Search Results (1,575)

Chronic hepatitis B remains difficult to cure because viral persistence is maintained within hepatocytes through covalently closed circular DNA and integrated viral sequences that continue to drive antigen production even when viral replication is effectively suppressed. Although current antiviral therapies improve clinical outcomes and slow disease progression, they rarely achieve a durable functional cure, defined as sustained loss of hepatitis B surface antigen (HBsAg), with or without anti-HBs seroconversion. This limitation has shifted attention toward therapeutic strategies that depend on precise and reliable drug delivery to the liver. Several recent reviews have focused on antiviral mechanisms or immune modulation. However, the specific contribution of drug delivery to therapeutic success has not been systematically addressed. This review examines hepatocyte-targeted drug delivery as a central determinant of success for emerging hepatitis B therapies. Rather than cataloging individual therapeutic agents, this review adopts a delivery-centered framework that links viral persistence biology with translational feasibility across therapeutic classes. Recent advances in ligand-mediated hepatocyte targeting have demonstrated consistent liver specificity and clinical feasibility, enabling meaningful reductions in viral transcripts and antigens. At the same time, we discuss why more complex delivery platforms continue to face challenges related to intracellular access, immunogenicity, scalability, and safety during repeated dosing, particularly for strategies intended to act within the nucleus. Translational and clinical considerations, including differences between experimental models and human infection, manufacturing and regulatory constraints, and the demands of long-term treatment, are also addressed. Overall, this review supports a pragmatic path toward functional cure based on rational combination therapies, coordinated delivery strategies, and patient-tailored approaches, with delivery science serving as the critical link between biological insight and durable clinical benefit. Full article

Systemic mastocytosis comprises a group of clonal mast cell disorders characterized by multisystem involvement. Bone involvement represents a major source of morbidity, particularly in young men affected by indolent systemic mastocytosis. This review provides an integrated and up-to-date overview of SM-related bone disease. We dissect the dual and context-dependent role of mast cells in bone remodeling, detailing how they promote osteoclastogenesis, suppress osteoblast function, and, in advanced disease, drive osteosclerosis. We critically appraise available treatments, including classic anti-resorptive therapy and emerging anabolic strategies. We further discuss the transformative impact of KIT-directed tyrosine kinase inhibitors, particularly avapritinib, which has demonstrated for the first time the ability to reverse not only osteoporosis but also osteosclerosis. Finally, we explore the emerging role of machine learning models in SM, proposing their application to individualized prediction of osteoporosis and fracture risk in SM. By bridging clinical care, bone biology, and therapeutic advances, this review underscores the need for a paradigm shift in which SM-related bone disease is recognized as a dynamic process requiring early identification, integrated risk stratification, and coordinated use of anti-resorptive, disease-modifying, and data-driven precision approaches to prevent fractures and improve long-term outcomes and quality of life in this delicate category of patients. Full article

Polynomial exact solutions of the Navier–Stokes equations for describing micropolar incompressible fluid flows with energy dissipation are reported. The transformation of mechanical energy into thermal energy is taken into account. The heat equation for the Rayleigh function contains the sum of the squares of the components of the Cauchy velocity tensor (the main component for the dissipative function). Unidirectional homogeneous and non-homogeneous fluid flows with moment stresses are considered. The solvability of overdetermined systems for studying homogeneous and non-homogeneous shear flows is studied. The paper pays attention to the exact integration of equations for three-dimensional flows. The construction of classes of exact solutions is carried out first using the Lin–Sidorov–Aristov solution family. In other words, the velocity field depends linearly on part of the coordinates. The coefficients of the linear forms of the velocity field depend on the third coordinate and time. The pressure field and the temperature field are quadratic forms with similar functional arbitrariness. In addition, exact solutions for the velocity field with a nonlinear dependence on part of the coordinates are considered. Full article

This study examines multi-celebrity deployment as a destination branding practice, using Seoul as an empirical case. The analysis draws on 172 official tourism promotional videos released by the Seoul Tourism Organization between 2011 and 2025, featuring 67 identifiable celebrities and 438 destination references. A qualitative content analysis examines how celebrity endorsement is organized as a branding mechanism, focusing on who appears, what is represented, and how representations are communicated across media formats over time. The findings show that Seoul’s tourism promotion operates through a structured multi-celebrity branding system in which multiple endorsers are coordinated across campaigns and periods. Endorser selection is anchored in Hallyu-affiliated celebrities who function as primary carriers of destination meaning, while emerging, non-Hallyu, and heritage-linked figures occupy complementary roles that broaden representational scope and reduce reliance on individual figures. Celebrity endorsement continues to emphasize major and symbolically dense attractions, while also extending visibility to everyday neighborhoods and locally oriented urban landscapes. Long-term ambassador-led campaigns coexist with travel vlogs and other creative video formats, enabling variation in narrative tone and experiential framing. Theoretically, the study extends celebrity endorsement research by conceptualizing multi-celebrity deployment as a coordinated branding system. Practically, the findings show how destination marketing organizations can mobilize a broad pool of celebrity resources to structure endorsement portfolios over time. Coordinated use of celebrities with different levels of familiarity supports wider spatial representation, enables ongoing narrative renewal, and maintains promotional continuity across changing media environments. This configuration is most applicable to destinations with strong cultural visibility and an established celebrity ecosystem, and may be less transferable to destinations with limited access to influential figures. Full article

OGG1 and MUTYH are base excision repair (BER) DNA glycosylases (DGs) from the Helix–hairpin–Helix superfamily responsible for initiating and coordinating the repair of 8-oxo-7,8-dihydroguanine (OG), and its replication-derived mispair with adenine (OG:A), respectively. The DNA repair activities of these DGs are pivotal to safeguarding nuclear and mitochondrial genomes. Indeed, DG functional impairment is associated with numerous pathologies, including neurodegenerative diseases, metabolic syndromes, and cancer. The timely and precise localization and processing of oxidized nucleobases carried out by these DGs are modulated by a complex regulatory network at both transcriptional and posttranslational levels, as well as intricate protein–protein interaction networks. In the absence of regulation, inappropriate and imbalanced DG activity may trigger telomeric instability, changes in transcriptional profiles and cell death. This review focuses on summarizing key features of OGG1 and MUTYH function, with a special emphasis on structure, regulation, and novel emerging roles. Full article

In order to identify an efficient and environmentally friendly washing agent for heavy metal-contaminated soil, this study selected seven natural amino acids—arginine (Arg), alanine (Ala), glycine (Gly), cysteine (Cys), lysine (Lys), threonine (Thr), and glutamic acid (Glu)—based on their water solubility, effectiveness, and functional group characteristics. According to the removal efficiencies for zinc (Zn), lead (Pb), and cadmium (Cd), Cys, which contains a specific sulfhydryl group (-SH), was chosen as the target leaching agent for the remediation of composite-contaminated soil. The optimal process conditions were determined as follows: 0.02 mol/L of cysteine concentration, liquid-to-soil ratio of 20:1 (mL/g), 10 min of ultrasonic time, and pH = 8.0. The order of removal efficiency was Pb (40.8%) > Zn (21.6%) > Cd (19.9%). The leaching process selective effects on the speciation fractions of Zn, Pb, and Cd in the soil, and these differences can be explained by the hard–soft acid–base theory and the strength of coordination between the metals and cysteine. Mechanism analysis revealed that soil washing essentially achieves selective extraction of the target metal through strong chemical interactions between functional groups of cysteine and active metal sites of secondary minerals in the soil. Cysteine is a green remediation agent with high selectivity and environmental compatibility for contaminated soil. Its application requires precise design and risk assessment based on the chemical properties of the target metals, while ensuring the sustainability of the soil to maintain the ecological functions and long-term health of the remediated soil. Full article

Micro-foundational HRM has advanced our understanding of how employees perceive and respond to HR practices, yet explanations of how HR systems can generate and sustain coordinated action in day-to-day work remain underspecified. This article presents a theory-building integrative review that specifies a constrained, generative mechanism grounded in observable interaction episodes. We propose a functional architecture that assigns constructs to distinct explanatory roles: enabling states (Role A), interaction episodes as the behavioral engine (Role B), and emergent coordination products (Role C). Psychological safety is positioned as an enabling condition that shifts the likelihood and quality of enactment, whereas collective leadership behavior (CLB) is defined as response-inclusive influence episodes (an influence attempt plus an observable response such as uptake, contestation, neglect, or sanction). We formalize a recursive safety–CLB cycle in which response patterns update subsequent safety and influence dispersion over time, which can yield divergent coordination trajectories even when HR conditions are broadly similar. The framework generates discriminant predictions about response profiles, dispersion versus centralization of influence, and temporal signatures, and it clarifies minimal design requirements for testing recursion with episode-level and intensive longitudinal evidence. We discuss implications for micro-foundational HRM, measurement alignment, and testable design-relevant implications for HR system design as an interaction-relevant cue environment. Full article

Background: Gum Arabic (GA) is a natural polysaccharide widely recognized for its antioxidant and anti-inflammatory properties; however, its functional behavior as a biopolymeric gel and the mechanisms underlying its selective effects on cancer-related redox microenvironments remain insufficiently characterized. It is imperative to note that the interaction between its physicochemical properties and its biological activity in colorectal cancer remains to be fully clarified. Methods: This study aimed to evaluate the antineoplastic potential of GA in human colorectal cancer (CRC) cell lines (HT-29 and HCT-116) compared to normal fibroblasts (MRC-5) using the MTS assay. Oxidative stress-related molecular responses were assessed by quantitative PCR analysis of GPX4, GSTA2, CAT, NFKB, and SOD1 expression. In parallel, extracellular concentrations of key metal ions (Fe²⁺, Zn²⁺, Mn²⁺, Mg²⁺, Cu²⁺, and Al³⁺) were quantified following GA exposure. To establish its functional gel characteristics, rheological measurements were performed to assess viscosity and shear-dependent behavior, and USP-compliant in vitro kinetic studies were conducted to evaluate time-dependent release properties. Results: GA induced dose-dependent cytotoxicity in HT-29 and HCT-116 colorectal cancer cells, while MRC-5 fibroblasts exhibited comparatively higher viability across the tested concentration range, indicating reduced sensitivity in normal cells. Rheological analysis revealed concentration- and ion-dependent viscoelastic behavior, identifying a 10% (w/w) GA formulation as optimal due to its balanced low-shear viscosity and controlled shear-thinning properties. Kinetic studies demonstrated a defined, diffusion-governed release profile under physiologically relevant conditions. At the molecular level, significant upregulation of GPX4 and GSTA2 was observed in both cancer cell lines, whereas NFKB expression increased selectively in HT-29 cells, with no notable changes in CAT or SOD1 expression. Additionally, GA treatment resulted in marked increases in Fe²⁺, Zn²⁺, and Mn²⁺ levels, indicating modulation of the redox–ionic microenvironment. Conclusions: These findings demonstrate that GA functions as a natural, ion-responsive biopolymeric system with defined rheological and kinetic properties, capable of selectively targeting colorectal cancer cells through coordinated genetic and ionic regulation of oxidative stress. Collectively, the results position GA as a promising functional gel-based platform for future redox-modulated therapeutic strategies in colorectal cancer. Full article

Coordinated control across multiple signalized intersections is essential for mitigating congestion propagation in urban road networks. However, existing DQN-based approaches often suffer from unstable action switching, limited interpretability, and insufficient capability to model spatial spillback between adjacent intersections. To address these limitations, this study proposes a Policy-Regulated and Aligned Deep Q-Network (PRA-DQN) for cooperative multi-intersection signal control. A differentiable policy function is introduced and explicitly trained to align with the optimal Q-value-derived target distribution, yielding more stable and interpretable policy behavior. In addition, a cooperative reward structure integrating local delay, movement pressure, and upstream–downstream interactions enables agents to simultaneously optimize local efficiency and regional coordination. A parameter-sharing multi-agent framework further enhances scalability and learning consistency across intersections. Simulation experiments conducted on a 2 × 2 SUMO grid show that PRA-DQN consistently outperforms fixed-time, classical DQN, distributed DQN, and pressure/wave-based baselines. Compared with fixed-time control, PRA-DQN reduces maximum queue length by 21.17%, average queue length by 18.75%, and average waiting time by 17.71%. Moreover, relative to classical DQN coordination, PRA-DQN achieves an additional 7.53% reduction in average waiting time. These results confirm the effectiveness and superiority of the proposed method in suppressing congestion propagation and improving network-level traffic performance. The proposed PRA-DQN provides a practical and scalable basis for real-time deployment of coordinated signal control and can be readily extended to larger networks and time-varying demand conditions. Full article

Drooling and dysphagia are frequent and disabling complications in Parkinson’s disease (PD) and often coexist, with drooling mainly resulting from impaired saliva clearance due to reduced oral motor control and potentially worsening swallowing function. This study aimed to evaluate whether botulinum toxin type A (BoNT/A) injections into the major salivary glands, beyond controlling drooling, could also improve swallowing performance using clinical and neurophysiological measures. Twenty PD patients with severe drooling and dysphagia underwent bilateral ultrasound-guided BoNT/A injections into the parotid and submandibular glands. Assessments were performed at baseline and at 1, 8, and 12 weeks post-injection. Dysphagia severity was evaluated using the Penetration–Aspiration Scale and the Dysphagia Severity Rating Scale. Neurophysiological assessment included electromyographic recordings from suprahyoid/submental and cricopharyngeal muscles, together with mechanomyography analysis of laryngeal movement during swallowing. Following BoNT/A treatment, a consistent reduction in drooling was observed, accompanied by significant improvements in clinical dysphagia scores and neurophysiological swallowing parameters across all follow-up time points. These findings suggest that incobotulinumtoxinA injections into salivary glands not only reduce drooling but also enhance swallowing function in PD patients, possibly by facilitating oral floor and oropharyngeal motor coordination secondary to improved saliva management. Full article

The increasing penetration of distributed generation in active distribution networks (ADNs) introduces significant voltage regulation challenges due to the intermittent nature of renewable energy sources. Electric springs (ESs) have emerged as a cost-effective alternative to conventional FACTS devices for voltage regulation, requiring minimal energy storage while providing fast, flexible reactive power compensation. This paper proposes a deep reinforcement learning (DRL)-based approach for voltage regulation in balanced active distribution networks with distributed generation. Electric springs are deployed at selected buses in series with noncritical loads to provide flexible voltage support. The main contributions of this work are: (1) a novel region-based penalized reward function that effectively guides the DRL agent to minimize voltage deviations; (2) a coordinated control strategy for multiple ESs using the Deep Deterministic Policy Gradient (DDPG) algorithm, representing the first application of DRL to ES-based voltage regulation; (3) a systematic hyperparameter tuning methodology that significantly improves controller performance; and (4) comprehensive validation demonstrating an approximately 40% reduction in mean voltage deviation relative to the no-control baseline. Three well-known continuous-control DRL algorithms, Twin Delayed Deep Deterministic Policy Gradient (TD3), Proximal Policy Optimization (PPO), and DDPG, are first evaluated using the default hyperparameter configurations provided by MATLAB R2022b.Based on this baseline comparison, a dedicated hyperparameter-tuning procedure is then applied to DDPG to improve the robustness and performance of the resulting controller. The proposed approach is evaluated through simulation studies on the IEEE 33-bus and IEEE 69-bus test systems with time-varying load profiles and fluctuating renewable generation scenarios. Full article

Background: Children with special healthcare needs (CSHCNs) face persistent barriers to timely immunization in China, but comparative evidence across disease groups and vaccines, and data on immune function, are limited. Methods: We conducted a retrospective cohort study linking electronic medical records, vaccination records, and a structured telephone and questionnaire follow-up. We estimated timely vaccination by National Immunization Program (NIP) dose definitions, assessed catch-up completion at follow-up, and compared cellular/humoral/complement immune indices with published pediatric reference ranges. Group differences used ANOVA/Kruskal–Wallis and chi-square (χ²)/Fisher’s exact tests with Bonferroni correction. Results: Timely vaccination was lower than the national healthy child benchmarks for all NIP vaccines (all p < 0.001); the Japanese encephalitis virus (JE; 24.0%) and measles-containing vaccine (MCV; 25.9%) had the lowest timely completion. A subset of CSHCNs did not receive recommended catch-up vaccinations, primarily due to persistent caregivers’ concern and point of vaccination (POV) staff’s hesitancy. Delays clustered in neonatal/perinatal disorders for Bacillus Calmette–Guérin (BCG) and hepatitis B vaccine, dose 1 (HepB1). Catch-up completion was highest for hepatitis B vaccine, dose 3 (HepB3) (86.3%) and BCG (81.8%), and lowest for the diphtheria and tetanus vaccine (DT) (49.4%); MCV2 completion was particularly low in hematological diseases. Immunoglobulin A (IgA) and immunoglobulin G (IgG) concentrations were significantly lower in neonatal/perinatal disorders and infectious disease groups versus neurological and immune disorder groups (p < 0.05). No severe adverse events were reported after catch-up. Conclusions: CSHCNs in China face substantial barriers to timely NIP immunization. Timeliness and catch-up vary substantially by vaccine and underlying condition; neonatal/perinatal disorders contribute disproportionately to early-life delays. Disease-specific guidance, strengthened POV–specialist clinic coordination, immunological monitoring, and supportive policies could improve the vaccination coverage and effectiveness in this vulnerable population. Full article

A target state estimation method based on multiple quadrotors is proposed for unknown maneuvering targets, and a distributed formation control method Image-Based Visual Servoing (IBVS) is also proposed to achieve encirclement tracking of unknown maneuvering targets. In the tracking control, collision avoidance constraints for nodes within the formation are also introduced, and based on the shared position information within the formation, the positions of other nodes within the Field of View (FOV) of each node are predicted for detecting unknown targets. Firstly, an Interacting Multiple Model (IMM) was designed based on multiple motion modes to estimate the position and velocity of the target. A virtual camera coordinate system containing translational and yaw rotations was established between the formation and the target based on the estimated values. Then, a distributed control method based on IBVS was further designed by combining image deviation. At the same time, a safe distance between nodes within the formation was introduced, and collision avoidance constraints of the Control Barrier Function (CBF) were designed. Finally, the position of the formation nodes within the FOV was predicted. The simulation results demonstrate that, utilizing the proposed estimation method, the estimation accuracy for target velocity improves by 26.5% in terms of Root Mean Square Error (RMSE) compared to existing methods. Furthermore, the proposed control method enables quadrotor formations to successfully achieve encirclement tracking of unknown maneuvering targets, significantly reducing tracking errors in comparison to conventional approaches. Full article

Cricket fast bowlers rely on the front leg as a mechanical lever during front foot contact, yet the underlying mechanisms that govern front leg behaviour remain unclear. This study examined front leg mechanics in 18 junior fast bowlers (17.2 ± 1.7 years) using a 14-camera 3D motion capture system and force platforms. Joint power and angular impulse analyses were performed to quantify hip and knee extension–flexion mechanics from front foot contact to ball release, enabling the classification of joint function as active (concentric), controlled (eccentric), or negligible. Power and angular impulse profiles revealed that front leg motion was dominated by controlled (eccentric) power at both the hip and knee, indicating that the regulation of knee angle occurred primarily through eccentric braking rather than concentric quadriceps extension. These findings suggest that achieving a “braced leg” position via isolated knee extensor strengthening may be ineffective. To evaluate whether kinematics and anthropometry contributed to performance, a multiple linear regression model was used. Run-up speed at back foot contact emerged as the strongest predictor of ball speed, whereas knee angle at front foot contact showed only a small and non-significant effect. Overall, the results indicate that front leg behaviour reflects coordinated whole-body dynamics, and performance interventions should prioritise momentum generation and timing across the kinetic chain rather than isolated joint actions. Full article

Cell adhesion molecules (CAMs) are key regulators of tissue structural integrity and functional coordination, yet their specific role in the adaptation of yak lung tissue to high-altitude hypoxia remains unelucidated. Thus, we employed transcriptomic sequencing (RNA-seq), molecular biology assays, and single-cell RNA-seq (scRNA-seq) to analyze the expression characteristics of CAMs in yak lung tissues at high and low altitudes. Trypsin or collagenase digestion showed higher cell counts in high-altitude yak lungs (p < 0.05). RNA-seq analysis revealed significant enrichment of differentially expressed genes (DEGs) in adhesion-related pathways. Inductively coupled plasma mass spectrometry detected elevated Ca²⁺ levels in high-altitude yak lungs (p < 0.05). Quantitative real-time PCR (qRT-PCR) detection of key genes from five major families of CAMs revealed the downregulation of cadherin and integrin family-related genes, and upregulation of immunoglobulin superfamily-related genes, in high-altitude yak lungs (p < 0.05), corroborated by immunohistochemical (IHC) staining. A 10× scRNA-seq revealed adhesion changes in 9 of 15 lung cell subpopulations, with differentially expressed CAMs involving integrins. This study demonstrates that yak lung tissue establishes a sophisticated adhesive homeostasis through differential CAMs regulation. This strategy optimizes pulmonary immune responses and energy allocation, ensures structural integrity and functional coordination, and thereby facilitates superior acclimatization to higher-altitude hypoxia. Full article