Search Results (44,309)

Caffeic acid (CA) is a phenolic compound commonly found in fruits, vegetables, and coffee, with preclinical evidence demonstrating its important role in disease management through different mechanisms of action. This review aimed to explore CA’s pharmacological effects in different pathological conditions, and sources were retrieved by using databases like PubMed, Scopus, Google Scholar, and Web of Science and based on preclinical studies. CA notably protects cells and tissues from oxidative stress and inflammation, highlighting its therapeutic role in the management of pathogenesis. The neuroprotective, cardioprotective, hepatoprotective, anti-microbial, and anti-obesity effects are reported through in vitro and in vivo studies. Moreover, its anticancer effects are linked to modulation of cell signaling pathways, together with angiogenesis, cell cycle, apoptosis, and the PI3K/Akt pathway. This article explores how caffeic acid influences health conditions, providing a comprehensive overview of its effects on disease processes. Reviewing the literature aims to enhance the understanding of caffeic acid’s role in disease management and as a natural therapeutic agent. Although several studies demonstrate the anticancer effects and its role in the management of various pathological conditions, most of the existing evidence is based on in vitro, in vivo, and xenograft models. Moreover, many natural compounds, including CA, that exhibit activity in preclinical settings fail to translate into clinical applications, due to restrictions of poor bioavailability, toxicity, rapid metabolism, and differences in the tumor microenvironment. Thus, future studies should emphasize well-designed in vivo studies as well as controlled clinical trials to better describe CA’s safety, efficacy, mechanism of action, and therapeutic application in humans. Further investigation of its interactions with other therapeutic agents may offer insights into synergistic effects that enhance treatment efficacy. Overall, a more comprehensive understanding of this compound will be indispensable for its development as a therapeutic agent in the treatment of chronic disease. Full article

Fibroblast Growth Factor 2 (FGF2) is a highly effective regulator of cell proliferation, differentiation, migration, and adhesion, suggesting a significant therapeutic potential as a tissue regeneration promoter both in acute and chronic tissue damage settings. Despite an extensive list of pathologies that lend themselves as viable targets for FGF2-based therapy (ranging from periodontics to burns to diabetic ulcers to coronary artery disease), the success record in the clinic remains modest, with no FDA approvals obtained so far. The inferior stability of this protein is frequently cited as the most significant factor behind its disappointing performance as a biotherapeutic. Multiple strategies have been designed and tested in an effort to ameliorate this problem, but the success remains elusive. We investigate the aggregation propensity of a recombinantly produced FGF2 using native mass spectrometry (MS) to identify conditions favoring formation of small soluble oligomers, which are considered precursors to larger aggregates. Tandem MS of proteolytic fragments produced by digestion of the oligomeric species allows the formation of external disulfide bonds to be identified as the process leading to oligomerization. Specifically, Cys-31 (one of the two unpaired cysteine residues in intact FGF2) appears to be a particularly active promoter of oligomerization by forming external disulfide bonds. As a high-pI protein, FGF2 readily associates with heparin, and molecular modeling identifies a positive charge basin proximal to Cys-31 as a potential heparin binding site, which can readily accommodate a synthetic heparin mimetic fondaparinux. Adding an equimolar amount of the latter to the FGF2 solution not only leads to formation of a stable protein/polyanion complex (as revealed by native MS), but also inhibits formation of FGF2 oligomers (presumably via a combination of steric hindrance and electrostatic repulsion). These findings advance our understanding of FGF2 stability, which will be invaluable for optimizing its formulation, storage, and administration. Full article

Imprinted proteins (IPs) are promising materials for producing artificial alternatives to natural recognition systems (antibodies, aptamers, etc.) due to their high sorption properties and specificity. However, contemporary understanding of the imprinting process at the atomic level is rather limited, which hinders the rational design of more efficient IPs. In this paper, we use computational modeling to provide a description of fundamental principles of protein imprinting at the atomic level. We have modeled several potential associates between the protein matrix and template molecules that form during the imprinting process up to the addition of the cross-linking agent. We used bovine serum albumin (BSA) as the protein matrix and 4-hydroxycoumarin (4–HC) as a molecular template. In combination with computational modeling, extensive experimental analyses including isothermal titration calorimetry (ITC) and NMR spectroscopic methods (¹H NMR and diffusion-ordered NMR spectroscopy (DOSY)) were used to evaluate the potential efficiency of imprinted BSA. This study represents a step toward the future rational in silico design of IPs. Full article

Understanding diurnal canopy orientation in crops is important for interpreting plant responses to light and environmental conditions, yet field-based quantification remains limited. In this study, we present Heliocot, a field RGB imaging approach that converts time-resolved images into reference-area standardized projected leaf area (PLA) time series to quantify within-day canopy orientation dynamics in early-season cotton. Leaf instance segmentation was performed using YOLOv8m-seg and refined through a 144-combination post-processing optimization. On the held-out early-stage validation/tuning set, the selected workflow showed strong agreement with manual ground truth (R² = 0.948; NRMSE = 0.082) and destructive leaf area measurements (R² = 0.836). Derived diurnal metrics, including Daily Orientation Amplitude (DOA) and Peak Orientation Index (POI), consistently revealed a midday maximum (13:15) in canopy projection. Exploratory genotype-level analysis suggested negative associations between orientation indices and selected plant traits, including specific leaf area (SLA) versus DOA (r = −0.71, p = 0.021, R² = 0.508), destructive leaf area (LA) versus DOA (r = −0.69, p = 0.028, R² = 0.471), and stem dry weight (SDW) versus POI (r = −0.74, p = 0.014, R² = 0.554), while plant height was not significantly associated with POI and DOA (p > 0.05). Although currently limited to early-season conditions and two field-imaging dates, this approach provides a practical workflow for field-based monitoring of canopy projection dynamics in cotton, while broader temporal and environmental validation remains necessary. Full article

To address the urgent need for electronics operable in extremely high-temperature environments, this paper presents a novel three-terminal, dual-gate, lateral 4H-SiC n-channel depletion-mode junction field effect transistor (JFET) without a backside electrode. Featuring a fully planar electrode layout, the device eliminates the back-gate effect and significantly improves integration compatibility. Experimental results demonstrate stable DC operation up to 500 °C, with an intrinsic gain of 9.79 at room temperature and 6.01 at 500 °C. Comparison with TCAD simulations confirms excellent agreement in the key physical trends of threshold voltage drift and mobility degradation, though quantitative discrepancies are observed and attributed to process-induced parasitic effects such as non-ideal ohmic contacts and interface states. Analysis shows that the new structure broadens the channel depletion layer by optimizing the depletion profile, thereby suppressing channel-length modulation and improving both output resistance and gate control. This work not only provides an effective device platform for high-temperature 4H-SiC analog integrated circuits (ICs) but also deepens the understanding of process-performance correlations, offering clear guidance for process-oriented device optimization. The proposed structure serves as a foundation for developing fully planar, high-temperature 4H-SiC analog ICs with promising potential in aerospace, automotive, and energy exploration systems. Full article

The interface design of conversational AI mobile applications is shaped by natural language interaction, multi-turn feedback, and dynamically generated content. While these features may reduce certain operational barriers, they can also create new difficulties for older adults in understanding system functions, judging generated results, and recovering from interaction errors. To address these challenges, this study integrates the KANO model and the Analytic Hierarchy Process (AHP) to develop a systematic framework for analyzing interface requirements in conversational AI mobile applications for older users. Field surveys and semi-structured interviews were first conducted to identify 15 interface design requirements. These requirements were then classified through a KANO questionnaire into must-be, one-dimensional, attractive, and indifferent categories, with no reverse requirements identified. On this basis, an AHP hierarchy was established to determine the relative priority of each requirement. The results show that clear functional explanations, interface simplicity, absence of advertising interference, voice interaction, and error-tolerant interaction design are the key factors influencing older adults’ experience with conversational AI interfaces. Basic usability requirements mainly reduce barriers to use, while functional explanations and voice interaction help older users understand system capabilities and task procedures. Error-tolerant interaction further enhances users’ sense of security and control in dynamic and uncertain conversational contexts. These findings suggest that age-friendly design for conversational AI mobile applications should not be limited to isolated adjustments of fonts, icons, or colors. Instead, it should adopt a systematic approach centered on low-complexity interfaces, clear task guidance, interpretable feedback, and recoverable interactions. Based on the classification and weighting results, this study proposes an interface design framework for age-friendly conversational AI mobile applications, providing a reference for requirement analysis, interface optimization, and design decision-making. Full article

Numerical simulation is an effective method for studying groundwater flow and heat transfer in geothermal energy projects. Describing the characteristics of thermal plumes is important for operational planning of geothermal energy projects. In contrast to shallow geothermal system, the injection temperature differs significantly from the natural temperature of thermal reservoir in high-temperature geothermal projects, which leads to changes in fluid density and dynamics viscosity. The purpose of this paper is to investigate the impacts of temperature-induced changes in density and dynamics viscosity on simulation. The Enhanced Geothermal System (EGS) in North Jiangsu Basin, China, is taken as a case project. Based on the theory of groundwater flow and heat transfer in porous-fracture dual medium, a numerical model of EGS is established to predict the thermal performance. The density and the dynamics viscosity in the model were set as either constant or temperature-dependent to simulate the hydraulic head and temperature of the production well. The influence of temperature-induced changes in density and dynamics viscosity on the simulation was quantitatively studied. The results show that temperature-induced change in dynamics viscosity has a greater impact on the simulation, with deviation in hydraulic head exceeding 20% if the dynamics viscosity is assumed constant. The temperature-dependent variation in viscosity should be incorporated into the simulation process to improve the accuracy of the calculation. In practice, EGS projects should maximize the temperature differential between produced and injected water. The increased viscosity of lower-temperature circulation water extends its residence time within the system, thereby facilitating more thorough heat extraction. This research enhances our understanding of the role of the temperature in groundwater flow and heat transfer within EGS. Full article

Acetylcholine (ACh) is an evolutionarily conserved neurotransmitter that is widely distributed in the central and peripheral nervous systems and plays essential roles in multiple physiological processes. This review summarizes the full biological cycle of ACh, including its synthesis, vesicular storage, release, degradation, and reuptake, and discusses the regulatory mechanisms underlying its functions in the nervous system and peripheral organs. Through nicotinic acetylcholine receptors (nAChRs) and muscarinic acetylcholine receptors (mAChRs), ACh is involved in central nervous system functions such as cognition, learning and memory, attention, arousal, reward, and decision-making, as well as peripheral processes including motor control, autonomic regulation, and immune modulation. In addition, ACh plays a pivotal role in the brain–body axis. At the central level, the nervous system regulates peripheral organ function through autonomic and neuroendocrine pathways. At the peripheral level, cholinergic signals derived from the enteric nervous system and immune cells convey information about the body’s internal state to the central nervous system through vagal and other afferent pathways, forming an important bottom-up regulatory network. Collectively, these findings indicate that ACh is not only a classical neurotransmitter but also a key molecular mediator of brain–body communication. A more comprehensive understanding of cholinergic signaling may provide new insights into physiological regulation and the pathogenesis of neurological, psychiatric, cardiovascular, and inflammatory diseases. Full article

The cell nucleus is a highly dynamic and complex organelle that orchestrates fundamental cellular processes through its spatial organization. Far from being merely the repository of genetic information, it acts as a regulatory hub whose architecture profoundly influences transcription, RNA maturation and genome maintenance. Dissecting such a multilayered organization requires approaches that integrate molecular profiling with spatially resolved technologies capable of capturing nuclear architecture in situ. In this Review, we discuss classical and emerging imaging strategies that are transforming our understanding of nuclear organization across scales, from multiplexed and super-resolution light microscopy to barcoding-based spatial methods, live-cell imaging, and ultrastructural electron microscopy. Together, these methods are providing crucial insights into the localization and dynamics of RNAs and genomic regions within distinct compartments revealing how nuclear architecture governs genome function. Full article

The lamprophyre dikes and multi-generational pyrite and arsenopyrite developed in the Jinshan gold deposit in the West Qinling metallogenic belt provide critical evidence for understanding the role of mantle-derived magmatism in gold mineralization processes. In this study, we conducted zircon U-Pb dating of lamprophyre to constrain the timing of magmatic activity and the mineralization age, and performed EMPA and LA-ICP-MS analyses on sulfides from the main metallogenic stage (Py II–III, Apy II–III) and lamprophyre-hosted pyrite (Py L) to constrain the formation conditions and metal sources of the Jinshan deposit. The results show that the mantle-derived magmatism represented by lamprophyre yields an age of 206 ± 2 Ma, which provides a lower-limit constraint on the timing of gold mineralization, corresponding to the subduction-to-extension transition period in the region. Stage II mineralization occurred at 270–320 °C with logƒS₂ of −9 to −5, dominantly as Au-HS complexes, indicating medium-temperature hydrothermal conditions with low sulfur fugacity, consistent with microscopic mineral assemblages and thermodynamic simulations. Systematic δ³⁴S variations reveal: stage II values (9.24–5‰) indicate granitic/Devonian sedimentary sources; Py L values (2.19–3.6‰) reflect mantle contributions; stage III signatures (−2.3–1.93‰) record late meteoric water mixing. Complementary δ⁵⁶Fe data show that Py II (0.2–0.3‰) and Py L (0.58–0.68‰) preserve magmatic fingerprints, while negative values of Py III (−2.29 to −0.71‰) document increasing sedimentary Fe incorporation. Combined with geochronology, S-Fe isotopes, and physicochemical constraints, we propose that the Jinshan gold deposit formed in a tectonic setting transitioning from compression to extension during the Late Indosinian (ca. 237–201 Ma). Mineralization was initiated by the partial melting of the metasomatized mantle, where hydrous magmas efficiently extracted Au and volatiles. These components ascended through transcrustal faults, with Au partitioning into exsolved fluids that precipitated gold through immiscibility and boiling in secondary structures. Full article

Exposure to blast waves without kinetic, penetrating, thermal, or toxic components causes a distinct form of traumatic brain injury, termed primary blast-induced TBI (pbTBI). Clinical manifestations of pbTBI span a wide spectrum, ranging from life-threatening intracranial hemorrhage, hyperemia, and delayed cerebral edema to mild and transient neurological symptoms without detectable structural abnormalities on routine imaging. At the mild end of the spectrum, symptoms after a single exposure may resolve quickly, yet repeated exposures—even at very low levels, termed “subconcussive”—can develop into post-concussive syndrome (PCS) or persistent post-concussive symptoms (PPCS) in a subset of individuals. Despite extensive studies, the molecular pathobiology linking primary blast exposure to delayed and sometimes chronic neurobehavioral deficits remains incompletely understood. A mechanistic framework connecting blast-wave physics to biomechanics to biological vulnerability may therefore help define exposure hazards, interpret clinical symptomatology, and guide diagnostic and therapeutic development. This review summarizes the physics of primary blast waves, the resulting biomechanical responses, and candidate biological substrates, emphasizing structures and interfaces with distinct acoustic impedances across anatomical, tissue, cellular, and molecular scales. We synthesize evidence supporting the hypothesis that the cerebral vasculature and endothelial cells represent critically vulnerable substrates of primary blast-wave injury, in part because the vascular tree constitutes the brain’s largest and most widely distributed interface between compartments with different acoustic impedances. Across experimental and human studies, endothelial stress, vascular injury, and downstream neuroinflammation emerge as convergent molecular responses to primary blast exposure. Temporal dynamics are central to understanding pbTBI because many blast-induced processes unfold in sequential phases. These observations support conceptualizing pbTBI as a condition characterized by prominent cerebrovascular injury of varying severity with secondary consequences for neuronal signaling, network function, and behavior. Within this framework, cerebrovascular and neurovascular unit (NVU) dysfunction provides a parsimonious bridge between primary blast-wave exposure and chronic symptom trajectories, where vascular pathology may offer more accessible therapeutic targets than neuronal injury. Key knowledge gaps include identifying which physical component(s) of the blast are most injurious, establishing biologically meaningful dose–response relationships at molecular and physiological levels, and defining windows of vulnerability during recovery that are relevant to repeated exposures. Addressing these gaps is essential for refining safety protocols, improving diagnostic specificity through mechanism-informed biomarkers, and developing evidence-based molecular and vascular therapeutic targets for pbTBI-associated conditions. Progress will require integrating waveform-aware dosimetry with longitudinal physiological and molecular monitoring across both preclinical and human cohorts. Such integration offers a practical path toward translating blast physics into actionable medical guidance for prevention, triage, and recovery management. Full article

The chiral-induced spin selectivity (CISS) effect enables the spin-selective transport of electrons through chiral systems, linking handedness with spin polarization. This review provides a comprehensive examination of the emerging field of chiral electrocatalysis, detailing also the extensive experimental and theoretical endeavor conducted to gain a deeper understanding of the fundamental physical principles and mechanistic characteristics of this phenomenon. In particular, the CISS effect has garnered significant attention within the scientific community due to its potential for broad applicability across several fields, ranging from spintronics to biology. Among them, the prospective harnessing of the CISS effect into electrocatalytic processes offers an innovative strategy to improve the performance of energy conversion and storage technologies. This review deeply examines the practical applications of the CISS effect across different electrocatalytic reactions, with particular emphasis on its influence on the oxygen reduction reaction (ORR) and its critical role in energy conversion systems where the ORR reaction is a key process, such as in metal–air batteries, whose safety and performance can be enhanced through spin-selective electron transport. Full article

Background/Objectives: Inborn errors of immunity (IEI) are rare and complex pediatric disorders that create significant information gaps for families and non-specialist healthcare professionals. Large language models (LLMs) such as ChatGPT are increasingly used as on-demand health information resources; however, evidence on their performance in rare pediatric diseases remains limited. This study aimed to evaluate the reliability, quality, readability, understandability, reproducibility, and safety-related concerns of ChatGPT-4o responses to frequently searched questions about pediatric IEI posed by healthcare professionals and patients/caregivers. Methods: This cross-sectional evaluation used the publicly accessible ChatGPT-4o interface to generate responses to 20 frequently searched questions about pediatric IEI, equally distributed between healthcare professional (n = 10) and patient/caregiver queries (n = 10). Three pediatric allergy-immunology specialists independently evaluated response quality using the modified DISCERN (mDISCERN) and Global Quality Scale (GQS) tools, supplemented by a structured expert-based assessment of misinformation, safety-related concerns, suspected factual issues, missing disclaimers, and clinically meaningful inter-iteration inconsistency. Text readability was assessed using four validated indices (ARI, FRES, FKGL, GFR), comprehensibility using the Patient Education Materials Assessment Tool (PEMAT), and reproducibility using natural language processing methods. Results: ChatGPT-4o demonstrated strong overall performance, with median mDISCERN and GQS scores of 4 (IQR: 3–5) for both query types. Readability scores substantially exceeded recommended thresholds, with FKGL scores of 12.96 ± 0.69 and 10.83 ± 0.67 for professional and patient/caregiver queries, respectively. Mean PEMAT understandability scores were 71.80 ± 5.75% for professional queries and 80.80 ± 4.73% for patient/caregiver queries (p = 0.001). Reproducibility was high, with semantic similarity rates of 86.10 ± 3.84% and 87.30 ± 3.68%, respectively. Suspected factual issues were identified in 4 of 20 responses (20%), safety-related concerns in 3 (15%), clinically meaningful inter-iteration inconsistencies in 3 (15%), and missing medical disclaimers in all 20 responses (100%). Conclusions: ChatGPT-4o showed strong performance across validated quality metrics for pediatric IEI information support; however, its high reading level, universal absence of medical disclaimers, and occasional clinically meaningful inconsistencies limit its suitability as a standalone source for clinically sensitive guidance. These findings underscore the need for AI-driven patient education tools with improved readability, adaptive complexity adjustment, and safety-oriented communication. Full article

Recent paradigms in traumatic brain injury have transitioned from focal-lesion models to an emphasis on diffuse axonal injury and white matter disruption as the primary drivers of cognitive morbidity. This selective review frames information processing speed as the functional signature of this connectivity loss. While processing speed is often theorized as a “cognitive bottleneck” that constrains higher-order functions, we identify critical methodological and conceptual pitfalls in the existing literature. Specifically, we argue that current research is frequently confounded by: (1) measurement impurity, where tasks like the SDMT and TMT-B recruit executive and mnemonic variance; (2) circularity, where speed measures are used to predict time-dependent outcomes; and (3) the neglect of speed–accuracy trade-offs, which may mask volitional cautiousness as neurobiological incapacity. To resolve these challenges, we offer evidence-based recommendations for the clinical setting, including the integration of construct-pure chronometric measures and dual-scoring protocols. We conclude that because white matter integrity functions as a rate-limiting substrate, processing speed must be prioritized as a primary target in early neurorehabilitation. By isolating processing speed from focal-driven deficits, clinicians can more accurately map the path from microstructural disruption to functional recovery. Recognizing this infrastructure is essential to understanding the full scope of cognitive consequences. Full article

Building healthy communities requires organizational arrangements that center on resident and community assets while using data to guide decisions. This study examines how the Evidence2Success framework was implemented in three communities, Kearns, UT, Mobile, AL, and Memphis, TN, to understand how citizen-led asset mapping, coalition processes, and funding strategies shape youth well-being efforts. Using an interpretive case-study design, we analyzed process-evaluation interviews, implementation milestones and benchmarks, strengths-and-concerns reports, and community case materials to trace how coalitions mobilized assets, reoriented institutional resources, and adapted evidence-based programs. The results show that broad, cross-sector Community Boards completed most implementation tasks, increased participation by people of color, and developed more inclusive decision-making structures that addressed historical inequities. Coalitions also strengthened data-use capacities, employing youth survey results and local qualitative input to select priorities, braid funding, and make culturally responsive adaptations while maintaining program fidelity. Overall, the findings suggest that when evidence-based planning frameworks are embedded within asset-based, resident-governed structures, communities can build sustainable organizational arrangements that support youth well-being and advance more equitable local systems. Full article