilirubin was elevated intratumorally, which could be partially reversed via Hmox1 knockdown. Further investigation revealed that bilirubin nearly ablates macrophage engulfment of dead tumor cells and significantly increases macrophage T cell suppression. Mammary tumors harboring Hmox1 knockdown had a significant decrease in tumor growth rate and number of pro-metastatic CD206+ macrophages upon treatment with αPD-1. Depletion of intratumoral bilirubin levels impacts pro-tumor macrophage populations, particularly in combination with immunotherapy, demonstrating that heme catabolism and bilirubin act as immunomodulators in cancer.