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Targeted metabolomics to assess positive effects of empagliflozin in a Parkinson’s disease model: focused on the kynurenine pathway and oxidative stress
Abstract Sodium-glucose cotransporter 2 inhibitors, such as empagliflozin (EMPA), have been increasingly investigated for their potential neuroprotective properties, but their overall metabolic impact in Parkinson’s disease (PD) remains incompletely understood. Using a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD, we investigated the effect of EMPA on tryptophan (TRP) metabolism, neurotransmitter levels and antioxidant markers in the striatum. Targeted ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC–MS/MS) was used for metabolite quantification. Pairwise group differences were assessed using Welch’s two-sample t -test, with false discovery rate correction, and multivariate analyses were applied for exploratory pattern recognition. EMPA treatment significantly enhanced the neuroprotective arm of the kynurenine pathway (KP), increasing kynurenic acid (KA), anthranilic acid (AA), xanthurenic acid (XA) and the corresponding enzymatic activity ratios in MPTP-induced PD animals. The selective elevation of the KA/TRP ratio without a corresponding change in KYN/TRP suggests that EMPA acts specifically on the KAT-mediated neuroprotective branch, potentially through restoration of astrocytic redox state in the striatum, rather than through generalized modulation of IDO/TDO-driven TRP catabolism. In Sirtuin3 knock-out (S3KO) mice, EMPA reduced 3-hydroxykynurenine (3OHK) levels and the Oxidative Stress Index (3OHK/(KA + AA + XA)), and improved glutathione redox status, as reflected by reduced GSSG levels and an improved GSH/GSSG ratio. These results demonstrate that EMPA exerts significant neurometabolic effects in a mouse model of PD, shifting KP flux towards neuroprotective metabolites and improving redox homeostasis—particularly in the context of mitochondrial dysfunction modelled by Sirtuin3 deficiency. Future studies extending these findings to additional experimental models and clinical settings will be essential to fully elucidate the translational potential of EMPA in neurodegeneration.
Prenatal depression increases the odds of preterm birth in a prospective cohort study in Hangzhou
Integrated in vitro and in vivo evaluation of ivermectin hydrogel formulation for management of scabies with pharmacological assessment
Abstract Scabies is a contagious skin disease caused by Sarcoptes scabiei mites, posing a significant health risk, especially in poor, crowded settings. Existing treatments are facing challenges due to poor compliance and side effects, necessitating alternative therapies. Hydrogel formulations offer promise by enhancing drug release and bioavailability. This study tested a novel topical ivermectin (IVR) hydrogel for scabies, evaluating its effectiveness, anti-inflammatory, and antioxidant properties. It also assessed treatment outcomes of skin structure and its effect on animal behavior and locomotor activity. IVR hydrogel (1% w/v) was formulated and evaluated based on its physicochemical properties, in vitro release kinetics, and acaricidal activity using a contact bioassay and scanning electron microscopy (SEM). An in vivo bioassay was performed using experimentally infested rabbits treated topically with IVR hydrogel. Treatment efficacy was evaluated via histopathology, oxidative stress, inflammatory and immunological markers, and behavioral changes measured through open-field testing. The IVR gel, at a 100% concentration, achieved complete mite mortality in vitro within 10 minutes, accompanied by extensive cuticular damage. In vivo , treated rabbits exhibited marked clinical improvement, attaining a clinical score near zero (0.17) by day 21, alongside enhanced skin condition and reduced inflammation. The treatment resulted in a statistically significant reduction in inflammatory markers (TNF-α, IL-6, P< 0.001) and oxidative stress (MDA, P< 0.001) without significant alterations in specific immunoglobulin levels (IgG and IgE). Histopathological analysis confirmed improvement of skin architecture, while behavioral assessments revealed no adverse effects on animal behavior. IVR hydrogel demonstrated significant, concentration-dependent acaricidal activity, biocompatibility, and effectiveness in reducing oxidative and inflammatory damage. Based on these findings, topical ivermectin hydrogel may offer a promising platform for further investigation as a treatment modality for scabies.
Perennial vegetative strips promote spillover of beneficial soil microorganisms into adjacent crop field
In vitro assessment of experimental bioactive tooth gel formulas containing L-arginine, ginger and eggshell for remineralization and anti-bacterial effect
Abstract The present study evaluates the effect of different novel tooth gel formulations combining L-arginine, ginger and eggshell on artificially demineralized enamel. This study used 50 bovine enamel specimens, divided into five groups according to the used toothpaste ( n = 10): G1: Elmex Pro Argin (commercial positive control containing L-arginine), and four experimental groups; G2: ginger extract, G3: experimental eggshell + ginger, G4: experimental L-arginine + ginger, and G5: experimental L-arginine + eggshell + ginger. White-spot lesions were induced then the tested formulations were applied twice daily for one month. Evaluations at baseline, post-demineralization, and post-remineralization included Vickers microhardness (VMH), Scanning electron microscope (SEM), Energy Dispersive X-ray Analysis (EDX), elemental mapping and Confocal Laser Scanning Microscopy (CLSM). Also, antibacterial activity was assessed against commensal and cariogenic bacteria. After remineralization, all experimental groups showed a statistically significant increase in microhardness compared to their corresponding demineralized values ( P < 0.001). Arginine-containing formulations (G4 and G5) showed statistically significant higher microhardness values and Calcium content following EDX analysis compared to the non-arginine formulations (G2 and G3) ( P < 0.05). In agar well diffusion assay, the arginine-containing formulations (G1, G4, and G5) produced statistically significantly larger inhibition zones against both cariogenic and commensal bacterial species compared with the arginine free formulations (G2 and G3) at P < 0.05. The synergy of L-arginine with ginger and eggshell extract provides enhanced enamel remineralization, and antimicrobial efficacy, positioning these natural tooth gel formulations as promising alternatives or adjuncts to conventional fluoride-based products.
Genomic characterization of multidrug-resistant Klebsiella pneumoniae clinical isolates from India
Author Correction: COX-2/PGE₂ signaling drives Toxocara canis-induced lung pathology by enhancing plasminogen activator activity and collagen VI degradation
Lineage topology, replication kinetics and cell cycle synchronization reveal regulated growth dynamics in human bone marrow stromal cell colonies
Abstract Bone marrow stromal cells (BMSC) – which include skeletal stem cells – are a promising tool in regenerative medicine. However, their heterogeneous and unpredictable in vivo behaviour remains a critical barrier preventing the development of standardized therapeutic approaches for skeletal tissue regeneration. Several studies have attempted to identify in vitro features that could correlate with the in vivo differentiation properties, yet the mechanisms ruling BMSC heterogeneity remain poorly understood. Here, using time-lapse imaging, we lineage-trace 32 single-cell-derived BMSC colonies through seven generations. We observe significant inter-colony and intra-colony heterogeneity in lineage topology (determined by the number of senescent or apoptotic cells) and in replicative kinetics (measured from proliferating cells only). Interestingly, topology and kinetics are strongly correlated, suggesting the existence of regulatory factors linking the non-dividing/apoptotic subpopulations with proliferating cells. Furthermore, BMSCs display a high degree of cell-cycle synchronization during early generations, indicating stage-specific regulatory mechanisms through which cells influence each other. By employing a non-interacting population growth model, we demonstrate that the observed synchronization cannot be explained by an uncorrelated branching process; instead, correlated division times among cells must be present. Our findings reveal fundamental mechanisms governing BMSC heterogeneity and growth dynamics that may inform strategies to control their regenerative potential.
Author Correction: The AIM2 inflammasome exacerbates atherosclerosis in clonal haematopoiesis
L arginine and radiofrequency electromagnetic field attenuate inflammatory and apoptotic injury after experimental subarachnoid hemorrhage
Author Correction: Postprandial lipid metabolism durably enhances T cell immunity
Darboux transformation and quasideterminant solutions of a noncommutative semi-discrete coupled dispersionless integrable system
Abstract We present a noncommutative generalization of the semi-discrete coupled dispersionless integrable system. The motivation stems from the role of noncommutative geometry in string theory and D-brane dynamics, and the need to understand soliton dynamics in matrix-valued field theories beyond the standard abelian setting. A matrix Lax pair for the noncommutative semi-discrete coupled dispersionless system is proposed, and the corresponding equations of motion are obtained as the compatibility conditions of this Lax pair. A Darboux transformation is constructed both for the Lax pair and for the nonlinear field equations, and its iteration yields multisoliton solutions written in a compact quasideterminant form. We then investigate noncommutative semi-discrete solutions of the matrix fields and discuss their qualitative behaviour on the space–time lattice. Furthermore, an equivalence is established between the noncommutative semi-discrete coupled dispersionless system and a noncommutative semi-discrete sine-Gordon equation. Finally, by applying an appropriate continuum limit, we recover multisoliton solutions of the corresponding noncommutative continuous coupled dispersionless system.
A high-gain, low-SAR UWB all-textile two-port MIMO antenna based on an AMC structure for wireless body area networks
GSA-YOLO enables high-efficiency real-time X-ray security inspection via structured sparsity and adaptive knowledge distillation
Interaction of PEGylated gold nanorods with HIF-1α/Ki-67 in inhibiting immunosuppression and arresting cancer proliferation in murine fibrosarcoma
Relativistic electron acceleration at the bow shock of Jupiter and beyond
Automated FDG uptake/PET-CT fused scan diagnosis of various lymph node tumors using object detection AI techniques
Abstract Lymph nodes (LN) constitute a vital component of the lymphatic system, serving a pivotal role in immune functioning and maintaining fluid balance in the body. Moreover, they serve as markers for tailoring treatments. Inaccurate assessment of LN status may lead to either inadequate treatment or an overly aggressive treatment approach, thereby heightening the risk of recurrence and postoperative complications. Many imaging techniques are used to assess and characterize LNs, but they are limited by low sensitivity for detecting small metastases. Therefore, artificial intelligence (AI) object detection techniques are utilized to localize the relevant objects in images and classify them into relevant classes. This paper proposes a method for detecting 13 LN classes across different body organs using real-world PET-CT datasets. We provide two modules: the first establishes a new LN dataset by fusing CT and PET images for each patient, then denoising and annotating the classes. The dataset was first divided into 80% training, 10% validation, and 10% testing, with data augmentation applied only to the training set to avoid data leakage. Subsequently, 5-fold cross-validation was conducted on the training and validation data to ensure a more reliable evaluation. The final results are reported based on the cross-validation protocol, while the hold-out test set is used for independent assessment. The second module is object detection based on a modified YOLOv8. We selected the kernel, optimized the feature-extraction backbone layers, and tuned other hyperparameters. We compared the performance of eight popular one-stage architectures: YOLOv7, YOLOv8, YOLOv9, YOLOv10, YOLOv11, YOLOv12, YOLONas, and the modified YOLOv8. Work performance has been measured using precision, recall, mean average precision (mAP50), and Dice similarity coefficient (DSC). The findings demonstrate the superiority of the proposed method, with improvements of 78%, 75%, 81%, and 76%, respectively.