Artificial snowmaking is used by winter recreation resorts to elongate the ski season in areas that lack sufficient snow, yet the occurrence of contaminants in artificial snow remains largely uncharacterized. Contaminants in artificial snow can lead to the introduction of pollutants into surrounding ecosystems (e.g., plants, water streams, soils) or create pathways for human exposure. Using the Arizona Snowbowl Ski Resort in Flagstaff, Arizona, as a case study, we characterized the chemical (organic and inorganic) profile of snow made from reclaimed water samples as compared to natural snow samples. Pharmaceuticals and anthropogenic compounds were identified in snowmaking from reclaimed water samples using nontargeted mass spectrometry paired with molecular networking, and identities of selected compounds were confirmed and quantified using targeted mass spectrometry alongside authentic chemical standards. Nineteen pharmaceuticals were found to be increased in high artificial snowmaking samples as compared to natural snow, including carbamazepine, fexofenadine, flecainide, and lamotrigine, which were present at low ng/L concentrations in one set of high artificial snowmaking samples. A suite of inorganic contaminants was also assessed and quantified using inductively coupled plasma mass spectrometry to reveal that nine metals(?)sodium, phosphorus, potassium, chromium, manganese, iron, zinc, arsenic, and barium(?)were increased in abundance in high artificial snowmaking samples compared to levels in normal snow. Taken together, this study suggests that snow made from reclaimed water may contain anthropogenic organic and inorganic analytes, warranting further study on their environmental and human health effects.

Circulating tumor plasma cells (CTCs) at diagnosis are independent prognostic markers in newly diagnosed multiple myeloma (NDMM). Flow cytometry (FC) enables sensitive and cost-effective CTC quantification, but prognostic cut-offs vary across studies. The methodological approach used for quantification may affect the determination of the CTC percentage. In this study we compare head-to-head two FC techniques [single-platform FC versus Next Generation Flow (NGF)] to measure CTC levels in NDMM patients. Methodological differences between the two techniques can be found in sample processing (NGF includes fixation and permeabilization steps that are not required for CTC quantification by single-platform FC) and analytical sensitivity, which is higher for NGF than for single-platform FC. The percentage of CTCs was simultaneously assessed with both techniques in the peripheral blood (PB) of 34 patients enrolled in the REAL MM trial (NCT03829371) at screening. Single-platform FC detected CTCs in 29/34 patients (85.3%) patients, while NGF detected CTCs in 31/34 patients (91.2%), including 2 cases that were negative by single-platform FC. The CTC percentage measured using the NGF technique (median 0.0049%, range 0%-0.377%) was significantly lower than that obtained using single-platform FC (median 0.009%, range 0%-0.59%) (p < 0.0001). Indeed, quantifying CTCs with FC after fixation and permeabilization (comparably to NGF) led to results that were similar to NGF. In conclusion, NGF demonstrated higher sensitivity than single-platform FC to detect CTCs at diagnosis in MM patients. Employing standardized techniques like NGF may avoid variability across different laboratories and centers.

Proprioceptive dysfunction is a common rehabilitation issue in neurological injury, and the muscle spindle (MS) is considered a critical structure in this dysfunction. The present study aimed to investigate the morphological alterations of MS in two classical neurological diseases: denervation and stroke, and to understand the role of MS in these two diseases preliminarily. The denervation and stroke model animals were constructed by using a surgical operation and middle cerebral artery occlusion (MCAO) protocol, respectively. The muscles from the affected-side limb and the healthy-side limb were harvested and then fixed, embedded, sliced, stained, and subjected to other laboratory analysis at the predetermined time point. The capsule thickness, cross-sectional area (CSA) of intrafusal fiber and extrafusal fiber, the collagen area percentage, and the hyaluronic acid were investigated in the denervation and stroke animal model. In denervation rats, the capsule thickness in the denervation-side limb increased significantly with the p value under 0.01, while the CSA of intrafusal fiber and extrafusal fiber both decreased with the p values under 0.01 and 0.0001, respectively, compared to the healthy-side. The collagen area percentage increased on the denervation side, with a p value under 0.01, but no difference was found in hyaluronic acid. In stroke mice, similar tendencies were found in the stroke-affected side regarding the capsule thickness and CSA of intrafusal fiber, but there was no statistical significance. The CSA of extrafusal fiber seems equal on the stroke-affected side and healthy-side as well as the collagen area percentage. The hyaluronic acid in the capsule of MS was higher in affected-side compared to healthy-side with a p value under 0.05. The alterations of MSs suggested that MS's roles in proprioception are diverse in these two typical neurological diseases. The changes of MS in denervation are aligned with the alterations of muscle and intramuscular connective tissue, but are not aligned in stroke, especially the hyaluronic acid. The present study provides a novel MS-based view to understand proprioception dysfunction in stroke and peripheral nerve injury.

Philadelphia-negative myeloproliferative neoplasms (MPN), a spectrum of blood malignancies characterized by uncontrolled myeloid proliferation, persist as a key challenge in onco-hematology due to their intricate molecular background, heterogeneous clinical phenotypes, and variable prognoses. Although generally accepted as indolent disorders, a considerable fraction of MPN patients exhibit progressive, and sometimes accelerated, bone marrow fibrosis, reflecting a critical shift toward a more debilitating condition marked by an increased symptom burden. As marrow scarring advances, hematopoietic capacity declines, severely compromising both patients' quality of life and survival. Increasing evidence highlights the crucial involvement of multiple players and mechanisms orchestrating marrow fibrotic transformation, thereby reflecting the multifaceted nature of this pathogenetic process. In this review, we untangle the pro-fibrotic programs underlying fibrosis progression in MPN, critically analyzing the available scientific literature. We explore the potential impact of the mutational landscape on the fibrotic transformation risk and examine the role of dysfunctional megakaryocytes as principal catalysts of fibrotic remodeling. Additionally, we provide insight into the influence of the bone marrow microenvironment, examining the contribution of both soluble factors and direct cell-cell communication in sustaining and exacerbating the fibrotic signature. The urgent need for earlier diagnoses, tailored prognoses, and more effective therapeutic strategies stresses the importance of investigating the pathological basis of fibrotic progression from a deeper perspective.

Temporal lobe epilepsy (TLE) is linked to progressive alterations in brain network dynamics, leading to behavioral comorbidities and emergence of drug resistance; yet the underlying mechanistic and synaptic substrates remain incompletely understood. Here, we performed longitudinal phase-specific characterization of network dysfunction in TLE employing a lithium-pilocarpine-induced model in 7-week male Wistar rats. We integrated behavioral and electroencephalographic (EEG) analyses at five timepoints: baseline, acute, latent, chronic phases, and after assessment of drug-resistant epilepsy (DRE). After the chronic phase, responsiveness to phenobarbital (PB), a standardized approach for DRE characterization, was assessed via video monitoring to identify drug-resistant (DRUG-R) and drug-sensitive (DRUG-S) subpopulations. Our data show that epileptic rats exhibited progressive and phase-dependent behavioral and EEG alterations. Behavioral profiling revealed a hypermotor phenotype, impairment in burrowing natural behavior, altered phase-specific response to anxiety and depressive-associated behavioral paradigms, and progressive memory impairment. Following PB treatment, the identified DRUG-R subpopulation displayed specific hyperactive behavioral traits compared with DRUG-S, especially in anxiety-associated and burrowing behaviors. Spectral EEG analysis revealed modulation of frequency bands across disease stages, particularly in Theta and Delta power, and descriptive analyses attempted to stratify animals based on different responsiveness to PB. Lastly, correlation analyses supported associations between EEG, frequency of seizures and behavioral measures, especially in the anxiety domain and declarative memory. This study, moving beyond a seizure-centric perspective, evidences that TLE induces progressive and phase-specific reorganization of cortical activity that relapse on distinct electrophysiological and behavioral features, offering a novel framework to identify translational stage-related signatures of epileptogenesis and DRE.

Oxidative stress is increasingly recognized as a key contributor to the biology of hematological malignancies. Excessive production of reactive oxygen species disrupts redox homeostasis, promotes genomic instability, alters cellular signaling pathways, and influences disease progression, therapeutic response, and resistance mechanisms. Among the downstream consequences of oxidative stress, lipid peroxidation represents a major source of cellular injury, generating reactive aldehydes capable of amplifying molecular damage. Malondialdehyde, a stable end product of lipid peroxidation, has emerged as one of the most widely investigated biomarkers of oxidative damage in hematologic cancers. This review summarizes current evidence regarding the role of malondialdehyde across major hematological malignancies, including acute and chronic myeloid leukemias, Philadelphia-negative myeloproliferative neoplasms, lymphomas, and multiple myeloma. Available evidence consistently demonstrates significantly elevated MDA levels across major hematological malignancies, including acute and chronic myeloid leukemias, Philadelphia-negative myeloproliferative neoplasms, lymphomas, and multiple myeloma. Increased MDA concentrations are frequently associated with disease activity, relapse, impaired antioxidant defenses, thrombotic complications, treatment resistance, and therapy-related toxicity. Furthermore, experimental studies indicate that MDA accumulation closely parallels ferroptosis induction and may serve as a pharmacodynamic marker of lipid peroxide-mediated cell death. Overall, the reviewed literature identifies MDA as one of the most consistent biomarkers of oxidative stress and lipid peroxidation in hematological cancers. Although methodological standardization remains necessary, MDA appears to have potential diagnostic, prognostic, and therapeutic relevance and may contribute to identifying redox vulnerabilities that can be exploited by emerging ferroptosis-based treatment strategies.

Malondialdehyde (MDA) is one of the main end-products of lipid peroxidation (LPO) and represents a widely investigated marker of oxidative stress (OS) and oxidative tissue damage. Beyond its role as a measurable byproduct of polyunsaturated fatty acid peroxidation, MDA can interact with proteins and nucleic acids, generating adducts that may contribute to mutagenic, genotoxic, and cytotoxic events involved in carcinogenesis and tumor progression. This narrative review summarizes current evidence on the role of MDA in cancers, including breast, lung, head and neck, colorectal, cervical, and cutaneous tumors. Across these cancer types, increased circulating or tissue MDA levels have frequently been associated with enhanced LPO, impaired antioxidant defenses, tumor burden, advanced disease stage, aggressive histopathological features, treatment-related oxidative injury, and, in selected studies, poorer clinical outcomes. MDA-derived DNA adducts may further reflect oxidative DNA damage and provide mechanistic insight into the relationship between chronic redox imbalance, inflammation, and malignant transformation. However, MDA remains a non-specific biomarker influenced by age, smoking, diet, metabolic disorders, systemic inflammation, comorbidities, treatment exposure, and analytical methodology. Current evidence therefore supports MDA as a biologically relevant indicator of oxidative damage rather than a validated stand-alone diagnostic, prognostic, or therapeutic biomarker. Larger prospective studies using standardized and specific analytical methods are needed to clarify its clinical utility and to integrate MDA within broader redox biomarker panels.

Arrays of cross-selective sensors, or electronic tongues, exploit the olfaction-inspired principle of combinatorial selectivity to classify samples based on their overall chemical profiles. This approach is particularly valuable in applications such as medical diagnostics and food quality control, where rapid and reliable analysis is essential. Here, we present a high-throughput electronic tongue that integrates advanced fabrication techniques-including Laser-Induced Graphene (LIG), conductive ink dispensing, and 3D printing-to construct a flow injection system comprising an array of 16 LIG electrodes each connected to the gate terminal of a Field-Effect Transistor. Fifteen electrodes were functionalized with solid-state porphyrinoid layers. The flow injection design allows minimal sample volumes to be injected into a continuous carrier stream, and under these brief exposure conditions, the sensors demonstrate reproducible and reversible responses, enabling rapid and reliable analysis of liquid samples. The electronic tongue was applied to a set of red wines sourced from a single region but produced from different grape varieties. Chemometrics analysis of the sensor signals enabled both classification of wines by variety and quantification of standard wine quality indicators. Optimal sensor subsets were identified for each task, and the predicted indicators preserved the information content of values obtained via conventional laboratory measurements.

Preclinical studies suggest that tamoxifen (TAM) may interact with the efflux transporter P-glycoprotein (P-gp); however, its effect on intestinal P-gp activity in vivo remains poorly characterized. This study evaluated intestinal P-gp activity in women receiving tamoxifen therapy using fexofenadine (FEXO) as a probe substrate. Sixteen women receiving tamoxifen (20 mg/day for ≥80 days) and 12 healthy women were enrolled. All participants received a single oral dose of fexofenadine (120 mg), and serial plasma samples were collected over 12 h. Pharmacokinetic parameters were determined by noncompartmental analysis, and plasma fexofenadine concentrations were quantified by LC-MS/MS. Systemic exposure to fexofenadine was lower in women receiving tamoxifen than in healthy women. Geometric mean (95% confidence interval [CI]) AUC0-12h was 646.55 ng.h/mL (523.50-798.52) in the tamoxifen group and 994.77 ng.h/mL (832.21-1189.07) in healthy women, whereas AUC0-∞ was 715.40 ng.h/mL (588.92-869.05) and 1123.66 ng.h/mL (919.98-1372.43), respectively (P < .05). Apparent oral clearance (CL/F) was higher in women receiving tamoxifen (167.74 vs 106.79 L/h; P < .05), whereas elimination half-life was unchanged between groups. The observed pharmacokinetic profile is consistent with reduced oral bioavailability and suggests modulation of intestinal transporter-mediated drug disposition during tamoxifen therapy. These findings may have implications for the disposition of concomitantly administered orally administered P-gp substrates and warrant further investigation in dedicated clinical pharmacology studies.