Search Results (1,306)

Background: The increased incidence of malignant melanoma is observed in patients with Parkinson’s disease. Methods: The anti-proliferative effects of carbidopa and rasagiline on four human malignant melanoma cell lines (A375, SK-MEL28, FM55P and FM55M2) were determined in MTT assay. The interaction profiles of rasagiline in combinations with cisplatin (CDDP) and mitoxantrone (MTX) in four human melanoma cell lines (A375, SK-MEL28, FM55P and FM55M2) were assessed by means of the isobolographic analysis in the MTT test; Results: Rasagiline, but not carbidopa, produced clear-cut anti-proliferative effects on various melanoma cell lines. The median inhibitory concentrations (IC₅₀ values) of rasagiline in the MTT were 280.69 µM for A375, 402.89 µM for SK-MEL28, 349.44 µM for FM55P, and 117.45 µM for FM55M2, respectively. The experimentally-derived selectivity index for rasagiline ranged from 8.22 to 28.18. Flow cytometry assay revealed, in two melanoma cell lines (FM55P and A375), a significant increase in the number of cells in the G0/G1 (up to 76.48% and 75.46% for cell lines, respectively), accompanied by a decrease in the percentage of cells in the S phase (decrease to 9.91% and 10.83% for cell lines, respectively), which may indicate potential cytostatic properties of rasagiline. The combinations of rasagiline with CDDP (at the fixed-ratio of 1:1) exerted either antagonistic interactions (p < 0.05) in the A375 and SK-MEL28, or additive interactions, with a tendency toward antagonism in the FM55P and FM55M2 cell lines in the MTT test. In contrast, the combinations of rasagiline with MTX (ratio of 1:1) produced either synergistic interaction (p < 0.05) in the FM55P cell line or additive interactions with a tendency toward synergy in the FM55M2, SK-MEL28, and A375 cell lines in the MTT test. Conclusions: Rasagiline combined with MTX exerted the most desirable synergistic interactions in relation to the anti-proliferative effects in four malignant melanoma cell lines, as assessed isobolographically. In contrast, rasagiline should not be combined with CDDP during the treatment of malignant melanoma due to the antagonistic interactions in the MTT assay. Full article

Tropical sandy beaches are dynamic ecosystems where microbial communities play crucial roles in biogeochemical processes and tracking human impact. Despite their importance, these habitats remain underexplored. Here, using amplicon-based sequencing of bacterial (V3-V4 16S rRNA) and fungal (ITS2) markers, we first describe microbial communities inhabiting supralittoral–intertidal sediments of two contrasting sandy beaches in the Tadjoura Gulf (Djibouti Republic): Sagallou-Kalaf (SK, rural, siliceous sand) and Siesta Plage (SP, urban, calcareous sand). Sand samples were collected at low tide along 10 m transects perpendicular to the shoreline. Bacterial communities differed significantly between sites and along the sea-to-land gradient, suggesting an influence from both anthropogenic activity and sediment granulometry. SK was dominated by Escherichia-Shigella, Staphylococcus, and Bifidobacterium, associated with human and agricultural sources. SP showed higher richness, with enriched marine-associated genera such as Hoeflea, Xanthomarina, and Marinobacter, also linked to hydrocarbon degradation. Fungal diversity was less variable, but showed significant shifts along transects. SK communities were dominated by Kluyveromyces and Candida, while SP hosted a broader fungal assemblage, including Pichia, Rhodotorula, and Aureobasidium. The higher richness at SP suggests that calcium-rich sands, possibly due to their buffering capacity and greater moisture retention, offer more favorable conditions for microbial colonization. Full article

Background/Objectives: Viral respiratory infections have a significant impact on global health and the economy. While vaccines are effective in preventing infection, they might not be available or sufficient when used alone and must be complemented by specific therapeutic strategies. The development of new antiviral agents is increasingly important due to the continual emergence of novel respiratory pathogens. Previously we identified bovine lactoferrin (bLf)-derived tetrapeptides and peptidomimetics that showed potent in vitro activity against the influenza A virus in the picomolar range. Methods: Inspired by these results, in this study, we evaluated the antiviral potential of these compounds against HCoV-229E, a human coronavirus that can cause severe disease in immunocompromised individuals, using a compound repositioning approach. Results: Functional studies revealed that SK(N-Me)HS (3) interferes with viral entry and replication, while compound SNKHS (5) primarily blocks infection in the early stages. Biophysical analyses confirmed the occurrence of high-affinity binding to the viral spike protein, and computational studies suggested that the compounds target a region involved in conformational changes necessary for membrane fusion. Conclusions: These findings highlight these compounds as promising candidates for coronavirus entry inhibition and underscore the value of compound repurposing in antiviral development. Full article

This study introduces the Skeptical Optimism Scale (SkO) and presents preliminary evidence of its content, construct, and criterion validity. Skeptical optimism refers to dispositional tendencies of having general positive expectations about the future, conditional on critical analysis and in-depth exploration of (potential negative) outcomes. We developed an initial pool of 31 items that explore positive expectations in three main life domains (finding solutions to difficult problems, mastering novel and challenging tasks, and effectively dealing with general life challenges) that were subject to content analysis by eight independent raters. The remaining items were tested for criterion and predictive validity in two samples (N = 198 and N = 417 participants). Factor analyses supported a three-factor structure and the refined 17-item version of the scale showed good reliability and validity. To support applications in settings requiring brief instruments, we also developed a 9-item version, preserving the factorial structure and psychometric qualities of the original scale. The results show that the 17 as well as 9-item SkO scales have a good criterion validity as they positively and significantly correlate with the core self-evaluation scale, critical thinking disposition, and grit. Moreover, our results show that the SkO has good predictive validity as it is the only significant predictor of the creativity quotient in our sample. Full article

B-raf (rapidly accelerated fibrosarcoma) is a crucial player within the ERK/MAPK signaling pathway. In the CNS, B-raf has been implicated in neuronal differentiation, long-term memory, and major depression. Mice with forebrain neuron-specific B-raf knockout show behavioral deficits in spatial learning tasks and impaired hippocampal long-term potentiation (LTP). To elucidate the mechanism(s) underlying diminished synaptic plasticity in B-raf-deficient mice, we performed whole-cell recordings from CA1 pyramidal cells in hippocampal slices of control and B-raf mutant mice. We found that the NMDA/AMPA ratio of excitatory postsynaptic currents (EPSCs) at the Schaffer collateral—CA1 pyramidal cell synapses was significantly reduced in B-raf mutants, which would at least partially account for their impaired LTP. Interestingly, the reduced NMDA component of field postsynaptic potentials in mutant preparations was partially reinstated by blocking the apamin-sensitive small-conductance Ca²⁺-activated K⁺ (SK) channels, which have also been reported to modulate hippocampal LTP and learning tasks. To determine the impact of B-raf-dependent signaling on SK current, we isolated the apamin-sensitive tail current after a strong depolarizing event and found indeed a significantly bigger SK current in B-raf-deficient cells compared to controls, which is consistent with the reduced action potential firing and the stronger facilitating effect of apamin on CA1 somatic excitability in B-raf-mutant hippocampus. Our data suggest that B-raf signaling readjusts the delicate balance between NMDA receptors and SK channels to promote synaptic plasticity and facilitate hippocampal learning and memory. Full article

An analog joint source-channel coding (AJSCC) based on Shannon–Kotel’nikov (S-K) mapping transmitting discrete-time encoded samples in orthogonal frequency division multiplexing (OFDM) systems over wireless channel has exhibited excellent performance. However, the phenomenon of carrier frequency offset (CFO) caused by the frequency mismatch between the transmitter’s and receiver’s local oscillators often exists in actual scenarios; thus, in this paper the performance of AJSCC-OFDM with CFO is analyzed and the S-K mapping is optimized. A joint optimization strategy is developed to maximize the signal-to-distortion ratio (SDR) subject to CFO constraints. Considering that the optimized AJSCC-OFDM strategies will change the amplitude distribution of encoded symbol, the peak-to-average power ratio (PAPR) characteristics under different AJSCC parameters are also analyzed. Full article

Background/Objectives: HIF-1α and ERRα are both implicated in breast cancer progression, yet their functional interplay remains poorly understood. This study investigates their molecular crosstalk in the context of hypoxia-induced drug resistance. Methods: MCF-7 (estrogen receptor, ER-positive) spheroids and CoCl₂-treated SK-BR-3 (ER-negative) cells were used to model tumor hypoxia. Protein expression, coimmunoprecipitation, chromatin immunoprecipitation (ChIP), pharmacological inhibition, and siRNA-mediated gene silencing were employed to assess physical and functional interactions. Immunohistochemistry (IHC) on a tissue microarray (TMA) of 168 invasive breast carcinomas was performed to evaluate clinical relevance. Results: ERRα levels remained unchanged under hypoxia, while its coactivator, Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 α (PGC-1α), was upregulated. ERRα physically interacted with HIF-1α and was required for HIF-1 transcriptional activity under hypoxic conditions. ChIP assays showed that ERRα-driven overexpression of Permeability glycoprotein 1 (P-gp) and Vascular Endothelial Growth Factor (VEGF) was mediated by HIF-1α binding to the MDR1 and VEGF promoters. Inhibition or silencing of ERRα reversed P-gp overexpression and restored intracellular doxorubicin. TMA analysis confirmed the clinical correlation between ERRα, HIF-1α, and P-gp expression, highlighting the role of ERRα in hypoxia-induced drug resistance. ERRα expression was independent of ER status, suggesting an estrogen-independent function. Conclusions: This study identifies a novel physical and functional interaction between ERRα and HIF-1α that promotes chemoresistance in hypoxic breast tumors. Targeting ERRα may represent a promising therapeutic strategy to overcome drug resistance in aggressive, ER-independent breast cancer subtypes. Full article

The decline in differentiation capacity during skeletal muscle (SkM) aging contributes to the deterioration of skeletal muscle function and impairs regenerative ability. Epicatechin gallate (ECG), a major functional component of catechins found in tea, has an unclear role in aging-related sarcopenia. In vivo experiments in 54-week-old C57BL/6J mice showed that ECG treatment improved exercise performance, muscle mass, and fiber morphology and downregulated the expression of the testosterone metabolic enzyme gene UGT2A3 in aged mice. In vitro experiments with Leydig cells (TM3) demonstrated that ECG upregulated the mRNA and protein expression levels of testosterone synthase genes, including StAR, P450scc, 3β-HSD, CYP17a1, and 17β-HSD. Network pharmacology analysis further suggested that ECG can influence testosterone secretion through the regulation of cytokines, thereby promoting skeletal muscle differentiation. These findings indicate that ECG enhances the differentiation of skeletal muscle cells by modulating testosterone levels, which helps alleviate age-related muscle function decline. Full article

Proteomics combined with peptidomics approaches were used to analyze the protein degradation and the release pattern of umami peptides in stewed chicken. The results showed that a total of 422 proteins were identified, of which 273 proteins consistently existed in samples stewed for 0–5 h. Myosin heavy chain exhibited the highest abundance (26.29–30.26%) throughout the stewing process. The proportion of proteins under 20 kDa increased progressively with the duration of stewing and reached 61% at 4–5 h of stewing. A total of 8018 peptides were detected in the soup samples, and 2323 umami peptides were identified using the prediction platforms iUmami-SCM, UMPred-FRL, Umami_YYDS, and TastePertides-DM. Umami peptides derived from titin (accession number A0A8V0ZZ81) were determined to be the most abundant, accounting for 24% of the total umami peptides, and Val534 and Lys33639 were the key N-terminal and C-terminal amino acids of these umami peptides. Abundance analysis showed that the umami peptides KK16 and SK18 ranked among the top 5 in the samples stewed for 0–5 h, and they were most abundant in the 3 h stewed samples. The results obtained will provide data support for promoting the industrialization of high-quality chicken soup products. Full article

The robust detection of small targets is crucial in infrared (IR) search and tracking applications. Considering that many state-of-the-art (SOTA) methods are still unable to suppress various edges satisfactorily, especially under complex backgrounds, an effective infrared small target detection algorithm inspired by modified fast saliency and the weighted guided image filter (WGIF) is presented in this paper. Initially, the fast saliency map modulated by the steering kernel (SK) is calculated. Then, a set of edge-preserving smoothed images are produced by WGIF using different filter radii and regularization parameters. After that, utilizing the fuzzy sets technique, the background image is predicted reasonably according to the results of the saliency map and smoothed or non-smoothed images. Finally, the differential image is calculated by subtracting the predicted image from the original one, and IR small targets are detected through a simple thresholding. Experimental results on four sequences demonstrate that the proposed method can not only suppress background clutter effectively under strong edge interference but also detect targets accurately with a low false alarm rate. Full article

Malania oleifera Chun & S.K. Lee, an endemic monotypic species that belongs to the family Olacaceae, is under continuous pressure of decline owing to several ecological and physiological factors. The present study aimed to establish an efficient in vitro protocol for callus-mediated indirect somatic embryogenesis in M. oleifera by alleviating tissue browning. Internodes and leaves obtained from seedlings were used as explants. Antioxidant pre-treatment (ascorbic acid, AA) followed by different carbon sources (sucrose, maltose, glucose, and fructose) and plant growth regulators in various concentrations and combinations were employed in Woody Plant Medium (WPM) to alleviate explant browning and induce callus formation from the explants. AA pre-treatment and subsequent culture on maltose at a concentration of 116.8 mM were optimal for controlling phenolic exudation on >90% of both explants. The highest responses of 53.77% and 57.43% for embryogenic calli were induced from internode and leaf explants, respectively. The highest responses, 85.22% and 93.80%, were observed for somatic embryos that matured into the globular, heart-shaped and torpedo stages at different percentages on NAA 2.5 mg/L in combination with BA 1.0 mg/L for both explants. The matured somatic embryos were finally germinated at a maximum concentration of GA₃, 2.0 mg/L. All plantlets were successfully hardened and acclimatized under culture room conditions and then transferred to the greenhouse. The current study suggests an efficient protocol for indirect somatic embryogenesis by alleviating phenolic exudation from the explants of M. oleifera. This first successful report of in vitro culture establishment in M. oleifera may offer an effective alternative measure to conserve this species and provide a system for analyzing bioactive chemicals and for use in the oil industry. Full article

Background/Objectives: Myasthenia Gravis (MG) and myasthenic syndrome (MSyn) are neurological disorders induced by different types of autoantibodies, characterized by generalized muscle weakness, sometimes involving the respiratory muscles and necessitating ventilatory support. One therapeutic option for severe Myasthenia Gravis (MG) is total plasma exchange (TPE). This procedure reduces the concentration of autoantibodies by extracting the patient’s plasma and replacing it with donor plasma. The TPE efficacy varies among different types of MG, and patient response to TPE is evaluated solely through clinical markers, such as muscle strength. So far, no laboratory method is available for monitoring TPE treatment progress. Objective: In this study, we aimed to determine whether differential scanning calorimetry (DSC) of blood plasma from myasthenic patients is an appropriate tool to monitor and evaluate their condition and the TPE effect. Methods: We performed DSC prior to and after TPE course on blood plasma from three patients with different types of MG: Case 1. Patient with Acetylcholine Receptor Myasthenia Gravis (AChR MG); Case 2. Patient with Muscle-specific tyrosine kinase Myasthenia Gravis (MuSK MG); Case 3. Patient with Myasthenic syndrome (MSyn). Results: DSC thermogram examination revealed increased plasma protein fractions, primarily immunoglobulins (IG), as well as to some extent fibrinogen, relative to a suppressed serum albumin fraction. Successive TPE procedures resulted in IG fraction decline in AChR MG (Case 1) and MSyn (Case 3), and upsurge of the IG fraction in MuSK MG (Case 2). These findings aligned with the clinical presentation of all three cases. Conclusions: DSC revealed distinct, very significant differences in the heat capacity profiles of blood plasma from MG patients relative to healthy controls, as well as strong TPE influence on the plasma thermal behavior. DSC showed promise as a reliable and informative technique for the monitoring of myasthenia and TPE effects across diverse myasthenic patient populations. Further research is needed to confirm and expand on these findings. Full article

Objective: The classification of skin cancer is very helpful in its early diagnosis and treatment, considering the complexity involved in differentiating AK from BCC and SK. These conditions are generally not easily detectable due to their comparable clinical presentations. Method: This paper presents a new approach to hyperspectral imaging for enhancing the visualization of skin lesions called the Spectrum-Aided Vision Enhancer (SAVE), which has the ability to convert any RGB image into a narrow-band image (NBI) by combining hyperspectral imaging (HSI) to increase the contrast of the area of the cancerous lesions when compared with the normal tissue, thereby increasing the accuracy of classification. The current study investigates the use of ten different machine learning algorithms for the purpose of classification of AK, BCC, and SK, including convolutional neural network (CNN), random forest (RF), you only look once (YOLO) version 8, support vector machine (SVM), ResNet50, MobileNetV2, Logistic Regression, SVM with stochastic gradient descent (SGD) Classifier, SVM with logarithmic (LOG) Classifier and SVM- Polynomial Classifier, in assessing the capability of the system to differentiate AK from BCC and SK with heightened accuracy. Results: The results demonstrated that SAVE enhanced classification performance and increased its accuracy, sensitivity, and specificity compared to a traditional RGB imaging approach. Conclusions: This advanced method offers dermatologists a tool for early and accurate diagnosis, reducing the likelihood of misclassification and improving patient outcomes. Full article

We use Co doping to alter the magnetic relaxation dynamics in superparamagnetic nanofluids made of 18 nm average diameter Fe₃O₄ nanoparticles immersed in Isopar M. Ac-susceptibility data recorded at different frequencies and temperatures, χ″vs. T|_f, reveals a major (~100 K) increase in the superspin blocking temperature of the Co_0.2Fe_2.8O₄-based fluid (CFO) compared to its Fe₃O₄ counterpart (FO). We ascribe this behavior to the strengthening of the interparticle magnetic dipole interactions upon Co doping, as demonstrated by the relative χ″-peak temperature variation per frequency decade $\mathsf{\Phi }={\displaystyle \frac{∆\mathrm{T}}{\mathrm{T}·∆\mathrm{l}\mathrm{o}\mathrm{g}\left(\mathrm{f}\right)}}$, which decreases from Φ~0.15 in FO to Φ~0.025 in CFO. In addition, χ″vs. T|_f datasets from the CFO fluid reveal two magnetic events at temperatures T_p1 = 240 K and T_p2 = 275 K, both above the fluid’s freezing point (T_F = 197 K). We demonstrate that the physical rotation of the nanoparticles within the fluid, the Brown mechanism, is entirely responsible for the collective superspin relaxation observed at T_p1, whereas the Néel mechanism, the superspin flip across an energy barrier within the particle, is dominant at T_p2. We confirm this finding through fits of models that describe the temperature dependence of the relaxation time via the two mechanisms: ${\mathsf{\tau }}_{\mathrm{B}}(\mathrm{T})={\displaystyle \frac{3{\mathsf{\eta }}_0{\mathrm{V}}_{\mathrm{H}}}{{\mathrm{k}}_{\mathrm{B}}\mathrm{T}}}\exp \left[{\displaystyle \frac{{\mathrm{E}}^{\prime }}{{\mathrm{k}}_{\mathrm{B}}\left(\mathrm{T}-{{\mathrm{T}}_0}^{\prime }\right)}}\right]$ and ${\mathsf{\tau }}_{\mathrm{N}}\left(\mathrm{T}\right)={\mathsf{\tau }}_0\exp \left[{\displaystyle \frac{{\mathrm{E}}_{\mathrm{B}}}{{\mathrm{k}}_{\mathrm{B}}\left(\mathrm{T}-{\mathrm{T}}_0\right)}}\right]$. The best fits yield ${\mathsf{\gamma }}_0={\displaystyle \frac{3{\mathsf{\eta }}_0{\mathrm{V}}_{\mathrm{H}}}{{\mathrm{k}}_{\mathrm{B}}}}$= 1.5 × 10⁻⁸ s·K, E′/k_B = 7 03 K, and T₀′ = 201 K for the Brown relaxation, and E_B/k_B = 2818 K and T₀ = 143 K for the Néel relaxation. Full article

In this study, we selected the production processes and main products of three typical chemical enterprises in Shanghai, namely SH Petrochemical (part of the oil-refining sector), SK Ethylene, and HS Chlor-Alkali, to quantitatively assess the synergistic effects across technology, policy, and emission mechanisms. The localized air pollutant levels and greenhouse gas emissions of the three enterprises were calculated. The synergistic effects between the end-of-pipe emission reductions for air pollutants and greenhouse gas emissions were analyzed using the pollutant reduction synergistic and cross-elasticity coefficients, including technology comparisons (e.g., acrylonitrile gas incineration (AOGI) technology vs. traditional flare). Based on these data, we used the SimaPro software and the CML-IA model to conduct a life cycle environmental impact assessment regarding the production and upstream processes of their unit products. By combining the life cycle method and the scenario simulation method, we predicted the trends in the environmental impacts of the three chemical enterprises after the implementation of low-carbon development policies in the chemical industry in 2030. We also quantified the synergistic effects of localized air pollutant and greenhouse gas (GHG) emission reductions within the low-carbon development scenario by using cross-elasticity coefficients based on life cycle environmental impacts. The research results show that, for every ton of air pollutant reduced through end-of-pipe treatment measures, the HS Chlor-Alkali enterprise would increase its maximum CO₂ emissions, amounting to about 80 tons. For SK Ethylene, the synergistic coefficient for VOC reduction and CO₂ emissions when using AOGI thermal incineration technology is superior to that for traditional flare thermal incineration. The activities of the three enterprises had an impact on several environmental indicators, particularly the fossil fuel resource depletion potential, accounting for 69.48%, 53.94%, and 34.23% of their total environmental impact loads, respectively. The scenario simulations indicate that, in a low-carbon development scenario, the overall environmental impact loads of SH Petrochemical (refining sector), SK Ethylene, and HS Chlor-Alkali would decrease by 3~5%. This result suggests that optimizing the upstream power structure, using “green hydrogen” instead of “grey hydrogen” in hydrogenation units within refining enterprises, and reducing the consumption of electricity and steam in the production processes of ethylene and chlor-alkali are effective measures in reducing carbon emissions in the chemical industry. The quantification of the synergies based on life cycle environmental impacts revealed that there are relatively strong synergies for air pollutant and GHG emission reductions in the oil-refining industry, while the chlor-alkali industry has the weakest synergies. Full article