Search Results (194,096)

New indazole and pyrazole nucleoside analogues were synthesized by enzymatic transglycosylation using E. coli purine nucleoside phosphorylase (PNP). Indazoles substituted at position 5 or 6 with bromine, pyrazole or pyrimidine fragments were used as heterocyclic bases. In the case of indazole-pyrazole hybrids, the selectivity of PNP in glycosylation of the pyrazole fragment, rather than the indazole one, was established. Molecular modeling methods allowed the identification of the preferred orientations of substrates in the active site of the enzyme, leading to the formation of N1- and N2-regioisomers of indazole. Unique substrate specificity ensured the possibility of glycosylation of the bases with conversion rates of 65–100% (according to HPLC analysis of the reaction mixtures) and isolated yields of 19–94%. It was shown that the synthesized nucleoside analogues are not inhibitors of E. coli adenosine deaminase (ADA). They do not exhibit cytotoxicity towards cancer cell lines (SH-SY5Y neuroblastoma cell lines, K-562 lymphoblastic cells, and HL-60 promyeloblastic cells). The activity of indazole derivatives against Mycobacterium tuberculosis (strain H37Rv) was determined by the microdilution method. 1-(β-D-2′deoxyribofuranosyl)-5-bromo-indazole and 5-(pyrimidin-5-yl)-1H-indazole at a concentration of 50 μg/mL were able to inhibit 50% and 90% of the culture growth, correspondingly. Full article

This study presents the first evaluation of the degree of nonlinearity in site response at strong-motion stations in Türkiye during the 6 February 2023 Kahramanmaraş earthquake sequence (Mw 7.8 and Mw 7.5) using earthquake horizontal-to-vertical spectral ratios (eHVSRs). The analysis uses 2050 weak-motion and 175 strong-motion records from 24 AFAD stations in the Kahramanmaraş and Hatay regions, where some of the strongest ground motions and most severe damage were observed. The selected stations cover a broad range of site conditions, from soft alluvial deposits to relatively stiff sites, as characterized by Vs30. Conventional assessments of nonlinear site response generally rely on peak ground-motion measures and one-dimensional site proxies, particularly Vs30. In contrast, this study evaluates nonlinear behavior within a record-based framework that accounts for the combined influence of source characteristics, propagation path, local site conditions, and basin-related wave effects. Nonlinear site response is quantified by comparing strong-motion and weak-motion eHVSR spectra, where the weak-motion reference is derived from records with peak ground velocity (PGV) lower than 1 cm/s. A principal methodological contribution is the use of record-specific S-wave windows selected according to the event-dependent energy content of each record, rather than a uniform fixed-duration window. This energy-based procedure focuses on the dominant S-wave energy while reducing pre-event noise and late-arriving coda effects. Incorporating record-specific S-wave duration improves degree of nonlinearity (DNL) estimates, proving that nonlinear response is driven not just by peak amplitude and near-surface stiffness but also by duration-dependent cyclic deformation demand. The proposed framework provides record-based constraints for empirical ground-motion models and regional three-dimensional physics-based earthquake simulations. Full article

This study evaluated the influence of the manufacturing method and cementation protocol on the fracture load of zirconia molar crowns. A total of 32 full-contour crowns with a wall thickness of 1 mm were fabricated from 3 mol% yttria-stabilized tetragonal zirconia polycrystal (3Y-TZP). Sixteen crowns were produced by 3D printing (LithaCon 3Y 210, Lithoz) and 16 by milling (e.max ZirCAD LT, Ivoclar Vivadent). Within each manufacturing group, eight crowns were adhesively luted with a dual-cure resin cement (Bifix QM, VOCO) and eight were conventionally cemented with a glass ionomer cement (Ketac Cem, Solventum). All crown–die complexes underwent thermomechanical aging (6000 thermal cycles between 5 °C/55 °C; 1.2 × 10⁶ cycles at 50 N) as a correlate of five years of clinical service, followed by axial loading to failure. The statistical analysis was a two-way ANOVA on log10-transformed fracture loads with manufacturing and cement as fixed effects (α = 0.05). All crowns survived thermomechanical loading without failure. Milled zirconia crowns showed significantly higher fracture loads when adhesively luted (7162 ± 1294 N) compared with conventional cementation (4021 ± 1126 N; p < 0.001). In contrast, no significant differences were observed between adhesive (4986 ± 1301 N) and conventional cementation (5581 ± 1618 N) for 3D-printed zirconia crowns. Additively manufactured crowns exhibited greater variability in fracture loads (broader interquartile ranges) than their milled counterparts. Two-way ANOVA detected a significant Manufacturing × Cement interaction (p < 0.001), indicating that the effect of cementation differed by manufacturing route. Adhesive cementation increased fracture load for milled zirconia, whereas no statistically significant cementation effect was detected for 3D-printed zirconia under the present conditions. Given the sample size and the observed variability, the study was powered to detect very large effects but not medium or small ones; therefore, this non-significant difference should not be interpreted as proof of no effect. Full article

Skeletal muscle regeneration is often impaired after acute muscle damage induced by viperid snake venoms, such as that of Bothrops asper, a medically relevant species in Latin America. It has been shown that traces of venom that remain in the damaged muscle affect myogenic cells in culture, raising the possibility of inhibiting these toxins during the regenerative process to improve regeneration. Using a mouse model of myonecrosis and regeneration, we evaluated the effects of Varespladib (a phospholipase A₂ inhibitor) or Marimastat (a metalloproteinase inhibitor) on muscle regeneration when administered intravenously 24 h after the onset of myonecrosis, i.e., after muscle damage has occurred. The regenerative process was evaluated 14 and 28 days after venom injection. Marimastat, or a combination of both inhibitors, increased the number and diameter of regenerating muscle fibers and reduced tissue fibrosis compared to tissues from mice receiving only venom, as judged by qualitative and quantitative histological assessment. These initial results underscore the deleterious role of traces of venom components, especially metalloproteinases, in damaged muscles during muscle regeneration. Full article

A naive Bayesian classifier (NBC) combined with principal component analysis (PCA) effectively differentiates the dose-dependent effects of certain groups of psychoactive drugs based on their impact on the amplitude–spectral characteristics of electrocorticograms (ECoG) in rats. This approach has been shown to be useful for pharmacological screening of agents with unknown or poorly understood activity. Despite previously obtained optimistic results, classification determination for some drugs was inaccurate, necessitating the search for possible ways to improve the predictive effectiveness of the proposed algorithm. One possible approach would be to use as input quantitative data not only the impact of the psychoactive drugs studied on the amplitude–spectral characteristics of ECoG but also connectivity changes, including the average coherence power of different pairs of leads. The aim of this study was to compare the accuracy of NBC in classifying the pharmacological mechanism of action of agents with well-known mechanisms (test set) using pharmaco-EEG data on changes in the amplitude–spectral characteristics of ECoG, coherence, and the combined use of two data sets. Materials and methods. Experiments were performed on Wistar rats with chronically implanted ECoG electrodes. The training set, relative to which the effects of the pharmacological agents from the test set were classified, were the matrices of effects of 12 pharmacological agents: the NMDA antagonist dizocilpine, the D2/D3 antagonists haloperidol and sulpiride, the M-anticholinergic tropicamide, the H1/5HT2A receptor blocker hydroxyzine, the acetylcholinesterase inhibitor galantamine, the alpha-2 adrenergic agonist dexmedetomidine, the alpha-2 adrenergic antagonist atipamezole, the adenosine receptor blocker caffeine and the GABA-mimetics aminophenylbutyric acid (phenibut), bromdihydrochlorophenylbenzodiazepine (phenazepam) and 5-ethyl-5-phenyl-2,4,6(1H,3H,5H)-pyrimidinetrione. The test set included various drugs with tropism for the targets of the training set drugs: dopamine receptor antagonists chlorpromazine, droperidol, tiapride and raclopride, H1-histamine blockers diphenhydramine and promethazine, 5-HT2-receptor blockers ritanserin and glemenserin, acetylcholinesterase inhibitor ipidacrine, alpha2-adrenergic receptor antagonist yohimbine, alpha2-adrenergic agonists medetomidine and xylazine, GABA-mimetics 5-ethyl-5-(1-methylbutyl)-2,4,6(1H,3H,5H)-pyrimidinetrione and chloral hydrate. The analysis of the ECoG signal included the calculation of 132 amplitude–spectral characteristics and 75 coherence indicators, which, using the PCA, led to new integrative indicators used for further classification of the NBC. Results and discussion. For each drug in the test set, the median similarity probability with a particular group from the training set was calculated, which was used to assess the classification quality. It was found that, when using the amplitude–spectral characteristics of ECoG, the proposed methodological approach allows for the identification of the ECoG effects of several groups of psychoactive drugs, including D2/D3-dopamine, M-cholinergic, H1-histamine, and 5-HT2-serotonin receptor blockers, AChE inhibitors, GABA-mimetics, and alpha-2-adrenergic receptor agonists and antagonists. This approach enabled the correct classification of 18 of 24 groups in the test set. When using changes in coherence indices as the initial data, the classification accuracy also amounted to 18 of 24 groups. When combining the two data sets, the number of correctly identified NBC groups was 20 of 24 groups. When comparing the classification during training (confusion matrix), it was found that coherence data or adding coherence data to the data based on changes in amplitude–spectral characteristics leads to a statistically significant (p < 0.01 in both cases) increase in accuracy. Conclusions. The obtained data demonstrated high accuracy in classifying the pharmacological activity of the test sample drugs using any of the three compared approaches. Despite the lack of statistically significant differences between them, classification based on the combined dataset demonstrated a higher number of “correct” similarities. This allows us to recommend the approach based on combined data of drug effects on amplitude–spectral characteristics and coherence as the most promising for further studies using pharmaco-EEG screening. Full article

In this work, Cu₂CoSnS₄ (CCTS) thin films were deposited on glass substrates by thermal evaporation and investigated for photovoltaic applications. The influence of substrate temperature, varied from 25 °C to 200 °C, on the structural, morphological, and optical properties of the films was experimentally studied using X-ray diffraction (XRD), scanning electron microscopy (SEM), and photoluminescence (PL) measurements. XRD analysis confirmed the formation of crystalline CCTS with a stannite structure and a preferential orientation along the (112) plane. SEM observations revealed rough and non-uniform surfaces accompanied by an increase in grain size with increasing substrate temperature. Room-temperature PL measurements indicated a band-gap energy of approximately 1.3 eV, suitable for photovoltaic applications, and confirmed the presence of secondary phases in the p-type stannite CCTS films. Despite the promising photovoltaic properties of CCTS, numerical studies on CCTS-based solar cells remain scarce in the literature. In this context, a numerical study of the CCTS-based solar structure grown on glass was also performed using SCAPS-1D, showing good agreement with experimental photovoltaic results and validating the simulation model. Replacing the glass substrate with silicon improved the device efficiency to 5.77%. Further optimization of the series and shunt resistances significantly enhanced the photovoltaic performance, achieving a power conversion efficiency of 16.77%, with FF = 52.94%, V_oc = 0.89 V and J_sc = 35.19 mA/cm². Full article

The rapid growth of rural e-commerce is reshaping rural development, yet its implications for territorial sustainability remain unclear. Using panel data from 1503 Chinese counties from 2014 to 2022, the effects of Taobao Village development and the mechanism of territorial sustainability are examined through causal, spatial, and mechanism analyses. The results show the following: (1) Taobao Village development significantly improves territorial sustainability, with stronger effects observed in central and northeastern China, while the impacts vary considerably across regions due to differences in economic foundations, digital infrastructure, and land-use conditions. (2) Spatial analysis reveals that the sustainability-enhancing effects of Taobao Villages are mainly localized, with no significant spillover effects to neighboring counties, indicating the constraints of existing administrative and spatial governance systems. (3) The ecological land-use change induced by Taobao Village development is characterized by quantity reduction with potential quality upgrading. The development of Taobao Village has reduced the ecological land area, but it does not mean a decline in ecological functions. The converted land may be composed of low-quality ecological plots, and the fiscal benefits driven by e-commerce and China’s land use compensation policy may maintain or enhance the overall ecological function. These findings highlight the importance of integrating digital rural development with ecological sustainability and territorial spatial governance. The study provides policy implications for promoting resilient and sustainable rural transformation through differentiated land-use strategies. Full article

In the last decade, significant progress has been made in understanding the crucial role of melanin in energy production in cells and tissues (which has been estimated to account for up to 90% of the total in organisms). This suggests the need to reconsider the central role of glucose and ATP, which instead are thought to play a primary role in building biomass. The mechanism by which melanin absorbs a wide range of the electromagnetic (em) spectrum (from FIR to far UV and ionizing radiation, helping organisms to cope with exposure to X- or γ rays) and dissociates water molecules (releasing oxygen, hydrogen, and free energy) has been observed in a number of experimental settings to occur in biological systems. This mechanism has also been reproduced in laboratory settings and has shown valuable applications in water revitalization and purification treatments. In terms of bioenergetics, these findings highlight the importance for mammals (including humans) of sunlight exposure (which provides the full em spectrum) while maintaining adequate hydration to maintain good homeostasis and optimal health. This process of hydrolysis and oxygen production through melanin and light has been proposed by Arturo Solìs Herrera and thus termed “human photosynthesis”. However, the proposed dissociation of water molecules (with an initial electron transition at around 7 eV and an ionization threshold of 12.62 eV) is not explainable within the still semi-classical vision of quantum mechanics (QM), especially when triggered by photons with much lower energy. In contrast, a description of water and biological matter in terms of quantum field theory (QFT) that takes into account the key role of coherence and the interplay with hydrophilic surfaces offers a coherent and physically grounded interpretive framework. In this paper, we propose a possible semi-quantitative theoretical framework for this fundamental biological process, which appears to underpin most metabolisms in heterotrophic organisms by interpreting water and living matter in terms of quantum electrodynamics (QED). This may open new perspectives in biochemistry and medicine. Full article

Epilobium parviflorum Schreb. is a medicinal plant used traditionally against inflammatory disorders whose cytotoxic potential is still incompletely revealed. The current study investigates the phytochemical composition and in vitro cytotoxic activity of four hydroalcoholic extracts prepared from the aerial parts of E. parviflorum by using maceration and Soxhlet extraction. The extracts were characterized in terms of total phenolic, flavonoid and tannins composition and LC-MS was used to identify its individual polyphenols. Their biological effects were assessed against four cancer cell lines (A375 melanoma, HT-29 colorectal adenocarcinoma, PANC-1 pancreatic carcinoma and SK-OV-3 ovarian adenocarcinoma cells), while using HaCaT keratinocytes as healthy cells in order to assess selectivity. Cell viability, cytoskeletal and nuclear morphology, mitochondrial respiration and network pharmacology were further investigated. A complex phenolic profile was revealed, with hyperoside being identified as the main component in all extracts while the extraction parameters strongly influenced the recovery of various phenolic compounds. All extracts reduced cancer cell viability in a dose-dependent manner after 24 h exposure, with the most pronounced effects observed at 720 and 1000 μg/mL, while HaCaT cells were left relatively unaffected. The morphological assessment indicated nuclear condensation, fragmentation and cytoskeletal disruption following the application of extracts. Moreover, high-resolution respirometry showed reduced oxidative phosphorylation and electron transfer system capacity thus indicating that early mitochondrial dysfunction may contribute to the cytotoxic effects. Network pharmacology revealed that ERBB2, CTNNB1, HSP90AA1 and HDAC6 might act as molecular targets in melanoma. Thus, these findings support the hypothesis that E. parviflorum hydroalcoholic extracts, particularly the 40% ethanol Soxhlet extract, may serve as important sources of bioactive phytocompounds with antiproliferative and apoptotic properties. Full article

Defect calculations for semiconductors demand both large supercells and accurate electronic structures, posing a significant challenge to first-principles methods. Conventional density functional theory (DFT) with local or semi-local exchange-correlation functionals severely underestimates the band gap, whereas hybrid functionals such as HSE06 provide higher accuracy but at a substantially increased computational cost. In this work, we demonstrate that shell DFT-1/2, a self-energy correction method for electronic structure calculations, may be used jointly with HSE06 to reach the optimal efficiency as well as accuracy. In particular, indium phosphide (InP) was taken as an example. The shell DFT-1/2 method was utilized to yield accurate band structures with a 1.44 eV direct gap, without any empirical parameter. Subsequently, the portion of exact exchange was tuned to match the shell DFT-1/2 electronic structure in HSE06 calculations. The charge transition levels of various point defects in InP were derived using HSE06, and HSE06 and shell DFT-1/2 may be employed alternatively to yield the density of states for the defective supercells. Their consistency proves the feasibility of the complementary employment of the two methods, and this strategy is readily extendable to other semiconductor research. Full article

Background/Objectives: Rapid surveillance tools are needed to monitor antimicrobial-resistant bacteria in the food chain. This study evaluated whether qPCR-based quantification of tetracycline resistance genes could replace culture-based quantification of tetracycline-resistant Escherichia coli in pig caecal content and carcass skin swabs. Methods: Caecal content (n = 89) and skin swab samples (n = 68) were collected across four Danish abattoirs and analysed by both qPCR and Petrifilm cultivation. Method comparisons were restricted to samples within the quantifiable range of Petrifilm. E. coli concentrations (uidA gene) and tetA/tetB gene concentrations were compared with Petrifilm counts of E. coli and culturable tetracycline-resistant E. coli. Method agreement was evaluated using paired t-tests, Bland–Altman analysis, and Spearman correlation. Results: In caecal samples (n = 84), no significant difference in mean log E. coli concentration was observed between uidA qPCR and Petrifilm counts (p = 0.33). However, Bland–Altman analysis showed poor agreement at the individual-sample level, with limits of agreement ranging from −1.09 to 1.21 log₁₀ CFU/g. In skin swab samples (n = 43), qPCR systematically overestimated E. coli counts compared with cultivation, with a significant bias of 0.75 log₁₀ CFU/1400 cm² (p < 0.001). No significant correlation was observed between tetA/tetB and culturable tetracycline-resistant E. coli in caecal (r_s = 0.091, p = 0.44) or skin swab samples (r_s = 0.13, p = 0.48). Conclusions: qPCR may be useful for population-level surveillance of tetracycline resistance genes in pig caecal samples but cannot replace culture-based methods for accurate quantification of tetracycline-resistant E. coli in individual samples. Full article

Skeleton-based action recognition has attracted considerable research interest because skeleton data are inherently robust to illumination changes, viewpoint variation, background clutter, and camera motion. Nevertheless, extracting informative representations from skeleton sequences remains a challenging problem, as it requires capturing both the spatial co-occurrence patterns among body joints and the fine-grained kinematic cues that distinguish different actions. In this paper, we propose a single-stream architecture that constructs an action-specific skeleton graph directly from motion and processes it with a kinematic-aware Transformer. Rather than relying on a fixed skeleton topology, a motion-guided dynamic-graph construction module infers a per-frame adjacency matrix from short-term motion cues through a differentiable edge predictor and Gumbel-Softmax sparsification, allowing the model to discover action-driven connections between distant joints that lack direct bone connectivity (e.g., coordinated hand motion during clapping). Each joint is described by kinematic node features that combine its 3D position, instantaneous velocity, and limb-angle encodings within a single descriptor, so that both motion dynamics and higher-order limb configurations are available to the spatial encoder from the outset. A graph-attention network (GAT) encodes the spatial configuration of every frame over the learned graph, and the resulting sequence of frame descriptors is processed by a Transformer encoder that models long-range temporal dependencies; a learnable classification token aggregates the sequence, and a multi-layer perceptron (MLP) produces the final action classification. The entire model is trained end-to-end from action labels alone. We conduct a comprehensive ablation study and evaluate the proposed method on the large-scale NTU RGB+D 60 and NTU RGB+D 120 benchmarks, where the results demonstrate that our approach achieves competitive performance compared to state-of-the-art architectures. Full article

Multi-server private information retrieval (PIR) based on function secret sharing (FSS) has emerged as a prominent paradigm for achieving sublinear communication. However, standard FSS constructions require full server participation, making them highly vulnerable to single-node fail-stop faults. Existing fault-tolerant schemes mitigate this but inevitably inflate the response overhead to scale with the database size N (e.g., $O\left(\sqrt{N}\right)$). To overcome this limitation, we propose a fault-tolerant PIR (FT-PIR) protocol based on a newly designed $(t,p)$-threshold distributed point function (FT-DPF). By introducing a hierarchical recursive patching mechanism, our scheme transforms rigid all-party evaluations into flexible t-out-of-p reconstructions. This architecture completely decouples the response communication from N and ensures efficient client-side reconstruction via lightweight XOR aggregations. Formal analysis proves that our stateless protocol guarantees $(t-1)$-computational privacy under the semi-honest model. Theoretical analysis demonstrates that the proposed FT-PIR achieves a response complexity bounded by $\mathcal{O}\left({\mathcal{F}}_{\mathrm{maxlevel}}(t,p)\right)$. Comprehensive experimental evaluations confirm that our implementation significantly reduces practical communication and computation overheads, outperforming the state-of-the-art scheme. Full article

Weather radar calibration is essential for ensuring data consistency and quantitative precipitation estimation in X-band radar networks. Existing absolute calibration methods (e.g., metal sphere, horn antenna) suffer from high cost, poor timeliness, and difficulty in automation due to meteorological conditions and airspace restrictions, while spatiotemporal matching methods based on volume scan data suffer from interpolation and matching inaccuracies. To address these issues, this study proposes a collaborative calibration method for X-band radar networks based on opposing Range–Height Indicator (RHI) scans. The method uses a rigorously calibrated reference radar as a benchmark and performs opposing RHI scans with the radar under calibration to obtain synchronized observations within the spatial overlap region. Precise spatial matching is achieved using the nearest-neighbor algorithm based on beam-broadening cross-coverage thresholds, and bias is extracted using both the midline 9-point averaging method (midline method) and spatially constrained regional Statistics method (regional method). Based on a total of 58 sets of opposing RHI scanning cases conducted under stratiform precipitation, scattered precipitation, and weak cloud conditions, the results show that under conditions where echo continuity is maintained near the midline of stratiform and scattered precipitation, both the midline method and the regional method can obtain stable matching data. The midline method achieves a median correlation coefficient (0.821–0.942) higher than that of the regional method (0.860–0.872), and its bias standard deviation remains relatively stable (midline method: 1.39–2.20 dB; regional method: 2.61–3.16 dB). Continuous RHI calibration tests confirm that within a 30-min window, the fluctuation of the data matching correlation coefficient is less than 0.05, and the fluctuation of the bias mean is controlled within ±0.3 dB. Under weak cloud conditions, although the midline method can still achieve a high correlation coefficient, the correctness of its results still requires auxiliary validation through other calibration means. This study provides a relatively efficient and effective technical approach for the automated collaborative calibration of dense X-band radar networks. Full article