Search Results (17,585)

Background: Trypanosoma cruzi, the causative agent of Chagas disease, remains a major public health concern, and there is a continued need for new antitrypanosomal agents. Thiosemicarbazone (TSC) derivatives have emerged as a promising class of compounds with potential antiparasitic activity. Objectives: This study aimed to report the synthesis, characterization, and biological profiling of a novel series of thiosemicarbazone derivatives as antitrypanosomal agents against Trypanosoma cruzi. Methods: Fourteen new compounds and six previously described analogues were prepared and characterized by ¹H/¹³C nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). As a preliminary in vitro screen, activity was assessed by direct parasite counting in epimastigote and bloodstream trypomastigote forms, as tractable models of replicative and infective stages sharing core metabolic targets with intracellular amastigotes. Epimastigote potency was quantified as half-maximal effective concentrations (EC₅₀) derived from dose–response curves, whereas trypomastigote response was evaluated as percent viability after treatment at a fixed concentration of 20 µM. Mechanistic profiling included inhibition assays against the cysteine protease cruzipain (CZP) and selected redox defense enzymes, complemented by in silico similarity clustering and binding-pose affinity scoring. Results: A nitro-methoxy-substituted TSC showed potent CZP inhibition but limited trypomastigote efficacy, whereas brominated analogues displayed dual-stage activity independent of CZP inhibition. Tanimoto similarity analysis identified distinct structure–activity clusters, linking nitro-methoxy substitution to epimastigote selectivity and brominated scaffolds to broader antiparasitic profiles, with hydrophobicity and steric complementarity as key determinants. Enzymatic assays revealed no significant inhibition of cytosolic tryparedoxin peroxidase (cTXNPx) or glutathione peroxidase type I (TcGPx-I), suggesting redox disruption is not a primary mode of action. In vitro and in silico analyses showed low or no non-specific cytotoxicity under the tested conditions, supporting further optimization of these derivatives as antitrypanosomal preliminary hits. Key hits included derivative 3e (epimastigote EC₅₀ = 0.36 ± 0.02 µM) and brominated analogues 2c and 2e (epimastigote EC₅₀ = 3.92 ± 0.13 and 4.36 ± 0.10 µM, respectively), while docking supported favorable binding-pose affinity (e.g., ΔG_S-pose = −20.78 ± 2.47 kcal/mol for 3e). Conclusions: These results support further optimization of the identified thiosemicarbazone derivatives as preliminary antitrypanosomal hits and provide insight into structure–activity relationships and potential mechanisms of action. Full article

The Transient Receptor Potential Ankyrin 1 (TRPA1) channel is a non-selective cation channel activated by a range of physical and chemical stimuli. While primarily studied in neuronal tissues, TRPA1 is also expressed in human keratinocytes, where its role remains poorly understood. Here, we investigated TRPA1 expression and function in keratinocytes and examined the effects of its activation on cellular proliferation, immune activation, and neuropeptide release under both basal and inflammatory stimuli. TRPA1 expression was detected in basal keratinocytes and was upregulated by pro-inflammatory cytokines. Stimulation with the TRPA1 agonist allyl isothiocyanate (AITC) induced a rapid calcium influx, confirming functional channel activity. AITC at 5 µM did not induce cytotoxicity but significantly reduced keratinocyte proliferation and caused cell cycle arrest. Under stimulation with TNF-α and IFN-γ, TRPA1 activation decreased the surface expression of HLA-DR and ICAM-1, and downregulated mRNA levels of CXCL10, CXCL8, CCL5, and CCL20, while IL-6 expression remained unchanged. Furthermore, AITC treatment reduced the secretion of Substance P, but not CGRP. These findings indicate that TRPA1 functions as a cytokine-inducible, immunomodulatory receptor in human keratinocytes, capable of attenuating proliferation and inflammatory activation without compromising cell viability, thereby suggesting a potential role in maintaining skin homeostasis and modulating cutaneous inflammation. Full article

The discovery of structurally novel anti-tumor agents remains a crucial objective in cancer drug research. In this study, we systematically explored the bioactivity potential of sarocladione (5), a structurally unique marine-derived 14-membered ring diketone steroid. Guided by a function-oriented strategy, seven new derivatives (6–13) were synthesized based on an efficient biomimetic synthesis of sarocladione. Evaluation of their antiproliferative activities against human cancer cell lines demonstrated that the intact macrocyclic scaffold is indispensable for activity. Extension of the conjugated π-system led to the identification of compound 8, which exhibited approximately four-fold enhanced potency against HCT116 cells (IC₅₀ = 1.86 µM) compared with the parent natural product. Stereochemical analysis further revealed the critical role of the (5R)-configuration at C-5. Phenotypic investigations indicated that compound 8 induces concentration-dependent G2/M phase cell cycle arrest, followed by apoptosis, suggesting a cell cycle-dependent antiproliferative effect. Overall, this study highlights sarocladione as a promising marine-derived scaffold for further antiproliferative optimization. Full article

Chalcones have garnered significant research interest due to their various medical bioactivities. Several chalcone compounds have been approved for marketing and clinical use in the treatment of various diseases. A critical aspect of the action of chalcones is their effect on microtubules. They are considered an excellent target for chemotherapeutic agents for the treatment of cancer. Consequently, scientists are constantly developing novel chalcone drug agents and also innovative drug delivery strategies. In this manuscript, we report the first synthesis of 12 new visible-light-activated, photoswitchable chalcone-based microtubule inhibitors (17a–17l). Among the obtained compounds, one photoswitch demonstrated light-dependent cytotoxicity in the PC-3 cancer cell line. The IC₅₀ value of the Z conformer was determined to be 4.75 ± 1.00 μM after 48 h of treatment. The E conformer exhibited slightly lower activity compared to the Z conformer, with an IC₅₀ value of 5.80 ± 0.80 µM following 48 h of incubation. In this study, NMR and UV spectroscopy, along with computational methods, were employed. Full article

This study investigated the spatial and seasonal dynamics of phytoplankton communities in Jaran Bay, inner Hansan Bay, and outer Hansan Bay, with particular emphasis on size structure and pigment-based indicators of productivity and physiological status. Water sampling was conducted during May, August, and October in 2020, 2022, and 2023 and phytoplankton communities were analyzed using size-fractionated chlorophyll a measurements and high-performance liquid chromatography (HPLC) pigment analysis. Chlorophyll a concentrations exhibited pronounced seasonality, with consistently elevated values in August across all bays. Diatoms were predominant throughout the study period; however, their relative contribution declined in outer Hansan Bay during summer, coinciding with increased contributions from cryptophytes and cyanobacteria. Size-fractionated analyses revealed that large-sized phytoplankton (>20 µm) predominantly consisted of diatoms, whereas small-sized phytoplankton (<20 µm) were composed of diatoms and cryptophytes. Comparisons between fluorometric and pigment-based approaches indicated that pigment-based diagnostics overestimated microphytoplankton contributions, attributable to the presence of small-sized diatoms. Pigment indices further revealed that large-sized phytoplankton were characterized by higher photosynthetic carotenoid concentrations and lower photoprotective carotenoid ratios, indicative of enhanced photosynthetic activity and productivity. Overall, these findings highlight the critical role of phytoplankton size structure in regulating productivity and physiological responses in aquaculture-dominated coastal bays. Full article

Tyrosinase (EC 1.14.18.1) is a binuclear copper enzyme responsible for the rate-limiting steps of melanogenesis, catalyzing the hydroxylation of L-tyrosine and oxidation of L-DOPA into o-quinones that polymerize melanin. Beyond its physiological role in pigmentation, tyrosinase is also implicated in food browning and oxidative stress–related disorders, making it a key target in cosmetic, food, and biomedical industries. This systematic review, conducted following PRISMA guidelines, aimed to identify and analyze microbial metabolites with tyrosinase inhibitory potential as sustainable alternatives to conventional inhibitors such as hydroquinone and kojic acid. Literature searches in Scopus and Web of Science (March 2025) yielded 156 records; after screening and applying inclusion criteria, 11 studies were retained for analysis. The inhibitors identified include indole derivatives, phenolic acids, peptides, and triterpenoids, mainly produced by fungi (e.g., Ganoderma lucidum, Trichoderma sp.), actinobacteria (Streptomyces, Massilia), and microalgae (Spirulina, Synechococcus). Reported IC₅₀ values ranged from micromolar to milli-molar levels, with methyl lucidenate F (32.23 µM) and p-coumaric acid (52.71 mM). Mechanisms involved competitive and non-competitive inhibition, as well as gene-level regulation. However, methodological heterogeneity, the predominance of mushroom tyrosinase assays, and limited human enzyme validation constrain translational relevance. Computational modeling, site-directed mutagenesis, and molecular dynamics are proposed to overcome these limitations. Overall, microbial metabolites exhibit promising efficacy, stability, and biocompatibility, positioning them as emerging preclinical candidates for the development of safer and more sustainable tyrosinase inhibitors. Full article

Melatonin is recognised as a multifunctional regulatory molecule that enhances plant tolerance to abiotic stresses, but its effectiveness is often strongly genotype-dependent. This study aimed to elucidate how exogenous melatonin (200 µM) modulates the physiological and biochemical responses of wheat during drought and subsequent recovery in two genotypes with contrasting grain pigmentation: the standard cv. Bohemia (red grain) and an experimental purple-pericarp (PP) line. Plants were exposed to drought at the early vegetative stage (BBCH 15), and gas exchange, leaf water potential, and biochemical markers (proline, malondialdehyde, phenolics, and flavonoids) were assessed during drought and after rehydration. In cv. Bohemia, water deficit led to a pronounced decrease in CO₂ assimilation, stomatal conductance, and leaf water potential, accompanied by strong increases in proline (Pro) and malondialdehyde (MDA). Melatonin application in this genotype markedly reduced the accumulation of Pro and MDA and accelerated the recovery of gas exchange, indicating a significant protective effect. The lower Pro levels in melatonin-treated Bohemia plants suggest that melatonin mitigated the perceived stress intensity, thereby reducing the physiological demand for osmotic adjustment. In contrast, the PP line exhibited higher inherent stability of the photosynthetic apparatus and more moderate biochemical shifts; its recovery was almost complete and independent of melatonin. Overall, these results indicate that the functional benefit of exogenous melatonin is greater in genotypes with a lower intrinsic stress-buffering capacity. This study highlights the importance of considering constitutive genotype traits and the recovery phase when using physiological regulators to improve wheat drought resilience. Full article

Background/Objectives: Trace metals, including copper (Cu) and zinc, are associated with the development and prognosis of hepatocellular carcinoma (HCC). However, their interference with magnetic resonance imaging (MRI) limits their use as potential biomarkers. This study investigated the usefulness of Synchrotron Radiation–excited X-ray Fluorescence (SR-XRF) imaging in studying the distribution of trace metals in HCC. Methods: This case–control study analyzed 33 specimens from 32 patients with HCC who underwent surgical resection (n = 29) or biopsy (n = 3) at Kobe University Hospital between December 1999 and November 2002. The findings of SR-XRF were compared with those of MRI and histopathology. Results: SR-XRF provided two-dimensional mapping of trace metal distribution with high spatial resolution (1.0 µm). The mean tumor-to-liver ratio (TLR) of Cu content was significantly higher in well-differentiated HCCs than in moderately and poorly differentiated HCCs (p < 0.05). Moreover, the mean TLRs of Cu content were significantly higher in high-intensity lesions than in iso- or low-intensity lesions on T1-weighted imaging (p < 0.05). Conclusions: This study supports previous evidence of the involvement of Cu in HCC development, suggesting its potential as a clinical biomarker for diagnosis and disease progression. Additionally, the results demonstrate that SR-XRF has potential for clinical application due to its ability to map trace metal distribution at high resolution. These findings suggest, rather than demonstrate, the association among Cu accumulation, tumor differentiation, and MRI signal characteristics. Full article

The present study involves the isolation, structural elucidation, and biological evaluation of eight compounds from Pouzolzia zeylanica. From the n-hexane and ethyl acetate extracts of the plant, eight compounds were successfully isolated and identified: oleanolic acid (1), ursolic acid (2), 2α-hydroxyursolic acid (3), 3β-O-acetyl-12-oleanen-28-oic acid (4), 5-hydroxy-6,7-dimethoxyflavanone (5), 4′-methoxytectochrysin (6), 3,4′,5,7-tetrahydroxyflavanone-3-O-L-rhamnopyranoside (7), and 3,3′,5,5′,7-pentahydroxyflavanone-3-O-L-rhamnopyranoside (8). These compounds were evaluated for in vitro antioxidant activity using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and lipid peroxidation inhibition (TBARS) assays, as well as anti-inflammatory activity via inhibition of nitric oxide (NO) production and the secretion of pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in RAW 264.7 macrophages. It was observed that compound 3 exhibited the strongest antioxidant activity with IC₅₀ values of 18.52 ± 1.50 µM (DPPH) and 10.34 ± 0.93 µM (TBARS), whereas compounds 2, 5, and 6 showed moderate to weak effects. Meanwhile, compound 8 demonstrated the most potent anti-inflammatory effect with IC₅₀ values of 16.25 ± 0.95 µM (NO inhibition), 12.97 ± 0.88 µM (TNF-α inhibition), and 22.52 ± 1.98 µM (IL-6 inhibition). Furthermore, in silico approaches were employed, including density functional theory (DFT) calculations to predict the antioxidant mechanisms of compounds 1 and 3 and molecular docking to assess the cyclooxygenase-2 (COX-2) and phosphodiesterase-4B (PDE4B) inhibitory potentials of compounds 4, 7, and 8. Computational results aligned well with experimental data, supporting the potential of these compounds as natural antioxidant and anti-inflammatory agents. Full article

Multispectral infrared detection plays a crucial role in advanced applications spanning environmental monitoring, military surveillance, and biomedical diagnostics, offering superior target identification accuracy compared to single-band imaging techniques. In this work, we synthesized four distinct bands of colloidal quantum dots (CQDs)—specifically, a cut-off of 1.3 µm with PbS CQDs and 1.8 µm, 2.6 µm, and 3.5 µm with HgTe CQDs—and employed them to construct planar multiband infrared photodetectors. The device exhibited a clear photoresponse at room temperature from 0.8 µm to 3.5 µm, with responsivity of 5.39 A/W and specific detectivity of 2.01 × 10¹¹ Jones at 1.8 µm. This materials–device co-design strategy integrates wavelength-selective CQD synthesis with planar pixel-level patterning, providing a versatile pathway for developing low-cost, solution-processed, multiband infrared photodetectors. Full article

This study investigated lithium beneficiation from nepheline syenite ore containing 242.57 ppm Li, identifying biotite as the primary lithium-bearing mineral. A high-intensity dry magnetic separation produced a pre-concentrate assaying at approximately 850–1000 ppm Li, and flotation tests were conducted on both the run-of-mine ore and this magnetic product. Flotation performance was systematically evaluated using two top sizes (−500 and −300 µm), six size fractions (−500 + 75, −500 + 53, −500 + 38, −300 + 75, −300 + 53, −300 + 38 µm), four pH values (2.5, 4.0, 6.5, 9.5), and three collectors (DAHC, Derna 7, and Der A4). Among the reagents, Der A4 yielded the most promising results. Optimization using sodium silicate as a depressant demonstrated that, at 20 g/t Der A4, 500 g/t Na₂SiO₃, and pH 4.0, the −300 + 75 µm fraction of the run-of-mine ore reached approximately 5300 ppm Li. Applying the same parameters to the magnetic pre-concentrate resulted in a 6326.46 ppm Li concentrate with roughly 80% of flotation recovery. Mineralogical characterization using MLA, XRD, modal mineralogy, and SEM-EDS confirmed that the optimized product consisted predominantly of biotite, accompanied by K-feldspar, nepheline, and albite. Liberation results showed high liberation levels and the free surface, supporting the efficiency of combining magnetic separation with flotation for upgrading nepheline syenite as a potential lithium resource. Full article

Background/Objectives: The use of zirconia implants is gaining traction as a potential alternative to titanium. Although having excellent properties, the zirconia surface has limited osteogenic potential. The purpose of this study was to produce, for the first time, mechanically stable, thick micron-scale hydroxyapatite coatings on zirconia implant material using radiofrequency (RF) magnetron sputtering. Methods: Zirconia samples were coated with HA using an RF magnetron sputtering device at a temperature of 125 °C for 20 h with 155 W of power. The procedure included rotating the substrate at a speed of 10 rpm while an argon gas flow was maintained continuously. Field emission scanning electron microscopy (FESEM), energy-dispersive X-ray (EDX) analysis, atomic force microscopy, and Vickers hardness measurements were used to evaluate the coat’s characteristics. Results: A smooth hydroxyapatite coating layer that was consistent and free of cracks was observed in all FESEM pictures. The EDX study revealed that the substrate surface contains HA particles, and the ratio of calcium (Ca) to phosphorus (P) was 16.58 to 11.31, which is very close to the ratio in original HA. FESEM cross-section pictures showed good adhesion between the coating and substrate without any gaps, and the coating thickness was 5 µm on average. A statistically significant difference was found in the roughness analysis between the samples of uncoated Zr and HA-coated Zr (p-value < 0.05). Conclusions: Zirconia implant material can be coated with a uniform layer of HA, displaying good adhesion and a thickness of a few micrometers when using magnetron sputtering for an extended period of time. Full article

PARP inhibitors are a clinically validated class of anticancer therapeutics that exploit synthetic lethality to target homologous recombination-deficient tumors, such as those carrying BRCA1/2 mutations. Nevertheless, the rational design of mitochondria-targeted PARP inhibitors capable of selective mitochondrial accumulation and organelle-specific PARP modulation remains an unresolved objective. To enable organelle-specific modulation of PARP activity, we synthesized a series of trialkyl(aryl)phosphonium conjugates of olaparib and rucaparib designed to target mitochondria by cardiolipin binding. Their activity was evaluated by PARP1 inhibition, cardiolipin affinity, and cytotoxicity in BRCA1-deficient HCC1937 breast cancer cells and non-malignant H9C2 cardiomyocytes. All conjugates retained potent PARP1 inhibition (IC₅₀ = 3.4–17 nM), comparable to the parent drugs. Several derivatives, particularly compounds 2d and 6c, exhibited strong cardiolipin binding (EC₅₀ = 12.99 µM and 6.77 µM, respectively) and significantly enhanced cytotoxicity in HCC1937 cells (IC₅₀ = 0.93 and 2.01 µM), outperforming olaparib and rucaparib. Notably, cytotoxicity toward H9C2 cells was lower, indicating a favorable selectivity profile. Phosphonium conjugation preserves PARP1 inhibitory activity while conferring mitochondrial targeting and enhanced anticancer potency. These findings support the development of mitochondria-targeted PARP inhibitors as a next-generation therapeutic strategy with the potential to improve efficacy and overcome resistance in HR-deficient tumors. Full article

This study presents a robust deep learning-based approach for temperature sensing using Fiber Specklegram Sensors (FSS), leveraging an extended experimental framework to evaluate model generalization. A convolutional neural network (CNN), specifically a customized MobileNet architecture (MNet-reg), was trained on multiple experimental datasets to assess the impact of increasing data availability on sensing accuracy. Generalization is evaluated as cross-dataset performance under unseen experimental realizations, rather than under controlled intra-dataset splits. The experimental setup utilized a multi-mode optical fiber (MMF) (core diameter 62.5 µm) subjected to controlled thermal cycles via a PID-regulated heating system. The curated dataset comprises 24,528 specklegram images captured over a temperature range of 25.00 °C to 200.00 °C with increments of ~0.20 °C. The experimental results demonstrate that models trained with an increasing number of datasets (from 1 to 13) significantly improve accuracy, reducing Mean Absolute Error (MAE) from 13.39 to 0.69 °C, and achieving a Root Mean Square Error (RMSE) of 0.90 °C with an R² score of 0.99. Our systematic analysis establishes that scaling experimental data diversity—through training on multiple independent realizations—is the foundational strategy to overcome domain shift and enable robust cross-dataset generalization. Full article

The development of functional polymer films on porous paper substrates is inherently constrained by substrate-induced defects that hinder film continuity and barrier performance. In this study, process-controlled amylose–Poly(Vinyl alcohol) (PVA) coatings incorporating ZnO nanoparticles (ZnO NPs) were fabricated via aqueous deposition to investigate the process-structure-property relationship governing oxygen barrier behavior on paper. The moisture resistance of the coating was also evaluated. Single-layer coatings exhibited severe barrier failure due to insufficient film formation and pervasive pinhole defects. In contrast, systematic multi-layer deposition enabled the formation of continuous polymer films. A pronounced non-linear reduction in oxygen transmission rate was observed once the dry coating thickness exceeded approximately 5 µm. Under these conditions, the oxygen transmission rate decreased to approximately 15 cc/m²·day·atm at 20 °C and 65% relative humidity. This transition was correlated with the elimination of substrate-induced defects, as confirmed by morphological analysis. In addition to enhanced barrier performance, ZnO NP-loaded coatings demonstrated strong and broad-spectrum antimicrobial activity against both Escherichia coli and Staphylococcus aureus, indicating their multifunctional potential for active packaging applications. Supporting evaluations further indicated adequate mechanical flexibility and high repulpability, highlighting the suitability of the coating for sustainable paper-based packaging. Overall, this work identifies a quantitative critical film thickness that serves as process-specific design guideline for engineering high-performance functional polymer coatings on porous paper substrates. Full article