Search Results (3,756)

Background/Objectives: Constitutive activation of the PI3K/AKT/mTOR signaling cascade underlies the aggressive phenotype of fibroblast-like synoviocytes (FLSs) in rheumatoid arthritis (RA); however, a quantitative synthesis of in vitro data on pathway inhibition remains lacking. This systematic review and meta-analysis aimed to (i) aggregate standardized effects of pathway inhibitors on proliferation, apoptosis, migration/invasion, IL-6/IL-8 secretion, p-AKT, and LC3; (ii) assess heterogeneity and identify key moderators of variability, including stimulus type, cell source, and inhibitor class. Methods: PubMed, Europe PMC, and the Cochrane Library were searched up to 18 May 2025 (PROSPERO CRD420251058185). Twenty of 2684 screened records met eligibility. Two reviewers independently extracted data and assessed study quality with SciRAP. Standardized mean differences (Hedges g) were pooled using a Sidik–Jonkman random-effects model with Hartung–Knapp confidence intervals. Heterogeneity (τ², I²), 95% prediction intervals, and meta-regression by cell type were calculated; robustness was tested with REML-HK, leave-one-out, and Baujat diagnostics. Results: PI3K/AKT/mTOR inhibition markedly reduced proliferation (to –5.1 SD), IL-6 (–11.1 SD), and IL-8 (–6.5 SD) while increasing apoptosis (+2.7 SD). Fourteen of seventeen outcome clusters showed large effects (|g| ≥ 0.8), with low–moderate heterogeneity (I² ≤ 35% in 11 clusters). Prediction intervals crossed zero only in small k-groups; sensitivity analyses shifted pooled estimates by ≤0.05 SD. p-AKT and p-mTOR consistently reflected functional changes and emerged as reliable pharmacodynamic markers. Conclusions: Targeted blockade of PI3K/AKT/mTOR robustly suppresses the proliferative and inflammatory phenotype of RA-FLSs, reaffirming this axis as a therapeutic target. The stability of estimates across multiple analytic scenarios enhances confidence in these findings and highlights p-AKT and p-mTOR as translational response markers. The present synthesis provides a quantitative basis for personalized dual-PI3K/mTOR strategies and supports the adoption of standardized long-term preclinical protocols. Full article

In this study, we propose a bidirectional chemical sensor platform based on a reconfigurable ion-sensitive field-effect transistor (R-ISFET) architecture. The device incorporates Ni-silicide Schottky barrier source/drain (S/D) contacts, enabling ambipolar conduction and bidirectional turn-on behavior for both p-type and n-type configurations. Channel polarity is dynamically controlled via the program gate (PG), while the control gate (CG) suppresses leakage current, enhancing operational stability and energy efficiency. A dual-control-gate (DCG) structure enhances capacitive coupling, enabling sensitivity beyond the Nernst limit without external amplification. The extended-gate (EG) architecture physically separates the transistor and sensing regions, improving durability and long-term reliability. Electrical characteristics were evaluated through transfer and output curves, and carrier transport mechanisms were analyzed using band diagrams. Sensor performance—including sensitivity, hysteresis, and drift—was assessed under various pH conditions and external noise up to 5 V_pp (i.e., peak-to-peak voltage). The n-type configuration exhibited high mobility and fast response, while the p-type configuration demonstrated excellent noise immunity and low drift. Both modes showed consistent sensitivity trends, confirming the feasibility of complementary sensing. These results indicate that the proposed R-ISFET sensor enables selective mode switching for high sensitivity and robust operation, offering strong potential for next-generation biosensing and chemical detection. Full article

pH is a critical parameter requiring precise monitoring across scientific, industrial, and biological domains. Fluorescent pH probes offer a powerful alternative to traditional methods (e.g., electrodes, indicators), overcoming limitations in miniaturization, long-term stability, and electromagnetic interference. By utilizing photophysical mechanisms—including intramolecular charge transfer (ICT), photoinduced electron transfer (PET), and fluorescence resonance energy transfer (FRET)—these probes enable high-sensitivity, reusable, and biocompatible sensing. This review systematically details recent advances, categorizing probes by operational pH range: strongly acidic (0–3), weakly acidic (3–7), strongly alkaline (>12), weakly alkaline (7–11), near-neutral (6–8), and wide-dynamic range. Innovations such as ratiometric detection, organelle-specific targeting (lysosomes, mitochondria), smartphone colorimetry, and dual-analyte response (e.g., pH + Al³⁺/CN⁻) are highlighted. Applications span real-time cellular imaging (HeLa cells, zebrafish, mice), food quality assessment, environmental monitoring, and industrial diagnostics (e.g., concrete pH). Persistent challenges include extreme-pH sensing (notably alkalinity), photobleaching, dye leakage, and environmental resilience. Future research should prioritize broadening functional pH ranges, enhancing probe stability, and developing wide-range sensing strategies to advance deployment in commercial and industrial online monitoring platforms. Full article

Cell culture models are of central importance for the investigation of cellular metabolism, proliferation and stress responses. In this study, the effects of different concentrations of glucose (1 g/L vs. 4.5 g/L) and fetal bovine serum (FBS; 5%, 10%, 15%) on viability, mitochondrial function and autophagy are investigated in four human cell lines: MRC-5, HeLa, Caco-2 and SW-620. Cells were cultured in defined media for 72 h, and viability was assessed by LDH release, mitochondrial membrane potential using Rhodamine 123, ATP content by luminescence and autophagy activity by dual fluorescence staining. The results showed that HeLa and SW-620 cancer cells exhibited increased proliferation and mitochondrial activity under high glucose conditions, while low glucose media resulted in decreased ATP content and increased membrane permeability in HeLa cells. MRC-5 fibroblasts and Caco-2 cells showed greater resilience to nutrient stress, with minimal changes in LDH release and consistent proliferation. Autophagy was activated under all conditions, with a significant increase only in selected cell-medium combinations. These results highlight the importance of medium composition in influencing cellular bioenergetics and stress responses, which has implications for cancer research, metabolic disease modelling and the development of serum-free culture systems for regenerative medicine. Full article

Cancer remains a significant global health challenge, with China being particularly affected because of its large population. Regulated cell death (RCD) mechanisms, including autophagy, apoptosis, necroptosis, pyroptosis, and ferroptosis, play complex roles in cancer development and progression. This review explores the dual roles of autophagy and apoptosis in cancer, highlighting their tumor-suppressive and tumor-promoting functions. Autophagy can maintain genomic stability, induce apoptosis, and suppress protumor inflammation, but it may also support tumor cell survival and drug resistance. Apoptosis, while primarily tumor-suppressive, can paradoxically promote cancer progression in certain contexts. Other RCD mechanisms, such as necroptosis, pyroptosis, and ferroptosis, also exhibit dual roles in cancer, influencing tumor growth, metastasis, and immune responses. Understanding these mechanisms is crucial for developing targeted cancer therapies. This review provides insights into the intricate interplay between RCD mechanisms and cancer, emphasizing the need for context-dependent therapeutic strategies. Full article

This study explores entertainment consumption patterns in Romania, a transitional digital culture characterized by high digital connectivity but underdeveloped physical infrastructure. Employing a dual qualitative coding methodology, this research combines inductive analysis of consumer focus groups with deductive analysis of expert interviews, enabling a multi-layered interpretation of both overt behaviors and latent emotional drivers. Seven key thematic dimensions, motivational depth, perceived barriers, emotional needs, clarity of preferences, future behavioral intentions, social connection, and identity construction, were analyzed and compared using a Likert-based scoring framework, supported by a radar chart and comparison matrix. Findings reveal both convergence and divergence between consumer and expert perspectives. While consumers emphasize immediate experiences and logistical constraints, experts uncover deeper emotional motivators such as validation, mentorship, and identity formation. This behavioral–emotional gap suggests that, although digital entertainment dominates due to accessibility, it often lacks the emotional richness associated with physical formats, which are preferred but less accessible. This study underscores the importance of triangulated qualitative inquiry in revealing not only stated preferences but also unconscious psychological needs. It offers actionable insights for designing emotionally intelligent and culturally responsive entertainment strategies in digitally saturated yet infrastructure-limited environments. Full article

The integration of large-scale wind power clusters significantly reduces the inertia level of the power system, increasing the risk of frequency instability. Accurately assessing the equivalent virtual inertia of wind farms is critical for grid stability. Addressing the dual bottlenecks in existing inertia assessment methods, where physics-based modeling requires full control transparency and data-driven approaches lack interpretability for inertia response analysis, thus failing to reconcile commercial confidentiality constraints with analytical needs, this paper proposes a symbolic regression framework for inertia evaluation in doubly fed wind farms with limited control information constraints. First, a dynamic model for the inertia response of DFIG wind farms is established, and a mathematical expression for the equivalent virtual inertia time constant under different control strategies is derived. Based on this, a nonlinear function library reflecting frequency-active power dynamic is constructed, and a symbolic regression model representing the system’s inertia response characteristics is established by correlating operational data. Then, sparse relaxation optimization is applied to identify unknown parameters, allowing for the quantification of the wind farm’s equivalent virtual inertia. Finally, the effectiveness of the proposed method is validated in an IEEE three-machine nine-bus system containing a doubly fed wind power cluster. Case studies show that the proposed method can fully utilize prior model knowledge and operational data to accurately assess the system’s inertia level with low computational complexity. Full article

Background/Objectives: Cancer suffers from unresolved therapeutic challenges owing to the lack of targeted therapies and heightened recurrence risk. This study aimed to investigate the new series of hydroxamate by structurally modifying the pharmacophore of vorinostat. Methods: The present work involves the synthesis of 15 differently substituted 2H-1,2,3-triazole-based hydroxamide analogs by employing triazole ring as a cap with varied linker fragments. The compounds were evaluated for their anticancer effect, especially their anti-breast cancer response. Molecular docking and molecular dynamics simulations were conducted to examine binding interactions. Results: Results indicated that among all synthesized hybrids, the molecule VI(i) inhibits the growth of MCF-7 and A-549 cells (GI₅₀ < 10 μg/mL) in an antiproliferative assay. Compound VI(i) was also tested for cytotoxic activity by employing an MTT assay against A549, MCF-7, and MDA-MB-231 cell lines, and the findings indicate its potent anticancer response, especially against MCF-7 cells with IC₅₀ of 60 µg/mL. However, it experiences minimal toxicity towards the normal cell line (HEK-293). Mechanistic studies revealed a dual-pathway activation: first, apoptosis (17.18% of early and 10.22% of late apoptotic cells by annexin V/PI analysis); second, cell cycle arrest at the S and G2/M phases. It also promotes ROS generation in a concentration-dependent manner. The HDAC–inhibitory assay, extended in silico molecular docking, and MD simulation experiments further validated its significant binding affinity towards HDAC 1 and 6 isoforms. DFT and ADMET screening further support the biological proclivity of the title compounds. The notable biological contribution of VI(i) highlights it as a potential candidate, especially against breast cancer cells. Full article

This paper addresses the trajectory tracking control problem of underactuated ships in ocean engineering, which faces the dual challenges of tracking error time–performance regulation and robustness design due to the system’s underactuated characteristics, model uncertainties, and external disturbances. Aiming to address the issues of traditional finite-time control (convergence time dependent on initial states) and fixed-time control (control chattering and parameter conservativeness), this paper proposes a predefined-time adaptive control framework that integrates an event-triggered mechanism and neural networks. By constructing a Lyapunov function with time-varying weights and designing non-periodic dynamically updated dual triggering conditions, the convergence process of tracking errors is strictly constrained within a user-prespecified time window without relying on initial states or introducing non-smooth terms. An adaptive approximator based on radial basis function neural networks (RBF-NNs) is employed to compensate for unknown nonlinear dynamics and external disturbances in real-time. Combined with the event-triggered mechanism, it dynamically adjusts the update instances of control inputs, ensuring prespecified tracking accuracy while significantly reducing computational resource consumption. Theoretical analysis shows that all signals in the closed-loop system are uniformly ultimately bounded, tracking errors converge to a neighborhood of the origin within the predefined-time, and the update frequency of control inputs exhibits a linear relationship with the predefined-time, avoiding Zeno behavior. Simulation results verify the effectiveness of the proposed method in complex marine environments. Compared with traditional control strategies, it achieves more accurate trajectory tracking, faster response, and a substantial reduction in control input update frequency, providing an efficient solution for the engineering implementation of embedded control systems in unmanned ships. Full article

Recent preclinical and clinical studies have confirmed the essential role of interferons in the host’s immune response against malignant cells. Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer strongly associated with Merkel cell polyomavirus (MCPyV). Despite progress in understanding MCC pathogenesis, the role of innate immune signaling, particularly interferon-γ (IFN γ) and its downstream pathways, remains underexplored. This review summarizes recent findings on IFN-γ in MCC, highlighting its dual role in promoting both antitumor immunity and immune evasion. IFN-γ enhances cytotoxic T cell responses, upregulates MHC class I/II expression, and induces tumor cell apoptosis. Transcriptomic studies have shown that IFN-γ treatment upregulates immune-regulatory genes including PD-L1, HLA-A/B/C, and IDO1 by over threefold; it also activates APOBEC3B and 3G, contributing to antiviral defense and tumor editing. Clinically, immune checkpoint inhibitors (ICIs) such as pembrolizumab and avelumab yield objective response rates of 30–56% and two-year overall survival rates exceeding 60% in advanced MCC. However, approximately 50% of patients do not respond, in part due to IFN-γ signaling deficiencies. This review further discusses IFN-γ’s crosstalk with the STAT1/3/5 pathways and emerging combination strategies aimed at restoring immune sensitivity. Understanding these mechanisms may inform personalized immunotherapeutic approaches and guide the development of IFN-γ–based interventions in MCC. Full article

Understanding the alterations to the shoot and root traits of rapeseed (Brassica napus) in response to salt stress is vital for improving its ability to thrive in saline-prone regions. This research aims to evaluate the responses of shoot and root traits of rapeseed at the vegetative stage under salt- and salicylic acid-induced stress in hydroponic culture. Five parents and ten F₃ segregants of rapeseed were subjected to three treatments: T1: control, T2: 8 dSm⁻¹ salt, and T3: 8 dSm⁻¹ salt + 0.1 mM salicylic acid at 21 days of age. Salinity stress significantly reduced the estimated root surface area by 54% compared to control, highlighting the plasticity of roots under stress. The simultaneous application of salt and SA did not alleviate the salinity stress, but rather reinforced the degree of stress and decreased the number of leaves, diameter of the main axis, chlorophyll content, and estimated root surface area by 18.5%, 15.4%, 38.8%, and 23%, respectively, compared to T2. The parental genotype M-245 followed by F₃ genotype M-232×M-223 accounted for the higher overall estimated root surface area. These results provide novel insights into the responses of root traits in rapeseed breeding lines under dual treatment, which hold promising implications for future rapeseed breeding efforts focused on sustainable rapeseed production. Full article

The red plant phenotype of R1 cotton is a genetic marker produced by light-induced anthocyanin accumulation. GhPAP1D controls this trait. There are two 228 bp tandem repeats upstream of GhPAP1D in R1 cotton. In this study, GUS staining assays in transgenic Arabidopsis thaliana (L.) Heynh. demonstrated that tandem repeats in the GhPAP1D promoter-enhanced transcriptional activity. GhPAP1D is a homolog of A. thaliana AtPAP1. AtPAP1’s expression is regulated by photomorphogenesis-related transcription factors such as AtHY5 and AtBBXs. We identified the homologs of A. thaliana AtHY5, AtBBX21, and AtBBX24 in R1 cotton, designated as GhHY5, GhBBX21, and GhBBX24, respectively. Y1H assays confirmed that GhHY5, GhBBX21, and GhBBX24 each bound to the GhPAP1D promoter. Dual-luciferase reporter assays revealed that GhHY5 weakly activated the promoter activity of GhPAP1D. Heterologous expression assays in A. thaliana indicated that GhBBX21 promoted anthocyanin accumulation, whereas GhBBX24 had the opposite effect. Dual-luciferase assays showed GhBBX21 activated GhPAP1D transcription, while GhBBX24 repressed it. Further study indicated that GhHY5 did not enhance GhBBX21-mediated transcriptional activation of GhPAP1D but alleviates GhBBX24-induced repression. Together, our results demonstrate that GhBBX21 and GhBBX24 antagonistically regulate anthocyanin accumulation in R1 cotton under GhHY5 mediation, providing insights into light-responsive anthocyanin biosynthesis in cotton. Full article

In the digital era, understanding the intention to use generative AI is critical, as it enhances productivity, transforms workflows, and enables humans to focus on higher-value tasks. Drawing upon the unified theory of acceptance and use of technology (UTAUT) and the technology threat avoidance theory (TTAT), this research integrates perceived AI literacy into the AI acceptance–avoidance framework as a central variable. This study gathered 583 valid survey responses from China and validated its model using a dual-phase, combined method that integrates structural equation modeling and artificial neural networks. Research findings indicate that the model explains 51.6% of the variance in generative AI usage intention. Except for social influence, all variables within the extended framework significantly impact the usage intention, with perceived AI literacy being the strongest predictor (β = 0.33, p < 0.001). Additionally, perceived AI literacy mitigates the adverse effect of perceived threats on the intention to use AI. Practical implications suggest that enterprises adopt a tiered strategy, as follows: maximize perceived benefits by integrating AI skills into reward systems and providing task-automation training; minimize perceived costs through dedicated technical support and transparent risk mitigation plans; and cultivate AI literacy via progressive learning paths, advancing from data analysis to innovation. Full article

Fecal microbiota transplantation (FMT) promotes growth performance and intestinal development in yellow-feathered broilers, but whether the virome and metabolites contribute to its growth-promoting effect remains unclear. This study removed the microbiota from FMT filtrate using a 0.45 μm filter membrane, retaining the virome and metabolites to perform fecal virome transplantation (FVT), aiming to investigate its regulatory role in broiler growth. Healthy yellow-feathered broilers with high body weights (top 10% of the population) were used as FVT donors. Ninety-six 8-day-old healthy male yellow-feathered broilers (95.67 ± 3.31 g) served as FVT recipients. Recipient chickens were randomly assigned to a control group and an FVT group. The control group was gavaged with 0.5 mL of normal saline daily, while the FVT group was gavaged with 0.5 mL of FVT solution daily. Growth performance, immune and antioxidant capacity, intestinal development and related gene expression, and microbial diversity were measured. The results showed that FVT improved the feed utilization rate of broilers (the feed conversion ratio decreased by 3%; p < 0.05), significantly increased jejunal length (21%), villus height (69%), and crypt depth (84%) (p < 0.05), and regulated the jejunal barrier: insulin-like growth factor-1 (IGF-1) (2.5 times) and Mucin 2 (MUC2) (63 times) were significantly upregulated (p < 0.05). FVT increased the abundance of beneficial bacteria Lactobacillales. However, negative effects were also observed: Immunoglobulin A (IgA), Immunoglobulin G (IgG), Immunoglobulin M (IgM), Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), and Interferon-gamma (IFN-γ) in broilers were significantly upregulated (p < 0.05), indicating immune system overactivation. Duodenal barrier-related genes Mucin 2 (MUC2), Occludin (OCLN), Claudin (CLDN1), and metabolism-related genes solute carrier family 5 member 1 (SLC5A1) and solute carrier family 7 member 9 (SLC7A9) were significantly downregulated (p < 0.05). The results of this trial demonstrate that, besides the microbiota, the gut virome and metabolites are also functional components contributing to the growth-promoting effect of FMT. The differential responses in the duodenum and jejunum reveal spatial heterogeneity and dual effects of FVT on the intestine. The negative effects limit the application of FMT/FVT. Identifying the primary functional components of FMT/FVT to develop safe and targeted microbial preparations is one potential solution. Full article

Titanium is widely recognized as an interesting material for electrodes due to its excellent corrosion resistance, mechanical strength, and biocompatibility. However, further functionalization is often necessary to impart advanced interfacial properties, such as selective ion transport or stimuli responsiveness. In this context, the integration of smart polymers, such as poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA)—noted for its dual pH- and thermo-responsive behavior—has emerged as a promising approach to tailor surface properties for next-generation devices. This work compares two covalent immobilization strategies for PDMAEMA on titanium: the “graft-to” method, involving the attachment of pre-synthesized polymer chains, and the “graft-from” method, based on surface-initiated polymerization. The resulting materials were characterized with size exclusion chromatography (SEC) for molecular weight, Fourier-transform infrared spectroscopy (FTIR) for chemical structure, scanning electron microscopy (SEM) for surface morphology, and contact angle measurements for wettability. Electrochemical impedance spectroscopy and polarization studies were used to assess electrochemical performance. Both strategies yielded uniform and stable coatings, with the mode of grafting influencing both surface morphology and functional stability. These findings provide valuable insights into the development of adaptive, stimuli-responsive titanium-based interfaces in advanced electrochemical systems. Full article