Search Results (15,714)

Background: Tobramycin is a key therapy for pulmonary exacerbations in children and adolescents with cystic fibrosis (CF), yet its variable pharmacokinetics (PK) combined with narrow therapeutic index necessitates therapeutic drug monitoring (TDM) during clinical care to optimize exposure while minimizing toxicity. Model-informed precision dosing (MIPD) is a potentially powerful tool to support dose individualization in clinical care that leverages population PK models and Bayesian forecasting. Herein, we evaluated the performance of an MIPD initiative at our hospital for once-daily tobramycin in pediatric patients with CF. Methods: Tobramycin practices at a single CF center before (2016–2018) and after (2019–2025) implementation of an MIPD initiative in CF patients < 21 years were evaluated. TDM during the pre-MIPD period used traditional log-linear AUC calculations, while the post-MIPD period used a commercial MIPD software platform integrated within the electronic health record. Outcomes included attainment of the target 24 h area-under-the-curve (AUC₂₄ 80–120 mg·h/L), number of TDM samples and dose adjustments during the first 7 days of treatment, and rates of acute kidney injury (AKI). Results: A total of 114 treatment courses were analyzed (77 pre-MIPD, 37 post-MIPD). Post-MIPD target attainment was 75.7% at TDM1, 89.2% at TDM2, and 100% at TDM3, significantly higher than pre-MIPD at corresponding cycles. The post-MIPD period required fewer TDM samples (4.2 vs. 7.1; p < 0.001) and dose adjustments (0.7 vs. 1.8; p < 0.001) in the first 7 days. AKI incidence remained low and comparable between periods. Conclusions: Implementation of an MIPD initiative for tobramycin in pediatric patients with CF led to the early attainment of therapeutic AUC₂₄ targets while reducing TDM burden and dose adjustments. Full article

Prostate cancer is one of the most common malignancies in men, and advanced or metastatic disease remains associated with substantial morbidity and mortality. Therapeutic progress in recent years has been driven by the introduction of targeted treatment strategies, notably poly (ADP-ribose) polymerase (PARP) inhibitors, prostate-specific membrane antigen (PSMA)–directed radioligand therapy (RLT), and androgen receptor pathway inhibitors (ARPIs). This review summarizes evidence from phase II and III clinical trials, meta-analyses, and real-world studies evaluating the efficacy, safety, and clinical integration of olaparib, lutetium (¹⁷⁷Lu) vipivotide tetraxetan, and abiraterone in advanced prostate cancer. Emphasis is placed on the practical clinical application of these agents, including patient selection, treatment sequencing, and combination strategies. PARP inhibition with olaparib has demonstrated clear benefits in metastatic castration-resistant prostate cancer (mCRPC) with homologous recombination repair (HRR) mutations, particularly BRCA1/2 alterations. PSMA-directed RLT offers a survival advantage in PSMA-positive mCRPC following AR pathway inhibition, with distinct toxicity considerations that influence patient selection. Abiraterone remains a cornerstone therapy across disease stages and plays an important role both as monotherapy and as a combination partner. Emerging data suggest a potential synergy between PARP inhibitors and AR-targeted agents, while also highlighting the limitations of biomarker-unselected approaches. We conclude that the optimal use of PARP inhibitors, PSMA-targeted RLT, and ARPIs requires a personalized strategy guided by molecular profiling, functional imaging, prior treatment exposure, and safety considerations. This clinically focused overview aims to support evidence-based decision-making in an increasingly complex treatment landscape. Full article

Phosphoenolpyruvate carboxykinase (PEPCK), a key gluconeogenic enzyme, is associated with adaptation to environmental stress. However, its potential role in diapause is not known. Here, two cytoplasmic genes encoding PEPCK (SmPEPCK1-1 and SmPEPCK1-2) in Sitodiplosis mosellana, a significant wheat pest undergoing obligatory larval diapause during the third instar, were cloned, and their expression patterns during diapause and thermal stress were assessed, together with the effects of SmPEPCK1-2 knockdown on larval development. Both SmPEPCK1-1 and SmPEPCK1-2 were evolutionarily conserved and contained canonical functional domains and motifs. Their expression was induced by diapause, and was found to be tissue-specific, with the highest levels observed in the fat bodies of diapausing larvae. Furthermore, exposure to heat stress in oversummering larvae or cold stress in overwintering larvae enhanced the expression of both genes within specific temperature ranges (35–40 °C and −10–0 °C, respectively). RNA interference-mediated knockdown of SmPEPCK1-2 did not affect cocoon-breaking rates and timing but significantly prolonged the duration of larval development from cocoon-breaking to pupation. These findings indicate that both SmPEPCK genes are closely involved in tolerance to diapause-related stress, with SmPEPCK1-2 also contributing to the regulation of larval development. Full article

The pharmacological effects of ginger extract from Zingiber officinale Roscoe are well-established; however, more refined extraction methods for higher-quality yields are needed. This study isolated and evaluated 6-, 8-, and 10-shogaol and 6-, 8-, and 10-gingerol from ginger extract, assessing their effects on glucose-stimulated insulin secretion (GSIS). To ensure safety, non-toxic concentrations were determined for pancreatic β-cells. Both non-processed and microwave-processed ginger extracts enhanced GSIS, with microwave-treated extracts exhibiting the strongest effect. Specifically, the microwave-processed ginger extract increased the glucose stimulation index (GSI) to 12.4 ± 0.4 at 5 μg/mL, compared to a GSI of 7.7 ± 0.2 observed for the non-processed ginger extract. Notably, fraction F4 of the microwave-processed extract demonstrated superior GSIS activity. In contrast, steam-processed ginger extract induced only a modest increase in GSI under limited exposure conditions. Furthermore, 6-shogaol emerged as a key compound, correlating with increased expression of proteins crucial for pancreatic β-cell regulation. Microwave-assisted processing notably altered the content and proportion of shogaols and gingerols, significantly impacting GSIS activity. These findings underscore the importance of extraction methods in enhancing ginger’s pharmacological potential in regulating insulin secretion and pancreatic β-cell function. Full article

Wetlands are a critical component of the global biogeochemical cycle and have great potential for carbon sequestration under the changing climate. However, previous studies have mainly focused on the dynamics of soil organic carbon while paying little attention to the vegetation carbon storage in wetlands. Poyang Lake is the largest freshwater lake in China, where intra-annual and inter-annual variations in water levels significantly affect the vegetation carbon storage in the floodplain wetland. Therefore, we assessed the seasonal distribution and carbon storage of six typical plant communities (Arundinella hirta, Carex cinerascens, Miscanthus lutarioriparius, Persicaria hydropiper, Phalaris arundinacea, and Phragmites australis) in Poyang Lake wetlands from 2019 to 2024 based on field surveys, the literature, and remote sensing data. Then, we used 16 preseason meteorological and hydrological variables for two growing seasons to investigate the impacts of environmental factors on vegetation carbon storage based on four correlation and regression methods (including Pearson and partial correlation, ridge, and elastic net regression). The results show that the C. cinerascens community was the most dominant contributor to vegetation carbon storage, occupying 12.68% to 44.22% of the Poyang Lake wetland area. The vegetation carbon storage in the Poyang Lake wetland was significantly (p < 0.01) higher in spring (87.75 × 10⁴ t to 239.10 × 10⁴ t) than in autumn (77.32 × 10⁴ t to 154.78 × 10⁴ t). Water body area emerged as a key explanatory factor, as it directly constrains the spatial extent available for vegetation colonization and growth by alternating inundation and exposure. In addition, an earlier start or end to floods could both enhance vegetation carbon storage in spring or autumn. However, preseason precipitation and temperature are negative to carbon storage in spring but exhibited opposite effects in autumn. These results assessed the seasonal dynamics of dominant vegetation communities and helped understand the response of the wetland carbon cycle under the changing climate. Full article

In marine aquaculture environments, microplastics (MPs) and cadmium (Cd) are widespread contaminants that may jointly affect host–microbe interactions. Here, we examined the combined effects of MPs (5 mg/L) and Cd (5 μg/L) on the intestinal microbial community of pearl oysters after a 48 h exposure, followed by a 5-day recovery period. Gut microbiota dynamics were characterized using 16S rRNA gene sequencing. Alpha diversity did not vary significantly, whereas beta diversity showed marked alterations in community composition among the different exposure treatments. LEfSe analysis revealed distinct microbial biomarkers and putative pathogens under each treatment: Sulfitobacter in the MPs-alone group; Vibrio and Candidatus_Megaira in the Cd-alone group; and Tenacibaculum, Roseibacillus, and Enterovibrio across different co-exposure and recovery groups. A brief recovery period partially decreased the abundance of certain pathogens (e.g., Vibrio), yet some taxa (e.g., Enterovibrio and Tenacibaculum) remained enriched. These results indicate that exposure to MPs and Cd, whether alone or in combination, disrupts gut microbial homeostasis in pearl oysters by reshaping community structure and promoting the proliferation of potential pathogens, with some disturbances persisting after exposure ceases. Generally, our findings will aid evaluation of the ecological risks of combined pollutants in marine aquaculture systems. Full article

Climate change has intensified summer drought and high solar radiation in Mediterranean ecosystems, generating abiotic stress that limits the establishment of riparian species. We conducted a nursery experiment to evaluate the effects of two levels of water availability and light intensity on the growth and physiological responses of two native riparian species from Mediterranean Chile: Drimys winteri and Persea lingue. A bi-factorial design combined two irrigation treatments (well-watered and water restriction) and two light intensity levels manipulated through a light protection treatment (20% shade mesh and full light exposure). Water restriction was applied gradually until 15–20% (v/v) substrate moisture, defined as maximum water restriction, followed by rehydration. Morphological variables (height, root collar diameter, and shoot-to-root ratio) and physiological traits (predawn water potential, chlorophyll fluorescence, and electron transport rate) were measured. Growth responses were affected by the light protection treatment, which promoted a significant height growth in both species. Water stress affected the global response of both species but they differed in their post-stress hydraulic recovery: P. lingue fully recovered its predawn water potential, whereas Drimys winteri did not. Our study provides measurable and quantifiable values that demonstrate the sensitivity of these species to water stress. Full article

Pesticides have been widely applied in agricultural practices over the past decades to protect crops from pests and other harmful organisms. However, their extensive use results in the contamination of soil, water, and agricultural products, posing significant risks to human and environmental health. Exposure to pesticides can lead to skin irritation, respiratory disorders, and various chronic health problems. Moreover, pesticides frequently enter surface water bodies such as rivers and lakes through agricultural runoff and leaching processes. Therefore, developing effective analytical methods for the rapid and sensitive detection of pesticides in food and water is of great importance. Electrochemical sensing techniques have shown remarkable progress in pesticide analysis due to their high sensitivity, simplicity, and potential for on-site monitoring. Two-dimensional (2D) carbon nanomaterials have emerged as efficient electrocatalysts for the precise and selective detection of pesticides, owing to their large surface area, excellent electrical conductivity, and unique structural features. In this review, we summarize recent advancements in the electrochemical detection of pesticides using 2D carbon-based materials. Comprehensive information on electrode fabrication, sensing mechanisms, analytical performance—including sensing range and limit of detection—and the versatility of 2D carbon composites for pesticide detection is provided. Challenges and future perspectives in developing highly sensitive and selective electrochemical sensing platforms are also discussed, highlighting their potential for simultaneous pesticide monitoring in food and environmental samples. Carbon-based electrochemical sensors have been the subject of many investigations, but their practical application in actual environmental and food samples is still restricted because of matrix effects, operational instability, and repeatability issues. In order to close the gap between laboratory research and real-world applications, this review critically examines sensor performance in real-sample conditions and offers innovative approaches for in situ pesticide monitoring. Full article

Seed biopriming is increasingly recognized as a strategy capable of inducing molecular memory that enhances plant performance under heavy-metal stress. Here, we investigated how biopriming Silene sendtneri seeds with Paraburkholderia phytofirmans PsJN establishes a transcriptional state that predisposes seedlings for improved cadmium (Cd) tolerance. RNA-seq profiling revealed that primed seeds exhibited differential gene expression prior to Cd exposure, with strong upregulation of detoxification enzymes, antioxidant machinery, metal transporters, photosynthetic stabilizers, and osmoprotectant biosynthetic genes. Enrichment of gene ontology categories related to metal ion detoxification, redox homeostasis, phenylpropanoid metabolism, and cell wall organization indicated that biopriming imprints a preparatory transcriptional signature resembling early stress responses. Upon Cd exposure, primed plants displayed enhanced physiological performance, including preserved integrity, elevated antioxidant activity, particularly peroxidases in roots, higher osmolyte accumulation, stabilized micronutrient levels, and substantially increased Cd uptake and sequestration. These coordinated responses demonstrate that biopriming induces a sustained molecular memory that accelerates and strengthens downstream defense activation. These findings demonstrate that PGPR-based biopriming establishes a stable transcriptomic memory in seeds that enhances cadmium tolerance, metal sequestration, and stress resilience, highlighting its potential for improving hyperaccumulator performance in phytoremediation and stress adaptation strategies. Full article

Volatile organic compounds (VOCs) produced by Medicinal Aromatic Plants (MAPs) are bioactive signaling molecules that play key roles in plant defense, acting against pathogens and triggering resistance responses. Intercropping with VOC-emitting MAPs can therefore enhance disease resistance. This study investigated VOCs emitted by sage (Salvia officinalis) as potential resistance inducers in grapevine (Vitis vinifera) against Plasmopara viticola, the causal agent of downy mildew, under consociated growth conditions. Sage and grapevine plants were co-grown in an airtight box system for 24 or 48 h, after which grape leaves were inoculated with P. viticola. Disease assessments were integrated with grapevine leaf metabolic profiling to evaluate responses to VOC exposure and pathogen infection. Untargeted and targeted metabolomic analysis revealed that sage VOCs consistently reprogrammed grapevine secondary metabolism, without substantial differences between 24 and 48 h exposures. Lipids, phenylpropanoids, and terpenoids were markedly accumulated following VOC exposure and persisted following inoculation. Correspondingly, leaves pre-exposed to sage VOCs exhibited a significant reduction in disease susceptibility. Overall, our results suggest that exposure to sage VOCs induces signaling and metabolic reprogramming in grapevine. Further research should elucidate how grapevines perceive and integrate these signals, as well as the broader processes underlying MAP VOC-induced defense, and evaluate their translation into sustainable viticultural practices. Full article

The ubiquity of microplastics (MPs) in the environment has raised significant concerns, yet their potential impacts on human health are not fully elucidated. This study aimed to quantify human exposure to MPs in feces and evaluate their associations with oxidative stress and cardiopulmonary function. A panel study was conducted in 16 male college students with three-round visits. Fecal MPs were quantified using infrared micro-spectroscopy, and health effects were assessed through urinary biomarkers of oxidative damage (MDA and 8-OHdG) and cardiopulmonary function tests. Associations between MP exposure and health outcomes were analyzed using linear mixed-effect models. We found that fecal MP amount across 48 samples from 16 participants showed high intra-individual variation and poor reproducibility (ICCs < 0.4). MPs in feces were predominantly identified as sheets and fragments in the 100–200 μm size range, with polyamide (PA), polyester, polyethylene (PE), and polypropylene as the primary polymer types. Significant relationships were observed between fecal MP amount and oxidative damage biomarkers. Each one-unit increase in MPs corresponded to a 0.827 increase in MDA (95% CI: 0.116, 1.54) and a 1.11 increase in 8-OHdG (95% CI: 0.235, 1.98), with fibrous shapes and specific polymers (PE and PA) being the primary drivers. No significant associations were found between MP exposure and lung function or blood pressure. These findings indicated that MP exposure was significantly linked to increased oxidative damage, highlighting a pressing public health concern regarding their subclinical biological effects. Full article

Radon is one of the leading causes of lung cancer worldwide. Following the implementation of the European Council Directive 2013/59/EURATOM, regular measurements of radon concentrations in workplaces have been carried out in European countries for approximately ten years. This provides a basis for assessing the exposure of workers and the general population to radon, as well as for determining the need to implement measures aimed at reducing this exposure. In addition to commonly used methods that focus on eliminating radon sources or minimizing its ingress into buildings, there are also temporary measures available, such as using air purifiers to improve indoor air quality. Although they are not recommended as a standalone or definitive solution, they can be useful as an interim measure—until appropriate actions to reduce indoor radon concentrations are implemented. In this study, five commercially available air purifiers were tested under controlled laboratory conditions to assess their impact on radon and its decay products. The results show that none of the tested devices significantly reduced gaseous radon concentrations. However, the air purifiers were highly effective in removing radon progeny, achieving a 95–99% reduction in potential alpha energy concentration (PAEC) and reducing the equilibrium factor from 48 to 76% to 0–2%. From a sustainability perspective, these findings are relevant for public health protection, responsible consumer decision-making, and evidence-based indoor air quality management. By distinguishing between ineffective radon gas removal and effective reduction of dose-relevant decay products, this study supports sustainable risk mitigation strategies and helps prevent the misuse of energy- and resource-intensive technologies for purposes they cannot fulfill. Full article

Microplastics (MPs) and antibiotics have emerged as contaminants of global concern, posing potential threats to ecosystem security and organismal health. To investigate the individual and combined toxicity of microplastics (PS-MPs) and sulfamethoxazole (SMX), we conducted a 120 h acute exposure experiment using embryo–larval zebrafish as a toxicological model. Our findings demonstrate that both PS-MPs and SMX can induce neurodevelopmental toxicity in embryo–larval zebrafish during embryonic development. Notably, PS-MPs and SMX exerted a significant synergistic effect. PS-MPs 1 µm in diameter were restricted to the chorion surface of pre-hatching zebrafish, whereas post-hatching, PS-MPs accumulated mainly in the gut and gills, with accumulation levels increasing progressively with exposure duration. Individual exposure to PS-MPs or SMX reduced spontaneous locomotion, decreased heart rate, and shortened body length in embryo–larval zebrafish. In addition to exacerbating these effects, coexposure further increased the incidence of malformations such as pericardial effusion and spinal curvature. PS-MPs and SMX significantly decreased the levels of dopamine (DA), serotonin (5-HT), and γ-aminobutyric acid (GABA) in zebrafish while also suppressing acetylcholinesterase (AChE) activity and increasing acetylcholine (ACh) levels. Moreover, upon coexposure at high concentrations, PS-MPs and SMX acted synergistically to reduce the levels of DA and GABA. The downregulation of key neurodevelopmental genes (elavl3, gap43, and syn2a) and related neurotransmitter pathway genes indicates that PS-MPs and SMX impaired structural development and functional regulation of the nervous system. An integrated biomarker response (IBR) index confirmed that PS-MPs and SMX significantly enhanced developmental neurotoxicity during early neurodevelopment in embryo–larval zebrafish through synergistic effects. Our study provides critical toxicological evidence for the scientific assessment of the ecological risks posed by microplastic–antibiotic cocontamination. Full article

The insect gut microbiome contributes to various host physiological processes and behaviors, such as digestion, nutrient absorption, immunity, mate choice, and fecundity. The social environment can shape gut microbial communities. Mixed-sex vs. female-only rearing is an important social context because it differs in exposure to the opposite sex and mating opportunities, which may in turn affect female physiology that may influence their gut microbiome. Despite the growing recognition of these social-microbial interactions, most studies have relied on 16S rRNA amplicon sequencing or qPCR, which provide only coarse taxonomic resolution and limited functional insight. In this study, we used whole-genome shotgun metagenomics to examine changes in microbial diversity and functional gene composition in the female field cricket Teleogryllus occipitalis (Serville) (Orthoptera: Gryllidae) reared under two social conditions: mixed-sex rearing and female-only rearing. Species richness and diversity analyses revealed that community composition separated between females from mixed-sex and female-only rearing. Functional profiling indicated higher relative abundances of genes annotated to nutrient processing and inter-bacterial competition in females from mixed-sex rearing, whereas females from female-only rearing showed relative enrichment of genes annotated to stress resistance and nitrogen fixation. These findings provide a genome-resolved foundation for testing how social rearing conditions covary with gut microbiome composition and functional potential in female crickets. Full article

Nanoplastics are persistent environmental pollutants with potential risks to human health. Due to their small size, nanoplastics are internalized by macrophages, potentially altering their function. In this study we found that, in macrophages, 50 nm polystyrene nanoplastics were predominantly present in endosomes, lysosomes, and in the endoplasmic reticulum. Internalization of polystyrene nanoplastics increased the bactericidal activity of macrophages, which was inhibited by the NADPH oxidase inhibitor diphenyleneiodonium. Consistently, measurements of cellular and mitochondrial reactive oxygen species by flow cytometry revealed that polystyrene nanoplastics induced reactive oxygen species production in macrophages. In contrast, internalization of polystyrene nanoplastics reduced the levels of nitric oxide released by macrophages in response to E. coli. Internalization of polystyrene nanoplastics followed by the addition of E. coli induced high expression levels of the aconitate decarboxylase 1 gene. In the absence of this gene, killing of E. coli by macrophages exposed to polystyrene nanoplastics was significantly attenuated with respect to control macrophages, indicating a role for the mitochondrial metabolite itaconate in the increased bactericidal activity of macrophages exposed to polystyrene nanoplastics. Collectively, our results indicate that exposure of macrophages to polystyrene nanoplastics increases their bactericidal activity through the production of reactive oxygen species and of itaconate. Full article