Search Results (387,849)

The survival and activation of both effector and regulatory CD4⁺T cells are promoted by cytokines in a complex series of interactions. Alloantigen-specific Regulatory T cells (Treg) constitutively express IL-2 receptor (CD25) and Foxp3. This discovery arose as the cells that transfer the alloantigen-specific transplant tolerance die in culture with specific alloantigens, unless the cultures are supplemented with cytokines from activated lymphocytes. One such cytokine was IL-2, but other cytokines are essential. We describe how the activation of Treg by antigens depends on cytokines produced by antigen-activated effector T cells. These cytokines also drive in parallel the activation of Treg. The Treg are induced to express similar transcription factors and chemokine receptors and have a similar cytokine responsiveness to the activated T effector cells. The activation of Treg by antigens is a two-step process: the first requires cytokines produced by effector T cells early in their activation, and the second step is driven by cytokines produced later by effector T cells during activation. Cytokines from Type 1 responses promote the induction of Th1-like Treg. Likewise, cytokines produced in Type 2, Type 3, and Tfh responses induce different pathways of Treg activation. Understanding the pathways for the activation and expansion of potent antigen-specific Treg will help produce Treg to control allograft rejection or autoimmunity. Currently, the complexity of the numerous potential pathways of activation of Treg remains incompletely understood. The dogma that IL-2 is the only driver of Treg activation may have hindered the development of highly potent antigen-specific Treg for therapy. Full article

Soil contamination by per- and polyfluoroalkyl substances (PFAS) represents a pressing environmental and public health concern due to the exceptional persistence of carbon–fluorine bonds, which prevent natural attenuation and limit the effectiveness of conventional remediation. Agricultural and industrial soils serve as long-term sinks for PFAS, continuously releasing these pollutants into groundwater and facilitating their transfer through the food chain. Conventional chemical and physical remediation methods are often costly, energy-intensive, and yield incomplete removal, underscoring the need for sustainable and biologically driven alternatives. Microbial consortia have emerged as a promising solution due to their metabolic complementarities, cross-feeding interactions, and ecological resilience, which together enable PFAS transformation and partial defluorination under complex soil and subsurface conditions. Key enzymes such as oxygenases, reductive dehalogenases, and hydrolases are often operating within co-metabolic networks, which play central roles in these processes. Advances in metagenomics, CRISPR-based functional screening, and metabolic modelling are rapidly uncovering novel PFAS-degrading microbes and pathways. Integration of machine learning with multi-omics and environmental datasets further enables the prediction of degradation mechanisms, identification of keystone degraders, and rational design of synthetic consortia. Emerging sustainable strategies, including biochar- and nutrient-amended soil microcosms, plant–microbe partnerships for coupled soil–groundwater phytoremediation, and bioelectrochemical systems that offer new avenues for enhancing PFAS biodegradation in situ. This review synthesises recent research progress and provides critical perspectives on the mechanistic, ecological, and engineering dimensions of PFAS bioremediation, proposing an integrated conceptual framework linking microbial consortia dynamics, enzymatic pathways, and environmental engineering interventions to guide scalable field applications and sustainable management of PFAS-contaminated soil–groundwater ecosystems. Full article

Background: One of the main causes of cancer-related mortality globally is lung adenocarcinoma (LUAD), necessitating the development of novel therapeutic targets. The parathyroid hormone type 2 receptor (PTH2R) exhibits differential expression across multiple cancers, yet its role in LUAD remains unclear. Methods: Through an integrated analysis of multiple public databases (including SangerBox 3.0, UALCAN, Kaplan–Meier Plotter, and TIMER), we identified PTH2R—a member of the family B1 GPCRs—as a candidate therapeutic target with significant prognostic value in LUAD. Subsequently, the antitumor effects of PTH2R knockdown and melatonin were evaluated through cell proliferation, colony formation, migration, and apoptosis assays. Transcriptome analysis revealed key biological processes and signaling pathways regulated by PTH2R, identified key genes modulated by PTH2R, and validated core gene expression via RT-qPCR. Results: PTH2R is a potential therapeutic target for lung adenocarcinoma. Both PTH2R knockdown and melatonin treatment significantly inhibited LUAD cell proliferation, colony formation, and migration capabilities while promoting apoptosis. Notably, the combination of PTH2R knockdown and melatonin treatment demonstrated synergistically enhanced antitumor effects. Transcriptome analysis revealed two key genes within the PTH2R signaling pathway, and RT-qPCR validated the expression of these two key genes. Conclusions: Our work provides the first evidence confirming the substantial value of PTH2R as a novel therapeutic target for LUAD. It preliminarily demonstrates the mechanism by which melatonin inhibits LUAD by targeting PTH2R, offering crucial experimental evidence and theoretical support for developing precision therapeutic strategies against this cancer. Full article

This study investigates the machinability of Continuous Fiber-Reinforced Thermoplastic Composite (CFRTP) produced via Material Extrusion (MEX) additive manufacturing, focusing on drilling as a critical post-processing step in hybrid manufacturing. CFRTP components, fabricated from 3K carbon fibers and a PLA matrix, were subjected to systematic drilling tests under varying cutting speeds (50–110 m/min) and feed rates (0.06–0.24 mm/rev). Thrust force (Fz) and torque (Mz) were recorded using a high-precision dynamometer to evaluate the influence of cutting parameters on mechanical loads and damage mechanisms. Results indicate that increasing the feed rate significantly increases Fz and Mz, promoting fiber pull-out, delamination, and edge deformation, particularly at hole entry and exit regions. Conversely, higher cutting speeds reduce Fz and Mz due to thermal softening of the PLA matrix, enabling more controlled fiber–matrix interaction. Microscopic analyses revealed that damage severity correlates strongly with mechanical load levels. While high feed rates caused pronounced surface irregularities and matrix smearing, low feed rates combined with high cutting speeds yielded smoother hole morphology and preserved fiber–matrix integrity. The study concludes that optimal drilling conditions for CFRTP materials involve low feed rates and high cutting speeds, minimizing mechanical loads and suppressing damage formation. These findings provide a scientific basis for precision finishing strategies in hybrid manufacturing, enhancing dimensional accuracy and structural reliability of CFRTP components for advanced engineering applications. Full article

The primary focus of enhancing the efficiency of operations in the Industry 4.0 setting is Predictive and Preventive Maintenance (PPM). The paper introduces a predictive-maintenance system based on the Unified Namespace (UNS), which involves real-time sensor measurements, photogrammetry, and modelling of a digital twin to improve fault prediction and responsiveness to maintenance. This experiment was conducted over six months in a medium-sized discrete electromechanical production plant equipped with motors, Variable Speed Drives (VSDs), robot/cobots, precision grip systems, pipework systems, Magnemotion/linear motor drives, and a CNC machine. The continuous data, such as high-frequency vibration, temperature, current, and pressure, were monitored and analysed with machine-learning models, including support-vector machines, Gradient Boosting, long-short-term memory, and Random Forest, through which temporal degradation can be predicted. UNS architecture integrated all sensor and imaging data into a vendor-neutral data model through OPC UA to help ensure that all experiments could be integrated consistently and be updated in real time to real digital twins. The suggested system correctly identified mechanical and electrical failures and predicted failures before they really took place. Consequently, machine downtime was reduced by 42.25%, and Mean Time to Repair (MTTR) by 36%, compared to the prior six-month baseline period. These improvements were associated with earlier anomaly detection and digital-twin-supported pre-inspection. Overall, the findings indicate that the integration of UNS with multi-modal sensing and digital-twin technologies may enhance predictive maintenance performance in comparable industrial settings. The framework provides a data-driven, scalable solution to organisations that aim to modernise their maintenance processes, attain greater reliability and better equipment utilisation, as well as enhanced Industry 4.0 preparedness. Full article

Guaranteed annuity options (GAOs) allow policyholders to convert accumulated funds into life annuities at maturity at a guaranteed minimum rate. Thus, insurers are exposed to both investment and longevity risks. Accurate valuation of these long-term, survival-contingent contracts is essential for solvency assessment and risk management. Many existing approaches assume independence between interest rate and mortality risks. This paper develops a computationally efficient pricing framework for GAOs that jointly models interest and mortality rates as correlated stochastic processes with regime-switching dynamics governed by a finite-state continuous-time Markov chain. Model parameters are estimated using U.S. interest rates and cohort mortality data via quasi-maximum likelihood estimation. A semi-analytic valuation formula is derived based on the joint distribution of the underlying processes. Numerical results show that incorporating correlation and regime-switching materially increases GAO prices relative to conventional one-state models. The proposed semi-analytic approach delivers substantial computational advantages over standard Monte Carlo simulations. Sensitivity analysis further identifies the parameters most relevant for long-horizon pricing and solvency considerations. This highlights the practical relevance of the framework for managing longevity-linked guarantees under economic and demographic uncertainty. Full article

Determining the age and origin of the “Huoshan Sandstone” holds significant geological implications for the stratigraphic division and correlation of Precambrian sequences in the North China Craton, provenance analysis, reconstruction of tectonic–sedimentary patterns, and paleogeographic settings restoration. This paper investigates the petrology, zircon U-Pb dating, Hf isotopes analysis, and zircon microzonation geochemistry of the “Huoshan Sandstone”. The “Huoshan Sandstone” is grayish-white, light gray, light yellow, purplish-red quartzitic sandstone and quartz sandstone, with a quartz content ranging from 85.5% to 97.8%. The quartz grains exhibit relatively straight contact edges, characteristic of low-grade metamorphosed quartzite. The protolith of the “Huoshan Sandstone” is a medium-grained quartz sandstone with dominant grain sizes of 0.30~0.50 mm, exhibiting well-rounded to subrounded grains and highly developed siliceous cementation characterized by secondary overgrowth. The zircon Th/U ratio confirms that the zircons in the “Huoshan Sandston” are mainly magmatic zircons. Most zircons exhibit extreme HREE enrichment and left-sloping REE patterns, and show significant positive Ce anomalies (Ce/Ce* of 1.06~290.68) and negative Eu anomalies (Eu/Eu* of 0.065~0.61). The age range of zircon ²⁰⁷Pb/²⁰⁶Pb is 1770 ± 20~2732 ± 16 Ma, and there are two obvious peaks at 1800 and 2500 Ma in the U-Pb age frequency histogram, the age of the intersection point on the concordia line is 2521 ± 31 Ma, and the age of the intersection point on the lower part of the line is 1829 ± 22 Ma. These two ages correspond to the timing of Neoarchean TTG gneiss formation through oceanic crust partial melting in the central North China Craton, and the ~1.85 Ga Paleoproterozoic thermal metamorphic event recorded in the Zhongtiao Group of the same region, respectively. The maximum depositional age of the “Huoshan Sandstone”, constrained by the youngest detrital zircon U-Pb ages at 1770 ± 20 Ma, indicates that its sedimentation occurred after 1770 ± 20 Ma (Late Late Paleoproterozoic). Furthermore, as it underlies the red shales of the Cambrian Mantou Formation as a distinct tectonic layer, it must have formed prior to the deposition of the Cambrian Mantou Formation. In addition, in situ Lu-Hf isotopic analyses of these zircons yielded two-stage model ages, mainly between 2.5 and 2.8 Ga, suggesting the provenance to be the Precambrian basement of the Zhongtiao Mountain region in the central North China Craton. It is inferred that the Precambrian strata in the Zhongtiao Mountain area were involved in the process of subduction, collage, and collision of the two continental blocks of the eastern and western parts of the North China Craton, and further confirmation is provided that the final collision of the two continental blocks to form the central orogenic belt occurred in the late Palaeoproterozoic. Full article

This study is dedicated to the application of neural network technologies for determining aeration parameters in order to predict the efficiency of flotation separation. Within the framework of the research, digital technology solutions were actively employed, including a neural network for segmentation at the stage of determining the granulometric characteristics of bubbles and a convolutional neural network module for determining the froth layer height. An analysis was conducted to examine the variation in the statistical parameter d₃₂, which characterizes the bubble size distribution, as a function of flotation time and measurement height. The analysis revealed that the d₃₂ values determined by neural network processing remained within the range of acceptable dispersion and are therefore suitable for subsequent analytical procedures. Furthermore, a comparative evaluation of the obtained size distributions indicated the absence of statistically significant differences between the neural network measurements and manually labelled data with a p-value equal to 0.64. A neural network for object detection was used to record the height of the froth layer during the experiment to obtain a time series, that were subsequently processed with data processing approaches including Savitzky–Golay and Singular Spectra Analysis. Based on the analysis of the sum of the obtained dependences, a criterion is proposed and modeled for evaluating the selectivity of frother by connecting the diameter of bubble in pulp and bubble in froth. Based on the modeling results, it was determined that the optimal range of bubble sizes and froth size ratios for MIBC is constrained to d₃₂ values ranging from 1.058 to 1.089 mm, with the ratio of froth bubble radius to d₃₂ ranging from 1.302 to 2.098, depending on the floatability ratios of the respective fractions. When employing OPF, the values for d₃₂ fall within the interval of 0.868 to 1.113 mm, while the Dₓ parameter ranges from 0.559 to 0.931. Full article

The momentum transport and scale-dependent motion characteristics within vegetation canopies play a crucial role in shaping near-surface turbulent structures and exchange processes, yet the interactions among different turbulent scales and their statistical representations remain insufficiently understood. Based on a series of controlled wind tunnel experiments, this study identifies coherent turbulent structures using a phase-space algorithm constructed from streamwise velocity fluctuation u′, acceleration a, and jerk j, and compares transport efficiency (exuberance η). This study uses scale-wise (cut-off frequency) momentum flux contribution analysis, natural visibility graph (NVG), and large–small-scale amplitude modulation to examine transport and multiscale behaviors across different canopy densities, array layouts, and inflow conditions. Results show that canopy density (different C_d drag coefficient) is a primary factor governing transport efficiency. Under low-wind staggered configurations, increasing canopy density strengthens the contribution of low-frequency large-scale motions to total momentum flux. In contrast, high-wind aligned configurations intensify canopy-top shear, enhancing small-scale motions and thereby reducing the relative contribution of large-scale motions. NVG analysis further reveals that in high-density canopies, large-scale acceleration and deceleration events tend toward equilibrium, whereas deceleration events dominate consistently in low- and medium-density cases. Amplitude modulation results indicate that high-density cases exhibit highly consistent modulation behavior, followed by low-density cases, while medium-density cases display a pronounced height-dependent variation, characterized by a distinct modulation critical point. This study proposes a unified analytical framework integrating coherent structure detection, graph-theoretic analysis, multiscale transport characterization, and large–small-scale modulation, providing a comprehensive description of momentum transport and scale motions within canopy flows, and it offers new insight into the mechanisms governing complex vegetation canopy turbulence. Full article

Background: Temporomandibular disorders (TMDs) are common musculoskeletal conditions associated with pain, functional limitation, and reduced quality of life (QoL). Despite the widespread use of conservative and minimally invasive treatments, the available evidence remains fragmented across heterogeneous interventions, diagnostic criteria, and outcome measures, limiting comparative interpretation and clinical applicability. Objectives: The primary objective of this systematic review is to evaluate the effectiveness of conservative and minimally invasive interventions for pain reduction in adult patients with temporomandibular disorders. Secondary objectives include assessing effects on mandibular function and QoL and exploring differences across intervention categories, TMD subtypes, diagnostic criteria, and follow-up durations. Methods: This protocol is registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420251250251) and adheres to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines. A systematic search will be conducted in PubMed/MEDLINE, Web of Science, Scopus, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) for randomized controlled trials (RCTs) published from 1 January 2015, up to the date of study initiation, using controlled vocabulary terms and free-text keywords combined with Boolean operators. Eligible studies will include adult patients (≥18 years) diagnosed with temporomandibular disorders using validated diagnostic criteria and treated with conservative or minimally invasive interventions, compared with placebo/sham, no treatment or usual care, or active comparators, in accordance with the PICOS framework. Two reviewers will independently screen studies and extract data, with disagreements resolved by consensus or consultation with a third reviewer; the study selection process will be documented using a PRISMA 2020 flow diagram. Interventions will be synthesized within predefined clusters (e.g., physical and manual therapies, occlusal splint therapy, physical agent modalities, and minimally invasive joint procedures). Risk of bias will be assessed using the revised Cochrane Risk of Bias tool (RoB 2). The primary outcome will be pain intensity, while secondary outcomes will include mandibular function and QoL. Where appropriate, meta-analysis using a random-effects model will be performed; otherwise, a structured narrative synthesis will be provided. Expected Impact: The systematic review is expected to deliver an updated and methodologically rigorous synthesis of evidence on conservative and minimally invasive interventions for TMDs. By addressing existing research gaps such as the fragmentation of evidence across intervention types, heterogeneity in diagnostic criteria, and variability in outcome measures, this review will support evidence-based clinical decision-making and identify priorities for future research. Full article

Decellularization removes immunogenic intracellular components of fish tissues while keeping the extracellular matrix (dECM) structure, mechanical integrity, and bioactivity. Fish-derived dECM retains native bioactive components, exhibiting high biocompatibility, low immunogenicity, and biodegradability, while supporting cell adhesion, proliferation, and tissue regeneration. Due to its abundance, minimal ethical concerns, and low zoonotic risks, fish wastes are emerging as sustainable sources of dECM, offering an eco-friendly alternative to mammalian biomaterials. This review highlights advances in decellularizing fish wastes such as skin, scales, bones, viscera, and swim bladders from species including tilapia, tuna, milkfish, carp, goldfish, and sturgeon. Physical, chemical, biological, and hybrid decellularization methods are assessed for cell removal, ECM preservation, and mechanical performance. Recent advances in polymer-dECM composites, crosslinking, and 3D bioprinting have significantly improved scaffold performance, making fish-derived dECM applicable for healing of wounds, regeneration of bone and cartilage, and repair of soft tissues. Despite its potential, challenges remain in optimizing perfusion rates, temperature variations, and tissue-specific protocols, as well as developing eco-friendly decellularization techniques using biodegradable reagents. Future perspectives include expanding decellularized fish tissue sources, innovating bio-inks for 3D bioprinting, and refining tissue-specific processing methods to maximize the potential of fish-derived dECM in regenerative medicine and tissue engineering. Full article

Older adults with disabilities face compounded vulnerabilities due to both functional limitations and socioeconomic disadvantage. In South Korea, where public welfare systems remain fragmented and cultural values emphasize independence and productivity, understanding the mechanisms linking socioeconomic status (SES) to health outcomes is critical. This study investigates whether reserve capacity mediates the relationship between SES and self-rated health (SRH) in older adults with disabilities. Data were drawn from the supplementary survey on people with disabilities in the 18th wave (2023) of the Korea Welfare Panel Study (KWePS). The analytic sample included older adults aged 65 and above with registered disabilities. A multiple mediation analysis was conducted using Model 4 of the PROCESS macro in SPSS to examine whether three dimensions of reserve capacity—intrapsychic resources (self-esteem), interpersonal resources (social support satisfaction), and tangible resources (use of public disability services)—mediated the relationship between SES and SRH. Demographic and health-related covariates were statistically controlled. The results are as follows: The direct effect of SES on SRH was not significant; however, significant indirect effects were found through all three mediators. Higher SES was positively associated with intrapsychic and interpersonal resources and negatively associated with tangible resource use. Among the mediators, interpersonal resources had the strongest positive effect on SRH, while tangible resources showed a negative association—possibly due to compensatory activation or increased disease awareness among service users. The findings highlight the importance of psychosocial and relational resources in shaping perceived health among disabled older adults in Korea. Policy interventions should move beyond material assistance and focus on strengthening social networks and psychological resilience to reduce health disparities in this population. Full article

To address the challenge of purifying bioactive polyphenols from the complex matrix of Ziziphus jujuba Mill. var. spinosa pulp, this study established an integrated purification protocol combining Deep Eutectic Solvent (DES) extraction with macroporous adsorption resin (MAR) enrichment. Among five screened resins, AB-8 exhibited superior selectivity, achieving a maximum adsorption capacity of 62.48 mg polyphenols/g dry resin and a desorption ratio of 83.40%. Kinetic analysis revealed that the adsorption process strictly followed a pseudo-second-order model (R² = 0.999), indicating a mechanism dominated by chemisorption. Through dynamic optimization, optimal column parameters were determined as a loading concentration of 2.4 mg/mL, a flow rate of 1.0 mL/min, and elution with 70% (v/v) ethanol. Structural characterization via UV-Vis and FT-IR confirmed the effective removal of polysaccharide and protein impurities, while High-Performance Gel Permeation Chromatography (HPGPC) indicated a low-molecular-weight distribution (M_w approx. 1073 Da). Furthermore, HPLC-MS profiling definitively identified eight key constituents, including chlorogenic acid, catechin, rutin, and quercetin. Collectively, this work elucidates the adsorption mechanism and provides a scalable, efficient technical foundation for the high-purity preparation of jujube polyphenols. Full article

This study presents an innovative and interdisciplinary didactic approach for teaching biodiversity to high school students, aiming to enhance basic learning skills and promoting deeper understanding of biological concepts. The designed educational proposal aims to support policy-driven collaboration between schools and botanical gardens within the framework of coordinated and long-term educational policies. The intervention was designed to cultivate both cognitive and metacognitive skills within three (3) didactic hours, offering a holistic learning experience through the study of Tulipa members used as an alluring model. A total of 168 Greek first- and second-grade high school students (on average 16 years old) participated in the study. Biodiversity was examined in a multidisciplinary fashion, focusing on species’ diversity (phenotypic), genetic-karyological diversity, and habitat diversity. The core components of the approach included: (a) the completion of a corresponding worksheet module, which effectively engaged students in the learning process using the 5E didactic model, and (b) a karyotype lab experiment using living Tulipa specimens. The learning process was evaluated through two questionnaires assessing the acquisition of scientific knowledge and behavioral outcomes. The results showed a positive impact on students’ understanding regarding the genetic material and biodiversity, with the karyotype experiment playing a key role in achieving high performance in both cognitive and affective learning objectives. Knowledge scores were higher in the second-grade students (53–73%) than in the first-grade students (44–69%) of high school, especially regarding concepts such as karyotype applications and biodiversity-ecosystem balance. The karyotype experiment positively correlated with both the evaluation of the intervention and the shifts in biodiversity beliefs (Pearson’s r = 0.649, 0.515; p < 0.05, respectively). The modeled inquiry-based approach with living tulips and karyotype experiments can help schools and botanic gardens counteract plant blindness by enhancing cognitive and affective learning outcomes within a limited instructional timeframe. Full article

Natural soy protein isolate (SPI) exhibits suboptimal functional characteristics, including limited solubility, reduced foaming capacity, and diminished emulsifying ability. Conventional singular-modification techniques are unable to enhance multiple functional properties concurrently, thereby posing challenges in fulfilling the varied requirements of food processing. Therefore, this study employed ultrasonic and pepsin enzymatic modification techniques on SPI. By varying ultrasonic frequency (20 kHz, 207 kHz) and sonic energy density (295 W/L, 590 W/L), different modified protein samples were obtained. The effects of single treatment, combined treatment, and varying ultrasonic parameters on their structure and functionality were investigated. The results indicate that compared to single enzymatic hydrolysis, combination-treated SPI exhibited reduced fluorescence intensity and UV absorbance, along with significant decreases in methionine (Met) and free-sulfhydryl (SH) content (p < 0.05). Particle size decreased while distribution became more uniform, and relative molecular weight also diminished. This indicates that combined processing induces more pronounced changes in the protein’s primary to higher-order structures, thereby enhancing functional properties. Specifically, surface hydrophobicity (H₀) and emulsification stability (ESI) improved, while emulsifying capacity (EAI) significantly increased (p < 0.05). In summary, ultrasonication combined with enzymatic hydrolysis exhibits synergistic effects, optimizing protein structure and functional characteristics. This approach facilitates the development of functional foods and broadens their application scope. Full article