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Targeting colorectal cancer with pyrazolo[4,3-e][1,2,4]triazine and pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulfonamides: comprehensive in vitro evaluation
Abstract Colorectal cancer (CRC) remains a major global health challenge, ranking as the third most common malignancy and the second leading cause of cancer-related mortality worldwide. This study aimed to evaluate a novel series of pyrazolo[4,3- e ][1,2,4]triazine and pyrazolo[4,3- e ]tetrazolo[1,5- b ][1,2,4]triazine sulfonamides as potential anticancer agents, with a focus on their cytotoxic and mechanistic effects against CRC cell lines. Incorporation of the tetrazole ring significantly increased cytotoxic activity (up to 50-fold) and selectivity (3.6-9.2-fold) compared to non-tetrazole analogues (2.2–3.3). Pyrazolo-tetrazolo-triazine derivatives exhibited IC₅₀ values ranging from 0.12 to 1.1 µM and demonstrated enhanced solubility and consistent biological activity. Selected derivatives (MM134, MM136, MM137, MM139) induced marked DNA damage and inhibition of cell proliferation, with cell cycle analysis confirming apoptotic and necrotic features depending on the compound and exposure time. Electrochemical analyses confirmed direct interactions between MM compounds and double-stranded DNA. Notably, MM137 was the potent inducer of cell death in both HCT-116 and HT-29 3D spheroids at concentrations as low as 5 µM, comparable to the most pre-clinically advanced MM129 derivative. In conclusion, the study highlights pyrazolo[4,3- e ]tetrazolo[1,5- b ][1,2,4]triazine sulfonamides as promising anticancer candidates with potent cytotoxicity, favorable selectivity, and potential multimodal mechanisms of action.
MedNet-FS: a few-shot learning framework for 3D MRI-based knee injury classification
Oribatid mites like lichens—feeding preferences among three Cladonia species with different chemistry
Abstract Lichens in general and members of the genus Cladonia in particular are known for their repertoire of chemical substances. These substances have been attributed various roles, including a role in the defence against herbivores. Unsurprisingly, Cladonia species share habitats with many small invertebrates, like mites. Mites have been suggested to regularly feed on lichens, with potential detrimental effects for the lichen. Here we tested the feeding preferences of two oribatid mite species ( Carabodes areolatus and C. marginatus ) for three members of the lichen genus Cladonia . Cladonia coniocraea , C . norvegica and C . rubrotincta have similar morphology, ecology, and they regularly share their habitats with the selected mites, but produce different chemical compounds (barbatic acid in Cladonia norvegica , barbatic and rhodocladonic acids in Cladonia rubrotincta , and the fumarprotocetraric acid complex in Cladonia coniocraea ), some of which are considered to have antiherbivore properties. Our experiments conducted over a period of 14 days revealed that none of the three lichens was rejected as a food source. When given a choice between two different lichens, mites prefer C. rubrotincta over C. norvegica , but feed to a similar extent on C. coniocraea and C. rubrotincta . In experiments only with C. rubrotincta , which produces the red chemical compound rhodocladonic acid, a substance with suggested antiherbivore activity, mites surprisingly seem to prefer red-pigmented over unpigmented tissue.
SHARP: a hybrid metaheuristic approach for intelligent robotic path planning
Abstract Robotic path planning is a fundamental requirement for autonomous navigation, where a robot must reach a target while avoiding obstacles and producing a feasible, smooth, and efficient trajectory. This paper presents SHARP, a hybrid metaheuristic planning framework based on Particle Swarm Optimization, Sine Cosine search, and lightweight Nelder–Mead simplex refinement. The proposed framework introduces two scalarization-based multi-criteria decision layers for robotic path planning: Priority-PSN, which prioritizes path length while penalizing obstacle and boundary violations, and No-Preference-PSN, which selects a balanced solution by minimizing the normalized distance to an ideal point. Cubic-spline interpolation is further applied to convert optimized waypoints into smoother executable trajectories. The approach is validated in static and dynamic two-dimensional environments with different obstacle densities and motion patterns. In six static benchmark environments, PSN consistently produces shorter collision-free paths than PSO, GWO, and SCA. Additional ablation and function-evaluation-normalized experiments show that the full hybrid improves average path quality in cluttered maps, although this improvement is accompanied by higher computational cost. In dynamic replanning experiments, PSN achieves the highest success rate among the evaluated variants, but with increased latency. SHARP provides a practical and adaptable optimization-based framework for intelligent robotic path planning under static and dynamic constraints.
Influence of new residential construction varying in housing density on bird species, human tolerance guilds, and communities
Effect of slit-regulated 3D embroidered sensor structures on contact area-variation-based strain sensing performance in smart gloves
Cenomanian theropod teeth from Algora (central Spain), new evidence for majungasaurine abelisaurids in Europe
New approaches of N-acetylcysteine on fatty acid transport and metabolism in a rat model of MASLD induced by high-fat diet
Abstract The number of individuals suffering from metabolic dysfunction-associated steatotic liver disease (MASLD) has increased. The worldwide occurrence of fatty liver diseases is estimated to affect between 30% and 38% of adults from all races, ethnic group and sex in diet dependent manner, positioning these conditions as leading causes of chronic liver diseases. It is crucial to identify a natural substance that can safeguard against alterations in the lipid balance. There is a significant amount of research indicating that n-acetylcysteine (NAC) helps prevent inflammation and lipid deposition in peripheral tissues. The aim of this study was to investigate the effects of NAC on lipid metabolism and fatty acid composition in the liver of rats fed a high-fat diet (HFD). An experiment was conducted on male Wistar rats that received a standard diet or an HFD, divided into 4 groups ( n = 6). Half of the rats from the Control and HFD groups received and intragastrically NAC solution. After 8 weeks of experimental procedures, rats were anaesthetized, and the liver tissue was used for further analysis. Gas-liquid chromatography was used to determine the content of total lipid fractions and fatty acid composition in each fraction. Western blot and real-time PCR methods were used to measure the expression of protein or mRNA of fatty acid (FA) transporters and enzymes that regulated lipid metabolism. NAC decreased FA transport into hepatocytes by a decline in the expression of FATP2, FABPpm, and CD36. Supplementation of NAC also significantly reduced elongation of C16:0, PA to C18:0 and enlarged the C20:0/C18:0 elongation ratio with simultaneous enhancement in C20:5 n-3, EPA and C22:6 n-3, DHA levels. Based on our results, we concluded that NAC point anti-inflammatory and pro-resolving properties, suggesting its potential role in the limitation of the development of simple steatosis changes by altering lipid disruption in rats receiving a high-fat diet.
Real-time ultrasound-guided versus landmark techniques for thoracic epidural placement in elderly patients: A randomized comparative study
Training squared-hinge support vector machines by an explicit QUBO–Ising construction with quantum-annealing execution
Abstract Quantum annealers natively minimize quadratic unconstrained binary optimization (QUBO) problems, yet faithfully compiling continuous convex objectives into discrete binary forms with formal guarantees remains challenging. We present a complete, algebraically verifiable pipeline for training a linear squared-hinge support vector machine on quantum annealing hardware. The construction comprises four stages with rigorous justification: (i) an exact epigraph reformulation eliminating the hinge nonlinearity, (ii) equality conversion via surplus variables with a quadratic penalty whose exactness on the finite binary domain is formally established, (iii) closed-form QUBO coefficients and a provably energy-preserving Ising mapping, and (iv) a moment-based three-component decoder that reconstructs continuous parameters from noisy annealer samples using empirical first- and second-order statistics. We execute this pipeline end-to-end on D-Wave Advantage systems and evaluate under a rigorous protocol with 30 stratified splits, bootstrap confidence intervals, paired tests, and effect sizes. The feature-wise solver achieves 87–89% test accuracy on the Iris benchmark, competitive with classical baselines at this scale. We contribute a fully auditable reduction from convex SVM training to Ising optimization rather than claiming quantum advantage, and explicitly characterize limitations from discretization, embedding overhead, and feature-wise decomposition.
A pilot study in the swine model of lethal cyanide intoxication indicates efficacy of a platinum-methionine complex countermeasure
Data-driven spatial metamodeling for non-Gaussian digital roughness mapping in precision machining
Analysis of toxicity and mechanism of xylazine on testis with network toxicology and molecular docking strategy
Performance analysis of electrostatic and transport characteristics of underlap-engineered gate-all-around carbon nanotube (CNT) FETs for nanoelectronics circuitry applications
Interactive roles of mineralogy, microbial community composition and litter quality in regulating organic matter turnover
Self-care practices among women with gestational diabetes in low-resource settings in Ghana: a phenomenological study
Research on attention mechanism and loss function based on YOLOv5 to improve the detection method of underground personnel wearing safety helmets
Enhanced bioavailability of a novel double-layered nano-liposomal curcumin (BNT–C060): a randomized, double-blind, clinical trial
Abstract Curcumin exhibits potent anti-inflammatory, antioxidant, and neuroprotective effects. However, its therapeutic potential is severely limited by poor oral bioavailability due to low solubility, rapid metabolism, and poor intestinal permeability. This study evaluated the single-dose pharmacokinetics and relative bioavailability of BNT–C060, a novel double-layered chitosan/alginate-coated nano-liposomal curcumin, versus conventional free curcumin in healthy male volunteers. In this randomized, double-blind, parallel-group trial, 18 healthy males ( n = 9/group) received single oral doses of BNT–C060 (400 mg curcumin-equivalent) or free curcumin (2,000 mg) under fasting conditions. Plasma and urine samples were collected over 24 h for total curcumin analysis (LC–MS/MS after β-glucuronidase treatment). BNT–C060 demonstrated superior dose-normalized pharmacokinetics: 23.2-fold higher plasma AUC 0–t (5.00 vs. 0.22 ng·h/mL/mg), 53-fold higher C max (1.06 vs. 0.02 ng/mL/mg), and 35.3-fold higher urinary exposure. T max was earlier (0.86 vs. 3.3 h). A single oral dose of BNT–C060 was generally well tolerated in healthy male volunteers within the evaluated dose range, with no clinically significant safety signals observed under the study conditions. BNT–C060 achieved substantially higher plasma concentrations (C max 423 ng/mL vs. 34 ng/mL free curcumin) compared with free curcumin, suggesting improved systemic exposure with the nano-liposomal formulation. These proof-of-concept findings provide a rationale for further clinical investigation of this advanced nano-liposomal delivery system.