Search Results (33,377)

Ring finger protein 126 (RNF126) is a RING-type E3 ubiquitin ligase that has recently emerged as a multifaceted regulator of cellular homeostasis, stress adaptation, and disease progression. Through its structurally distinct zinc-finger and catalytic RING domains, RNF126 orchestrates substrate recognition and ubiquitin transfer, generating diverse ubiquitin linkages with both proteolytic and nonproteolytic functions. Initially characterized as a component of the protein quality control (PQC) machinery, RNF126 cooperates with chaperones such as BAG6 and UBQLN1 to eliminate mislocalized and misfolded proteins, thereby maintaining proteostasis. Beyond PQC, RNF126 plays pivotal roles in DNA damage response pathways by regulating homologous recombination, non-homologous end joining, checkpoint signaling, and genome stability through substrates, including MRE11, Ku80, RNF168, and 14-3-3σ. Genetic studies have further demonstrated its importance in embryogenesis and male fertility, and accumulating evidence has identified RNF126 as a critical driver of malignancy in multiple cancers. RNF126 promotes tumor progression by degrading or modulating key regulators, such as p21, PTEN, p53, PDKs, and LKB1, thereby enhancing proliferation, metabolic reprogramming, anoikis resistance, metastasis, and chemo/radioresistance. Intriguingly, RNF126 exhibits context-dependent functions, acting as an oncogene or tumor suppressor depending on the tissue type and substrate selection. In addition to cancer, RNF126 has been implicated in neurodegeneration, cardiac pathology, antiviral immunity and adaptive immune regulation. This review summarizes the current knowledge of RNF126 structure, ubiquitin signaling mechanisms, physiological functions, and pathological roles, while discussing emerging therapeutic strategies and future challenges for targeting RNF126 in precision medicine. Full article

Background/Objectives: Chiropractors serve as first-contact practitioners in South Africa and frequently encounter patients with systemic conditions that may mimic musculoskeletal complaints. Non-musculoskeletal (non-MSK) examinations are essential for identifying red flags, ruling out serious pathologies, and facilitating timely referrals. Despite their importance for patient safety and integration into primary healthcare, limited research exists on the frequency with which South African chiropractors perform these assessments. This study aimed to describe the frequency and indications for non-MSK examinations performed by South African chiropractors and to explore variations across examination types, demographic factors, years of experience, and training institutions in secondary analyses. Methods: A cross-sectional online survey was distributed to 898 registered chiropractors, yielding 186 responses (20.7%). The questionnaire assessed the frequency of non-MSK examinations using a five-point Likert scale. Data were analysed using descriptive statistics (frequencies, percentages, medians, interquartile ranges). Exploratory subgroup comparisons were conducted using nonparametric tests, but these findings should be interpreted with caution due to small and uneven sample sizes in some subgroups. Ethical approval was obtained (REC-3366-2025). Results: Most respondents were female (57.5%) and practising in Gauteng (49.5%). Blood pressure (84.4%) and heart rate (81.2%) were the most frequently performed examinations, while respiratory rate (12.4%), oxygen saturation (9.7%), and temperature (11.8%) were the least frequently performed vital signs. Breast (3.8%), abdominal (10.2%), and genitourinary (1.1%) examinations were rarely conducted. Exploratory subgroup observations suggested provincial variation: chiropractors in KwaZulu-Natal performed non-MSK examinations more frequently than those in Gauteng and the Western Cape (mean differences ranging from 0.21 to 1.19 on a five-point scale), whereas no meaningful differences were found across years in practice. Conclusions: South African chiropractors perform a selective range of non-MSK examinations, supporting their role as first-contact practitioners. However, many systemic examinations are conducted infrequently, with observed provincial variation. These descriptive findings highlight the need for greater consistency and standardisation in non-MSK screening to enhance patient safety and interdisciplinary care. Future adequately powered studies are needed to confirm the exploratory subgroup observations. Full article

This study explores the selection of a heat recovery system for cogeneration units based on gas engines supplying the district heating system in Opole in order to enhance the efficiency and sustainability of the system. The proposed modifications focus on utilizing low-temperature (LT) waste heat from engine cooling circuits and improving exhaust heat recovery. The research examines retrofitting three cogeneration engines (total thermal capacity of 7.6 MW) by integrating water-to-water heat pumps to upgrade low-temperature waste heat (55–45 °C up to 700 kW), enhancing heat supply to the district heating network. Additionally, a second stage of economizers is evaluated to maximize condensation-based exhaust heat recovery from the existing 95–135 °C system. These system modifications increase the overall thermal capacity up to 9–9.1 MW. To maintain heat supply during cogeneration unit shutdowns (due to failures or electricity price fluctuations), an auxiliary air-to-water cascade heat pump provides an additional 0.8–1 MW. With increasing electricity price volatility, these system modifications provide crucial operational flexibility. Computational simulations confirm that the hybrid configuration successfully upgrades waste heat while strictly maintaining the existing engine return water safety limit. The evaluation demonstrates high economic profitability alongside stable emission reductions. This research presents a case study in optimizing heat recovery in cogeneration-based district heating networks, demonstrating practical and scalable applications for sustainable energy systems. Full article

Background: Titanium implant osseointegration is hierarchically governed by surface properties directing protein adsorption, cell recognition, immune modulation, and bone formation. Photofunctionalization creates ultrahydrophilic surfaces by removing hydrocarbons. To integrate it with 3D-printed architectures requires systematic synthesis. Problem: The classical static view of osseointegration obscures its dynamic, multiscale nature. How photofunctionalization-induced ultrahydrophilicity modulates the surface–protein–cell–bone interface as a continuous, hierarchical system remains unclear. Scope: This review synthesizes evidence on how photofunctionalized ultrahydrophilic titanium surfaces control protein adsorption, integrin-mediated mechanotransduction, immune responses, and in vivo osseointegration, with an emphasis on 3D-printed porous architectures. Conclusions: Photofunctionalization enhances protein adsorption, preserves bioactive conformation, and stabilizes protein layers, selectively engaging osteogenic integrins and amplifying FAK–Src/YAP–TAZ signaling. In 3D-printed implants, ultrahydrophilicity enables capillary-driven fluid infiltration and uniform bone ingrowth. Through this review, knowledge gaps—in surface aging and limited in situ characterization—are identified, and an interface-informed design integrating surface chemistry, architecture, and biological timing is proposed. Full article

The rapid advancement of machine learning and artificial intelligence (AI) has created new opportunities to enhance diagnostic accuracy in dermatology, particularly within primary care settings. Computer-aided diagnosis (CAD) systems have demonstrated potential to support General Practitioners (GPs) by enabling earlier and more consistent identification of skin diseases. This review critically examines the literature on explainable artificial intelligence (XAI) for skin disease classification, with a specific focus on the evolution of explainability frameworks and the methodological implications of dataset selection. A comprehensive review of studies published between 2020 and 2025 was conducted across multiple academic databases, encompassing research on skin lesion detection, classification, and monitoring. The analysis reveals that deep learning architectures, particularly those leveraging transfer learning with models such as EfficientNet, ResNet, and Xception, frequently report high classification accuracies—often exceeding 90% when evaluated on single benchmark datasets. However, studies employing multiple datasets consistently demonstrate more stable and generalisable performance, albeit with modest reductions in reported accuracy, highlighting a critical trade-off between performance optimisation and real-world robustness. The review further identifies a clear temporal progression in the adoption of XAI techniques. Early studies relied on a broader range of post hoc explainability while later work increasingly consolidated around Grad-CAM, SHAP, and related attribution techniques, followed by gradual diversification into more specialised frameworks such as TCAVs (Testing with Concept Activation Vectors) and Prototype-based Networks. Despite these advances, the lack of clinically grounded explanations, limited integration of ethical considerations, and reliance on non-clinical imagery continue to constrain clinical applicability which we have explored using a GRADE-style narrative. Notably, evidence suggests that CAD systems can improve GP diagnostic accuracy for conditions such as melanoma and seborrhoeic keratosis; however, sustained clinical adoption remains contingent on transparent, reliable, and context-aware explainability mechanisms. Full article

This study critically addresses the challenge of selecting optimal insulation materials for contemporary, energy-efficient building envelopes, a decision with profound environmental, structural, and occupational health consequences. The paper responds to the growing demand for sustainable, resilient solutions by comparing wool, a bio-based, regenerative material, and expanded polystyrene (EPS), a synthetic polymer widely implemented in the construction industry, and advanced laboratory testing (thermal conductivity, moisture buffering, freeze–thaw resistance) is discussed in a comprehensive synthesis of the recent literature. Also, field evaluations from European retrofits and pilot projects (UK, Denmark, Finland, Iceland, Norway, Sweden, Germany and France) further contextualize performance outcomes, and life cycle impacts are considered. Recent results reveal that wool insulation achieves a moisture buffering value (MBV) between 1.8 and 2.7 (g/m²) % RH, minimal vapor resistance (mvr = 1–2), and preserves functional and structural integrity through more than 100 freeze–thaw cycles, leading to significant stabilization of the interior microclimate and enhanced durability. In contrast, EPS delivers lower thermal conductivity (0.032–0.037 (W/mK), critical for reducing heating/cooling demand, but exhibits limited vapor permeability (lvp = 60–150 MN·s/(g·m)), increased risk of condensation and mold, and reduced compressive strength (<22% after 30 cycles), especially when ventilation details are inadequate. Hybrid envelope systems leveraging both EPS and wool are demonstrated to optimize energy efficiency (up to 23% seasonal savings) and reduce interior humidity fluctuations, while lifecycle and recycling assessments show wool panels to be markedly superior in carbon footprint reduction and circularity. The stratification of insulation layers incorporating wool for vapor and moisture control, and EPS for pure thermal resistance is emerging as best practice in sustainable retrofit and new-build projects. Recommendations highlight the necessity for rigorous laboratory validation, international standards alignment, and integrated material design for robust hygrothermal comfort and environmental performance. The review also covers wool- and EPS-based hybrid composites, showing how natural fibers can improve key mechanical properties without compromising thermal insulation performance or environmental benefits. Full article

Recently, the Quality by Design (QbD) principle has been implemented in the pharmaceutical industry to enhance product and process understanding through a science- and risk-based approach. This study aimed to apply QbD principles to the formulation development of felodipine push–pull osmotic pump (PPOP) capsules. The quality target product profile (QTPP) and critical quality attributes (CQAs) were established. A Box–Behnken experimental design was employed to optimize the formulation variables, including the amounts of Polyox WSR N80, Polyox WSR Coagulant, and sodium chloride, selected based on the initial risk assessment. Four responses were monitored: lag time, release rate and R² based on zero-order release kinetics, and drug release at 24 h. Results indicated that the optimal formulation consisted of 125 mg Polyox WSR N80, 26 mg Polyox WSR Coagulant, and 30 mg sodium chloride. This formulation met the predefined criteria for lag time (≤6 h) and release kinetics (R² ≥ 0.95), while drug release at 24 h remained below the target value (≥80%). Because most fitted response surface models were not statistically significant, the generated regression equations and response surfaces were interpreted qualitatively to identify formulation trends rather than as predictive models. Experimental verification showed reasonable consistency in overall response trends, although substantial deviations between predicted and observed values were observed for some responses, particularly drug release at 24 h. Therefore, the present work should be considered a formulation-development and QbD feasibility study rather than a definitive optimization study. These findings demonstrate that the QbD-based approach enabled systematic, multivariate optimization and design space establishment, providing a more structured framework for formulation refinement compared with prior exploratory development and supporting controlled drug release characteristics of felodipine PPOP capsules. Full article

The molecular mechanisms governing the efficient packaging of the large SARS-CoV-2 RNA genome into progeny virions remain incompletely understood, with the role of untranslated regions (UTRs) being particularly enigmatic. Leveraging proximity ligation sequencing data, we identified direct, high-frequency interactions between the viral packaging signal PS9 and both the 5′ and 3′ UTRs during intracellular replication stages. Functional validation using an infectious virus-like particle (iVLP) system demonstrated that genomes incorporating SARS-CoV-2 UTRs exhibited significantly enhanced packaging efficiency, yielding an increase in both packaged RNA copies and reporter gene expression post-infection. Competitive packaging assays confirmed the UTRs confer a selective advantage during particle assembly. Mechanistically, Western blot and digital Western analysis revealed that UTR-containing iVLPs incorporated approximately 2-fold more nucleocapsid (N) proteins, suggesting enhanced N recruitment or retention. The deletion of specific core sequences within the UTRs predicted to form a base pair with PS9 abrogated this enhancement, suggesting the functional significance of the UTR-PS9 interaction interface. Collectively, these results establish that the 5′ and 3′ UTRs act synergistically through direct RNA-RNA interactions with PS9 to promote N protein recruitment and enhance packaging efficiency in a PS9-dependent iVLPs system. This UTR-PS9 regulatory axis presents a novel target for therapeutic intervention against SARS-CoV-2 and related coronaviruses. Full article

Simple and non-invasive transdermal vaccination is an attractive alternative to conventional injection-based immunization. However, the effectiveness of transdermal vaccines is often constrained by the stratum corneum barrier. Although the use of solid-in-oil (S/O) nanodispersion technology has successfully facilitated skin permeation to induce an immunological response, the antibody titers remain suboptimal. Herein, a dectin-1 selective ligand, laminarin, was used as an immunostimulatory adjuvant to enhance the immune response. S/O nanodispersions loaded with laminarin and ovalbumin (OVA) were systematically developed and characterized in terms of particle size, in vitro OVA release behavior, and skin permeation performance using excised mouse skin. In vivo immunization via transcutaneous administration was performed to evaluate biocompatibility and antigen-specific immunoglobulin-G (IgG) responses. Laminarin-loaded S/O nanodispersions demonstrated long-term stability and efficient ex vivo skin permeability. All the prepared laminarin-loaded S/O nanodispersions showed increased OVA-specific IgG responses compared with the laminarin-free S/O formulation. Among the formulations, the S/O nanodispersion containing OVA and laminarin at a 1:4 weight ratio induced 20-fold higher OVA-specific IgG responses than PBS and 7-fold higher responses than laminarin-free S/O formulations. This study clearly demonstrates the potential of laminarin-loaded S/O nanodispersions as a non-invasive vaccine delivery platform for enhancing antigen-specific antibody responses. Full article

Background and Objectives: Low participation rates in exercise programs among older adults highlight the need for theory-driven, biopsychosocial interventions that enhance adherence, self-efficacy, and functional outcomes. Grounded in principles of motor learning and behavioral reinforcement within physiotherapy practice, this study aimed to examine the effect of periodic assessments combined with verbal feedback on functional and psychological outcomes in community-dwelling older adults. Methods: A pilot RCT was conducted involving 54 individuals aged ≥65 years (53 women and 1 man), recruited from senior community centers. Participants were randomly allocated to an intervention group (periodic assessment and verbal feedback; n = 27) or a control group (n = 27). Both groups participated in an identical 12-week structured exercise program, delivered twice weekly, focusing on balance, gait, and lower-limb functional training. An intention-to-treat approach was applied. Data were analyzed using Linear Mixed Models, with statistical significance set at p < 0.05. Results: Significant group × time interactions were observed in favor of the intervention group for key kinesiology-related functional outcomes, including the Short Physical Performance Battery (SPPB; p < 0.001), Timed Up and Go test (TUG; p = 0.011), and Activities-specific Balance Confidence Scale (ABC; p < 0.001). No statistically significant differences were identified between groups for the Behavioral Regulation in Exercise Questionnaire–2 (BREQ-2; p = 0.164) and the Self-Efficacy for Exercise Scale (ESE; p = 0.108), indicating that the primary psychological outcome (ESE) was not confirmed. However, both ESE and BREQ-2 demonstrated significant baseline differences favoring the intervention group, and, therefore, these findings should be interpreted with caution despite statistical adjustment. Conclusions: Periodic assessments followed by verbal feedback appear to selectively improve the functional effectiveness of structured exercise programs in older women, particularly physical performance, functional mobility, and balance confidence, with no significant differential effect on the primary psychological outcome (ESE; group × time interaction: p = 0.108). These findings support assessment-informed and feedback-driven physiotherapy strategies as a promising adjunct to exercise programs in older adults, with potential implications for optimizing functional outcomes within applied kinesiology and rehabilitation contexts. Full article

Epichloë endophytes can confer diverse benefits to host grasses, but the differences in effects between strains from different populations are poorly understood. In this study, we compared the impacts of two Epichloë bromicola strains isolated from distinct geographic populations of Hordeum bogdanii: GS1 (from Linze County, Gansu Province) and WS1 (from Wensu County, Xinjiang Province). Through controlled inoculation experiments, we established two new symbionts—HE2 (WS1 transferred to endophyte-free GF plants) and HE3 (GS1 transferred to endophyte-free WF plants)—alongside the natural symbionts GI (GS1-harboring) and WI (WS1-harboring) and corresponding endophyte-free controls (GF and WF). Symbiosis was confirmed by microscopic observation of blue-stained hyphae, re-isolation of fungi, and molecular identification using tef and tub gene sequences. Strikingly, the two strains exerted opposite effects on host photosynthesis. GS1-colonized plants (GI and HE3) maintained normal chloroplast ultrastructure, showed increased chlorophyll a, chlorophyll b, and carotenoid contents, and exhibited enhanced net photosynthetic rate, transpiration rate, and stomatal conductance, comparable to or exceeding those of control WF. In contrast, WS1-colonized plants (WI and HE2) had deformed chloroplasts, reduced pigment contents, and depressed gas exchange parameters, similar to control GF. Both newly generated symbionts accumulated more starch grains than their natural counterparts, indicating altered carbon partitioning. Phenotypic patterns were consistent across natural and novel associations, suggesting that fungal genotype drives outcomes. Differing physiological effects caused by strains from the same species and the same host but different populations indicate the importance of strain-level selection in agricultural applications. GS1 shows promise as a growth-promoting bioinoculant to enhance photosynthesis and productivity in forage grasses, particularly under marginal conditions. This study highlights how intraspecific variation and local adaptation shape grass–endophyte interactions and informs targeted use of symbionts in sustainable agriculture. Full article

The Asian swamp eel (Monopterus albus), a commercially important freshwater aquaculture species in China and Southeast Asia, has attracted growing scientific interest owing to its natural protogynous hermaphroditism and substantial economic significance. Recent advances in genomics technologies have provided new insights into genetic improvement, disease resistance, and growth optimization in this species. However, a cohesive, up-to-date synthesis of the current genomic research landscape remains lacking. This review systematically summarizes progress in Asian swamp eel genomics: (i) reference genome development; (ii) population-level genetic diversity analysis; (iii) genome annotation and functional gene prediction; and (iv) applications of genomics in selective breeding, disease resistance enhancement, and growth performance optimization. We further evaluate emerging tools and platforms, highlight key technical constraints, and address ethical considerations and regulatory gaps in genome-informed aquaculture practices. Finally, we propose priority research avenues to strengthen the scientific foundation for resilient and sustainable swamp eel aquaculture. Full article

Naringinase is an enzyme complex composed of α-L-rhamnosidase and β-D-glucosidase, capable of deglycosylating flavonoids such as hesperidin. α-L-rhamnosidase converts hesperidin into rhamnose and hesperetin 7-O-glucoside (Hes-7-G), while β-D-glucosidase further hydrolyses Hes-7-G to hesperetin. Selective inactivation of β-D-glucosidase enables accumulation of Hes-7-G, a compound with higher water solubility and bioavailability than hesperidin or hesperetin, making it valuable for food and biotechnological applications. This study aimed to identify conditions allowing selective inhibition of β-D-glucosidase while preserving α-L-rhamnosidase activity for efficient Hes-7-G production. The effects of pH, temperature, and incubation time were investigated, together with the influence of polyols and sugars, including inositol, sucrose, glycerol, xylose, erythritol, xylitol, and sorbitol, on α-L-rhamnosidase thermostability. Among the tested additives, erythritol significantly improved α-L-rhamnosidase thermostability. The highest selectivity was achieved by incubating the enzyme in 1.4 M erythritol at 70 °C for 10 min, resulting in ~5% residual β-D-glucosidase activity and 50% α-L-rhamnosidase activity. Under these conditions, α-L-rhamnosidase activity exceeded β-D-glucosidase activity by more than 60-fold. Selective thermal inactivation of β-D-glucosidase in the presence of erythritol provides an effective strategy for producing Hes-7-G from hesperidin and may enhance flavonoid bioavailability for industrial applications. Full article

Non-attributed graph sequence offers a powerful formalism for modeling the structural dynamics of complex systems—such as social networks, urban infrastructures, and document transmission pathways—where vertex interactions evolve over time without explicit attribute information. Mining association rules from such sequences to uncover recurring topological patterns have attracted growing interest. Yet two fundamental challenges remain: (1) how to effectively encode edge-level temporal dynamics in non-attributed settings, and (2) how to perform efficient and semantically meaningful temporal association rule mining under structural uncertainty. To address these within a systems-oriented framework, we propose two novel algorithms: the weighted temporal association rule mining algorithm and the fuzzy weighted temporal association rule mining algorithm. The first algorithm introduces time-dependent numerical weights to quantify the strength and persistence of vertex connectivity, integrating them into support and confidence measures to capture both the intensity and evolution of interactions. The second algorithm extends this by incorporating fuzzy set theory, modeling ambiguous or context-sensitive relationships (e.g., indistinct links or weakly correlated vertices) and generating fuzzy-weighted rules that enhance interpretability for real-world system analysis. Evaluated through five comprehensive experiments across diverse datasets and scales using standard metrics (support, confidence, rule count, running time), our methods produce more selective rule sets and achieve lower computational times compared to the classical Apriori algorithm. The proposed approaches thus establish a robust, data-driven foundation for analyzing temporal evolution and structural uncertainty in dynamic complex systems—providing a generalizable methodology applicable beyond domain-specific constraints. Full article

This experiment aimed to investigate the metabolism of L-Citrulline (L-Cit) in the intestinal tract of ewes and its effects on fecal microbiota composition, plasma metabolism, and reproductive hormone levels. Twelve 18-month-old non-pregnant multiparous Turpan black ewes weighing 51.65 kg ± 2.49 kg were selected and randomly assigned to a control group (Con) and an experimental group (L-Cit), with six ewes in each group. Both groups were fed identical nutrient-dense rations. In the Con group, 100 mL of saline was administered through the duodenal fistula, while the L-Cit group received an additional 0.25 g/kg BW⁻¹ of L-Cit solution. On day 7, the crude protein and amino acid concentrations in feces and urine were assessed using total feces and urine collection methods. Fecal and blood samples were collected to evaluate microbiological and reproductive hormone indices, with blood samples also collected for plasma non-targeted metabolomics analysis two hours post-infusion. Compared to the Con group, the L-Cit group exhibited a significant reduction in crude protein content in feces (p < 0.05) and a highly significant decrease in urine (p < 0.01). Nitrogen metabolism indices did not differ significantly between groups (p > 0.05), but the L-lysine content in feces was significantly higher in the L-Cit group (p < 0.05). 16S rRNA sequencing revealed no significant PCA separation between the two groups. However, the relative abundance of Lachnospiraceae_NK3A20_group, Oscillibacter, and Mogibacterium was significantly higher in the Con group (p < 0.01), while SP3-e08, Parvibacter, Anaerosporobacter, Butyricimonas, and Peptococcus were more abundant in the L-Cit group (p < 0.05). LC-MS analysis showed significant up-regulation of purine and nucleotide metabolism pathways in the L-Cit group (p < 0.05). Plasma levels of estradiol (E₂), progesterone (P₄), gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were significantly elevated in the L-Cit group at both 1 and 2 h post-infusion (p < 0.01). These results suggest that duodenal infusion of L-Cit enhances intestinal nitrogen utilization, alters specific bacterial populations, promotes purine and nucleotide metabolism, and stimulates reproductive hormone secretion in ewes. Full article