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BackgroundPenetratin is a positively charged cell-penetrating peptide (CPP) that has the ability to bind negatively charged membrane components, such as glycosaminoglycans and anionic lipids. Whether this primary interaction of penetratin with these cell surface components implies that the peptide will be further internalized is not clear.MethodologyUsing mass spectrometry, the amount of internalized and membrane bound penetratin remaining after washings, were quantified in three different cell lines: wild type (WT), glycosaminoglycans- (GAG(neg)) and sialic acid-deficient (SA(neg)) cells. Additionally, the affinity and kinetics of the interaction of penetratin to membrane models composed of pure lipids and membrane fragments from the referred cell lines was investigated, as well as the thermodynamics of such interactions using plasmon resonance and calorimetry.Principal findingsPenetratin internalized with the same efficacy in the three cell lines at 1 µM, but was better internalized at 10 µM in SA(neg)>WT>GAG(neg). The heat released by the interaction of penetratin with these cells followed the ranking order of internalization efficiency. Penetratin had an affinity of 10 nM for WT cells and µM for SA(neg) and GAG(neg) cells and model membrane of phospholipids. The remaining membrane-bound penetratin after cells washings was similar in WT and GAG(neg) cells, which suggested that these binding sites relied on membrane phospholipids. The interaction of penetratin with carbohydrates was more superficial and reversible while it was stronger with phospholipids, likely because the peptide can intercalate between the fatty acid chains.Conclusion/significanceThese results show that accumulation and high-affinity binding of penetratin at the cell-surface do not reflect the internalization efficacy of the peptide. Altogether, these data further support translocation (membrane phospholipids interaction) as being the internalization pathway used by penetratin at low micromolecular concentration, while endocytosis is activated at higher concentration and requires accumulation of the peptide on GAG and GAG clustering.

This study introduces a high-resolution wind nowcasting model designed for aviation applications at Madeira International Airport, a location known for its complex wind patterns. By using data from a network of six meteorological stations and deep learning techniques, the produced model is capable of predicting wind speed and direction up to 30-minute ahead with 1-minute temporal resolution. The optimized architecture demonstrated robust predictive performance across all forecast horizons. For the most challenging task, the 30-minute ahead forecasts, the model achieved a wind speed Mean Absolute Error (MAE) of 0.78 m/s and a wind direction MAE of 33.06°. Furthermore, the use of Gaussian noise concatenation to both input and label training data yielded the most consistent results. A case study further validated the model's efficacy, with MAE values below 0.43 m/s for wind speed and between 33.93° and 35.03° for wind direction across different forecast horizons. This approach shows that combining strategically deployed sensor networks with machine learning techniques offers improvements in wind nowcasting for airports in complex environments, possibly enhancing operational efficiency and safety., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Alves et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

A study was conducted to investigate the serum virome of sows with and without stillbirths after farrowing. Sera from sows with at least one stillbirth or with normal litters were collected immediately after farrowing. Viral DNA was extracted from serum pools and submitted to high throughput sequencing. No differences in the proportion of virus-related reads were found in both groups (p > 0.05). A variety of viral DNA genomes were identified, mostly representative of three viral families: Anelloviridae, Circoviridae and Smacoviridae. Besides, a number of novel unclassified circular Rep-encoding single stranded DNA (CRESS DNA) viruses were also identified. These findings suggest that the presence of such viral genomes in sows' sera bears no correlation with stillbirths' occurrence; it seems likely that these constitute part of the normal serum microbiome of sows at farrowing., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Ibrutinib is an oral covalent inhibitor of Bruton's tyrosine kinase approved for the treatment of patients with chronic lymphocytic leukemia (CLL), mantle cell lymphoma and Waldenstrӧm's macroglobulinemia. Ibrutinib has an increased risk of atrial fibrillation but the mechanism is unknown, and hypertension may play a role in the pathogenesis of this adverse drug reaction., Methods: We aimed to review the risk of hypertension and atrial fibrillation as adverse events associated with ibrutinib through a systematic review with meta-analysis of randomized controlled trials (RCTs) retrieved in December 2018 on MEDLINE, EMBASE, CENTRAL and ClinicalTrials.gov. The data were pooled using random-effects meta-analyses using the risk ratio (RR) with the 95% confidence interval (95%CI). The confidence on the pooled estimates was ascertained through the grading of recommendations assessment, development, and evaluation (GRADE) approach., Results: There were 8 eligible RCTs (2580 patients), all reporting safety data of interest. Ibrutinib was associated with a significant increase in the risk of hypertension with a RR of 2.82 (95%CI 1.52-5.23) with moderate quality evidence. Ibrutinib increased significantly the risk of atrial fibrillation with a RR of 4.69 (95%CI 2.17-7.64) with high quality evidence., Conclusions: Ibrutinib was associated with significantly increased risks of both hypertension and atrial fibrillation., Competing Interests: DC has participated in educational meetings and/or attended a conferences or symposia with Bristol-Myers Squibb, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Merck Serono, Ferrer, Pfizer, Novartis and Roche. DA received speaker fees from Janssen, Roche, Gillead and Takeda. JJF had speaker and consultant fees with GlaxoSmithKline, Novartis, TEVA, Lundbeck, Solvay, Abbott, Bial, Merck-Serono, Grunenthal, and Merck Sharp and Dohme; FJP had consultant and speaker fees with Astra Zeneca, Bayer, BMS, Boehringer Ingelheim and Daiichi Sankyo. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

A series of phenylselanyl-1H-1,2,3-triazole-4-carbonitriles with different substituents were screened for their binding affinity with serotonin transporter (SERT) and dopamine transporter (DAT) by docking molecular. 5-(4methoxyphenyl)-1-(2-(phenylselanyl)phenyl)-1H-1,2,3-triazole-4-carbonitrile (SeTACN) exhibited the best conformation with SERT even higher than fluoxetine and serotonin, suggesting a competitive inhibition. SeTACN demonstrated additional affinity to other serotonergic receptors involved in antidepressant effects: 5HT1a, 5HT2a and 5HT3. In another set of experiments, SeTACN led to significant reductions in the immobility time of mice submitted to forced swimming test (FST) in the dose range of 0.1- 20mg/kg, suggesting an antidepressant-like effect. The possible mechanism of action was investigated using serotonergic and dopaminergic antagonists. The antidepressant-like effect of SeTACN (0.1mg/kg i.g.) was prevented by the pretreatment with WAY100635 (a selective 5HT1a antagonist), ketanserin (a 5HT2a/c antagonist) and ondansetron (a selective 5ht3 antagonist), PCPA (an inhibitor of serotonin synthesis) but not with SCH23390 (dopaminergic D1 antagonist) and sulpiride (D2 antagonist). Sub-effective dose of fluoxetine was able to potentiate the effects of a sub-effective dose of SeTACN in FST. None of the treatments affected locomotor activity in open field test (OFT). These results together, suggest that the SeTACN antidepressant-like effect is mediate, at least in parts, by serotonergic system.

In general, in composting facilities the active, or intensive, stage of the process is done separately from the maturation stage, using a specific technology and time. The pre-composted material to be matured can contain enough biodegradable substrates to cause microbial proliferation, which in turn can cause temperatures to increase. Therefore, not controlling the maturation period during waste management at an industrial level can result in undesired outcomes. The main hypothesis of this study is that controlling the maturation stage through turning provides one with an optimized process when compared to the static approach. The waste used was sludge from a seafood-processing plant, mixed with shredded wood (1:2, v/v). The composting system consists of an intensive stage in a 600L static reactor, followed by maturation in triplicate in 200L boxes for 112 days. Two tests were carried out with the same process in reactor and different treatments in boxes: static maturation and turning during maturation when the temperature went above 55°C. PLFAs, organic matter, pH, electrical conductivity, forms of nitrogen and carbon, hydrolytic enzymes and respiratory activity were periodically measured. Turning significantly increased the duration of the thermophilic phase and consequently increased the organic-matter degradation. PCA differentiated significantly the two treatments in function of tracking parameters, especially pH, total carbon, forms of nitrogen and C/N ratio. So, stability and maturity optimum values for compost were achieved in less time with turnings. Whereas turning resulted in microbial-group stabilization and a low mono/sat ratio, static treatment produced greater variability in microbial groups and a high mono/sat ratio, the presence of more degradable substrates causes changes in microbial communities and their study during maturation gives an approach of the state of organic-matter degradation. Obtaining quality compost and optimizing the composting process requires using turning as a control mechanism during maturation., Competing Interests: The authors have declared that no competing interests exist.

Background: The lack of high-quality data to support evidence-based policies continues to be a concern in African cities, which present marked social, economic and cultural disparities that may differently impact the health of the groups living in different urban contexts. This study explores three urban units--formal, transition and informal--of the capital of Cape Verde, in terms of overweight/obesity, cardiometabolic risk, physical activity and other aspects related to the urban environment., Methods: Quantitative and qualitative research methods were used in this intra-urban study. A proportional stratified random sample (n = 1912 adults), based on geographical coordinates of private households, was selected to apply the UPHI-STAT questionnaire. In a second stage (n = 599), local nutritionists collected anthropometric measurements (e.g., height, waist circumference) and body composition by bioelectric impedance (e.g., body weight, body fat, muscle mass). In a third stage, pedometers were used to count study participants' steps on working and non-working days for one week (n = 118). After a preliminary statistical analysis, a qualitative study was developed to complement the quantitative approach. Generalized linear models, among others, were used in the multivariate analysis., Results: Insecurity was the main concern among survey respondents in the three units, notwithstanding with significant differences (p < 0.001) among units. About three-quarters (76.6%) of the participants of the informal unit emphasised the need for more security. The formal unit presents an older age structure (61.3% above 40 years old) and the transition unit a younger age structure (only 30.5% above 40 years old). Some health-related variables were analysed in each unit, revealing an excess of chronic conditions reported by inhabitants of informal unit, compared with the formal unit despite the informal unit's younger age profile. The self-reported hypertension varied significantly among urban units (p < 0.001), with 19.3% in the formal unit, 11.4% in the transition unit and 22.5% in the informal unit. Women of the urban units present significant differences (5% level) for body mass index calculated from self-reported measures (p < 0.001), fat mass (p = 0.005), waist circumference (p = 0.046) and waist-to-height ratio (p = 0.017). For women, overall physical activity was 67.4% (95%CI [64.8,70.0]), with differences among urban units (p = 0.025). For men it was of 85.2% (95%CI [82.3,87.6]), without significant differences among urban units (p = 0.266). The percentage of women and men who reported physical activity in leisure time was discrepant, with 95%CI [22.6, 27.4] and [53.2, 60.2], respectively. The results of pedometers also indicated that men walk significantly more than women (p < 0.001), with a difference of approximately 2000 steps/day., Conclusions: The data collection process itself also gave us some clues on the involvement of local communities, exploring the potential of social capital of these settings and the role of the woman in family and society in Cape Verde. The higher participation of women and residents of informal unit (the most disadvantaged groups) suggests these as the priority target groups for health promotion campaigns. The link between health planning, urban planning and security of the city needs to be reinforced to minimize health, social and gender inequalities.

Abundant evidence exists to support a role for lignin as an important element in biomass recalcitrance. However, several independent studies have also shown that factors apart from lignin are also relevant and overall, the relative importance of different recalcitrance traits remains in dispute. In this study we used two genetically distant sugarcane genotypes, and performed a correlational study with the variation in anatomical parameters, cell wall composition, and recalcitrance factors between these genotypes. In addition we also tracked alterations in these characteristics in internodes at different stages of development. Significant differences in the development of the culm between the genotypes were associated with clear differential distributions of lignin content and composition that were not correlated with saccharification and fermentation yield. Given the strong influence of the environment on lignin content and composition, we hypothesized that sampling within a single plant could allow us to more easily interpret recalcitrance and changes in lignin biosynthesis than analysing variations between different genotypes with extensive changes in plant morphology and culm anatomy. The syringyl/guaiacyl (S/G) ratio was higher in the oldest internode of the modern genotype, but S/G ratio was not correlated with enzymatic hydrolysis yield nor fermentation efficiency. Curiously we observed a strong positive correlation between ferulate ester level and cellulose conversion efficiency. Together, these data support the hypothesis that biomass enzymatic hydrolysis recalcitrance is governed by a quantitative heritage rather than a single trait.