Search Results (17,155)

Gastric-type cervical adenocarcinoma (GCA) is a rare and aggressive subtype of cervical adenocarcinoma. Despite its clinical significance, its molecular carcinogenesis and therapeutic targets remain poorly understood. This study aimed to compare the clinicopathological, immunohistochemical, and molecular profiles of GCA and usual-type cervical adenocarcinoma (UCA), exploring prognostic and therapeutic biomarkers in a Japanese population. A total of 110 cervical adenocarcinoma cases, including 16 GCA and 94 UCA cases, were retrospectively analyzed for clinicopathological features, and a panel of immunohistochemical markers was assessed. Sanger sequences were performed for the KRAS, PIK3CA, and BRAF genes, and survival and clinicopathological correlations were assessed using Kaplan–Meier and Cox regression analyses. GCA was significantly associated with more aggressive features than UCA, including lymph node involvement, advanced FIGO stages, increasing recurrence rate, and poor survival status. High ARID1B expression was observed in a subset of GCA cases and correlated with worse progression-free and overall survival. Additionally, PD-L1 expression was more frequent in GCA than UCA and was associated with unfavorable prognostic factors. Conversely, UCA cases showed strong p16 expression, supporting their HPV-driven pathogenesis. Molecular profiling revealed KRAS and PIK3CA mutations in both subtypes, while BRAF mutations were identified exclusively in GCA. These findings reveal distinct clinical and molecular profiles for both tumor types and underscore ARID1B and PD-L1 as predictive prognostic and therapeutic biomarkers in GCA, implicating the use of subtype-specific treatment strategies. Full article

Background/Objectives: Cancer suffers from unresolved therapeutic challenges owing to the lack of targeted therapies and heightened recurrence risk. This study aimed to investigate the new series of hydroxamate by structurally modifying the pharmacophore of vorinostat. Methods: The present work involves the synthesis of 15 differently substituted 2H-1,2,3-triazole-based hydroxamide analogs by employing triazole ring as a cap with varied linker fragments. The compounds were evaluated for their anticancer effect, especially their anti-breast cancer response. Molecular docking and molecular dynamics simulations were conducted to examine binding interactions. Results: Results indicated that among all synthesized hybrids, the molecule VI(i) inhibits the growth of MCF-7 and A-549 cells (GI₅₀ < 10 μg/mL) in an antiproliferative assay. Compound VI(i) was also tested for cytotoxic activity by employing an MTT assay against A549, MCF-7, and MDA-MB-231 cell lines, and the findings indicate its potent anticancer response, especially against MCF-7 cells with IC₅₀ of 60 µg/mL. However, it experiences minimal toxicity towards the normal cell line (HEK-293). Mechanistic studies revealed a dual-pathway activation: first, apoptosis (17.18% of early and 10.22% of late apoptotic cells by annexin V/PI analysis); second, cell cycle arrest at the S and G2/M phases. It also promotes ROS generation in a concentration-dependent manner. The HDAC–inhibitory assay, extended in silico molecular docking, and MD simulation experiments further validated its significant binding affinity towards HDAC 1 and 6 isoforms. DFT and ADMET screening further support the biological proclivity of the title compounds. The notable biological contribution of VI(i) highlights it as a potential candidate, especially against breast cancer cells. Full article

Understanding species composition and forest dynamics is essential for predicting biomass productivity and informing conservation in tropical montane ecosystems. We evaluated floristic, demographic, and biomass changes in eighteen 0.1 ha permanent plots in the Colombian Sub-Andean forest, including both primary (ca. 60 y old) and secondary forests (ca. 30 years old). Two censuses of individuals (DBH ≥ 2.5 cm) were conducted over 7–13 years. We recorded 516 species across 202 genera and 89 families. Floristic composition differed significantly between forest types (PERMANOVA, p = 0.001), and black oak (Trigonobalanus excelsa Lozano, Hern. Cam. & Henao) forests formed distinct assemblages. Demographic rates were higher in secondary forests, with mortality (4.17% yr), recruitment (4.51% yr), and relative growth rate (0.02% yr) exceeding those of primary forests. The mean aboveground biomass accumulation and the rate of annual change were higher in primary forests (447.5 Mg ha⁻¹ and 466.8 Mg ha⁻¹ yr⁻¹, respectively) than in secondary forests (217.2 Mg ha⁻¹ and 217.2 Mg ha⁻¹ yr⁻¹, respectively). Notably, black oak forests showed the greatest biomass accumulation and rate of change in biomass. Annual net biomass production was higher in secondary forests (8.72 Mg ha⁻¹ yr⁻¹) than in primary forests (5.66 Mg ha⁻¹ yr⁻¹). These findings highlight the ecological distinctiveness and recovery potential of secondary Sub-Andean forests and underscore the value of multitemporal monitoring to understand forest resilience and assess vulnerability to environmental change. Full article

High-strength steel has high strength and low thermal conductivity, and its thin-walled parts are very susceptible to residual stress and deformation caused by cutting heat during the drilling process, which affects the machining accuracy and quality. High-strength steel thin-walled components are widely used in aerospace and other high-end sectors; however, systematic investigations into their temperature fields during drilling remain scarce, particularly regarding the evolution characteristics of the temperature field in thin-wall drilling and the quantitative relationship between drilling parameters and these temperature variations. This paper takes the thin-walled parts of AF1410 high-strength steel as the research object, designs a special fixture, and applies infrared thermography to measure the bottom surface temperature in the thin-walled drilling process in real time; this is carried out in order to study the characteristics of the temperature field during the thin-walled drilling process of high-strength steel, as well as the influence of the drilling dosage on the temperature field of the bottom surface. The experimental findings are as follows: in the process of thin-wall drilling of high-strength steel, the temperature field of the bottom surface of the workpiece shows an obvious temperature gradient distribution; before the formation of the drill cap, the highest temperature of the bottom surface of the workpiece is distributed in the central circular area corresponding to the extrusion of the transverse edge during the drilling process, and the highest temperature of the bottom surface can be approximated as the temperature of the extrusion friction zone between the top edge of the drill and the workpiece when the top edge of the drill bit drills to a position close to the bottom surface of the workpiece and increases with the increase in the drilling speed and the feed volume; during the process of drilling, the highest temperature of the bottom surface of the workpiece is approximated as the temperature of the top edge of the drill bit and the workpiece. The maximum temperature of the bottom surface of the workpiece in the drilling process increases nearly linearly with the drilling of the drill, and the slope of the maximum temperature increases nearly linearly with the increase in the drilling speed and feed, in which the influence of the feed on the slope of the maximum temperature increases is larger than that of the drilling speed. Full article

Urochloa brizantha (Brizantha) is cultivated under varying altitudinal and management conditions. Twelve full-sun (monoculture) plots and twelve shaded (silvopastoral) plots were established, proportionally distributed at 170, 503, 661, and 1110 masl. Evaluations were conducted 15, 30, 45, 60, and 75 days after establishment. The conservation and integration of trees in silvopastoral systems reflected a clear anthropogenic influence, evidenced by the preference for species of the Fabaceae family, likely due to their multipurpose nature. Although the altitudinal gradient did not show direct effects on soil properties, intermediate altitudes revealed a significant role of CaCO₃ in enhancing soil fertility. These edaphic conditions at mid-altitudes favored the leaf area development of Brizantha, particularly during the early growth stages, as indicated by significantly larger values (p < 0.05). However, at the harvest stage, no significant differences were observed in physiological or productive traits, nor in foliar chemical components, underscoring the species’ high hardiness and broad adaptation to both soil and altitude conditions. In Brizantha, a significant reduction (p < 0.05) in stomatal size and density was observed under shade in silvopastoral areas, where solar radiation and air temperature decreased, while relative humidity increased. Nonetheless, these microclimatic variations did not lead to significant changes in foliar chemistry, growth variables, or biomass production, suggesting a high degree of adaptive plasticity to microclimatic fluctuations. Foliar ash content exhibited an increasing trend with altitude, indicating greater efficiency of Brizantha in absorbing calcium, phosphorus, and potassium at higher altitudes, possibly linked to more favorable edaphoclimatic conditions for nutrient uptake. Finally, forage quality declined with plant age, as evidenced by reductions in protein, ash, and In Vitro Dry Matter Digestibility (IVDMD), alongside increases in fiber, Neutral Detergent Fiber (NDF), and Acid Detergent Fiber (ADF). These findings support the recommendation of cutting intervals between 30 and 45 days, during which Brizantha displays a more favorable nutritional profile, higher digestibility, and consequently, greater value for animal feeding. Full article

Cinnamaldehyde (CA) is a potential substitute for antibiotic growth promoters in animal breeding. In this study, we investigated its effects as a dietary supplement on growth performance, serum antioxidant capacity, intestinal digestive enzyme activities, intestinal morphology, and caecal microbiota in meat rabbits. Weaned meat rabbits (n = 450) were randomly assigned to five groups, Groups A, B, C, D, and E, and fed 0, 50, 100, 150, and 200 mg/kg CA diets, respectively, for 47 days. Biological samples including serum (antioxidants), duodenal/caecal content (enzymes), intestinal tissue (morphology), and caecal digesta (microbiota) were collected at day 47 postweaning for analysis. Groups C and D showed significantly higher final body weights than Group A, with Group D (150 mg/kg CA) demonstrating superior growth performance including 11.73% longer duodenal villi (p < 0.05), 28.6% higher microbial diversity (p < 0.01), and 62% lower diarrhoea rate versus controls. Digestive enzyme activity as well as serum antioxidant capacity increased with increasing CA dose, Microbiota analysis revealed CA increased fibre-fermenting Oscillospiraceae (+38%, p < 0.01) while reducing Ruminococcaceae (−27%, p < 0.05). Thus, dietary CA supplementation at 150 mg/kg was identified as the optimal CA dose for improving meat rabbit production. These findings highlight CA as a functional feed additive for promoting sustainable rabbit production. Full article

Leishmaniasis is an infectious disease common in tropical and subtropical regions worldwide. This study aimed to develop a topical meglumine antimoniate gel (MA-gel) for the treatment of cutaneous leishmaniasis. The MA-gel was characterized in terms of morphology, pH, swelling, porosity, rheology, and thermal properties by differential scanning calorimetry (DSC). Biopharmaceutical evaluation included in vitro drug release and ex vivo skin permeation. Safety was evaluated through biomechanical skin property measurements and cytotoxicity in HaCaT and RAW 267 cells. Leishmanicidal activity was tested against promastigotes and amastigotes of Leishmania infantum, and in silico studies were conducted to explore possible mechanisms of action. The composition of the MA-gel included 30% MA, 20% Pluronic^® F127 (P407), and 50% water. Scanning electron microscopy revealed a sponge-like and porous internal structure of the MA-gel. This formula exhibited a pH of 5.45, swelling at approximately 12 min, and a porosity of 85.07%. The DSC showed that there was no incompatibility between MA and P407. Drug release followed a first-order kinetic profile, with 22.11 µg/g/cm² of the drug retained in the skin and no permeation into the receptor compartment. The MA-gel showed no microbial growth, no cytotoxicity in keratinocytes, and no skin damage. The IC₅₀ for promastigotes and amastigotes of L. infantum were 3.56 and 23.11 µg/mL, respectively. In silico studies suggested that MA could act on three potential therapeutic targets according to its binding mode. The MA-gel demonstrated promising physicochemical, safety, and antiparasitic properties, supporting its potential as a topical treatment for cutaneous leishmaniasis. Full article

Background: Transient elastography (TE), using Fibroscan^® and point shear wave elastography (pSWE), are two techniques used to estimate liver fibrosis. The aim of our study was to compare, for the first time, these two techniques in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), stratifying the analysis on the basis of the grades of steatosis. Methods: We recruited 85 consecutive MAFLD patients who underwent liver stiffness (LS) measurement performed by Fibroscan^® and pSWE on the same day. Severity of steatosis was estimated by Fibroscan^® and expressed as controlled attenuation parameter (CAP), ranging from S0 to S3. Spearman’s “r” coefficient was used to calculate the correlation and Bland–Altman graphs was used to evaluate the agreement. Results: In general, the correlation and agreement between Fibroscan^® and pSWE were substantial (r = 0.66, p < 0.001 and bias= −0.64 ± 2.48, respectively). When data were analyzed according to the grade of steatosis, an increasing significant correlation was observed going from S0 to S2 (r = 0.79, r = 0.81, and r = 0.85, respectively), whereas a low correlation and agreement were observed for S3 patients (r = 0.48, p = 0.003, bias= −0.95 ± 2.51). Conclusions: Fibroscan^® and pSWE are equivalent techniques to estimate liver fibrosis in patients with mild to moderate steatosis, while in presence of severe steatosis their agreement is low. Full article

This work investigated the ion exchange technique for selective separation of rare earth elements (REE) from acid mine drainage (AMD), using different column systems, pH values, and eluent concentrations. Systematic analysis of pH and eluent concentration showed that an initial pH of 6.0 and 0.02 mol L⁻¹ NH₄EDTA are the optimal conditions, achieving 98.4% heavy REE purity in the initial stage (0 to 10 bed volumes). This represents a 32-fold increase compared to the original AMD (6.7% heavy REE). The speciation of REE and impurities was determined by Visual Minteq 4.0 software using pH 2.0, which corresponds to the pH at the inlet of the fractionation column. Under this condition, La and Nd and the impurities (Ca, Mg, and Mn) remained in the fractionation column, while Al was partially retained. In addition, the heavy REE (Y and Dy) were mainly in the form of REE-EDTA complexes and not as free cations, which made fractionation more feasible. The fractionation column minimized impurities, retaining 100% of Ca and 67% of Al, generating a liquor concentrated in heavy REE. This sustainable approach adopted herein meets the critical needs for scalable recovery of REE from diluted effluents, representing a circular economy strategy for critical metals. Full article

This study explores how corporate governance reforms can enhance financial reporting quality and organizational transparency, focusing on Greece’s transition from Law 3016/2002 to Law 4706/2020. The legislative reform aimed to modernize governance structures, align national practices with international standards, and strengthen investor protection in a post-crisis economic environment. Moving beyond a simple legal comparison, the study examines how Law 3016/2002’s formal compliance model contrasts with Law 4706/2020’s more substantive accountability framework. We hypothesize that Law 4706/2020 introduces substantively stronger governance mechanisms than its predecessor, thereby improving transparency and investor protection, while compliance with the new law imposes materially greater administrative and financial burdens, especially on small- and mid-cap firms. Methodologically, the research employs a narrative literature review and a structured comparative legal analysis to assess the administrative and financial implications of the new law for publicly listed companies, focusing on board composition and diversity, internal controls, suitability policies, and disclosure requirements. Drawing on prior comparative evidence, we posit that Law 4706/2020 will foster governance and disclosure improvements, enhanced oversight, and clearer board roles. However, these measures also impose compliance burdens. Due to the heterogeneity of listed companies and the lack of firm-level data following Law 4706/2020’s implementation, the findings are neither fully generalizable nor quantifiable; future quantitative research using event studies or panel data is required to validate the hypotheses. We conclude that Greece’s new framework is a critical step toward sustainable corporate governance and more transparent financial reporting, offering regulators, practitioners, and scholars examining legal reform’s impact on governance effectiveness and financial reporting integrity. Full article

Background and Objectives: Malnutrition is one of the most common complications in patients undergoing hemodialysis (HD) and is closely linked to increased morbidity and mortality. This study aimed to investigate the nutritional status of HD patients and the clinical relevance of bioelectrical impedance analysis (BIA) parameters such as the percent body fat (PBF), skeletal muscle mass index (SMI), extracellular water-to-total body water ratio (ECW/TBW), and phase angle (PhA) in assessing malnutrition in Vietnamese HD patients. Materials and Methods: This cross-sectional study was conducted among 184 patients undergoing hemodialysis in Hanoi, Vietnam. The BIA parameters were measured by the InBody S10 body composition analyzer, while malnutrition was assessed by the geriatric nutritional risk index (GNRI), with a GNRI <92 classified as a high risk of malnutrition. The independent BIA variables for predicting malnutrition and its cut-off values were explored using logistic regression models and a receiver operating characteristic (ROC) curve analysis, respectively. Results: Among the study population, 42.9% (79/184) of patients were identified as being at a high risk of malnutrition. The multivariate logistic regression analysis revealed that a higher ECW/TBW was independently associated with an increased risk of malnutrition, while the PBF, SMI, and PhA expressed significant and inverse associations with the malnutrition risk after adjusting for multiple confounders. The cut-off values for predicting the high risk of malnutrition in overall HD patients were determined to be 20.45%, 7.75 kg/m², 5.45°, and 38.03% for the PBF, the SMI, the PhA, and the ECW/TBW ratio, respectively. Conclusions: BIA parameters, including the PBF, SMI, PhA, and ECW/TBW ratio, could serve as indicators of malnutrition in general Vietnamese patients with HD. Full article

Background/Objectives: Neuromodulation is under investigation as a possibly effective add-on therapy in Alzheimer’s disease (AD). While transcranial pulse stimulation (TPS) has shown positive short-term effects, long-term effects have not yet been fully explored. This study aims to evaluate the long-term feasibility, safety, and potential cognitive benefits of TPS over one year in patients with Alzheimer’s disease, focusing on domains such as memory, speech, orientation, visuo-construction, and depressive symptoms. Methods: We analyzed preliminary data from the first ten out of thirty-five patients enrolled in a prospective TPS study who completed one year of follow-up and were included in a dedicated long-term database. The protocol consisted of six initial TPS sessions over two weeks, followed by monthly booster sessions delivering 6000 pulses each for twelve months. Patients underwent regular neuropsychological assessments using the Alzheimer Disease Assessment Scale (ADAS), Mini-Mental Status Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Beck Depression Inventory (BDI-II). All adverse events (AEs) were documented and monitored throughout the study. Results: Adverse events occurred in less than 1% of stimulation sessions and mainly included mild focal pain or transient unpleasant sensations, as well as some systemic behavioral or vigilance changes, particularly in patients with underlying medical conditions, with some potentially related to the device’s stimulation as adverse device reactions (ADRs). Cognitive test results showed significant improvement after the initial stimulation cycle (ADAS total improved significantly after the first stimulation cycle (M_pre = 28.44, M_post = 18.56; p = 0.001, d = 0.80, 95% CI (0.36, 1.25)), with stable scores across all domains over one year. Improvements were most notable in memory, speech, and mood. Conclusions: TPS appears to be a generally safe and feasible add-on treatment for AD, although careful patient selection and monitoring are advised. While a considerable number of participants were lost to follow-up for various reasons, adverse events and lack of treatment effect were unlikely primary causes. A multifocal stimulation approach (F-TOP2) is proposed to enhance effects across more cognitive domains. Full article

Inflammatory arthritis (IA) is a chronic condition marked by joint dysfunction and pain, posing significant challenges for effective drug delivery. This study separated Perilla frutescens leaf-derived exosome-like nanovesicles (PFE) to effectively penetrate the stratum corneum barrier. These nanovesicles and indomethacin (IND) were subsequently developed into a nanogel designed for topical drug delivery systems (PFE-IND-GEL). PFE exhibited a typical vesicular structure with a mean diameter of 98.4 ± 1.3 nm. The hydrodynamic size and zeta potential of PFE-IND-GEL were 129.6 ± 5.9 nm and −17.4 ± 1.9 mV, respectively. Mechanistic investigations in HaCaT keratinocytes showed that PFE significantly downregulated tight junction proteins (ZO-1 and Occludin, p < 0.01) via modulation of the IL-17 signaling pathway, as evidenced by transcriptomic analysis. In a sodium urea crystal-induced rat IA model, the topical application of PFE-IND-GEL significantly reduced joint swelling (p < 0.05) and serum levels of inflammatory cytokines (IL-6, IL-1α, TNF-α) compared to control groups. Histopathological analysis confirmed the marked attenuation of synovial inflammation and cartilage preservation in treated animals. These findings underscore the dual role of PFE as both a topical permeation enhancer and an anti-inflammatory agent, presenting a promising strategy for managing IA. Full article

Enhancing osseointegration is a common goal for many titanium implant coatings, since the naturally forming oxides are often bioinert and exhibit less than ideal bone-to-implant contact. Oxide coating surface topographies, chemistries, and crystallinities are known to play key roles in enhancing bone–implant interactions. In the present study, two novel anodization processes were developed in electrolytes based on juiced navel oranges to create bioactive oxide coatings on commercially pure titanium (CPTi) surfaces. Both oxide groups revealed multi-scaled micro and nano surface topographies, significant Ca and P-dopant incorporation exhibiting Ca/P ratios similar to human bone (1.7 and 1.8), and physiologically relevant Mg uptake levels of <0.1% and 1.4 at%. XRD and FTIR analyses of each oxide revealed a combination of tricalcium phosphate and hydroxyapatite phases that showed carbonate substitutions indicative of bone-like apatite formation. Finally, VDI indentation testing revealed good adhesion strengths, minimal cracking, and no visible delamination for both oxides. In summary, the anodization processes in the present study were shown to produce carbonated tricalcium phosphate and apatite containing oxides with contrasting levels of Mg uptake that show much promise to improve future implant clinical outcomes. Full article

Gypsum (CaSO₄·2H₂O) crystallization underpins numerous industrial processes, yet its response to chemical admixtures remains incompletely understood. This study investigates diffusion-controlled crystal growth in a coaxial test tube system to evaluate how three Sika^® ViscoCrete^® superplasticizers—430P, 111P, and 120P—affect nucleation, growth kinetics, morphology, and thermal behavior. The superplasticizers, selected for their surface-active properties, were hypothesized to influence crystallization via interfacial interactions. Ion diffusion was maintained quasi-steadily for 12 weeks, with crystal evolution tracked weekly by macro-photography; scanning electron microscopy and thermogravimetric/differential scanning were performed at the final stage. All admixtures delayed nucleation in a concentration-dependent manner. Lower dosages (0.5–1.0 wt%) yielded platy-to-prismatic morphologies and higher dehydration enthalpies, indicating more ordered lattice formation. In contrast, higher dosages (1.5–2.0 wt%) produced denser, irregular crystals and shifted dehydration to lower temperatures, suggesting structural defects or increased hydration. Among the additives, 120P showed the strongest inhibitory effect, while 111P at 0.5 wt% resulted in the most uniform crystals. These results demonstrate that ViscoCrete^® superplasticizers can modulate gypsum crystallization and thermal properties. Full article