Search Results (1,236)

Background/Objectives: The dual targeting of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) represents an effective approach for cancer treatment. The current study involved the design, synthesis, and biological evaluation of a new series of purine-containing hydrazones, 6–24 (a,b), as anticancer agents targeting EGFR and HER2 kinases. Methods: The proposed compounds were initially screened in silico using molecular docking to investigate their expected binding affinity to the active sites of EGFR and HER2 kinase domains. Subsequently, the compounds were synthesized and evaluated in vitro for their antiproliferative activity, using the MTT assay, against the various cancer cell lines A549, SKOV-3, A2780, and SKBR-3, with lapatinib as the reference drug. The most active derivatives were then examined to determine their inhibitory activity against EGFR and HER2 kinases. Results: Among the assessed compounds, significant antiproliferative activity was demonstrated by 19a, 16b, and 22b. 19a exhibited substantial anticancer efficacy against A549 and SKBR-3, with IC₅₀ values of 0.81 µM and 1.41 µM, respectively. This activity surpassed lapatinib, which has an IC₅₀ of 11.57 µM on A549 and 8.54 µM on SKBR-3 cells. Furthermore, 19a, 16b, and 22b exhibited superior EGFR inhibitory efficacy compared with lapatinib (IC₅₀ = 0.13 µM), with IC₅₀ values of 0.08, 0.06, and 0.07 µM, respectively. Regarding HER2, 22b demonstrated the greatest potency with an IC₅₀ of 0.03 µM, equipotent to lapatinib (IC₅₀ = 0.03 µM). Flow cytometry analysis of A549 cells treated with 19a and 22b indicated their ability to arrest the cell cycle during the G1 phase and to trigger cellular apoptosis. Conclusions: Compounds 19a, 16b, and 22b represent intriguing candidates for the development of an anticancer agent targeting EGFR and HER2 kinases. Full article

Background and Objectives: The efficacy of newly synthesized water-soluble octa-mercaptopyridine-substituted oxotitanium (IV) phthalocyanine (oxo-TiPc) and copper (II) phthalocyanine (CuPc) compounds in photodynamic therapy (PDT) was investigated using human tongue squamous cell cancer cell line (SCC-9, ATCC) cultures. Materials and Methods: A laser light source with a wavelength of 635 nm was used for this study. The cytotoxic values of the cancerous (SCC-9) and healthy (L-929) cell samples to which different Pc concentrations were applied under laser light were evaluated spectroscopically with the XTT method. Results: The oxo-TiPc compound exhibited a significantly lower IC50 value (46.8 µM) for SCC-9 cells compared to the CuPc compound (286.2 µM), indicating higher anticancer activity. This cytotoxicity may be due to decreased aggregation and enhanced reactive oxygen species (ROS) formation. Double-staining tests confirmed that oxo-TiPc-induced cell death included both apoptosis and necrosis. Conclusions: The findings show that the oxo-TiPc compound, unlike the CuPc compound, exhibited more selective toxicity to the SCC-9 cell line and has a higher phototoxic effect. Full article

Background/Objective: Programmed cell death ligand-1 (PD-L1), which is overexpressed in certain tumors, inhibits the body’s natural immune response by providing an “off” signal that enables cancer cells to evade the immune system. It has been demonstrated that [¹⁷⁷Lu]Lu-DOTA-iPD-L1 (PD-L1 inhibitor cyclic peptide) promotes immune responses. This study aimed to synthesize and evaluate [¹⁸F]AlF-NOTA-iPD-L1 as a novel radiotracer for PD-L1 positron emission tomography (PET) imaging and as a potential theranostic pair for [¹⁷⁷Lu]Lu-DOTA-iPD-L1. Methods: The NOTA-iPD-L1 peptide conjugate was synthesized and characterized by U.V.-vis, I.R.-FT, and UPLC-mass spectroscopies. Radiolabeling was performed using [¹⁸F]AlF as the precursor, and the radiochemical purity (HPLC), partition coefficient, and serum stability were assessed. Cellular uptake and internalization (in 4T1 triple-negative breast cancer cells), binding competition, immunofluorescence, and Western blot assays were applied for the radiotracer in vitro characterization. Biodistribution in mice bearing 4T1 tumors was performed, and molecular imaging (Cerenkov images) of [¹⁸F]AlF-NOTA-iPD-L1 and [¹⁷⁷Lu]Lu-DOTA-iPD-L1 in the same mouse was obtained. Results: [¹⁸F]AlF-NOTA-iPD-L1 was prepared with a radiochemical purity greater than 97%, and it demonstrated high in vitro and in vivo stability, as well as specific recognition by the PD-L1 protein (IC₅₀ = 9.27 ± 2.69 nM). Biodistribution studies indicated a tumor uptake of 6.4% ± 0.9% ID/g at 1-hour post-administration, and Cerenkov images showed a high tumor uptake of both [¹⁸F]AlF-NOTA-iPD-L1 and ¹⁷⁷Lu-iPD-L1 in the same mouse. Conclusions: These results warrant further studies to evaluate the clinical usefulness of [¹⁸F]AlF-NOTA-iPD-L1/[¹⁷⁷Lu]Lu-DOTA-iPD-L1 as a radiotheranostic pair in combination with anti-PD-L1/PD1 immunotherapy. Full article

Background/Objectives: Neurocognitive disorders (NCDs) encompass a spectrum of conditions that significantly impact cognitive domains, including attention, memory, and language. Mild NCD, increasingly prevalent with aging, represents an early stage of these disorders, characterized by cognitive deficits that do not interfere with daily functioning. Non-pharmacological therapies, especially cognitive stimulation, are widely recommended to preserve cognitive function of older adults. This study aimed to evaluate the effectiveness of a 12-week individual cognitive stimulation (iCS) program on cognitive performance, mood, and prefrontal cortex activation in older adults with mild NCD using a single-blind, randomized, parallel two-arm RCT. Methods: A sample of 36 older adults were selected from a central region of Portugal. The intervention group (n = 18) received 24 iCS sessions, twice weekly for 12 weeks. The control group (n = 18) completed their regularly scheduled activities. Outcomes included global cognitive function, executive functioning, and mood. All participants were assessed at baseline and after the intervention. Functional near infra-red spectroscopy (fNIRS) was also collected to measure prefrontal cortex activity at both time points in the intervention group. Results: The intervention group showed a significant improvement in global cognition and executive functions, and reduced depressive symptomatology compared to the control group. fNIRS data revealed enhanced activation and functional efficiency in the lateral prefrontal cortex following the iCS program. Adherence and degree of collaboration to the intervention were very high. Conclusions: These findings suggest that iCS is an effective approach to improving cognitive function and mood in mildly cognitively impaired older adults. Full article

Electric vehicles (EVs) have been the most dependable and feasible choice for decarbonizing road transport over the last decade. To ensure the advancement of EVs and establish them as a sustainable alternative to internal combustion engine (ICE) vehicles, the EV sector and technological growth have largely relied on government subsidies. A significant challenge for EVs is their faster depreciation compared to ICE vehicles, primarily owing to swift technological advancements that propel the market while simultaneously rendering older EV models outdated too soon. Another factor that leads to the quicker depreciation of EVs is subsidies. The anticipated cessation of subsidies is expected to provide the required leverage to mitigate the rapid value decline in EVs, given the larger price disparity between new and used EVs. Batteries, which enable EVs to be a viable option, significantly contribute to the depreciation of EVs. In addition to the potential decline in EV battery performance, advancements in technology and reduced prices provide newer models with improved range at a more affordable cost. The used EV market accurately represents the rapid devaluation of EVs; consequently, the two topics are tightly related. Though it might not be immediately apparent, it seems evident that the pace of depreciation of EVs significantly contributes to the small size of the second-hand EV market. Depreciation is a key factor influencing the used EV market. This manuscript outlines the key aspects of depreciation and sustainability in the EV transition, especially those linked to rapid technological advancements, such as batteries, in addition to subsidies and the used EV market. The objective of this manuscript is to expose and analyze the relation between the drivers of the second-hand EV market, such as the cost of ownership, technology, and subsidies, and, on the other hand, present the interplay perspectives and challenges. Full article

To investigate the slope instability caused by differential frost heaving mechanisms from the slope crest to the toe during frost heave processes, this study takes a typical silty clay slope in Xinjiang, China, as the research object. Through indoor triaxial consolidated undrained shear tests, eight sets of natural and frost-heaved specimens were prepared under confining pressure conditions ranging from 100 to 400 kPa. The geotechnical parameters of the soil in both natural and frost-heaved states were obtained, and a spatiotemporal thermo-hydro-mechanical coupled numerical model was established to reveal the dynamic evolution law of anchor rod axial forces and the frost heave response mechanism between the frame and slope soil. The analytical results indicate that (1) the frost heave process is influenced by slope boundaries, resulting in distinct spatial variations in the temperature field response across the slope surface—namely pronounced responses at the crest and toe but a weaker response in the mid-slope. (2) Under the coupled drive of the water potential gradient and gravitational potential gradient, the ice content in the toe area increases significantly, and the horizontal frost heave force exhibits exponential growth, reaching its peak value of 92 kPa at the toe in February. (3) During soil freezing, the reverse stress field generated by soil arching shows consistent temporal variation trends with the temperature field. Along the height of the soil arch, the intensity of the reverse frost heave force field displays a nonlinear distribution characteristic of initial strengthening followed by attenuation. (4) By analyzing the changes in anchor rod axial forces during frost heaving, it was found that axial forces during the frost heave period are approximately 1.3 times those under natural conditions, confirming the frost heave period as the most critical condition for frame anchor design. Furthermore, through comparative analysis with 12 months of on-site anchor rod axial force monitoring data, the reliability and accuracy of the numerical simulation model were validated. These research outcomes provide a theoretical basis for the design of frame anchor support systems in seasonally frozen regions. Full article

Background/Objectives: Mycobacterium avium, a member of Mycobacterium avium complex (MAC), is an emerging opportunistic pathogen causing MAC-pulmonary disease (PD). Fluoroquinolones (FQs), along with ethambutol (EMB) and rifampicin, are recommended for macrolide-resistant MAC-PD; however, FQ-resistant M. avium have been reported worldwide. WQ-3810 is an FQ with high potency against FQ-resistant pathogens; however, its activity against M. avium has not yet been studied. Methods: In this study, we conducted a DNA supercoiling inhibitory assay to evaluate the inhibitory effect of WQ-3810 on recombinant wild-type (WT) and four mutant DNA gyrases of M. avium and compared the IC₅₀s of WQ-3810 with those of ciprofloxacin (CIP), levofloxacin (LVX), and moxifloxacin (MXF). In addition, we examined WQ-3810’s antimicrobial activity against 11 M. avium clinical isolates, including FQ-resistant isolates, with that of other FQs. Furthermore, we assessed the synergistic action of WQ-3810 with the combination of either EMB or isoniazid (INH). Results: In a DNA supercoiling inhibitory assay, WQ-3810 showed 1.8 to 13.7-fold higher efficacy than LVX and CIP. In the MIC assay, WQ-3810 showed 4 to 8-fold, 2 to 16-fold, and 2 to 4-fold higher antimicrobial activity against FQ-resistant isolates than CIP, LVX, and MXF, respectively. The combination of WQ-3810 and INH exhibited a synergistic relationship. Conclusions: The overall characteristics of WQ-3810 demonstrated greater effectiveness than three other FQs, suggesting that it is a promising option for treating FQ-resistant M. avium infections. Full article

Background/Objectives: This study aimed to investigate the antioxidant and anti-inflammatory properties of a Hand and Foot Soaking Formulary composed of ten medicinal plants, with curcumin as a major bioactive marker, to provide scientific validation for its traditional use. Methods: The formulation was evaluated for total phenolic and flavonoid contents, with curcumin quantified using HPLC. Antioxidant activity was assessed using DPPH, ABTS, and FRAP assays. Cytotoxicity was evaluated in RAW264.7 cells using the MTT assay. Anti-inflammatory activity was determined by measuring nitric oxide (NO), PGE₂, TNF-α, IL-1β, and IL-6 levels in LPS-stimulated RAW264.7 macrophages using ELISA. Results: The Hand and Foot Soaking Formulary exhibited promising antioxidant and anti-inflammatory properties, consistent with its traditional use. Phytochemical analysis confirmed the presence of bioactive compounds, with measurable levels of total phenolics, flavonoids, and significant curcumin content. Antioxidant activity was demonstrated through free radical scavenging and ferric-reducing assays, while cytotoxicity testing in RAW264.7 macrophages indicated low toxicity (IC₅₀ = 48.61 ± 3.80 µg/mL). The formulary significantly reduced LPS-induced nitric oxide, PGE₂, TNF-α, IL-1β, and IL-6 production. These effects were comparable to turmeric extract and curcumin, though curcumin displayed higher potency. Conclusions: The Hand and Foot Soaking Formulary demonstrates antioxidant and anti-inflammatory properties in vitro, supporting its traditional use. Its polyherbal composition may offer synergistic effects and holds promise as a safe, natural topical remedy. Full article

Background: Liposomes and, more recently, structured nanolipid particles have demonstrated effectiveness as carriers for delivering hydrophilic or lipophilic anticancer agents, enhancing their biocompatibility, bioavailability, and sustained release to target cells. Objective: Herein, four doxorubicin formulations—comprising either the acidic or neutral form—were encapsulated into liposomes (Lipo) or nanostructured lipid carriers (NLCs) and characterized in terms of size, entrapment efficiency, morphology, and effects on two cancer cell lines (melanoma B16-F10 and breast carcinoma Walker 256 cells). Methods and Results: While liposomal formulations containing acidic doxorubicin displayed IC₅₀ values ranging from 1.33 to 0.37 µM, NLC-based formulations, particularly NLC-Doxo@Ac, demonstrated enhanced cytotoxicity with IC₅₀ values as low as 0.58 µM. Neutral Doxorubicin demonstrated lower cytotoxicity in both the nanoformulations and cell lines. Differences were also observed in their internalization patterns, cell-cycle impact, and apoptotic/necrotic effects. Compared to liposomes, NLCs exhibited distinct internalization patterns and induced stronger cell-cycle arrest and necrosis, especially in melanoma cells. Notably, NLC-Doxo@Ac outperformed liposomal counterparts in melanoma cells, while liposomal formulations showed slightly higher efficacy in Walker cells. Early and late apoptosis were more pronounced in Walker cells, whereas necrosis was more prominent in melanoma B16-F10 cells, particularly with the nanolipid formulations. Conclusions: These results correlated positively with cell-cycle measurements, highlighting the potential of NLCs as an alternative to liposomes for the delivery of neutral or acidic doxorubicin, particularly in tumor types that respond poorly to conventional formulations. Full article

Background/Objectives: This research reports the synthesis and evaluation of novel charged thienobenzo-triazoles as non-selective cholinesterase inhibitors (AChEs and BChEs), their anti-inflammatory properties, and a computational study. Methods: Fifteen derivatives were created through photochemical cyclization and quaternization of the triazole core. The compounds were tested for AChE and BChE inhibition. They showed greater potency and selectivity toward BChE. Results: The most potent compound, derivative 14, inhibited BChE with an IC₅₀ of 98 nM, while derivative 9 also displayed significant anti-inflammatory activity by inhibiting LPS-induced TNF-α production (IC₅₀ = 0.66 µM). Molecular docking revealed that triazolinium salts form key π-π and electrostatic interactions within enzyme active sites. In silico predictions indicated favorable ADME-Tox properties for compounds 9 and 11, including low mutagenicity and moderate CNS permeability. Conclusions: These findings highlight the potential of new charged triazolinium salts as peripherally selective cholinesterase inhibitors with additional anti-inflammatory potential. Full article

Aircraft icing and snow accumulation are significant threats to flight safety and operational efficiency, necessitating rapid and accurate detection methods. The aim of this study was to develop and comparatively evaluate artificial intelligence (AI) models for the real-time detection of ice and snow on aircraft surfaces using vision systems. A custom dataset of annotated aircraft images under various winter conditions was prepared and augmented to enhance model robustness. Two training approaches were implemented: an automatic process using the YOLOv8 framework on the Roboflow platform and a manual process in the Google Colab environment. Both models were evaluated using standard object detection metrics, including mean Average Precision (mAP) and mAP@50:95. The results demonstrate that both methods achieved comparable detection performance, with final mAP50 values of 0.25–0.3 and mAP50-95 values around 0.15. The manual approach yielded lower training losses and more stable metric progression, suggesting better generalization and a reduced risk of overfitting. The findings highlight the potential of AI-driven vision systems to support intelligent de-icing decision-making in aviation. Future research should focus on refining localization, minimizing false alarms, and adapting detection models to specific aircraft components to further enhance operational safety and reliability. Full article

Mars’ south polar cap hosts dynamic landforms known as Swiss cheese features (SCFs), which form through the sublimation of carbon dioxide (CO₂) ice driven by the planet’s extreme seasonal and diurnal solar insolation cycles. These shallow, rounded depressions—first identified by Mars Global Surveyor in 1999 and later monitored by the Mars Reconnaissance Orbiter (MRO)—have been observed to increase in size over time. However, large-scale analysis of SCF formation and growth has been limited by the slow and labor-intensive nature of manual mapping techniques. This study applies object-based image analysis (OBIA) to automate the detection and measurement of SCFs using High-Resolution Imaging Science Experiment (HiRISE) images spanning five Martian years. Results show that SCFs exhibit a near-linear increase in area, suggesting that summer sublimation consistently outpaces winter CO₂ deposition. Validation against manual digitization shows discrepancies of less than 1%, confirming the reliability of the OBIA method. Regression-based extrapolation of growth trends indicates that the current generation of SCFs likely began forming between Martian years 7 and 16, approximately corresponding to Earth years 1976 to 1998. These findings provide a quantitative assessment of SCF evolution and contribute to our understanding of recent climate-driven surface changes on Mars. HiRISE images were processed using the eCognition software to detect, classify, and measure SCFs, demonstrating that OBIA is a scalable and effective tool for analyzing dynamic planetary landforms. Full article

Background/Objectives: Catheter ablation has become the standard of care for patients with symptomatic and drug-refractory atrial fibrillation (AF). Both Class IC and Class III antiarrhythmic drugs (AADs) are effective in preventing early recurrences of AF, but not late recurrences, compared with the usual care. We aimed to compare the effects of two months of Class IC versus Class III AADs following AF catheter ablation on clinical outcomes, including arrhythmia recurrence and safety endpoints. Methods: All patients undergoing AF catheter ablation between January 2015 and November 2024 were screened, and cases meeting the inclusion criteria were included. Primary outcome was defined as atrial tachycardia recurrence-free survival. Results: A total of 98 patients (mean age 54.2 ± 14.0 years; 55.1% male) were enrolled, with 66.3% presenting with paroxysmal atrial fibrillation (AF). The mean left atrial diameter was 38.7 ± 5.1 mm, and 78.6% underwent cryoballoon ablation. Class IC AADs were administered to 62 cases, while the remaining 36 patients received amiodarone following catheter ablation. The rate of atrial tachycardia (ATa) recurrence was comparable between the patients treated with Class IC and Class III AADs (9.7% vs. 19.4%; p = 0.169). Predictors of ATa recurrence were identified as history of direct current cardioversion—DCCV (HR: 5.86; 95%CI: 1.44–23.82)—and LA diameter (HR: 1.17; 95%CI: 1.04–1.31). The most frequent AAD-related adverse event was symptomatic bradycardia (6.1%), which resolved in all cases following dose reduction. Conclusions: Class IC and Class III antiarrhythmics show comparable efficacy in terms of preventing ATa recurrence following AF catheter ablation. AAD-related adverse event rates are negligible for short-term use. Full article

Under the influence of global climate change, water conservancy projects located in the high-latitude cold regions of the world are facing severe challenges. This study addresses the contradiction between water supply stability and ecological flow during the dry season in cold regions. Taking Linhai Reservoir as the core, it integrates the HEC-RAS hydrodynamic model with multi-source data such as basin topography, hydro-meteorological data, and water conservancy project parameters to construct a multi-scenario water supply scheduling model during the dry season. The aim is to provide scientific recommendations for different reservoir operation strategies in response to varying frequencies of upstream inflow, based on simulations conducted after the reservoir’s completion. Taking into account winter runoff reduction characteristics and engineering parameters, we simulated the relationships between water level and flow, ecological flow requirements, and urban water shortages. The results indicate that in both flood and normal years, dynamic coordination of storage and discharge can achieve a daily water supply of 120,000 cubic meters, with 100% compliance for the ecological flow rate. For mild and moderate drought years, additional water diversion becomes necessary to achieve 93.5% and 89% supply reliability, respectively. During severe and extreme droughts, significantly reduced reservoir inflows lower ecological compliance rates, necessitating emergency measures, such as utilizing dead storage capacity and exploring alternative water sources. The study proposes operational strategies tailored to different drought intensities: initiating storage adjustments in September for mild droughts and implementing peak-shifting measures by mid-October for extreme droughts. These approaches enhance storage efficiency and mitigate ice blockage risks. This research supports the water supply security and river ecological health of urban and rural areas in Mudanjiang City and Hailin City and provides a certain scientific reference basis for the multi-objective coordinated operation of reservoirs in the same type of high-latitude cold regions. Full article

Objectives: The aim of this work was to determine the phenolic composition of sweet wormwood (Artemisia annua L., Asteraceae) from controlled cultivation in Serbia and to assess the potential antioxidant effects and cytotoxicity. Methods: High-performance liquid chromatography was used to determine the phenolic composition of Artemisia annua ethanolic extract. The antioxidant activity was studied using in vitro tests of inhibition of the neutralization of 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl (OH), and nitroso (NO) radicals, as well as the process of inhibiting lipid peroxidation and the ferric reducing antioxidant power (FRAP). The cytotoxicity was evaluated by the effect on three cell lines (the rat pancreatic insulinoma cell line (Rin-5F), the rat hepatoma cell line (H4IIE), and human hepatocellular carcinoma (Hep G2)) using the MTT test of viability. Results: Ethanol extract showed the highest potency in inhibiting the DPPH radical, and the half maximal inhibitory concentration (IC₅₀) was 5.17 μg/mL. Chlorogenic acid was the dominant phenolic compound with an amount of 651 μg/g of dry extract. The results of the MTT viability test showed that the extract has the potential to inhibit the growth of the Rin-5F and Hep G2 cell lines, while no growth inhibition was observed on the H4IIE cell line. Conclusions: Undoubtedly, Artemisia annua is a powerful plant and a rich source of phenolic compounds. Inhibitory activity on causes of oxidative stress shows that the plant has a good antioxidant effect. Also, the anticancer activity shown through the inhibition of cell growth is not negligible. Full article