Search Results (37,195)

The current study focuses on a preliminary evaluation of the use of solid residues produced from the distillation of selected medicinal and aromatic plants (MAP) as fertilizers for alkaline soils. Specifically, the residues of hemp (Cannabis sativa L.), helichrysum (Helichrysum Italicum (Roth) G. Don), lavender (Lavandula angustifolia Mill.), oregano (Origanum vulgare L.), rosemary (Rosmarinus officinalis L.) and sage (Salvia officinalis L.) were added in an alkaline and calcareous soil at the rates of 0 (control), 1, 2, 4 and 8%, in three replications (treatments), and the treated soils were analyzed. The results showed that upon application of the residues, soil electrical conductivity (EC), organic C, total N and the C/N ratio significantly increased, especially at the 4 and 8% rates. The same was found for soil available P, K, B, Cu and Mn. The effects of the residues on soil pH, cation exchange capacity (CEC) and available Zn and Fe were rather inconclusive, whereas soil available N significantly decreased, which was somewhat unexpected. From the different application rates tested, it seems that all residues could improve soil fertility (except N?) when they were applied to soil at rates of 2% and above, without exceeding the 8% rate. The reasons for the latter statement are soil EC and available Mn: the doubling of EC upon application of the residues and the excessive increase in soil available Mn in treatments with 8% residues raise concerns of soil salinization and Mn phytotoxicity risks, respectively. This work provides the first step towards the potential agronomic use of solid residues from MAP distillation in alkaline soils. However, for the establishment of such a perspective, further research is needed in respect to the effect of residues on plant growth and soil properties, by means of at least pot experiments. Based on the results of the current study, the undesirable effect of residues on soil available N should be investigated in depth, since N is the most important essential element for plant growth, and possible risks of micronutrient phytotoxicities should also be studied. In addition, application rates between 2 and 4% should be studied extensively in order to recommend optimum application rates of residues to producers. Full article

In this study, GH19 chitinase (Chi) gene family was systematically identified and characterized using genomic assemblies from four cotton species: Gossypium barbadense, G. hirsutum, G. arboreum, and G. raimondii. A suite of analyses was performed, including genome-wide gene identification, physicochemical property characterization of the encoded proteins, subcellular localization prediction, phylogenetic reconstruction, chromosomal mapping, promoter cis-element analysis, and comprehensive expression profiling using transcriptomic data and qRT-PCR (including tissue-specific expression, hormone treatments, and Fusarium oxysporum infection assays). A total of 107 GH19 genes were identified across the four species (35 in G. barbadense, 37 in G. hirsutum, 19 in G. arboreum, and 16 in G. raimondii). The molecular weights of GH19 proteins ranged from 9.9 to 97.3 kDa, and they were predominantly predicted to localize to the extracellular space. Phylogenetic analysis revealed three well-conserved clades within this family. In tetraploid cotton, GH19 genes were unevenly distributed across 12 chromosomes, often clustering in certain regions, whereas in diploid species, they were confined to five chromosomes. Promoter analysis indicated that GH19 gene promoters contain numerous stress- and hormone-responsive motifs, including those for abscisic acid (ABA), ethylene (ET), and gibberellin (GA), as well as abundant light-responsive elements. The expression patterns of GH19 genes were largely tissue-specific; for instance, GbChi23 was predominantly expressed in the calyx, whereas GbChi19/21/22 were primarily expressed in the roots and stems. Overall, this study provides the first comprehensive genomic and functional characterization of the GH19 family in G. barbadense, laying a foundation for understanding its role in disease resistance mechanisms and aiding in the identification of candidate genes to enhance plant defense against biotic stress. Full article

To develop sustainable strategies for mitigating ruminal methanogenesis and improving nitrogen efficiency in dairy systems, this study investigated how low-dose tannic acid (T), tea polyphenols (TP), and their combination (T+TP; 50:50) modulate rumen microbiota and function. A sample of Holstein cows were given four dietary treatments: (1) control (basal diet); (2) T (basal diet + 0.4% DM tannic acid); (3) TP (basal diet + 0.4% DM tea polyphenols); and (4) T+TP (basal diet + 0.2% DM tannic acid + 0.2% DM tea polyphenols). We comprehensively analyzed rumen fermentation, methane production, nutrient digestibility, milk parameters, and microbiota dynamics. Compared with the control group, all diets supplemented with additives significantly reduced enteric methane production (13.68% for T, 11.40% for TP, and 10.89% for T+TP) and significantly increased milk protein yield. The crude protein digestibility significantly increased in the T group versus control. The results did not impair rumen health or fiber digestion. Critically, microbiota analysis revealed treatment-specific modulation: the T group showed decreased Ruminococcus flavefaciens abundance, while all tannin treatments reduced abundances of Ruminococcus albus and total methanogens. These microbial shifts corresponded with functional outcomes—most notably, the T+TP synergy drove the largest reductions in rumen ammonia-N (34.5%) and milk urea nitrogen (21.1%). Supplementation at 0.4% DM, particularly the T+TP combination, effectively enhances nitrogen efficiency and milk protein synthesis while reducing methane emissions through targeted modulation of key rumen microbiota populations, suggesting potential sustainability benefits linked to altered rumen fermentation. Full article

Endotoxins, lipopolysaccharides released from the outer membrane of Gram-negative bacteria, pose a significant risk in healthcare environments, particularly in Central Sterile Supply Departments (CSSDs), where the delivery of sterile pyrogen-free medical devices is critical for patient safety. Traditional methods for controlling endotoxins in water systems, such as ultraviolet (UV) disinfection, have proven ineffective at reducing endotoxin concentrations to comply with regulatory standards (<0.25 EU/mL). This limitation presents a significant challenge, especially in the context of reverse osmosis (RO) permeate used in CSSDs, where water typically has very low conductivity. Despite the established importance of endotoxin removal, a gap in the literature exists regarding effective chemical-free methods that can meet the stringent endotoxin limits in such low-conductivity environments. This study addresses this gap by evaluating the effectiveness of the eBooster™ electrochemical technology—featuring proprietary electrode materials and a reactor design optimized for potable water—for endotoxin removal from water, specifically under the low-conductivity conditions typical of RO permeate. Laboratory experiments using the B250 reactor achieved >90% endotoxin reduction (from 1.2 EU/mL to <0.1 EU/mL) at flow rates ≤5 L/min and current densities of 0.45–2.7 mA/cm². Additional real-world testing at three hospitals showed that the eBooster™ unit, when installed in the RO tank recirculation loop, consistently reduced endotoxin levels from 0.76 EU/mL (with UV) to <0.05 EU/mL over 24 months of operation, while heterotrophic plate counts dropped from 190 to <1 CFU/100 mL. Statistical analysis confirmed the reproducibility and flow-rate dependence of the removal efficiency. Limitations observed included reduced efficacy at higher flow rates, the need for sufficient residence time, and a temporary performance decline after two years due to a power fault, which was promptly corrected. Compared to earlier approaches, eBooster™ demonstrated superior performance in low-conductivity environments without added chemicals or significant maintenance. These findings highlight the strength and novelty of eBooster™ as a reliable, chemical-free, and maintenance-friendly alternative to traditional UV disinfection systems, offering a promising solution for critical water treatment applications in healthcare environments. Full article

Glioblastoma multiforme (GBM) remains one of the most aggressive and treatment-resistant brain tumors, with poor prognosis and limited therapeutic options. Background/Objectives: Integrin α_vβ₃, a cell surface receptor overexpressed in GBM, specifically binds to cyclic arginine-glycine-aspartate-D-phenylalanine-lysine (c(RGDfK)) motif, making it a valuable target for tumor-specific delivery and PET imaging. This study explores a novel radiotheranostic agent, [⁶⁴Cu]Cu-NOTA-TP-c(RGDfK), which combines the imaging and therapeutic capabilities of copper-64 (⁶⁴Cu) and the cytotoxic activity of a terpyridine-platinum (TP) complex, conjugated to c(RGDfK). Methods: A robust protocol was developed for the small-scale preparation of NOTA-TP-c(RGDfK). Comparative cellular studies were conducted using U87 MG glioblastoma (GBM) cells and SVG p12 human astrocytes to evaluate the performance of [⁶⁴Cu]Cu-NOTA-TP-c(RGDfK) relative to [⁶⁴Cu]Cu-NOTA-c(RGDfK), [⁶⁴Cu]Cu-NOTA-TP, ^natCu-NOTA-TP-c(RGDfK), cisplatin, and temozolomide. Results: ⁶⁴Cu-radiolabeling of NOTA-TP-c(RGDfK) was achieved with >99% radiochemical purity, and competition assays confirmed high binding affinity to integrin α_vβ₃ (IC₅₀ = 16 ± 8 nM). Cellular uptake, internalization, and retention studies demonstrated significantly higher accumulation of [⁶⁴Cu]Cu-NOTA-TP-c(RGDfK) in U87 MG cells compared to control compounds, with 38.8 ± 1.8% uptake and 28.0 ± 1.0% internalization at 24 h. Nuclear localization (6.0 ± 0.5%) and stable intracellular retention further support its therapeutic potential for inducing localized DNA damage. Importantly, [⁶⁴Cu]Cu-NOTA-TP-c(RGDfK) exhibited the highest cytotoxicity in U87 MG cells (IC₅₀ = 10 ± 2 nM at 48 h), while maintaining minimal toxicity in normal SVG p12 astrocytes. Conclusions: These results highlight [⁶⁴Cu]Cu-NOTA-TP-c(RGDfK) as a promising targeted radiotheranostic agent for GBM, warranting further preclinical development Full article

Introduction: Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer entity in Germany, following basal cell carcinoma. Its incidence has increased fourfold over the past three decades. Early diagnosis and treatment are essential for achieving favorable outcomes. Our study aims to identify prognostic factors based on real-world data to improve follow-up protocols and raise clinical vigilance. Methods: We conducted a retrospective, monocenter analysis with a total of 124 patients with at least one cSCC thicker than 3 mm, treated at the Department of Dermatology, University Medical Center Mainz, between 2010 and 2020. Tumor-specific criteria were correlated with patient-specific data, such as gender, age, immunosuppression, UV exposure and mortality. Results: A higher incidence of cSCC was found on UV-exposed skin (91.1%); however, tumors on non-UV-exposed skin were on average thicker (6.55 mm vs. 9.25 mm, p = 0.011) and associated with higher metastasis rates (10.6% vs. 63.3%, p < 0.001). Immunosuppression was strongly associated with a younger age at diagnosis (74 years vs. 81 years), a higher metastasis rate (29% vs. 10.8%, p = 0.021) and a worse 5Y-OS-rate (36.1% vs. 97.8%, p = 0.04). SLNB was performed in eight patients, with one positive SLN identified (12.5%). Local recurrence was observed in 18.1% (n = 21) of patients who did not experience SLNB, whereas no local recurrences (0%) were reported in patients with SLNB (p = 0.349). Discussion: Tumors on non-UV-exposed areas were thicker and more often metastatic, suggesting delayed detection or more aggressive tumor subtypes. Immunosuppression was associated with worse outcomes, underscoring the need for intensified follow-up. SLNB was rarely performed, and larger studies are needed to assess its role. Full article

Cell-based therapies emerge as potential treatment options for various debilitating diseases. Preclinical research and clinical studies involving cells increased exponentially in the past decade. In addition to cell-based approaches, the use of extracellular vesicles (EVs), which are released by nearly all cell types, emerged as a promising cell-free alternative. Those approaches are also being explored in the field of ophthalmology. Several clinical trials involving EVs are underway to develop potential treatments for advanced ocular surface diseases, including corneal disorders, injuries, and dry eye disease. The cargo carried by EVs has been shown to include a diverse array of functional molecules such as transcription factors, cytokines, growth factors, mRNA, tRNA, rRNA, miRNA, and fragments of dsDNA. While the molecular composition of EVs is already well characterised, the specific activity of these molecules upon delivery to recipient cells remains poorly understood. In this review, we summarise recent studies investigating the bioactive molecules within EVs shown to influence or modulate cellular activity on the ocular surface. Among these, various miRNAs have most commonly been identified as therapeutic agents targeting distinct molecular pathways. The EVs studied were predominantly derived from various mesenchymal stem cells. Full article

Background: Exposure-based cognitive behavioral therapy (Ex-CBT) is widely seen as the gold-standard treatment for anxiety and obsessive-compulsive disorder (OCD). Yet, minoritized youth are underrepresented in efficacy studies, raising questions about the applicability of Ex-CBT to minoritized youth. Effectiveness data suggest systematic adaptation of Ex-CBT to address youth culture and context is likely needed, and many clinicians make adaptations and augmentations in practice. However, research on the specific strategies clinicians use to address their youth clients’ culture and context within anxiety and OCD treatment is lacking. In the current study, we assess practice-based adaptations, augmentations, and process-based approaches utilized when delivering treatment to youth for OCD and anxiety in public mental health clinics. Methods: We conducted qualitative interviews with 16 clinicians from both specialty anxiety and general mental health clinics serving youth with anxiety or OCD in the public mental health system. Participating clinicians had a mean age of 32.19 (SD = 5.87) and 69% of therapists identified as female; 69% identified as White, 25% identified as Asian, and 6% as Black or African American. In qualitative interviews, clinicians shared how they addressed clients’ culture and context (e.g., social identities, stressors and strengths related to social identities and lived environment). Thematic analysis identified the strategies clinicians employed to address culture and context. Results: Clinicians reported incorporating culture and context through process-based approaches (e.g., building trust gradually, considering clients’ social identity stressors, engaging in self-awareness to facilitate cultural responsiveness) and through culturally adapting and augmenting treatment to promote person-centered care. Core strategies included proactive and ongoing assessment of clients’ cultural and contextual factors, adapting exposures and augmenting Ex-CBT with strategies such as case management and discussion of cultural context, and taking a systems-informed approach to care. Conclusions: Examining practice-based adaptations, augmentations, and process-based approaches to treatment for minoritized youth with OCD or anxiety can inform efforts to understand what comprises person-centered culturally responsive Ex-CBT. Empirical testing of identified strategies is a needed area of future research. Full article

The ongoing global climate change has led to an increase in the frequency and complexity of drought events. Pinus yunnanensis, a native tree species in southwest China that possesses significant ecological and economic value, exhibits a high sensitivity to drought stress, particularly in its seedlings. This study investigates the response mechanisms of non-structural carbohydrates (NSCs, defined as the sum of soluble sugars and starch) and the stoichiometric characteristics of carbon (C), nitrogen (N), and phosphorus (P) to repeated drought conditions in Pinus yunnanensis seedlings. We established three treatment groups in a potting water control experiment involving 2-year-old Pinus yunnanensis seedlings: normal water supply (CK), a single drought (D1), and three drought–rewatering cycles (D3). The findings indicated that the frequency of drought occurrences, organ responses, and their interactions significantly influenced the non-structural carbohydrate (NSC) content and its fractions, as well as the C/N/P content and its stoichiometric ratios. Under D3 treatment, stem NSC content increased by 24.97% and 29.08% compared to CK and D1 groups (p < 0.05), respectively, while root NSC content increased by 41.35% and 49.46% versus CK and D1 (p < 0.05). The pronounced accumulation of soluble sugars and starch in stems and roots under D3 suggests a potential stress memory effect. Additionally, NSC content in the stems increased significantly by 77.88%, while the roots enhanced their resource acquisition by dynamically regulating the C/P ratio, which increased by 23.26% (p < 0.05). Needle leaf C content decreased (18.77%) but P uptake increased (8%) to maintain basal metabolism (p < 0.05). Seedling growth was N-limited (needle N/P < 14) and the degree of N limitation was exacerbated by repeated droughts. Phenotypic plasticity indices and principal component analysis revealed that needle nitrogen and phosphorus, soluble sugars in needles, stem C/N ratio (0.61), root C/N ratio (0.53), and stem C/P ratio were crucial for drought adaptation. This study elucidates the physiological mechanisms underlying the resilience of Pinus yunnanensis seedlings to recurrent droughts, as evidenced by their organ-specific strategies for allocating carbon, nitrogen, and phosphorus, alongside the dynamic regulation of nitrogen storage compounds (NSCs). These findings provide a robust theoretical foundation for implementing drought-resistant afforestation and ecological restoration initiatives targeting Pinus yunnanensis in southwestern China. Full article

The literature clearly indicates that both academia and industry are strongly committed to developing comprehensive processes for spent Li-ion battery (LIB) recycling. In this regard, the current study presents an original contribution by providing a quantitative assessment of a large-scale recycling plant designed for the treatment of completely spent LIBs. In addition to a concept of the basic process, this assessment also considers a case study of a thermal integration and CO₂ capture subsystem. Process flow modeling software was used to evaluate the contribution of all process steps and equipment to overall energy consumption and to mass balance the data required for the technical assessment of the large-scale recycling plant. To underline the advantages and identify the optimal novel process concept, several key performance indicators were determined, such as recovery efficiency, specific energy/material consumption, and specific CO₂ emissions. In addition, the economic potential of the recycling plants was evaluated for the defined case studies based on capital and O&M costs. The results indicate that, even with CO₂ capture applied, the thermally integrated process with the combustion of hydrogen produced in the recycling plant remains the most promising large-scale configuration for spent LIB recycling. Full article

Accurately predicting patient clinical outcomes is a complex task that requires integrating diverse factors, including individual characteristics, treatment histories, and environmental influences. This challenge is further exacerbated by missing data and inconsistent data quality, which often hinder the effectiveness of traditional single-task learning (STL) models. Multi-Task Learning (MTL) has emerged as a promising paradigm to address these limitations by jointly modeling related prediction tasks and leveraging shared information. In this study, we proposed MTLNFM, a multi-task learning framework built upon Neural Factorization Machines, to jointly predict patient clinical outcomes on a cohort of 2001 ICU patients. We designed a preprocessing strategy in the framework that transforms missing values into informative representations, mitigating the impact of sparsity and noise in clinical data. We leveraged the shared representation layers, composed of a factorization machine and dense neural layers that can capture high-order feature interactions and facilitate knowledge sharing across tasks for the prediction. We conducted extensive comparative experiments, demonstrating that MTLNFM outperforms STL baselines across all three tasks (i.e., frailty status, hospital length of stay and mortality prediction), achieving AUROC scores of 0.7514, 0.6722, and 0.7754, respectively. A detailed case analysis further revealed that MTLNFM effectively integrates both task-specific and shared representations, resulting in more robust and realistic predictions aligned with actual patient outcome distributions. Overall, our findings suggest that MTLNFM is a promising and practical solution for clinical outcome prediction, particularly in settings with limited or incomplete data, and can support more informed clinical decision-making and resource planning. Full article

Over the past decade, numerous innovative immunotherapy strategies have transformed the treatment of cancer and improved the survival of patients unresponsive to conventional chemotherapy and radiation therapy. Immune checkpoint inhibition approaches aim to block negative regulatory pathways that limit the function of endogenous T cells, while adoptive cell therapy produces therapeutic T cells with high functionality and defined cancer specificity. While CAR engineering successfully targets cancer surface antigens, TCR engineering enables targeting of the entire cancer proteome, including mutated neo-antigens. To date, TCR engineering strategies have focused on the identification of target cancer antigens recognised by well-characterised therapeutic TCRs. In this review, we explore whether antigen-focused approaches could be complemented by TCR-focused approaches, whereby information of the TCR repertoire of individual patients provides the basis for selecting TCRs to engineer autologous T cells for adoptive cell therapy. We discuss how TCR clonality profiles, distribution in T cell subsets, and bioinformatic screening against continuously improving TCR databases can guide the selection of TCRs for therapeutic application. We further outline in vitro approaches to prioritise TCR candidates to confirm cancer reactivity and exclude recognition of healthy autologous cells, which could provide validation for their therapeutic use even when the target antigen remains unknown. Full article

Cyclin-dependent kinase (CDK)4/6 inhibitors have become a key component of adjuvant treatment for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) early breast cancer who are at high risk of recurrence. The addition of abemaciclib and ribociclib to standard endocrine therapy has demonstrated clinically meaningful improvements in invasive disease-free survival, supported by the monarchE and NATALEE trials, respectively. With expansion of patient eligibility for CDK4/6 inhibitors, multidisciplinary coordination among medical oncologists, surgeons, nurses, pharmacists, and other health care providers is critical to optimizing patient identification, monitoring, and management of adverse events. This expert guidance document provides practical recommendations for implementing adjuvant CDK4/6 inhibitor therapy in routine clinical practice, incorporating insights from multiple specialties and with patient advocacy representation. Key considerations include patient selection based on clinical trial data, treatment duration, dosing schedules, adverse event profiles, monitoring requirements, drug–drug interactions, and patient-specific factors such as tolerability, cost, and quality of life. This guidance aims to support Canadian clinicians in effectively integrating CDK4/6 inhibitors into clinical practice, ensuring optimal patient outcomes through a multidisciplinary and patient-centric approach. Full article

Ischemic heart disease (IHD) represents a leading cause of global morbidity and mortality. Despite significant advances in treatment achieved over recent decades, as well as various therapeutic strategies available to manage IHD progression currently, the global incidence of this disorder remains high. This review examines essential cell biology aspects of adenosine receptors (ARs), along with the effects of known synthetic small-molecule AR ligands, to provide an up-to-date view on the therapeutic potential towards IHD treatment. In particular, we report here advancements made on a selection of AR synthetic ligands that have demonstrated efficacy in pre-clinical or clinical studies, thereby holding promise as new therapeutic candidates in the field of IHD. Although this work adds further evidence that clinically valid small-molecule therapeutic agents targeting ARs exist, their use represents an emerging area, with most drug prototypes still in the pre-clinical developmental stage and many lacking large-scale clinical trials. The future lies in identifying improved AR synthetic ligands with enhanced efficacy and selectivity, as well as reduced adverse side effects, along with establishing a platform of specific and diversified pre-clinical tests, to inform in turn the resulting clinical investigations. Full article

Tau protein is essential for the structural stability of neurons, particularly through its role in microtubule assembly and axonal transport. However, when abnormally hyperphosphorylated or cleaved, Tau can aggregate into insoluble forms that disrupt neuronal function, contributing to the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (AD). Emerging evidence suggests that similar Tau-related alterations may occur in individuals with chronic exposure to psychoactive substances. This review compiles experimental, clinical, and postmortem findings that collectively indicate a substance-specific influence on Tau dynamics. Alcohol and opioids, for instance, promote Tau hyperphosphorylation and fragmentation through the activation of kinases such as GSK-3β and CDK5, as well as proteases like caspase-3, leading to neuroinflammation and microglial activation. Stimulants and dissociatives disrupt insulin signaling, increase oxidative stress, and impair endosomal trafficking, all of which can exacerbate Tau pathology. In contrast, cannabinoids and psychedelics may exert protective effects by modulating kinase activity, reducing inflammation, or enhancing neuroplasticity. Psychedelic compounds such as psilocybin and harmine have been demonstrated to decrease Tau phosphorylation and facilitate cognitive restoration in animal models. Although the molecular mechanisms differ across substances, Tau consistently emerges as a convergent target altered in substance-related cognitive disorders. Understanding these pathways may provide not only mechanistic insights into drug-induced neurotoxicity but also identify Tau as a valuable biomarker and potential therapeutic target for the prevention or treatment of cognitive decline associated with substance use. Full article