Search Results (10,264)

Veraison represents a pivotal transition point in grape berry ripening, driven by a cascade of temporally coordinated physiological and molecular events. Studies have shown that the onset of veraison is initially triggered by a decline in cell turgor, regulated by osmotic potential and water status, which subsequently leads to fruit softening. This softening process is accompanied by extensive cell wall remodeling, establishing a structural basis for enhanced sugar influx. A rapid accumulation of sugars follows, acting not only as metabolic substrates but also as signaling molecules that synergize with abscisic acid (ABA) to activate transcriptional programs, including the induction of anthocyanin biosynthesis that drives skin color change. ABA accumulates at the early stages of veraison and functions as a key hormonal regulator initiating the ripening process. In contrast, auxin (IAA) and gibberellin (GA) levels decline prior to veraison, thereby releasing their inhibitory effects on ripening. Environmental factors such as water availability, light, and temperature significantly influence the timing and intensity of veraison by modulating hormonal signaling pathways. The initiation of grape berry ripening exemplifies a multilayered regulatory network that progresses through turgor signaling, hormonal regulation, metabolic reprogramming, and transcriptional activation, thereby providing a mechanistic framework for understanding non-climacteric fruit ripening. offering a mechanistic framework for understanding non-climacteric fruit ripening. This review provides an integrated perspective on the initiation mechanism of veraison, offering theoretical insights and practical implications for improving grape quality and vineyard management. Full article

Background/Objectives: Overactivation of the HGF/c-MET pathway is implicated in various cancers, making its inhibition a promising therapeutic strategy. While several MET-targeting agents are currently approved or in advanced clinical development, patient selection often relies on invasive tissue-based assays. The development of a specific c-MET radioligand for PET imaging and radioligand therapy represents a non-invasive alternative, enabling real-time monitoring of target expression and offering a pathway to personalized treatment. Methods: Radiosynthesis of [⁶⁸Ga]Ga-DOTA-EMP100 was performed using a GMP-certified ⁶⁸Ge/⁶⁸Ga generator connected to an automated synthesis module. The radiopharmaceutical production was optimized by scaling down the amount of DOTA-EMP-100 from 50 to 20 μg. Synthesis efficiency and release criteria were assessed according to Ph. Eur. for all the final products by evaluating radiochemical yield (RY%), radiochemical purity, presence of free gallium (by Radio-UV-HPLC) and gallium colloids (by Radio-TLC), molar activity (Am), chemical purity, pH, and LAL test results. Results: An optimized formulation of [⁶⁸Ga]Ga-DOTA-EMP-100, using 40 μg of precursor, provided the best outcome in terms of radiochemical performance. Process validation across three independent productions confirmed a consistent radiochemical yield of 64.5% ± 0.5, high radiochemical purity (>99.99%), and a molar activity of 53.41 GBq/µmol ± 0.8. Conclusions: [⁶⁸Ga]Ga-DOTA-EMP-100 was successfully synthesized with high purity and reproducibility, supporting its potential for multi-dose application in clinical PET imaging and targeted radioligand therapy. Full article

The purpose of this paper is to develop sustainable bio-colored healthcare cotton fabrics using chitosan/pectin layer-by-layer coatings enriched with strawberry pomace extract. Ultrasound-assisted extraction of bioactive compounds from strawberry pomace was optimized using a Box–Behnken experimental design to maximize the total polyphenol content (29.6 mg GAE/g DW). HPLC analysis confirmed the presence and quantity of anthocyanins in the extract obtained under optimized conditions (time: 37 min, ethanol concentration: 48.4%, liquid-to-solid ratio: 40.4 mL/g). This extract was used to enrich chitosan/pectin coatings, and applied onto cotton fabric using a layer-by-layer technique. Among the fabrics with 0, 4, 8, and 12 bilayers of chitosan/pectin coating enriched with extract, the 12-bilayer coated fabric exhibited the best bioactivity: 98.4% antioxidant activity, outstanding antibacterial efficacy, and the highest release of extract over 24 h. The last two properties showed a strong linear correlation with the number of bilayers, adsorbed extract, and weight gain. In vitro cytotoxicity testing proved the non-cytotoxic nature of 12-bilayer fabric extract. Additionally, the performed 12-bilayer coating imparted a natural reddish-brown color, high color strength (K/S = 1.45), and excellent UV protection (UPF 79.4), offering a sustainable, multifunctional approach for obtaining bio-colored cotton fabrics suited for wound dressing and other healthcare applications. Full article

A new type of household/therapeutic air freshener is proposed, in which beneficial components are released from compositions containing plant raw materials through induction heating under an alternating-frequency electromagnetic field. The composition is heated by metal elements (e.g., pieces of metal foil) included in its composition. The advantage of the proposed air freshener is the possibility of using a wide range of plant raw materials without prior additional processing. Another advantage of this air freshener is the possibility of controlling it via a smartphone, which is in line with the concept of a ‘smart home.’ The proposed approach bypasses labour-intensive production of simple oils, reduces the product cost, and expands the number of plants (helpful for small-scale cultivation in countries such as Kazakhstan). At the same time, however, it remains possible to use traditional compositions based on industrially produced aromatic oils. Specific examples of the implementation of the proposed method are presented. Prospects include programme-controlled emission of odours from polymer matrices, Internet of Things applications, implementation of sound–visual effects (colour–aroma–music), and even integration with neuromorphic materials. Full article

Diabetes mellitus is a serious public health problem, mainly due to the difficulty in healing chronic wounds, which present an inflammatory response for long periods of time and are more vulnerable to infections. Hydrogels are a promising therapeutic solution due to their biocompatibility, biodegradability, and ability to allow controlled release of therapeutic agents. The addition of bioactive glasses doped with therapeutic ions to hydrogels can also provide specific biological responses to the system and thus improve tissue regeneration. In this study, a hydrogel based on carboxymethylcellulose and polyethylene glycol with different degrees of crosslinking and enriched with 10% by weight of CeO₂-doped Bioglass 45S5 was developed. Structural, morphological, mechanical, and biological characterizations were performed on bioactive glass, hydrogels, and hydrogels enriched with bioactive glass. Structural analyses confirmed the preservation of the typical amorphous structure of Bioglass 45S5, even after the incorporation of 5% molar CeO₂, as well as the effectiveness of the polymer matrix crosslinking process. Structural analyses demonstrated the preservation of the typical amorphous structure of Bioglass 45S5, even after the incorporation of 5 mol% CeO₂, as well as the effectiveness of the polymer matrix cross-linking process. The hydrogels exhibited distinct behaviours in terms of water absorption and degradation, showing that the sample with the lowest concentration of crosslinkers and bioactive glass allowed for a higher expansion rate and a higher degradation rate. The hydrogel with 10 wt% BG did not compromise cell viability and showed structural integrity after being subjected to cyclic flexible deformations, indicating its safety and suitability for use in tissue engineering. Full article

Background/Objectives: This study explores the integration of Design of Experiments (DoE) with Physiologically Based Biopharmaceutics Modeling (PBBM) to streamline the development of extended-release (XR) formulations. Using donepezil (DPZ) as a model drug, we developed an optimized XR formulation exhibiting a dissolution profile comparable to the reference product, Aricept^® (Eisai GmbH, Frankfurt, Germany). Methods: A Box–Behnken experimental design was applied to systematically evaluate how formulation variables—HPMC 100, HPMC 4000, and NaCMC—affect drug release kinetics, tablet hydration, and erosion. This strategy enabled the identification of optimal excipient concentrations with minimal experimental effort. Results: The in vitro dissolution data were then integrated into a PBBM framework to simulate drug release and pharmacokinetics, enabling virtual bioequivalence (VBE) assessments. The combined approach provided robust predictive insights into formulation performance, substantially reducing reliance on resource-intensive in vivo studies. Beyond its successful application with DPZ, this integrated methodology offers a scalable and generalizable strategy for efficiently developing bioequivalent XR formulations for various clinically relevant drugs. Conclusions: Our findings highlight the importance of leveraging advanced statistical methods and in silico modeling to overcome contemporary pharmaceutical development challenges, paving the way for innovative, cost-effective solutions that significantly accelerate time-to-market. Full article

Background/Objectives: To analyze the behavior and release of bisphenol A (BPA) in the saliva of patients wearing clear aligners, and to evaluate differences in BPA levels between patients treated with aligners from the market-leading brand and those treated with in-office aligners. For the in-office group, 0.762 mm (0.30”) thick thermoforming sheets from Ortolan^® were used to fabricate the aligners. Methods: Patients about to begin orthodontic treatment with clear aligners in the Master’s degree program in Orthodontics at the University of Valencia were recruited for this prospective observational study. Patients were divided into two groups based on the type of aligners: The Invisalign^® group and the In-Office aligner group. Four saliva samples were taken from each patient at different times during treatment, with a one-week follow-up. The samples were stored at −80 °C and analyzed using mass spectrometry. Results: A total of 24 patients were included in the study, with 12 patients in each group. A statistically significant difference was found between baseline BPA levels and the increase observed half an hour after bonding the attachments. After a week, values returned to pre-treatment levels. Furthermore, BPA levels changed significantly during the follow-up period and were similar in both groups. Conclusions: An immediate increase was observed when the attachments were bonded with both treatments; however, differentiation from the ‘peak’ and recovery to baseline values was faster in patients treated with In-Office aligners. In those treated with Invisalign^®, after the placement of the aligners, values recorded were not significantly different from baseline, nor from the previous peak. Full article

In the Yangquan coal mining region, China, muffled blasting sounds commonly occur in mine surrounding rocks resulting from instantaneous energy release following the elastic deformation of overlying brittle rock layers; they are related to fracture development. Although these events rarely cause immediate hazards, their acoustic signatures contain critical information about cumulative rock damage. Currently, conventional monitoring of muffled blasting sounds and surrounding rock stability relies on microseismic systems and on-site sampling techniques. However, these methods exhibit low identification efficiency for muffled blasting events, poor real-time performance, and strong subjectivity arising from manual signal interpretation and empirical threshold setting. This article proposes retentive depthwise gated network (RDGNet). By combining retentive network sequence modeling, depthwise separable convolution, and a gated fusion mechanism, RDGNet enables multimodal feature extraction and the fusion of acoustic emission sequences and audio Mel spectrograms, supporting real-time muffled blasting sound recognition and lithology classification. Results confirm model robustness under noisy and multisource mixed-signal conditions (overall accuracy: 92.12%, area under the curve: 0.985, and Macro F1: 0.931). This work provides an efficient approach for intelligent monitoring of coal mine rock stability and can be extended to safety assessments in underground engineering, advancing the mining industry toward preventive management. Full article

This study addresses the fabrication challenges associated with producing diverse geometries for concrete dry connections, particularly regarding cost, time, and geometric limitations. The research investigates methods for fabricating precise, rebar-free dry connections in concrete, focusing on stamping and green-state computer numerical control (CNC) milling. These methods are evaluated using metrics such as dimensional accuracy, tool abrasion, and energy consumption. In the stamping process, a design of experiments (DOE) approach varied water content, concrete age, stamping load, and operational factors (vibration and formwork) across cone, truncated cone, truncated pyramid, and pyramid geometries. An optimal age range of 90 to 105 min, within a broader operational window of 90 to 120 min, was identified. Geometry-specific exceptions, such as approximately 68 min for the truncated cone and 130 min for the pyramid, were attributed to interactions between shape and age rather than deviations from general guidance. Within the tested parameters, water fraction primarily influenced lateral geometric error (diameter or width), while age most significantly affected vertical error. For green-state milling, both extrusion- and shotcrete-printed stock were machined at 90 min, 1 day, and 1 week. From 90 min to 1 week, the total milling energy increased on average by about 35%, and at one week end-face (head) passes caused substantially higher tool wear, with mean circumference losses of about 3.2 mm for head engagement and about 1.0 mm for side passes. Tool abrasion and energy demand increased with curing time, and extrusion required marginally more energy at equivalent ages. Milling was conducted in two engagement modes: side (flank) and end-face (head), which were evaluated separately. End-face engagement resulted in substantially greater tool abrasion than side passes, providing a clear explanation for tolerance drift in final joint geometries. Additionally, soil-based forming, which involves imprinting the stamp into soft, oil-treated fine sand to create a reversible mold, produced high-fidelity replicas with clean release for intricate patterns. This approach offers a practical alternative where friction and demolding constraints limit the effectiveness of direct stamping. Full article

HER2 (human epidermal growth factor receptor 2) is a receptor tyrosine kinase which is overexpressed in ~20% of patients with oesophagogastric adenocarcinoma (EGA). HER2 represents a targetable transmembrane glycoprotein receptor of the epidermal growth factor receptor (EGFR) family, which plays a crucial role in cell proliferation, survival, and differentiation. HER2 significantly influences the tumour microenvironment (TME) through various mechanisms, creating a niche that supports tumour progression, immune evasion, and therapeutic resistance. In HER2-positive EGA, aberrant signalling pathways, such as PI3K/AKT and MAPK/ERK, enhance tumour cell survival and proliferation, whilst upregulation of angiogenic factors like VEGF fosters vascularization, meeting a tumour’s metabolic demands and facilitating its proliferation. HER2 also modulates the tumour immune microenvironment (TIME) by downregulating MHC molecules and recruiting immunosuppressive cells, including regulatory T-cells (T-reg) and tumour-associated macrophages (TAMs), which release cytokines that further inhibit anti-tumour immune responses. Together, these factors foster a pro-inflammatory, immunosuppressive microenvironment that underpins resistance to HER2-targeted therapies. As more HER2-directed treatments become available, such as trastuzumab–deruxtecan (T-DXd), gaining a deeper understanding of the multifaceted influence of HER2 on the TME in EGA will be crucial for the development of improved targeted treatments that can overcome these challenges and lead to advancements in targeted treatment for HER2-overexpressing EGA. This review provides a comprehensive overview of the impact of HER2 on the TME in EGA and highlights the challenge it represents as well as the opportunity for novel therapeutic development and the implications for patients in terms of clinicopathological outcomes. Full article

Parkinson’s disease (PD) is frequently complicated by dysphagia, undermining timely and reliable oral dopaminergic medication. Levodopa’s short half-life and delayed gastric emptying in advanced PD result in inconsistent absorption, delayed “ON” periods, and challenges to adherence. Orally disintegrating tablets (ODTs) dissolve without water and can mitigate swallowing limitations. Research indicates that selegiline ODT achieves a faster time to peak and higher relative bioavailability via partial buccal absorption, whereas carbidopa/levodopa ODTs are bioequivalent to immediate release tablets (with similar AUC/C_max and approximately 1 h T_max) without consistent motor advantages but with higher patient acceptability. This review synthesizes the clinical burden of dysphagia in PD, pharmacokinetic constraints of current formulations, and the reasons for ODTs. We highlight 3D printing as a route to personalized, dysphagia friendly therapy, which enables dose individualization, polypills, engineered disintegration or release, and point-of-care production. Feasibility studies underscore stability considerations such as carbidopa, throughput and regulatory requirements (QbD/GMP), and bioequivalence information. We outline priorities to integrate 3D printed ODTs into PD care, aligning formulation, pharmacokinetics, and human factors to improve adherence and clinical outcomes. Full article

Agriculture faces growing pressure to optimize water use, particularly in woody perennial crops where irrigation systems are installed once and seldom redesigned despite changes in canopy structure, soil conditions, or plant mortality. Such static layouts may accumulate inefficiencies over time. This study introduces a decision support system (DSS) that evaluates the hydraulic adequacy of existing irrigation systems using two new concepts: the Resource Overutilization Ratio (ROR) and the Irrigation Ecolabel. The ROR quantifies the deviation between the actual discharge of an installed irrigation network and the theoretical discharge required from crop water needs and user-defined scheduling assumptions, while the ecolabel translates this value into an intuitive A+++–D scale inspired by EU energy labels. Crop water demand was estimated using the FAO-56 Penman–Monteith method and adjusted using canopy cover derived from UAV-based canopy height models. A vineyard case study in Galicia (Spain) serves an example to illustrate the potential of the DSS. Firstly, using a fixed canopy cover, the FAO-based workflow indicated moderate oversizing, whereas secondly, UAV-derived canopy measurements revealed substantially higher oversizing, highlighting the limitations of non-spatial or user-estimated canopy inputs. This contrast (A+ vs. D rating) illustrates the diagnostic value of integrating high-resolution geospatial information when canopy variability is present. The DSS, released as open-source software, provides a transparent and reproducible framework to help farmers, irrigation managers, and policymakers assess whether existing drip systems are hydraulically oversized and to benchmark system performance across fields or management scenarios. Rather than serving as an irrigation scheduler, the DSS functions as a standardized diagnostic tool for identifying oversizing and supporting more efficient use of water, energy, and materials in perennial cropping systems. Full article

Background/Objectives: Hypoxic–ischemic encephalopathy (HIE) is a common neurological outcome of perinatal asphyxia, with cerebral palsy (CP) being the most severe lasting effect. Perinatal brain injury activates the immune system and induces the release of inflammatory mediators. Matrix Metalloproteinases (MMPs) play a crucial role in neuroinflammation and neurodegeneration. This study explored the potential link between MMP2 promoter polymorphisms and the development of CP in children with a history of perinatal asphyxia. Methods: We enrolled 212 patients (130 males and 82 females) with documented perinatal asphyxia, who underwent a comprehensive neurological assessment and neuroimaging, including ultrasound and magnetic resonance imaging (MRI). We genotyped the MMP2 promoter polymorphisms rs243866, rs243865, and rs243864 using real-time polymerase chain reaction. Haplotype frequencies were calculated using Haploview software. Results: As expected, patients with HIE are more likely to develop CP (p = 0.000). In a study of 104 patients who developed CP, the frequencies of the A (rs243866), T (rs243865), and G alleles (rs243864) were nearly twice as high compared to those without CP (p = 0.008, p = 0.019, and p = 0.008, respectively). Haplotype analysis supported these findings, showing that the ATG haplotype was significantly more common among patients who developed CP (p = 0.004). Additionally, in patients with MRI-confirmed brain damage, the ATG haplotype was more frequently observed (p = 0.019). Conclusions: The ATG haplotype of the MMP2 promoter may indicate a risk factor for developing cerebral palsy (CP) in patients who experience perinatal asphyxia and could serve as a potential diagnostic predictor of CP. Full article

Bone is a structurally complex and dynamic tissue that plays a crucial role in mobility and skeletal stability. However, conditions such as osteoporosis, osteoarthritis, trauma-induced fractures, infections, and malignancies often necessitate the use of orthopedic and dental implants. Despite significant progress in implant biomaterials, challenges such as bacterial infection, inflammation, and loosening continue to compromise implant longevity, frequently leading to revision surgeries and extended recovery times. Smart coatings have emerged as a next-generation solution to these problems by providing on-demand, localized therapeutic responses to microenvironmental changes around implants and promoting bone regeneration. Such coatings can minimize antibiotic resistance by enabling controlled, stimulus-triggered drug release. Although the idea of using pH-sensitivity as a tool to make smart coatings is not a new thought, there are no options currently good enough to enter clinical studies. This review provides a comprehensive overview of recent advances in pH-sensitive polymers, hybrid composites, porous architectures, and bioactive linkers designed to dynamically respond to pathological pH variations at implant sites. By investigating the mechanisms of action, antibacterial and anti-inflammatory effects, and roles in bone regeneration, it is shown that the ability to provide time-dependent drug release for both short-term and long-term infections, as well as keeping the environment welcoming to the bone cell growth and replacement, is not an easy goal to reach, even with a fully biocompatable, non-toxic, and semi-biodegradable (one that releases the drug, but does not fade away) coating material compound. Reviewing all available options, including their functions and failures, finally, emerging trends, translational barriers, and future opportunities for clinical implementation are highlighted, underscoring the transformative potential of bioresponsive coatings in orthopedic and dental implant technologies. Full article

Since it is expensive and takes considerable time to synthesize a new drug or improve an old one, a drug carrier can be used instead for control and targeted release of the drug. In this study, hydrogel beads were used as drug carriers for the controlled release of doxorubicin hydrochloride. Aiming to incorporate doxorubicin hydrochloride into hydrogel, various metal crosslinked alginate beads were prepared. Doxorubicin hydrochloride was incorporated by adsorption into the beads and studied the factors affecting the adsorption of drug onto the hydrogel beads. The results showed that ferric crosslinked alginate (Fe(III)–Alg) and stannous crosslinked alginate (Sn-Alg) hydrogel beads had a better adsorption percentage which was more than 21%. The amount of hydrogel, time, drug concentration, and pH of the solution all influenced the adsorption percentage. Hence, the adsorption was the best at neutral pH after 24 h when 100 mg of Fe(III)–Alg was added to the drug. Moreover, the release of the drug at different body simulation pH was investigated. The time and pH of the solution influenced the drug release where maximum drug release percentage was 82.822% after 25 h when the solution’s pH was 1.52. This system is assumed to follow the Higuchi kinetic release model. Full article