Search Results (472)

In this study, a series of novel β-phenylalanine derivatives were synthesised and evaluated for their anticancer activity. The 3-(4-methylbenzene-1-sulfonamido)-3-phenylpropanoic acid (2) was prepared using β-phenylalanine as a core scaffold. The β-amino acid derivative 2 was converted to the corresponding hydrazide 4, which enabled the development of structurally diverse heterocyclic derivatives including pyrrole 5, pyrazole 6, thiadiazole 8, oxadiazole 11, triazoles 9 and 12 with Schiff base analogues 13 and series1,2,4-triazolo [3,4-b][1,3,4]thiadiazines 14. These modifications were designed to enhance chemical stability, solubility, and biological activity. All compounds were initially screened for cytotoxicity against the A549 human lung adenocarcinoma cell line, identifying N-[3-(3,5-dimethyl-1H-pyrazol-1-yl)-3-oxo-1-phenylpropyl]-4-methylbenzenesulfonamide (5) and (E)-N-{2-[4-[(4-chlorobenzylidene)amino]-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl]-1-phenylethyl}-4-methylbenzenesulfonamide (13b) as the most active. The two lead candidates were further evaluated in H69 and H69AR small cell lung cancer lines to assess activity in drug-sensitive and multidrug-resistant models. Schiff base 13b containing a 4-chlorophenyl moiety, retained potent antiproliferative activity in both H69 and H69AR cells, comparable to cisplatin, while compound 5 lost efficacy in the resistant phenotype. These findings suggest Schiff base derivative 13b may overcome drug resistance mechanisms, a limitation commonly encountered with standard chemotherapeutics such as doxorubicin. These results demonstrate the potential role of β-phenylalanine derivatives, azole-containing sulphonamides, as promising scaffolds for the development of novel anticancer agents, particularly in the context of lung cancer and drug-resistant tumours. Full article

Identity-based cryptography introduced by Shamir (Crypto’84) has seen many advances through the years. In the context of post-quantum identity-based schemes, most of the efficient designs are based on lattices. In this work, we propose an identity-based identification (IBI) scheme and an identity-based signature (IBS) scheme based on codes. Our design combines the hash-and-sign signature scheme, Wave, with a Stern-like signature scheme, BGKM-SIG1, instantiated over a ternary field using the large-weight Syndrome Decoding Problem (SDP). Our scheme significantly outperforms existing code-based identity-based signature constructions. Full article

Background: Crystalline glucosamine sulfate (cGS) claims to be a stabilized form of glucosamine sulfate with a defined crystalline structure intended to enhance chemical stability. It is proposed to offer pharmacokinetic advantages over regular glucosamine sulfate (rGS) which is stabilized with potassium or sodium chloride. However, comparative human bioavailability data are limited. Since both forms dissociate in gastric fluid into constituent ions, the impact of cGS formulation on absorption remains uncertain. This pilot study aimed to compare the bioavailability of cGS and rGS using a randomized, double-blind, crossover design. Methods: Ten healthy adults received a single 1500 mg oral dose of either cGS or rGS with a 7-day washout between interventions. Capillary blood samples were collected over 24 h. Glucosamine and its metabolite concentrations were quantified by Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS), and pharmacokinetic parameters—including maximum concentration (C_max), time to reach C_max (T_max), and area under the curve (AUC)—were calculated. Results: Mean AUC_0–24, C_max, T_max, and T_½ values for glucosamine and glucosamine-6-sulfate (GlcN-6-S) were comparable between cGS and rGS. Although the AUC_0–24 for glucosamine was modestly higher with rGS (18,300 ng·h/mL) than with cGS (12,900 ng·h/mL), the difference was not statistically significant (p = 0.136). GlcN-6-S exposure was also similar between formulations (rGS: 50,700 ng·h/mL; cGS: 50,600 ng·h/mL), with a geometric mean ratio of 1.39, a delayed T_max (6–8 h) and longer half-life, consistent with its role as a downstream metabolite. N-acetylglucosamine levels remained stable, indicating potential homeostatic regulation. Conclusions: This pilot study found no significant pharmacokinetic advantage of cGS over rGS. These preliminary findings challenge claims of cGS’ pharmacokinetic superiority, although the small sample size limits definitive conclusions. Larger, adequately powered studies are needed to confirm these results. Full article

Previous phylogeographic study of the root vole (Alexandromys oeconomus) revealed four mitochondrial cytochrome b lineages—North and Central European, North (=Central) Asian and Beringian. Three of them were studied in detail, while the North Asian lineage, which occupies the most extensive territory and is considered to be the place of origin for the species, was understudied. In the framework of the current study, we obtained 95 new sequences (34 localities) from the wide territory of Northern Asia and in total, examined 940 specimens from 181 localities throughout the species’ distribution range. The North Asian lineage was found to be more diverse than the Beringian and the European lineages. Southern Siberia and especially the Altai–Sayan region displayed the highest haplotype and nucleotide diversity, suggesting the region’s role as a genetic diversity hotspot. We suppose that the expansion of the North Asian lineage started from Western Transbaikalia. Its representatives colonised the territory from the Urals to the northern shore of the Okhotsk Sea, and then spread in the opposite direction, to Southern Siberia. As a result, a mixture of haplogroups is observed in the Altai–Sayan region. According to the BEAST analysis calibrated with the first A. oeconomus records, the MRCA of North Asian and Beringian lineages is dated back to ~0.82 Mya, and the first divergence within the North Asian lineage may have occurred ~0.6 Mya. When compared with colonisation times of other representatives of the Arvicolinae subfamily, our dating seems to be overestimated. In this regard, molecular data for dated fossil remains of the root vole are essential for subsequent studies. Full article

Maintenance dredging produces large volumes of fine sediments that are commonly discarded, despite increasing pressure for beneficial reuse. Lime–cement stabilization offers one pathway, yet field performance is highly variable. This study juxtaposes two French marine dredged sediments—DS-F (low plasticity, organic matter (OM) ≈ 2 wt.%) and DS-M (high plasticity, OM ≈ 18 wt.%)—treated with practical hydraulic road binder (HRB) dosages. This is the first French study that directly contrasts two different DS types under identical HRB treatment and proposes practical boundary thresholds. Physical indexes (particle size, methylene-blue value, Atterberg limits, OM) were measured; mixtures were compacted (Modified Proctor) and tested for immediate bearing index (IBI). IBI, unconfined compressive strength, indirect tensile strength, and elastic modulus were determined. DS-F reached IBI ≈ 90–125%, UCS ≈ 4.7–5.9 MPa, and ITS ≈ 0.40–0.47 MPa with only 6–8 wt.% HRB, satisfying LCPC-SETRA class S2–S3 requirements for road subgrades. DS-M never exceeded IBI ≈ 8%, despite 3 wt.% lime + 6 wt.% cement. A decision matrix distilled from these cases and recent literature shows that successful stabilization requires MBV < 3 g/100 g, plastic index < 25%, OM < 7 wt.%, and fine particles < 35%. These thresholds permit rapid screening of dredged lots before costly treatment. Highlighting both positive and negative evidence clarifies the realistic performance envelope of soil–cement reuse and supports circular-economy management of DS. Full article

Background: Silymarin, a flavonoid complex, and the main bioactive component of milk thistle (Silybum marianum), is known for its hepatoprotective properties but suffers from poor bioavailability due to its low solubility and extensive first-pass metabolism. Method: This study aimed to evaluate the pharmacokinetics and tolerability of a novel micellar milk thistle formulation designed to enhance silymarin absorption, compared to an unformulated/standard milk thistle product, in a small-scale human bioavailability trial. In a randomized, double-blinded, crossover study, 16 healthy participants received a single dose of either the micellar formulation (LipoMicel Milk Thistle; LMM) or the standard formulation (STD) at a total daily dose of 130 mg silymarin. Blood concentrations were measured over 24 h, and key pharmacokinetic parameters—maximum plasma concentration (C_max), time to reach maximum concentration (T_max), and area under the curve (AUC)—were calculated. Tolerability and safety were assessed through adverse event monitoring during the study period. Results: Results demonstrated a significant increase in bioavailability with the micellar formulation, with 18.9-fold higher C_max (95% CI: 1.9–30.7 ng/mL vs. 74.4–288.3 ng/mL; p = 0.007) and 11.4-fold higher AUC_0–24 (95% CI: 7.40–113.5 ng·h/mL vs. 178–612.5 ng·h/mL; p = 0.015). T_max was 0.5 (95% CI: 0.5–4.0) hours for the micellar formulation versus 2.5 (95% CI: 0.5–8.0) hours for the standard product (p = 0.015) indicating faster absorption of LMM. The standard formulation exhibited a significantly longer mean residence time compared to the LMM formulation (95% CI: 4.4–7.5 h vs. 2.8–4.2 h; p = 0.015). Conclusions: No adverse events or significant safety concerns were observed in either group. Compared to the standard, the micellar formulation showed superior pharmacokinetic outcomes, suggesting it may enhance silymarin’s clinical efficacy in liver health. Full article

Butterflies (Lepidoptera: Papilionoidea), considered bioindicators of habitat conservation status, are one of the groups used to assess the impact of habitat management and improvement efforts in the Biological Station of Torretes (Ibi, Alicante, Spain). This area also houses the Botanical Garden of the University of Alicante. The study was focused on the period from autumn 2022 to late spring 2023, and data on butterfly diversity and abundance from the current study were compared with historical data. Our results highlight that open spaces and the availability of trophic resources (nutritional plants) were key factors influencing the richness and abundance of Papilionoidea. The program for the creation and maintenance of new habitats at the biological station has increased spatial heterogeneity and the availability of trophic resources, which has led to a significant increase in the richness and abundance of butterflies in a short period. To support the conservation of Mediterranean ecosystems, and entomofauna in general, the Papilionidae are proposed as model groups for designing conservation projects based on traditional habitat management. These projects should promote spatial heterogeneity, include programs to enrich plant diversity, and be complemented by environmental education and outreach initiatives. Full article

Background and Objectives: Despite advances in immunotherapy, predicting survival outcomes in patients with non-small-cell lung cancer (NSCLC) remains challenging. Inflammatory and nutritional indices such as the Prognostic Nutritional Index (PNI), Geriatric Nutritional Risk Index (GNRI), Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Inflammatory Burden Index (IBI) have emerged as promising prognostic markers associated with overall survival (OS) in NSCLC patients. Materials and Methods: We retrospectively analyzed a total of 196 NSCLC patients treated with second-line nivolumab across multiple centers in Turkey. Of these, 101 patients aged ≥ 65 years were included in the elderly subgroup analysis. PNI, GNRI (in patients aged ≥ 65), and inflammation-based indices were calculated using pre-treatment laboratory values. ROC analysis determined optimal cut-off values. The Kaplan–Meier method and Cox proportional hazards models were used for survival analysis. Results: Median overall survival (OS) was 12.9 months in the full cohort and 12.1 months in patients aged ≥ 65. In univariate analysis, ECOG performance status (0–1), lower NLR (<3.3), lower PLR (<196.8), higher PNI (≥45.2), and higher GNRI (≥98.0) were significantly associated with longer OS. However, in the multivariate analysis adjusted for ECOG PS, NLR, PLR, and GNRI, only PNI remained an independent prognostic factor for OS in both the overall cohort [HR: 0.49, 95% CI: 0.26–0.92; p = 0.02] and elderly patients [HR: 0.45, 95% CI: 0.24–0.84; p = 0.01]. PNI is an independent prognostic biomarker for OS in NSCLC patients treated with immune checkpoint inhibitors. Conclusions: These findings support incorporating simple, cost-effective nutritional indices into clinical decision-making, particularly in elderly patients with NSCLC. Full article

Pine nuts hold significant economic value due to their rich plant protein and healthy fats, yet precise variety classification has long been hindered by limitations of traditional techniques such as chemical analysis and machine vision. This study proposes a novel near-infrared (NIR) spectral feature selection algorithm, termed the improved binary equilibrium optimizer with selection probability (IBiEO-SP), which incorporates a dynamic probability adjustment mechanism to achieve efficient feature dimensionality reduction. Experimental validation on a dataset comprising seven pine nut varieties demonstrated that, compared to particle swarm optimization (PSO) and the genetic algorithm (GA), the IBiEO-SP algorithm improved average classification accuracy by 5.7% (p < 0.01, Student’s t-test) under four spectral preprocessing methods (MSC, SNV, SG1, and SG2). Remarkably, only 2–3 features were required to achieve optimal performance (MSC + random forest: 99.05% accuracy, 100% F1/precision; SNV + KNN: 97.14% accuracy, 100% F1/precision). Furthermore, a multimodal data synergy strategy integrating NIR spectroscopy with morphological features was proposed, and a classification model was constructed using a soft voting ensemble. The final classification accuracy reached 99.95%, representing a 2.9% improvement over single-spectral-mode analysis. The results indicate that the IBiEO-SP algorithm effectively balances feature discriminative power and model generalization needs, overcoming the contradiction between high-dimensional data redundancy and low-dimensional information loss. This work provides a high-precision, low-complexity solution for rapid quality detection of pine nuts, with broad implications for agricultural product inspection and food safety. Full article

Retinal prostheses have been utilized in the treatment of blindness resulting from retinal degeneration. However, they have not met patient expectations, leading to market withdrawals. As a result, research continues to focus on improving visual perception, such as by modeling retinal neural activation. The retina’s electrical resistivity profile is key, as it influences the current spread during electrical stimulation. To advance efficient stimulation parameters, more data on the electrical properties of the retina in both its healthy and diseased state is needed. While this question has been addressed in mouse models, few data are available from rat models, whose bigger size is advantageous for many applications. To address this knowledge gap, we used flexible penetrating microelectrode arrays to measure intraretinal impedance and electrophysiological activity in retinas from both healthy (WT) and diseased RCS rats, an established model of retinal degeneration. Consequently, we calculated resistivity profiles, consistent with previous mouse retina findings, and correlated them with spontaneous spiking activity. Hence, both impedance and electrophysiological measurements across retinal depths are demonstrated as valuable tools to identify the optimal stimulation depth and simulate the electric field spread during electrical stimulation, which is particularly useful for the development of retinal prostheses. These findings demonstrate that resistivity changes in the degenerated retina significantly impact stimulation protocols and electric field propagation. Full article

To investigate the spatiotemporal characteristics of periphytic algae community structure and the Benthic Index of Biotic Integrity (B-IBI) in the Jinsha River, this study conducted two sampling surveys on periphytic algae and physicochemical factors at 15 representative sampling sites in November 2023 (dry season) and May 2024 (normal water period). Results showed that a total of 118 species of periphytic algae belonging to 59 genera and 7 phyla were detected, including 48 species from 5 phyla in the dry season of 2023 and 95 species from 6 phyla in the normal water period of 2024. Spatially, the distribution trends of total species richness and abundance of periphytic algae were basically consistent, both showing a gradually increasing trend from the downstream reservoir section of the Jinsha River to the upstream conservation section of the Yangtze River. Temporally, both the abundance and species richness of periphytic algae in the normal water period were higher than those in the dry season. Overall, the physicochemical indices of the Jinsha River water showed a decreasing trend from the reservoir areas to the river channels, with slightly higher values in the normal water period than in the dry season. Through parameter value distribution range analysis, discriminant ability analysis, and redundancy analysis of candidate parameters, the B-IBI index system for the study area was determined. The baseline values of the periphytic algae integrity index were 6.04 in the dry season of 2023 and 6.62 in the normal water period of 2024. The water ecological health status of the conservation section of the upper reaches of the Yangtze River is generally in a healthy state, and the overall water ecological health status gradually improves with the increase of the distance from the cascade reservoirs in the lower reaches of the Jinsha River. Full article

To study the structure and distribution characteristics of the phytoplankton community in the Huaihe River Basin, Yangtze River Basin, and Taihu Lake Basin in Jiangsu Province, 126 sampling sites were set up in 35 rivers in the region, and samples were collected during the wet season (August–September) in 2023. Based on the monitoring results of phytoplankton, the study selected 20 candidate indicators and conducted range screening, discriminative ability analysis, and correlation analysis. Finally, seven core indicators were determined to construct the Phytoplankton Biological Integrity Index (P-IBI) evaluation system. The rating standards were determined by the ratio method, and the phytoplankton integrity of Jiangsu Province was evaluated. The differences were analyzed. As the results showed, the overall health status of rivers in Jiangsu Province was general. From the point of view of the basin scope, the Huaihe River Basin and the Yangtze River Basin were in sub-healthy state, and the Taihu Lake Basin was general. There were significant differences in the phytoplankton density community structure in the Yangtze River, Huaihe River, and Taihu Lake Basins. Phytoplankton integrity was positively correlated with total nitrogen and nitrate nitrogen, but not with other environmental factors. Nitrogen is the main factor affecting the integrity of river phytoplankton in Jiangsu Province. Full article

The Onil and Ibi sections (Prebetic Zone, Betic Cordillera: Alicante, SE Spain) record a late Ypresian (Cuisian) to early Lutetian (~51 to ~43 Myr) carbonate platform succession, dated using larger benthic foraminifera (LBF) and planktonic foraminifera. Seven field lithofacies (L1 to L7) and five thin-section microfacies (Mf1–Mf5) were identified, indicating inner- to mid-ramp environments (from seagrass meadows to Maërl-LBF-dominated) in warm-water and low-latitude conditions. A distinctive feature of these platforms is their dominance by LBF in association with rhodophyceae, contrasting with typical coral reef factories. We propose a novel carbonate production model, “TC-factory”, to describe these warm-temperate systems. Integrated field logging, drone imagery, and microfacies data allowed us to define a sequence stratigraphic framework comprising five lower-frequency sequences (LFS: ~2 Myr average duration), each of them nesting various numbers of high-frequency sequences (HFS: ~0.25 to ~1 Myr). The LFSs belong to a higher-rank sequence bounded by regional unconformities. The five LFSs only broadly match the upper Ypresian and lower Lutetian cycles in global eustatic curves (~51 to ~43 Myr), indicating that other regional or local controls were important. The number of HFSs being fewer than expected also suggests additional controls, such as local tectonics, erosion during lowstands, or carbonate production feedback. Full article

Blow flies (Diptera: Calliphoridae) are among the first insects to arrive on a corpse, and so they are particularly important in forensic entomology. To use blow flies in forensic investigations, there must be information available on their species diversity, abundance, and distribution in the areas where investigations are conducted. Several factors can contribute to species distribution, and elevation is one of those factors. The purpose of this study was to document the distribution of Calliphoridae across four elevational gradients in Sicily and Ecuador, where little information is available. Baited traps were placed at elevations ranging from 20 m to 1552 m in Sicily (a major island and region of Italy and a distinct ecoregion) and 561 m to 3336 m in Ecuador. Species richness, relative abundance, and diversity were calculated, as well as the ratio of female to male blow flies and community assemblage. Twelve species were collected in Sicily, and seventeen species were collected in Ecuador. In Sicily, the most abundant species was Lucilia sericata (Meigen) (68.50% of the total capture), while in Ecuador, it was Compsomyiops verena (Walker) (51.67% of the total capture). In Sicily, significant differences were only observed in the relative abundance of L. sericata across elevations. In Ecuador, significant differences were observed in the relative abundance of Calliphora nigribasis (Macquart), Chrysomya albiceps (Wiedemann), C. verena, Hemilucilia semidiaphana (Rondani), Lucilia ibis (Shannon), L. purpurascens (Walker), and Paralucilia sp. across elevations. These data can help build a checklist of blow fly species in these two regions and can be instrumental in environmental and forensic investigations. Full article

Spontaneous cell detachment describes an effect in which eukaryotic cells first sediment onto a heated chip and then detach from it spontaneously and collectively after a sharply defined dwell time t_d. This behavior is triggered by the temperature gradient between the chip and the colder supernatant liquid. Notably, t_d allows distinguishing between different yeast strains and cancer-cell lines. At the same time, it also varies in the presence of nutrients and cytotoxins, suggesting an added value of this method for pharmacological studies. In the present work, we study the role of fluid convection on the detachment of yeast cells experimentally and by simulations using a sample compartment with a variable aspect ratio. Hereby, we found that the absolute chip temperature, the strength of the temperature gradient and the number of cells inside the sample compartment all affect the dwell time t_d. To demonstrate the concept, we show that the spontaneous-detachment method can measure the impact of an antibiotic and an antiseptic drug on yeast cultures and corroborate this with reference assays. Full article