Search Results (8,080)

Pesticide residues in human diets pose significant health hazards, particularly for vulnerable populations such as infants and children. This study aimed to determine pesticide residues in apples and to assess the cumulatively chronic risk posed to adult and child consumers from simultaneous exposure to multiple residues. During the 2022–2023 harvest seasons, 100 apple samples from Turkey were analyzed for the presence of 225 different pesticide residues. Pesticide extraction was performed using the QuEChERS method, followed by detection through liquid chromatography coupled with tandem mass spectrometry. Fifteen distinct pesticides (ten insecticides and five fungicides) were detected in 64 out of the 100 apple samples analyzed. Eleven samples contained pesticide residues that exceeded the maximum residue limit (MRL) set by the Turkish Food Codex and the European Union. Thiophanate-methyl was the most frequently detected pesticide (34%) in apples, with concentrations ranging from 0.012 to 0.108 mg kg⁻¹, all of which were well below the MRL of 0.5 mg kg⁻¹. Other commonly detected residues included chlorantraniliprole (28%), acetamiprid (24%), sulfoxaflor (22%), bifenazate (18%), indoxacarb (13%), diflubenzuron (12%), and carbendazim (10%). Under a worst-case scenario, the hazard index (HI) values for adults and children were 0.85% and 2.60%, respectively, indicating that these values remain significantly below the risk threshold of 100%, suggesting no associated health risks from apple consumption. However, regular monitoring of pesticide residues in fresh fruits and vegetables remains critically important. Full article

The autophagy–lysosome axis is an evolutionarily conserved intracellular degradation pathway which constitutes an important component of host innate immunity against microbial infections. Here, we show that African swine fever virus (ASFV), one of most devastating pathogens to the worldwide swine industry, can reshape the autophagy–lysosome axis by recruiting the critical lysosome membrane proteins (LAMP1 and LAMP2) to viral factories while inhibiting autophagic induction in macrophages. The screening of viral membrane proteins led to the identification of several ASFV membrane proteins, exemplified by viral protein pEP153R, that could significantly alter the subcellular localization of LAMP1/2 when expressed alone in transfected cells. Further analysis showed that pEP153R was also a component of viral factories and could induce endoplasmic reticulum (ER) retention of LAMP1/2, leading to the inhibition of the fusion of autophagosomes with lysosomes. Interestingly, the ASFV mutant lacking EP153R could still actively recruit LAMP into viral factories (VFs) and inhibit autophagic flux, indicating the existence of a functional redundancy of other viral proteins in the absence of pEP153R and highlighting the complexity of ASFV replication biology. Taken together, our results reveal novel information about the interplay of ASFV with the autophagy–lysosome axis and a previously unrecognized function of ASFV protein pEP153R in regulating the cellular autophagic process. Full article

This study evaluates the potential of erbium, chromium-doped:yttrium, scandium, gallium, and garnet (Er,Cr:YSGG) laser irradiation to modify the titanium surface for optimal seeding of fibroblasts and osteoblasts in the treatment of peri-implantitis. Titanium discs were treated using the Er,Cr:YSGG laser, an ultrasonic device with a stainless tip, or titanium scalers. Changes in surface properties were analyzed by profilometer and scanning electron microscopy (SEM). Murine fibroblast and osteoblast adhesion and proliferation were evaluated qualitatively and quantitatively at 24 and 72 h. Profilometric surface topography and SEM showed that titanium scalers and ultrasonic debridement techniques significantly changed the structure of the machined and rough titanium surfaces. The Er,Cr:YSGG laser irradiation, on the other hand, did not alter titanium microstructures. The Er,Cr:YSGG laser irradiation with the 40 Hz group showed a significantly higher attached fibroblast cell numbers than the titanium scaler group at 72 h after treatment (p = 0.023). Additionally, the number of the attached osteoblasts in the Er,Cr:YSGG laser irradiation with the 40 Hz group was significantly higher than that of the no-treatment groups 24 h after treatment (p = 0.045). The Er,Cr:YSGG laser effectively promoted adherence of fibroblasts and osteoblasts to the titanium surface without significantly altering the titanium surface, suggesting its superiority for treating peri-implantitis. Full article

Regular exercise as part of one’s lifestyle is well-recognized for its beneficial effect on several diseases such as cardiovascular disease and obesity; however, many questions remain unanswered regarding the effects of exercise on the gut environment. This study aimed to investigate the impact of long-term endurance exercise on modulating inflammation and endoplasmic reticulum (ER) stress. Fifteen-week-old male Sprague-Dawley (SD) rats were subjected to six months of endurance treadmill training, while age-matched controls remained sedentary. Results showed that IL-6 mRNA levels in colon tissues were significantly higher in the exercise group compared to the sedentary group. Exercise activated a significant ER stress-induced survival pathway by increasing BiP and phosphorylation of eIF2α (p-eIF2α) expressions in the liver and colon, while decreasing CHOP in the liver. Gene expressions of MUC2, Occludin, and Claudin-2 were increased in the colon of the exercise group, indicating enhanced intestinal integrity. Furthermore, the data showed a positive correlation between microbiota α-diversity and BiP (r = 0.464~0.677, p < 0.05). Populations of Desulfovibrio C21 c20 were significantly greater in the exercise group than the sedentary group. Additionally, predicted functions of the gut microbial community in terms of enzymes and pathways supported the enhancement of fatty-acid-related processes by exercise. These findings suggest that prolonged endurance exercise can affect the colon environment, which is likely related to changes in inflammation, ER stress, mucin layers and tight junctions, associated with modifications in the gut microbiome. Full article

Despite the increasing understanding of the pathogenesis of glioblastoma (GBM), treatment options for this tumor remain limited. Recently, the therapeutic potential of natural compounds has attracted great interest. Thus, dietary flavonoids quercetin (QCT) and kaempferol (KMF) were investigated as potential cytostatic agents in GBM. Moreover, the physicochemical properties of QCT and KMF, determining their bioavailability and therapeutic efficiency, were evaluated. We proved that both polyphenols significantly reduced the viability of GBM cells. We also demonstrated that both QCT and KMF evoked the cytotoxic effect in T98G cells via induction of apoptotic cell death as shown by increased activity of caspase 3/7 and caspase 9 together with an overexpression of the cleaved form of PARP. Apoptosis was additionally accompanied by the activation of stress responses in QCT- and KMF-treated cells. Both polyphenols caused oxidative stress and endoplasmic reticulum (ER) stress, as demonstrated by the increased generation of reactive oxygen species (ROS), deregulated expressions of superoxide dismutases (SOD2 and Sod1 on protein and transcriptomic levels, respectively), as well as an overexpression of ERO1α, GRP78, p-JNK, and an up-regulation of Chop, Atf4 and Atf6α genes. The antitumor effect of QCT and KMF was also confirmed in vivo, showing reduced growth of tumor xenografts in the chick chorioallantoic membrane (CAM) experiment. Moreover, electrophoretic light scattering (ELS) was used to measure the zeta potential of cell membranes upon exposition to QCT and KMF. Additionally, on the basis of existing physicochemical data, the drug-likeness score of QCT and KMF was evaluated. Analyses showed that both compounds accomplish Lipinski’s Rule of 5, and they both fit into the criteria of good central nervous system (CNS) drugs. Altogether, our data support the idea that QCT and KMF might be plausible candidates for evaluation as therapeutic agents in preclinical models of glioblastoma. Full article

EMC1 is part of the endoplasmic reticulum (ER) membrane protein complex, whose functions include the insertion of transmembrane proteins into the ER membrane, ER–mitochondria contact, and lipid exchange. Here, we show that the Drosophila melanogaster EMC1 gene is expressed in the somatic musculature and the protein localizes to the sarcoplasmic reticulum (SR) network. Muscle-specific EMC1 RNAi led to severe motility defects and partial late pupae/early adulthood lethality, phenotypes that are rescued by co-expression with an EMC1 transgene. Motility impairment in EMC1-depleted flies was associated with aberrations in muscle morphology in embryos, larvae, and adults, including tortuous and misaligned fibers with reduced size and weakness. They were also associated with an altered SR network, cytosolic calcium overload, and mitochondrial dysfunction and dysmorphology that impaired membrane potential and oxidative phosphorylation capacity. Genes coding for ER stress sensors, mitochondrial biogenesis/dynamics, and other EMC components showed altered expression and were mostly rescued by the EMC1 transgene expression. In conclusion, EMC1 is required for the SR network’s mitochondrial integrity and influences underlying programs involved in the regulation of muscle mass and shape. We believe our data can contribute to the biology of human diseases caused by EMC1 mutations. Full article

Gas Chromatography Tandem Mass Spectrometry (GC-MS/MS) with modified QuEChERS sample preparation has been applied to the high-throughput screening of pesticide residuals in rice collected from Bangladesh and Saudi Arabia markets. Both countries consume high volumes of rice, which is a fundamental food for their populations. We report optimized sample preparation and mass spectrometry analysis protocols, which can be rapidly deployed in analytical laboratories. The screening of four groups (organophosphorus, synthetic pyrethroid, organonitrogen, and organochlorine) of a total of 115 pesticides can be performed within ~10 min using a matrix-matched calibration. For most compounds, the limits of detection and quantification (LOD/LOQ) are well below the maximum residue levels (MRLs) of the main regulators. The method generally demonstrates acceptable recovery values (91 compounds 75–125% and 10 compounds 30–75%). Out of 55 rice samples analyzed, 16 samples (29%) contained pesticide residues above LOQ. Four samples contained chlorpyrifos with concentrations ranging from 21.3 to 71.9 µg/kg, ten samples contained tebuconazole (34.7–69.0 µg/kg), and three samples contained pirimiphos methyl (10.7–20.7 µg/kg). The concentrations of the pesticide residues detected in these samples are well below MRL of FAO/WHO (chlorpyrifos, 500 µg/kg; tebuconazole, 1500 µg/kg; pirimiphos methyl, 7000 µg/kg). Full article

The screening of 166 extracts from tropical marine organisms (invertebrates, macroalgae) and 3 cyclolipopeptides from microorganisms against yeast prions highlighted the potential of Verongiida sponges to prevent the propagation of prions. We isolated the known compounds purealidin Q (1), aplysamine-2 (2), pseudoceratinine A (3), aerophobin-2 (4), aplysamine-1 (5), and pseudoceratinine B (6) for the first time from the Wallisian sponge Suberea laboutei. We then tested compounds 1–6 and sixteen other bromotyrosine and bromophenol derivatives previously isolated from Verongiida sponges against yeast prions, demonstrating the potential of 1–3, 5, 6, aplyzanzine C (7), purealidin A (10), psammaplysenes D (11) and F (12), anomoian F (14), and N,N-dimethyldibromotyramine (15). Following biological tests on mammalian cells, we report here the identification of the hitherto unknown ability of the six bromotyrosine derivatives 1, 2, 5, 7, 11, and 14 of marine origin to reduce the spread of the PrP^Sc prion and the ability of compounds 1 and 2 to reduce endoplasmic reticulum stress. These two biological activities of these bromotyrosine derivatives are, to our knowledge, described here for the first time, offering a new therapeutic perspective for patients suffering from prion diseases that are presently untreatable and consequently fatal. Full article

The esterification of 1-methoxy-2-propanol (PM) and acetic acid (AA) is an important reaction for the production of 1-methoxy-2-propyl acetate (PMA). Herein, we used the macroporous ion-exchange resin Amberlyst-35 as a catalyst to explore the effects of reaction conditions on the reaction rate and equilibrium yield of PMA. Under the optimized conditions of a reaction temperature of 353 K, using the initial reactant PM/AA with a molar ratio of 1:3, and a catalyst loading of 10 wt%, the PMA equilibrium yield reached 78%, which is the highest equilibrium yield so far. The reaction equilibrium constants and activity coefficients were estimated to obtain reaction thermodynamic properties, indicating the exothermicity of the reaction. Furthermore, pseudo-homogeneous (PH), Eley–Rideal (ER), and Langmuir–Hinshelwood–Hougen–Watson (LHHW) kinetic models were fitted based on experimental reaction kinetic data. The results demonstrate that the LHHW model is the most consistent with experimental data, indicating a surface reaction-controlled process and exhibiting an apparent activation energy of 62.0 ± 0.2 kJ/mol. This work represents a valuable example of calculating reaction thermodynamics and kinetics, which are particularly essential for promising industrial reactor designs. Full article

This study evaluates the use of remote sensing data to improve the understanding of groundwater resources in climate-sensitive regions with limited data availability and increasing agricultural water demands. The research focuses on estimating groundwater reserve dynamics in two major river basins in Morocco, characterized by significant local variability. The study employs data from Gravity Recovery and Climate Experiment satellite (GRACE) and ERA5-Land reanalysis. Two GRACE terrestrial water storage (TWS) products, CSR Mascon and JPL Mascon (RL06), were analyzed, along with auxiliary datasets generated from ERA5-Land, including precipitation, evapotranspiration, and surface runoff. The results show that both GRACE TWS products exhibit strong correlations with groundwater reserves, with correlation coefficients reaching up to 0.96 in the Oum Er-rbia River Basin and 0.95 in the Tensift River Basin (TRB). The root mean square errors (RMSE) were 0.99 cm and 0.88 cm, respectively. GRACE-derived groundwater storage (GWS) demonstrated a moderate correlation with observed groundwater levels in OERRB (R = 0.59, RMSE = 0.82), but a weaker correlation in TRB (R = 0.30, RMSE = 1.01). On the other hand, ERA5-Land-derived GWS showed a stronger correlation with groundwater levels in OERRB (R = 0.72, RMSE = 0.51) and a moderate correlation in TRB (R = 0.63, RMSE = 0.59). The findings suggest that ERA5-Land may provide more accurate assessments of groundwater storage anomalies, particularly in regions with significant local-scale variability in land and water use. High-resolution datasets like ERA5-land are, therefore, more recommended for addressing local-scale heterogeneity in regions with contrasted complexities in groundwater storage characteristics. Full article

Crimped wool in Tan sheep gradually transitions to straight wool after 35 days (the er-mao stage), which reduces its commercial value. To investigate the changes in wool proteins during this stage, we performed comparative proteomic analysis of the straight and crimped wool using tandem mass tag (TMT)-based quantification. The mean fur curvature (MFC) of crimped wool was significantly greater than that of straight wool (p < 0.001). We identified 1218 proteins between the two types of wool, including 50 keratins (Ks) and 10 keratin-associated proteins (KAPs). There were 213 differentially expressed proteins, including 13 Ks and 4 KAPs. Crimped wool showed relatively high abundances of KAP24-1, K84, K32, K82, and intermediate filament rod domain-containing protein (IRDC), whereas straight wool had relatively high abundances of K6A, K27, K80, KAP16-1, KAP27-1, and trichohyalin (TCHH). The expression levels of KAP16-1, KAP24-1, and KAP27-1 were related to the ratio of paracortex, which may be associated with wool crimp formation. Additionally, high expressions of TCHH, K27, and K6A in the inner root sheath (IRS) were linked to fiber fineness in straight wool. These findings provide insight into the overall expression and distribution patterns of Ks and KAPs, offering opportunities to improve wool quality and enhance its economic potential in the textile industry. Full article

Background/Objectives: Breast cancer is diagnosed in 2.3 million women each year and kills 685,000 (~30% of patients) worldwide. The prognosis for many breast cancer subtypes has improved due to treatments targeting the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). In contrast, patients with triple-negative breast cancer (TNBC) tumors, which lack all three commonly targeted membrane markers, more frequently relapse and have lower survival rates due to a lack of tumor-selective TNBC treatments. We aim to investigate TNBC mechanistic markers that could be targeted for treatment. Methods: We performed a secondary TNBC analysis of 196 samples across 10 publicly available bulk RNA-sequencing studies to better understand the molecular mechanism(s) of disease and predict robust mechanistic markers that could be used to improve the mechanistic understanding of and diagnostic capabilities for TNBC. Results: Our analysis identified ~12,500 significant differentially expressed genes (FDR-adjusted p-value < 0.05), including KIF14 and ELMOD3, and two significantly modulated pathways. Additionally, our novel findings include highly accurate mechanistic markers identified using machine learning methods, including CIDEC (97.1% accuracy alone), CD300LG, ASPM, and RGS1 (98.9% combined accuracy), as well as TNBC subtype-differentiating mechanistic markers, including the targets PDE3B, CFD, IFNG, and ADM, which have associated therapeutics that can potentially be repurposed to improve treatment options. We then experimentally and computationally validated a subset of these findings. Conclusions: The results of our analyses can be used to better understand the mechanism(s) of disease and contribute to the development of improved diagnostics and/or treatments for TNBC. Full article

Background: Despite the benefits of physical activity (PA), Italy ranks low in leisure-time PA among European countries. Integrating virtual (VR)/enhanced (ER) reality with exercise equipment could boost PA engagement. Limited studies have explored how VR/ER-integrated cycling activity, compared to outdoor settings, influences PA among university students. Therefore, this study aimed to evaluate the acute effects of a brief cycling session outdoors and indoors on psychological and physiological outcomes, and secondly, investigate the potential of VR/ER-mediated nature experiences as a tool to promote green exercise. Methods: In February 2024, thirty-one subjects (20 M and 11 F; age 24.3 ± 3.2 years; BMI 23.5 ± 3.6 kg/m²) were involved in this randomized crossover-controlled trial, where they were assigned to three different conditions: ER cycling (ERC), VR cycling (VRC), and outdoor cycling (OUTC). Heart rate (HR), Physical Activity Enjoyment (PACE), Intrinsic Motivation Inventory (IMI), and Intention to Perform Green Exercise (INT-GE) were assessed at the end of each condition. Results: The OUTC condition showed significantly greater PACE, IMI, and INT-GE than ERC/VRC (p < 0.001), lower HR_mean than ERC/VRC (p < 0.001 and p < 0.05, respectively), and lower HRmax than ERC (p < 0.05). Conclusions: VRC and ERC enhanced engagement and physiological responses during indoor cycling, but outdoor cycling offered superior benefits in motivation, enjoyment, and future engagement intentions. No significant differences were found between VRC and ERC in promoting intentions for outdoor activities, suggesting both technologies could be equally effective. Full article

As a component of circulating lipoproteins, APOE binds to cell surface receptors mediating lipoprotein metabolism and cholesterol transport. A growing body of evidence, including the identification of a broad variety of cellular proteins interacting with APOE, suggests additional independent functions. Investigating cellular localization and protein–protein interactions in cultured human hepatocytes, we aimed to contribute to the elucidation of hitherto unnoted cellular functions of APOE. We observed a strong accumulation of APOE in MAMs, equally evident for the two major isoforms APOE3 and APOE4. Using mass spectrometry proteome analyses, novel and previously noted APOE interactors were identified, including the mitochondrial proteins TOMM40, LONP1 and VDAC1. All three interactors were present in MAM fractions, which we think initially facilitates interactions with APOE. LONP1 is a protease with chaperone activity, which migrated to MAMs in response to ER stress, displaying a reinforced interaction with APOE. We therefore hypothesize that APOE may help in the unfolded protein response (UPR) by acting as a co-chaperone in cooperation with LONP1 at the interface of mitochondria and ER membranes. The interaction of APOE with the integral proteins TOMM40 and VDAC1 may point to the formation of bridging complexes connecting mitochondria with other organelles. Full article

Photodynamic therapy (PDT) is a medical treatment that utilizes photosensitizing agents, along with light, to produce reactive oxygen species that can kill nearby cells. When the photosensitizer is exposed to a specific wavelength of light, it becomes activated and generates reactive oxygen that can destroy cancer cells, bacteria, and other pathogenic micro-organisms. PDT is commonly used in dermatology for treating actinic keratosis, basal cell carcinoma, and other skin conditions. It is also being explored for applications in oncology, such as treating esophageal and lung cancers, as well as in ophthalmology for age-related macular degeneration. In this study, we provide a comprehensive review of PDT, covering its fundamental principles and mechanisms, as well as the critical components for its function. We examine key aspects of PDT, including its current clinical applications and potential future developments. Additionally, we discuss the advantages and disadvantages of PDT, addressing the various challenges associated with its implementation and optimization. This review aims to offer a thorough understanding of PDT, highlighting its transformative potential in medical treatments while acknowledging the areas requiring further research and development. Full article