Search Results (1,064)

Liposomal systems are advanced carriers of active substances which, thanks to their ability to encapsulate these substances, significantly improve their pharmacokinetics, bioavailability, and selectivity. This article presents the results of spectroscopic studies for a selected compound from the 1,3,4-thiadiazole group, namely 4-[5-(naphthalen-1-ylmethyl)-1,3,4-thiadiazol-2-yl]benzene-1,3-diol (NTBD, see below in the text), in selected liposomal systems formed from the phospholipid 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). Detailed spectroscopic analyses were carried out using electronic absorption and fluorescence spectroscopy; resonance light scattering (RLS) spectra measurements; dynamic light scattering (DLS); as well as time-resolved methods—fluorescence lifetime measurements using the TCSPC technique. Subsequently, based on the interpretation of spectra obtained by FTIR infrared spectroscopy, the preliminary molecular organization of the above-mentioned compounds within lipid multilayers was determined. It was found that NTBD preferentially occupies the region of polar lipid headgroups in the lipid multilayer, although it also noticeably interacts with the hydrocarbon chains of the lipids. Furthermore, X-ray diffraction (XRD) techniques were used to study the effect of NTBD on the molecular organization of DPPC lipid multilayers. Monomeric structures and aggregated forms of the above-mentioned 1,3,4-thiadiazole analogue were characterized using X-ray crystallography. Interesting dual fluorescence effects observed in steady-state fluorescence measurements were linked to the excited-state intramolecular proton transfer (ESIPT) effect (based on our earlier studies), which, in the obtained biophysical systems—liposomal systems with strong hydrophobicity—is greatly enhanced by aggregation-induced emission (AIE) effects. In summary, the research presented in this study, concerning the novel 1,3,4-thiadiazole derivative NTBD, is highly relevant to drug delivery systems, such as various model liposomal systems, as it demonstrates that depending on the concentration of the selected fluorophore, different forms may be present, allowing for appropriate modulation of its biological activity. Full article

Background: The hemoglobin–albumin–lymphocyte–platelet (HALP) score integrates the immunonutritional and inflammatory status. We evaluated whether baseline HALP predicts the 3-month response after lumbar medial branch radiofrequency ablation (RFA), defined as a Visual Analogue Scale (VAS) reduction of ≥50% and an Oswestry Disability Index (ODI) reduction of ≥40%, and identified a Youden-optimal cut-off. The discrimination and calibration of multivariable models were also assessed. Methods: This single-center retrospective cohort (N = 120) included rigorously selected patients (≥50% pain relief after two comparative medial branch blocks) undergoing standardized RFA. Multivariable logistic regression was adjusted for age, sex, Body Mass Index (BMI), smoking status, paraspinal tenderness, and baseline scores. We quantified the Area Under the Receiver Operating Characteristic Curve (AUC), Hosmer–Lemeshow (HL) goodness-of-fit, Brier score, and calibration slope; optimism was corrected using a 500-bootstrap method. Results: Responses occurred in 64.2% (VAS) and 65.8% (ODI) of participants. HALP independently predicted ODI (OR = 1.06, 95% CI 1.02–1.09; p < 0.001) and VAS (OR = 1.05, 95% CI 1.02–1.08; p = 0.001). As a single predictor, HALP showed fair discrimination (AUC 0.717 [VAS], 0.731 [ODI]). The Youden cut-off of 39.8 yielded high sensitivity (~0.87) with modest specificity (~0.58–0.61). Multivariable AUCs were 0.744 (VAS) and 0.774 (ODI), optimism-corrected to 0.680 and 0.720; calibration was acceptable (HL p > 0.05; slopes ≈ 0.74–0.78; Brier 0.188/0.179). Conclusions: HALP is a simple, low-cost adjunct that independently predicts short-term pain and functional outcomes after lumbar medial branch RFA. Incorporation into post-block triage may refine selection, especially for functional improvement, pending prospective external validation and recalibration of the cut-off. Full article

G-quadruplexes (G4s) are four-stranded DNA or RNA structures formed by guanine-rich sequences. They occur in functional regions of the genomic material, including the promoter part of genes, regulatory region, and telomeric threads. G4s play a key role in various biological processes, including transcription, replication, and telomere maintenance. Guanidine-containing derivatives can bind to G-quadruplexes, either by intercalating into the structure or by interacting with the grooves or loops. The binding can stabilize the G-quadruplex, potentially affecting its biological function. In this paper, the ability of guanidinium-containing hordatines to interact with G4 was evaluated. Analogues lacking the guanidinium group or showing the benzofuran system instead of the dihydrobenzofuran core were prepared and tested as well. NMR titration and docking calculations were used to probe the binding of the compounds to G4 of c-MYC oncogene. Spectroscopic analyses were consistent with a significant interaction of benzofurans 3 and 4 at the 5′-end and 3′-end tetrads and with the formation of ligand/G-quadruplex complexes with a 2:1 stoichiometry. The resulting data were supported by docking simulations. Cytotoxic activity was evaluated on a model of U2OS osteosarcoma (ATCC HTB-96) and breast cancer (MDA-MB-231) cell lines, further highlighting the key role of the guanidinium fragment and the benzofuran core in the G-quadruplex stabilization. Full article

Spinal cord injury (SCI) is a devastating, debilitating, and life-altering condition that lacks a cure or effective treatment as of today. An altered excitation/inhibition ratio after an injury, with an increase in inhibitory input, limits motor and sensory function. Together with the limited endogenous regeneration capacity of the affected neuronal circuits, this results in further loss of function. Hingorani and collaborators recently reported that transplantation of dissociated sensory neurons from neonatal dorsal root ganglia (DRGs) expressing the bacterial sodium channel NaChBac significantly improved locomotion in a severe SCI by increasing the excitatory neuronal input at the injury site. Here, we additionally target the potential axonal regeneration of endogenous and transplanted cells, using cytoskeleton-modulating drugs to enhance axonal length. We employ, alone or in combination, blebbistatin and epothilone B, tested in vitro. We found that individually, each compound significantly induced the sensory neurons’ axonal elongation; however, their combination completely abolished it. Interestingly, a combinatory treatment including the modification of DRGs to express the NaChBac sodium channel and the treatment with blebbistatin increased the axonal elongation in vitro. Nevertheless, when applied in vivo in a model of SCI, local and single para-amino-blebbistatin (a stable analogue of blebbistatin) administration and the transplanted NaChBac expressing sensory neurons limit the functional recovery enabled by neuronal transplantation alone. Thus, despite the beneficial outputs of isolated neuronal cultures that allow selection of in vivo combinatory strategies, the multifaced characteristics of CNS injuries limit the potential success of single and local treatment administration, demanding extended and sustained treatments. Full article

Selective depression of serpentine remains a major challenge in the flotation of low-grade nickel sulphide ores because serpentine slimes impair concentrate grade and recovery. In this study, four structurally related micromolecular depressants bearing amino and phosphonic functionalities were designed, synthesized and systematically evaluated. Micro-flotation screening (depressant range: 0–20 mg·L⁻¹) and bench-scale tests identified an operational optimum near pH 9 and a reagent dosage of ≈18 mg·L⁻¹; potassium butyl xanthate (PBX) was used as a collector and methyl isobutyl carbinol (MIBC) as a frother. Phosphonate-containing molecules (PMIDA and GLY) delivered the largest gains in pentlandite recovery and concentrate selectivity compared with carboxylate analogues and a benchmark depressant. Mechanistic studies (zeta potential, adsorption isotherms, FT-IR, and XPS) indicated that selective adsorption of amino and phosphonate groups on serpentine occurs via coordination with surface Mg sites and by altering the electrical double layer. The DLVO modelling showed that these reagents generate an increased repulsive barrier, mitigating slime coating and entrainment. Contact-angle measurements confirmed selective hydrophilization of serpentine while pentlandite remained hydrophobic. These findings demonstrate that incorporating targeted phosphonate chelation into small-molecule depressants is an effective strategy to control serpentine interference and to enhance flotation performance. Full article

The family dog is a valid model for studying complex human functions and psychological disorders such as Attention-Deficit/Hyperactivity Disorder (ADHD). Based on prior human research indicating impairments in cognitive flexibility related to ADHD, this study investigates the association between dogs’ ADHD-like traits and reversal learning performance. Since sleep improves learning both in humans and dogs, we also examined its impact in this context. Family dogs (N = 64) completed a two-way choice spatial reversal learning task, followed by a one-hour non-invasive sleep electroencephalography (EEG), and then a second reversal task. We used a validated human analogue questionnaire to assess ADHD. Dogs with higher ADHD scores required more trials to pass the first reversal test, but not after sleep. Electrode application was slower and sleep measurement more likely to fail in dogs with higher ADHD scores. Performance improved more from pre- to post-sleep in high-ADHD dogs if they spent at least 40% of the recording asleep. Our findings align with the human literature showing associations between ADHD and cognitive flexibility in dogs. The main novelty here is the ADHD-related potential benefits of repeated task exposure after sufficient sleep on cognitive flexibility. Cognitive training offers a promising direction to mitigate ADHD-related impairments in dogs. Full article

The article introduces the Guarantee-Based Bandwidth Traffic Engineering Queue (GB(Bw)-TEQ) and Guarantee-Based Utilization Traffic Engineering Queue (GB(U)-TEQ) models for queue management on router interfaces. These models implement the principles of Traffic Engineering Queues and support both DiffServ and IntServ. Their novelty lies in the ability to provide guarantees either for the bandwidth allocated to a class queue or for its utilization coefficient. Such guarantees stabilize and control the average queue length, positively affecting key Quality of Service (QoS) indicators, particularly average delay and packet loss probability. The unreserved portion of the interface bandwidth is allocated among queues in proportion to their classes. Therefore, the higher-priority queues have lower utilization, while lower-priority queues operate with higher utilization, which is consistent with DiffServ principles. The models are formulated as a mixed-integer linear programming problem with an optimality criterion and a system of constraints. Computational experiments confirmed the operability and efficiency of GB(Bw)-TEQ and GB(U)-TEQ compared to the known analogue CB-TEQ model, which does not provide service-level guarantees. The results demonstrate that the proposed models achieve the stated guarantees and enable differentiated service without blocking the lowest-class queues. These solutions can be applied to automate queue management in IP/MPLS switches and routers as well as in software-defined networks. Full article

Background/Objectives: COVID-19 was responsible for millions of deaths worldwide. This study aimed to identify substances with in vitro and in vivo effects against the SARS-CoV-2 virus. Methods: Compounds PQM-243 and PQM-249, two terpene-N-acyl-aryl-hydrazone analogues, were evaluated in vitro against SARS-CoV-2 to a antiviral activity and inhibitory effect against angiotensin converting enzyme 2 (ACE2). A possible inhibitory effect affecting the interaction between the receptor-binding domain (RBD) protein and/or ACE2 was evaluated using LUMMIT kit. A SARS-CoV-2-induced pulmonary pneumonia model was developed to evaluate the effects of the compounds after 3 days of treatment. Results: Compounds PQM-243 and PQM-249 exhibited IC₅₀ values of 0.0648 ± 0.041 µM and 0.2860 ± 0.057 µM against SARS-CoV-2 with a selective index of >1543.21 and 349.65, respectively, and IC₅₀ values of 12.1 nM and 13.3 nM, respectively, against ACE2. All concentrations used significantly reduced interactions between ACE2 and RBD. Computational studies suggest that these new compounds are potent direct anti-SARS-CoV-2 agents, capable of reducing both virus viability and its invasive ability in the host cells by reducing the interaction between RBD and ACE2. It was also demonstrated that even when administered by the oral route, both compounds reduced SARS-CoV-2-induced lung inflammation. Our data suggests that both compounds can act as potent direct anti-SARS-CoV-2 agents, reducing both viral viability and host cell entry. In addition, they exhibited a significant multi-target-directed pharmacological profile, also reducing SARS-CoV-2-induced lung inflammation when administered orally. Conclusions: Overall, these findings support further investigation of PQM-243 and PQM-249 as promising antiviral and anti-inflammatory multi-target prototypes for the development of innovative drug candidates targeting SARS-CoV-2 and other virus-related respiratory diseases. Full article

Phosphorus (P) is essential to life yet constrained by finite reserves, heterogeneous distribution, and strong chemical binding to soil minerals. Pedogenesis progressively alters the availability of P: in ‘young’ soils, P associated with Ca and Mg is relatively labile, while in ‘old’ soils, acidification and leaching deplete base cations, shifting P into organic matter and recalcitrant Al- and Fe-bound pools. Podzolized soils (Spodosols) provide a unique lens for studying this transition because podzolization vertically segregates these dynamics into distinct horizons. Organic cycling dominates the surface horizon, while downward translocation of Al, Fe, and humus creates a spodic horizon that immobilizes P through sorption and co-precipitation in amorphous organometal complexes. This spatial separation establishes two contrasting P pools—biologically dynamic surface P and mineral-stabilized deep P—that may be variably accessible to plants and microbes depending on depth, chemistry, and hydrology. We synthesize mechanisms of spodic P retention and liberation, including redox oscillations, ligand exchange, root exudation, and physical disturbance, and contrast these with strictly mineral-driven or biologically dominated systems. We further propose that podzols serve as natural experimental models for ecosystem aging, allowing researchers to explore how P cycling reorganizes as soils develop, how vertical stratification structures biotic strategies for nutrient acquisition, and how deep legacy P pools may be remobilized under environmental change. By framing podzols as a spatial analogue of long-term weathering, this paper identifies them as critical systems for advancing our understanding of nutrient limitation, biogeochemical cycling, and sustainable management of P in diverse ecosystems. Full article

Ticks transmit diseases and harm animals worldwide, and their control primarily relies on pesticides. Resistance to these pesticides has developed consistently over centuries. Arginine Kinase (AK, EC 2.7.3.3) is a conserved, ancestral enzyme that provides reserve energy in emergency situations and a viable target for novel antiparasitic drugs. Our aim was to evaluate six carbamoyl carboxylic acid analogues (CCAs) as potential lead compounds by investigating their interaction with the active site of Rhipicephalus sanguineus AK (RsAK) using a structural modeling approach. The binding was characterized using fluorescence quenching (Stern–Volmer analysis) and molecular dynamics simulations. The simulations, performed with GROMACS using the CHARMM 26 force field over 100 ns, provided atomic-level insight into the ligand–protein interactions and stability. CCA4 exhibited the lowest dissociation constant (K_D~13·10⁻⁶ M) among the analogues, which we attribute to its end moieties (carboxylate and a pyridine on the ends). Purely aromatic ends (CCA1) or those with dual carboxylates (CCA6) showed lower affinity, suggesting that electrostatic complementarity and steric fit are processes involved in the binding. Despite requiring optimization, the CCA scaffold represents a novel strategy for tick control. These compounds provide a foundation for developing synergistic agents to enhance the efficacy of sustainable acaricides. Full article

In this paper we present a detailed study of bonded knots and their related structures, integrating recent developments into a single framework. Bonded knots are classical knots endowed with embedded bonding arcs modeling physical or chemical bonds. We consider bonded knots in three categories (long, standard, and tight) according to the type of bonds, and in two categories, topological vertex and rigid vertex, according to the allowed isotopy moves, and we define invariants for each category. We then develop the theory of bonded braids, the algebraic counterpart of bonded knots. We define the bonded braid monoid, with its generators and relations, and formulate the analogues of the Alexander and Markov theorems for bonded braids in the form of L-equivalence for bonded braids. Next, we introduce enhanced bonded knots and braids, incorporating two types of bonds (attracting and repelling) corresponding to different interactions. We define the enhanced bonded braid group and show how the bonded braid monoid embeds into this group. These models capture the topology of chains with inter and intra-chain bonds and suggest new invariants for classifying biological macromolecules. Full article

This paper outlines the process of developing a low-cost system for home appliance control via real-time hand gesture classification using Computer Vision and a custom lightweight machine learning model. This system strives to enable those with speech or hearing disabilities to interface with smart home devices in real time using hand gestures, such as is possible with voice-activated ‘smart assistants’ currently available. The system runs on a Raspberry Pi 5 to enable future IoT integration and reduce costs. The system also uses the official camera module v2 and 7-inch touchscreen. Frame preprocessing uses MediaPipe to assign hand coordinates, and NumPy tools to normalise them. A machine learning model then predicts the gesture. The model, a feed-forward network consisting of five fully connected layers, was built using Keras 3 and compiled with TensorFlow Lite. Training data utilised the HaGRIDv2 dataset, modified to consist of 15 one-handed gestures from its original of 23 one- and two-handed gestures. When used to train the model, validation metrics of 0.90 accuracy and 0.31 loss were returned. The system can control both analogue and digital hardware via GPIO pins and, when recognising a gesture, averages 20.4 frames per second with no observable delay. Full article

Survival rates for those with metastatic osteosarcoma (OS) have not improved over the last four decades. It is imperative that novel approaches to treating and curing OS be sought. We, therefore, turned our attention to Brusatol (Bru), a naturally occurring Nrf2 inhibitor reported to elicit anti-cancer effects in a multitude of tumour models. Importantly there is emerging evidence that Nrf2 is implicated in chemoradiotherapy resistance in OS and that inhibiting Nrf2 may represent a desirable route to treating OS. Surprisingly, using the human OS cell line, MG63, we actually found that Bru promoted cell growth. Compared to control, normoxic cultures, the application of Bru (50 nM) over 3 days led to an increase in cell number by approximately 1.7-fold. A similar outcome occurred for cells under hypoxic conditions, although the extent of cell growth was significantly less at around 1.3-fold. Furthermore, Bru prevented MG63 differentiation in response to co-treatment with the calcitriol analogue, EB1089, and the lipid growth factor, lysophosphatidic acid. The extent of inhibition was profound at approximately 2.8-fold. The application of the Nrf2 activator, dimethyl fumarate, did not rescue these phenotypes. Whilst Bru has shown promise in other cancer models, it would appear, from our findings, that this agent may not be suitable for the treatment of OS. Full article

Advances in multimodal artificial intelligence enable new sensor-inspired approaches to lie detection by combining behavioral perception with generative reasoning. This study presents a deception detection framework that integrates deep video and audio processing with large language models guided by chain-of-thought (CoT) prompting. We interpret neural architectures such as ViViT (for video) and HuBERT (for speech) as digital behavioral sensors that extract implicit emotional and cognitive cues, including micro-expressions, vocal stress, and timing irregularities. We further incorporate a GPT-5-based prompt-level fusion approach for video–language–emotion alignment and zero-shot inference. This method jointly processes visual frames, textual transcripts, and emotion recognition outputs, enabling the system to generate interpretable deception hypotheses without any task-specific fine-tuning. Facial expressions are treated as high-resolution affective signals captured via visual sensors, while audio encodes prosodic markers of stress. Our experimental setup is based on the DOLOS dataset, which provides high-quality multimodal recordings of deceptive and truthful behavior. We also evaluate a continual learning setup that transfers emotional understanding to deception classification. Results indicate that multimodal fusion and CoT-based reasoning increase classification accuracy and interpretability. The proposed system bridges the gap between raw behavioral data and semantic inference, laying a foundation for AI-driven lie detection with interpretable sensor analogues. Full article

Objective: Mental fatigue (MF) worsens soccer performance. Further knowledge is needed to understand MF’s effects on soccer players and its underlying mechanisms. Our aim was to analyze the subjective, objective, and neural MF-related outcomes induced by different type of tasks. Methods: A randomized crossover experimental design with repeated measures was used. Thirteen amateur soccer players (M_age = 23 ± 5.43) completed three conditions: cognitive (30 min. Stroop.), physical (30 min. cycling), or combined (30 min. Stroop while cycling). Ratings of mental fatigue (measured via the Visual Analogue Scale), electroencephalographical signals (electroencephalography), and psychomotor performance (Brief-Psychomotor Vigilance Test) were measured pre- and post-condition. Soccer-related decision-making (TacticUP^® test) was assessed post-condition. Results: Linear Mixed Models analysis revealed increments in perceived mental fatigue in all conditions, especially cognitive (p = 0.004) and combined (p < 0.0001) conditions. Psychomotor performance worsened, especially for cognitive (p = 0.039) and combined (p = 0.009) conditions. The Individual Alpha Peak Frequency was lower after the cognitive task (p = 0.040) and compared with the physical task (p = 0.021). The Alpha midline power increased after the cognitive task in the central-frontal (p = 0.047) and central-posterior brain regions (p = 0.043). Conclusions: Cognitive and combined conditions were found to be more mentally demanding and fatiguing than single physical tasks. This was also reflected by an impaired reaction time. Based on the neural activity recorded, the performance impairments caused by mental fatigue were caused by reduced brain readiness (i.e., a lower Alpha Peak Frequency). However, non-significant changes were found in soccer-related decision-making. Coaches should consider the type of training tasks they recommend in light of their different effects on mental fatigue and performance. Full article