Search Results (12,729)

Biliary tract carcinoma (BTC) is a group of highly heterogeneous malignancies arising from the biliary epithelium. Anatomically, BTC is categorized into gallbladder cancer (GBC) and cholangiocarcinoma (CCA), with the latter further subdivided into intrahepatic (iCCA), perihilar (pCCA), and distal cholangiocarcinoma (dCCA). Epidemiological studies reveal a dismal five-year survival rate of less than 20% for BTC patients, with limited responses to current chemotherapy regimens, underscoring the urgent need to unravel its complex molecular pathogenesis. Recent research has increasingly focused on the regulatory networks of post-translational modifications, particularly the ubiquitin-proteasome system (UPS), in tumorigenesis. As the largest subfamily of deubiquitinating enzymes (DUBs), ubiquitin-specific proteases (USPs) regulate the stability of key oncoproteins such as phosphatase and tensin homolog (PTEN) and c-Myc, playing pivotal roles in tumor cell proliferation, apoptosis evasion, invasion, and metastasis. This review systematically summarizes the differential expression profiles of USP family members (e.g., USP1, USP3, USP7, USP8, USP9X, USP21, and USP22) in BTC and their clinical significance, with a focus on elucidating how specific USPs regulate tumor progression through key substrates, including poly(ADP-ribose) polymerase 1 (PARP1), dynamin-1-like protein (DNM1L), and O-GlcNAc transferase (OGT). Furthermore, based on recent advances, we discuss the therapeutic potential of small-molecule USP inhibitors in BTC targeted therapy, providing a theoretical foundation for developing novel precision treatment strategies. Full article

Turbulence and wind gusts pose significant risks to the safety and efficiency of UAVs (uncrewed aerial vehicles) in urban environments. In these settings, wind dynamics are strongly influenced by interactions with buildings and terrain, giving rise to small-scale phenomena such as vortex shedding and gusts. These wind speed oscillations generate unsteady forces that can destabilise UAV flight, particularly for small vehicles. Additionally, predicting their formation requires high-resolution Computational Fluid Dynamics (CFD) models, as current weather forecasting tools lack the resolution to capture these phenomena. However, such models require 3D representations of study areas with high geometric consistency and detail, which are not available for most cities. To address this issue, this work introduces an automated methodology for urban CFD mesh generation using open-source data. The proposed method generates error-free meshes compatible with OpenFOAM and includes tools for geometry modification, enhancing solver convergence and enabling adjustments to mesh complexity based on computational resources. Using this approach, CFD simulations are conducted for the city of Ourense, followed by an analysis of their impact on UAV operations and the integration of the system into a trajectory optimisation framework. The CFD model is also validated using experimental anemometer measurements. Full article

The role of distributed energy resources in distribution networks is evolving to support system operation, facilitated by their participation in local flexibility markets. Future scenarios envision a significant share of low-power resources providing ancillary services to efficiently manage network congestions, offering a competitive alternative to conventional grid reinforcement. Additionally, the interaction between distribution and transmission systems enables the provision of flexibility services at higher voltage levels for various applications. In such cases, the aggregated flexibility of low-power resources is typically represented as a capability envelope at the interface between the distribution and transmission network, constructed by accounting for distribution grid constraints and subsequently communicated to the transmission system operator. This paper revisits this concept and introduces a novel approach for envelope construction. The proposed method is based on a surrogate model composed of a limited set of standard power flow components—loads, generators, and storage units—enhancing the integration of distribution network flexibility into transmission-level optimization frameworks. Notably, this advantage can potentially be achieved without significant modifications to the optimization tools currently available to grid operators. The effectiveness of the approach is demonstrated through a case study in which the adoption of distribution network surrogate models within a coordinated framework between transmission and distribution operators enables the provision of ancillary services for transmission resilience support. This results in improved resilience indicators and lower control action costs compared to conventional shedding schemes. Full article

Retinoids are central regulators of skin biology, influencing keratinocyte proliferation, differentiation, immune modulation, and barrier maintenance. Their therapeutic relevance has long been attributed to retinoic acid receptor (RAR)-mediated transcriptional activity; however, recent studies have revealed additional layers of regulation, including epigenetic modifications, kinase signaling networks, and interactions with the skin microbiome. These mechanisms not only refine our understanding of retinoid function but also inform strategies to overcome therapeutic limitations such as resistance, irritation, and systemic toxicity. Advances in medicinal chemistry have yielded synthetic retinoids with enhanced receptor selectivity, particularly for RAR-γ agonists such as trifarotene, as well as inhibitors of cytochrome P450–mediated retinoic acid metabolism, which sustain endogenous activity and mitigate resistance (DX314 and other RAMBAs). In parallel, the development of nanocarriers, stimuli-responsive gels, and other targeted delivery systems has improved drug stability, bioavailability, and tolerability. Together, these innovations underscore the evolving role of retinoid-based interventions in precision dermatology, providing opportunities to optimize treatment outcomes for acne, psoriasis, photoaging, and other dermatological disorders while addressing the shortcomings of earlier generations. Full article

This study examines binary blends of three types of polyhydroxyalkanoates (PHAs)—poly(3-hydroxybutyrate) (PHB), poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBH), and poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P3HB4HB)—with a focus on their rheological, thermal, and mechanical behavior. The blends exhibit partial miscibility in both the melt and solid states. Glass transition analysis revealed that semicrystalline/amorphous PHA combinations are fully miscible (single Tg) at amorphous PHA contents below 30 wt%. Above this threshold, a two-phase morphology develops, consisting of crystalline spherulites embedded in an amorphous matrix. When the amorphous PHA content reached ≥30 wt%, the blends could be oriented by stretching, yielding materials that display thermoplastic elastomer (TPE)-like behavior without chemical modification of the base polymers. Thermal and mechanical characterization, supported by X-ray diffraction of samples before and after orientation, confirmed that the elastomeric properties originate from the multiphase architecture formed by crystalline and amorphous domains interconnected through a miscible amorphous fraction. Full article

The evolving bitumen market is increasingly complex due to variations in crude sources and transitions in refining processes, affecting the properties of bitumen. Unexpected additions of materials to alter bitumen’s properties could occur, where traditional PEN grade testing fails to detect modifications by inclusion of, for example, Re-refined Engine Oil Bottoms. This is the first study to comprehensively compare REOBs from European vs. North American sources and assess their effects on binder performance in a unified framework, performed by assessing the REOB-modified binders by identification, stability, compatibility, ageing susceptibility, and low-temperature properties. Two series of REOB-modified bitumen were prepared by blending 5, 10, and 15 wt.% REOB into hard grade bitumen. Results showed increased carbonyl formations (likely caused by lubricant additives) and phase instability during storage which can be attributed to saturates exudation. Rheological assessment demonstrated that REOB softens bitumen, although ageing causes a pronounced gain in stiffness. Low temperature rheological measurements showed that REOB-modified bitumen is prone to brittle fracture, suggesting a loss of relaxation properties. This study highlights that REOB is a material of inconsistent nature, with complex interactions with molecular groups of the base bitumen, causing increased ageing, phase instability, and brittle fracture susceptibilities. Full article

Background: Gastric cancer currently has the third highest mortality rate worldwide among cancer types. Despite gradual declines in mortality rates attributed to improvements in early detection and treatment, outcomes for advanced-stage disease are still poor. The identification of new biomarkers such as fibroblast growth factor receptor 2 (FGFR2) has opened new pathways for directed therapy in gastric cancer. Objective: This review aims to synthesize the current evidence on the role of FGFR2 in gastric cancer, focusing on its biological function and oncogenic mechanisms, diagnostic and prognostic modification, therapeutic targeting, and possible roadblocks in clinical application. Methods: A comprehensive literature search was conducted, selecting studies published between 2015 and 2025 using the MeSH terms “FGFR2 protein, human” [Supplementary Concept]) AND “Stomach Neoplasms”. Articles were screened based on relevance to gastric cancer, language (English), and availability of full text, yielding a final selection of 75 studies, including preclinical research, clinical trials, and reviews. Findings: We compiled and reported the evidence on FGFR2 detection methods, intra-tumoral heterogeneity of FGFR2 expression, effects of FGFR2 expression on prognosis, current therapy options targeting FGFR2, and challenges in pursuing this modality of treatment. Conclusion: FGFR2 represents a promising biomarker and therapeutic target in gastric cancer. Full article

This article examines the methodological challenges inherent in the digital 3D reconstructions of historical buildings using archival documentation. Unlike photogrammetry or laser scanning, archival-based modeling is crucial for buildings that never existed, no longer exist, or have undergone extensive modifications. Present research insights from a pilot educational project where 65 university students reconstructed 70 heritage buildings from Budapest (Hungary) in Archicad based solely on archival sources. In total, 75% of the buildings lacked at least one façade drawing, while nearly 20% showed contradictions between different plans (e.g., floor plan and section). Common challenges were identified, including missing drawings, contradictory plans, stylistic uncertainty, and software constraints, and their patterns were analyzed. To enhance modeling transparency, structured methods for recording paradata were proposed. Findings contribute to methodological rigor in virtual heritage reconstruction and support the reuse of archival models in architectural practice, research, and conservation. This study is among the first to propose a structured paradata framework tailored explicitly to archival-based 3D reconstructions, bridging methodological gaps between educational practice and professional heritage research. Full article

Blockchain technology, originally designed as a secure and immutable ledger, has expanded its applications across various domains. However, its scalability remains a fundamental bottleneck, limiting throughput, specifically Transactions Per Second (TPS) and increasing confirmation latency. Among the many proposed solutions, sharding has emerged as a promising Layer 1 approach by partitioning blockchain networks into smaller, parallelized components, significantly enhancing processing efficiency while maintaining decentralization and security. In this paper, we have conducted a systematic literature review, resulting in a comprehensive review of sharding. We provide a detailed comparative analysis of various sharding approaches and emerging AI-assisted sharding approaches, assessing their effectiveness in improving TPS and reducing latency. Notably, our review is the first to incorporate and examine the standardization efforts of the ITU-T and ETSI, with a particular focus on activities related to blockchain sharding. Integrating these standardization activities allows us to bridge the gap between academic research and practical standardization in blockchain sharding, thereby enhancing the relevance and applicability of our review. Additionally, we highlight the existing research gaps, discuss critical challenges such as security risks and inter-shard communication inefficiencies, and provide insightful future research directions. Our work serves as a foundational reference for researchers and practitioners aiming to optimize blockchain scalability through sharding, contributing to the development of more efficient, secure, and high-performance decentralized networks. Our comparative synthesis further highlights that while Bitcoin and Ethereum remain limited to 7–15 TPS with long confirmation delays, sharding-based systems such as Elastico and OmniLedger have reported significant throughput improvements, demonstrating sharding’s clear advantage over traditional Layer 1 enhancements. In contrast to other state-of-the-art scalability techniques such as block size modification, consensus optimization, and DAG-based architectures, sharding consistently achieves higher transaction throughput and lower latency, indicating its position as one of the most effective Layer 1 solutions for improving blockchain scalability. Full article

In the search for new materials to open up creative pathways for industry and research, modification is one of the best methods to implement. Developing materials with high sensitivity and selectivity for specific applications, such as ion sensing, remains a significant challenge. This work aims to introduce a novel metal–organic framework (MOF) derived from the well-established 2-amino-[1,1′-biphenyl]-4,4′-dicarboxylic acid MOF by modifying its structure to enhance its properties and applications. A luminescent 2-naphthyl moiety was attached to the amino group of the linker to form the new luminescent Al-based MOF Al-BP-Naph with a surface area of 456 m² g⁻¹ and a pore volume of 0.55 cm³ g⁻¹. Al-BP-Naph showed high selectivity towards Fe³⁺ sensing due to the overlapping absorption and excitation spectra of both Fe³⁺ and MOF. The MOF demonstrated a detection limit of approximately 6 × 10⁻⁶ mol L⁻¹ with a limit of quantification of about 19 × 10⁻⁶ mol L⁻¹ and a very fast response time (less than 10 s). It also had a Stern–Volmer constant of approximately 0.09 × 10⁵ L mol⁻¹, distinguishing it from other ions. Our work contributes to the expanding repertoire of functional materials with promising applications in sensing technologies, offering a novel MOF with superior properties for iron(III) ion detection. Full article

In the last twenty years, an increasing volume of research has characterized lipids as dynamic signaling molecules that play essential roles in various physiological and pathological processes, especially concerning chronic diseases such as cardiovascular disorders, diabetes, liver disease, neurodegeneration, cancer, obesity, diabetic and chronic kidney diseases and atherosclerosis. Dysregulation of lipid synthesis and storage, lipolysis, fatty acid oxidation, lipid signaling pathways, and organelle-specific lipid modifications, including mitochondrial phospholipid remodeling and endoplasmic reticulum stress induced by saturated fatty acids, are recognized as contributors to the initiation and progression of this pathogenesis. Concurrently with the increasing comprehension of lipid metabolism, the last decade has seen progress in the understanding of genome control, especially with non-coding RNAs (ncRNAs). MicroRNAs, long non-coding RNAs, and circular RNAs, as ncRNAs, are essential modulators of gene expression at the epigenetic, transcriptional, and post-transcriptional levels that affect a number of lipid metabolism-related processes, such as fatty acid synthesis and oxidation, cholesterol homeostasis, and lipid droplet dynamics. Therapeutically, ncRNAs hold considerable promise owing to their tissue specificity and modularity, with antisense oligonucleotides and CRISPR-based editing currently under preclinical evaluation. In this context, we review recent studies exploring the interplay between ncRNAs and the regulatory networks governing lipid metabolism, and how disruptions in these networks contribute to chronic disease. This emerging paradigm underscores the role of ncRNA–lipid metabolism interactions as central nodes in metabolic and inflammatory pathways, highlighting the need for a holistic approach to therapeutic targeting. Full article

Background: Bone marrow-derived mesenchymal stem cell exosomes (EXOs) are attractive in biotechnology and biomedical research, as they possess natural cell-targeting properties and can cross biological barriers by influencing the SDF-1/CXCR4 axis. Lipid calcium phosphate (LCP) consists of a calcium phosphate core and an asymmetric phospholipid bilayer containing abundant Ca²⁺ ions. AMD3100 modification of targeted LCP (T-LCP) can achieve targeted delivery to ischemic lesions via specific binding to CXCR4 receptors on various neuronal cell surfaces. Methods: Herein, a fused membrane formulation that simultaneously possesses EXO characteristics and enables targeted modification with AMD3100 was produced. The characteristics of biologically derived EXOs, artificially designed T-LCP, and the fused membrane formulation, including targeted delivery and gene loading efficiency, were then compared. Results: The fusion of artificially designed T-LCP with EXOs of natural origin is feasible and combines the advantages of both to achieve more prominent targeted delivery effects. Conclusions: MiRNA210-based gene therapy was effective in this study and provides a strategy for therapeutic efficacy in delivery systems with different targeting efficiencies. Full article

Owing to the inherent safety, environmental friendliness, and high theoretical capacity (820 mAh g⁻¹) of zinc metal, aqueous zinc-ion batteries (AZIBs) have emerged as up-and-coming alternatives to organic lithium-ion batteries. However, the insufficient electrochemically active sites, poor structural stability, and severe interfacial side reactions of cathode materials have always been key challenges, restricting battery gravimetric energy density and cycling stability. This article systematically reviews current mainstream AZIB cathode material systems, encompassing layered manganese- and vanadium-based metal oxides, Prussian blue analogs, and emerging organic polymers. It focuses on analyzing the energy storage mechanisms of different material systems and their structural evolution during Zn²⁺ (de)intercalation. Furthermore, mechanisms of innovative strategies for improving cathodes are thoroughly examined here, such as nanostructure engineering, lattice doping control, and surface coating modification, to address common issues like structural degradation, manganese/vanadium dissolution, and interface passivation. Finally, this article proposes future research directions: utilizing multi-scale in situ characterization to elucidate actual reaction pathways, constructing artificial interface layers to suppress side reactions, and optimizing full-cell design. This review provides a new perspective for developing practical AZIBs with high specific energy and long lifespans. Full article

The rapid growth of e-commerce has intensified the need for efficient last-mile delivery, making unmanned aerial vehicles (UAVs) a promising solution. However, despite their potential, practical deployment remains limited by how to effectively plan depot locations and UAV fleet sizes under stochastic customer demands with probabilistic same-day modifications. Existing approaches often address the strategic and operational decisions separately, leading to inefficiencies and infeasible solutions in practice. This study develops a unified two-stage decision framework integrating strategic depot location and UAV fleet allocation with operational assignment and scheduling. Three strategic models are considered: a deterministic model, a stochastic model solved via Sample Average Approximation (SAA), and a robust optimization model. Operational decisions assign UAV trips to realized requests while respecting time-slot and UAV availability constraints. Deterministic and SAA models are solved directly as integer programs, whereas the robust model is tackled via a logic-based Benders decomposition framework, with all approaches evaluated through simulation. The results show that the robust model provides overly conservative solutions, resulting in higher costs; the deterministic model minimizes cost but risks service failures; and the SAA approach balances cost and service across demand scenarios. The findings demonstrate the value of jointly considering strategic and operational decisions in UAV delivery design and provide practical guidance for UAV logistics operators. The proposed framework helps firms select appropriate planning models that align with their risk tolerance and service reliability goals, thereby improving the feasibility and competitiveness of UAV-based delivery systems. Full article

Physical activity practice and excessive screen time affect adolescent girls’ body satisfaction and body image. This study aimed to estimate the association between screen time and physical activity in relation to body dissatisfaction and body image among girls from different Brazilian regions, considering both the direct effect and the influence of sociodemographic characteristics and school affiliation. This is a cross-sectional study based on secondary data analysis. The outcomes were body dissatisfaction and body image dissatisfaction due to excessive thinness and excessive fat. Physical activity and screen time were independent variables. The moderating variables included sociodemographic characteristics and school affiliation. Direct effects were observed in active girls with a lower odds ratio (OR) of dissatisfaction due to excessive thinness (Southeast region, OR: 0.56, 95% CI: 0.34–0.90; South region, OR: 0.43, 95% CI: 0.19–0.43), whereas those with high screen times were more likely to report dissatisfaction due to excessive fat (Southeast region, OR: 1.80, 95% CI: 1.35–2.40; Northeast region, OR: 1.97, 95% CI: 1.28–3.03). Effect modification was observed based on sociodemographic characteristics and school affiliation. These behaviors were directly associated with body dissatisfaction, and age, school affiliation, skin color, and maternal education were important moderators of the relationship between physical activity and screen time. Full article