Search Results (45,695)

Background/Objectives: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with ischemic stroke, systemic thromboembolism, heart failure, and mortality. Although oral anticoagulation (OAC) remains the cornerstone of stroke prevention, long-term therapy may be limited by bleeding risk, contraindications, intolerance, nonadherence, or thromboembolic events despite treatment. Left atrial appendage closure (LAAC) has therefore emerged as a non-pharmacological alternative for selected patients with nonvalvular AF. This review aimed to synthesize current evidence on LAAC, focusing on comparative efficacy versus OAC, device evolution, imaging-guided strategies, antithrombotic management, procedural optimization, unresolved challenges, and emerging technologies. Methods: This state-of-the-art narrative review was informed by targeted, non-systematic searches of PubMed and Scopus for publications from January 2009 to June 2026. Evidence was selected purposively to represent clinically relevant guidelines, randomized trials, registries, comparative observational studies, systematic reviews, meta-analyses, imaging studies, device-comparison studies, and reports of emerging technologies. The selected evidence was synthesized narratively; no exhaustive screening process, PRISMA flow diagram, formal risk-of-bias assessment, or quantitative synthesis was performed. Results: Randomized evidence was context dependent. OPTION supported LAAC as an alternative to oral anticoagulation in selected anticoagulation-eligible patients undergoing atrial fibrillation ablation. CHAMPION-AF established noninferiority of Watchman FLX to non–vitamin K antagonist oral anticoagulants for its composite efficacy endpoint in a predominantly moderate-risk, anticoagulation-eligible population and demonstrated less non-procedural bleeding, although ischemic stroke occurred numerically more often after LAAC. In contrast, CLOSURE-AF did not establish noninferiority of LAAC to physician-directed medical therapy in an older population at high risks of both stroke and bleeding. These findings indicate that the comparative value of LAAC depends strongly on patient selection, comparator therapy, endpoint composition, procedural risk, and trial design. Observational, registry, and emerging evidence was considered supportive or hypothesis-generating rather than equivalent to randomized evidence. OPTION enrolled only patients undergoing or recently undergoing AF ablation who were suitable for anticoagulation. CHAMPION-AF included 3000 anticoagulation-eligible patients but had relatively low baseline bleeding risk, while CLOSURE-AF studied 912 substantially older, higher-risk patients and did not meet its noninferiority criterion. Conclusions: LAAC has evolved into a precision-guided intervention integrating patient risk, left atrial appendage anatomy, device choice, imaging, antithrombotic therapy, and structured surveillance. Further studies are needed to optimize patient selection, standardize post-procedural therapy, and clarify its long-term role compared with contemporary direct oral anticoagulant therapy. Full article

Cultural ecosystem service (CES) assessment is essential for comprehensively understanding and evaluating ecosystem services. Optimizing the spatial zoning of CESs can provide more targeted information for ecosystem management. By identifying the typical landscape characteristics of different CESs, rural landscape value can be more effectively recognized. This study constructed a set of rural landscape characteristics indicators, identified the typical characteristics of different CESs based on public preferences, mapped their spatial distributions using the Maxent model, and applied K-means clustering analysis to optimize the spatial zoning in rural Huzhou. The results show that the four CESs categories are associated with different rural landscape characteristics. The spatial distributions of the CESs showed substantial overlap and were mainly concentrated in southern Anji County, around the Moganshan Scenic Area, and along the shoreline of Lake Taihu. Five types of rural landscapes were identified based on spatial distribution of the CESs. This study provides a reference for identifying the landscape value of CESs in rural areas and supports the incorporation of CES assessment into rural landscape management decision-making. Full article

Essential thrombocythemia (ET) is a Ph(-) myeloproliferative neoplasm characterized by elevated platelet counts. Patients most often have one of the three following driver mutations: JAK2, MPL, or CALR. However, these mutations are not detected in approximately 10–15% of patients, who are thus referred to as “triple-negative” (TN). Background/Objectives: In recent years, there have been breakthroughs in the genetic diagnosis of hematological diseases and progress in understanding their epigenetic basis. Aim: This study aimed to review the available literature and systematize the current knowledge on the molecular abnormalities in essential thrombocythemia. Particular attention was paid to the impacts of genetic mutations and epigenetic changes—such as abnormalities in non-coding RNA expression, DNA methylation, and histone modifications—on disease development and their clinical significance in patients with essential thrombocythemia. The most important publications on genetic and epigenetic mechanisms in essential thrombocythemia were reviewed and summarized. Methods: A review of the available literature was conducted using selected online databases. Publications from 2003 to 2026 were considered, covering the diagnosis and classification criteria for essential thrombocythemia, its genetic and epigenetic basis, and the associated impacts on the disease course. Conclusions: Although understanding the precise roles of genetic and epigenetic abnormalities in essential thrombocythemia remains challenging, they offer many opportunities for use as new diagnostic biomarkers and for the development of novel targeted treatment options. Further research is needed to better understand the genetic and epigenetic changes occurring in ET. Full article

Diabetes mellitus induces endothelial dysfunction and oxidative stress, contributing to the development of vascular complications. Although metformin exerts well-established vasculoprotective and antioxidant effects, the molecular mechanisms underlying these actions remain incompletely understood. Novel miR-1133 was previously identified as a metformin-responsive putative microRNA (miRNA), and bioinformatic analysis identified PIK3CA as a biologically plausible candidate target for further investigation. This study investigated the functional significance of novel miR-1133 in the antioxidant effects of metformin in hyperglycemia-induced human umbilical vein endothelial cells (HUVECs). HUVECs were exposed to normal glucose (5.5 mmol/L), hyperglycemia (33.3 mmol/L), or hyperglycemia supplemented with metformin (10 μM) for 24 h. Metformin-treated hyperglycemic HUVECs were subsequently transfected with a novel miR-1133 mimic during continued hyperglycemic and metformin exposure. PIK3CA expression and oxidative stress markers, including reactive oxygen species (ROS), superoxide dismutase (SOD), and 8-hydroxy-2′-deoxyguanosine (8-OHdG), were evaluated. Hyperglycemia increased novel miR-1133 expression, whereas metformin reduced its expression. Metformin treatment was associated with increased PIK3CA mRNA and protein expression, reduced ROS and 8-OHdG levels, and increased SOD expression and activity. Novel miR-1133 mimic transfection was associated with reduced PIK3CA expression, increased ROS and 8-OHdG levels, and decreased SOD expression and activity compared with the corresponding transfection control. Collectively, these findings demonstrate that metformin attenuates oxidative stress in hyperglycemia-induced endothelial cells and overall provide the first functional characterization of novel miR-1133. The reciprocal changes in PIK3CA expression and oxidative stress observed following novel miR-1133 mimic transfection suggest that novel miR-1133 may represent a candidate mediator of the endothelial antioxidant responses associated with metformin. Further studies are required to validate the direct interaction between novel miR-1133 and PIK3CA and to elucidate the underlying molecular mechanisms. Full article

Geopolitical instability can reshape trade routes, prices, and energy-security risks. Using a monthly country-level panel from January 2015 to June 2025, this study estimates a difference-in-differences (DID) model for the logarithm of China’s fossil-fuel import values (USD) from Russia and four Central Asian suppliers relative to seven comparison suppliers. The corrected benchmark coefficient is −0.582. This estimate means that after March 2022, import values from the treated suppliers were lower relative to the counterfactual trend represented by the control group; it does not mean that every treated supplier experienced an absolute decline. Indeed, several country- and commodity-specific import values increased in levels, partly because the outcome combines quantity and price effects. Commodity-specific international price benchmarks are included as controls, but physical-volume data are not available in the submitted dataset. With only 11 country clusters, conventional clustered significance levels are interpreted cautiously. A 500-assignment placebo exercise provides a randomization-based robustness check, with no simulated coefficient as extreme as the benchmark estimate (empirical p ≤ 0.002 under the stated assignment scheme). Logistics performance, government stability, and energy OFDI are positively associated with import values in conditional regressions; because the article does not report interaction terms, these results are not interpreted as moderation effects. The findings support targeted attention to corridor reliability and supplier diversification, while broader operational policies require additional evidence. Full article

Background/Objectives: Prostate cancer remains one of the most common malignancies in men, and prognosis remains particularly challenging in patients with lymph node metastases. Cyclooxygenase-2 (COX-2), an inducible enzyme involved in inflammation and tumor progression, has been investigated as a potential prognostic biomarker and therapeutic target, but its expression in lymph node metastases remains unclear. While COX-2 overexpression in primary prostate tumors has been reported, its expression in lymph node metastases has not been thoroughly investigated. Therefore, this study aimed to compare COX-2 expression in primary prostate tumors and corresponding lymph node metastases and to evaluate its association with clinicopathological characteristics and survival. Methods: This study included 77 treatment-naïve patients with prostate cancer and histologically confirmed lymph node metastases who underwent radical prostatectomy with extended lymphadenectomy. COX-2 expression was assessed using immunohistochemistry in paired samples from primary tumors and corresponding lymph node metastases. Statistical comparisons were conducted using the Mann–Whitney U test and survival analyses were performed using Kaplan–Meier curves with the log-rank test. Results: COX-2 expression was detected in both primary tumors and lymph node metastases, with no significant difference in staining intensity between the two sites. High COX-2 expression in primary tumors was significantly associated with a higher percentage of involved lymph nodes (30.0% vs. 11.8%, p = 0.026), elevated postoperative PSA levels (1.98 vs. 0.10 ng/mL, p = 0.007), and reduced surgical radicality (11.1% vs. 63.2%, p = 0.008). Moreover, elevated COX-2 expression in both primary and metastatic tissues correlated with worse five-year overall survival (41.7% vs. 92.8%, p = 0.033; and 40.0% vs. 95.6%, p < 0.001, respectively). Conclusions: High COX-2 expression is associated with adverse clinicopathological features and poorer survival in lymph node–positive prostate cancer. The association of COX-2 expression with the extent of lymph node involvement and survival suggests that COX-2 may have prognostic value in this setting. However, the present findings do not establish a causal role of COX-2 in disease progression or lymphangiogenesis. Further studies are warranted to validate the prognostic significance of COX-2 and to clarify its potential biological and therapeutic relevance in lymph node–positive prostate cancer. Full article

The transition from high school to university is a critical developmental period marked by substantial academic, social, and lifestyle changes that may increase vulnerability to academic difficulties, disengagement, and dropout. Given the importance of academic achievement for student retention and long-term success and the growing recognition of sleep as a modifiable determinant of academic performance, this scoping review examined how the relationship between sleep and academic achievement has been investigated among first-year university students. Following PRISMA guidelines, a systematic search identified 20 records representing 21 studies published between 2013 and 2026. Sleep duration and sleep quality were the most frequently examined domains, although findings were heterogeneous. Nevertheless, shorter sleep duration, particularly below 6–7 h per night, was generally associated with poorer academic achievement. Poor sleep quality was also linked to lower academic performance in some studies, with affective factors influencing this relationship. Sleep problems, including chronic sleep deprivation and risk of sleep disorders, showed consistent associations with poorer academic outcomes. Similarly, an evening chronotype was generally associated with poorer academic performance and adjustment. These findings emphasize sleep as an essential target for future research and initiatives aimed at promoting academic success and student retention during the transition to higher education. Full article

Ankylosing spondylitis (AS) is a chronic inflammatory disease strongly associated with human leukocyte antigen B27 (HLA-B27). However, the incomplete penetrance of HLA-B27 suggests that additional molecular mechanisms contribute to AS pathogenesis. Circular RNAs (circRNAs) have emerged as important regulators of immune responses, but their roles in AS pathogenesis remain incompletely understood. In this study, circRNA expression profiles were examined by high-throughput RNA sequencing and selected circRNAs were validated by quantitative RT-PCR in T cells from AS patients and healthy controls. Among the validated circRNAs, circRNPS1 was significantly up-regulated in T cells from AS patients. Overexpression of circRNPS1 in activated Jurkat cells increased IL-2, IL-17A, and interferon-γ expression and enhanced JAK2/STAT1 and MEK1/2-ERK signaling. RNA pull-down followed by proteomic analysis identified heterogeneous nuclear ribonucleoprotein K (hnRNPK) that binds to the back-splicing junction region of circRNPS1. CircRNPS1 increased the stability of hnRNPK and vav-1, whereas hnRNPK knockdown attenuated circRNPS1-mediated MEK1/2-ERK activation and inflammatory cytokine expression. Furthermore, an antisense RNA fragment targeting the back-splicing junction region of circRNPS1 suppressed IL-2, IL-17A, and interferon-γ expression in activated circRNPS1-overexpressing Jurkat cells and T cells from AS patients. Disrupting the interaction between circRNPS1 and hnRNPK therefore warrants further investigation as a potential therapeutic strategy for AS. Full article

Electric dynamometer test benches generate heterogeneous multi-channel logs whose structural completeness, physical consistency, and operating-condition support vary across files. We propose Coupling-Gated Data Quality Index (CG-DQI) sample weighting, a fold-local preparation protocol for 60 s next-window temperature-change prediction. Deployable weights use training-side structural and physical quality signals, while a target-magnitude coupling gate screens candidate association with the absolute target. The dataset contains 30,093 valid windows from 134 files and 30 date-defined campaigns. File-level leave-one-file-out validation reduced Ridge MAE from 0.7035 to 0.6932 ${}^{\circ }$C and the mean MAE across three fixed Random Forest initializations from 0.4556 to 0.4489 ${}^{\circ }$C per window. Strict nested leave-one-campaign-out analysis retained sparse CG-DQI in all 30 folds and yielded a campaign-level Ridge MAE difference of 0.0152 ${}^{\circ }$C with a 95% bootstrap confidence interval (CI) of 0.0054–0.0309, while the 99th percentile absolute error (P99) increased by 0.0710 ${}^{\circ }$C. Fixed-parameter XGBoost preserved a positive mean MAE direction, although its campaign interval crossed zero. CG-DQI, therefore, provides a traceable MAE-oriented preparation option within the present bench and campaign range; tail-sensitive and cross-device use requires an explicit constraint or recalibration. Full article

Background/Objectives: Digital transformation is a strategic priority for healthcare systems, requiring nurses to develop competencies that enable the safe, effective, and critical use of digital technologies in clinical practice. Understanding nurses’ digital competence profile is essential to inform leadership, education, and workforce development strategies. This study aimed to assess digital competence among Portuguese nurses, examine its relationship with soft skills, and identify priority areas for professional development. Methods: A quantitative, descriptive-correlational, cross-sectional study was conducted with a nationally recruited convenience sample of Portuguese nurses. Data were collected using a Digital Competence Assessment Questionnaire based on the European Digital Competence Framework for Citizens (DigComp) and Soft Skills Inventory. Associations between digital competence and soft skills were analysed using descriptive, inferential, and multivariable statistical methods with IBM SPSS Statistics version 30.0. Results: Based on the exploratory classification of the knowledge/performance score, 52.0% of participants fell within the Intermediate and 27.2% within the Advanced proficiency intervals. Adapting and Coping, Analyzing and Interpreting, and Interacting and Presenting were positively associated with self-reflected digital competence. Multivariable analysis showed that soft skills accounted for a larger proportion of variance in self-reflected digital competence than in the knowledge/performance test score; however, the explanatory value of the latter model was limited. Conclusions: Participants were predominantly classified within the Intermediate and Advanced proficiency intervals, although comparatively lower descriptive performance was observed in Safety. The findings highlight the potential complementary role of technical competencies and soft skills in digital capability and suggest the value of further investigating targeted educational approaches. These findings may inform nursing leadership, education, and workforce-development strategies aimed at supporting digital competence and sustainable digital transformation. Full article

Biotherapeutics are medicinal agents derived from or related to naturally occurring molecules in the body and are designed to modulate specific immune targets. This review examines clinically established biologics and targeted small molecules that affect cytokine-driven transcriptional programs, principally JAK/STAT and canonical and non-canonical NF-κB signaling, across autoimmune, neoplastic, hematological, dermatological, and rheumatic diseases. Periodontitis is used as a translational model because dysbiotic mucosal inflammation, cytokine signaling, and osteoclastogenesis may also intersect with systemic autoimmunity. In particular, Porphyromonas gingivalis-associated protein citrullination provides a plausible link to anti-citrullinated protein antibody-positive rheumatoid arthritis in genetically susceptible individuals, although causality remains unproven. The review also evaluates plant-derived modulators of JAK/STAT and related transcriptional pathways. Curcumin and resveratrol have entered small rheumatoid arthritis studies, whereas evidence for catechins, celastrol, and artemisinin derivatives in autoimmune disease remains predominantly preclinical. These compounds may inform adjunctive or locally delivered strategies, but clinical translation requires better target selectivity, bioavailability, dose standardization, and safety data. Full article

Cancer cachexia is a multifactorial systemic syndrome characterized by progressive muscle loss, with or without adipose tissue depletion, that cannot be reversed by conventional nutritional support. It affects cancer patients and is associated with reduced treatment tolerance, impaired physical function, poor quality of life, and increased mortality. The understanding of cachexia has evolved recently, from the perception of a simple nutritional disorder to a complex immune–metabolic syndrome, based on tumor–host interactions, systemic inflammation, metabolic dysregulation, and multi-organ dysfunction. This review summarizes the progression of cachexia research, highlighting key findings involving inflammatory cytokines, proteolytic pathways, mitochondrial dysfunction, and immune dysregulation. The development of therapeutic strategies is examined, from early nutritional and appetite-stimulating interventions to contemporary targeted therapies, including ghrelin receptor agonists, cytokine inhibitors, and anabolic agents. Despite advances in mechanistic understanding, numerous trials targeting single pathways have failed to produce meaningful functional or survival benefits, underscoring the limitations of reductionist approaches. Emerging evidence supports a paradigm shift toward multimodal, biomarker-guided, and patient-centered interventions that address the interconnected biological mechanisms underlying cachexia. Particular emphasis is given to novel immunomodulatory strategies, including agents such as R-ketorolac, which may restore immune homeostasis and target the root causes of cachexia. It is hypothesized that future therapeutic success will likely depend on integrated approaches combining immunological, metabolic, nutritional, and rehabilitative interventions. Full article

Bauxite mining causes severe soil degradation in the ecologically fragile karst region of Southwest China, yet targeted vegetation restoration schemes remain poorly developed. This study aimed to screen promising selected restoration species and preliminarily explore their soil improvement characteristics in karst bauxite mine wastelands through a field observational survey. We investigated six vegetation-soil conditions at 0–10 cm topsoil (two-year monocultures of Robinia pseudoacacia, Ligustrum lucidum, Zea mays, Miscanthus sinensis, topsoil from >15-year Z. mays with straw return, and unvegetated bare land), alongside paired 10–20 cm subsoil from the same long-term Z. mays stand as a depth-profile reference, and analyzed soil physicochemical properties, enzyme activities, and bacterial/fungal communities via high-throughput sequencing. Results showed that vegetation cover neutralized strongly acidic mine soil and significantly increased soil organic matter (SOM), total nitrogen (TN), and available nutrients compared with the bare control (p < 0.05). The long-term Z. mays cropland showed the strongest soil nutrient accumulation, with topsoil SOM, available phosphorus, and available potassium, increased by 428.6%, 250.0%, and 65.3%, respectively, relative to the bare control. Notably, the subsoil of long-term Z. mays also maintained high nutrient levels, but its absolute values are not directly comparable with topsoil treatments due to different sampling depths. All vegetation conditions elevated soil enzyme activities and microbial alpha diversity and significantly shifted bacterial and fungal community structure (beta diversity) compared with the control. Several bacterial phyla (including Chloroflexi and Proteobacteria) that have been associated with carbon-cycling functions in prior studies were relatively more abundant in revegetated soils; however, their functional roles in this system remain to be verified. Redundancy analysis identified SOM, TN, and available potassium as key environmental correlates of bacterial community variation. Overall, the long-term crop–straw return pattern shows comprehensive soil improvement effects, providing observational baseline data and reference for ecological restoration of karst bauxite mining areas in Southwest China. Full article

Background: Triple-negative breast cancer (TNBC) lacks effective targeted therapies, and its dependence on glycolysis represents a potential metabolic vulnerability. EIF3H, the largest subunit of the eukaryotic translation initiation factor 3 complex and a putative deubiquitinase, has been implicated in tumor progression, but its role in TNBC metabolism remains unclear. Methods: EIF3H expression and prognostic value were evaluated in public datasets, clinical TNBC specimens, and cell lines. Functional roles were examined using proliferation, colony formation, migration, and xenograft assays. Mechanisms were investigated by mass spectrometry, co-immunoprecipitation, ubiquitination and glycolytic rate assays, macrophage co-culture, and single-cell transcriptomic analysis. Results: EIF3H was significantly upregulated in TNBC and associated with poor survival. Transcriptionally activated by TRPS1, EIF3H bound to lactate dehydrogenase A (LDHA), reduced its ubiquitination, and prevented its proteasomal degradation. LDHA stabilization enhanced glycolysis and lactate production, thereby promoting TNBC cell proliferation and migration in vitro and tumor growth in vivo; these effects were abolished by LDHA knockdown and restored by LDHA re-expression. In addition, tumor-derived lactate induced M2 macrophage polarization via GPR65, which in turn reinforced malignant progression. Conclusions: Our findings define a TRPS1–EIF3H–LDHA axis that drives glycolysis-dependent TNBC progression and reveal lactate–GPR65 signaling as a mediator of tumor–macrophage crosstalk, supporting EIF3H as a potential prognostic biomarker and therapeutic target in TNBC. Full article

High-temperature stress impairs plant growth and alters secondary metabolism. Polymethoxyflavones (PMFs) are citrus-specific flavonoids with important nutritional benefits; however, their transcriptional responses to heat stress remain poorly understood. Here, five-month-old ‘Ponkan’ citrus seedlings were exposed to 40 °C for 6, 11, and 21 days. HPLC analysis showed that the accumulation of four major PMFs (sinensetin, nobiletin, tangeretin, and 5-demethylnobiletin) was significantly reduced in leaves under heat stress. RNA-seq identified 3424 differentially expressed genes shared across all three time points, which were enriched in pathways associated with microtubule cytoskeleton organization, cell cycle regulation, and glyoxylate and dicarboxylate metabolism. Further analysis of the PMF biosynthetic pathway revealed that 14 of 18 key structural genes, including CHS, CHI, FNSII, and OMT family members, were downregulated by heat treatment. In addition, several bHLH, AP2/EREBP, and MYB transcription factors, known regulators of flavonoid biosynthesis, exhibited expression patterns closely associated with PMF accumulation. RT-qPCR analysis validated the transcriptome results. Collectively, these findings suggest that heat stress suppresses PMF accumulation through coordinated repression of PMF biosynthetic genes and their potential regulators. This study provides new insights into the molecular basis of heat-responsive PMF metabolism and offers potential targets for maintaining citrus nutritional quality under elevated temperatures. Full article