Search Results (21,868)

Background: Despite the widespread implementation of treat-to-target strategies and modern disease-modifying antirheumatic drugs, a substantial proportion of patients with rheumatoid arthritis (RA) continue to report unmet needs (UNs), defined as a mismatch between patient expectations and symptom burden on the one hand and outcomes achieved with current care on the other. Patient–physician discordance in global assessments may reflect multidimensional influences, including pain mechanisms, psychosocial factors, functional impairment, and communication gaps, extending beyond inflammatory disease activity. Methods: In this cross-sectional study, 133 patients with RA and 57 healthy controls were included. UNs were operationalized as the signed difference between patient global assessment and physician global assessment (ΔPGA–PhGA). Clinical variables, patient-reported outcomes, and Short Form-36 (SF-36) domains were incorporated into two regularized partial correlation network models estimated using the extended Bayesian information criterion graphical least absolute shrinkage and selection operator (EBICglasso). Node centrality indices (strength, signed strength, betweenness, and closeness) were calculated. Network stability was evaluated using 2000 bootstrap resamples and correlation stability (CS) coefficients. Results: In the clinical network, pain intensity demonstrated the highest strength centrality and the strongest direct association with UNs. In contrast, Disease Activity Score in 28 joints with C-reactive protein (DAS28-CRP) showed no direct association with UNs after accounting for shared variance. In the SF-36-based quality-of-life network, UNs exhibited inverse associations, particularly with perceived health change and role–emotional functioning. Stability analyses indicated acceptable to good robustness (clinical network: CS = 0.59 for edge weights and 0.44 for strength; SF-36 network: CS = 0.59), supporting the reliability of the estimated network structures. Conclusions: UNs in RA are not solely determined by inflammatory disease activity but are embedded within interconnected clinical and psychosocial domains. Pain occupies a structurally central position in the clinical network, whereas perceived health change and emotional role limitations characterize the quality-of-life context of UNs. These findings underscore the importance of multidimensional and patient-centered assessment strategies in RA management. Full article

Paeoniae Radix Alba Carbonisata (PRAC), carbonized decoction pieces of the traditional Chinese medicine Paeoniae Radix Alba, has been used in clinical practice for hepatoprotective purposes. Hepatic amyloidosis (HA), a severe complication of systemic AA amyloidosis, is characterized by the deposition of fibrillar amyloid proteins leading to progressive hepatic dysfunction. However, its role in HA remains unclear. Amyloid lysozyme (LYSO-6) was used to induce the NCTC1469 cell injury model and the HA mouse model. The effects of PRAC extract (PRAC-E) on liver injury were then evaluated using biochemical assays, enzyme-linked immunosorbent assay (ELISA), Congo red (CR) staining, Hematoxylin and Eosin (H&E) staining, and immunohistochemical staining. Liver transcriptomics combined with Western blotting was used to analyze the expression levels of key proteins in the cGMP/PKG/ATP2A1 signaling axis. UHPLC-Q-Exactive Orbitrap MS combined with network pharmacology was used to characterize the chemical components of PRAC-E and identify its core active constituents against HA. Quantitative analysis of core components was performed by UHPLC-QTRAP-MS/MS. Molecular docking predicted the binding stability of core components and key targets. The results showed that PRAC-E significantly alleviated HA. Collectively, PRAC-E restored calcium pump activity, corrected calcium homeostasis imbalance, reduced inflammatory factor levels, regulated Phosphodiesterase 5A (PDE5A), and activated the cGMP/PKG/ATP2A1 signaling axis. The main components of PRAC-E were phenolic acids, terpenoids, and flavonoids. Among these, six core components (SCCs) related to HA were Gallate (16.96 mg/g), Paeoniflorin (14.27 mg/g), Albiflorin (7.20 mg/g), Benzoyl paeoniflorin (5.33 mg/g), Methyl gallate (0.78 mg/g), and Catechin (0.09 mg/g). Molecular docking analysis demonstrated that SCCs formed stable complexes (∆G ≤ −6.2 kcal/mol) with ATP2A1. Full article

Objective: This study aimed to develop the Infectious Diseases Knowledge Questionnaire (IDKQ) and evaluate its psychometric properties for use in community settings. Methods: This methodological study was conducted with 533 adults aged ≥ 18 years. Data were collected using a sociodemographic information form and the IDKQ. Content validity was assessed by expert evaluation. Construct validity was examined using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). Reliability was evaluated through item–total correlations, internal consistency (KR-20), test–retest reliability, and intraclass correlation coefficients (ICC). Data analyses were performed using SPSS 25.0 and AMOS 21.0. Results: Content validity index values ranged from 0.94 to 1.00. EFA revealed a four-factor structure consisting of 17 items, explaining 45.66% of the total variance (KMO = 0.784; Bartlett’s test, p < 0.001). CFA demonstrated good model fit (χ²/df = 2.329, RMSEA = 0.074, CFI = 0.946, AGFI = 0.847, GFI = 0.887, SRMR = 0.045). The KR-20 coefficient was 0.735, the test–retest correlation was 0.604, and the ICC was 0.781. Conclusions: The IDKQ demonstrates acceptable internal consistency and moderate temporal stability, providing preliminary evidence of reliability and construct validity. It may serve as a tool for assessing infectious disease knowledge, although further validation in independent samples is recommended. Full article

The effects of different finishing rolling temperatures on the microstructure and mechanical properties of a 580HE hole expansion steel were systematically investigated using optical microscopy, scanning electron microscopy, electron backscatter diffraction, and transmission electron microscopy. The results show that the yield strength increases with decreasing finishing rolling temperature, whereas the tensile strength and total elongation exhibit relatively small variations. Significant changes in phase fraction, grain size, spatial distribution, and NbC precipitation behavior are observed under different finishing rolling temperatures. The microstructure mainly consists of polygonal ferrite and granular bainite, while acicular ferrite is formed at higher finishing rolling temperatures. With decreasing finishing rolling temperature, the ferrite and bainite grains are markedly refined and become more uniformly distributed. Meanwhile, the ferrite fraction slightly increases, the crystallographic texture is weakened, and, more importantly, the number density of precipitates increases while their size is significantly reduced. The hole expansion ratio increases noticeably with decreasing finishing rolling temperature, which is mainly attributed to grain refinement, improved microstructural and strain homogeneity, and the selective strengthening effect of fine NbC precipitates. These factors effectively reduce stress concentration and hardness mismatch between soft and hard phases, thereby delaying crack initiation during hole expansion. Full article

This study investigates the potential of Quercus robur leaves as a bio-coagulant for the removal of heavy metal ions, including zinc (II), iron (III), copper (II), and chromium (VI), from water. The Quercus robur leaves were used in two forms: Quercus robur powder (QRP) and Quercus robur extract (QRE). The extract was prepared using distilled water to extract the active compounds responsible for coagulation, such as proteins, polysaccharides, and total phenolics. The QRP was characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD), and zeta potential analysis to identify the active functional groups, surface morphology, crystallinity, and surface charge, all of which are key factors influencing its performance in the coagulation–flocculation process. In this work, the Response Surface Methodology (RSM)-based Central Composite Design (CCD), with two factors (bio-coagulant dosage and initial metal concentration), was used examine the effects of each factor and their interaction, while the responses were zinc (II) removal, iron (III) removal, copper (II) removal, and chromium (VI). The results revealed high removal efficiency for these metal ions, reaching up to 100% for all metal ions treated with QRP and QRE. The quality of the model predictions was evaluated using analysis of variance (ANOVA). For all metal ions, the R² (≥97%), R² adjusted (≥95%), and p-values (<0.05), indicating an excellent model accuracy. These results show that bio-coagulants (QRP and QRE) based a Quercus robur leaves are a promising, effective, and reliable option for removing heavy metal ions from water, and that the models developed can be used to optimize the coagulation-flocculation process. Full article

Landslide hazard potential is high across the St. Lawrence lowlands of Québec, Canada, due to sensitive glaciomarine clay deposits and the presence of moderate seismic activity, causing slope failures in the region. The main objectives of the study are to develop a working database for landslides in the region and use that database to improve regional landslide susceptibility analysis. Using high-resolution (1 m by 1 m cells) digital terrain models dated from 2009 and validated with satellite photogrammetry from 2012, a landslide inventory of 263 cases related to the 2010 Val-des-Bois earthquake (moment magnitude 5.0) is created. Relationships between landslide susceptibility factors, such as slope angle, and seismic conditioning factors, such as peak ground acceleration, are examined through machine learning methods. For landslide detection, an overall accuracy of approximately 85% (AUC 0.914) is achieved using random forest and logistic regression models cross-validated through 5-fold analysis, showing improvement over the currently employed Hazus method, which achieves an accuracy of approximately 67%. From a regional perspective, the developed inventory and resultant susceptibility models are unique and form the foundation for future studies to improve the understanding of earthquake-induced landslides in the Western Québec Seismic Zone, which historically lacks detailed landslide inventories. Full article

Based on temperature–stress coupling simulation, a thermal source model for nanosecond pulsed hollow cathode electron beam surface modification is proposed. Dynamic thermal-stress changes from beam–surface interaction and their influence on micro–nano characteristics were systematically investigated. By analyzing maximum temperature/stress dynamics, cross-sectional remelted layer variations, and heating/cooling rates, the temperature and stress distribution in the micron-scale surface layer was comprehensively revealed, validating the model’s rationality. Combined with low, medium, and high pulse count experiments, the effects of thermal and stress factors on surface morphology and grain refinement were studied, elucidating underlying mechanisms through numerical correspondence. Results show irradiation effects confined to a 1.5–2 mm localized region, with extreme temperature changes (~10³ K) and stress variations (10³–10⁴ MPa) within tens of nanoseconds. Heating rates reached 10¹¹ K/s, cooling rates 10⁹–10¹⁰ K/s, exceeding microsecond pulsed beams by one to two orders. Simulated remelting zone diameter and thickness agreed well with experiments, confirming model validity. Grain refinement is primarily driven by rapid temperature distribution, generating instant solidification nucleation sites, with a secondary contribution from high-stress-induced plastic deformation forming sub-grains. Full article

Sarcopenia and glucocorticoid-induced myopathy are significant forms of muscle atrophy that pose considerable public health challenges. In this regard, preventing muscle atrophy is crucial for enhancing quality of life and increasing life expectancy. In this study, we investigated the effect of recombinant human KAI1 (rhKAI1) on myogenic differentiation and its protective effect against dexamethasone-induced muscle atrophy. rhKAI1 enhanced myogenic differentiation in both murine C2C12 myoblasts and primary human endometrial stromal cells, as evidenced by upregulation of myogenic regulatory factors and increased myotube formation. These effects were accompanied by increased phosphorylation of Akt and AMPK. In a dexamethasone (Dex)-induced atrophy model, rhKAI1 increased myotube diameter, restored MyHC expression, and reduced the expression of the E3 ligase atrogin-1, accompanied by increased phosphorylation of Akt and AMPK. In addition, rhKAI1 administration improved Dex-induced functional impairment in mice, as reflected by increased grip strength and improved rotarod performance. Molecular analyses further showed that rhKAI1 modulated Dex-induced fiber-type-related gene expression by restoring MYH7 (type I) and reducing MYH4 (type IIb) expression. Collectively, our findings demonstrate that rhKAI1 promotes myogenic differentiation and alleviates several functional and molecular features associated with glucocorticoid-induced muscle deterioration. These results support the potential of rhKAI1 as a candidate molecule for further investigation in steroid-induced muscle dysfunction. Full article

β-thalassaemia (β-thal) is part of a group of diseases, the β-hemoglobinopathies, affecting the levels or functionality of the β-globin subunit of hemoglobin, which are the most widespread monogenic diseases throughout the world. The severity of β-thal is determined by different genetic factors, but in the gravest form, affected patients are constrained to a program of blood transfusion and iron chelation regimens for their entire life. Although definitive cures, such as bone marrow transplantation or gene therapy, are now available, they are still far from being applied worldwide. Therefore, there is growing attention towards the use of drugs to cure or ameliorate β-thal disorder. Among all the strategies, pharmacological increase of fetal HbF and/or adult HbA2 can represent an advantageous approach as high levels of both hemoglobins are effective against β-thal. Therefore, the identification of therapeutic targets that can modulate, by the use of drugs, these hemoglobins is increasingly urgent. In this paper, we analyze the effects of the absence of the CCND3 gene, a druggable target associated with HbF and HbA2 levels, in a humanized mouse model of β-thal to assess the impact against the disorder. Upregulation of γ- and δ-globin levels in mice lacking Ccnd3 expression contributes to partial restoration of the α/β balance, with a consequent increase in hemoglobin levels, improvement of iron levels, and reduction of splenomegaly. Moreover, we present data supporting the enhancement of erythropoiesis. Our data indicate the CCND3 gene as a possible target for drugs against β-thal. Full article

Botulism is a neuroparalytic disease caused by exposure to botulinum neurotoxins produced by anaerobic spore-forming bacteria of the genus Clostridium. This disease occurs in both humans and wild and domestic animals, and is currently becoming an increasingly serious problem worldwide due to high animal mortality and economic losses. The clinical signs observed during the progression of botulism are nonspecific and difficult to unequivocally associate with this disease entity. The aim of this study is to present laboratory diagnostics of suspected botulism cases reported in Poland in 2022–2024, as well as to present the challenges encountered during laboratory investigations. The material for the study consisted of samples of liver, serum, digestive tract, feed, feces, straw, and water from drinking lines, sent to the National Veterinary Research Institute (NVRI) in relation to thirteen suspected cases of botulism, predominantly reported in poultry, but also in mink and cattle farms. The samples were analyzed using a mouse bioassay and conventional culture methods, as well as real-time PCR methods aimed at detecting the ntnh and bont genes, which determine the production of botulinum neurotoxins. Of the thirteen suspected cases analyzed, ten were confirmed by the detection of botulinum toxin (BoNTs) and/or the presence of the ntnh and bont genes in the tested material. Based on the results obtained, it was concluded that botulinum toxin type C was the etiological factor of botulism poisoning in most of the analyzed cases. In one case reported in cattle, poisoning occurred as a result of the mosaic variant of BoNT D/C. Due to the nonspecific signs of botulism and the time required for them to appear, laboratory diagnostics play a key role in detecting the disease. However, this process is complicated due to the high heterogeneity observed among Clostridium spp. strains, as well as difficulties encountered during the isolation of the microorganism and the possibility of loss of toxin-producing capacity at later stages of analysis. Full article

Resource-based cities in the Yellow River Basin are important pillars of national energy security and regional coordinated development, and their green transformation is closely related to the overall strategy of ecological protection and high-quality development in the basin. This study takes 34 resource-based cities within the basin as the research objects and employs a combination of methods, including the Super Slacks-Based Measure (SBM) model, the Malmquist–Luenberger index, the standard deviational ellipse, the Dagum Gini coefficient, and the geographical detector, to systematically analyze the spatio-temporal evolution characteristics and driving mechanisms of green development efficiency from 2012 to 2022. The results indicate that: (1) green development efficiency shows an overall upward trend, forming a pattern of leading performance in the lower reaches, lagging development in the middle reaches, and accelerated catching-up in the upper reaches, with efficiency improvements jointly driven by technical efficiency enhancement and technological progress; (2) the gravity center of efficiency shifts southwestward overall, and interregional disparities constitute the main source of overall differences; (3) economic development level, science and technology investment, fiscal expenditure, and energy intensity are the key driving factors, with significantly strengthened interactions among multiple factors. From the dual perspectives of basin location and the urban life cycle, this study constructs a multidimensional analytical framework that provides a reference for categorized regulation and coordinated regional governance of resource-based cities. Full article

Background/Objectives: Cholesterol is an essential lipid required for membrane structure and normal physiological functions. However, dysregulation of cholesterol homeostasis, manifesting as hypercholesterolemia, can precipitate a range of metabolic and cardiovascular diseases. Blautia species are important gut commensals, but their role in cholesterol metabolism remains poorly defined. Methods: A total of 63 Blautia strains isolated from human fecal samples were screened for cholesterol conversion using the o-phthalaldehyde colorimetric assay in cholesterol-containing media with or without oxgall. Cholesterol removal by live and heat-inactivated cells was compared. Metabolomic, transcriptomic, and proteomic analyses were employed to investigate molecular mechanisms and involved genes. Results: Nine strains significantly lowered cholesterol levels (live cells: 31–78%; heat-inactivated cells: 8–64%), with the B. hominis strain HA2291, the Blautia sp. strain HA3515, and the B. coccoides strain HA4419 showing the strongest activity. Oxgall increased cholesterol removal by live cells to 74–83%, indicating bile-tolerant metabolism activity. Metabolomic profiling revealed that B. hominis HA2291 transformed cholesterol into cholest-4-en-3-one and epicholestanol. An SCP2-like protein, RS03310, was identified as a candidate cholesterol-interacting factor; its recombinant form catalyzed measurable NAD⁺-dependent cholesterol oxidation in vitro. Conclusions: Blautia hominis HA2291 may employ multiple in vitro strategies for cholesterol-lowering, including cell-surface adsorption (heat-inactivated cells), bile-enhanced removal (oxgall effect), and enzymatic transformation, with the gene RS03310 implicated as the main contributor. These findings provide in vitro mechanistic insights into Blautia-mediated cholesterol metabolism, highlight RS03310 as a candidate gene associated with cholesterol biotransformation, and advance our understanding of the potential role of Blautia in host cholesterol homeostasis. Full article

This study investigates four rock–soil profiles developed from Proterozoic intermediate–acid rocks in the Maoniushan area of Xichang, Sichuan Province. Through systematic geochemical analysis of major and trace elements and X-ray diffraction analysis of clay minerals, we aim to clarify the dominant controlling factors and environmental response mechanisms of chemical weathering under similar lithological and soil-forming age conditions. The results indicate the following: (1) Major element geochemistry shows that the Chemical Index of Alteration (CIA) of all profiles ranges from 61 to 74, while Na/K ratios and A-CN-K diagrams collectively reveal that the profiles are in a transitional stage from weak weathering (Ca and Na depletion) to moderate weathering (K depletion), with the weathering intensity ranking in the order TP1711 > TP1709 > TP1714 ≈ TP2801. (2) Trace elements exhibit significant differences among profiles: Cu, Zn, and Pb are significantly leached relative to Al₂O₃ in the TP1711 profile, whereas most trace elements are enriched in the TP1714, TP1709, and TP2801 profiles. Variations in ∑LREE/∑HREE ratios further support differences in the weathering stages of the profiles. (3) The clay mineral assemblages are dominated by illite, chlorite, and vermiculite. The TP1714 profile lacks vermiculite and has the highest illite content (54–60%), reflecting a relatively cold and dry local microclimate. In contrast, the other profiles show widespread vermiculite development, accompanied by minor kaolinite, indicating moderate weathering intensity under warm and humid climatic conditions. This study confirms that under similar lithological and soil-forming age conditions, the microclimatic differentiation induced by altitude variation is the key external controlling factor leading to spatial differences in the chemical weathering intensity of granite–soil profiles in the Maoniushan area. Full article

This article investigates the phenomenon of numismatic forgery legitimisation and its impact on the fields of numismatics, archaeology, history and law. Forgery legitimisation is a broad phenomenon that encompasses both physical forgery and the presentation of fake artifacts as genuine in research literature, auction catalogues, and other contexts. Using the qualitative case-study methodology, the authors propose an analytical framework for suspected forgery legitimisation that incorporates a novel classification of forms and types of forgery, as well as socio-legal mens rea elements. The framework also accounts for factors contributing to the legitimisation of forgeries, including lack of competence, low competition in coin catalogue publication, tradition, closed numismatic communities, and insufficient academic and legal attention. Using this framework, the authors examine two cases of legitimisation of fake coins in medieval Polish–Lithuanian numismatics. The analysis shows how repetition across sources can legitimise fake artifacts, complicating later correction and corrupting heritage research, history and museum science, as well as market integrity. The proposed analytical framework can be useful for investigating other dubious artifacts and for developing analysis methods for forgery legitimisation cases. Full article

Myocarditis is a complex inflammatory myocardial disease. Although traditionally regarded as exclusively immune-mediated, recent evidence highlights the significant role of underlying genetics on susceptibility, phenotypic variability, and long-term prognosis. This narrative review examines the evolving genetic architecture of myocarditis and its relationship to inherited cardiomyopathies, integrating mechanistic insights from molecular, imaging, and clinical studies. Variants in desmosomal genes such as desmoplakin (DSP) and plakophilin-2 (PKP2) are increasingly linked to recurrent myocarditis that may evolve into arrhythmogenic cardiomyopathy, supporting the concept of a genetically predisposed myocardium in which inflammatory stressors can act as triggers. Truncating variants in titin (TTN) and Filamin C (FLNC) are associated with fulminant or dilated phenotypes. Conversely, mutations in Lamin A/C (LMNA), Desmin (DES), and BCL2-Associated Athanogene 3 (BAG3) contribute to inflammatory myocardial remodeling and other forms of inherited cardiomyopathies. These findings collectively have the potential to redefine myocarditis as an inflammatory disorder influenced by genetic factors. Furthermore, advancements in genetic testing and multi-omics approaches show promise in enhancing diagnostic accuracy and informing management strategies. Full article