Search Results (10,455)

Type 2 diabetes mellitus (T2D) is a major and growing global health burden that is associated with substantial cardiovascular, renal, and metabolic complications and is increasingly recognized as a systemic disorder involving multiple organs, particularly the liver. Metabolic dysfunction-associated steatotic liver disease (MASLD) affects more than half of individuals with T2D, and the two conditions have a bidirectional relationship: T2D promotes the development and progression of MASLD, including advanced fibrosis and increased liver-related mortality, while MASLD worsens insulin resistance and metabolic control, favoring the onset of T2D. In this context, the liver is increasingly viewed not only as a metabolic organ but also as an endocrine one, secreting hepatokines that act on distant tissues to regulate insulin sensitivity, inflammation, glucose metabolism, and lipid homeostasis. Through these actions, hepatokines are thought to represent one of the mechanistic links between MASLD and T2D. This narrative review summarizes current evidence on several of the most extensively studied hepatokines, including fibroblast growth factor 21, fetuin-A, fetuin-B, leukocyte cell-derived chemotaxin-2, selenoprotein P, angiopoietin-like proteins, and retinol-binding protein 4. As a distinctive feature, the review also discusses emerging pharmacological strategies targeting hepatokine pathways and evaluates how commonly used antidiabetic therapies may modulate hepatokine secretion. Full article

Halogenated ketones (HKs) and aldehydes (HAs) are prevalent emerging disinfection by-products (DBPs) threatening drinking water safety. Although pre-oxidation and coagulation are widely applied in drinking water treatment, critical knowledge gaps remain regarding the precursor-specific effects of KMnO₄ and O₃ pre-oxidation on chlorinated ketone/aldehyde formation potential, as well as the interaction between coagulation optimization and DBP yields. This study systematically investigates the effects of KMnO₄/O₃ pre-oxidation and optimized coagulation on the formation potential (FP) of 1,1-dichloroacetone (1,1-DCP), 1,1,1-trichloroacetone (1,1,1-TCP), and chloral hydrate (CH) from four typical precursors (fulvic acid, citric acid, L-threonine, L-asparagine). Batch pre-oxidation and chlorination experiments were performed; three-dimensional excitation–emission matrix (3D-EEM) fluorescence spectroscopy was used to characterize organic-precursor structural changes, while gas chromatography–mass spectrometry (GC-MS) was adopted to quantify target DBPs. Results show that KMnO₄ and O₃ pre-oxidation significantly promote (p < 0.05) DBP formation from fulvic acid but exert precursor-specific effects on small-molecule precursors: KMnO₄ enhances CKs while inhibiting CH from amino acids, and O₃ suppresses all three DBPs from small-molecule precursors. Coagulation pretreatment weakly inhibits DBP formation (reduction rate < 20%) by removing partial precursors. This study clarifies the mechanism of process-driven DBP modulation and provides a theoretical basis for optimizing water treatment processes to control chlorinated ketone/aldehyde DBPs. Full article

Conceptual metaphors structure abstract domains through concrete, perceptual, affective, or bodily experience, but they are accessed through metaphorical expressions. Controlled experimental work requires normed materials characterizing expressions, not only the conceptual mappings they instantiate. This is particularly relevant for European Portuguese, where research on metaphors lacks multidimensional normative resources for everyday metaphorical expressions. We introduce ME6D-PT, a database of 213 European Portuguese metaphorical expressions instantiating 20 conceptual metaphors and accompanied by English counterparts. Portuguese native speakers rated the expressions on six dimensions relevant to language processing: familiarity, concreteness, valence, arousal, embodiment, and transparency. Items were presented individually without context, organized in seven lists in a within-subject design. Aggregated item-level reliability ranged from moderate to excellent across dimensions. Descriptive results showed that the expressions were generally familiar and transparent while varying substantially in concreteness, valence, arousal, and embodiment. Further analyses showed strong positive associations among familiarity, transparency, and concreteness, whereas embodiment was weakly related to experiential and semantic dimensions. Exploratory quadratic models revealed nonlinear patterns involving valence, including the expected U-shaped association with arousal, and a decelerating positive association between transparency and familiarity. ME6D-PT provides a controlled resource for stimulus selection and research on metaphors, abstract language, embodiment, and future cross-linguistic research. Full article

The aim of this study was to investigate the effect of 3D printing parameters on the surface topography and surface wettability properties of PET-G samples intended for potential tribological applications. Surfaces produced with varying fill rates and two layer heights were examined using focus variation microscopy and water contact angle measurements. The statistical analysis showed that the infill percentage has a significant influence on wettability, but did not reveal a significant influence of layer height on the observed contact angles. The results showed that surface characteristics are strongly dependent on process conditions, and the relationships between roughness parameters and wettability are mostly nonlinear. The parameters Są and Sq tended to decrease the contact angle as roughness increased, whereas Sp, Sv, and Sz showed no clear relationship with contact angle values. In contrast, Ssk and Sku showed a positive, linear correlation with the contact angle, indicating an important role of the statistical shape of the surface height distribution. The results confirm that the functional properties of additively manufactured surfaces depend not only on the amplitude of surface irregularities but also on their spatial organization and asymmetry. Full article

Due to the high saturated fat content, increasing cost, and supply instability of cocoa butter (CB), the development of structured lipid systems with improved nutritional profiles and suitable technological functionality has received increasing attention. This study aimed to optimize a coriander seed oil-based oleogel (COG) using a D-optimal mixture design and evaluate its potential as a structured lipid phase for dark chocolate formulation. The effects of coriander seed oil, monoglycerides, candelilla wax, xanthan gum, and polyglycerol polyricinoleate (PGPR) on the physicochemical, rheological, and mechanical properties of the oleogel were investigated. The optimized COG formulation exhibited a maximum crystallization temperature of 30.159 °C, enhanced viscoelastic characteristics, and a stable three-dimensional lipid network. The optimized oleogel retained substantial amounts of bioactive compounds, including α-tocopherol, phenolic compounds, flavonoids, and linalool, together with antioxidant activity, and showed a lower accumulation of primary oxidation products during storage than the non-structured oil. Dark chocolate prepared with the optimized oleogel (COG-Ch) was evaluated in comparison with cocoa butter-based chocolate (CB-Ch) in terms of thermal behavior, rheological properties, texture, and storage-related whitening changes. Although COG-Ch showed comparable onset and maximum melting temperatures and a lower increase in whiteness index during storage at 35 °C, significant differences remained in melting enthalpy, hardness, and several rheological parameters compared with CB-Ch. These differences reflect the distinct lipid organization and crystallization behavior of the oleogel system. Therefore, the developed coriander seed oil oleogel should be considered a promising structured lipid phase for chocolate applications rather than a complete functional equivalent of cocoa butter. Further investigations involving sensory evaluation, crystal polymorphism analysis, microstructural characterization, and comprehensive oxidative stability assessment are required to determine its broader applicability in chocolate manufacturing. Full article

Rare surviving examples of late eighteenth-century French dress are exceptional. The robe à la circassienne examined in this study is preserved in an unusually intact state, likely due to its small size, which limited its suitability for later wearers, and the rapid shift in fashion that further reduced incentives for alteration or reuse. Discrepancies between the garment’s present coloration, early cataloguing records, and a non-matching reproduction petticoat prompted an investigation into its original appearance. The dress features a ground fabric woven with a pink warp and white weft, accented by vertical multicolored stripes. Organic colorants were analyzed using liquid chromatography–diode array detection–quadrupole time-of-flight mass spectrometry (LC-DAD-qToF-MS), and elemental composition was determined by X-ray fluorescence (XRF) spectroscopy. The dark pink stripe contained safflower (Carthamus tinctorius), a highly fugitive dye. The blue and green stripes showed mixtures of weld (Reseda luteola), an indigoid dye (Indigofera spp.), and Brazilwood (Caesalpinia or Haematoxylum spp.), consistent with historical recipes for bronze and wood shades. Brazilwood and an orchil dye detected in the ground fabric suggest an original reddish-purple hue rather than the pale pink visible today. Arsenic found in the pink fabric and trim provides the first material evidence for the French orchil-dyeing process known as Parelle d’Auvergne. By integrating analytical results with historical dye recipes and curatorial records, this study proposes a hypothesis for the garment’s original appearance and demonstrates how combined scientific and historical approaches deepen our understanding of fragile textile artifacts and the factors that shaped their creation and survival. Full article

Considering the limited information available on the use of elephant grass juice (EGJ) as a liquid co-substrate, this study aimed to evaluate its feasibility and biogas production potential for anaerobic co-digestion with dairy cattle wastewater (DCW), focusing on substrate ratios and reactor operating conditions. Initially, batch tests were conducted at different temperatures to evaluate the effects of varying substrate mixture ratios (EGJ/DCW). In the reactor with 20% EGJ/80% DCW at 39 °C, a biogas volume of 414.35 mL was generated, which was considerably higher than that in the test at 25 °C, where 258.7 mL was generated over the 30-day experimental period. Greater efficiency in organic matter removal and other analyzed parameters was also observed under these conditions. The best configuration was selected for the semi-continuous tests. To this end, an Upflow Anaerobic Sludge Blanket (UASB) reactor was operated with hydraulic retention times of 10, 6, 2, and 1 d and volumetric organic loading rates of 2.06, 3.39, 10.40, and 20.70 kg VS m⁻³ d⁻¹, respectively. Volatile solids were removed by 29–58%, with biogas yields ranging from 0.78 to 2.28 m³ m⁻³ d⁻¹ and a maximum CH₄ concentration of 72% (v/v). The co-digestion of the analyzed agricultural waste substrates proved to be a promising approach for bioenergy recovery. These results provide useful guidelines for optimizing co-digestion systems, improving reactor performance, and waste treatment processes. Full article

Endometriosis is a chronic estrogen-dependent systemic inflammatory disorder characterized by ectopic implantation of endometrial-like tissue, primarily on the ovaries, pelvic peritoneum, and bowel. According to the World Health Organization (WHO) estimate updated in 2025, endometriosis affects approximately 10% (about 190 million) of reproductive-age women worldwide and is a major contributor to chronic pelvic pain, dysmenorrhea, dyspareunia, and infertility. Standard medical therapies focus on ovarian suppression, which alleviates symptoms but precludes conception and carries significant metabolic and skeletal adverse effects. Recent multi-omics research has raised interest in the gut microbiome and the estrobolome, defined as the microbial gene repertoire involved in estrogen metabolism, as potential modulators of systemic estrogen exposure and immune homeostasis. Altered microbiota composition and microbial β-glucuronidase activity may influence enterohepatic estrogen recirculation; however, endometriosis-specific evidence is predominantly associative or preclinical and does not establish a causal pathway. Dysbiosis and increased bacterial β-glucuronidase activity promote enterohepatic recirculation of estrogens, contributing to hyperestrogenism and ectopic lesion proliferation. Concurrently, oxidative stress, peritoneal inflammation, aberrant macrophage polarization, and neoangiogenesis sustain lesion survival and contribute to chronic pelvic pain. This comprehensive review synthesizes mechanistic, preclinical, and clinical evidence regarding microbiome-targeted interventions and nutritional compounds, including probiotics, prebiotics, N-acetyl cysteine (NAC), curcumin, resveratrol, epigallocatechin gallate (EGCG), omega-3 polyunsaturated fatty acids (PUFAs), and vitamin D, in modulating the estrobolome, immune responses, and oxidative microenvironment in endometriosis. We further discuss dietary patterns, bioavailability challenges, and the potential of precision nutrition to optimize reproductive outcomes. These approaches may be considered complementary or investigational adjuncts; current evidence is insufficient to demonstrate disease modification or improvements in spontaneous pregnancy, assisted reproductive technology (ART) outcomes, or live birth. Here, “fertility-sparing” denotes the absence of intentional ovulation suppression rather than proven fertility enhancement. Full article

Material extrusion 3D printing has been widely used in industrial, educational and residential environments. However, the associated emissions and exposure health impacts need to be evaluated, especially for the new and emerging filament materials. This study characterized particle and chemical emissions from 3D printing using five different metal composite filaments, which contain over 90% (by weight) of metal powder blended with polymer binders. The emission characterization was conducted using an exposure chamber following a standard testing method. Real-time particle measurements showed that particle emission rates ranged from 8 × 10⁹ to 2 × 10¹¹ particles/h for particle number and 200 to 1400 µg/h for particle mass. Over 98% of the emitted particles were smaller than 1 µm, which poses an inhalation hazard. Inductively coupled plasma–mass spectrometry analysis detected manganese, copper, zinc, and selenium in emitted particles from all filaments. However, metal powder in raw filaments tended not to be transferred into particle emissions, resulting in the total metals (and metalloids) accounting for 0.07% to 0.95% of emitted particle mass. Sorbent tube sampling and analytical analyses showed various volatile organic compounds emitted during printing, including hydrocarbons, alcohols, aldehydes, and aromatic compounds. Overall, metal composite filaments generated lower levels of volatile organic compounds (VOCs) compared to thermoplastic polymer filaments; in addition, the emitted VOC compositions differed. Organic chemicals associated with metal composite filament emissions included formaldehyde, benzaldehyde, acetaldehyde, naphthalene, and trimethylbenzene, exposure to which may cause irritations or other adverse health impacts. This study estimated personal exposure to hazardous components assuming a person is close to the printer with low ventilation to represent an acute worst-case exposure scenario. Modeled personal exposure to emissions showed potential exceedances of exposure to fine (PM_2.5) and coarse (PM₁₀) particulate matter, arsenic, manganese, formaldehyde, caprolactam, acetaldehyde, and naphthalene compared to reference levels. A modeled office room with ventilation showed reduced exposure levels by up to two orders of magnitude, assuming the same emission source. Users can avoid close proximity to an operating printer and increase dilution through larger room volumes and higher air change rates to reduce potential inhalation exposures at given printing conditions. Full article

Modern scientific and technological developments are driving major advances in drug research and development. This narrative review, based on a structured search of PubMed, Scopus, and Web of Science (2018–2026), examines how artificial intelligence (AI) and machine learning (ML) are accelerating a historically prolonged and expensive process, alongside pharmacogenomics, organ-on-a-chip systems, three-dimensional (3D) bioprinting, and nanotechnology. In benchmark studies, deep learning techniques have achieved an area under the receiver operating characteristic curve (AUROC) of over 0.85 for a subset of absorption, distribution, metabolism, excretion, and toxicity (ADMET) endpoints. AI-powered models show promising, albeit platform-dependent, accuracy in predicting candidate drug properties. Pharmacogenomics enables personalized medicine by tailoring therapies according to patients’ genetic profiles, whereas organ-on-a-chip systems and 3D bioprinting provide physiologically relevant human tissue models for preclinical evaluation. In a blinded benchmark study, the Emulate Liver-Chip showed 87% sensitivity and 100% specificity for drug-induced liver injury, outperforming animal models in that specific comparison. Nanotechnology is advancing drug delivery through the use of nanoparticle systems, such as Doxil^® and Onpattro^®. Obstacles remain, including regulatory constraints, ethical considerations, data quality limitations, and the need for stronger validation, although ongoing funding, interdisciplinary collaboration, and evolving regulatory frameworks may support further development. Overall, these technologies show meaningful potential to shorten development time and improve treatment safety, although further prospective validation is required before realizing this potential at scale. Full article

Plants are continuously exposed to volatile organic compounds (VOCs) emitted by neighbors. Although the mechanisms governing VOC uptake and metabolism remain unclear, cytochrome P450 monooxygenases (CYP450s) are thought to participate in the detoxification and metabolic conversion of absorbed VOCs. Data from previously conducted cDNA microarray transcriptomic profiling in potato exposed to French marigold essential oil (FM-EO) was here used to filter differentially expressed sequences, and identified 54 unique CYP450 transcripts. Among the 10 most highly expressed sequences, two CYP81D1-like (81D1-1 and 81D1-2) and one CYP81D11-like (81D11-1) transcripts were found. RT-qPCR confirmed their strong induction within 8 h of volatile exposure. Comprehensive bioinformatics identified the most highly induced 81D1-1 gene as a CYP450 containing a predicted N-terminal hydrophobic signal or membrane-anchor region, the conserved heme-binding signature motif, and regulatory elements associated with oxidative stress responses. The other 81D11-1 gene, exhibiting a comparable expression level, was annotated only as a heme-binding protein but possessed seven distinct cis-regulatory elements, suggesting high transcriptional plasticity. Machine learning predictions assigned the highest interaction probability to (Z)-β-ocimene, whereas structure-based docking yielded the most favorable mean score for piperitone. This study provides the first characterization of the potato CYP450 superfamily in the context of volatile-mediated plant–plant interactions and identifies two CYP81D members as strong candidates for the oxidative metabolism of absorbed VOCs. The results support a proposed detoxification pathway in which CYP81-mediated oxidation precedes glutathione conjugation and intracellular sequestration of VOCs. These candidate genes provide a valuable foundation for future functional studies and may facilitate the development of sustainable crop protection strategies based on volatile-mediated plant defense. Full article

Background and Objectives: Intra-corporeal esophagojejunostomy after totally laparoscopic total gastrectomy (TLTG) remains one of the most technically demanding steps of minimally invasive gastric surgery. The management of the common entry hole in linear stapler-based reconstructions still relies on advanced intra-corporeal suturing. The sutureless L-shape esophagojejunostomy with endoscopic assistance (SLEJ) technique, previously described by our group, was developed to overcome this limitation by combining an L-shaped linear stapler configuration with intraoperative endoscopic quality control. Building upon our initial results on the perioperative feasibility of the technique, the present study aimed to evaluate its intermediate-term anastomotic, functional, and oncological outcomes. Materials and Methods: Patients who underwent TLTG with D2 lymph node dissection and SLEJ reconstruction for gastric cancer between July 2024 and January 2026 were evaluated. Eligibility criteria included a minimum postoperative follow-up of six months, clinical and endoscopic surveillance, and complete contrast-enhanced thoraco-abdominopelvic computed tomography records. Protocol-based upper gastrointestinal endoscopy was performed at six-month intervals irrespective of symptoms to objectively assess anastomotic lumen width, mucosal healing, reflux findings, and possible intraluminal recurrence. The primary endpoint was anastomosis complication-free survival (anastomotic stenosis, alkaline reflux/reflux esophagitis, marginal ulcer, bleeding due to ulceration, and intraluminal recurrence); secondary endpoints were disease-free survival (DFS), local recurrence and changes to nutritional status. Results: A total of 26 patients (18 men and 8 women; mean age 59.0 ± 7.8 years) were analyzed. Anastomotic stricture developed in two patients and was successfully managed with two sessions of endoscopic balloon dilation in both. Similarly, alkaline reflux was documented in two additional patients and resolved under medical treatment. None of the patients required surgical revision. The mean ACFS follow-up duration was 12.42 months with ACFS rates of 92.3% at six months and 81.1% from the twelfth month onward. No local anastomotic recurrence was detected during follow-up. Disease progression occurred in four patients (15.4%), presenting as distant organ metastasis (n = 2) or peritoneal carcinomatosis (n = 2). The mean DFS follow-up duration was 12.62 ± 6.18 months, and the twelve-month OS and DFS rates were 82.1% and 84.0%. Postoperative body weight decreased significantly compared with preoperative values (76.69 ± 15.59 kg vs. 63.23 ± 10.55 kg; p < 0.001). A significant decrease was observed in the mean SMI between the preoperative and follow-up assessments (p < 0.001). The mean preoperative SMI was 49.90 ± 9.04 cm²/m², compared with 44.53 ± 7.98 cm²/m² at follow-up. No statistically significant changes were observed between the preoperative and follow-up periods for serum albumin and PNI variables (p = 0.703 and p = 0.970). Conclusions: The present intermediate-term analysis suggests that the SLEJ technique is feasible and associated with acceptable intermediate-term anastomotic, functional, and oncological outcomes in this preliminary single-center cohort. By standardizing common entry-hole management without intra-corporeal suturing and incorporating intraoperative endoscopic quality control, the technique offers a feasible alternative to established linear stapler-based reconstructions. Full article

Telecommunications infrastructures are increasingly cloud-native, multi-vendor, and mission-critical environments, integrating 5G core networks, virtualized network functions, and software-defined infrastructure that expand the operational attack surface and make robust security architecture a core engineering requirement. Zero-Trust Architecture (ZTA) has emerged as the leading technical paradigm for securing these environments through continuous authentication and policy-based access control; however, technical Zero-Trust controls alone do not guarantee successful deployment, and large-scale deployment introduces significant socio-technical and governance challenges that existing engineering-focused frameworks only partially address. This study makes two contributions: it provides longitudinal evidence on the impact of ZTA on organizational trust using an extended Technology Acceptance Model (TAM) that incorporates Perceived Trust, and it proposes a Proactive Trust Management Playbook (PTMP) for telecommunications infrastructure organizations that complements technical Zero-Trust deployments through organizational governance. The study draws on a five-wave repeated cross-sectional longitudinal case study conducted between 2020 and 2023 in a multinational telecommunications infrastructure organization. The five waves span three organizational phases, enabling an assessment of employee perceptions of usefulness, ease of use, and trust before and after ZTA deployment and following a structured governance intervention. The findings reveal a substantial decline in the composite TAM index following ZTA implementation (−24%, Cohen’s d = 1.12), with no meaningful spontaneous recovery over time (d = 0.08). A structured Communication Campaign was associated with a partial but incomplete recovery (d approximately 0.47), indicating that trust erosion under ZTA is measurable and suggesting that trust recovery is shaped more by governance interventions than by technological adaptation alone. The proposed PTMP complements technical Zero-Trust architectures by strengthening organizational trust and governance in telecommunications infrastructure environments. Full article

Cancer remains a major global health challenge, and the limitations of conventional therapies, including systemic toxicity, drug resistance, and poor tumor selectivity, continue to drive the development of advanced nanomedicine strategies. In this context, nanocarriers offer promising opportunities to improve pharmacokinetics, enhance tumor accumulation, and enable controlled or stimuli-responsive drug release. Among them, inorganic nanoparticles (NPs) have gained considerable attention because of their structural stability, tunable surface chemistry, and multifunctional capabilities. Their performance depends on a structure–property–function relationship in which composition, morphology, porosity, degradability, and surface characteristics strongly influence interactions at the nano–bio interface. This review examines the main classes of nanoplatforms currently explored for cancer therapy, including inorganic, polymeric, lipid-based, and hybrid organic–inorganic systems. Particular attention is given to the trade-offs that define each platform in terms of loading capacity, biodegradability, multifunctionality, and translational potential. The discussion also highlights the role of predictive biological models, emphasizing that 3D spheroids, organoids, and organ-on-chip systems provide more realistic insights than conventional 2D assays for evaluating tumor penetration and microenvironment-responsive delivery. In addition, the review considers emerging directions in AI-guided nanoparticle engineerization design and natural-compound-based nanomedicines, both of which are expanding the therapeutic landscape. Overall, the field is moving toward more integrated, application-specific, and clinically translatable nanomedicine platforms capable of addressing the complex biological barriers of cancer treatment. Full article

Suspended particles are key components of aquatic ecosystems that modulate the biogeochemical processes of natural waters. The filter feeder Daphnia magna can alter suspended particle characteristics and aquatic habitats, while habitat variations in turn affect its growth and reproduction. This study primarily investigated the impacts of D. magna on the concentration and size distribution of suspended particles, and explored its particle size selectivity. Three particle types, namely kaolinite (KN), montmorillonite (MN) and natural particles (NP), were adopted for experiments, and natural particles were further divided into three size fractions (<150 μm, <96 μm, <75 μm). The results demonstrated that D. magna significantly reduced suspended particle concentrations via ingestion, with the most prominent effect observed within the initial three hours of experimentation, verifying its practical value for wastewater remediation. Though classified as a non-selective filter feeder, D. magna exhibited distinct particle size selectivity for identical substances. Fine particles (<8 μm) presented higher bioavailability and were preferentially ingested by D. magna. Additionally, the regulatory effects of D. magna on particle size distribution were closely associated with its particle digestion process, which depended on inherent particle properties, including composition and organic matter content. Full article