Search Results (56)

Idiopathic pulmonary fibrosis (IPF) is characterized by excessive extracellular matrix (ECM) deposition driven by aberrant fibroblast-to-myofibroblast transition (FMT). However, the upstream regulators and downstream effectors of this process remain incompletely understood. Here, we identify acyl-CoA synthetase long-chain family member 4 (ACSL4), a lipid metabolic enzyme, as a critical mediator linking complement component 5a (C5a)/C5a receptor 1 (C5aR1) signaling to FMT via calcium signaling. In bleomycin (BLM)-induced pulmonary fibrosis of C57BL/6JGpt mice, and in C5a-stimulated primary lung fibroblasts, the expression of ACSL4 was markedly upregulated. Pharmacological inhibition of ACSL4 (PRGL493) or C5aR1 (PMX53) attenuated the deposition of ECM and suppressed the expression of fibrotic markers in vivo and in vitro. Mechanistically, the activation of C5a/C5aR1 signaling increased intracellular calcium levels and promoted the expression of ACSL4, while inhibition of calcium signaling (FK506) reversed the upregulation of ACSL4 and FMT-related changes, including the expression of α-smooth muscle actin (αSMA) and the migration of fibroblasts. Notably, inhibition of ACSL4 did not affect the proliferation of fibroblasts, suggesting its specific role in phenotypic transition. These findings demonstrate that ACSL4 functions downstream of C5a/C5aR1-induced calcium signaling to promote FMT and the progression of pulmonary fibrosis. Targeting ACSL4 may therefore offer a novel therapeutic strategy for IPF. Full article

According to the World Health Organization (WHO), indoor air quality (IAQ) is becoming a serious global concern due to its significant impact on human health. However, not all relevant health parameters are currently regulated. For example, particle number concentration (PNC) and its associated carbonaceous species, such as black carbon (BC), which are classified as carcinogenic by the International Agency for Research on Cancer (IARC), are not currently regulated. Compared with IAQ studies in other types of buildings, studies focusing on IAQ in hospitals or other healthcare facilities are scarce. Therefore, this study aims to evaluate the impact of these outdoor pollutants, among others, on the indoor environment of a hospital under different atmospheric conditions. To identify the seasonal influence, two different periods of two consecutive seasons (summer 2020 and winter 2021) were selected for the measurements. Regulated pollutants (NO, NO₂, O₃, PM₁₀, and PM_2.5) and nonregulated pollutants (PM₁, PNC, and equivalent BC (eBC)) in outdoor air were simultaneously measured indoor and outdoor. This study also investigated the impact of indoor activities on indoor air quality. In the absence of indoor activities, outdoor sources significantly contribute to indoor traffic-related pollutants. Indoor and outdoor (I-O) measurements showed similar behavior, but indoor concentrations were lower, with peak levels delayed by up to two hours. Seasonal variations in indoor/outdoor ($\mathrm{I}/\mathrm{O}$) ratios were lower for particles than for associated gaseous pollutants. Particle infiltration depended on particle size, with it being higher the smaller the particle size. Indoor activities also significantly affected indoor pollutants. PM_x (especially PM₁₀ and PM_2.5) concentrations were mainly modulated by walking-induced particle resuspension. Vertical eBC profiles indicated a relatively well-mixed environment. Ventilation through open windows rapidly altered indoor air quality. Outdoor-dominant pollutants (PNC, eBC, and NO_X) had $\mathrm{I}/\mathrm{O}$ ratios ≥ 1. Staying in the room with an open window had a synergistic effect, increasing the $\mathrm{I}/\mathrm{O}$ ratios for all pollutants. Higher I/O ratios were associated with turbulent outdoor conditions in both unoccupied and occupied conditions. Statistically significant differences were observed between stable (TKE ≤ 1 m² s⁻²) and unstable (TKE > 1 m² s⁻²) conditions, except for NO₂ in summer. This finding was particularly significant when the wind direction was westerly or easterly during unstable conditions. The results of this study highlight the importance of understanding the behavior of indoor particulate matter and related pollutants. These pollutants are highly variable, and knowledge about them is crucial for determining their health effects, particularly in public buildings such as hospitals, where information on IAQ is often limited. More measurement data is particularly important for further research into I-O transport mechanisms, which are essential for developing preventive measures and improving IAQ. Full article

Reactive oxygen species (ROS) generated by cold atmospheric plasma (CAP) cause irreversible damage to cancer cell DNA, RNA, mitochondria, and antioxidant defense systems, leading to apoptosis. Plasma-induced disruption of the antioxidant defense system of cancer cells by cystine uptake via xC⁻ antiporter has been widely studied, while folate uptake by cancer cells via high expression of hSLC19A1, which generates Nicotinamide Adenine Dinucleotide Phosphate (NADPH) via one-carbon metabolism, is also an important component of the antioxidant defense mechanism of cancer cells. Disrupting folate transport in cancer cells is an important potential pathway for synergizing with pemetrexed (PMX) to induce apoptosis in cancer cells, which is of great research value. In this paper, classical molecular dynamics simulations were employed to study the effect of plasma oxidation of hSLC19A1 on the uptake of 5-Methyltetrahydrofolate (5-MTHF), which is the predominant dietary and circulatory folate, and the antifolate chemotherapeutic agent PMX by cancer cells. The results showed that the channel radius of hSLC19A1 for transporting 5MTHF after oxidation became narrower and the conformation tended to be closed, which was unfavorable for the transport of 5-MTHF; hydrogen bonding and hydrophobic interactions between hSLC19A1 and 5-MTHF decreased, the predicted docking affinity decreased, and the binding energy decreased from −28.023 kcal/mol to −16.866 kcal/mol, while that with PMX was stable around −28 kcal/mol, suggesting that the oxidative modification reduced the binding capacity of hSLC19A1 and 5-MTHF while barely affecting the transport of PMX, which contributed to weakening the antioxidant defense system of cancer cells and synergizing with PMX to induce apoptosis in cancer cells. Our simulations provide theoretical insights for CAP-induced apoptosis in cancer cells at the microscopic level and help promote the further development of cold atmospheric plasma in the field of cancer therapy. Full article

Background/Objectives: Pharmacogenomics (PGx) has revolutionized personalized medicine, notably by predicting drug responses through the study of the metabolic genotype of drug-metabolizing enzymes. However, these genotypes rely heavily on the availability and completeness of drug metabolism information and do not account for (all) “phenoconversion” factors, like drug–drug interactions and comorbidities. To address these limitations, a more phenotypic approach would be desirable, for which pharmacometabolomics (PMx) could be useful by studying and elucidating drug metabolism in patient samples, such as blood and urine. Methods: This study explored the potential of PMx to analyze real-world drug metabolite profiles of the extensively studied drug cyclosporine (CsA) using 24-h urine samples from 732 kidney and 350 liver transplant recipients included in the TransplantLines Biobank and Cohort Study (NCT identifier NCT03272841). Detected metabolites were matched with existing information on CsA metabolism gathered through a comprehensive literature review, aiming to confirm previously reported metabolites and identify potentially unreported ones. Results: Our analyses confirmed the urinary presence of CsA and six known metabolites. Additionally, we detected three known metabolites not previously reported in urine and identified one unreported metabolite, potentially suggesting the involvement of glutathione conjugation. Lastly, the observed metabolic patterns showed no notable differences between kidney and liver transplant recipients. Conclusions: Our findings demonstrate the potential of PMx to enhance the understanding of drug metabolism, even for well-studied compounds such as CsA. Moreover, this study highlights the value of PMx in real-world drug metabolism research and its potential to complement PGx in advancing personalized medicine. Full article

Previous conventional mist devices can induce a detrimental effect of leaf burn by intense, focused sunlight in summer. A mist generator is designed to prevent particulate matter (PM) damage to trees by combining mist with PM during high PM episodes. We measured changes in microclimate conditions and the concentration of PM before, during, and after mist spraying in urban parks (Yangjae Citizen Forest, YCF; Cheongdam Road Park, CRP) from May 6 to 8, 2020. PM changes in YCF and CRP were observed immediately after mist spraying and were found to return to the previous concentrations. Mist spraying had no significant effects on the meteorological traits of air temperature, humidity, and wind speed but had significant effects on the concentration of PMx and the ratio of PM during a short time. Also, the ratio of PMx was partially affected by mist spraying. During the morning rush hour and lunch, mist, high wind speed, and low relative humidity conditions were related to the increase in mist movement, resulting in increasing PM (2.5–10 μm) and the deposition of these PM. During the evening rush hour, high relative humidity and low wind speed affected PM concentrations more than mist. This prototype of mist spraying could effectively condense and deposit the PM during high PM episodes. Full article

The polar motion (PM, including two parameters PMx and PMy) ultra-short-term prediction (1–10 days) is demanded in the real-time navigation of satellites and spacecrafts. Improving the PMx and PMy ultra-short-term predictions accuracies are a key to optimize the performance of these related applications. Currently, the least squares (LS)+autoregressive (AR) hybrid method is regarded as one of the most capable approaches for ultra-short-term predictions of PMx and PMy. The Kalman filter has proven to be effective in improving the ultra-short-term prediction performance of the LS+AR hybrid method, but the PMx and PMy ultra-short-term predictions accuracies are still not able to satisfy some related applications. In order to improve the performance of PM ultra-short-term prediction, it is worth exploring the combinations of existing methods. Throughout the existing predicted methods, the LS+multivariate autoregressive (MAR) hybrid method by using the Kalman filter has the potential to improve the accuracy of PM ultra-short-term prediction. In addition, a PM prediction performance analysis of the LS+MAR hybrid method by using the Kalman filter, namely the LS+MAR+Kalman hybrid method, is still missing. In this contribution, we proposed the LS+MAR+Kalman hybrid method for PM ultra-short-term prediction. The data sets for PM predictions, which range from 1 to 10 days, have been tested based on the International Earth Rotation and Reference Systems Service Earth Orientation Parameter (IERS EOP) 14 C04 series to assess the performance of the LS+MAR+Kalman hybrid model. The experimental results illustrated that the LS+MAR+Kalman hybrid method can effectively execute PMy ultra-short-term predictions. The improvement of PMy prediction accuracy can rise up to 12.69% for 10-day predictions, and the improvement of ultra-short-term predictions is 7.64% on average. Full article

Seminal extracellular vesicles (SemEVs) are repositories of biomolecules, including metabolites involved in the regulation of sperm function. The correlation between the metabolite profile of SemEVs and semen parameters, along with their role in regulating sperm function, is an unexplored area. This preliminary study evaluated the metabolomic content of SemEVs. Semen samples were obtained from 18 healthy men, and SemEVs were extracted from seminal plasma using the size exclusion chromatography qEV Gen 2–35 nm column coupled with an automatic fraction collector. The physical characterization of SemEVs was carried out with the ZetaView PMX-430-Z QUATT laser system. EV protein markers were detected using Western blot. In addition, these SemEVs were used for metabolomic profiling and functional bioinformatic analysis. The mean concentration of isolated SemEVs was 1.7 ± 1.1 × 10¹¹/mL of seminal plasma, whereas SemEVs size and zeta potential were 129.5 ± 5.5 nm and −40.03 ± 3.99 mV, respectively. Western blot analysis confirmed the presence of EV specific markers such as CD81, ALIX, and TSG101. A total of 107 metabolites were identified using this untargeted metabolomic approach in SemEVs. Bioinformatics analysis further revealed that metabolites associated with tyrosine metabolism were highly enriched in these SemEVs. Ingenuity Pathway Analysis (IPA) also indicated that these metabolites present in SemEVs were involved in the regulation of the free radical scavenging pathway. Furthermore, our metabolomic results suggest that these SemEV-associated metabolites may play a pivotal role in the maintenance of seminal plasma redox homeostasis. Full article

To address the path planning problem for automated guided vehicles (AGVs) in challenging and complex industrial environments, a hybrid optimization approach is proposed, integrating a Kalman filter with grey wolf optimization (GWO), as well as incorporating partially matched crossover (PMX) mutation operations and roulette wheel selection. Paths are first optimized using GWO, then refined with Kalman filter corrections every ten iterations. Moreover, roulette wheel selection guides robust parent path selection, while an elite strategy and partially matched crossover (PMX) with mutation generate diverse offspring. Extensive simulations and experiments were carried out under a densely packed goods scenario and complex indoor layout scenario, within a fully automated warehouse environment. The results showed that this hybrid method not only enhanced the various optimization metrics but also ensured more predictable and collision-free navigation paths, particularly in environments with complex obstacles. These improvements lead to increased operational efficiency and safety, highlighting the method’s potential in real-world applications. Full article

The antiparasitic drug ivermectin is approved for persons > 15 kg in the US and EU. A pharmacometric (PMX) population model with clinical PK data was developed (i) to characterize the effect of the patient-friendly ivermectin formulation CHILD-IVITAB on the absorption process and (ii) to evaluate dosing for studies in children < 15 kg. Simulations were performed to identify dosing with CHILD-IVITAB associated with similar exposure coverage in children ≥ 15 kg and < 15 kg as observed in adults receiving the reference formulation STROMECTOL^®. A total of 448 ivermectin concentrations were available from 16 healthy adults. The absorption rate constant was 2.41 h⁻¹ (CV 19%) for CHILD-IVITAB vs. 1.56 h⁻¹ (CV 43%) for STROMECTOL^®. Simulations indicated that 250 µg/kg of CHILD-IVITAB is associated with exposure coverage in children < 15 kg consistent with that observed in children ≥ 15 kg and adults receiving 200 µg/kg of STROMECTOL^®. Performed analysis confirmed that CHILD-IVITAB is associated with faster and more controlled absorption than STROMECTOL^®. Simulations indicate that 250 µg/kg of CHILD-IVITAB achieves equivalent ivermectin exposure coverage in children < 15 kg as seen in children ≥ 15 kg and adults. Full article

Urban air pollution poses a significant threat to human health, with metropolitan areas particularly affected due to high emissions from human activities. Particulate matter (PM_x) is among the most harmful pollutants to human health, being composed of a complex mixture of substances related to severe pulmonary conditions. Urban green spaces play a vital role in mitigating air pollution by capturing PM_x, and it is essential to select plant species with a high capacity for PM_x accumulation to effectively enhance air quality. This study aimed to evaluate and compare the accuracy of two PM_x quantification methods—light microscopy and filtration—which demonstrated a high correlation (R² = 0.72), suggesting that both methods are reliable for assessing PM_x accumulation on leaves. Light microscopy allowed for the visualization of PM_x deposition, revealing the species warranting further analysis using the filtration method. Among the species analyzed, Euonymus japonicus, Ligustrum lucidum, Alnus glutinosa, Rubus ulmifolius, and Laurus nobilis demonstrated the highest total PM_x accumulation, exceeding 50 µg cm⁻², making them particularly valuable for air pollution mitigation. This study examined the correlation between leaf traits such as specific leaf area (SLA), leaf area (LA), leaf dissection index (LDI), and leaf roundness and PM_x accumulation across the 30 different plant species. A multiple linear regression analysis indicated that these leaf traits significantly influenced PM_x accumulation, with SLA and LA showing negative correlations and leaf roundness exhibiting a positive correlation with PM_x deposition. In conclusion, this study highlights the importance of selecting plant species with specific leaf traits for effective air quality improvement in urban environments particularly in highly polluted areas, to enhance air quality and public health. Full article

Phosphosidesterases (PDEs) are key regulators of cyclic nucleotide signaling, controlling many hallmarks of cancer and playing a role in resistance to chemotherapy in non-small-cell lung cancer (NSCLC). We evaluated the anti-tumor activity of the anti-folate agent pemetrexed (PMX), alone or combined with biochemical inhibitors of PDE5, 8, 9, or 10, against squamous and non-squamous NCSLC cells. Genomic alterations to PDE genes (PDE^mut) or PDE biochemical inhibition (PDEi) can sensitize NSCLC to PMX in vitro (observed in 50% NSCLC evaluated). The synergistic activity of PDEi with PMX required microdosing of the anti-folate drug. As single agents, none of the PDEis evaluated have anti-tumor activity. PDE biochemical inhibitors, targeting either cAMP or cGMP signaling (or both), resulted in significant cross-modulation of downstream pathways. The use of PDEi may present a new strategy to overcome PMX resistance of PDE^wt NSCLC tumors but comes with important caveats, including the use of subtherapeutic PMX doses. Full article

A couple of air quality (AQ) parameters were monitored with two types of low-cost sensors (LCSs) before, during and after the garden fence rebuilding of a dwelling house, located at the junction of a main road and a side street in a suburban area of Budapest, Hungary. The AQ variables, recorded concurrently indoors and outdoors, were particulate matter (PM₁, PM_2.5, PM₁₀) and some gaseous trace pollutants, such as CO₂, formaldehyde (HCHO) and volatile organic compounds (VOCs). Medium-size aerosol (PM_2.5-1), coarse particulate (PM_10-2.5) and indoor-to-outdoor (I/O) ratios were calculated. The I/O ratios showed that indoor fine and medium-size PM was mostly of outdoor origin; its increased levels were observed during the renovation. The related pollution events were characterized by peaks as high as 100, 95 and 37 µg/m³ for PM₁, PM_2.5-1 and PM_10-2.5, respectively. Besides the renovation, some indoor sources (e.g., gas-stove cooking) also contributed to the in-house PM₁, PM_2.5-1 and PM_10-2.5 levels, which peaked as high as 160, 255 and 220 µg/m³, respectively. In addition, these sources enhanced the indoor levels of CO₂, HCHO and, rarely, VOCs. Increased and highly fluctuating VOC levels were observed in the outdoor air (average: 0.012 mg/m³), mainly due to the use of paints and thinners during the reconstruction, though the use of a nearby wood stove for heating was an occasional contributing factor. The acquired results show the influence of the fence renovation-related activities on the indoor air quality in terms of aerosols and gaseous components, though to a low extent. The utilization of high-resolution LCS-assisted monitoring of gases and PM_x helped to reveal the changes in several AQ parameters and to assign some dominant emission sources. Full article

Sustainable urban development in the era of energy and digital transformation is crucial from a societal perspective. Utilizing modern techniques for analyzing large datasets, including machine learning and artificial intelligence, enables a deeper understanding of historical data and the efficient prediction of future events based on data from IoT sensors. This study conducted a multidimensional historical analysis of air pollution to investigate the impacts of energy transformation and environmental policy and to determine the long-term environmental implications of certain actions. Additionally, machine learning (ML) techniques were employed for air pollution prediction, taking spatial factors into account. By utilizing multiple low-cost air sensors categorized as IoT devices, this study incorporated data from various locations and assessed the influence of neighboring sensors on predictions. Different ML approaches were analyzed, including regression models, deep neural networks, and ensemble learning. The possibility of implementing such predictions in publicly accessible IT mobile systems was explored. The research was conducted in Krakow, Poland, a UNESCO-listed city that has had long struggle with air pollution. Krakow is also at the forefront of implementing policies to prohibit the use of solid fuels for heating and establishing clean transport zones. The research showed that population growth within the city does not have a negative impact on PMx concentrations, and transitioning from coal-based to sustainable energy sources emerges as the primary factor in improving air quality, especially for PMx, while the impact of transportation remains less relevant. The best results for predicting rare smog events can be achieved using linear ML models. Implementing actions based on this research can significantly contribute to building a smart city that takes into account the impact of air pollution on quality of life. Full article

This study investigated compensation in skeletal Class III subjects to compare various severities of abnormal jaws. A retrospective analysis of 137 skeletal Class III cephalograms (63 males and 74 females) was conducted, with cephalometric assessments determining skeletal and dental values. The results were compared with Class I cephalograms. Incisor compensation was examined by pairing normal jaws with varied abnormal jaws, classified by severity using one standard deviation (SD). Statistical analyses included Kruskal–Wallis tests, Bonferroni tests, Spearman’s correlations, and multiple linear regression. Four skeletal Class III groups were identified: OMx+PMd, RMx+OMd, OMx+OMd, and PMx+PMd (P = prognathic; O = orthognathic; R = retrognathic; Mx = maxilla; Md = mandible.). The upper central incisor (U1) showed proclination, and the lower central incisor (L1) showed retroclination across all groups except for U1 in PMx+PMd and L1 in OMx+OMd, which exhibited normal inclination. U1 exhibited limited compensation even with progressive maxillary retrognathism, while L1 showed limited compensation after one SD of mandibular prognathism. Maxilla (SNA) and jaw discrepancy (ANB) were inversely related to the U1 degree, whereas only jaw discrepancy (ANB) was positively related to the L1 degree. U1 in PMx+PMd and L1 in OMx+OMd showed no incisor compensation. U1 had limited compensation even with progressive maxillary retrognathism while L1 showed limited compensation after one SD mandibular prognathism. Full article

Superhydrophobic coatings can be a suitable solution for protecting vulnerable electrical infrastructures in regions with severe meteorological conditions. Regenerative superhydrophobicity, the ability to regain superhydrophobicity after being compromised or degraded, could address the issue of the low durability of these coatings. In this study, we fabricated a superhydrophobic coating comprising hydrophobic aerogel microparticles and polydimethylsiloxane (PDMS)-modified silica nanoparticles within a PDMS matrix containing trifluoropropyl POSS (F-POSS) and XIAMETER PMX-series silicone oil as superhydrophobicity-regenerating agents. The fabricated coating exhibited a static contact angle of 169.5° and a contact angle hysteresis of 6°. This coating was capable of regaining its superhydrophobicity after various pH immersion and plasma deterioration tests. The developed coating demonstrated ice adhesion as low as 71.2 kPa, which remained relatively unchanged even after several icing/de-icing cycles. Furthermore, the coating exhibited a higher flashover voltage than the reference samples and maintained a minimal drop in flashover voltage after consecutive testing cycles. Given this performance, this developed coating can be an ideal choice for enhancing the lifespan of electrical insulators. Full article