Five neutral heteroleptic mononuclear vanadium(IV) hydrazone complexes ([VOL(bpy)]), derived from 2-hydroxy-5-methylacetophenone and various acid hydrazides (furoic, thiophene, benzoic, nicotinic, and isoniazid), were synthesized and shown to exhibit improved antidiabetic efficacy in streptozotocin-induced diabetic rats, with reduced toxicity and minimal bioaccumulation compared to maltolato- and picolinato-based vanadium species. Structural identity was established by spectroscopic methods. Crystal structures were obtained for four complexes, providing insight into their solid-state chemistry. Stability studies in simulated intestinal and gastric fluids showed that the complexes largely retained their integrity under intestinal conditions, whereas decomposition occurred in the highly acidic gastric environment within several minutes. In vivo experiments revealed a structure-antihyperglycemic activity relationship. The nicotinic-containing complex showed the highest activity, reducing blood glucose levels by 67% within 7 days of treatment, while the remaining complexes improved glycemic control by more than 50%. Bioaccumulation studies demonstrated <1.1% uptake in the liver and kidneys and negligible accumulation in the brain. The presented vanadium compounds enhance antidiabetic potential by addressing key limitations, particularly bioaccumulation and toxicity, associated with vanadium agents previously evaluated in clinical trials.

Ždralovac peatland in the karst field Livanjsko polje in southwestern Bosnia and Herzegovina with an area of about 3.500 ha has always been drained and used for the regional people. But drainage, agriculture and climate change cause the peat drying in the summer and create the conditions for frequent fires and serious changes of peat properties. Since 1.000 ha of peatland was used for agriculture (abandoned areas for 25 years that are being cultivated again today), and the extracted peat is used as a raw material for the plant growing substrate. The presence of certain pollutants is a good indicator of the suitability of peat for the plant production. In this paper, the state of peat related to contamination with heavy metals, polycyclic aromatic hydrocarbons - PAHs and pesticide residues was investigated in undrained peat areas, reclamation areas and peat burning sites. The presence of heavy metals in concentrations higher than permitted was not recorded. The presence of combustion products PAHs was recorded on all surfaces, but only naphthalene exceeds the permitted concentrations of organic pollutants. Only pesticide residue of dichlorodiphenyltrichloroethane (DDT) was recorded in abandoned meliorated areas used in agriculture, and the concentration exceeded the level of uncontaminated land.

Digital twins (DTs) are increasingly used to monitor and secure Industrial Control Systems (ICS), yet detecting stealthy False Data Injection Attacks (FDIAs) that manipulate system states within normal physical bounds remains challenging. Deep learning anomaly detectors often over-generalize such subtle manipulations, while classical fault detection methods do not scale well in highly correlated multivariate systems. We propose a closed-loop Information-Theoretic Digital Twin (IT-DT) framework for real-time anomaly detection. N4SID identification is combined with steady-state Kalman filtering to quantify residual distribution shifts via closed-form KL divergence, capturing both mean deviations and malicious cross-covariance shifts. Evaluations on the SWaT and WADI datasets show that IT-DT achieves F1-scores of 0.832 and 0.615, respectively, with better precision than deep learning baselines such as TranAD. Computational profiling indicates that the analytical approach requires minimal memory and provides approximately a 600x inference speedup over transformer-based methods on CPU hardware. This makes the framework suitable for resource-constrained industrial edge controllers without GPU acceleration.

OBJECTIVE This study aimed to investigate which of the two vitamin K antagonists, warfarin or acenocoumarol, provides more stable anticoagulation control in patients with mechanical heart valves and atrial fibrillation. PATIENTS AND METHODS This was a prospective, one-year clinical cohort study. In total, 73 outpatients with mechanical heart valves and atrial fibrillation who were already treated with warfarin or acenocoumarol were recruited from the Blood Transfusion Institute of the Federation of Bosnia and Herzegovina. The prothrombin time target values, expressed as the international normalized ratio (INR), were 2.0-3.0/4.0. Numerical data between the treatment groups were summarized descriptively. RESULTS Patients in the warfarin (N=35) and acenocoumarol (N=38) treatment groups were similar in terms of sex, age, body mass index, body surface area, and number of concomitant drugs known to interact with vitamin K antagonists. The number of INR measurements per patient, number of INR measurements within the therapeutic range per patient, mean time interval between successive INR measurements, and mean INR values across consecutive measurements were similar in both groups. However, compared to acenocoumarol, warfarin treatment seemed to be associated with more stable anticoagulation, i.e., with a higher mean time in the therapeutic range (TTR) (76.1±24.2 vs. 69.1±21.5%) and a smaller proportion of patients below all predefined TTR thresholds (<60%, <65%, and <70%). CONCLUSION Our unadjusted descriptive results suggested that warfarin, compared to acenocoumarol, may provide more stable and therefore safer anticoagulation control in patients with mechanical heart valves and atrial fibrillation. To confirm this, larger prospective clinical studies are needed in patients with mechanical heart valves with or without atrial fibrillation.

Background/Objectives: Patients with local/locally advanced gastric cancer (GC) undergo gastrectomy/lymphadenectomy, but recurrences are common and the disease usually progresses to death. Tertiary lymphoid structures (TLS) of varying maturity can be observed in the immune microenvironment of the primary tumor. The aim of the study was to analyze the association of TLSs and their immune cellular composition with clinicopathological variables and overall survival (OS). Methods: In a cohort of 92 GC patients who underwent gastrectomy, the characteristics of tumor core TLSs were assessed and the density of cytotoxic CD8+ T cells and regulatory FOXP3+ T cells was analyzed. Results: Patients with TLS had a better OS than patients without TLS, 19.4 months vs. 9.2 months (p = 0.001). Immature TLSs were more frequently associated with lymphovascular invasion and regional lymph node metastasis (p = 0.014 and p = 0.034). Mature TLSs had a higher FOXP3+ T lymphocyte density and lower CD8+/FOXP3+ ratio than immature TLSs (p = 0.029 and p = 0.013), and patients had a longer OS than patients with immature TLSs, 34.55 months vs. 15.2 months (p = 0.033). In patients with TLS-positive GC, cases with FOXP3+ T cells had a shorter OS, 12.7 months vs. 47.5 months (p < 0.001). Conclusions: The presence of FOXP3+ cells in TLS is associated with significantly shorter OS of patients with local/locally advanced GC.

Background and Objectives: Mitogen-activated protein kinases (p38, JNK, ERK1/2) regulate key cellular processes essential for kidney development. Disruptions in these signaling pathways can lead to congenital anomalies of the kidney and urinary tract (CAKUT), a major cause of pediatric kidney disease. This study investigates and compares the expression of these molecules in normal fetal kidneys and CAKUT-affected tissues. Materials and Methods: Forty-three human fetal kidney samples, including controls and specimens with horseshoe, hypoplastic, and dysplastic kidneys, were analyzed across developmental phases 2–4 using immunofluorescence. Quantitative image analysis and statistical comparisons were performed between developmental stages and phenotypes. Results: ERK1/2 expression increased during late development in control kidneys but was significantly reduced in hypoplastic kidneys. p38 showed phase-dependent alterations, with early upregulation in dysplastic kidneys and late elevation in horseshoe kidneys. JNK exhibited significant phase-dependent upregulation in horseshoe kidneys. P38 displayed dynamic expression associated with nephron maturation. Conclusions: MAPK pathways show distinct developmental and phenotype-specific expression patterns in human fetal kidneys. These differences reflect divergent pathogenic mechanisms in CAKUT and may support improved molecular characterization of congenital renal anomalies.

Background/Objectives: Congenital anomalies of the kidney and urinary tract (CAKUTs) represent the leading cause of pediatric chronic kidney disease, yet the molecular mechanisms underlying these malformations remain incompletely understood. While genetic studies have identified numerous CAKUT-associated genes, conventional knockout approaches often result in embryonic lethality or fail to reveal tissue-specific gene functions. This review aims to synthesize findings from conditional knockout mouse studies that have elucidated the spatiotemporal requirements of key signaling pathways during kidney development. Methods: We conducted a narrative synthesis of studies employing Cre-loxP conditional gene targeting in mouse models, identified through systematic searches of PubMed and cross-referencing of key primary research. Studies were selected based on their use of lineage-specific Cre drivers (Six2-Cre, Hoxb7-Cre, Foxd1-Cre) to investigate nephron progenitor maintenance, ureteric bud branching morphogenesis, and stromal–epithelial interactions. Results: Conditional knockout studies have redefined CAKUT pathogenesis as a disorder of dose-dependent signaling, temporal regulation, and inter-compartmental communication. WNT/β-catenin signaling operates in a biphasic, dose-dependent manner in nephron progenitors, with Six2-Cre-mediated β-catenin deletion causing premature progenitor depletion. BMP and FGF pathways demonstrate dose-dependent and context-specific functions in progenitor maintenance, while GDNF/RET signaling is essential for ureteric bud outgrowth and branching. Importantly, stromal-specific deletions have uncovered non-cell-autonomous mechanisms regulating nephron formation. Haploinsufficiency studies demonstrate that partial pathway disruption can reduce nephron endowment without overt CAKUT, predisposing to adult-onset hypertension and chronic kidney disease. Conclusions: Conditional gene targeting has mechanistically redefined CAKUT from a collection of structural malformations to a spectrum of disorders arising from quantitative perturbations in lineage-specific signaling networks. These findings establish that phenotypic severity is determined by the degree of pathway disruption, the developmental timing of insult, and the compartment affected, providing a framework for interpreting oligogenic interactions and variable penetrance in human CAKUTs.