Search Results (275)

Background/Objectives: Sepsis-associated liver injury (SALI) is a critical and often early complication of sepsis, defined by distinct hyper-inflammatory and immunosuppressive phases that shape patient phenotypes. Methods: Characterizing these phases establishes a foundation for immunomodulation strategies tailored to individual immune responses, as discussed subsequently. Results: The initial inflammatory response activates pathways such as NF-κB and the NLRP3 inflammasome, leading to a cytokine storm that damages hepatocytes and is frequently associated with higher SOFA scores and a higher risk of 28-day mortality. Kupffer cells and infiltrating neutrophils exacerbate hepatic injury by releasing proinflammatory cytokines and reactive oxygen species, thereby causing cellular damage and prolonging ICU stays. During the subsequent immunosuppressive phase, impaired infection control and tissue repair can result in recurrent hospital-acquired infections and a poorer prognosis. Concurrently, hepatocytes undergo significant metabolic disturbances, notably impaired fatty acid oxidation due to downregulation of transcription factors such as PPARα and HNF4α. This metabolic alteration corresponds with worsening liver function tests, which may reflect the severity of liver failure in clinical practice. Mitochondrial dysfunction, driven by oxidative stress and defective autophagic quality control, impairs cellular energy production and induces hepatocyte death, which is closely linked to declining liver function and increased mortality. The gut-liver axis plays a central role in SALI pathogenesis, as sepsis-induced gut dysbiosis and increased intestinal permeability allow bacterial products, including lipopolysaccharides, to enter the portal circulation and further inflame the liver. This process is associated with sepsis-related liver failure and greater reliance on vasopressor support. Protective microbial metabolites, such as indole-3-propionic acid (IPA), decrease significantly during sepsis, removing key anti-inflammatory signals and potentially prolonging recovery. Clinically, SALI most commonly presents as septic cholestasis with elevated bilirubin and mild transaminase changes, although conventional liver function tests are insufficiently sensitive for early detection. Novel biomarkers, including protein panels and non-coding RNAs, as well as dynamic liver function tests such as LiMAx (currently in phase II diagnostics) and ICG-PDR, offer promise for improved diagnosis and prognostication. Specifying the developmental stage of these biomarkers, such as identifying LiMAx as phase II, informs investment priorities and translational readiness. Current management is primarily supportive, emphasizing infection control and organ support. Investigational therapies include immunomodulation tailored to immune phenotypes, metabolic and mitochondrial-targeted agents such as pemafibrate and dichloroacetate, and interventions to restore gut microbiota balance, including probiotics and fecal microbiota transplantation. However, translational challenges remain due to limitations of animal models and patient heterogeneity. Conclusion: Future research should focus on developing representative models, validating biomarkers, and conducting clinical trials to enable personalized therapies that modulate inflammation, restore metabolism, and repair the gut-liver axis, with the goal of improving outcomes in SALI. Full article

This study employs a mixed-methods approach to investigate the current use and evolving needs of dormitory environments through a cross-analysis of existing research and user experience. A two-phased PRISMA-guided systematic literature review for both global and China-based content was conducted, which was then linked to an examination of eight high-density dormitory spaces in Shanghai. The case studies were analyzed using qualitative content analysis methods, incorporating both spatial analysis and netnography to provide a comprehensive understanding of dormitory use. The cross-analysis highlights a persistent design–use gap: efficiency-driven layouts underdeliver on privacy and comfort, prompting compensatory user modifications. Findings also reveal that most rooms fell below suggested standards; circulation was mainly limited to a single central aisle with no entrance buffer, constraining flexibility and privacy. Students responded to these limitations with small-scale personalization, such as bed curtains, mattress toppers, chair swaps, lighting, and storage hacks, to mitigate acoustic/visual exposure and comfort deficits. With the rising demand for dormitories and based on these insights, we identified three critical dimensions for future dormitory design: privacy, equity, and personalization. These findings underscore that current designs fail to fully satisfy even basic functional requirements, making it essential to develop strategies that respond to evolving needs and integrate considerations of well-being, comfort, and user autonomy. Full article

Tidal dynamics substantially govern nearshore circulation patterns. The discharge of sewage at different tidal stages may have a significant impact on the dilution of pollutants. However, discussions on tidal phase sewage discharge strategy are still rare. This study focuses on the narrow tidal passage in the Ningbo-Zhoushan sea area, which receives a large amount of coastal wastewater, but the role of the unique hydrodynamic processes in the dilution of pollutants in this region remains unclear. By using a combination of on-site measurements and the FVCOM-dye simulation method, the scenario of high-concentration sewage retention in the tidal passage was demonstrated. The coastal residual circulation formed by strong tidal currents confined over 78% of the tracers within a 3 km range near the shore, and a subsurface dye accumulation zone emerged along the 25–50 m isobaths. Monsoon transitions regulated pollution plumes, inducing 5–8% seasonal variability in pollution footprints controlled by wind-tide-stratification interplay. The tidal phase discharge strategy was revealed to be highly effective in this study; both submerged discharge in deep-water zones and intermittent discharge strategies implemented in shallow-water zones significantly reduce the spatial coverage of high-concentration sewage plumes. Our findings highlight the importance of formulating discharge strategies based on tidal phases in typical narrow and deep tidal passages. Full article

Gastroesophageal cancers including esophageal and gastric cancer remain major causes of global cancer mortality, primarily due to late diagnosis and high recurrence rates after curative treatment. Current surveillance methods, such as endoscopy and imaging, are invasive, costly, and often inadequate for detection. Blood-based biomarkers (“liquid biopsies”) offer a minimally invasive alternative capable of real-time tumor monitoring. In this review, we summarize recent advances across all major classes of blood-derived biomarkers: circulating tumor DNA (ctDNA), methylated DNA, cell-free RNAs (microRNAs, lncRNAs, circRNAs), circulating proteins, autoantibodies, circulating tumor cells, extracellular vesicles, and metabolites. Reviewing the existing literature on gastroesophageal cancers, we highlight current evidence, validation phases, performance metrics, and limitations. Special attention is given to clinical trial evidence, including ctDNA monitoring studies, that demonstrated earlier recurrence detection compared to imaging. While blood-based biomarker analysis has not yet supplanted endoscopy as standard of care in gastroesophageal cancer surveillance, the convergence of multi-analyte assays, AI, and clinical validation trials positions liquid biopsy as a transformative tool in the surveillance of gastroesophageal cancers. Full article

This paper investigates the channel performance through a high-gain, circularly polarized microstrip patch antenna that is developed for contemporary wireless communication systems. The proposed antenna creates two orthogonal modes for circular propagation with slightly varying resonance frequencies by using a cross line and truncations to circulate surface currents. Compactness, reduced surface wave losses, and enhanced impedance bandwidth are made possible by the coaxial probe feed, periodic electromagnetic gap (EBG) slots, and fractal patch geometry. For in-phase reflection and beam focusing, a specially designed single-layer metasurface (MTS) reflector with an 11 × 11 circular aperture array is placed 20 mm behind the antenna. A log-normal shadowing model was used to test the antenna in real-world scenarios, and the results showed a strong correlation between the model predictions and actual data. At up to 250 m, the polarization-agile, high-gain antenna demonstrated reliable performance across a variety of channel conditions, enabling accurate characterization of the Channel Quality Indicator (CQI), Signal-to-Noise Ratio (SNR), and Reference Signal Received Power (RSRP). By combining cutting-edge antenna architecture with an empirical channel performance study, this research presents a compact, affordable, and fabrication-friendly solution for increased wireless coverage and efficiency. Full article

The molten salt reactor (MSR) is a prominent Generation IV nuclear reactor concept that offers substantial advantages over conventional solid-fueled systems, including enhanced fuel utilization, inherent passive safety features, and significant reductions in long-lived radioactive waste. Central to its safety strategy is a reliance on natural circulation (NC) mechanisms, which eliminate the need for active pumping systems and enhance system reliability during normal and off-normal conditions. However, the challenges associated with molten salts, such as their high melting points, corrosivity, and material compatibility issues, render experimental investigations inherently complex and demanding. Therefore, the use of high-Pr-number surrogate fluids represents a practical alternative for studying molten salt behavior under safer and more accessible experimental conditions. In this study, a single-phase natural circulation loop setup at the University of Idaho’s Thermal–Hydraulics Laboratory was employed to investigate NC behavior under various operating conditions. The RELAP5-3D code was initially validated against water-based experiments before employing Therminol-66, a high-Prandtl-number surrogate for molten salts, in the natural circulation loop for the first time. The RELAP5-3D results demonstrated good agreement with both steady-state and transient experimental results, thereby confirming the code’s ability to model NC behavior in a single-phase flow regime. The results also highlighted certain experimental limitations that should be addressed to enhance the NC loop’s performance. These include increasing the insulation thickness to reduce heat losses, incorporating a dedicated mass flow measurement device for improved accuracy, and replacing the current heater with a higher-capacity unit to enable testing at elevated power levels. By identifying and addressing the main causes of these limitations and uncertainties during water-based experiments, targeted improvements can be implemented in both the RELAP5 model and the experimental setup, thereby ensuring that tests using a surrogate fluid for MSR analyses are conducted with higher accuracy and minimal uncertainty. Full article

The novel goose parvovirus (NGPV), an agent of short beak and dwarfism syndrome (SBDS), has been circulating in China since 2015; however, the absence of systematic genetic evolution and diversity analysis has limited our understanding of the viral epidemic tendency and genetic basis for cross-species transmission and pathogenicity attenuation. In this study, five NGPVs were isolated in 2022–2023, and their genomes were sequenced. A comprehensive analysis of genetic evolution and diversity was conducted using sequences of representative waterfowl parvoviruses isolated at different periods. Subsequently, pathogenicity and sero-response studies in ducks were also conducted. The results indicated that circulating NGPV in China could be divided into two genotypes and two subtypes and three epidemic phases from evolutionary and temporal dimensions, respectively. Currently, NGPV Ia is the dominant genotype across China. Phylogenetic analysis demonstrated that VP1 was the leading factor in viral evolution. The genetic diversity analysis showed regular mutation sites in both proteins. According to their location and resultant structural changes, combining the results of pathogenicity and humoral immune response, several substitutes are possibly latent residues for the virus to achieve cross-host infection, escape from antibody recognition, and undergo pathogenicity alteration. The findings of this study provide novel insights into the viral epidemic tendency and genetic basis for cross-species transmission and pathogenicity attenuation and will help to facilitate the development of vaccines and antiviral therapy. Full article

The parallel operation of converters is increasingly being adopted to meet higher power demands and improve reliability. However, open-circuit faults in semiconductor switches must be located quickly to prevent unnecessary derating and costly offshore interventions. In parallel topologies, zero-sequence circulating current (ZSCC) distorts phase current residuals at fault inception, making conventional residual-based fault diagnosis methods unreliable. This paper proposes a fast fault diagnosis method that integrates phase current residual analysis with real-time ZSCC polarity. The method monitors which residuals exceed a fixed threshold and compares the polarity of the dominant residual with that of the ZSCC. In this way, it can distinguish and locate single-switch, same-converter dual-switch, and cross-converter dual-switch faults. A three-stage timing window mechanism captures residual and ZSCC signatures within only a few sampling periods, enabling precise fault location without additional sensors. Experimental and simulation results verify the accuracy and robustness of the proposed method, demonstrating its potential for practical deployment in offshore wind turbines. Full article

Multilevel active bridge converters are potential candidates for many modern high-power DC applications due to their ability to integrate multiple sources while minimizing weight and volume. Therefore, this paper deals with an analytical, simulation-based, and experimentally verified investigation of their circulating current behavior, power factor performance, and power loss characteristics. A high-frequency link analysis framework is developed to characterize voltage, current, and power transfer waveforms, providing insight into reactive power generation and its impact on overall efficiency. By introducing a modulation-based control approach, the proposed converters significantly reduce circulating currents and enhance the power factor, particularly under varying phase-shift conditions. Compared to quadruple active bridge topologies, the discussed multilevel architectures offer reduced transformer complexity and improved power quality, making them suitable for demanding applications such as electric vehicles and aerospace systems. Full article

The article presents an analysis of current (during the period 1985–2022) and projected (during the period 2025–2099) changes in the hydrological regime of the Buktyrma, Yesil, and Zhaiyk river basins in Kazakhstan under the conditions of global climate change. This study is based on the integration of data from General Circulation Models (GCMs) of the sixth phase of the CMIP6 project, socio-economic development scenarios SSP2-4.5 and SSP5-8.5, as well as the results of hydrological modelling using the SWIM model. The studies were carried out with an integrated approach to hydrological change assessment, taking into account scenario modelling, uncertainty analysis and the use of bias correction methods for climate data. A calculation method was used to analyse the intra-annual distribution of runoff, taking into account climate change. Detailed forecasts of changes in runoff and intra-annual water distribution up to the end of the 21st century for key water bodies in Kazakhstan were obtained. While the projections of river flow and hydrological parameters under CMIP6 scenarios are actively pursued worldwide, few studies have explicitly focused on forecasting intra-annual flow distribution in Central Asia, calculated using a methodology appropriate for this region and using CMIP6 ensemble scenarios. There have been studies on changes in the intra-annual distribution of runoff for individual river basins or local areas, but for the historical period, there have also been studies on modelling runoff forecasts using CMIP6 climate models, but have been very few systematic publications on the distribution of predicted intra-annual runoff in Central Asia, and this issue has not been fully studied. The projections suggest an intensification of flow seasonality (1), earlier flood peaks (2), reduced summer discharges (3) and an increased likelihood of extreme hydrological events under future climatic conditions. Changes in the seasonal structure of river flow in Central Asia are caused by both climatic factors—temperature, precipitation and glacier degradation—and significant anthropogenic influences, including irrigation and water management structures. These changes directly affect the risks of flooding and water shortages, as well as the adaptive capacity of water management systems. Given the high level of water management challenges and interregional conflicts over water use, the intra-annual distribution of runoff is important for long-term planning, the development of adaptation measures, and the formulation of public policy on sustainable water management in the face of growing climate challenges. This is critically important for water, agricultural, energy, and environmental planning in a region that already faces annual water management challenges and conflicts due to the uneven seasonal distribution of resources. Full article

Stroke is a leading global cause of mortality and long-term disability, with cerebral edema constituting a major contributor to early neurological deterioration and poor outcomes. Aquaporin-4 (AQP4), the predominant water channel in the central nervous system, plays a paradoxical role in stroke-related brain edema, facilitating both the formation and clearance of excess fluid depending on the pathological context. This review explores the biphasic function of AQP4 across cytotoxic and vasogenic edema, emphasizing its dynamic regulation, subcellular localization, and implications for therapeutic intervention. Evidence from rodent models shows that AQP4 exacerbates cytotoxic edema in acute ischemia by promoting intracellular water influx into astrocytes, whereas in vasogenic edema, it supports fluid reabsorption and glymphatic clearance, thereby alleviating brain swelling. Human studies corroborate AQP4 upregulation in infarcted regions and suggest a potential role for AQP4 polymorphisms and circulating levels as biomarkers of stroke severity and outcome, although larger cohorts and more robust methodological designs are needed. This review also discusses emerging pharmacological strategies to modulate AQP4 activity, including inhibitors, trafficking modulators, and gene-targeted delivery systems, while highlighting challenges in achieving phase-specific modulation. Given its central role in both injury and recovery, AQP4 emerges as a promising yet complex therapeutic target for personalized management of stroke-induced brain edema. Future directions include real-time imaging of AQP4 function, genotype-stratified clinical trials, and integration of AQP4 modulation with current stroke treatment protocols. Full article

This paper presents a comprehensive dynamical analysis of a nonlinear oscillator subjected to both deterministic and stochastic excitations. Utilizing a diverse suite of analytical tools—including phase portraits, Poincaré sections, Lyapunov exponents, recurrence plots, Fokker–Planck equations, and sensitivity diagnostics—we investigate the transitions between quasi-periodicity, chaos, and stochastic disorder. The study reveals that quasi-periodic attractors exhibit robust topological structure under moderate noise but progressively disintegrate as stochastic intensity increases, leading to high-dimensional chaotic-like behavior. Recurrence quantification and Lyapunov spectra validate the transition from coherent dynamics to noise-dominated regimes. Poincaré maps and sensitivity analysis expose multistability and intricate basin geometries, while the Fokker–Planck formalism uncovers non-equilibrium steady states characterized by circulating probability currents. Together, these results provide a unified framework for understanding the geometry, statistics, and stability of noisy nonlinear systems. The findings have broad implications for systems ranging from mechanical oscillators to biological rhythms and offer a roadmap for future investigations into fractional dynamics, topological analysis, and data-driven modeling. Full article

This study presents a comprehensive analysis of hydration heat-induced temperature and stress fields in a U-shaped aqueduct during the casting phase, integrating field measurements and numerical simulations. The key findings are as follows: (1) Thermal Evolution Characteristics: Both experimental and numerical results demonstrated consistent thermal behavior, characterized by a rapid temperature rise, subsequent rapid cooling, and eventual stabilization near ambient conditions. The peak temperature is observed at the centroid of the bearing section’s base slab, reaching 83.8 °C in field tests and 87.0 °C in simulations. (2) Stress Field Analysis: Numerical modeling reveals critical stress conditions in the outer concrete layers within high-temperature zones. The maximum tensile stress reaches 6.37 MPa, exceeding the allowable value of the tensile strength of the current concrete (1.85 MPa) by 244%, indicating a significant risk of thermal cracking. (3) Temperature Gradient and Cooling Rate Anomalies: Both methodologies identify non-compliance with critical control criteria. Internal-to-surface temperature differentials exceed the 25 °C threshold. Daily cooling rates at monitored locations surpass 2.0 °C/d during the initial 5–6 days of the cooling phase, elevating cracking risks associated with excessive thermal gradients. (4) Mitigation Strategy Proposal: Implementation of a hydration heat control system is recommended; compared to single-layer systems, the proposed mid-depth double-layer steel pipe cooling system (1.2 m/s flow) reduced peak temperature by 23.8 °C and improved cooling efficiency by 28.7%. The optimized water circulation maintained thermal balance between concrete and cooling water, achieving water savings and cost reduction while ensuring structural quality. (5) The cooling system proposed in this paper has certain limitations in terms of applicable environment and construction difficulty. Future research can combine with a BIM system to dynamically control the tube cooling system in real time. Full article

Bone metastasis remains a significant cause of morbidity and diminished quality of life in patients with advanced breast, prostate, and lung cancers. Emerging research highlights the pivotal role of reversible epigenetic alterations, including DNA methylation, histone modifications, chromatin remodeling complex dysregulation, and non-coding RNA networks, in orchestrating each phase of skeletal colonization. Site-specific promoter hypermethylation of tumor suppressor genes such as HIN-1 and RASSF1A, alongside global DNA hypomethylation that activates metastasis-associated genes, contributes to cancer cell plasticity and facilitates epithelial-to-mesenchymal transition (EMT). Key histone modifiers, including KLF5, EZH2, and the demethylases KDM4/6, regulate osteoclastogenic signaling pathways and the transition between metastatic dormancy and reactivation. Simultaneously, SWI/SNF chromatin remodelers such as BRG1 and BRM reconfigure enhancer–promoter interactions that promote bone tropism. Non-coding RNAs, including miRNAs, lncRNAs, and circRNAs (e.g., miR-34a, NORAD, circIKBKB), circulate via exosomes to modulate the RANKL/OPG axis, thereby conditioning the bone microenvironment and fostering the formation of a pre-metastatic niche. These mechanistic insights have accelerated the development of epigenetic therapies. DNA methyltransferase inhibitors (e.g., decitabine, guadecitabine) have shown promise in attenuating osteoclast differentiation, while histone deacetylase inhibitors display context-dependent effects on tumor progression and bone remodeling. Inhibitors targeting EZH2, BET proteins, and KDM1A are now advancing through early-phase clinical trials, often in combination with bisphosphonates or immune checkpoint inhibitors. Moreover, novel approaches such as CRISPR/dCas9-based epigenome editing and RNA-targeted therapies offer locus-specific reprogramming potential. Together, these advances position epigenetic modulation as a promising axis in precision oncology aimed at interrupting the pathological crosstalk between tumor cells and the bone microenvironment. This review synthesizes current mechanistic understanding, evaluates the therapeutic landscape, and outlines the translational challenges ahead in leveraging epigenetic science to prevent and treat bone metastases. Full article

This paper investigates the dependencies between the design parameters of the armature (stator) winding of a high-speed PMSM machine and the electrical losses in its windings resulting from eddy currents. In addition, the factors accounting for the occurrence of parasitic circulating currents, whose presence in the phase windings is associated with the design specificity, are analyzed. Quantitative analysis is carried out by the application of a newly developed mathematical model for the calculation of fundamental and additional losses in a multi-turn coil enclosed in the slots of a ferromagnetic core. The analysis takes into account the actual design of the slot and the conductor, the variable arrangement of individual conductors in the slot, the core saturation and the presence of the excitation field—to represent the main factors that affect the process of additional losses in the slot of the electric machine. The verification of the mathematical model developed in this study was carried out by comparing the distribution of power losses in the slot section of the coil, consisting of several elementary conductors connected in parallel and located in a rectangular open slot, with an identical distribution derived on the basis of an analytical method from the classical circuit theory. For the purpose of confirming the results and conclusions derived from simulation studies, a number of physical experiments were carried out, consisting in determining the power losses in multi-turn coils of different designs. Recommendations have been developed to minimize additional losses by optimizing the arrangement of conductors within the slot, selecting the appropriate cross-sectional size of a single conductor and the saturation level of the tooth zone. Full article